Valdez, Avelardo; Neaigus, Alan; Cepeda, Alice
SUMMARY This study examines potential risk factors for resuming and transitioning to injecting among a prospective cohort of 300 Mexican American non-injecting heroin users (NIUs) with distinct injecting histories (i.e., never vs. former injectors). Overall. findings revealed NIUs with an injecting history are more likely to be at greater risk for resuming injecting practices. Of interest, scoring high on acculturation decreased the risk of being a former injector. The present analysis supports previous research, and more importantly further identifies potential risk factors for injecting that are unique to the cultural and social context of the Mexican American community. PMID:18192204
Valdez, Avelardo; Neaigus, Alan; Kaplan, Charles D.
Noninjecting heroin use (NIU) is spreading among social networks of young Mexican American polydrug users. This article examines the influence of family and peer networks on NIU behavior and other drug practices and risks. This study delineates the extent to which a culturally relevant modification of the “network facilitation” theoretical approach can increase both a theoretical and practical understanding of drug use and related risk behaviors. Using the methods of analytic ethnography, it identifies, describes, and explains variations in the social networks among this marginalized population and how specific aspects of Mexican American culture (familismo, and collectivismo) affects risk behaviors. PMID:19337564
Darke, Shane; Hetherington, Kate; Ross, Joanne; Lynskey, Michael; Teesson, Maree
A sample of 535 entrants to opioid dependence treatments across three treatment modalities were administered a structured interview to ascertain the prevalence of non-injecting heroin use. Ten per cent of participants had used heroin primarily by smoking/inhaling in the month preceding interview, and 9% had used heroin and other drugs exclusively by non-injecting routes. Non-injectors were younger (25.3 vs. 29.5 years), had higher levels of education (10.6 vs. 10.0 years), were more likely to be employed (33 vs. 18%) and had lower levels of recent crime (31 vs. 56%). They also had shorter heroin using careers (5.1 vs. 9.9 years), fewer symptoms of dependence (5.1 vs. 5.6), had been enrolled in fewer previous treatment episodes (3.3 vs. 11.5) and had less extensive lifetime (8.0 vs. 9.1 drug classes) and recent (3.6 vs. 4.9) polydrug use. Non-injectors were substantially less likely to report lifetime (13% vs. 58%) or recent (2% vs. 29%) heroin overdoses. There were no differences between the general physical and psychological health of the two groups. While non-injectors had a lower level of post-traumatic stress disorder (29% vs. 34%), there were no differences in levels of major depression, attempted suicide, antisocial personality disorder, or borderline personality disorder. A substantial minority of Australian treatment entrants are now using heroin exclusively by non-injecting routes. While this group is younger, and has substantially reduced risk of overdose and blood borne virus transmission, the physical and psychological health of non-injectors mirrors that of injectors.
Novak, Scott P; Kral, Alex H
Research examining the demographic and substance use characteristics of illicit drug use in the United States has typically failed to consider differences in routes of administration or has exclusively focused on a single route of administration?injection drug use. Data from National Survey on Drug Use and Health were used to compare past-year injection drug users and non-injection drug users' routes of administration of those who use the three drugs most commonly injected in the United States: heroin, methamphetamine, and cocaine. Injection drug users were more likely than those using drugs via other routes to be older (aged 35 and older), unemployed, possess less than a high school education, and reside in rural areas. IDUs also exhibited higher rates of abuse/dependence, perceived need for substance abuse treatment, and co-occurring physical and psychological problems. Fewer differences between IDUs and non-IDUs were observed for heroin users compared with methamphetamine or cocaine users.
Ciccarone, Daniel; Unick, George J; Kraus, Allison
Background The past two decades have seen an increase in heroin-related morbidity and mortality in the United States. We report on trends in US heroin retail price and purity, including the effect of entry of Colombian-sourced heroin on the US heroin market. Methods The average standardized price ($/mg-pure) and purity (% by weight) of heroin from 1993 to 2004 was from obtained from US Drug Enforcement Agency retail purchase data for 20 metropolitan statistical areas. Univariate statistics, robust Ordinary Least Squares regression and mixed fixed and random effect growth curve models were used to predict the price and purity data in each metropolitan statistical area over time. Results Over the 12 study years, heroin price decreased 62%. The median percentage of all heroin samples that are of South American origin increased an absolute 7% per year. Multivariate models suggest percent South American heroin is a significant predictor of lower heroin price and higher purity adjusting for time and demographics. Conclusion These analyses reveal trends to historically low-cost heroin in many US cities. These changes correspond to the entrance into and rapid domination of the US heroin market by Colombian-sourced heroin. The implications of these changes are discussed. PMID:19201184
... Loss Surgery? A Week of Healthy Breakfasts Shyness Heroin KidsHealth > For Teens > Heroin A A A What's ... How Can Someone Quit? Avoiding Heroin What Is Heroin? Heroin is a highly addictive drug made from ...
Dolan, M. P.; And Others
Assessed personality differences among Black, White, and Hispanic-American heroin addicts (N=423). Results confirmed the hypotheses that minority group heroin addicts (Blacks and Hispanics) would show better adjustment than White heroin addicts and that Hispanic-American heroin addicts would evidence personality characteristics unlike those of…
Demaret, I; Lemaître, A; Ansseau, M
Heroin (or diacetylmorphine), a depressant nervous central system, is a semi-synthetic opiate. Its main adverse effect, respiratory depression, can lead to death, especially after an intravenous injection. By loss of tolerance, an overdose can be lethal following heroin use after a period of abstinence (voluntary or not). Mortality rate among heroin users is between 1 and 3%. Addiction, following a regular and continuous use, occurs in less than a quarter of persons who ever tried heroine. Heroin addicts often present with different problems (for instance, a criminal behaviour), without any obvious link with addiction. For a fraction of the addicts, addiction becomes a chronic relapsing disease, requiring a long term maintenance substitution therapy. However, relapses and sometimes continuous heroin use are frequent, For treatment resistant and severe heroin addicts, heroin-assisted treatment can be a solution. Despite the numerous available therapies, heroin is considered to be the drug with the most negative effects on the user.
... 19-23, 2016 DEA Museum and Visitors' Center Heroin Last Updated: Monday, April 3, 2017 What is ... from morphine and extracted from certain poppy plants. Heroin comes in a white or brownish powder, or ...
... Heroin is a highly addictive drug made from morphine, a psychoactive (mind-altering) substance that is extracted ... an opioid. It is related to chemically to morphine and other prescription opiates like vicodin, which are ...
In October 2008, the North American Opiate Medication Initiative (NAOMI) research team released the primary outcomes of a randomized controlled trial aimed at testing whether the provision of pharmaceutical-grade heroin under medical supervision benefits people suffering from chronic opiate addictions who have not benefitted from other treatments. The treatment phase was completed in June 2008. Retention and response rates were high, suggesting that heroin-assisted therapy is a safe and highly effective treatment for people with chronic heroin addiction.
Harris, Jennie L; Lorvick, Jennifer; Wenger, Lynn; Wilkins, Tania; Iguchi, Martin Y; Bourgois, Philippe; Kral, Alex H
In this paper, we explore the understudied phenomenon of "low-frequency" heroin injection in a sample of street-recruited heroin injectors not in drug treatment. We conducted a cross-sectional study of 2,410 active injection drug users (IDUs) recruited in San Francisco, California from 2000 to 2005. We compare the sociodemographic characteristics and injection risk behaviors of low-frequency heroin injectors (low-FHI; one to 10 self-reported heroin injections in the past 30 days) to high-frequency heroin injectors (high-FHI; 30 or more self-reported heroin injections in the past 30 days). Fifteen percent of the sample met criteria for low-FHI. African American race, men who have sex with men (MSM) behavior, and injection and noninjection methamphetamine use were independently associated with low-FHI. Compared to high-FHI, low-FHI were less likely to report syringe sharing and nonfatal heroin overdose. A small but significant proportion of heroin injectors inject heroin 10 or less times per month. Additional research is needed to qualitatively examine low-frequency heroin injection and its relationship to drug use trajectories.
Keen, Larry; Khan, Maria; Clifford, Lisa; Harrell, Paul T.; Latimer, William W.
Purpose The current study examines differences in the prevalence of biologically-confirmed hepatitis C virus (HCV), HIV, and coinfection between Black and White adult cocaine/heroin users across three drug use subgroups identified in previous research (Harrell et al, 2012): non-injection smoking crack/nasal heroin users, heroin injectors, and polydrug injectors. Results 59% of the 482 participants in the study were male. Significant race differences emerged between drug use subgroup memberships. Non-injection smoking crack/nasal heroin users were predominantly Black (75%), while heroin injectors and polydrug injectors were predominantly White (69% and 72%, respectively). Polydrug injectors accounted for nearly three quarters of the HCV positive diagnoses in Whites. Though HIV disease status, stratified by race, did not differ significantly between drug use subgroups, the non-injection smoking crack/nasal heroin subgroup contained over half of the HIV positive diagnoses in the sample and was predominantly Black. Despite much lower rates of injection, Blacks (8%) had a higher prevalence of coinfection than Whites (3%; X2 (2) = 6.18, p = .015). Conclusions The current findings are consistent with trends in recent HIV transmission statistics where sexual activity has overtaken injection drug use as a HIV risk factor. The current findings also provide further support to the notion of injection drug use as an exceedingly high-risk behavior for HCV and coinfection, specifically those who are polysubstance injectors. PMID:24837755
Walker, Robrina; Maxwell, Jane Carlisle; Adinoff, Bryon; Carmody, Thomas; Coton, Casey E.; Tirado, Carlos F.
Clinical and cultural characteristics of Hispanic adolescent heroin users are not well described. The current exploratory study was conducted to describe a sample of in-treatment Hispanic adolescents with opioid dependence, specifically, cheese heroin. Mexican and Mexican American adolescents with heroin dependence (N = 72) in three treatment programs were interviewed and completed self-report measures. Participants reported, on average, first using cheese heroin at 13.5 years old and daily use at age 14.2. The majority (74%) reported a previous overdose. Adolescents being raised by caregivers other than both biological parents, who used drugs with relatives, and whose immediate family members have documentation to be in the U.S. fared worse on several indicators of drug use severity and other risky behaviors. The self-reported brief time period from first use to daily use strongly suggests the need for early prevention efforts. Additional research is needed to add to these preliminary results and inform prevention efforts. PMID:25176119
Walker, Robrina; Maxwell, Jane Carlisle; Adinoff, Bryon; Carmody, Thomas; Coton, Casey E; Tirado, Carlos F
Clinical and cultural characteristics of Hispanic adolescent heroin users are not well described. The current exploratory study was conducted to describe a sample of in-treatment Hispanic adolescents with opioid dependence, specifically, cheese heroin. Mexican and Mexican American adolescents with heroin dependence (N = 72) in three treatment programs were interviewed and completed self-report measures. Participants reported, on average, first using cheese heroin at age 13.5 years and daily use at age 14.2 years. The majority (74%) reported a previous overdose. Adolescents being raised by caregivers other than both biological parents, who used drugs with relatives, and whose immediate family members have documentation to be in the United States fared worse on several indicators of drug use severity and other risky behaviors. The self-reported brief time period from first use to daily use strongly suggests the need for early prevention efforts. Additional research is needed to add to these preliminary results and inform prevention efforts.
Valdez, Avelardo; Kaplan, Charles D.; Cepeda, Alice
This study focuses on the process of paradoxical autonomy and survival in the heroin careers of Mexican American women. We explore how gender roles among Mexican American female heroin users influence the emergence of a paradoxical autonomy. Five key subprocesses of this autonomy were identified from 14 life history narratives: sustaining employment, working the welfare system, illegal activities, emotional aloofness, and loss of family and children. Dependency on drugs did not lead simply to the reproduction of traditional gender dependency but, paradoxically, seemed to contribute to a new type of gender autonomy. This autonomy did not necessarily make the survival less arduous, only more independent from gendered responsibilities associated with men and often with family and children. We discuss how this paradoxical autonomy is not acquired without ambiguity by some of these women, who place a value on maintaining relationships with men and family. Our study makes a contribution to a better understanding of the diverse processes by which Mexican American female heroin users struggle to survive. Although this struggle leads to a paradoxical autonomy from their traditional gender roles, it does little to change other barriers to self-development originating from poverty, ethnic discrimination, and the severity of their drug addiction. PMID:21057594
Torres, Luis R.; Kaplan, Charles; Valdez, Avelardo
Objectives Research on the health consequences of long-term injection drug use (IDU) is limited. This article examines these consequences among aging, male Mexican American injecting heroin users. Concern for this group is crucial, given its health disparities and the association of IDU with disease transmission. Method Aging, male Mexican American IDUs (N = 227) were recruited through intensive outreach. Participants self-reported health status, medical and substance use history, and completed behavioral and psychometric health scales. Results are compared to Hispanic national samples. Results Participants had significantly poorer self-rated health and negative health conditions. Selected medical conditions not associated with the heroin-use lifestyle (i.e., hypertension, diabetes, arthritis) were lower relative to the comparison samples. Discussion This population has a complex profile of health consequences linked to a heroin-using lifestyle. The study concludes that routine screening of infectious diseases and medical and behavioral conditions among aging substance using populations may contribute to reducing Hispanic health disparities. PMID:21451118
Kalisch, P A
Experiences of female Army nurses-their devotion to duty, contributions, and successes as well as their trials, tribulations, and sufferings--during the Spanish-American War and afterwards are described. How service by the heroines of '98 led to a change of attitude by the Army Medical Department is sketched. At the beginning of the War with Spain, the Medical Department had been reluctant to use female nurses; by the end of the war, the nurses had so demonstrated their value that Congress established permanent Army Reserve Nurse Corps.
Evans, Gerald D
Clara Barton was a nineteenth century woman driven to greatness. She was a teacher, a nurse, a Civil War heroine and founder of the American Red Cross. In order to cut a path into the future we must know where we have been. The story of Clara Barton is about someone who cut that path. It is about courage, overcoming obstacles, never giving up and doing the job that needs doing. What makes it fascinating is the human side, the weaknesses that coloured her life. We can learn from her journey as we develop our own path into the future.
Bowser, Benjamin; Fullilove, Robert; Word, Carl
Heroin abuse as an outcome of the prior use of painkillers increased rapidly over the past decade. This "new epidemic" is unique because the new heroin users are primarily young White Americans in rural areas of virtually every state. This commentary argues that the painkiller-to-heroin transition could not be the only cause of heroin use on such a scale and that the new and old heroin epidemics are linked. The social marketing that so successfully drove the old heroin epidemic has innovated and expanded due to the use of cell-phones, text messaging and the "dark web" which requires a Tor browser, and software that allows one to communicate with encrypted sites without detection. Central city gentrification has forced traffickers to take advantage of larger and more lucrative markets. A second outcome is that urban black and Latino communities are no longer needed as heroin stages areas for suburban and exurban illicit drug distribution. Drug dealing can be done directly in predominantly white suburbs and rural areas without the accompanying violence associated with the old epidemic. Denial of the link between the new and old heroin epidemics racially segregates heroin users and more proactive prevention and treatment in the new epidemic than in the old. It also cuts off a half-century of knowledge about the supply-side of heroin drug dealing and the inevitable public policy measures that will have to be implemented to effectively slow and stop both the old and new epidemic.
Oviedo-Joekes, Eugenia; Nosyk, Bohdan; Brissette, Suzanne; Chettiar, Jill; Schneeberger, Pascal; Marsh, David C; Krausz, Michael; Anis, Aslam; Schechter, Martin T
The North American Opiate Medication Initiative (NAOMI) is a randomized controlled trial evaluating the feasibility and effectiveness of heroin-assisted treatment (HAT) in the Canadian context. Our objective is to analyze the profile of the NAOMI participant cohort in the context of illicit opioid use in Canada and to evaluate its comparability with patient profiles of European HAT studies. Recruitment began in February 2005 and ended in March 2007. Inclusion criteria included opioid dependence, 5 or more years of opioid use, regular opioid injection, and at least two previous opiate addiction treatment attempts. Standardized assessment instruments such as the European Addiction Severity Index and the Maudsley Addiction Profile were employed. A total of 251 individuals were randomized from Vancouver, BC (192, 76.5%), and Montreal, Quebec (59, 23.5%); 38.5% were female, the mean age was 39.7 years (SD:8.6), and participants had injected drugs for 16.5 years (SD:9.9), on average. In the prior month, heroin was used a mean of 26.5 days (SD:7.4) and cocaine 16 days (SD;12.6). Vancouver had significantly more patients residing in unstable housing (88.5 vs. 22%; p < 0.001) and higher use of smoked crack cocaine (16.9 days vs. 2.3 days in the prior month; p < 0.001), while a significantly higher proportion of Montreal participants reported needle sharing in the prior 6 months (25% vs. 3.7%; p < 0.001). In many respects, the patient cohort was similar to the European trials; however, NAOMI had a higher proportion of female participants and participants residing in unstable housing. This study suggests that the NAOMI study successfully recruited participants with a profile indicated for HAT. It also raises concern about the high levels of crack cocaine use and social marginalization.
Heroin is an illicit, highly addictive drug. It is either the most abused or the most rapidly acting member of opioids. Abusers describe a feeling of a surge of pleasurable sensation, named as "rush" or "high". Repeated administration of high doses of heroin results in the induction of physical dependence. Physical dependence refers to an altered physiological state produced by chronic administration of heroin which necessitates the continued administration of the drug to prevent the appearance of a characteristic syndrome, the opioid withdrawal or abstinence syndrome. Withdrawal symptoms may occur within a few hours after the last administration of heroin. Symptoms of the withdrawal include restlessness, insomnia, drug craving, diarrhea, muscle and bone pain, cold flashes with goose bumps, and leg movements. Major withdrawal symptoms peak between 48 and 72 hours after the last dose of heroin and subside after about a week. At this time, weakness and depression are pronounced and nausea and vomiting are common. Nevertheless, some chronic addicts have shown persistent withdrawal signs for many months or even years. Heroin addiction is considered as a behavioural state of compulsive drug use and a high tendency to relapse after periods of abstinence. It is generally accepted that compulsive use and relapse are typically associated with the status of heroin craving or heroin hunger that are difficult to define but appear to be powerful motivational significance in the addiction process. The route of administering heroin varies largely and may indicate the degree of seriousness of the individual's addiction. Intravenous administration seems to be the predominant method of heroin use, but recently a shift in heroin use pattern has been found, i.e. from injection to sniffing and smoking. Frequent injections coupled with widespread sharing of syringes increase the risk of contracting HIV, hepatitis B, C and other blood-borne infectious diseases. Long-term use of heroin
Krumm, Bernita L.
This article profiles Susan LaFlesche Picotte, the first Native American woman doctor in the United States. Several accounts record that at a very young age Picotte witnessed an incident involving a Caucasian doctor who refused to care for a dying Native American woman. Picotte was inspired by that incident to become a physician, ultimately…
... overdose. This type of medicine is called an antidote. Naloxone is injected under the skin or into ... effects of the heroin Outlook (Prognosis) If an antidote can be given, recovery from an acute overdose ...
This script, with music, lyrics and dialog, was written especially for youngsters to inform them of the potential dangers of various drugs. The author, who teaches in an elementary school in Harlem, New York, offers Miss Heroin as her answer to the expressed opinion that most drug and alcohol information available is either too simplified and…
Do It Now Foundation, Phoenix, AZ.
The document presents a collection of articles about heroin. Article 1 provides general information on heroin identification, drug dependence, effects of abuse, cost, source of supply, and penalties for illegal heroin use. Article 2 gives statistical information on heroin-related deaths in the District of Columbia between 1971 and 1982. Article 3…
The discovery of heroin and the development of heroin abuse are introduced. Heroin, the hydrochloride of diacetylmorphine, was discovered by acetylation of morphine. Heroin, in pharmacological studies, proved to be more effective than morphine or codeine. The Bayer Company started the production of heroin in 1898 on a commercial scale. The first clinical results were so promising that heroin was considered a wonder drug. Indeed, heroin was more effective than codeine in respiratory diseases. It has turned out, however, that repeated administration of heroin results in the development of tolerance and the patients become heroin-addicts soon. In the early 1910s morphine addicts "discovered" the euphorising properties of heroin and this effect was enhanced by intravenous administration. Heroin became a narcotic drug and its abuse began to spread quickly. Restrictions on its production, use and distribution were regulated by international treties. The total ban on heroin production was also proposed. As a result of the strict regulations the production and cosumption of heroin showed a significant decrease after 1931. At the same time the underworld recognized the shortage of heroin and started the illicit production and trafficking. The quantity of heroin seized by law enforcement agencies in the past decades rose gradually. As an indicator of the worldwide heroin market, the quantity of confiscated heroin underwent a tenfold increase since 1970. The paper surveys the most important heroin-producing and trafficking countries. Heroin, prepared in clandestine ("kitchen" or "jungle") laboratories, is diluted ("cut") by every member of the illegal heroin distributing chain, i.e. smugglers, traffickers, dealers and vendors.
... areas west of the Mississippi River. 3 The dark color associated with black tar heroin results from ... have shown some deterioration of the brain’s white matter due to heroin use, which may affect decision- ...
... Badge NIDA TV Spotlight: Heroin in the Twin Cities YouTube embedded video: http://www.youtube-nocookie.com/ ... a highlight on heroin use in the Twin Cities from her June 2013 Report on "Drug Abuse ...
Demaret, I; Lemaître, A; Ansseau, M
Before implementing the TADAM project in Belgium (a heroin-assisted treatment trial), our research team studied the trials in other countries. Since 1994, six randomised controlled trials have been developed using the same treatment model of heroin-assisted treatment (HAT). Each trial concluded that HAT had more efficacy than methadone treatment. We analysed those trials in order to find on which levels patients in a HAT treatment are expected to improve. Improvements appeared after at least six months on the level of street heroin use, (physical and mental) health and criminal behaviour. In the longer term, the continuation of treatment had positive but limited effects on the social level. Due to his higher cost, this treatment should remain a second-line treatment for this special target group: severe heroin addicts, using continuously street heroin in spite of a methadone treatment.
Bradvik, Louise; Frank, Arne; Hulenvik, Per; Medvedeo, Alvaro; Berglund, Mats
Nonfatal heroin overdoses and suicide attempts are both common among heroin addicts, but there is limited knowledge about the association between them. The sample in the present study consisted of 149 regular heroin users in Malmo, Sweden. Out of these 98 had taken an unintentional heroin overdose at some time and 51 had made at least one attempt…
Hosztafi, Sáandor; Fürst, Zsuzsanna
Heroin addiction is one of the most devastating and expensive of public health problems. The most effective treatment is opioid replacement therapy. Replacement of heroin, a short-acting euphoriant with methadone or other opioids that have significantly longer duration of action provides a number of therapeutic benefits. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Opioid-based detoxification is based on the principle of cross-tolerance, in which one opioid is replaced with another one that is slowly tapered. For the treatment of heroin addicts a wide range of psychosocial and pharmacotherapeutic treatments are available; of these, methadone maintenance therapy has the most evidence of benefit. Methadone maintenance reduces and/or eliminates the use of heroin, reduces the death rate and criminality associated with heroin use, and allows patients to improve their health and social productivity. In addition, enrollment in methadone maintenance has the potential to reduce the transmission of infectious diseases associated with heroin injection, such as hepatitis and HIV. The principal effects of methadone maintenance are to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with heroin. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. Buprenorphine which is a long-acting partial agonist was also approved as pharmacotherapy for opioid dependence. Opioid antagonists can reduce heroin self-administration and opioid craving in detoxified addicts. Naltrexone, which is a long-acting competitive antagonist at the opioid receptors, blocks the subjective and objective responses produced by intravenous opioids. Naltrexone is employed to accelerate opioid detoxification by displacing heroin and as a maintenance agent for detoxified formerly heroin-dependent patients who want to
Bautista, Josef Edrik Keith; Merhi, Basma; Gregory, Oliver; Hu, Susie; Henriksen, Kammi; Gohh, Reginald
In this paper we present an interesting case of acute kidney injury and severe metabolic alkalosis in a patient with a history of heavy heroin abuse. Urine microscopy showed numerous broomstick-like crystals. These crystals are also identified in light and electron microscopy. We hypothesize that heroin crystalizes in an alkaline pH, resulting in tubular obstruction and acute kidney injury. Management is mainly supportive as there is no known specific therapy for this condition. This paper highlights the utility of urine microscopy in diagnosing the etiology of acute kidney injury and proposes a novel disease called heroin crystal nephropathy.
Wilson, James Q.; And Others
Argues that most of the underlying assumptions of presently recommended solutions to the problem of heroin addiction are unreasonable, unwarranted, or at least open to more than one interpretation. (DM)
... Families? Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use Hurts Other People Drug ... was addicted to heroin. Here, he describes the drug's effects on his life. Read Deon's story The Prescription ...
... seeds from poppy plants. Prescription opioids , like oxycodone, morphine and codeine, are used as painkillers after an ... a street (illegal) drug made from the opioid morphine. Heroin can be a white or brown powder, ...
Meacham, M.C.; Rudolph, A.E.; Strathdee, S.A.; Rusch, M.L.; Brouwer, K.C.; Patterson, T.L.; Vera, A.; Rangel, G.; Roesch, S.C.
Background Although most people who inject drugs (PWID) in Tijuana, Mexico, primarily inject heroin, injection and non-injection use of methamphetamine and cocaine is common. We examined patterns of polydrug use among heroin injectors to inform prevention and treatment of drug use and its health and social consequences. Methods Participants were PWID residing in Tijuana aged ≥ 18 years who reported heroin injection in the past 6 months and were recruited through respondent driven sampling (n=1025). Latent class analysis was conducted to assign individuals to classes on a probabilistic basis, using four indicators of past 6 month polydrug and polyroute use: cocaine injecting, cocaine smoking or snorting, methamphetamine injecting, methamphetamine smoking or snorting. Latent class membership was regressed onto covariates in a multinomial logistic regression. Results Latent class analyses testing 1, 2, 3, and 4 classes were fit, with the 3-class solution fitting best. Class 1 was defined by predominantly heroin use (50.2%, n=515); class 2 by methamphetamine and heroin use (43.7%, n=448), and class 3 by methamphetamine, cocaine, and heroin use (6.0%, n=62). Bivariate and multivariate analyses indicated a group of methamphetamine and cocaine users that exhibited higher risk sexual practices and lower heroin injecting frequency, and a group of methamphetamine users who were younger and more likely to be female. Conclusions Discrete subtypes of heroin PWID were identified based on methamphetamine and cocaine use patterns. These findings have identified subtypes of heroin injectors who require more tailored interventions to reduce the health and social harms of injecting drug use. PMID:26444185
Elliott, Jennifer C.; Hasin, Deborah S.; Stohl, Malka; Des Jarlais, Don C.
Individuals using illicit drugs are at risk for heavy drinking and infection with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV). Despite medical consequences of drinking with HIV and/or HCV, whether drug users with these infections are less likely to drink is unclear. Using samples of drug users in treatment with lifetime injection use (n = 1309) and non-injection use (n = 1996) participating in a large, serial, cross-sectional study, we investigated the associations between HIV and HCV with abstinence from alcohol. About half of injection drug users (52.8 %) and 26.6 % of non-injection drug users abstained from alcohol. Among non-injection drug users, those with HIV were less likely to abstain [odds ratio (OR) 0.55; adjusted odds ratio (AOR) 0.58] while those with HCV were more likely to abstain (OR 1.46; AOR 1.34). In contrast, among injection drug users, neither HIV nor HCV was associated with drinking. However, exploratory analyses suggested that younger injection drug users with HIV or HCV were more likely to drink, whereas older injection drug users with HIV or HCV were more likely to abstain. In summary, individuals using drugs, especially non-injection users and those with HIV, are likely to drink. Age may modify the risk of drinking among injection drug users with HIV and HCV, a finding requiring replication. Alcohol intervention for HIV and HCV infected drug users is needed to prevent further harm. PMID:26080690
Bazoukis, G; Spiliopoulou, A; Mourouzis, K; Grigoropoulou, P; Yalouris, A
Background: Heroin use by non-injecting routes of administration (snorting, swallowing, “chasing the dragon”) is considered to be safer but is not risk-free for fatal overdose or serious side effects. We report the case of an adolescent who was transferred unconscious to the emergency department after heroin inhalation. Description of the case: A 17-year-old male was transferred to the emergency department unconscious (Glasgow coma scale: 6/15) after heroin inhalation. He was treated with non-rebreather mask and intravenous infusion of naloxone with gradual improvement of consciousness and arterial blood gasses. The chest computed tomography showed signs of acute respiratory distress syndrome. Laboratory exams on the second day of hospitalization showed elevated creatine kinase (CK) and troponin-I levels while his electrocardiography (ECG) showed J-point elevation in V1, V2, and V3 precordial leads. On the second day of hospitalization the pulmonary infiltrates were not present in his chest X-ray while on the eighth day, troponin-I and CK levels were normalized without dynamic ECG changes and the patient was discharged uneventfully. Conclusion: Heroin inhalation may cause severe complications, such as non-cardiogenic pulmonary edema, rhabdomyolysis or myocardial injury. Hippokratia 2016, 20(1): 84-87 PMID:27895451
Rudd, Rose A; Paulozzi, Len J; Bauer, Michael J; Burleson, Richard W; Carlson, Rick E; Dao, Dan; Davis, James W; Dudek, Jennifer; Eichler, Beth Ann; Fernandes, Jessie C; Fondario, Anna; Gabella, Barbara; Hume, Beth; Huntamer, Theron; Kariisa, Mbabazi; Largo, Thomas W; Miles, JoAnne; Newmyer, Ashley; Nitcheva, Daniela; Perez, Beatriz E; Proescholdbell, Scott K; Sabel, Jennifer C; Skiba, Jessica; Slavova, Svetla; Stone, Kathy; Tharp, John M; Wendling, Tracy; Wright, Dagan; Zehner, Anne M
Nationally, death rates from prescription opioid pain reliever (OPR) overdoses quadrupled during 1999-2010, whereas rates from heroin overdoses increased by <50%. Individual states and cities have reported substantial increases in deaths from heroin overdose since 2010. CDC analyzed recent mortality data from 28 states to determine the scope of the heroin overdose death increase and to determine whether increases were associated with changes in OPR overdose death rates since 2010. This report summarizes the results of that analysis, which found that, from 2010 to 2012, the death rate from heroin overdose for the 28 states increased from 1.0 to 2.1 per 100,000, whereas the death rate from OPR overdose declined from 6.0 per 100,000 in 2010 to 5.6 per 100,000 in 2012. Heroin overdose death rates increased significantly for both sexes, all age groups, all census regions, and all racial/ethnic groups other than American Indians/Alaska Natives. OPR overdose mortality declined significantly among males, persons aged <45 years, persons in the South, and non-Hispanic whites. Five states had increases in the OPR death rate, seven states had decreases, and 16 states had no change. Of the 18 states with statistically reliable heroin overdose death rates (i.e., rates based on at least 20 deaths), 15 states reported increases. Decreases in OPR death rates were not associated with increases in heroin death rates. The findings indicate a need for intensified prevention efforts aimed at reducing overdose deaths from all types of opioids while recognizing the demographic differences between the heroin and OPR-using populations. Efforts to prevent expansion of the number of OPR users who might use heroin when it is available should continue.
Bashore, R A; Ketchum, J S; Staisch, K J; Barrett, C T; Zimmermann, E G
Pregnant heroin addicts tend to be younger than nonaddicted pregnant patients, unmarried or separated from spouses, and a disproportionately large number are members of minority ethnic groups. Heroin addiction during pregnancy is associated with several significant medical and obstetrical complications and may result in both acute and chronic abnormalities in neonates. Malnutrition, venereal disease, hepatitis, pulmonary complications, preeclampsia and third-trimester bleeding are the most common maternal complications, while fetal death, intrauterine growth retardation, prematurity and withdrawal symptoms affect the fetus and neonate. There is controversy about treating addicts with methadone during pregnancy. The findings of studies in animals suggest that there may be a long-lasting drug-induced syndrome, characterized by growth retardation, delayed motor development and behavior abnormalities in offspring of heroin-addicted or methadone-treated mothers.
Draus, Paul; Roddy, Juliette; Greenwald, Mark
In this paper, we employ data drawn from economic and ethnographic interviews with Detroit heroin users, as well as other sources, to illustrate the relationship between heroin users’ mobility patterns and urban and suburban environments, especially in terms of drug acquisition and the geography of opportunity. We explore how the “spatial mismatch” (Kain 1968; 1992) between legal work opportunities and central city residents is seemingly reversed in the case of heroin users. We find that while both geographic location and social networks associated with segregation provide central city residents and African Americans with a strategic advantage over white suburbanites in locating and purchasing heroin easily and efficiently, this same segregation effectively focuses the negative externalities of heroin markets in central city neighborhoods. Finally, we consider how the heroin trade reflects and reproduces the segregated post-industrial landscape, and we discuss directions for potential future research on the relationship between ethnic and economic ghettos and regional drug markets. PMID:22679895
Palamar, Joseph J.; Shearston, Jenni A.; Dawson, Eric W.; Mateu-Gelabert, Pedro; Ompad, Danielle C.
Background Nonmedical use of opioids has become increasingly problematic in recent years with increases in overdoses, treatment admissions, and deaths. Use also appears to be contributing to heroin initiation, which has increased in recent years. Further research is needed to examine which adolescents are at highest risk for nonmedical use of opioids and heroin and to explore potential links between nonmedical opioid use and heroin use. Methods Data were analyzed from a nationally representative sample of American high school seniors in the Monitoring the Future study (2009–2013, Weighted N = 67,822). We examined associations between frequency and recency of nonmedical use of opioids and heroin. Sociodemographic correlates of use of each drug were also examined. Results 12.4% of students reported lifetime nonmedical opioid use and 1.2% reported lifetime heroin use. As frequency of lifetime nonmedical opioid use increased, so too did the odds for reporting heroin use, with over three-quarters (77.3%) of heroin users reporting lifetime nonmedical opioid use. Recent (30-day) nonmedical opioid use was a robust risk factor for heroin use and almost a quarter (23.2%) of students who reported using opioids ≥40 times reported lifetime heroin use. Black and Hispanic students were less likely to report nonmedical opioid or heroin use than white students, but they were more likely to report heroin use in absence of nonmedical opioid use. Discussion Recent and frequent nonmedical opioid use are risk factors for heroin use among adolescents. Prevention needs to be targeted to those at highest risk. PMID:26653341
Draus, Paul; Roddy, Juliette; Greenwald, Mark
In this article, the authors used data from economic and ethnographic interviews with heroin users from Detroit, Michigan, as well as other sources, to illustrate the relationship between heroin users' mobility patterns and urban and suburban environments, especially in terms of drug acquisition and the geography of opportunity. The authors found that although geographic location and social networks associated with segregation provided central city residents and African Americans with a strategic advantage over White suburbanites in locating and purchasing heroin easily and efficiently, this same segregation effectively focuses the negative externalities of heroin markets in central city neighborhoods. Finally, the authors consider how the heroin trade reflects and reproduces the segregated post-industrial landscape and discuss directions for future research about the relationship between ethnic and economic ghettos and regional drug markets.
Chen, Shaw-Ji; Liao, Ding-Lieh; Shen, Tsu-Wang; Yang, Hsin-Chou; Chen, Kuang-Chi; Chen, Chia-Hsiang
Heroin addiction is a complex psychiatric disorder with a chronic course and a high relapse rate, which results from the interaction between genetic and environmental factors. Heroin addiction has a substantial heritability in its etiology; hence, identification of individuals with a high genetic propensity to heroin addiction may help prevent the occurrence and relapse of heroin addiction and its complications. The study aimed to identify a small set of genetic signatures that may reliably predict the individuals with a high genetic propensity to heroin addiction. We first measured the transcript level of 13 genes (RASA1, PRKCB, PDK1, JUN, CEBPG, CD74, CEBPB, AUTS2, ENO2, IMPDH2, HAT1, MBD1, and RGS3) in lymphoblastoid cell lines in a sample of 124 male heroin addicts and 124 male control subjects using real-time quantitative PCR. Seven genes (PRKCB, PDK1, JUN, CEBPG, CEBPB, ENO2, and HAT1) showed significant differential expression between the 2 groups. Further analysis using 3 statistical methods including logistic regression analysis, support vector machine learning analysis, and a computer software BIASLESS revealed that a set of 4 genes (JUN, CEBPB, PRKCB, ENO2, or CEBPG) could predict the diagnosis of heroin addiction with the accuracy rate around 85% in our dataset. Our findings support the idea that it is possible to identify genetic signatures of heroin addiction using a small set of expressed genes. However, the study can only be considered as a proof-of-concept study. As the establishment of lymphoblastoid cell line is a laborious and lengthy process, it would be more practical in clinical settings to identify genetic signatures for heroin addiction directly from peripheral blood cells in the future study.
Few heroin addicts get high'' in their dreams. An exploration of the reasons for this failure provides some clues to the conflicts and other problems that retard an addict's progress in therapy. (Author)
Coleman, Jonathan R. I.; Ducci, Francesca; Aliev, Fazil; Newhouse, Stephen J.; Liu, Xiehe; Ma, Xiaohong; Wang, Yingcheng; Collier, David A.; Asherson, Philip; Li, Tao; Breen, Gerome
Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10-7) and BRSK2 (BR serine/threonine 2; p = 4.110−6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field. PMID:27936112
Davey, Jeremy; Richards, Naomi; Lang, Cathryne P.; Davies, Amanda
Young injecting drug users are a particularly vulnerable group for Hepatitis C (HCV) infection. One method for minimising the risk of contraction of Hepatitis C for amphetamine users (not widely explored in the research to date) is through encouraging non-injecting routes of administration (NIROA). Self-report data from 150 young injecting…
... gov/news/fullstory_164350.html Heroin Epidemic Expands Its Grip on America Use of the narcotic grew ... people transition from painkillers to heroin, Martins explained. It is also related to availability, lower cost and ...
... glamorization of “heroin chic” in films, fashion, and music, heroin use can have tragic consequences that extend far beyond its users. Fetal effects, HIV/AIDS, tuberculosis, violence, and crime are all ...
... Resources Law Enforcement Resources Opioids: The Prescription Drug & Heroin Overdose Epidemic Opioids are natural or synthetic chemicals ... in your brain or body. Common opioids include heroin and prescription drugs such as oxycodone, hydrocodone, and ...
Rodovalho, Aurélio Goulart; Fernandes, Inaina Lara; Silva, Graciele Cristina; de Felipe, Rodrigo Lopes; Vera, Ivânia; Gregório, Valéria Duarte; Lucchese, Roselma
Noninjecting illicit drug users (NIDUs) present high risk for HIV infection, due especially to transactional sex. This study aimed to estimate the prevalence and risk factors for transactional sex among NIDUs in the Southwest region of Goiás State, Central Brazil. The prevalence of self-reported transactional sex was 22.8%. Prevalence in women and men was 52.7% and 16.8%, respectively, a significant difference (p < 0.001). Crack use and history of sexually transmitted infections (STI) were risk factors for transactional sex in men. Homelessness, crack use, sex under the influence of drugs, and history of sexual violence were risk factors for transactional sex in women. A high prevalence of transactional sex was observed among NIDUs. This risk behavior may contribute to the high rates of HIV among this population and their social networks and in the general population. PMID:27648467
Hu, X; Kan, J; Yuan, B
In this paper, practical measured X-ray diffraction spectra of heroin and opium are given and the parameters of each diffraction peak of the heroin are listed. The heroin belongs to orthorhombic crystal system; the basic vectors of the primitive cell are: a = 8.003, b = 14.373, c = 16.092 x 10(-10) m. As compared with the standard spectra of pure heroin and sucrose, the main doped additive checked by us, is sugar affirmatively.
DuPont, Robert L.; Greene, Mark H.
Discusses recent trends in heroin addiction in Washington, D.C. In 1969 a comprehensive, multimodal treatment program for addicts was introduced and a major law enforcement commitment was made to reduce the heroin supply. These factors, together with changing community attitudes, may be responsible for a remarkable decline in heroin addiction. (JR)
Raleigh, Michael D; Pentel, Paul R; LeSage, Mark G
The purpose of this study was to evaluate the effects of a morphine-conjugate vaccine (M-KLH) on the acquisition, maintenance, and reinstatement of heroin self-administration (HSA) in rats, and on heroin and metabolite distribution during heroin administration that approximated the self-administered dosing rate. Vaccination with M-KLH blocked heroin-primed reinstatement of heroin responding. Vaccination also decreased HSA at low heroin unit doses but produced a compensatory increase in heroin self-administration at high unit doses. Vaccination shifted the heroin dose-response curve to the right, indicating reduced heroin potency, and behavioral economic demand curve analysis further confirmed this effect. In a separate experiment heroin was administered at rates simulating heroin exposure during HSA. Heroin and its active metabolites, 6-acetylmorphine (6-AM) and morphine, were retained in plasma and metabolite concentrations were reduced in brain in vaccinated rats compared to controls. Reductions in 6-AM concentrations in brain after vaccination were consistent with the changes in HSA rates accompanying vaccination. These data provide evidence that 6-AM is the principal mediator of heroin reinforcement, and the principal target of the M-KLH vaccine, in this model. While heroin vaccines may have potential as therapies for heroin addiction, high antibody to drug ratios appear to be important for obtaining maximal efficacy.
Raleigh, Michael D.; Pentel, Paul R.; LeSage, Mark G.
The purpose of this study was to evaluate the effects of a morphine-conjugate vaccine (M-KLH) on the acquisition, maintenance, and reinstatement of heroin self-administration (HSA) in rats, and on heroin and metabolite distribution during heroin administration that approximated the self-administered dosing rate. Vaccination with M-KLH blocked heroin-primed reinstatement of heroin responding. Vaccination also decreased HSA at low heroin unit doses but produced a compensatory increase in heroin self-administration at high unit doses. Vaccination shifted the heroin dose-response curve to the right, indicating reduced heroin potency, and behavioral economic demand curve analysis further confirmed this effect. In a separate experiment heroin was administered at rates simulating heroin exposure during HSA. Heroin and its active metabolites, 6-acetylmorphine (6-AM) and morphine, were retained in plasma and metabolite concentrations were reduced in brain in vaccinated rats compared to controls. Reductions in 6-AM concentrations in brain after vaccination were consistent with the changes in HSA rates accompanying vaccination. These data provide evidence that 6-AM is the principal mediator of heroin reinforcement, and the principal target of the M-KLH vaccine, in this model. While heroin vaccines may have potential as therapies for heroin addiction, high antibody to drug ratios appear to be important for obtaining maximal efficacy. PMID:25536404
Sánchez, Jesús; Chitwood, Dale D; Koo, Dixie J
The purpose of this paper is to identify characteristics of heroin sniffers likely to shift to injection by evaluating the street addict role theory as an informing theoretical framework to explain transition from heroin sniffing to injection. A nested case-control research design was used to identify 142 heroin sniffers who never had injected a drug (controls) and 146 recently transitioned injection drug users (cases) from a larger study of 600 African-American, Hispanic, and non-Hispanic white men and women who were street recruited from multiple communities known for high drug use. Univariate and multivariate logistic regression analyses were conducted to test the proposed hypotheses derived from the street addict role theory. Our findings partially support the utility of the street addict role perspective as an explanatory framework for understanding the role played by sociocultural factors in the transition to injection. This perspective can help contextualize this HIV-related behavior within the high risk social environment of heroin users. The development of effective prevention strategies for this group should be guided by a comprehensive understanding of the social environment where HIV-related risk behaviors occur.
Saint Onge, Jarron M; Cepeda, Alice; Lee King, Patricia A; Valdez, Avelardo
We used an intersectional minority stress perspective to examine the association between family/cultural stress and mental health among substance-using Mexican-Americans. Employing a unique longitudinal sample of 239 socioeconomically disadvantaged, non-injecting heroin-using Mexican-Americans from San Antonio, Texas, we examined how culturally relevant stressors are related to depression and suicidal ideation. First, we identified depression and suicidal ideation prevalence rates for this disadvantaged sample. Second, we determined how cultural stress is experienced over time using stress trajectories. Third, we evaluated how family/cultural stressors and stress trajectories are related to depression and suicidal ideation outcomes. Results showed high rates of baseline depression (24 %) and suicidal ideation (30 %). We used latent class growth analysis to identify three primary stress trajectories (stable, high but decreasing, and increasing) over three time points during 1 year. We found that the increasing stressors trajectory was associated with higher rates of depression and suicidal ideation, and that stress trajectories had unique relationships with mental illness. We also showed that baseline stressors, sum stressors, and high but decreasing stressors maintained positive associations with mental illness after controlling for baseline depression. Our results highlight the importance of focusing on within-group, culturally specific stressors and addressing both operant and cumulative stressors in the study of mental health for marginalized populations and suggest the importance of early intervention in minimizing stressors.
Pap, Ágota; Hegedűs, Katalin
Drug use can be defined as a kind of self destruction, and it is directly linked to attitudes toward death and suicide occurring in a significant number of users of different narcotics. The aim of the authors was to look for the background of this relationship between drug and death and examine the origin, development, and motives behind heroin overdose based on an analysis of previous studies. It seems clear that pure heroin overdose increased gradually over the years. The fear of the police is the inhibitory factor of the overdose prevention and notification of emergency health care service. Signs of suicide could be the own home as the chosen location for heroin overdose and the presence of partners ("moment of death companion"). Interventions should include simple techniques such as first aid, naloxone administration, resuscitation, prevention of relapse of prisoners and social network extension involving maintenance programs.
Furnham, A; Thomson, L
This study examined the structure and determinants of lay people's implicit theories of heroin addiction. A questionnaire was derived from interviews with lay people about their beliefs and theories of heroin addiction and academic literature on the subject. One hundred and forty-four subjects completed the questionnaire, in which they rated 105 statements about the causes, correlates and cures of heroin addiction. The three parts of the questionnaire were individually factor analyzed and a clear, interpretable factor structure emerged for each. The factors seemed similar to explicit academic theories, but the exception was beliefs about cure, which did not show overall support for the most clinically used models. When the three factor analyses were combined into a single 'higher-order' factor analysis four factors emerged, labelled moralistic, psychosocial, sociocultural and drug treatment, which reflect more or less coherent views on the nature of heroin addiction. Subjects' political beliefs was the greatest (demographic and attitudinal) determinant of lay beliefs in these factors, with experience of addiction, addicts, drugs and age also highly correlated. Vote was the main determinant and best predictor of the four 'higher-order' structured lay theories: right-wing voters emphasizing moralistic and individualistic theory and left-wing voters supporting the psychological and societal ideas. Implications for policy and interventions to addicts of these lay theories are considered.
Uusküla, A; McMahon, J M; Kals, M; Talu, A; Abel-Ollo, K; Rüütel, K; Des Jarlais, D C
The HIV epidemic in Estonia, as with other eastern European countries, is currently concentrated among injection drug users (IDUs). Non-IDUs who have IDU sex partners could serve as a potential bridge in an expanding epidemic. We applied HIV transmission modelling to data collected from non-IDU/IDU heterosexual couples in Kohtla-Järve, Estonia to estimate HIV risk from IDUs to their sex partners based on self-reported sexual behaviors shared by the couple. IDUs and their current main non-injecting sex partners were recruited for an interviewer-administered survey and HIV testing. Bernoulli modelling techniques were applied to estimate the risk of HIV transmission (incidence) among HIV negative non-injecting female partners of male IDUs. The estimated HIV incidence in this population of non-injecting women with only main sexual partners in the last 6 months ranged from 3.24 to 4.94 HIV seroconversions per 100 person years depending on the value used in the models for the per act transmission rate during acute stage infection. Non-IDUs who have IDU sex partners are at high risk for HIV and could serve as a potential bridge to a more generalized epidemic. Whether this might lead to an expansion of the HIV epidemic beyond core groups in Estonia or other Eastern European countries warrants closer study.
Collins, Courtney L C; Kerr, Thomas; Tyndall, Mark W; Marsh, David C; Kretz, Patricia S; Montaner, Julio S; Wood, Evan
Many cities are experiencing ongoing infectious disease epidemics and substantial community harm as a result of illicit drug use. In an effort to reduce these public order and public health concerns, consideration has been given to the opening in Vancouver of a safer smoking facility (SSF). The present review was conducted to examine if there is a rationale to support the evaluation of a SSF in the Canadian context. Available evidence suggests that conventional drug control strategies are insufficient to address the health and community harms of non-injection drug use, and that the public order benefits of supervised injection facilities may be relevant to SSFs. In addition, there is persuasive evidence to suggest there is potential for blood-borne disease transmission through the sharing of smoking paraphernalia, and the potential for SSFs to address this concern is a pressing public health question. Also relevant to this topic are interventions to prevent transition into injection drug use, and SSFs may also be evaluated as a potential strategy to address this concern.
Monodispersed CdS nanocrystals with controllable shape and phase have been successfully synthesized in this study by adding cationic surfactant in noninjection synthesis system. With the increase of the amount of cetyltrimethylammonium chloride (CTAC) added, the shape of the CdS nanocrystals changed from spherical to multi-armed, and the phase changed from zinc-blende to wurtzite. It was found that halide ion Cl- plays a key role in the transformation, and other halide ions such as Br- can also induce similar transformation. We proposed that the strong binding between Cd2+ and halide ions reduced the reactivity of the precursors, decreased the nuclei formed in the nucleation stage, and led to the high concentration of precursor in the growth stage, resulting in the increase of size and phase transformation of CdS nanocrystals. In addition, it was found that the multi-armed CdS nanocrystals lost quantum confinement effect because of the increase of the size with the increase of the concentration of CTAC. PMID:21711888
This paper uses Australian heroin seizure data, along with estimates of the size of the Australian heroin market to evaluate the impact of drug law enforcement on the 2001 Australian heroin shortage from the percentage of the market seized. It also critically examines international heroin production trends and published reports on the causes of the Australian heroin shortage. Its conclusion is that previous studies may have overstated the success of drug law enforcement and that the most likely explanation for Australia's 2001 heroin shortage was a significant decline in heroin production world-wide, due to a general move away from heroin production in the countries of Southeast Asia and the prohibition on opium growing by the Taliban regime in Afghanistan.
Stoltman, Jonathan J K; Woodcock, Eric A; Lister, Jamey J; Lundahl, Leslie H; Greenwald, Mark K
Delay discounting (DD) refers to how rapidly an individual devalues goods based on delays to receipt. DD usually is considered a trait variable but can be state dependent, yet few studies have assessed commodity valuation at short, naturalistically relevant time intervals that might enable state-dependent analysis. This study aimed to determine whether drug-use impulsivity and intelligence influence heroin DD at short (ecologically relevant) delays during two pharmacological states (heroin satiation and withdrawal). Out-of-treatment, intensive heroin users (n = 170; 53.5% African American; 66.7% male) provided complete DD data during imagined heroin satiation and withdrawal. Delays were 3, 6, 12, 24, 48, 72, and 96 hours; maximum delayed heroin amount was thirty $10 bags. Indifference points were used to calculate area under the curve (AUC). We also assessed drug-use impulsivity (subscales from the Impulsive Relapse Questionnaire [IRQ]) and estimated intelligence (Shipley IQ) as predictors of DD. Heroin discounting was greater (smaller AUC) during withdrawal than satiation. In regression analyses, lower intelligence and IRQ Capacity for Delay as well as higher IRQ Speed (to return to drug use) predicted greater heroin discounting in the satiation condition. Lower intelligence and higher IRQ Speed predicted greater discounting in the withdrawal condition. Sex, race, substance use variables, and other IRQ subscales were not significantly related to the withdrawal or satiation DD behavior. In summary, heroin discounting was temporally rapid, pharmacologically state dependent, and predicted by drug-use impulsivity and estimated intelligence. These findings highlight a novel and sensitive measure of acute DD that is easy to administer.
Stoltman, Jonathan J.K.; Woodcock, Eric A.; Lister, Jamey J.; Lundahl, Leslie H.; Greenwald, Mark K.
Delay discounting (DD) refers to how rapidly an individual devalues goods based on delays to receipt. DD usually is considered a trait variable but can be state-dependent; yet few studies have assessed commodity valuation at short, naturalistically relevant time intervals that might enable state-dependent analysis. This study aimed to determine whether drug-use impulsivity and intelligence influence heroin DD at short (ecologically relevant) delays during two pharmacological states (heroin satiation and withdrawal). Out-of-treatment, intensive heroin users (n=170; 53.5% African-American; 66.7% male) provided complete DD data during imagined heroin satiation and withdrawal. Delays were 3, 6, 12, 24, 48, 72, and 96 hours; maximum delayed heroin amount was thirty $10 bags. Indifference points were used to calculate area under the curve (AUC). We also assessed drug-use impulsivity (subscales from the Impulsive Relapse Questionnaire, IRQ) and estimated intelligence (Shipley IQ) as predictors of DD. Heroin discounting was greater (smaller AUC) during withdrawal than satiation. In regression analyses, lower intelligence and IRQ Capacity for Delay as well as higher IRQ Speed (to return to drug use) predicted greater heroin discounting in the satiation condition. Lower intelligence and higher IRQ Speed predicted greater discounting in the withdrawal condition. Sex, race, substance use variables, and other IRQ subscales were not significantly related to the withdrawal or satiation DD behavior. In summary, heroin discounting was temporally rapid, pharmacological state-dependent, and predicted by drug-use impulsivity and estimated intelligence. These findings highlight a novel and sensitive measure of acute DD that is easy to administer. PMID:26595426
Hancock, Dana B.; Levy, Joshua L.; Gaddis, Nathan C.; Glasheen, Cristie; Saccone, Nancy L.; Page, Grier P.; Hulse, Gary; Wildenauer, Dieter; Kelty, Erin; Schwab, Sibylle; Degenhardt, Louisa; Martin, Nicholas G.; Montgomery, Grant W.; Attia, John; Holliday, Elizabeth G.; McEvoy, Mark; Scott, Rodney J.; Bierut, Laura J.; Nelson, Elliot C.; Kral, Alex; Johnson, Eric O.
Background No opioid receptor, mu 1 (OPRM1) gene polymorphisms, including the functional single nucleotide polymorphism (SNP) rs1799971, have been conclusively associated with heroin/other opioid addiction, despite their biological plausibility. We used evidence of polymorphisms altering OPRM1 expression in normal human brain tissue to nominate and then test associations with heroin addiction. Methods We tested 103 OPRM1 SNPs for association with OPRM1 mRNA expression in prefrontal cortex from 224 European Americans and African Americans of the BrainCloud cohort. We then tested the 16 putative cis-quantitative trait loci (cis-eQTL) SNPs for association with heroin addiction in the Urban Health Study and two replication cohorts, totaling 16,729 European Americans, African Americans, and Australians of European ancestry. Results Four putative cis-eQTL SNPs were significantly associated with heroin addiction in the Urban Health Study (smallest P=8.9×10−5): rs9478495, rs3778150, rs9384169, and rs562859. Rs3778150, located in OPRM1 intron 1, was significantly replicated (P=6.3×10−5). Meta-analysis across all case-control cohorts resulted in P=4.3×10−8: the rs3778150-C allele (frequency=16%-19%) being associated with increased heroin addiction risk. Importantly, the functional SNP allele rs1799971-A was associated with heroin addiction only in the presence of rs3778150-C (P=1.48×10−6 for rs1799971-A/rs3778150-C and P=0.79 for rs1799971-A/rs3778150-T haplotypes). Lastly, replication was observed for six other intron 1 SNPs which had prior suggestive associations with heroin addiction (smallest P=2.7×10−8 for rs3823010). Conclusions Our findings show that common OPRM1 intron 1 SNPs have replicable associations with heroin addiction. The haplotype structure of rs3778150 and nearby SNPs may underlie the inconsistent associations between rs1799971 and heroin addiction. PMID:25744370
Wang, Ji-fen; Yu, Jing; Guo, Xin; Sun, Xing-long; Wang, Ding-fang
The method of rapid analysis of added ingredients in heroin was studied in the present paper. Adding sucrose, fructose, glucose, starch, caffeine and phenacetin to heroin with a certain percentage, the changes in the infrared spectrum with the concentration of heroin increasing and the detection limit of the additives were determined. Whether or not heroin can be detected in the sample with high concentration of added ingredients was studied using Raman spectroscopy. Similarly, in high purity of heroin, whether or not Raman spectroscopy can detect the added ingredients was tested. Through systematic experiments, the results showed that: using infrared spectroscopy and Raman spectroscopy to test the added ingredients of heroin is a rapid and effective method. Each has both advantages and disadvantages. We should select the appropriate method according to the actual cases.
Hancock, Dana B.; Levy, Joshua L.; Gaddis, Nathan C.; Glasheen, Cristie; Saccone, Nancy L.; Page, Grier P.; Bierut, Laura J.; Kral, Alex H.; Johnson, Eric O.
Heroin addiction is heritable, but few specific genetic variants have been reproducibly associated with this disease. The zinc finger protein 804A (ZNF804A) gene is a biologically plausible susceptibility gene for heroin addiction, given its function as a transcription factor in human brain. Novel associations of two common ZNF804A single nucleotide polymorphisms (SNPs), rs7597593 and rs1344706, with heroin addiction have been reported in Han Chinese. Both SNPs have also been implicated for regulating ZNF804A expression in human brain, including the addiction-relevant dorsolateral prefrontal cortex. In this independent replication study, we tested the rs7597593 and rs1344706 SNP genotypes and their corresponding haplotypes for association with heroin addiction using cases drawn from the Urban Health Study and population controls: total N=10,757 (7,095 European Americans and 3,662 African Americans). We independently replicated both ZNF804A SNP associations in European Americans: the rs7597593-T (P=0.016) and rs1344706-A (P=0.029) alleles both being associated with increased risk of heroin addiction, consistent with the prior report. Neither SNP was associated in African Americans alone, but meta-analysis across both ancestry groups resulted in significant associations for rs1344706-A (P=0.016, odds ratio [95% confidence interval] = 1.13 [1.02–1.25]) and its haplotype with rs7597593-T (P=0.0067, odds ratio [95% confidence interval] = 1.16 [1.04–1.29]). By demonstrating consistent associations across independent studies and diverse ancestry groups, our study provides evidence that these two ZNF804A SNPs and their risk haplotype are among the few replicable genetic associations with heroin addiction. PMID:26382569
Rook, Elisabeth J; Huitema, Alwin D R; van den Brink, Wim; Hillebrand, Michel J X; van Ree, Jan M; Beijnen, Jos H
The aim of this study was to investigate the use of illicit heroin among patients in a heroin-assisted treatment program. In this program, pharmaceutical-grade heroin was administered to heroin-addicted patients. Monitoring of illicit heroin use was considered important for the evaluation of this treatment program. Acetylcodeine and codeine, common adulterants of "street" heroin, were used as markers for illicit heroin. A liquid chromatography method with tandem mass spectrometric detection (LC-MS-MS) was developed, for quantitative analysis of heroin and methadone, their metabolites, and the simultaneous detection of acetylcodeine. One-hundred patients in a heroin-assisted treatment program were screened for acetylcodeine in plasma. Furthermore, patients were interviewed about illicit heroin use, and they were tested for alcohol and cocaine use. In plasma samples of 16% of the patients, acetylcodeine was detected. Overall agreement between self-report and plasma samples was 95% (kappa: 0.81). Patients who tested positive for acetylcodeine had visited the outpatients' clinics significantly less frequently than the patients who tested negative. Alcohol and cocaine use was more common in patients who tested positive for acetylcodeine. Illicit heroin use was observed in a limited percentage of patients. Overall agreement between self-report and markers of illicit heroin use was good.
Background Heroin coming into the United States historically comes from three widely dispersed geographical regions: Southwest Asia, Southeast Asia and Mexico. A fourth source of US-bound heroin, from Colombia, originated in the early 1990s. The fact that the four heroin sources produce differing morphologies and qualities of heroin has not been critically examined. In addition, it is not well established how the contemporary competing dynamics of interdiction, or restriction of heroin flows across international boundaries, and neoliberal, e.g., global expansion of free trade, policies are affecting heroin markets. This paper will highlight changes in the US heroin market, including source trends, the political economy of the now dominant source and the resultant effects on the heroin risk environment by US region. Methods Using a structural and historical framework this paper examines two decades of secondary data sources, including government and drug control agency documents, on heroin flows together with published work on the political and economic dynamics in Latin America. Results Co-occurring neoliberal economic reforms may have contributed to paradoxical effects of US/Colombian interdiction efforts. Since entering the US market, heroin from Colombia has been distributed at a much higher quality and lower retail price. An increasingly exclusive market has developed with Mexican and Colombian heroin gaining market share and displacing Asian heroin. These trends have had dramatic effects on the risk environment for heroin consumers. An intriguing factor is that different global sources of heroin produce substantially different products. Plausible associations exist between heroin source/form and drug use behaviours and harms. For example, cold water-soluble powdered heroin (sources: Asia, Colombia) may be associated with higher HIV prevalence in the US, while low-solubility “black tar” heroin (BTH; source: Mexico) is historically used in areas with reduced
Winek, C L; Wahba, W W; Rozin, L
Death due to heroin overdose and/or rapid injection of heroin is a frequent occurrence among opioid addicts. We present an unusual case of heroin fatality due to the injection of the drug in the penis. Blood, urine, bile, and vitreous humor concentrations of morphine were 0.68, 0.49, 0.32 and 0.062 microg/ml, respectively. Ethanol was detected at concentrations of 104, 124, 106, and 94 mg/dl in the blood, urine, bile, and vitreous humor, respectively. The cause of death was determined to be due to heroin and ethanol intoxication.
Bourgois, Philippe; Schonberg, Jeff
Ten years of participant-observation fieldwork and photography among a multi-ethnic social network of homeless heroin injectors and crack smokers in California reveal hierarchical interpersonal relations between African Americans, whites and Latinos despite the fact that they all share a physical addiction to heroin and live in indigent poverty in the same encampments. Focusing on tensions between blacks and whites, we develop the concept of ‘ethnicized habitus’ to understand how divisions drawn on the basis of skin color are enforced through everyday interaction to produce ‘intimate apartheid’ in the context of physical proximity and shared destitution. Specifically, we examine how two components of ethnic habitus are generated. One is a simple technique of the body, a preference for intravenous versus intramuscular or subcutaneous heroin injection. The second revolves around income-generation strategies and is more obviously related to external power constraints. Both these components fit into a larger constellation of ethnic distinction rooted in historically entrenched political, economic and ideological forces. An understanding of the generative forces of the ethnic dimensions of habitus allows us to recognize how macro-power relations produce intimate desires and ways of being that become inscribed on individual bodies and routinized in behavior. These distinctions are, for the most part, interpreted as natural attributes of genetics and culture by many people in the United States, justifying a racialized moral hierarchy. PMID:19777125
Heroin is prepared by treating morphine with acetyl chloride or acetic anhydride. It is a simple reaction and the yields are generally quantitative. Nowadays the whole process is illegal. Morphine is the major alkaloid present in the opium poppy. Opium is manufactured illicitly then morphine is extracted from it in clandestine laboratories. Numerous studies were carried out on heroin to investigate its rate of hydrolysis. It has been shown that heroin is rapidly deacylated in aqueous solution at alkaline or acidic pH to form 6-acethylmorphine and finally, to morphine. Heroin also rapidly decomposes in biological medium yielding first 6-acetylmorphine and then morphine. Hydrolysis can be performed in blood and in tissue homogenates. Heroin can be administered by several routes. Smoking and intravenous administration are preferred, but intranasal, intramuscular and subcutaneous administration are also common. Recently, there has been a shift in heroin use patterns from injection to sniffing and smoking. Sharing of the injection equipment can result in several severe infectious diseases, such as AIDS, hepatitis B and C. Soon after administration, heroin metabolizes to 6-acetylmorphine and morphine. Most of the pharmacological activities of heroin are due to these active metabolites. Therefore, knowledge of distribution of 6-acetylmorphine and morphine is essential to understand pharmacological properties of heroin. Heroin, which is relatively nonpolar compound compared with morphine, has high lipid solubility facilitating rapid absorption from the bloodstream and passage through the blood-brain barrier. When heroin is administered by intravenously the drug takes 10 s to reach the brain i.e. pharmacological effects appear quickly.
Heroin beckons like the sweet seductive calls of Ulysses' sirens. The alluring nectar of the poppy seed, once experienced is not easy to escape. The greed for pleasure is endless. Gratification begets gratification. This paper explores issues and complications of treatment intervention in heroin addiction. The author is a general practitioner with 25 years experience and special interest in substance abuse medicine.
Gordon, Susan M.
The rise in heroin use in the 1990s is attributed to an increase in snorting and smoking heroin as opposed to earlier epidemics that relied on intravenous use. An increase in purity has also added to the addiction problem. The trend towards use by young people was confirmed by the 2000 Monitoring the Future Study, which reported that 10.6% of high…
Branson, Christopher E.; Clemmey, Philip; Harrell, Paul; Subramaniam, Geetha; Fishman, Marc
This study examined posttreatment patterns of polysubstance use and heroin relapse in a sample of 43 adolescents (ages 14-20) entering short-term residential treatment for primary heroin use. At 12-month follow-up, youths that achieved heroin abstinence (N = 19) were significantly less likely than youths that relapsed to heroin (N = 24) to endorse…
Does addiction to heroin undermine the voluntariness of heroin addicts' consent to take part in research which involves giving them free and legal heroin? This question has been raised in connection with research into the effectiveness of heroin prescription as a way of treating dependent heroin users. Participants in such research are required to give their informed consent to take part. Louis C. Charland has argued that we should not presume that heroin addicts are competent to do this since heroin addiction by nature involves a loss of ability to resist the desire for heroin. In this article, I argue that Charland is right that we should not presume that heroin addicts are competent to consent, but not for the reason he thinks. In fact, as Charland's critics correctly point out, there is plenty of evidence showing that heroin addicts can resist their desire for heroin. These critics are wrong, however, to conclude from this that we should presume that heroin addicts are competent to give their voluntary consent. There are, I shall argue, other conditions associated with heroin addiction that might constrain heroin addicts' choice in ways likely to undermine the voluntariness of their consent. In order to see this, we need to move beyond the focus on the addicts' desires for heroin and instead consider the wider social and psychological circumstances of heroin addiction, as well as the effects these circumstances may have on the addicts' beliefs about the nature of their options.
Roddy, Juliette; Steinmiller, Caren L; Greenwald, Mark K
Semi-structured interviews were used to assess behavioral economic drug demand in heroin dependent research volunteers. Findings on drug price, competing purchases, and past 30-day income and consumption, established in a previous study, are replicated. We extended these findings by having participants indicate whether hypothetical environmental changes would alter heroin purchasing. Participants (n = 109) reported they would significantly (p < .005) decrease heroin daily purchasing amounts (DPA) from past 30-day levels (M = $60/day) if: (a) they encountered a 33% decrease in income (DPA = $34), (b) family/friends no longer paid their living expenses (DPA = $32), or (c) they faced four-fold greater likelihood of police arrest at their purchasing location (DPA = $42). Participants in higher income quartiles (who purchase more heroin) show greater DPA reductions (but would still buy more heroin) than those in lower income quartiles. For participants receiving government aid (n = 31), heroin purchasing would decrease if those subsidies were eliminated (DPA = $28). Compared to participants whose urine tested negative for cocaine (n = 31), cocaine-positive subjects (n = 32) reported more efficient heroin purchasing, that is, they live closer to their primary dealer; are more likely to have heroin delivered or walk to obtain it (and less likely to ride the bus), thus reducing purchasing time (52 vs. 31 min, respectively); and purchase more heroin per episode. These simulation results have treatment and policy implications: Daily heroin users' purchasing repertoire is very cost-effective, more so for those also using cocaine, and only potent environmental changes (income reductions or increased legal sanctions) may impact this behavior.
Walsh, H; Martins, S; O'Neill, E E; Kerry, J P; Kenny, T; Ward, P
The aim was to investigate the effect of different cooking regimes on the cook yield and tenderness of non-injected and brine injected (0.5% residual NaCl) bovine M. triceps brachii caput longum (TB), M. supraspinatus (SP) and M. pectoralis profundus (PP). Injected and non-injected TB, SP and PP muscle sections (400 g) were (a) conventionally oven cooked to 72 degrees C or cooked slowly (using a Delta10 programme) to 72 degrees C or (b) cooked in a water bath to 72 degrees C or cooked in a water bath to 55 degrees C and held at this temperature for 2 h before heating to 72 degrees C. In addition, injected PP muscle sections were oven cooked to 69 degrees C and held at this temperature for up to 12 h. Slow cooking using a Delta10 programme had no significant (P<0.05) effect on WBSF values of injected or non-injected SP and TB muscles but significantly (P<0.05) decreased the WBSF values of injected and non-injected PP muscles when compared to conventional cooking. Slow cooking significantly (P<0.05) increased % cook yield of injected PP, SP and TB muscles. Staged cooking significantly (P<0.05) decreased the WBSF values and had no significant effect on sensory tenderness ratings of non-injected TB, SP and PP muscles and injected PP muscles. Staged cooked injected or non-injected PP, SP and TB muscles had lower % cook yield values than those cooked straight to 72 degrees C. Increasing the cooking time of injected PP muscles at 69 degrees C to 8 and 12 h decreased % cook yield, decreased WBSF values and increased sensory tenderness ratings. It also alleviated the problem of residual chewiness which was evident in PP muscles cooked using the other regimes.
Hancock, D B; Levy, J L; Gaddis, N C; Glasheen, C; Saccone, N L; Page, G P; Bierut, L J; Kral, A H; Johnson, E O
Heroin addiction is heritable, but few specific genetic variants have been reproducibly associated with this disease. The zinc finger protein 804A (ZNF804A) gene is a biologically plausible susceptibility gene for heroin addiction, given its function as a transcription factor in human brain. Novel associations of two common ZNF804A single nucleotide polymorphisms (SNPs), rs7597593 and rs1344706, with heroin addiction have been reported in Han Chinese. Both SNPs have also been implicated for regulating ZNF804A expression in human brain, including the addiction-relevant dorsolateral prefrontal cortex. In this independent replication study, we tested the rs7597593 and rs1344706 SNP genotypes and their corresponding haplotypes for association with heroin addiction using cases drawn from the Urban Health Study and population controls: total N = 10 757 [7095 European Americans (EAs) and 3662 African Americans (AAs)]. We independently replicated both ZNF804A SNP associations in EAs: the rs7597593-T (P = 0.016) and rs1344706-A (P = 0.029) alleles both being associated with increased risk of heroin addiction, consistent with the prior report. Neither SNP was associated in AAs alone, but meta-analysis across both ancestry groups resulted in significant associations for rs1344706-A [P = 0.016, odds ratio (95% confidence interval) = 1.13 (1.02-1.25)] and its haplotype with rs7597593-T [P = 0.0067, odds ratio (95% confidence interval) = 1.16 (1.04-1.29)]. By showing consistent associations across independent studies and diverse ancestry groups, our study provides evidence that these two ZNF804A SNPs and their risk haplotype are among the few replicable genetic associations with heroin addiction.
Koski, Anniina; Bramante, Simona; Kipar, Anja; Oksanen, Minna; Juhila, Juuso; Vassilev, Lotta; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli
In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients. PMID:26156245
Gallagher, J; McKeganey, N
There have been recent calls from within both Scotland and England for the wider prescription of heroin to heroin addicts as a way of coping with our burgeoning drug problem and as a route to reducing drug related criminality. But how feasible is heroin prescribing in this context? This paper considers some of the existing research evidence relating to heroin prescribing and looks also at the ethics and practicalities of prescribing heroin to heroin addicts in Scotland. We conclude that whilst the evidence on the benefits of heroin prescribing is far from clear cut there is a case for mounting a Scottish trial of heroin prescribing. Such a trial would need to be tightly controlled and rigorously evaluated. It would need to show that heroin prescribing was associated not only with a comparable level of harm reduction, as methadone prescribing, but that it was also an effective route towards drug users' eventual recovery and drug cessation.
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Platt, Jerome J.
A carefully controlled comparison of the personality characteristics of heroin addict (n=27) and nonaddict (n=20) offenders was carried out so as to avoid methodological problems associated with earlier studies. (Editor)
... Families? Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use Hurts Other People Drug ... was addicted to heroin. Here, he describes the drug's effects on his life. Read Deon's story About the ...
Lefaucheur, Romain; Lebas, Axel; Gérardin, Emmanuel; Grangeon, Lou; Ozkul-Wermester, Ozlem; Aubier-Girard, Carole; Martinaud, Olivier; Maltête, David
A 29-year-old man was admitted for acute cognitive impairment. Three weeks earlier, he had been admitted for coma due to sniffed heroin abuse responsive to naloxone infusion. At admission, the patient presented with apraxia, severe memory impairment and anosognosia. Brain MRI revealed symmetric hyperintensities of supratentorial white matter, sparing brainstem and cerebellum, on FLAIR and B1000 sequences. Four months later, repeated neuropsychological assessment revealed dramatic improvement of global cognitive functions. Toxic leucoencephalopathy excluding the cerebellum and brainstem is a rare complication of heroin abuse, and seems to concern especially patients that use heroin by sniff or injection. In these patients, cognitive troubles are predominant, prognosis seems better and infratentorial brain structures can be spared. In conclusion, our observation emphasizes that heroin-induced encephalopathy can have a favourable outcome and that imaging and clinical patterns can indicate the mode of drug administration.
Black, Heather; Chapman, Ann; Inverarity, Donald; Sinha, Satyajit
In 2010, during an outbreak of anthrax affecting people who inject drugs, a heroin user aged 37 years presented with soft tissue infection. He subsequently was found to have anthrax. We describe his management and the difficulty in distinguishing anthrax from non-anthrax lesions. His full recovery, despite an overall mortality of 30% for injectional anthrax, demonstrates that some heroin-related anthrax cases can be managed predominately with oral antibiotics and minimal surgical intervention.
... En Español Making a Change – Your Personal Plan Hot Topics Am I in a Healthy Relationship? Who ... restlessness muscle and bone pain diarrhea vomiting alternating hot and cold flashes with goosebumps kicking movements severe ...
Degenhardt, Louisa; Day, Carolyn; Gilmour, Stuart; Hall, Wayne
Heroin use causes considerable harm to individual users including dependence, fatal and nonfatal overdose, mental health problems, and blood borne virus transmission. It also adversely affects the community through drug dealing, property crime and reduced public amenity. During the mid to late 1990s in Australia the prevalence of heroin use increased as reflected in steeply rising overdose deaths. In January 2001, there were reports of an unpredicted and unprecedented reduction in heroin supply with an abrupt onset in all Australian jurisdictions. The shortage was most marked in New South Wales, the State with the largest heroin market, which saw increases in price, dramatic decreases in purity at the street level, and reductions in the ease with which injecting drug users reported being able to obtain the drug. The abrupt onset of the shortage and a subsequent dramatic reduction in overdose deaths prompted national debate about the causes of the shortage and later international debate about the policy significance of what has come to be called the "Australian heroin shortage". In this paper we summarise insights from four years' research into the causes, consequences and policy implications of the "heroin shortage".
Castrillo, Fernando Montero; Bourgois, Philippe; Mars, Sarah; Karandinos, George; Unick, Jay; Ciccarone, Daniel
Background We hypothesize that the location of highly segregated Hispanic and in particular Puerto Rican neighborhoods can explain how Colombian-sourced heroin, which is associated with a large-scale decade long decline in heroin price and increase in purity, was able to enter and proliferate in the US. Methods Our multidisciplinary analysis quantitatively operationalizes participant-observation ethnographic hypotheses informed by social science theory addressing complex political economic, historical, cultural and social processes. First, we ethnographically document the intersection of structural forces shaping Philadelphia's hypersegregated Puerto Rican community as a regional epicenter of the US heroin market. Second, we estimate the relationship between segregation and: a) the entry of Colombian heroin into the US, and b) the retail price per pure gram of heroin in 21 Metropolitan Statistical Areas. Results Ethnographic evidence documents how poverty, historically-patterned antagonistic race relations, an interstitial socio-cultural political and geographic linkage to both Caribbean drug trafficking routes and the United States and kinship solidarities combine to position poor Puerto Rican neighborhoods as commercial distribution centers for high quality, low cost Colombian heroin. Quantitative analysis shows that heroin markets in cities with highly segregated Puerto Rican communities were more quickly saturated with Colombian-sourced heroin. The level of Hispanic segregation (specifically in cities with a high level of Puerto Rican segregation) had a significant negative association with heroin price from 1990–2000. By contrast, there is no correlation between African-American segregation and Colombian-sourced heroin prevalence or price. Discussion Our iterative mixed methods dialogue allows for the development and testing of complex social science hypotheses and reduces the limitations specific to each method used in isolation. We build on prior research
Etcheverry, M Florencia; Lum, Paula J; Evans, Jennifer L; Sanchez, Emilia; de Lazzari, Elisa; Mendez-Arancibia, Eva; Sierra, Ernesto; Gatell, José M; Page, Kimberly; Joseph, Joan
Being able to recruit high-risk volunteers who are also willing to consider future participation in vaccine trials are critical features of vaccine preparedness studies. We described data from two cohorts of injection- and non-injection drug users in Barcelona, Spain [Red Cross centre] and in San Francisco, USA, [UFO-VAX study] at high risk of HIV/HCV infection to assess behaviour risk exposure and willingness to participate in future preventive HIV vaccine trials. We successfully identified drug-using populations that would be eligible for future HIV vaccine efficacy trials, based on reported levels of risk during screening and high levels of willingness to participate. In both groups, Red Cross and UFO-VAX respectively, HCV infection was highly prevalent at baseline (41% and 34%), HIV baseline seroprevalence was 4.2% and 1.5%, and high levels of willingness were seen (83% and 78%).
Etcheverry, M. Florencia; Lum, Paula J.; Evans, Jennifer L.; Sanchez, Emilia; de Lazzari, Elisa; Mendez-Arancibia, Eva; Sierra, Ernesto; Gatell, José M.; Page, Kimberly; Joseph, Joan
Being able to recruit high-risk volunteers who are also willing to consider future participation in vaccine trials are critical features of vaccine preparedness studies. We described data from two cohorts of injection- and non-injection drug users in Barcelona, Spain [Red Cross centre] and in San Francisco, USA, [UFO-VAX study] at high risk of HIV/HCV infection to assess behaviour risk exposure and willingness to participate in future preventive HIV vaccine trials. We successfully identified drug-using populations that would be eligible for future HIV vaccine efficacy trials, based on reported levels of risk during screening and high levels of willingness to participate. In both groups, Red Cross and UFO-VAX respectively, HCV infection was highly prevalent at baseline (41% and 34%), HIV baseline seroprevalence was 4.2% and 1.5%, and high levels of willingness were seen (83% and 78%). PMID:21241735
Mital, Sasha; Miles, Gillian; McLellan-Lemal, Eleanor; Muthui, Mercy; Needle, Richard
Introduction While relatively rare events, abrupt disruptions in heroin availability have a significant impact on morbidity and mortality risk among those who are heroin dependent. A heroin shortage occurred in Coast Province, Kenya from December 2010 to March 2011. This qualitative analysis describes the shortage events and consequences from the perspective of heroin users, along with implications for health and other public sectors. Methods As part of a rapid assessment, 66 key informant interviews and 15 focus groups among heroin users in Coast Province, Kenya were conducted. A qualitative thematic analysis was undertaken in Atlas.ti. to identify salient themes related to the shortage. Results Overall, participant accounts were rooted in a theme of desperation and uncertainty, with emphasis on six sub-themes: (1) withdrawal and strategies for alleviating withdrawal, including use of medical intervention and other detoxification attempts; (2) challenges of dealing with unpredictable drug availability, cost, and purity; (3) changes in drug use patterns, and actions taken to procure heroin and other drugs; (4) modifications in drug user relationship dynamics and networks, including introduction of risky group-level injection practices; (5) family and community response; and (6) new challenges with the heroin market resurgence. Conclusions The heroin shortage led to a series of consequences for drug users, including increased risk of morbidity, mortality and disenfranchisement at social and structural levels. Availability of evidence-based services for drug users and emergency preparedness plans could have mitigated this impact. PMID:26470646
Toprak, Sadik; Cetin, Ilhan
Turkey has continuously experienced problems with abuse of, and addiction to, opium derivatives. In this study, we analyzed the relationship between heroin overdose deaths and the characteristics of seized opium derivatives. Data were gathered from the Council of Forensic Medicine of the Ministry of Justice in Istanbul from 1990 to 2000. There were 636 heroin-related deaths during this period, 595 of which were classified as heroin overdose deaths. Mean crude and weighted heroin purities remained relatively constant and were calculated to be 46% (57-34%) and 51% (39-59%), respectively. The weight of heroin and the number of heroin seizures, but not the heroin purity, were significantly associated with the number of heroin-related deaths. Prevention strategies are needed to reduce the number of deaths caused by overdoses in countries situated on drug trafficking routes. These strategies should focus on drug trafficking, by providing increased levels of, and support for, law enforcement, stopping the supply of precursor chemicals, and combating corruption among border officials.
Lyons, Tara; Kerr, Thomas; Duff, Putu; Feng, Cindy; Shannon, Kate
Despite increasing evidence of enhanced HIV risk among sexual minority populations, and sex workers (SWs) in particular, there remains a paucity of epidemiological data on the risk environments of SWs who identify as lesbian or bisexual. Therefore, this short report describes a study that examined the individual, interpersonal and structural associations with lesbian or bisexual identity among SWs in Vancouver, Canada. Analysis drew on data from an open prospective cohort of street and hidden off-street SWs in Vancouver. Bivariate and multivariable logistic regressions were used to examine the independent relationships between individual, interpersonal, work environment and structural factors and lesbian or bisexual identity. Of the 510 individuals in our sample, 95 (18.6%) identified as lesbian or bisexual. In multivariable analysis, reporting non-injection drug use in the last six months (adjusted odds ratio [AOR] = 2.89; 95% confidence intervals [CI] = 1.42, 5.75), youth ≤24 years of age (AOR = 2.43; 95% CI = 1.24, 4.73) and experiencing client-perpetrated verbal, physical and/or sexual violence in the last six months (AOR = 1.85; 95% CI = 1.15, 2.98) remained independently associated with lesbian/bisexual identity, after adjusting for potential confounders. The findings demonstrate an urgent need for evidence-based social and structural HIV prevention interventions. In particular, policies and programmes tailored to lesbian and bisexual youth and women working in sex work, including those that prevent violence and address issues of non-injection stimulant use are required.
Walter, Marc; Denier, Niklaus; Gerber, Hana; Schmid, Otto; Lanz, Christian; Brenneisen, Rudolf; Riecher-Rössler, Anita; Wiesbeck, Gerhard A; Scheffler, Klaus; Seifritz, Erich; McGuire, Philip; Fusar-Poli, Paolo; Borgwardt, Stefan
The compulsion to seek and use heroin is frequently driven by stress and craving during drug-cue exposure. Although previous neuroimaging studies have indicated that craving is mediated by increased prefrontal cortex activity, it remains unknown how heroin administration modulates the prefrontal cortex response. This study examines the acute effects of heroin on brain function in heroin-maintained patients. Using a crossover, double-blind, placebo-controlled design, 27 heroin-maintained patients performed functional magnetic resonance imaging 20 minutes after the administration of heroin or placebo (saline) while drug-related and neutral stimuli were presented. Images were processed and analysed with statistical parametric mapping. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Region of interest analyses showed a drug-related cue-associated blood-oxygen-level-dependent activation in the orbitofrontal cortex (OFC) in heroin-dependent patients during both treatment conditions (heroin and placebo). This activation of the OFC was significantly higher after heroin than after placebo administration. These findings may indicate the importance of OFC activity for impulse control and decision-making after regular heroin administration and may emphasize the benefit of the heroin-assisted treatment in heroin dependence.
Lenoir, Magalie; Cantin, Lauriane; Vanhille, Nathalie; Serre, Fuschia; Ahmed, Serge H
Epidemiological research shows that the proportion of drug users who become addicted to heroin is higher than to cocaine. Here we tested whether this difference could be due to a difference in the addiction liability between the two drugs. Addiction liability was assessed under a discrete-trials choice procedure by measuring the proportion of rats that prefer the drug over a potent alternative reward (ie, water sweetened with saccharin). Previous research on choice between self-administration of i.v. cocaine or sweet water showed that the proportion of cocaine-preferring rats remains relatively low and invariable (ie, 15%), even after extended drug access and regardless of past drug consumption (ie, total drug use before choice testing). By contrast, the present study shows that under similar choice conditions, the proportion of heroin-preferring rats considerably increases with extended heroin access (6-9 h per day for several weeks) and with past heroin consumption, from 11 to 51% at the highest past drug consumption level. At this level, the proportion of drug-preferring rats was about three times higher with heroin than with cocaine (51% vs 15%). This increase in the rate of heroin preference after extended heroin access persisted even after recovery from acute heroin withdrawal. Overall, these findings show that choice procedures are uniquely sensitive to different drugs and suggest that heroin is more addictive than cocaine. This higher addiction liability may contribute to explain why more drug users become addicted to heroin than to cocaine in epidemiological studies.
Kaya, C Yalçin; Tugai, Yuliya; Filar, Jerzy A; Agrawal, Manju R; Ali, Robert L; Gowing, Linda R; Cooke, Richard
The aim of this paper is to identify certain important population trends among heroin users in Australia for the period 1971 - 97, such as: population growth, initiation, i.e. the number who were initiated to heroin in a given year, and quitting, i.e. the number that quit using heroin. For this purpose, we summarize and extract relevant characteristics from data from National Drug Strategy Household Survey (NDSHS 1998) conducted in Australia in 1998. We devise a systematic procedure to estimate historical trends from questions concerning past events. It is observed from our findings that the size of the heroin user population in Australia is in a sharp increase, especially from the early 1980s onwards. The general trend obtained for the period 1971 - 97 is strikingly similar to that obtained by Hall et al. (2000) for the dependent heroin user population in Australia, even though their study was based on different datasets and a different methodology. In our reconstruction of the time history we also detect a levelling-off prior to 1990. Initiation is also observed to be on a sharp increase. The latter trend is accompanied by a similar trend of quitting, perhaps indicating a relatively short heroin use career. A sharp decrease in both initiation and quitting is observed after 1990. In conclusion, in the case of the trend in the population of heroin users a high rate of growth has been identified that is consistent with the existing literature. In the process, we demonstrated that even a static survey such as NDSHS 1998 can, sometimes, be used to extract historical (dynamic) trends of certain important variables.
Lerner, Steven E.; Linder, Ronald L.
The purpose of this study was to determine the significance of possible relationships between birth order and polydrug use patterns of heroin addicts prior to undergoing treatment. Overrepresentation of "only child" heroin addicts was evident among the population studied. (Author)
McLauchlin, J; Mithani, V; Bolton, F J; Nichols, G L; Bellis, M A; Syed, Q; Thomson, R P M; Ashton, J R
In 2000, an unusual increase of morbidity and mortality among illegal injecting drug users in the UK and Ireland was reported and Clostridium novyi was identified as the likely source of the serious infection, although infections due to C. botulinum and Bacillus cereus were also reported. Because heroin was a possibile source of infection, this study investigated the microflora of heroin samples seized in England during 2000 and 2002. Two methods were developed for the examination of the microflora of heroin. The first consisted of suspension of the drug in maximum recovery diluent (MRD) which was inoculated directly into Clostridium Botulinum Isolation Cooked Meat Broth (CBI). The second method rendered the heroin soluble in citric acid, concentrated particulate material (and bacterial cells) by filtration and removed heroin residues by washing with citric acid and phosphate-buffered saline before placing the filter in CBI broth. Duplicate CBI broths from both methods were incubated without heating and after heating at 60 degrees C for 30 min. Subcultures were made after incubation for 7 and 14 days on to eight different solid media. The methods were evaluated with heroin samples spiked with either C. botulinum or C. novyi spore suspensions; recovery of 10 spores in the original sample was demonstrated. Fifty-eight heroin samples were tested by citric acid solubilisation and 34 by the MRD suspension technique. Fifteen different gram-positive species of four genera were recognised. No fungi were isolated. Aerobic endospore-forming bacteria (Bacillus spp. and Paenibacillus macerans) were the predominant microflora isolated and at least one species was isolated from each sample. B. cereus was the most common species and was isolated from 95% of all samples, with B. licheniformis isolated from 40%. Between one and five samples yielded cultures of B. coagulans, B. laterosporus, B. pumilus, B. subtilis and P. macerans. Staphylococcus spp. were isolated from 23 (40
Smith, Rachel J; Aston-Jones, Gary
The orexin/hypocretin system is involved in several addiction-related behaviors. In the present experiments, we examined the involvement of orexin in heroin reinforcement and relapse by administering the orexin 1 receptor antagonist SB-334867 prior to heroin self-administration or prior to cue-induced or heroin-induced reinstatement of extinguished heroin seeking in male Sprague Dawley rats. SB-334867 (30 mg/kg, intraperitoneal) reduced heroin intake during self-administration under fixed ratio-1 and progressive ratio schedules. SB-334867 also attenuated reinstatement of heroin seeking elicited by cues, but not reinstatement elicited by a heroin prime. These results indicate that orexin antagonism reduces heroin self-administration, and they support a role for orexin in cue-triggered drug relapse.
Greene, M H
Prospectively collected drug abuse trend surveillance data suggest that the rate of heroin use in Washington, D.C. is rising following a two year decline in the magnitude of this problem. Supportive data include increased potency of street level heroin, increased numbers of heroin-related deaths, increased detection of heroin positive urine specimens in the D.C. Superior Court arrestee population, increased demand for addiction treatment services and rising property crime rates. Increased prevalence of heroin use has not yet been associated with an increase in incidence, suggesting that former heroin users have begun to use once again following a period of abstinence. Analysis of heroin specimens seized across the United States suggests that cities formerly dependant upon European (white) heroin have now developed a new heroin distribution system which supplies Mexican (brown) heroin. This has offset the reduction in heroin use observed during 1972-1973 concomitant with the East Coast heroin shortage and widespread introduction of addiction treatment services.
... Room? What You Need to Know About Drugs: Heroin KidsHealth > For Kids > What You Need to Know About Drugs: Heroin A A A en español Lo que necesitas ... sobre las drogas: La heroína What It Is: Heroin (say: HAIR-uh-win) comes from the opium ...
Guo, Zhen; Zheng, Hui; Lu, Yanzhen; Wei, Yun
The present study established a novel method using preparative high performance liquid chromatography to isolate and purify heroin·HCl from heroin street samples to be used as a reference standard. Different kinds of mobile phases and columns were used, ultimately the mobile phase consisting of hexane-isopropanol-methanol (65:28:7, v/v) and the SIL preparative column prepared in laboratory were selected as the final condition. Heroin was further purified by the drowning-out crystallization method using isopropanol-methanol (50:1, v/v) and hexane as drowning-out anti-solvents and salting-out agents, respectively. The purity was assessed by analytical high performance liquid chromatography and the confirmation of the chemical structure was performed by IR and NMR. About 110.7mg of heroin·HCl at a purity of over 99.52% was obtained from 180mg of heroin street samples which contained 156.15mg of heroin·HCl component by preparative high performance liquid chromatography. This method is suitable for preparing heroin standards in forensic science area.
Maccari, S; Bassi, C; Zanoni, P; Plancher, A C
We examined total cholesterolemia, triglyceridemia, high density lipoproteins- (HDL) cholesterolemia, apolipoproteins A1 and B, body mass index, albuminemia and alanine aminotransferase in 60 heroin addicts. After comparing 23 control subjects with the heroin addicts the result was that the latter have significantly lower mean values of total cholesterolemia and of HDL-cholesterolemia and higher values of triglyceridemia. They also have significantly higher prevalences of cases of hypocholesterolemia and of hypo-HDL-cholesterolemia. Within the addict group there is no linear correlation between total cholesterolemia and body mass index; there is, however, an inverse linear correlation between total cholesterolemia and alanine aminotransferase. Therefore, the alterations found in the lipid pattern of heroin addicts are not due to malnutrition but hypothetically to liver diseases which are frequent in these patients.
The paper presents toxicological characteristics of 198 cases of acute parenteral heroin intoxication, analyzes the clinically encountered range of blood and urinary concentrations of its metabolites. The principal causes of death are elucidated in victims of heroin poisoning at the hospital stage. Where there is a relationship of death probability to the detection of morphine in the victims' biological fluids is considered; its blood and urinary concentrations are determined, which undoubtedly suggests the occurrence of poisoning-related death. It has been established that death from poisoning by heroin may occur in the whole range of its detectable concentrations. There is no doubt that the blood morphine concentrations of at least 2.0 microg/ml should be considered to be fatal.
In recent years, methamphetamine use has dramatically increased in Iran while there is a crucial misunderstanding about the colloquial words related to methamphetamine among health providers, policy makers, clinicians, scholars and people in the community. The word Crystal refers to methamphetamine in some parts of Iran while in some other parts of the country, Crystal refers to a high purity street-level heroin which is called Kerack and its abuse is epidemic. Methamphetamine and heroin Kerack are different drugs in Iran. Methamphetamine is a stimulant drug while heroin Kerack is an opioid. Health providers especially clinicians and emergency medicine specialists should consider colloquial words that Iranian drug users apply. Special training courses should be designed and implemented for clinicians in Iran to inform them about methamphetamine and its frequently used colloquial words in the community. This issue has important clinical and health implications. PMID:23497450
Turkel, Ann Ruth
The need to escape reality and the taste for adventure with the unknown fills a universal need for both adults and children. Fairy tales have a powerful grip on the imagination because they are homespun versions of myths and have passionate intensity without epic grandeur. The happy ending of fairy tales reflects gender stereotyping because the heroine usually does very little except sit, wish, and wait for marriage. She has no control over her destiny and no active involvement in selecting or planning her future. These heroines are really passive victims. Sexism was once rampant in children's books. The Oz books, with their independent, courageous, and active heroine were way ahead of their time. The advent of women's liberation has led to a reappraisal of the female in folk literature. Anthropologists have now discovered stories of admirable women who were strong characters in their own epic dramas.
Bokhan, N A; Baturin, E V
On the model of heroin addiction in adolescents the premises for grounding the concept of gender heteronomy of addictions have been identified. The clinical-dynamic patterns associated with gender--so called gender associated types of disease in which the leading factors of difference formation are biological sex, valuable orientation structure, sexual experience and social status were singled out. The gender-associated types of heroin addiction in boys and girls were specified as dominant, repressive, partner, utilitarian, integrating and independent. Gender-differentiated programs of pharmaco- and psychotherapy are proposed.
Walter, M; Bentz, D; Schicktanz, N; Milnik, A; Aerni, A; Gerhards, C; Schwegler, K; Vogel, M; Blum, J; Schmid, O; Roozendaal, B; Lang, U E; Borgwardt, S; de Quervain, D
Heroin dependence is a severe and chronically relapsing substance use disorder with limited treatment options. Stress is known to increase craving and drug-taking behavior, but it is not known whether the stress hormone cortisol mediates these stress effects or whether cortisol may rather reduce craving, for example, by interfering with addiction memory. The aim of the present study was to determine the effects of cortisol administration on craving in heroin-dependent patients and to determine whether the effects depend on the daily dose of heroin consumption. We used a double-blind, placebo-controlled, cross-over study in 29 heroin-dependent patients in a stable heroin-assisted treatment setting. A single oral dose of 20 mg of cortisol or placebo was administered 105 min before the daily heroin administration. The primary outcome measure was cortisol-induced change in craving. Secondary measures included anxiety, anger and withdrawal symptoms. For the visual analog scale for craving, we found a significant interaction (P=0.0027) between study medication and heroin-dose group (that is, daily low, medium or high dose of heroin). Cortisol administration reduced craving in patients receiving a low dose of heroin (before heroin administration: P=0.0019; after heroin administration: P=0.0074), but not in patients receiving a medium or high dose of heroin. In a picture-rating task with drug-related pictures, cortisol administration did not affect the ratings for the picture-characteristic craving in all the three heroin-dose groups. Cortisol also did not significantly affect secondary outcome measures. In conclusion, a single administration of cortisol leads to reduced craving in low-dose heroin addicts. The present findings might have important clinical implications with regard to understanding stress effects and regarding treatment of addiction. PMID:26218852
Walter, M; Bentz, D; Schicktanz, N; Milnik, A; Aerni, A; Gerhards, C; Schwegler, K; Vogel, M; Blum, J; Schmid, O; Roozendaal, B; Lang, U E; Borgwardt, S; de Quervain, D
Heroin dependence is a severe and chronically relapsing substance use disorder with limited treatment options. Stress is known to increase craving and drug-taking behavior, but it is not known whether the stress hormone cortisol mediates these stress effects or whether cortisol may rather reduce craving, for example, by interfering with addiction memory. The aim of the present study was to determine the effects of cortisol administration on craving in heroin-dependent patients and to determine whether the effects depend on the daily dose of heroin consumption. We used a double-blind, placebo-controlled, cross-over study in 29 heroin-dependent patients in a stable heroin-assisted treatment setting. A single oral dose of 20 mg of cortisol or placebo was administered 105 min before the daily heroin administration. The primary outcome measure was cortisol-induced change in craving. Secondary measures included anxiety, anger and withdrawal symptoms. For the visual analog scale for craving, we found a significant interaction (P = 0.0027) between study medication and heroin-dose group (that is, daily low, medium or high dose of heroin). Cortisol administration reduced craving in patients receiving a low dose of heroin (before heroin administration: P = 0.0019; after heroin administration: P = 0.0074), but not in patients receiving a medium or high dose of heroin. In a picture-rating task with drug-related pictures, cortisol administration did not affect the ratings for the picture-characteristic craving in all the three heroin-dose groups. Cortisol also did not significantly affect secondary outcome measures. In conclusion, a single administration of cortisol leads to reduced craving in low-dose heroin addicts. The present findings might have important clinical implications with regard to understanding stress effects and regarding treatment of addiction.
Walter, Marc; Wiesbeck, Gerhard A; Degen, Bigna; Albrich, Jürgen; Oppel, Monika; Schulz, André; Schächinger, Hartmut; Dürsteler-MacFarland, Kenneth M
Heroin dependence (HD) is a chronic relapsing brain disorder characterized by a compulsion to seek and use heroin. Stress is seen as a key factor for heroin use. Methadone maintenance and the prescription of pharmaceutical heroin [diacetylmorphine (DAM)] are established treatments for HD in several countries. The present study examined whether DAM-maintained patients and methadone-maintained patients differ from healthy controls in startle reflex and cortisol levels. Fifty-seven participants, 19 of each group matched for age, sex and smoking status, completed a startle session which included the presentation of 24 bursts of white noise while eye-blink responses to startling noises were recorded. Salivary cortisol was collected three times after awakening, before, during and after the startle session. DAM was administered before the experiment, while methadone was administered afterwards. Both heroin-dependent patient groups exhibited significantly smaller startle responses than healthy controls (P < 0.05). Whereas the cortisol levels after awakening did not differ across the three groups, the experimental cortisol levels were significantly lower in DAM-maintained patients, who received their opioid before the experiment, than in methadone-maintained patients and healthy controls (P < 0.0001). Opioid maintenance treatment for HD is associated with reduced startle responses. Acute DAM administration may suppress cortisol levels, and DAM maintenance treatment may represent an effective alternative to methadone in stress-sensitive, heroin-dependent patients.
Spano, Maria Sabrina; Fattore, Liana; Fratta, Walter; Fadda, Paola
Opiate addiction is a chronic relapsing disorder characterized by high rates of relapse. The gamma-aminobutyric acid GABA(B) receptor agonist baclofen is known to affect the reinforcing effects of several drugs of abuse, including heroin, as well as to decrease cue-maintained responding for heroin, cocaine and nicotine and suppress alcohol deprivation effect in rats. Here we studied the effect of baclofen on the reinstatement of extinguished heroin-seeking behavior triggered by a priming injection of heroin in abstinent rats trained to stably self-administer heroin (30 microg/kg per infusion) under a continuous reinforcement schedule. Following extinction, the effect of non-contingent non-reinforced primings with heroin, baclofen or heroin/baclofen combination on the resumption of responding was evaluated. Results indicate that heroin priming (0.25mg/kg) promptly reinitiated heroin-seeking behavior, an effect dose-dependently reduced by baclofen at doses (0.625 and 1.25mg/kg) not affecting responding per sè. Importantly, baclofen did not affect locomotion either alone or in combination with heroin, dispelling any doubt as to the eliciting of possible non-specific (motor) effects. The present results show that GABA(B) receptor activation may reduce the propensity to resume drug-induced heroin-seeking behavior thus offering a possible approach in maintaining opiate abstinence.
Raleigh, M D; Pravetoni, M; Harris, A C; Birnbaum, A K; Pentel, P R
Morphine conjugate vaccines have effectively reduced behavioral effects of heroin in rodents and primates. To better understand how these effects are mediated, heroin and metabolite distribution studies were performed in rats in the presence and absence of vaccination. In non-vaccinated rats 6-monoacetylmorphine (6-MAM) was the predominant opioid in plasma and brain as early as 1 minute after i.v. administration of heroin and for up to 14 minutes. Vaccination with morphine conjugated to keyhole limpet hemocyanin (M-KLH) elicited high titers and concentrations of antibodies with high affinity for heroin, 6-MAM, and morphine. Four minutes after heroin administration vaccinated rats showed substantial retention of all three opioids in plasma compared to controls and reduced 6-MAM and morphine, but not heroin, distribution to brain. Administration of 6-MAM rather than heroin in M-KLH vaccinated rats showed a similar drug distribution pattern. Vaccination reduced heroin-induced analgesia and blocked heroin-induced locomotor activity throughout 2 weeks of repeated testing. Higher serum opioid-specific antibody concentrations were associated with higher plasma opioid concentrations, lower brain 6-MAM and morphine concentrations, and lower heroin-induced locomotor activity. Serum antibody concentrations over 0.2 mg/ml were associated with substantial effects on these measures. These data support a critical role for 6-MAM in mediating the early effects of i.v. heroin and suggest that reducing 6-MAM concentration in brain is essential to the efficacy of morphine conjugate vaccines.
Pravetoni, M.; Harris, A.C.; Birnbaum, A.K.; Pentel, P.R.
Morphine conjugate vaccines have effectively reduced behavioral effects of heroin in rodents and primates. To better understand how these effects are mediated, heroin and metabolite distribution studies were performed in rats in the presence and absence of vaccination. In non-vaccinated rats 6-monoacetylmorphine (6-MAM) was the predominant opioid in plasma and brain as early as 1 minute after i.v. administration of heroin and for up to 14 minutes. Vaccination with morphine conjugated to keyhole limpet hemocyanin (M-KLH) elicited high titers and concentrations of antibodies with high affinity for heroin, 6-MAM, and morphine. Four minutes after heroin administration vaccinated rats showed substantial retention of all three opioids in plasma compared to controls and reduced 6-MAM and morphine, but not heroin, distribution to brain. Administration of 6-MAM rather than heroin in M-KLH vaccinated rats showed a similar drug distribution pattern. Vaccination reduced heroin-induced analgesia and blocked heroin-induced locomotor activity throughout 2 weeks of repeated testing. Higher serum opioid-specific antibody concentrations were associated with higher plasma opioid concentrations, lower brain 6-MAM and morphine concentrations, and lower heroin-induced locomotor activity. Serum antibody concentrations over 0.2 mg/ml were associated with substantial effects on these measures. These data support a critical role for 6-MAM in mediating the early effects of i.v. heroin and suggest that reducing 6-MAM concentration in brain is essential to the efficacy of morphine conjugate vaccines. PMID:23220743
Schrock, Andreas; Jakob, Mark; Wirz, Stefan; Bootz, Friedrich
Sudden sensorineural hearing loss is a symptom of cochlear injury. Potential aetiologies are vascular diseases, viral infections, allergic reactions, autoimmune disorders, and traumatic rupture of the intralabyrinthe membrane. Unlike in unilateral cases bilateral sensorineural hearing loss is often associated with specific disease entities. We report a case of sudden bilateral deafness after intravenous heroin abuse. The putative pathophysiological mechanisms are discussed.
Phillips, John R
Rhythms of Martha Rogers' life and work are presented showing her evolution as a heretic and a heroine through her heretical thinking. New concepts of unitariology, energyspirit, wellbecoming, integral presence, and soul are presented with their relevance for advancing Rogers' science of unitary human beings. New dimensions of practice make explicit pandimensional ministering to humankind and living in the universe.
The first X-ray structure of human carboxylesterase 1 (hCE1) and the structures of hCE1 with drug analogs bound reveal important molecular details of how the drugs cocaine, heroin, and tacrine are metabolized and cleared.
Preller, Katrin H; Wagner, Michael; Sulzbach, Christian; Hoenig, Klaus; Neubauer, Julia; Franke, Petra E; Petrovsky, Nadine; Frommann, Ingo; Rehme, Anne K; Quednow, Boris B
Models of addiction and addiction memory propose that drug-associated cues elicit incentive effects in drug users, which play an important role in maintenance of drug use and relapse. Incentive effects have been demonstrated for smoking and alcohol-related cues but evidence for heroin-related cues has been inconclusive. Furthermore, it is unknown whether appetitive effects of heroin-related cues persist after prolonged abstinence, although heroin addiction is known to have high relapse rates. Therefore, we investigated implicit and explicit valence of heroin-related cues in dependent users at different stages of abstinence using affective startle modulation. In Study I, 15 current heroin users were measured before and after detoxification. Correspondingly, 15 healthy control participants were tested twice at an interval of 14 days. In Study II, 14 long-term abstinent heroin users were additionally measured in a single session. Implicit processing of drug-related stimuli was assessed using affective startle modulation by pictures of heroin and smoking scenes. Explicit reactions were measured using ratings of valence and craving. In contrast to controls, heroin-dependent participants showed a clear reduction of startle response during heroin-related pictures (p<0.05). Detoxification did not significantly change their startle responses to heroin-cues. No difference between non-detoxified current and long-term abstinent heroin users was found in implicit reactions to heroin-cues, whereas explicit measures differed between both groups (all p<0.05). After detoxification and even after prolonged abstinence, heroin cues still exert implicit appetitive effects in heroin users. This implies that drug-induced adaptations of reward circuits are long-lasting, resulting in a highly stable addiction memory.
Heroin availability and purity decreased and prices increased in Australia suddenly in early 2001. The heroin market in Australia has still not returned to the status quo ante after more than six years. Benefits of the heroin shortage, including a substantial reduction in drug overdose deaths and property crime, are generally considered to have outweighed adverse effects which included increased use of other drugs, especially stimulants, with a subsequent increase in aggression, violence and mental illness. Some commentators attributed the heroin shortage to a combination of factors, while an influential study highlighted the importance of supply control asserting that increased funding and improved effectiveness of domestic drug law enforcement produced critical heroin seizures which disrupted major syndicates, thereby producing the heroin shortage. Evidence to support a critical role for drug law enforcement in the heroin shortage is weak with some recent evidence contradicting key assertions used to support the supply control hypothesis. Although the most likely interpretation is still a combination of multiple factors, the most important factors appear to have been a substantial recent reduction in source opium cultivation and heroin production in Burma, but probably also increased heroin consumption en route through China and a switch from heroin to amphetamine production in Burma. This interpretation is consistent with the international experience of several recent decades in numerous countries where national heroin shortages have occurred rarely and generally only briefly, notwithstanding vigorous and very well resourced supply control efforts. The recent reduction in heroin supply in Australia, the most severe, longest lasting and best-documented heroin shortage in the world, cannot be confidently attributed, solely or largely, to improved domestic drug law enforcement. At best, domestic law enforcement may have made a small contribution compared to several
Proudnikov, D; Kroslak, T; Sipe, J C; Randesi, M; Li, D; Hamon, S; Ho, A; Ott, J; Kreek, M J
Alterations in expression of a cannabinoid receptor (CNR1, CB1), and of fatty acid amide hydrolase (FAAH) that degrades endogenous ligands of CB1, may contribute to the development of addiction. The 385C>A in the FAAH gene and six polymorphisms of CNR1 were genotyped in former heroin addicts and control subjects (247 Caucasians, 161 Hispanics, 179 African Americans and 19 Asians). In Caucasians, long repeats (>or=14) of 18087-18131(TAA)(8-17) were associated with heroin addiction (P=0.0102). Across three ethnicities combined, a highly significant association of long repeats with heroin addiction was found (z=3.322, P=0.0009). Point-wise significant associations of allele 1359A (P=0.006) and genotype 1359AA (P=0.034) with protection from heroin addiction were found in Caucasians. Also in Caucasians, the genotype pattern, 1359G>A and -6274A>T, was significantly associated with heroin addiction experiment wise (P=0.0244). No association of FAAH 385C>A with heroin addiction was found in any group studied.
Dubois, N; Demaret, I; Ansseau, M; Rozet, E; Hubert, Ph; Charlier, C
The objective of the present study was to verify if severe physical health problems frequently encountered in heroin addicts and the concomitant use of alcohol and legal or illegal drugs other than heroin influenced the pharmacokinetics of the major metabolites of heroin. We conducted a 90 minutes follow-up of the plasma concentrations of the pharmaceutical heroin, named diacetylmorphine (DAM), in patients recruited in a DAM assisted treatment centre. TADAM (Traitement Assisté par DiAcétylMorphine) aimed to compare the efficacy of heroin-assisted treatment (HAT) compared with methadone maintenance treatment (MMT) for heroin users considered as treatment resistant patients and who have severe physical and mental health problems. Eleven patients were recruited. Blood samples were collected at baseline and 15, 45 and 90 minutes after DAM administration. All patients received DAM by the "chasing the dragon" route. Plasma samples were analyzed by a previously described ultra-high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS) method. A principal component analysis (PCA) was performed and 8 metabolite concentrations ratios were calculated to evaluate the influence of various factors (DAM dose, patient pathologies, concomitant use of medications, methadone, street heroin, alcohol and cocaine) on heroin metabolite pharmacokinetics. It seemed to be not affected by the DAM dose, patient pathologies and the concomitant use of medications, methadone, street heroin and alcohol. Cocaine use was the only parameter which showed differences in heroin pharmacokinetics.
Lai, Miaojun; Zhu, Huaqiang; Sun, Anna; Zhuang, Dingding; Fu, Dan; Chen, Weisheng; Zhang, Han-Ting; Zhou, Wenhua
Inhibition of phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP) increases intracellular cAMP/cAMP-response element binding protein (CREB) signaling. Activation of this signaling is considered as an important compensatory response that decreases motivational properties of drugs of abuse. However, it is not known whether PDE4 is involved in heroin seeking. Self-administration of heroin (50 μg/kg/infusion) was performed under the fixed ratio 1 (FR1) schedule for 14 d and then drug seeking was extinguished for 10 d. The progressive ratio schedule was used to evaluate the relative motivational value of heroin reinforcement. After training, the conditioned cue or heroin priming (250 μg/kg) was introduced for the reinstatement of heroin-seeking behavior. Pretreatment (i.p.) with rolipram (0.03-0.3 mg/kg), a prototypical, selective PDE4 inhibitor, failed to inhibit heroin self-administration under the FR1 schedule, but decreased the reward values under the progressive ratio schedule in a dose-dependent manner. In addition, rolipram decreased the reinstatement of heroin seeking induced by cues or heroin priming even at the lowest dose (0.03 mg/kg); in contrast, the highest dose (0.3 mg/kg) of rolipram was required to decrease sucrose reinforcement. Finally, the effects of rolipram on heroin-seeking behavior were correlated with the increases in expression of phosphorylated CREB in the nucleus accumbens. The study demonstrated that rolipram inhibited heroin reward and heroin-seeking behavior. The results suggest that PDE4 plays an essential role in mediating heroin seeking and that PDE4 inhibitors may be used as a potential pharmacotherapeutic approach for heroin addiction.
Hendriks, V M; van den Brink, W; Blanken, P; Bosman, I J; van Ree, J M
In this controlled clinical study, the bioavailability and pharmacodynamics of inhaled heroin are evaluated and compared between 'chasing the dragon' and inhalation from a heating device, and at three dose levels, 25, 50 and 100 mg heroin, in two separate study phases. In study phase 1, no differences between the inhalation methods were detected on any of the physiological or behavioral measures, nor in bioavailability. Subjectively, the participants had a strong preference for the method of chasing, which was therefore used in study phase 2. In phase 2, heroin produced a dose-related increase in subjective drug-liking, body temperature and heart rate, and a clear, dose-related decline in reaction time. Linearly dose-related differences were found in the amount of total morphine in urine, amounting to an average of 45% of the parent heroin base received. Based on these findings, it is concluded that chasing is quite an effective route of heroin administration, producing rapid, dose-related subjective and objective effects and a sufficiently high and reproducible bioavailability.
Denooz, R; Dubois, N; Charlier, C
The results of heroin analysis from seizures in the Liege area during the last two years are presented in this article. Between January 2003 and January 2005, 50 samples were analysed in the Laboratory of Clinical Toxicology and Forensic Toxicology of the University of Liege. Mean heroin concentration was 14,7%. Noscapine and papaverine, other opium alcaloïds, were simultaneously present with heroin. As diluents, we only identified caffein and acetaminophen.
Page, J B; Fraile, J S
Preliminary observations and responses to interviews in Valencia, Spain reveal that injecting drug users (IDUs) dissolve heroin before injection with two or three drops of lemon juice. Solution in lemon juice makes heating of heroin in water unnecessary. This pattern apparently developed spontaneously in Spain, but is almost unknown elsewhere in the world. Its implications for IDUs' health remain speculative, but use of lemon juice to dissolve heroin for injection deserves further scientific study.
Zerell, U; Ahrens, B; Gerz, P
The present article documents an authentic process of heroin manufacturing in Afghanistan: white heroin hydrochloride produced using simple equipment and a small quantity of chemicals. The quantities of chemicals actually used corresponded to the minimum needed for manufacturing heroin. The only organic solvent used was acetone, and only a very small quantity of it was used. Because the chemicals used in the demonstration were from actual seizures in Afghanistan, some of the chemicals had been disguised or repackaged by smugglers. Others had been put into labelled containers that proved to be counterfeit, and some glass containers used were not the original containers of the manufacturer displayed on the label. The brown heroin base prepared as an intermediate step in the process shares some of the characteristics of the South-West Asia type of heroin preparations often seized in Germany. The final product of the documented heroin manufacturing process was white heroin hydrochloride, which shares the key characteristics of the white heroin occasionally seized in Germany and other countries in Western Europe since 2000. The present article demonstrates that this kind of heroin can be produced in Afghanistan.
Uusitalo, Susanne; Broers, Barbara
Can heroin addicts give consent to research on trials in which heroin is prescribed to them? Analyses of addicts and informed consent have been objects of debate in several articles. Informed consent requires the agent not only to be competent but also to give consent voluntarily. This has been questioned because of alleged features of heroin addiction. Until recently the discussion has focused on heroin addicts' desires for heroin, whether these are irresistible and thus pose a problem for giving consent. Still, in light of empirical evidence, there seems to be a consensus more or less that the problem is not whether the addicts can resist their desire for heroin. A recent article concentrates specifically on heroin addicts' false assumptions of options and voluntariness. We argue that the prevailing framing of the options in this discussion in terms of heroin and access to it is problematic. The way in which the options are typically laid out suggests an assumption that participation in the research is allegedly based on the addicts' views on using the drug. We argue that this way of presenting the options is, first, a mismatch to the studies carried out and, second, symptomatic of potential misconceptions about heroin addiction and addicts. Furthermore, we also suggest that the account of voluntariness needs to be realistic in order for subjects to be able to give consent voluntarily in actual situations, and for medical research to carry out studies on improving outcomes in addiction treatment in an ethical way.
Hogen Esch, A J; van der Heide, S; van den Brink, W; van Ree, J M; Bruynzeel, D P; Coenraads, P J
After the start of heroin (diacetylmorphine)-assisted treatment to a selected group of chronic treatment-resistant heroin-dependent patients in the Netherlands, we reported about work-related eczema and positive patch tests to heroin in some nurses and nasal and respiratory complaints. To investigate the prevalence of heroin contact allergy, we started a questionnaire-based study with follow-up by allergological examinations. Of 120 questionnaires sent, 101 (84%) was returned: 67 from nurses and 34 from other employees. Of 101 workers, 38 (38%) had reported work-related complaints: 33 of 67 (49%) nurses and 5 of 34 (15%) other employees. Patch tests to heroin were performed in 24 nurses and were positive in 8 (33%). All the 8 had eyelid or facial eczema and, in 6, accompanied by mucosal or respiratory complaints. The prevalence of heroin contact allergy in this study was 8% (8/101) among all employees and 12% (8/67) among nurses. Respiratory and mucosal complaints could not be ascribed to a contact allergy, and in these cases, serum was analysed for specific immunoglobulin E to heroin. A type 1 allergy to heroin could not be shown. These complaints are possibly due to the histamine-liberating effect of heroin, to atopic constitution, to a combination of these factors or - less likely - to other non-allergic factors.
Namboodiri, Vasudevan; George, Sanju; Boulay, Sylvie; Fair, Mandy
Heroin misuse in pregnancy is a significant health and social problem, and it can have an adverse effect on the mother and the baby. Although heroin and methadone have no specific teratogenic potential, 48–94% of children exposed in utero will have neonatal abstinence syndrome (NAS). The primary aim of this case report is to raise awareness of NAS among clinicians and to remind them that although very common, it is not inevitable. The risk of NAS can be further minimised by offering comprehensive and co-ordinated antenatal care that addresses the various biopsychosocial needs of the pregnant woman. Further, a brief description of NAS and a review of evidence in the field of management of opioid misuse in pregnancy, as relevant to this case, are provided. We have also included the patient’s own reflections on her pregnancy and treatment. PMID:22328902
Galassi, Giuliana; Ariatti, Alessandra; Gozzi, Manuela; Cavazza, Stefano
A 24-year-old female with 5 year history of heroin abuse experienced painless stiffness of elbow joints and weakness of shoulder and upper limb muscles. She was injecting herself 4-6 times daily alternatively in the upper extremities, sparing the lower limbs. Electromyography (EMG) showed myopathic changes in clinically affected and unaffected muscles. Magnetic resonance imaging (MRI) revealed muscle fibrosis in directly injected muscles, whereas in subcutaneous fat and within muscles of anterior and posterior compartments of both thighs, not directly injected, there were signal changes supportive of oedema and inflammation. EMG and MRI were congruent in showing abnormalities in muscles not directly injected, suggesting long distant effects of heroin or adulterants with a mechanism either toxic or immunologically mediated.
104 Bibliography .............................................. log vii Figures 1.1. Worldwide Opium Production: NNICC and INCSR Estimates from 1983 to...United States (18 to 25 Years Old) ........................................ 5 2.1. The World’s Three Principal Opium Producing Regions ......... 10 2.2... Opium Production by the Major Producing Countries in 1991 ..... 11 2.3. Heroin Availability in the United States by Source Region ....... 14 3.1
Kuchkarov, U I; Ashurov, Z Sh; Sultanov, Sh Kh
24 patients with heroin addiction have been observed with the purpose to assess cognitive and neurosis-like disorders during the treatment with Noofen. The methods of research included clinical-psychopathological examination. The course therapy with Noofen reduced intensity of memory and attention disorders and improved general cognitive status of the patients. The therapy with Noofen has not increased a pathological drive to narcotics. Noofen use has improve cognitive sphere alongside with reduction in concomitant psychopathological symptoms including depressive and other disorders.
Klous, Marjolein G; Rook, Elisabeth J; Hillebrand, Michel J X; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H
In preparation for a treatment program concerning the medical coprescription of heroin and methadone to treatment-resistant addicts in the Netherlands, we studied a novel strategy for monitoring co-use of illicit (nonprescribed) heroin. A deuterated analogue of heroin was added (1:20) to pharmaceutical, smokable heroin (a powder mixture of 75% w/w diacetylmorphine base and 25% w/w caffeine anhydrate), to be used by inhalation after volatilization ("chasing the dragon"). Plasma and urine samples were collected from nine male patients who had used pharmaceutical, smokable heroin during a four-day stay in a closed clinical research unit, and these samples were analyzed by liquid chromatography coupled with tandem mass spectrometry. Ratios of deuterated and undeuterated diacetylmorphine and 6-acetylmorphine (MAM/MAM-d3) in plasma and urine were calculated from peak areas of these substances in the respective chromatograms. The MAM/MAM-d3 ratios in plasma and urine were normally distributed (with small standard deviations) and independent from concentrations of 6-acetylmorphine and from time after use of pharmaceutical heroin. A MAM/MAM-d3 ratio in urine above 32.8 was considered indicative of co-use of illicit heroin, and this value was associated with a false-positive rate of only 1% (95% confidence interval: -1 to 3%). The MAM/MAM-d3 ratio was detectable in urine for 4-9.5 h after use of pharmaceutical, smokable heroin. Addition of stable, isotopically labelled heroin to pharmaceutical, smokable heroin is considered to be a feasible strategy for the detection of co-use of illicit heroin by patients in heroin-assisted treatment.
Dancer, S J; McNair, D; Finn, P; Kolsto, A B
Concern exists over recent unexplained deaths among intravenous drug users. This report describes a patient with crepitant cellulitis who was admitted complaining of severe pain in the right forearm. Ultrasonography demonstrated gas in the tissues and he was referred for early surgical debridement of the arm. He was treated with intravenous benzyl penicillin, gentamicin and metronidazole and made a full recovery. Aspirate samples grew Bacillus cereus, morphologically similar to the isolate obtained from a sample of the patient's own heroin. Antibiogram and API 50CHB profiles were also similar. Further typing included 'H' flagellar serotyping, which found both blood and heroin strains to be non-typable, and amplified fragment polymorphism analysis, which showed that the strains were indistinguishable. Genotyping of two selected genes from B. cereus confirmed almost certain identity between the two strains. This case illustrates the potential virulence of B. cereus when inoculated into tissues, and to our knowledge, is the first report to demonstrate a conclusive microbiological link between contaminated heroin and serious sepsis in a drug user due to B. cereus.
Li, Fuying; Cheng, Kejun; Antoline, Joshua F G; Iyer, Malliga R; Matyas, Gary R; Torres, Oscar B; Jalah, Rashmi; Beck, Zoltan; Alving, Carl R; Parrish, Damon A; Deschamps, Jeffrey R; Jacobson, Arthur E; Rice, Kenner C
Three haptens have been synthesized with linkers for attachment to carrier macromolecules at either the piperidino-nitrogen or via an introduced 3-amino group. Two of the haptens, with a 2-oxopropyl functionality at either C6, or at both the C3 and C6 positions on the 4,5-epoxymorphinan framework, as well as the third hapten (DiAmHap) with diamido moieties at both the C3 and C6 positions, should be much more stable in solution, or in vivo in a vaccine, than a hapten with an ester in one of those positions, as found in many heroin-based haptens. A "classical" opioid synthetic scheme enabled the formation of a 3-amino-4,5-epoxymorphinan which could not be obtained using palladium chemistry. Our vaccines are aimed at the reduction of the abuse of heroin and, as well, at the reduction of the effects of its predominant metabolites, 6-acetylmorphine and morphine. One of the haptens, DiAmHap, has given interesting results in a heroin vaccine and is clearly more suited for the purpose than the other two haptens.
Negus, S Stevens; Rice, Kenner C
Opioid withdrawal can produce a constellation of physiological and behavioral signs, including an increase in opioid self-administration. Different mechanisms mediate different withdrawal signs, and the present study used pharmacologic tools to assess mechanisms underlying withdrawal-associated increases in opioid reinforcement. Five rhesus monkeys were rendered heroin dependent via daily 21-h heroin self-administration sessions. One hour after each heroin self-administration session, monkeys chose between heroin (0-0.1 mg/kg per injection) and food (1 g pellets) during 2-h choice sessions. Under these conditions, heroin maintained a dose-dependent increase in heroin choice, such that monkeys responded primarily for food when low heroin doses were available (0-0.01 mg/kg per injection) and primarily for heroin when higher heroin doses were available (0.032-0.1 mg/kg per injection). Periods of spontaneous withdrawal were intermittently introduced by omitting one 21-h heroin self-administration session, and test drugs were administered during these withdrawal periods. Untreated withdrawal robustly increased heroin choice during choice sessions. Withdrawal-associated increases in heroin choice were completely suppressed by the mu opioid agonist morphine (0.032-0.32 mg/kg/h, i.v.), but not by the alpha-2 noradrenergic agonist clonidine (0.01-0.1 mg/kg/h, i.v.), the dopamine/norepinephrine releaser amphetamine (0.032-0.1 mg/kg/h, i.v.), or the kappa-opioid antagonist 5'-guanidinonaltrindole (1.0 mg/kg, i.m.). The corticotropin-releasing factor 1 antagonist antalarmin (1.0-10 mg/kg per day, i.m.) produced a morphine-like suppression of withdrawal-associated increases in heroin choice in one of three monkeys. These results suggest that mechanisms of withdrawal-associated increases in the relative reinforcing efficacy of opioid agonists may be different from mechanisms of many other somatic, mood-related, and motivational signs of opioid withdrawal.
Goldberger, B A; Caplan, Y H; Maguire, T; Cone, E J
Hair samples from 20 documented heroin users contained 6-acetylmorphine, a unique metabolite of heroin, in all samples. Heroin was identified in smaller amounts in seven of these samples. The identity of 6-acetylmorphine and heroin was established by comparison of full scan spectra of extracts to standard reference materials. The presence of 6-acetylmorphine generally predominated over heroin, morphine, and codeine. The mean concentrations of analytes were as follows: 6-acetylmorphine, 0.90 ng/mg, N = 20; heroin, 0.17 ng/mg, N = 7; morphine, 0.26 ng/mg, N = 20; codeine, 0.18 ng/mg, N = 15. Analysis of hair samples obtained from 10 drug-free control subjects were negative for 6-acetylmorphine, morphine, and codeine. However, a small interfering peak was observed at the retention time for heroin. Control samples soaked in aqueous solutions of heroin and 6-acetylmorphine were found to be contaminated, even though an initial wash step was included in the analysis. These data suggest that hair analysis for 6-acetylmorphine can be used to differentiate heroin users from other types of opiate exposure (e.g., poppy seed, licit morphine, and codeine); however, environmental contamination can potentially produce false positives during opiate testing.
Jones, Jermaine D; Vadhan, Nehal P; Luba, Rachel R; Comer, Sandra D
Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and continued use despite negative consequences. Behavioral impulsivity is a strong predictor of the initiation and maintenance of drug addiction. Preclinical data suggest that heroin may exacerbate impulsive characteristics in an individual but this has yet to be assessed in clinical samples. The current secondary data analysis sought to investigate the effects of heroin on impulsivity along with the effects of exposure to drug cues. Using the current data set, we also tentatively assessed the etiological relationship between impulsivity and heroin abuse. Sixteen heroin-dependent participants were recruited to complete Immediate Memory Task/Delayed Memory Task (IMT/DMT) and GoStop tasks following repeated heroin administration, following acute heroin administration, and following a drug cue exposure session. Four preceding days of active heroin availability, compared to four preceding days of placebo drug availability, increased impulsivity assessed using the IMT and DMT. Presentation of drug cues similarly acted to increase impulsivity assessments on all three tasks. It also appears that heavier users were more susceptible to the influence of drug cues on impulsivity. The present study represents a step toward a more comprehensive understanding of the interaction between opioid abuse and impulsivity. A better understanding of these factors could provide critical insight into the maintenance of heroin use and relapse.
Schmidt, André; Borgwardt, Stefan; Gerber, Hana; Schmid, Otto; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Bendfeldt, Kerstin; Smieskova, Renata; Lang, Undine E; Rubia, Katya; Walter, Marc
Neuroimaging studies have reported reduced activity in a broad network of brain regions during response inhibition in heroin-dependent patients. However, how heroin in an acute dose modulates the neural correlates of response inhibition and the underlying brain connectivity has not yet been investigated. In this double-blind placebo-controlled study, we used functional magnetic resonance imaging to examine whether acute heroin administration changed whole brain activity during response inhibition in 26 heroin-dependent patients. We then applied dynamic causal modelling to investigate the effect of an acute dose of heroin on the functional interactions between the dorsal anterior cingulate cortex (dACC) and the bilateral inferior frontal gyri (IFG). Heroin acutely reduced dACC activity, as well as the inhibition-induced modulation of connectivity from the dACC to the right IFG compared with placebo. Furthermore, dACC activity was positively related to false alarm rates after placebo but not heroin administration. These results suggest that acute heroin administration impairs cognitive control in dependent patients by reducing the activity in the dACC activity and the functional connectivity from the dACC to the right IFG.
Join Together, Boston, MA.
This action kit was created in response to a rise in heroin use. Facts are provided about the scope of heroin use since it is the one illegal drug that is growing in popularity in some areas among young people. A brief explanation of some treatment options is provided including detoxification, methadone treatment, other medications, and behavioral…
Beck, Aaron T.; And Others
Administered the Beck Hopelessness Scale to alcoholic (N=20) and heroin-addicted (N=20) women. Results indicated that although both groups expressed comparable levels of overall hopelessness, alcoholic women anticipated more success and better lives in the next 10 years than did the heroin-dependent women. (LLL)
Cheng, Gordon L F; Liu, Yu-Pin; Chan, Chetwyn C H; So, Kwok-Fai; Zeng, Hong; Lee, Tatia M C
Neurobiological investigation of heroin revealed that abusers of this highly addictive substance show dysregulation in brain circuits for reward processing and cognitive control. Psychologically, personality traits related to reward processing and cognitive control differed between heroin abusers and non-abusers. Yet, there is no direct evidence on the relationship between these neurobiological and psychological findings on heroin abusers, and whether such relationship is altered in these abusers. The present study filled this research gap by integrating findings obtained via magnetic resonance imaging (structural volume and resting-state functional connectivity) and self-reported personality trait measures (Zuckerman׳s Sensation Seeking Scale and Barratt Impulsivity Scale) on 33 abstinent heroin users and 30 matched healthy controls. The key finding is a negative relationship between high sensation seeking tendency and midbrain structural volume in the heroin users. Importantly, there was stronger coupling between the midbrain and ventromedial prefrontal cortex and weaker coupling between the midbrain and dorsolateral prefrontal cortex in heroin users. Our findings offer significant insight into the neural underpinning of sensation seeking in heroin users. Importantly, the data shed light on a novel relationship between the mesolimbic-prefrontal pathway of the reward system and the high sensation seeking personality trait in heroin abusers.
Brenneisen, Rudolf; Hasler, Felix; Würsch, Daniel
Acetylcodeine (ACOD) is a synthesis byproduct present in street heroin but not in pharmaceutical diacetylmorphine (DAM) as used in the Swiss program Heroin-Assisted Treatment for Opiate Dependent Drug Users (HAT). ACOD was evaluated and validated as an urine marker to detect the consumption of street heroin by HAT participants. A gas chromatography-mass spectrometry method allowing the quantitation of ACOD concentrations as low as 0.2 ng/mL urine has been developed. In opiate-naïve subjects, intravenous (i.v.) ACOD showed a plasma elimination half-life of 237 +/- 18 min, urine peak concentrations 2 h after administration, and a detection window of 8 h. Only 0.4 +/- 0.1% was excreted unchanged, with codeine (COD) as the main metabolite. ACOD may be formed by transacetylation when i.v. DAM and oral codeine are co-administered. To avoid false-positive results, the calculation of COD/ACOD ratios is recommended. In a study with 105 HAT participants, 14% of the tested urines were ACOD positive. Only a low correlation was found between the anonymously self-declared consumption of street heroin and the ACOD positive rate.
Malliarakis, Kate Driscoll
Heroin use may be under-recognized among older adults. Baby Boomers are the largest age as well as the largest drug-using cohort in modern history. Although some drug users age out of their addiction, others do not. Nurses caring for older adults may come into contact with heroin users due to associated conditions or sequelae of their drug use that cause them to seek care. Few nurses are prepared to provide the care needed when heroin use accompanies other health problems. Using an individual example, the current article provides guidance for identifying heroin addiction, essential information about heroin use, and resources for guiding patients to experts for the comprehensive care needed for recovery.
Lenoir, Magalie; Ahmed, Serge H
Escalation of drug consumption-a hallmark of addiction-has been hypothesized to be associated with a relative devaluation of alternative nondrug rewards and thus with a decrease in their ability to compete with or to substitute for the drug. In a behavioral economic framework, decreased substitutability of nondrug rewards for drug would explain why drug consumption is behaviorally dominant and relatively resistant to change (eg price-inelastic) in drug-addicted individuals. The goal of the present study was to test this hypothesis using a validated rat model of heroin intake escalation. Escalation was precipitated by long (6 h, long access (LgA)), but not short (1 h, short access (ShA)), daily access to i.v. heroin self-administration. After escalation, the effects of price (ie fixed-ratio value) on heroin consumption were assessed under two alternative reward conditions: in the presence or absence of a nondrug substitute for heroin (ie four freely available chow pellets). As expected, escalated heroin consumption by LgA rats was less sensitive to price than heroin consumption by ShA rats, showing that heroin had acquired greater reinforcing strength during escalation. However, supplying a substitute during access to heroin was sufficient to reverse this post-escalation increase in the reinforcing effectiveness of heroin. Thus, escalated heroin consumption is not associated with a decreased sensitivity to competing nondrug rewards. Escalated drug use may therefore persist, not so much because of a relative devaluation of nondrug substitutes, but because of a loss or reduction of their availability.
Vendruscolo, Leandro F; Schlosburg, Joel E; Misra, Kaushik K; Chen, Scott A; Greenwell, Thomas N; Koob, George F
The prevalence of opioid abuse and dependence has been on the rise in just the past few years. Animal studies indicate that extended access to heroin produces escalation of intake over time, whereas stable intake is observed under limited-access conditions. Escalation of drug intake has been suggested to model the transition from controlled drug use to compulsive drug seeking and taking. Here, we directly compared the pattern of heroin intake in animals with varying periods of heroin access. Food intake was also monitored over the course of escalation. Rats were allowed to lever press on a fixed-ratio 1 schedule of reinforcement to receive intravenous infusions of heroin for 1, 6, 12, or 23h per day for 14 sessions. The results showed that heroin intake in the 12 and 23h groups markedly increased over time, whereas heroin intake in the 1h group was stable. The 6h group showed a significant but modest escalation of intake. Total heroin intake was similar in the 12 and 23h groups, but the rate of heroin self-administration was two-fold higher in the 12h group compared with the 23h group. Food intake decreased over sessions only in the 12h group. The 12 and 23h groups showed marked physical signs of naloxone-precipitated withdrawal. These findings suggest that 12h heroin access per day may be the optimal access time for producing escalation of heroin intake. The advantages of this model and the potential relevance for studying drug addiction are discussed.
Macedo, T R; Relvas, J; Fontes Ribeiro CA; Pacheco, F; Morgadinho, M T; Pinto, C M; Gomes, P C; Ventura, M; Henriques, V; Nunes, S V; Ruis, G R; Ramalheira, C; Boto, I; Vale, L L
The adrenergic system has long been known to be activated in a situation of stress and thus during opiate withdrawal. A method for detoxification that decreases the stimulation of the sympathetic nervous system will prevent changes of catecholamine levels. Some of such methods have been developed. One of them uses direct transition from heroin to oral naltrexone after deep sedation with midazolam in conjunction with naloxone, droperidol, ondansetron, and clonidine treatment for 24 hours. Can such method prevent adrenergic changes? Moreover, 5-HT has been related to mood disorders. This study aims to determine plasma catecholamines and 5-HT before heroin withdrawal, during the day of the withdrawal, and at the ends of the first day, the first week, and the first 6 months. Forty-three patients with more than 6 years of drug abuse volunteered to seek help to detoxify. After clinical evaluation, blood samples were taken. Plasma catecholamines were isolated by standard alumina procedures and measured by high-performance liquid chromatography with electrochemical detection. Only for NE was there a significant decrease in the day of heroin withdrawal with deep sedation, followed the next day by an increase. During the following days, NE plasma concentrations returned slowly to basal levels. Epinephrine and dopamine plasma levels did not significantly change. Platelet 5-HT levels progressively decreased from the day before detoxification until the last period of observation. We also found that there were no abrupt changes in cardiovascular functions. In conclusion, our results suggest that this type of ultrarapid opiate detoxification prevents the dramatic activation of the autonomic nervous system.
el-Nakah, A; Frank, O; Louria, D B; Quinones, M A; Baker, H
Circulating thiamine, riboflavin, nicotinates, folates, vitamin B12, B6, A, and carotenes of 149 heroin addicts aged 17-60 years were compared to 204 healthy subjects not using drugs or vitamins. Only 24 per cent of the addicts had no evidence of hypovitaminemia; 45 per cent and 37 per cent had vitamin B6 and folate deficit respectively, whereas deficits of thiamine, vitamin B12, riboflavin, and nicotinate were recorded for 13-19 per cent of the addict population; impaired liver function in addicts did not influence these results.
Olmstead, Todd A.; Alessi, Sheila M.; Kline, Brendan; Pacula, Rosalie Liccardo; Petry, Nancy M.
This paper reports estimates of the price elasticity of demand for heroin based on a newly constructed dataset. The dataset has two matched components concerning the same sample of regular heroin users: longitudinal information about real-world heroin demand (actual price and actual quantity at daily intervals for each heroin user in the sample) and experimental information about laboratory heroin demand (elicited by presenting the same heroin users with scenarios in a laboratory setting). Two empirical strategies are used to estimate the price elasticity of demand for heroin. The first strategy exploits the idiosyncratic variation in the price experienced by a heroin user over time that occurs in markets for illegal drugs. The second strategy exploits the experimentally-induced variation in price experienced by a heroin user across experimental scenarios. Both empirical strategies result in the estimate that the conditional price elasticity of demand for heroin is approximately −0.80. PMID:25702687
Rook, Elisabeth J; Huitema, Alwin D R; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H
This article reviews the pharmacokinetics of heroin after intravenous, oral, intranasal, intramuscular and rectal application and after inhalation in humans, with a special focus on heroin maintenance therapy in heroin dependent patients. In heroin maintenance therapy high doses pharmaceutically prepared heroin (up to 1000 mg/day) are prescribed to chronic heroin dependents, who do not respond to conventional interventions such as methadone maintenance treatment. Possible drug-drug interactions with the hydrolysis of heroin into 6-monoacetylmorphine and morphine, the glucuronidation of morphine and interactions with drug transporting proteins are described. Since renal and hepatic impairment is common in the special population of heroin dependent patients, specific attention was paid on the impact of renal and hepatic impairment. Hepatic impairment did not seem to have a clinically relevant effect on the pharmacokinetics of heroin and its metabolites. However, some modest effects of renal impairment have been noted, and therefore control of the creatinine clearance during heroin-assisted treatment seems recommendable.
Olmstead, Todd A; Alessi, Sheila M; Kline, Brendan; Pacula, Rosalie Liccardo; Petry, Nancy M
This paper reports estimates of the price elasticity of demand for heroin based on a newly constructed dataset. The dataset has two matched components concerning the same sample of regular heroin users: longitudinal information about real-world heroin demand (actual price and actual quantity at daily intervals for each heroin user in the sample) and experimental information about laboratory heroin demand (elicited by presenting the same heroin users with scenarios in a laboratory setting). Two empirical strategies are used to estimate the price elasticity of demand for heroin. The first strategy exploits the idiosyncratic variation in the price experienced by a heroin user over time that occurs in markets for illegal drugs. The second strategy exploits the experimentally induced variation in price experienced by a heroin user across experimental scenarios. Both empirical strategies result in the estimate that the conditional price elasticity of demand for heroin is approximately -0.80.
Harris, Brett R
Overdose deaths from heroin and prescription opioids have reached epidemic proportions in recent years. Deaths specifically involving heroin have more than tripled since 2011, and for the first time, drug overdose deaths have exceeded deaths resulting from motor vehicle accidents. This epidemic has been receiving attention among policymakers and the media which has resulted in efforts to provide training and education on prescribing practices, increase the use of naloxone, and expand the availability and use of Medication-Assisted Treatment (MAT). What is not being talked about is the relationship between early initiation of less harmful substances such as alcohol and marijuana and subsequent use of prescription opioids and heroin. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a model which shows promise for preventing initiation and reducing risky substance use among adolescents before it progresses to use of harder drugs such as heroin. Unfortunately, though recommended by the American Academy of Pediatrics, health care providers are not even screening their adolescent patients for substance use. The heroin and prescription opioid epidemic and the dissemination of information regarding federal, state, and local efforts to combat the epidemic provide a platform for increasing awareness of SBIRT, garnering support for more research, and facilitating uptake and integration into practice. It is time to add SBIRT to the conversation.
Schechter, Martin T; Kendall, Perry
The prescription of medically-supervised diacetylmorphine, the active ingredient in heroin, to individuals with treatment-refractory opioid dependence is a controversial and often politically charged subject. Just as methadone maintenance was opposed in the 1960s by some treatment providers who preferred abstinence-based therapies, heroin-assisted therapy is now being opposed by some methadone treatment providers--this despite the fact that the effectiveness of heroin-assisted treatment has been demonstrated in no less than six randomized trials in Switzerland, the Netherlands, Spain, Germany, Canada and the UK. The North American Opiate Medication Initiative (NAOMI) trial in Canada clearly showed heroin-assisted therapy to be superior to methadone in individuals with chronic, treatment-refractory heroin addiction both in terms of retention in addiction treatment and clinical response. An international internal review panel, three Research Ethics Boards, the CIHR RCT review panel, the Therapeutic Products Directorate of Health Canada, and several journal peer-reviewers reviewed the NAOMI trial. Nevertheless, authors of a commentary in this issue of CJPH find fault with the trial in terms of methadone prescribing, use of intention-to-treat analysis, safety and cost. We take this opportunity to respond to the numerous misconceptions and errors in their commentary.
Seifert, Christian L; Magon, Stefano; Sprenger, Till; Lang, Undine E; Huber, Christian G; Denier, Niklaus; Vogel, Marc; Schmidt, André; Radue, Ernst-Wilhelm; Borgwardt, Stefan; Walter, Marc
The neural mechanisms of heroin addiction are still incompletely understood, even though modern neuroimaging techniques offer insights into disease-related changes in vivo. While changes on cortical structure have been reported in heroin addiction, evidence from subcortical areas remains underrepresented. Functional imaging studies revealed that the brain reward system and particularly the nucleus accumbens (NAcc) play a pivotal role in the pathophysiology of drug addiction. The aim of this study was to investigate whether there was a volume difference of the NAcc in heroin addiction in comparison to healthy controls. A further aim was to correlate subcortical volumes with clinical measurements on negative affects in addiction. Thirty heroin-dependent patients under maintenance treatment with diacetylmorphine and twenty healthy controls underwent structural MRI scanning at 3T. Subcortical segmentation analysis was performed using FMRIB's Integrated Registration and Segmentation Tool function of FSL. The State-Trait Anxiety Inventory and the Beck Depression Inventory were used to assess trait anxiety and depressive symptoms, respectively. A decreased volume of the left NAcc was observed in heroin-dependent patients compared to healthy controls. Depression score was negatively correlated with left NAcc volume in patients, whereas a positive correlation was found between the daily opioid dose and the volume of the right amygdala. This study indicates that there might be structural differences of the NAcc in heroin-dependent patients in comparison with healthy controls. Furthermore, correlations of subcortical structures with negative emotions and opioid doses might be of future relevance for the investigation of heroin addiction.
Vassileva, Jasmin; Petkova, Pavlina; Georgiev, Stefan; Martin, Eileen M; Tersiyski, Ruslan; Raycheva, Margarita; Velinov, Vladimir; Marinov, Peter
Substance-dependent individuals (SDIs) often show neurocognitive deficits in decision-making, such that their choices are biased toward the greatest immediate reward rather than the optimal future outcome. However, studies of SDIs are often hampered by two significant methodological challenges: polysubstance dependence and comorbid conditions, which are independently associated with neurocognitive impairments. We addressed these methodological challenges by testing heroin addicts in Bulgaria, where heroin addiction is highly prevalent but polysubstance dependence is rare. The goal of the current study was to evaluate the potential contribution of psychopathy to decision-making processes among this group of Bulgarian heroin addicts. We tested 78 male currently abstaining heroin addicts, classified as psychopathic or non-psychopathic using the Hare Psychopathy Checklist, Revised (PCL-R). Psychopathic heroin addicts showed notable deficits in decision-making in that they made significantly more disadvantageous decisions relative to non-psychopathic heroin addicts. Results indicate that the presence of psychopathy may exacerbate decision-making deficits in heroin addicts.
Sutlović, Davorka; Definis-Gojanović, Marija
Drug abuse with alcohol consumption have been on the rise in Split-Dalmatian County for a while now. This article reports two separate cases with three deaths due to fatal combinations of heroin and alcohol. The first case of poisoning is related to a young couple, a 30-year-old man and a 28-year-old woman, who were found dead in a car, surrounded by cans of a variety alcoholic drinks. Two needles were found beside the bodies as well. The victims were registered drug abusers who had been in withdrawal programs. The second case was a 29-year-old man who was found dead in a house. Three fresh injection marks were visible on his right arm, and two needles were near his body. He was not known as a drug addict, but he had tried to commit suicide recently. Carboxyhaemoglobin was found in blood samples of both victims from the first case. The concentration was 25% and that could contribute to their death. In both described cases blood alcohol concentration was higher then 1.60 g kg(-1). Toxicology tests were positive for heroin, meconin, acetaminophen, 6-acetylmorphine, codeine, noscapine and papaverine. Ethanol, being a respiratory depressant, combined with morphine drastically increases the risk of rapid death due to respiration failure.
Gerra, Gilberto; Zaimovic, Amir; Moi, Gabriele; Bussandri, Monica; Bubici, Cristina; Mossini, Matteo; Raggi, Maria Augusta; Brambilla, Francesca
Objective measures of experimentally induced aggressiveness were evaluated in 20 abstinent heroin-dependent subjects, in comparison with 20 normal healthy male subjects. All the subjects were preliminarily submitted to DSM-IV interviews, Buss-Durkee Hostility Inventory (BDHI) and Minnesota Multiphasic Personality Inventory (MMPI II). During a laboratory task, the Point Subtraction Aggression Paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses and were provoked by the subtraction of money, which was attributed to a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). Money-earning responses were not different in drug-free heroin addicts and controls during the first two sessions and significantly lower during the third session in heroin-dependent subjects (t=2.99, P<.01). Aggressive responses were significantly higher (F=4.9, P<.01) in heroin addicted individuals, in comparison with controls. During the experimentally induced aggressiveness, plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) concentrations increased less significantly, and norepinephrine (NE) and epinephrine (EPI) levels, together with heart rate (HR), increased more significantly in abstinent heroin-dependent subjects than in healthy subjects. PSAP aggressive responses positively correlated with catecholamine changes, BDHI "direct" and "irritability" scores, MMPI "psychopathic deviate" scores in heroin-dependent subjects and controls, and with CORT responses only in healthy subjects. No correlation was found between heroin-exposure extent (substance abuse history duration) and aggressiveness levels. The present findings suggest that heroin-dependent patients have higher outward-directed aggressiveness than healthy subjects, in relation with monoamine hyperreactivity, after long-term opiate discontinuation. Aggressiveness in heroin addicts seems to be related more to the
Greenwald, Mark K; Steinmiller, Caren L; Sliwerska, Elzbieta; Lundahl, Leslie; Burmeister, Margit
Brain-derived neurotrophic factor (BDNF) Val(66)Met genotype has been associated with neurobehavioral deficits. To examine its relevance for addiction, we examined BDNF genotype differences in drug-seeking behavior. Heroin-dependent volunteers (n = 128) completed an interview that assessed past-month naturalistic drug-seeking/use behaviors. In African Americans (n = 74), the Met allele was uncommon (carrier frequency 6.8%); thus, analyses focused on European Americans (n = 54), in whom the Met allele was common (carrier frequency 37.0%). In their natural setting, Met carriers (n = 20) reported more time- and cost-intensive heroin-seeking and more cigarette use than Val homozygotes (n = 34). BDNF Val(66)Met genotype predicted 18.4% of variance in 'weekly heroin investment' (purchasing time × amount × frequency). These data suggest that the BDNF Met allele may confer a 'preferred drug-invested' phenotype, resistant to moderating effects of higher drug prices and non-drug reinforcement. These preliminary hypothesis-generating findings require replication, but are consistent with pre-clinical data that demonstrate neurotrophic influence in drug reinforcement. Whether this genotype is relevant to other abused substances besides opioids or nicotine, or treatment response, remains to be determined.
Barbier, Estelle; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Juergens, Nathan; Park, Paula E; Misra, Kaushik K; Cheng, Kejun; Rice, Kenner C; Schank, Jesse; Schulteis, Gery; Koob, George F; Heilig, Markus
Genetic deletion of the neurokinin 1 receptor (NK1R) has been shown to decrease the reinforcing properties of opioids, but it is unknown whether pharmacological NK1R blockade has the same effect. Here, we examined the effect of L822429, a rat-specific NK1R antagonist, on the reinforcing properties of heroin in rats on short (1 h: ShA) or long (12 h: LgA) access to intravenous heroin self-administration. ShA produces heroin self-administration rates that are stable over time, whereas LgA leads to an escalation of heroin intake thought to model important dependence-related aspects of addiction. L822429 reduced heroin self-administration and the motivation to consume heroin, measured using a progressive-ratio schedule, in both ShA and LgA rats. L822429 also decreased anxiety-like behavior in both groups, measured on the elevated plus maze, but did not affect mechanical hypersensitivity observed in LgA rats. Expression of TacR1 (the gene encoding NK1R) was decreased in reward- and stress-related brain areas both in ShA and LgA rats compared with heroin-naïve rats, but did not differ between the two heroin-experienced groups. In contrast, passive exposure to heroin produced increases in TacR1 expression in the prefrontal cortex and nucleus accumbens. Taken together, these results show that pharmacological NK1R blockade attenuates heroin reinforcement. The observation that animals with ShA and LgA to heroin were similarly affected by L822429 indicates that the SP/NK1R system is not specifically involved in neuroadaptations that underlie escalation resulting from LgA self-administration. Instead, the NK1R antagonist appears to attenuate acute, positively reinforcing properties of heroin and may be useful as an adjunct to relapse prevention in detoxified opioid-dependent subjects.
O’Brien, Charles P.
Heroin addiction is a complicated medical and psychiatric issue, with well-established as well as newer modes of treatment. The case of Ms W, a 50-year-old woman with a long history of opiate addiction who has been treated successfully with methadone for 9 years and who now would like to consider newer alternatives, illustrates the complex issues of heroin addiction. The treatment of heroin addiction as a chronic disease is reviewed, including social, medical, and cultural issues and pharmacologic treatment with methadone and the more experimental medication options of buprenorphine and naltrexone. PMID:18594026
Demaret, I; Lemaître, A; Ansseau, M
Heroin-assisted treatment (HAT) is a solution for improving the condition of treatment-resistant heroin addicts. Since 1994, six randomized controlled trials have concluded that HAT is more efficacious than oral methadone for severe heroin addicts. We visited seven HAT treatment centres in four countries in order to observe diacetylmorphine (DAM) administration and to study the main concerns of the staff. Nurses were concerned by the risk taken if a previously intoxicated patient received his dose of DAM. Another concern was the smuggling of DAM doses. The HAT centres face a dilemma: treating patients while at the same time allowing their risky street habits in the centre.
Greenwald, Mark K
A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n=12) received $4.00 for completing assessments at each thrice-weekly visit during dose tapering; 10 of 12 lapsed to heroin use 1 day after discharge. The abstinence reinforcement group (n=10) received $30.00 for each consecutive opioid-free urine sample; this significantly delayed heroin lapse (median, 15 days).
Jolley, Caroline J; Bell, James; Rafferty, Gerrard F; Moxham, John; Strang, John
Opioids are respiratory depressants and heroin/opioid overdose is a major contributor to the excess mortality of heroin addicts. The individual and situational variability of respiratory depression caused by intravenous heroin is poorly understood. This study used advanced respiratory monitoring to follow the time course and severity of acute opioid-induced respiratory depression. 10 patients (9/10 with chronic airflow obstruction) undergoing supervised injectable opioid treatment for heroin addiction received their usual prescribed dose of injectable opioid (diamorphine or methadone) (IOT), and their usual prescribed dose of oral opioid (methadone or sustained release oral morphine) after 30 minutes. The main outcome measures were pulse oximetry (SpO2%), end-tidal CO2% (ETCO2%) and neural respiratory drive (NRD) (quantified using parasternal intercostal muscle electromyography). Significant respiratory depression was defined as absence of inspiratory airflow >10s, SpO2% < 90% for >10s and ETCO2% per breath >6.5%. Increases in ETCO2% indicated significant respiratory depression following IOT in 8/10 patients at 30 minutes. In contrast, SpO2% indicated significant respiratory depression in only 4/10 patients, with small absolute changes in SpO2% at 30 minutes. A decline in NRD from baseline to 30 minutes post IOT was also observed, but was not statistically significant. Baseline NRD and opioid-induced drop in SpO2% were inversely related. We conclude that significant acute respiratory depression is commonly induced by opioid drugs prescribed to treat opioid addiction. Hypoventilation is reliably detected by capnography, but not by SpO2% alone. Chronic suppression of NRD in the presence of underlying lung disease may be a risk factor for acute opioid-induced respiratory depression.
Matyas, Gary R; Rice, Kenner C; Cheng, Kejun; Li, Fuying; Antoline, Joshua F G; Iyer, Malliga R; Jacobson, Arthur E; Mayorov, Alexander V; Beck, Zoltan; Torres, Oscar B; Alving, Carl R
Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphoryl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 ("true") specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine.
Mills, Katherine L; Teesson, Maree; Darke, Shane; Ross, Joanne; Lynskey, Michael
This paper examines the patterns and correlates of heroin use in a cohort of 210 young Australians aged between 18 and 24, who were participants in the Australian Treatment Outcome Study, a longitudinal study of treatment outcomes for heroin dependence. Of major importance were the high rates of psychiatric comorbidity found among this group (37% lifetime Post Traumatic Stress Disorder, 23% current Major Depression, 75% Anti-Social Personality Disorder, and 51% Borderline Personality Disorder). Seventeen percent had attempted suicide in the preceding year. Although both the young (aged 18-24 years) heroin users and their older counterparts (aged 25-56 years) initiated drug use at the same age, young heroin users progressed to heroin use, regular heroin use, and treatment for heroin use, twice as quickly as older heroin users. These findings suggest that there is a limited window of opportunity in which early interventions may be applied before young heroin users progress to problematic use.
... to a group of pain-relieving drugs called narcotics. Although certain narcotics such as codeine and morphine are legal if ... or breaks a bone, heroin is an illegal narcotic because it is has dangerous side effects and ...
Christie, D.J.; Walker, R.H.; Kolins, M.D.; Wilner, F.M.; Aster, R.H.
Profound thrombocytopenia developed in a 22-year-old man after intravenous use of heroin. A high-titer, quinine-dependent, platelet-specific antibody was detected in his serum using lysis of normal platelets labeled with chromium 51 and an electroimmunoassay for measurement of platelet-associated IgG. The antibody was specific for quinine and failed to react with platelets in the presence of quinidine hydrochloride or two structural analogues of heroin. Quinine, a common adulterant found in heroin, was detected in the patient's blood and urine. On the basis of these observations, the patient was judged to have quinine-induced immunologic thrombocytopenia. To our knowledge, this report is the first to confirm that quinine used as an adulterant can induce immunologic thrombocytopenia following an injection of heroin.
Gerra, G; Ferri, M; Zaimovic, A; Giucastro, G; Palladino, M; Sartori, R; Delsignore, R; Maestri, D; Marzocchi, G; Brambilla, F
The function of the GABAergic system was examined in 20 subjects with heroin dependence and abuse, 2 months after detoxification, and in 10 healthy volunteers, by measuring the growth hormone (GH) response to a challenge with the GABA B receptor agonist baclofen. Ten heroin addicts had comorbid anxiety disorder (Group A), while the other ten had heroin addiction uncomplicated by Axis I and II psychopathologies (Group B). GH responses to baclofen stimulation of Group A patients were significantly blunted, while those of Group B subjects did not differ from responses of healthy volunteers. Our data show that the function of the GABAergic system is impaired only in heroin addicts with comorbid anxiety disorders (anxious cluster), suggesting that the GABA system is not persistently influenced by prolonged exposure to opioid receptor stimulation.
Knight, Julie; Puet, Brandi L; DePriest, Anne; Heltsley, Rebecca; Hild, Cheryl; Black, David L; Robert, Timothy; Caplan, Yale H; Cone, Edward J
Surveys of current trends indicate heroin abuse is associated with nonmedical use of pain relievers. Consequently, there is an interest in evaluating the presence of heroin-specific markers in chronic pain patients who are prescribed controlled substances. A total of 926,084 urine specimens from chronic pain patients were tested for heroin/diacetylmorphine (DAM), 6-acetylmorphine (6AM), 6-acetylcodeine (6AC), codeine (COD), and morphine (MOR). Heroin and markers were analyzed using liquid chromatography tandem mass spectrometry (LC-MS-MS). Opiates were analyzed following hydrolysis using LC-MS-MS. The prevalence of heroin use was 0.31%, as 2871 were positive for one or more heroin-specific markers including DAM, 6AM, or 6AC (a known contaminant of illicit heroin). Of these, 1884 were additionally tested for the following markers of illicit drug use: 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine (MAMP), 11-nor-9-carboxy-Δ(9)-tetracannabinol (THCCOOH), and benzoylecgonine (BZE); 654 (34.7%) had positive findings for one or more of these analytes. The overall prevalence of heroin markers were as follows: DAM 1203 (41.9%), 6AM 2570 (89.5%), 6AC 1082 (37.7%). MOR was present in 2194 (76.4%) and absent (
Zhao, Bin; Zhu, Yongsheng; Wang, Wei; Cui, Hai-Min; Wang, Yun-Peng; Lai, Jiang-Hua
The glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor was recently shown to be involved in the development of opiate addiction. Genetic polymorphisms in GRIN2A have a plausible role in modulating the risk of heroin addiction. An association of GRIN2A single-nucleotide polymorphisms (SNPs) with heroin addiction was found earlier in African Americans. To identify markers that contribute to the genetic susceptibility to heroin addiction, we examined the potential association between heroin addiction and forty polymorphisms of the GRIN2A gene using the MassARRAY system and GeneScan in this study. The frequency of the (GT)26 repeats (rs3219790) in the heroin addiction group was significantly higher than that in the control group (χ(2) = 5.360, P = 0.021). The allele frequencies of three polymorphisms (rs1102972, rs1650420, and rs3104703 in intron 3) were strongly associated with heroin addiction (P<0.001, 0.0002, and <0.001, after Bonferroni correction). Three additional SNPs from the same intron (rs1071502, rs6497730, and rs1070487) had nominally significant P values for association (P<0.05), but did not pass the threshold value. Haplotype analysis revealed that the G-C-T-C-C-T-A (block 6) and T-T (block 10) haplotypes of the GRIN2A gene displayed a protective effect (P = <0.001 and 0.003). These findings point to a role for GRIN2A polymorphisms in heroin addiction among the Han Chinese from Shaanxi province, and may be informative for future genetic or neurobiological studies on heroin addiction.
Sneyd, J R; Meyer-Witting, M
Intrathecal diamorphine (heroin, diacetyl morphine) 2.5 mg in isotonic saline 2.5 ml was given to 13 patients in labour through a 26 gauge Quincke needle. Three patients were given epidural bupivacaine at a mean of 295 min after injection of diamorphine and a further 2 used 50% nitrous oxide during the second stage of labour. Eight patients needed no additional analgesia for labour although 1 received a pudendal nerve block for forceps delivery. No neonatal complications attributable to diamorphine were observed. There was a high incidence of post partum headache (6/13 cases). The use of a Sprotte needle and a fine spinal catheter might overcome the limitations of spinal headache and limited duration of action respectively.
Hatem, G; Merritt, J C; Cowan, C L
Two healthy young black men developed panophthalmitis after intravenous heroin injections. Bacillus cereus, considered to be a relatively noncommon pathogen for man, was found to be the causative agent as it was recovered from the anterior chamber and viterous cavity of both cases. The ocular findings were unilateral in each case, and neither patient had any sistemic involvement from the bacteremia. The onset of visual symptoms varied from 24 to 36 hours after the last intravenous injection with the eye becoming rapidly blind. Photographs of the early fundus lesions included preretinal hypopyon-like lesions and peculiar changes in the blood vasculature. Intracameral gentamicin and steroids did not alter the cause, and treatment was enucleation.
Zamir, Ashira; Cohen, Yaron; Azoury, Myriam
A large amount of heroin street doses are seized and examined for drug content by the Israel police. These are generally wrapped in heat-sealed plastic. Occasionally it is possible to visualize latent fingerprints on the plastic wrap itself, but the small size of the plastic item and the sealing process makes the success rate very low. In this study, the possibility of extracting and profiling DNA from the burnt edge of the plastic wrap was investigated. The idea was based on the assumption that epithelial cells might be trapped during the sealing process. The results show that there are sufficient quantities of DNA deposited at the "amorphic" burnt edges of sealed street doses for DNA profiling to be carried out. A controlled experiment using a known donor was performed. This subject carried out sealing of "street drug" packages and consequent DNA extractions were performed to show that known DNA profiles could be recovered from such packages, as a result of handling by the "packer." "Square-like" burnt edges did not yield DNA profiles, probably because of differences in the sealing process. It was also shown that DNA could be recovered from the plastic wrap itself and not only from the amorphic burnt edges. As heroin dealers and drug users are often involved in other crimes and run-ins with the law, the effective extraction and addition of their DNA profiles from such items of evidence to the newly established DNA database in Israel provides new avenues in the continued fight against crime and drug traffickers.
Motlagh, Farid; Ibrahim, Fatimah; Menke, J Michael; Rashid, Rusdi; Seghatoleslam, Tahereh; Habil, Hussain
Neuroelectrophysiological properties have been used in human heroin addiction studies. These studies vary in their approach, experimental conditions, paradigms, and outcomes. However, it is essential to integrate previous findings and experimental methods for a better demonstration of current issues and challenges in designing such studies. This Review examines methodologies and experimental conditions of neuroelectrophysiological research among heroin addicts during withdrawal, abstinence, and methadone maintenance treatment and presents the findings. The results show decrements in attentional processing and dysfunctions in brain response inhibition as well as brain activity abnormalities induced by chronic heroin abuse. Chronic heroin addiction causes increased β and α2 power activity, latency of P300 and P600, and diminished P300 and P600 amplitude. Findings confirm that electroencephalography (EEG) band power and coherence are associated with craving indices and heroin abuse history. First symptoms of withdrawal can be seen in high-frequency EEG bands, and the severity of these symptoms is associated with brain functional connectivity. EEG spectral changes and event-related potential (ERP) properties have been shown to be associated with abstinence length and tend to normalize within 3-6 months of abstinence. From the conflicting criteria and confounding effects in neuroelectrophysiological studies, the authors suggest a comprehensive longitudinal study with a multimethod approach for monitoring EEG and ERP attributes of heroin addicts from early stages of withdrawal until long-term abstinence to control the confounding effects, such as nicotine abuse and other comorbid and premorbid conditions.
Yue, Kai; Ma, Baomiao; Ru, Qin; Chen, Lin; Gan, Yongping; Wang, Daisong; Jin, Guozhang; Li, Chaoying
Opiate addiction is a chronic recrudescent disorder characterized by a high rate of relapse. Levo-tetrahydropalmatine (l-THP) is an alkaloid substance extracted from Corydalis and Stephania and is contained in a number of traditional Chinese herbal preparations. Compared to other dopamine receptor antagonists, l-THP has lower affinity for D2 receptors than for D1 receptors, and a recent study showed that l-THP also binds to D3 receptors, possibly functioning as an antagonist. The unique pharmacological profile of l-THP suggests that l-THP may be effective for the treatment of opiate addiction. In this study, we investigated the effects of l-THP on heroin self-administration and reinstatement triggered by a priming injection of heroin in abstinent rats trained to stably self-administer heroin under an extinction/reinstatement protocol, and found that l-THP (2.5 and 5 mg/kg, i.p.) decreased heroin self-administration on the fixed-ratio 1 schedule and dose-dependently (1.25, 2.5 and 5 mg/kg, i.p.) inhibited heroin-induced reinstatement of heroin-seeking behavior. Importantly, l-THP (1.25 and 2.5 mg/kg, i.p.) did not affect locomotion, indicating that the observed effects of l-THP on reinstatement do not appear to be due to motor impairments. The present results demonstrated that dopamine receptor antagonist l-THP attenuates heroin self-administration and heroin-induced reinstatement.
Sun, Yan; Zhao, Li-Yan; Wang, Gui-Bin; Yue, Wei-Hua; He, Yong; Shu, Ni; Lin, Qi-Xiang; Wang, Fan; Li, Jia-Li; Chen, Na; Wang, Hui-Min; Kosten, Thomas R; Feng, Jia-Jia; Wang, Jun; Tang, Yu-De; Liu, Shu-Xue; Deng, Gui-Fa; Diao, Gan-Huan; Tan, Yun-Long; Han, Hong-Bin; Lin, Lu; Shi, Jie
Drug addiction shares common neurobiological pathways and risk genes with other psychiatric diseases, including psychosis. One of the commonly identified risk genes associated with broad psychosis has been ZNF804A. We sought to test whether psychosis risk variants in ZNF804A increase the risk of heroin addiction by modulating neurocognitive performance and gray matter volume (GMV) in heroin addiction. Using case-control genetic analysis, we compared the distribution of ZNF804A variants (genotype and haplotype) in 1035 heroin abusers and 2887 healthy subjects. We also compared neurocognitive performance (impulsivity, global cognitive ability and decision-making ability) in 224 subjects and GMV in 154 subjects based on the ZNF804A variants. We found significant differences in the distribution of ZNF804A intronic variants (rs1344706 and rs7597593) allele and haplotype frequencies between the heroin and control groups. Decision-making impairment was worse in heroin abusers who carried the ZNF804A risk allele and haplotype. Subjects who carried more risk alleles and haplotypes of ZNF804A had greater GMV in the bilateral insular cortex, right temporal cortex and superior parietal cortex. The interaction between heroin addiction and ZNF804A variants affected GMV in the left sensorimotor cortex. Our findings revealed several ZNF804A variants that were significantly associated with the risk of heroin addiction, and these variants affected decision making and GMV in heroin abusers compared with controls. The precise neural mechanisms that underlie these associations are unknown, which requires future investigations of the effects of ZNF804A on both dopamine neurotransmission and the relative increases in the volume of various brain areas.
Maxwell, Jane Carlisle; Spence, Richard T.
Aims To undertake an exploratory study to examine the characteristics of patients in narcotic treatment programs who started their use of black tar heroin either as inhalers or as injectors and to compare them with those who started as inhalers but shifted to injecting. Other studies in this area have used subjects using other forms of heroin more amenable to inhaling. Participants, Design, and Measurement A purposive sample of 199 patients in 6 methadone programs in Texas were interviewed in 2002-2003 using a structured instrument. Findings At admission to treatment, those who were heroin inhalers were more likely to be African American, to live with their families, to have income from wages, and to report fewer days of problems on most of the ASI measures. Those who shifted from inhaling to injecting were more likely to be Hispanic and to have had mental health problems that interfered with their lives and to have had less nurturing while growing up. Injectors were older at this treatment admission, had more treatment episodes and more times in jail, and were more likely to have hepatitis C, AIDS, or gonorrhea. There were high levels of physical and mental problems and histories of traumatization as children and adults for almost all the respondents. Males were as likely as females to have been sexually abused as children or as adults. Conclusions The high rates of mental and physical problems among all the clients interviewed showed the need for comprehensive services to be delivered within the substance abuse treatment programs. Histories of trauma and sexual abuse should be addressed for both male and female clients. PMID:21552428
Darke, S; Sunjic, S; Zador, D; Prolov, T
Blood toxicology results for deaths attributed to heroin overdose during 1995 in the South Western Sydney (SWS) region (n = 39) were compared with those of a sample of 100 current SWS heroin users who had injected within the preceding 24 h. Heroin-related deaths had a higher median concentration of morphine than current heroin users (0.35 versus 0.09 mg/l). However, there was substantial overlap between the blood morphine concentrations of the two groups, ranging from 0.08-1.45 mg/l. This range incorporated 90% of heroin-related deaths. A third of current users had morphine concentrations over twice the toxic blood morphine concentration employed by the analytical laboratories, and 7% had morphine levels higher than the median recorded for fatal cases. Alcohol was detected in 51% of fatal cases (median = 0.10 g/100 ml) compared with 1% of current heroin user. There was a significant negative correlation among fatal cases between blood morphine and blood alcohol concentrations (r2 = -0.41). There was no significant difference between groups in the proportions of subjects positive for blood benzodiazepines. The results raise questions about the mechanisms of death in what are termed overdoses, and about the role of alcohol in these fatalities.
Lintzeris, Nicholas; Strang, John; Metrebian, Nicola; Byford, Sarah; Hallam, Christopher; Lee, Sally; Zador, Deborah
Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades, the numbers receiving injectable opioid treatment (IOT) has been steadily diminishing in recent years. In contrast, there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities, although the evidence regarding the safety, efficacy and cost effectiveness of this treatment approach remains equivocal. Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high-quality oral methadone treatment who continue to regularly inject heroin, and that treatment be initiated in newly-developed supervised injecting clinics. The Randomised Injectable Opioid Treatment Trial (RIOTT) is a multisite, prospective open-label randomised controlled trial (RCT) examining the role of treatment with injected opioids (methadone and heroin) for the management of heroin dependence in patients not responding to conventional substitution treatment. Specifically, the study examines whether efforts should be made to optimise methadone treatment for such patients (e.g. regular attendance, supervised dosing, high oral doses, access to psychosocial services), or whether such patients should be treated with injected methadone or heroin. Eligible patients (in oral substitution treatment and injecting illicit heroin on a regular basis) are randomised to one of three conditions: (1) optimized oral methadone treatment (Control group); (2) injected methadone treatment; or (3) injected heroin treatment (with access to oral methadone doses). Subjects are followed up for 6-months, with between-group comparisons on an intention-to-treat basis across a range of outcome measures. The primary outcome is the proportion of patients who discontinue regular illicit heroin use (operationalised as providing >50% urine drug screens negative for markers of
Solis, Ernesto; Bola, R Aaron; Fasulo, Bradley J; Kiyatkin, Eugene A
Glucose enters the brain extracellular space from arterial blood, and its proper delivery is essential for metabolic activity of brain cells. By using enzyme-based biosensors coupled with high-speed amperometry in freely moving rats, we previously showed that glucose levels in the nucleus accumbens (NAc) display high variability, increasing rapidly following exposure to various arousing stimuli. In this study, the same technology was used to assess NAc glucose fluctuations induced by intravenous heroin. Heroin passively injected at a low dose optimal for maintaining self-administration behavior (100 μg/kg) induces a rapid but moderate glucose rise (∼150-200 μM or ∼15-25% over resting baseline). When the heroin dose was doubled and tripled, the increase became progressively larger in magnitude and longer in duration. Heroin-induced glucose increases also occurred in other brain structures (medial thalamus, lateral striatum, hippocampus), suggesting that brain hyperglycemia is a whole-brain phenomenon but changes were notably distinct in each structure. While local vasodilation appears to be the possible mechanism underlying the rapid rise in extracellular glucose levels, the driving factor for this vasodilation (central vs peripheral) remains to be clarified. The heroin-induced NAc glucose increases positively correlated with increases in intracerebral heat production determined in separate experiments using multisite temperature recordings (NAc, temporal muscle and skin). However, glucose levels rise very rapidly, preceding much slower increases in brain heat production, a measure of metabolic activation associated with glucose consumption.
Postmortem sole incisions have been observed in a number of heroin overdose fatalities. Acqueintance of those victims confessed to producing those incisions as a life saving procedure in a futile attempt to help the comatose overdose victim. They thought that bleeding the unconscious victim would remove the overdose, in manner similar to bloodletting or phlebotomy which is still popular in the Gulf region. The presence of such wounds has become a first indication or rather "sign" of heroin poisoning. In such cases, laboratory investigation confirmed the pathologist's preliminary suspicion. In Dubai, postmortem sole incisions are important sign of death from heroin overdose even in the absence of other classical signs. This sign becomes more credible when accompanied by other signs and/or circumstantial evidence suggestive of heroin use. It is suggested that this should be called "bloodletting sign" of death from heroin overdose. The sign should not be confused with the self-inflicted cuts seen on the arms and forearms of drug misusers which are caused for other reasons.
Strandberg, Joakim J; Kugelberg, Fredrik C; Alkass, Kanar; Gustavsson, Anna; Zahlsen, Kolbjørn; Spigset, Olav; Druid, Henrik
In heroin overdose deaths the blood morphine concentration varies substantially. To explore possible pharmacokinetic explanations for variable sensitivity to opiate toxicity we studied mortality and drug concentrations in male Sprague-Dawley rats. Groups of rats were injected intravenously (i.v.) with heroin, 21.5 mg/kg, or morphine, 223 mg/kg, causing a 60-80% mortality among drug-naïve rats. Additional groups of rats were pre-treated with morphine for 14 days, with or without 1 week of subsequent abstinence. Brain, lung and blood samples were analyzed for 6-acetylmorphine, morphine, morphine-3-glucuronide and morphine-6-glucuronide. i.v. morphine administration to drug-naïve rats resulted in both rapid and delayed deaths. The brain morphine concentration conformed to an exponential elimination curve in all samples, ruling out accumulation of morphine as an explanation for delayed deaths. This study found no support for formation of toxic concentration of morphine-6-glucuronide. Spontaneous death among both heroin and morphine rats occurred at fairly uniform brain morphine concentrations. Morphine pre-treatment significantly reduced mortality upon i.v. morphine injection, but the protective effect was less evident upon i.v. heroin challenge. The morphine pre-treatment still afforded some protection after 1 week of abstinence among rats receiving i.v. morphine, whereas rats given i.v. heroin showed similar death rate as drug-naïve rats.
Kosel, Markus; Noss, Roger S; Hämmig, Robert; Wielepp, Peter; Bundeli, Petra; Heidbreder, Rebeca; Kinser, Jane A; Brenneisen, Rudolf; Fisch, Hans-Ulrich; Kayser, Sarah; Schlaepfer, Thomas E
We examined acute effects of intravenous diacetylmorphine (heroin) administration - which induces a characteristic biphasic response: A short rush-sensation associated with intense pleasurable feelings followed by a subjectively different period of euphoria on cerebral blood flow. This was assessed in nine male heroin dependent patients participating in a heroin maintenance program in a setting resembling everyday pattern of heroin abuse. 99mTc-HMPAO was administered 45 s (rush) and 15 min (euphoria) after administration of i.v. heroin and 45 s after administration of saline (placebo). Plasma concentration of diacetylmorphine and its metabolites were measured with high-pressure liquid chromatography (HPLC). Compared to the euphoria condition, rush was associated with blood flow increase in the left posterior cerebellar lobe, left anterior cingulate gyrus and right precuneus. Our results are in line with recent reports indicating that the cerebellum is an important component in functional brain systems subserving sensory and motor integration, learning, modulation of affect, motivation and social behaviour, which all play important roles in reinforcing properties of opioids.
Ornoy, Asher; And Others
Children born to heroin-dependent mothers (n=83) were compared to 76 children born to heroin-dependent fathers and to 3 control groups with and without environmental deprivation and health problems. Results found that developmental delays and behavioral disorders found among heroin-exposed children resulted primarily from severe environmental…
Greenwell, Thomas N; Walker, Brendan M; Cottone, Pietro; Zorrilla, Eric P; Koob, George F
Previous studies have reported that noradrenergic antagonists alleviate some of the symptoms of opiate withdrawal and dependence. Clinical studies also have shown that modification of the noradrenergic system may help protect patients from relapse. The present study tested the hypothesis that a dysregulated noradrenergic system has motivational significance in heroin self-administration of dependent rats. Prazosin, an alpha1-adrenergic antagonist (0.5, 1.0, 1.5 and 2.0 mg/kg, i.p.), was administered to adult male Wistar rats with a history of limited (1 h/day; short access) or extended (12 h/day; long access) access to intravenous heroin self-administration. Prazosin dose-dependently reduced heroin self-administration in long-access rats but not short-access rats, with 2 mg/kg of systemic prazosin significantly decreasing 1 h and 2 h heroin intake. Prazosin also reversed some changes in meal pattern associated with extended heroin access, including the taking of smaller and briefer meals (at 3 h), while also increasing total food intake and slowing the eating rate within meals (both 3 h and 12 h). Thus, prazosin appears to stimulate food intake in extended access rats by restoring meals to the normal size and duration. The data suggest that the alpha1 adrenergic system may contribute to mechanisms that promote dependence in rats with extended access.
Tortajada, Silvia; Herrero, Ma Jesús; Domingo-Salvany, Antònia; Molist, Gemma; Barrio, Gregorio; de la Fuente, Luís; Brugal, Ma Teresa
Drug abuse is a serious public health problem. Moreover, co-occurring mental health and substance abuse disorders are common among drug users. This paper examines psychiatric disorders of young cocaine and heroin users using the World Mental Health Composite International Diagnostic Interview (WMH-CIDI). A cohort of 1266 young (18-30 years) current regular cocaine (705) and heroin (561) users were recruited outside the health services in Barcelona, Madrid and Seville, Spain. The WMH-CIDI was used to evaluate mental disorders; the Severity of Dependence Scale (SDS) measured the degree of dependence; and the Duke-UNC Functional Social Support Questionnaire (FSSQ) assessed social support, in a crosssectional study design. About 43% was diagnosed with a lifetime mental disorder. The most common diagnoses were depression (37.5%) and specific phobia (6.8%). During the last 12 months, prevalence rates were also slightly higher in heroin group (26.4%) than in cocaine cohort (21.7%). Every day cocaine consumption, having unstable living conditions and low social support were variables highly associated with psychiatric morbidity in cocaine cohort. In heroin cohort, earning money through illegal activities was associated with psychiatric morbidity, while the moderate use of alcohol acted as a protective factor for mental pathology. Morbidity was associated to having received psychiatric/psychological treatment during the last 12 months in both cohorts. This study has shown a relatively high prevalence of psychiatric morbidity in cocaine and heroin users recruited in non-clinical settings. Future studies examining differences between cocaine and heroin patterns of consumption associated with mental diseases are necessary.
Comer, Sandra D; Collins, Eric D; Fischman, Marian W
Several sources indicate that intravenously administered buprenorphine may have significant abuse liability in humans. The present study evaluated the reinforcing effects of intravenously administered buprenorphine (0, 2, and 8 mg) in detoxified heroin-dependent participants during a 7.5-week inpatient study. Participants (n = 6) were detoxified from heroin over a 1.5-week period immediately after admission. Testing subsequently occurred in three 2-week blocks. During the first week of each 2-week block, the reinforcing effects of buprenorphine were evaluated. Participants first received a dose of buprenorphine and $20 and then were given either the opportunity to self-administer the dose or $20 during choice sessions. During the second week of each 2-week block, the direct effects of heroin were measured to evaluate potential long-lasting antagonist effects of buprenorphine. Progressive ratio break-point values were significantly higher after 2 and 8 mg of buprenorphine compared with placebo. Correspondingly, several positive subjective ratings increased after administration of active buprenorphine relative to placebo. Although there were few differences in peak effects produced by 2 versus 8 mg of buprenorphine, the higher buprenorphine dose generally produced longer-lasting effects. Heroin also produced dose-related increases in several subjective effects. Peak ratings produced by heroin were generally higher than peak ratings produced by buprenorphine. There was little evidence of residual antagonism produced by buprenorphine. These results demonstrate that buprenorphine served as a reinforcer under these conditions, and that it may have abuse liability in nonopioid-dependent individuals who abuse heroin.
Hyde, Sandra Teresa
This article focuses on one residential therapeutic community for the treatment of heroin and opiate addiction in contemporary China. It discusses 2 case vignettes and shows that although addictions are extremely difficult to treat, there are small successes being reached in China's southwest. Residential treatment communities follow mobile global practices that link Western models of 12-step Narcotics Anonymous, self-healing, to other Chinese practices like Maoist "speak bitterness." In China it is in the drug aid theaters where Sunlight-International traveled to do three things: (a) stave off the American drug market, (b ) reduce drug trafficking across national borders, and (c) address the psychosocial problems associated with global drug trafficking and consumption. Through the process of unraveling the on-the-ground practices of public health international humanitarian nongovernmental organizations and some of their therapeutic models, we begin to see new alliances formed across the globe around drug treatment and care that point toward important results.
Dayakar, MM; Akbar, SM
Aim: To study the efficacy of a noninjectable anesthetic gel with a thermosetting agent in the reduction of pain during scaling and root planing (SRP) in untreated chronic periodontitis patients. Materials and Methods: This study is a randomized, double-masked, split-mouth, placebo-controlled trial. Thirty patients were enrolled who underwent SRP in a split-mouth (right side/left side) manner. Before commencement of SRP, both quadrants on each side were isolated and had a randomized gel (either placebo or test gel) placed in the periodontal pockets for 30 s. The pain was measured using numerical rating scale (NRS) and verbal rating scale (VRS). Results: The median NRS pain score for the patients treated with the anesthetic test gel was 1 (range: 0-4) as opposed to 5 (range: 3-7) in the placebo treated patients. The mean rank of pain score using NRS in test gel was 16.18 as compared to 44.82 in placebo treated sites. Hence, significant reduction in pain was found in test gel as compared to placebo using NRS (P < 0.001). The VRS showed that the majority of patients reported no pain or mild pain with a median of 1 as compared to placebo treated sites with a median of 2 suggestive of moderate pain. Conclusions: The NRS and VRS pain scores showed that the side treated with anesthetic gel was statistically more effective than the placebo in reducing pain during SRP. PMID:27051372
Ringertz, S H; Høiby, E A; Jensenius, M; Maehlen, J; Caugant, D A; Myklebust, A; Fossum, K
Anthrax is rare in western Europe but may arise sporadically in people exposed to animal products from endemic areas. A heroin-injecting drug user presented with a severe soft-tissue infection at the injection site, septic shock, and meningitis. A gram-positive endospore-forming aerobic rod was isolated from the soft tissue and cerebrospinal fluid; confirmation of Bacillus anthracis was made by PCR. Since contaminated heroin was the probable source of infection, this case is of concern and warrants surveillance.
from a study of the metabolism of radiolabeled cocaine.6 Later, cocaine was found in the saliva of impaired drivers.7 Most studies show similar...reported.9,10 The latter was a controlled study examined the metabolism of heroin in plasma and saliva. This study followed the metabolism of heroin by...in Table 1. Table 1 - HPLC Conditions Column: Alltech/Applied Science Econosphere C8, 250 x 4.6 mm Solvent A: 0.1M Ammonium Acetate Solvent B: 10:90
In this short report the evidence is given (based on the analyses of 22 case samples) that noscapine can be used as an adulterant in illicit heroin samples. In this context, the appearance of illicit heroin samples characterised by a high noscapine content (up to 61%) and a high noscapine/whole morphine ratio (up to 3.5) is highlighted. All samples discussed in the paper (132) were seized in Slovenia, in the period from 1997 to 1999 and were analysed by gas chromatography-mass spectrometry.
drug deterrence program were raised from 300 ng/ml to 4000 ng/ml for morphine and 2000 ng/ml for codeine in an attempt to distinguish between poppy seed ...Naval Research Laboratory Washington, DC 20375-5000 NRL Memorandum Report 6512 Options to Distinguish Heroin and Poppy Seed Use r- I- FCTE DAVID...Options to Distinguish Heroin and Poppy Seed Use 12 PERSONAL AUTHOR(S) Kidwell. D.A. 13a TYPE OF REPORT 113b TIME COVERED 14 DATE OF REPORT (Year
Rambod, Mehdi; Elhanafi, Sherif; Mukherjee, Debabrata
Brugada phenocopy describes conditions with Brugada-like ECG pattern but without true congenital Brugada syndrome. We report a case of 44-year-old man with no known medical history who presented with loss of consciousness. Toxicology screening was positive for opiates and high serum alcohol level. His initial ECG showed Brugada type 1 pattern which resolved after several hours of observation and treatment with continuous naloxone infusion. Patient regained his consciousness and disclosed heroin abuse and drinking alcohol. This case highlights the heroin overdose as a possible cause of Brugada phenocopy.
Clatts, Michael C; Goldsamt, Lloyd A; Giang, Le Minh; Colón-López, Vivian
This paper examines changes in the interval between first heroin smoking and onset of injection in a large, out-treatment sample of male heroin users in Hanoi, Vietnam (n = 1,115). Mean age at initiation of heroin use (smoking) was 18.4 and mean age of onset of heroin injection was 20.9 years. Full multivariate analysis indicates that the interval between first heroin use (smoking) and first heroin injection has been significantly attenuated among more recent heroin initiates (P = 0.0043), suggesting that heroin users in Vietnam may be at increased risk for exposure to HIV relatively soon after onset of heroin use, highlighting the need for behavioral interventions that target heroin smokers. Critical intervention goals include delaying the onset of injection and improved education about safer drug sharing and drug injection practices.
White, Emma; Comiskey, Catherine
The UN [United Nations Office on Drugs and Crime (UNODC): World Drug Report, 2005, vol. 1: Analysis. UNODC, 2005.], EU [European Monitoring Centre for Drugs and Drug Addiction (EMCDDA): Annual Report, 2005.http://annualreport.emcdda.eu.int/en/home-en.html.] and WHO [World Health Organisation (WHO): Biregional Strategy for Harm Reduction, 2005-2009. HIV and Injecting Drug Use. WHO, 2005.] have consistently highlighted in recent years the ongoing and persistent nature of opiate and particularly heroin use on a global scale. While this is a global phenomenon, authors have emphasised the significant impact such an epidemic has on individual lives and on society. National prevalence studies have indicated the scale of the problem, but the drug-using career, typically consisting of initiation, habitual use, a treatment-relapse cycle and eventual recovery, is not well understood. This paper presents one of the first ODE models of opiate addiction, based on the principles of mathematical epidemiology. The aim of this model is to identify parameters of interest for further study, with a view to informing and assisting policy-makers in targeting prevention and treatment resources for maximum effectiveness. An epidemic threshold value, R(0), is proposed for the drug-using career. Sensitivity analysis is performed on R(0) and it is then used to examine the stability of the system. A condition under which a backward bifurcation may exist is found, as are conditions that permit the existence of one or more endemic equilibria. A key result arising from this model is that prevention is indeed better than cure.
Clarke, T-K; Ambrose-Lanci, L; Ferraro, T N; Berrettini, W H; Kampman, K M; Dackis, C A; Pettinati, H M; O'Brien, C P; Oslin, D W; Lohoff, F W
Genetic factors are believed to account for 30-50% of the risk for cocaine and heroin addiction. Dynorphin peptides, derived from the prodynorphin (PDYN) precursor, bind to opioid receptors, preferentially the kappa-opioid receptor, and may mediate the aversive effects of drugs of abuse. Dynorphin peptides produce place aversion in animals and produce dysphoria in humans. Cocaine and heroin have both been shown to increase expression of PDYN in brain regions relevant for drug reward and use. Polymorphisms in PDYN are therefore hypothesized to increase risk for addiction to drugs of abuse. In this study, 3 polymorphisms in PDYN (rs1022563, rs910080 and rs1997794) were genotyped in opioid-addicted [248 African Americans (AAs) and 1040 European Americans (EAs)], cocaine-addicted (1248 AAs and 336 EAs) and control individuals (674 AAs and 656 EAs). Sex-specific analyses were also performed as a previous study identified PDYN polymorphisms to be more significantly associated with female opioid addicts. We found rs1022563 to be significantly associated with opioid addiction in EAs [P = 0.03, odds ratio (OR) = 1.31; false discovery rate (FDR) corrected q-value]; however, when we performed female-specific association analyses, the OR increased from 1.31 to 1.51. Increased ORs were observed for rs910080 and rs199774 in female opioid addicts also in EAs. No statistically significant associations were observed with cocaine or opioid addiction in AAs. These data show that polymorphisms in PDYN are associated with opioid addiction in EAs and provide further evidence that these risk variants may be more relevant in females.
Yuan, Jie; Liu, Xing Dang; Han, Mei; Lv, Rong Bin; Wang, Yuan Kai; Zhang, Guang Ming; Li, Yu
To compare the effects of heroin and methamphetamine (METH) addiction on dopamine transporters (DATs) in the same dose and duration, we assessed DAT levels in the striatum by (99m) Tc-TRODAT-1 single-photon emission computed tomography (SPECT) brain images in people with heroin and METH dependence. We recruited 21 healthy human controls, 23 heroin-dependent subjects and 25 METH abusers. The heroin- and METH-dependent subjects exhibited negative urine toxicology after undergoing physiological detoxification. All subjects underwent SPECT brain imaging, and specific tracer uptake ratios (SURs) were assessed bilaterally in the regions of interest. A significant SUR reduction in heroin-dependent subjects and METH-dependent subjects compared with healthy controls was found in the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. There were no significant differences in the heroin group and METH group for the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. The scores of craving, HAMA (Hamilton Anxiety Rating Scale), in heroin abusers were lower than in the METH abusers. Our results show that people with heroin and METH dependence who are currently abstinent had lower DAT levels in the striatum than healthy controls. There were no differences in striatal DAT in heroin and METH users. These results suggest that chronic heroin and METH abuse appears to produce similar effects in striatal DAT in humans. METH users may have more serious craving and anxiety symptoms than heroin users with prolonged abstinence.
Tress, K H; El-Sobky, A A
1. Intravenous heroin was administered to volunteers, in doses of 2.5 and 5 mg to non-dependent subjects and does of 1/6, 1/3 and 1/2 of their prescribed daily does of opiates to dependent subjects, and pupillary responses measured before and three times during the 2 h after injection. 2. Tolerance to the miotic effects of heroin in the dependent subjects was demonstrated--larger doses of heroin were needed to produce the same pupil response in dependent subjects than in non-dependent subjects and the duration of action was shorter in the former group. 3. The effect of concurrent oral methadone medication on pupil response to heroin was demonstrated. Subjects prescribed both methadone and heroin showed smaller control pupil diameters and a reduced dose effect to heroin than did subjects prescribed heroin alone.
Heroin is currently being advocated by some as a superior therapeutic agent for use in terminal illness. However, a review of the literature on heroin presently available does not support this contention. Administered orally, heroin is approximately 1.5 times more potent than morphine in controlling chronic pain in terminal cancer patients. Its effects on mood and the incidence and nature of side effects do not differ from those of morphine except in males where poorer pain control probably accounts for the worse effect on mood. Given parenterally for acute pain, heroin is 2-4 times more potent than morphine and faster in onset of action. When the potency difference is accounted for, the pharmacological effects of heroin do not differ appreciably from those of morphine. Heroin is metabolized to 6-acetylmorphine and morphine. After oral administration of heroin, morphine but not heroin or 6-acetylmorphine is detected in blood. In this case, heroin is a prodrug for the delivery of systemic morphine. Following acute i.v. administration, heroin appears transiently in blood with a half-life of about 3 min. The half-life of heroin exposed to blood or serum in vitro is 9-22 min, indicating that organ metabolism is involved in blood clearance as well. Direct renal clearance of heroin is less than 1% of the administered dose. In animal studies, heroin and 6-acetylmorphine are both more potent and faster acting than morphine as analgesics, effects attributed to their greater lipid solubility and subsequent penetration of the blood-brain barrier. Given centrally, morphine is more potent than heroin and 6-acetylmorphine in producing analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Purpose: The purpose of this paper is to review the research evidence on recent British trends in the use of heroin and/or crack-cocaine by young people in order to appraise the scale and nature of the contemporary health problem they pose. Design/methodology/approach: The approach consists of a narrative review of the main current data sources on…
Faherty, John K.
This paper presents a review of relevant medical and psychological literature that addresses the psychological characteristics of heroin addiction and addicts: dependence (both physical and psychological); explanations of the phenomenon of addiction (both medical and behavioral); and other psychosocial views of causation including escapism,…
Chen, Dingyan; Liu, Yan; He, Wulong; Wang, Hongxing; Wang, Zengzhen
This study examined the effects of combined administration of tyrosine, lecithin, L-glutamine and L-5-hydroxytryptophan (5-HTP) on heroin withdrawal syndromes and mental symptoms in detoxified heroin addicts. In the cluster-randomized placebo-controlled trial, 83 detoxified heroin addicts were recruited from a detoxification treatment center in Wuhan, China. Patients in the intervention group (n=41) were given the combined treatment with tyrosine, lecithin, L-glutamine and 5-HTP and those in the control group (n=42) were administered the placebo. The sleep status and the withdrawal symptoms were observed daily throughout the study, and the mood states were monitored pre- and post-intervention. The results showed that the insomnia and withdrawal scores were significantly improved over time in participants in the intervention group as compared with those in the control group. A greater reduction in tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia and total mood disturbance, and a greater increase in their vigor-activity symptoms were found at day 6 in the intervention group than in the control group (all P<0.05). It was concluded that the neurotransmitter-precursor-supplement intervention is effective in alleviating the withdrawal and mood symptoms and it may become a supplementary method for patients' recovery from heroin addiction.
Pascual Calvet, J; Pou, A; Pedro-Botet, J; Gutiérrez Cebollada, J
The spectrum of neurological complications associated with heroin addiction has changed in the past six years because of the progressive knowledge of the neurological complications related to HIV infection. We reviewed 48 heroin addicts with neurological complications and 452 heroin overdose who were seen in the Emergency Unit of our hospital during 1988 and the publications since 1967. Regarding the overdose we present the results of a prospective study leading to determine the causes. We emphasize the relationship with the level of total morphine in serum, instead of conjugate morphine, and with the presence of high levels of benzodiazepines found in the plasma rather than an hypothetic hypersensitivity phenomenon. We resume the neurological complications related with heroin addiction: spongiform leukoencephalopathy, epileptic seizures, stroke, transverse myelopathy and neuromuscular complications such mononeuropathy, plexopathy, acute inflammatory demyelinating polyradiculoneuropathy, rhabdomyolysis, fibrosing myopathy, musculoskeletal syndrome and acute bacterial myopathy. Some of such complications (i.e. transverse myelitis, polyradiculoneuropathy, leucoencephalopathy) must rise the suspicion of an HIV infection. Likewise, in patients assisted for overdosage we believe it's necessary rule out myoglobinuria by means of CPK serum levels and detection of urine hematic pigments without red blood cels in the urine sediment, in order to prevent and treat the renal failure. We report the results of muscular biopsy found in the musculoskeletal syndrome, which are similar to those found in alcoholic myopathy. Finally, we describe the clinical and diagnostic aspects in an unusually neuromuscular complication: the acute bacterial myopathy.
In order to examine risk factors for attempting suicide in heroin dependent patients, a group of 527 abstinent opiate dependent patients had a psychiatric interview and completed the Childhood Trauma Questionnaire. Patients who had or had never attempted suicide were compared on putative suicide risk factors. It was found that 207 of the 527…
Discusses the identification of critical elements that will induce and maintain behavior change in drug education. Demonstrates how the Theory of Reasoned Action can be used to identify these elements. Data were gathered from a sample of heroin injectors and the cognitive structures underlying drug use were investigated. Discusses findings with…
Antonelli Incalzi, R.; Ludovico Maini, C.; Giuliano Bonetti, M.; Campioni, P.; Pistelli, R.; Fuso, L.
A severe pulmonary vascular derangement, usually reported in drug addicts, was diagnosed in a 28-year-old asymptomatic ex-heroin user by means of fortuitously performed pulmonary perfusion imaging. Neither physical findings nor pulmonary function tests, aroused suspicion of the diagnosis. A search for asymptomatic pulmonary vascular disease probably should be undertaken in drug addicts.
Hirt, Michael; Greenfield, Heywood
Examined effectiveness of implosive therapy with heroin addicts during detoxification from methadone. Treatment groups received 12 sessions of implosive therapy or eclectic counseling and were followed for a six-week period. The implosive therapy group were the only ones to significantly reduce their methadone level during treatment and follow-up.…
Harold, Christine L.
Discusses how a recent fashion trend known as "heroin chic" challenges conventional modes of argumentation. Considers how its popularization of abject, emaciated bodies presents an alternative to a logic of rationalism that grounds traditional argumentation. Discusses how by foregrounding corporeal performativity as a form of argument,…
Greenwald, Mark K.
A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing…
Kim, Yung Su; Yang, Mei; Mat, Wai-Kin; Tsang, Shui-Ying; Su, Zhonghua; Jiang, Xianfei; Ng, Siu-Kin; Liu, Siyu; Hu, Taobo; Pun, Frank; Liao, Yanhui; Tang, Jinsong; Chen, Xiaogang; Hao, Wei; Xue, Hong
Substance dependence is a frequently observed comorbid disorder in schizophrenia, but little is known about genetic factors possibly shared between the two psychotic disorders. GABRB2, a schizophrenia candidate gene coding for GABAA receptor β2 subunit, is examined for possible association with heroin dependence in Han Chinese population. Four single nucleotide polymorphisms (SNPs) in GABRB2, namely rs6556547 (S1), rs1816071 (S3), rs18016072 (S5), and rs187269 (S29), previously associated with schizophrenia, were examined for their association with heroin dependence. Two additional SNPs, rs10051667 (S31) and rs967771 (S32), previously associated with alcohol dependence and bipolar disorder respectively, were also analyzed. The six SNPs were genotyped by direct sequencing of PCR amplicons of target regions for 564 heroin dependent individuals and 498 controls of Han Chinese origin. Interestingly, it was found that recombination between the haplotypes of all-derived-allele (H1; OR = 1.00) and all-ancestral-allele (H2; OR = 0.74) at S5-S29 junction generated two recombinants H3 (OR = 8.51) and H4 (OR = 5.58), both conferring high susceptibility to heroin dependence. Additional recombination between H2 and H3 haplotypes at S1-S3 junction resulted in a risk-conferring haplotype H5 (OR = 1.94x109). In contrast, recombination between H1 and H2 haplotypes at S3-S5 junction rescued the risk-conferring effect of recombination at S5-S29 junction, giving rise to the protective haplotype H6 (OR = 0.68). Risk-conferring effects of S1-S3 and S5-S29 crossovers and protective effects of S3-S5 crossover were seen in both pure heroin dependent and multiple substance dependence subgroups. In conclusion, significant association was found with haplotypes of the S1-S29 segment in GABRB2 for heroin dependence in Han Chinese population. Local recombination was an important determining factor for switching haplotypes between risk-conferring and protective statuses. The present study
Andersen, Jannike Mørch; Ripel, Ase; Boix, Fernando; Normann, Per Trygve; Mørland, Jørg
We investigated the relative importance of heroin and its metabolites in eliciting a behavioral response in mice by studying the relationship between concentrations of heroin, 6-monoacetylmorphine (6MAM), and morphine in brain tissue and the effects on locomotor activity. Low doses (subcutaneous) of heroin (< or =5 micromol/kg) or 6MAM (< or =15 micromol/kg) made the mice run significantly more than mice given equimolar doses of morphine. There were no differences in the response between heroin and 6MAM, although we observed a shift to the left of the dose-response curve for the maximal response of heroin. The behavioral responses were abolished by pretreatment with 1 mg/kg naltrexone. Heroin was detected in brain tissue after injection, but the levels were low and its presence too short-lived to be responsible for the behavioral response observed. The concentration of 6MAM in brain tissue increased shortly after administration of both heroin and 6MAM and the concentration changes during the first hour roughly reflected the changes in locomotor activity. Both the maximal and the total concentration of 6MAM were higher after administration of heroin than after administration of 6MAM itself. The morphine concentration increased slowly after injection and could not explain the immediate behavioral response. In summary, the locomotor activity response after injection of heroin was mediated by 6MAM, which increased shortly after administration. Heroin acted as an effective prodrug. The concentration of morphine was too low to stimulate the immediate response observed but might have an effect on the later part of the heroin-induced behavioral response curve.
Zhou, Yan; Leri, Francesco; Ho, Ann; Kreek, Mary Jeanne
It is known that heroin dependence and withdrawal are associated with changes in the hypothalamic-pituitary-adrenal (HPA) axis. The objective of these studies in rats was to systematically investigate the level of HPA activity and response to a heroin challenge at two time points during heroin withdrawal, and to characterize the expression of associated stress-related genes 30 minutes after each heroin challenge. Rats received chronic (10-day) intermittent escalating-dose heroin administration (3×2.5 mg/kg/day on day 1; 3×20 mg/kg/day by day 10). Hormonal and neurochemical assessments were performed in acute (12 hours after last heroin injection) and chronic (10 days after the last injection) withdrawal. Both plasma ACTH and corticosterone levels were elevated during acute withdrawal, and heroin challenge at 20 mg/kg (the last dose of chronic escalation) at this time point attenuated this HPA hyperactivity. During chronic withdrawal, HPA hormonal levels returned to baseline, but heroin challenge at 5 mg/kg decreased ACTH levels. In contrast, this dose of heroin challenge stimulated the HPA axis in heroin naïve rats. In the anterior pituitary, pro-opiomelanocortin (POMC) mRNA levels were increased during acute withdrawal and retuned to control levels after chronic withdrawal. In the medial hypothalamus, however, the POMC mRNA levels were decreased during acute withdrawal, and increased after chronic withdrawal. Our results suggest a long-lasting change in HPA abnormal responsivity during chronic heroin withdrawal. PMID:23771528
Musshoff, Frank; Trafkowski, Jens; Lichtermann, Dirk; Madea, Burkhard
Urine samples of patients from a heroin maintenance program (HMP) and a methadone maintenance program (MMP) were chromatographically analyzed 1 month before and 6 and 12 months into treatment for the presence of classical markers of heroin use as well as for the presence of markers for illicit heroin abuse. Furthermore, the samples were immunochemically tested for cannabinoids, cocaine metabolites, amphetamine, methylendioxyamphetamines and benzodiazepines. A co-consumption of illicit heroin (HER) in the HMP was determined to be 50% but was significantly lower compared to the MMP with a co-use of 71%. The incidence was high because not only acetylcodeine (AC) as a very specific marker was considered but also other marker substances for illicit HER use. Amphetamines played only a minor part in both collectives, and the proportion of HER and methadone patients using cocaine was similar and decreased during treatment. Also, the benzodiazepine use decreased, and cannabis use was high in both collectives during treatment. Considering only the AC in the present study, a co-use of illicit HER in the HMP was similar to previous reports concerning HER-assisted treatment programs. If additional marker substances were examined, the suspicion of a co-use of illicit HER is markedly enhanced.
Yuan, Yi; Zhu, Zude; Shi, Jinfu; Zou, Zhiling; Yuan, Fei; Liu, Yijun; Lee, Tatia M. C.; Weng, Xuchu
Numerous studies have documented cognitive impairments and hypoactivity in the prefrontal and anterior cingulate cortices in drug users. However, the relationships between opiate dependence and brain structure changes in heroin users are largely unknown. In the present study, we measured the density of gray matter (DGM) with voxel-based…
Kong, Lingcan; Chu, Xuefeng; Wang, Chuanxi; Yang, Xiaotian; Zhou, Lei
Europium ion-doped CdSe hybrid nanocrystals (CdSe:Eu3+ NCs) as a class of new luminescent materials have drawn increasing attention in recent years owing to their remarkable optical properties. In this paper, we report a facile method to prepare CdSe:Eu3+ NCs using oleic acid (OA) as the capping agent. With this non-injection and one-pot synthesized approach, the formation and surface passivation of CdSe:Eu3+ NCs are performed simultaneously and result in intrinsic luminescence. The as-prepared CdSe:Eu3+ NCs are characterized by transmission electron microscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy (EDX). Their optical properties are also studied by UV-vis and photoluminescence spectra. Moreover, the effects of feed ratios and reaction temperatures on the optical properties are further investigated. The results show that the luminescent spectra of CdSe:Eu3+ NCs are tunable from green (490 nm) to red (630 nm) and gradually redshift with the increase of the nanoparticle size from 2.5 to 4.4 nm. Upon decoration with 2-thenoyltrifluoroacetone (TTA), the luminescence of europium ion drastically increases and efficient energy transfer from CdSe host to the europium ion is proposed. In addition, an MTT and apoptosis assay show CdSe:Eu3+ NCs have low cellular toxicity and could be used as fluorescence imaging for human epithelial type 2 (Hep-2) cells. These properties make CdSe:Eu3+ NCs a potential candidate for biological labeling, immunoassays, and optical sensing.
Bogen, Inger Lise; Boix, Fernando; Nerem, Elisabeth; Mørland, Jørg; Andersen, Jannike Mørch
Immunotherapy against drugs of abuse is being studied as an alternative treatment option in addiction medicine and is based on antibodies sequestering the drug in the bloodstream and blocking its entry into the brain. Producing an efficient vaccine against heroin has been considered particularly challenging because of the rapid metabolism of heroin to multiple psychoactive molecules. We have previously reported that heroin's first metabolite, 6-monoacetylmorphine (6-MAM), is the predominant mediator for heroin's acute behavioral effects and that heroin is metabolized to 6-MAM primarily prior to brain entry. On this basis, we hypothesized that antibody sequestration of 6-MAM is sufficient to impair heroin-induced effects and therefore examined the effects of a monoclonal antibody (mAb) specific for 6-MAM. In vitro experiments in human and rat blood revealed that the antibody was able to bind 6-MAM and block the metabolism to morphine almost completely, whereas the conversion of heroin to 6-MAM remained unaffected. Mice pretreated with the mAb toward 6-MAM displayed a reduction in heroin-induced locomotor activity that corresponded closely to the reduction in brain 6-MAM levels. Intraperitoneal and intravenous administration of the anti-6-MAM mAb gave equivalent protection against heroin effects, and the mAb was estimated to have a functional half-life of 8 to 9 days in mice. Our study implies that an antibody against 6-MAM is effective in counteracting heroin effects.
Liu, Xiaoshan; Wang, Guangyong; Pu, Hongwei; Jing, Hualan
The cellular mechanisms by which opiate addiction develops with repetitive use remain largely unresolved. Intercellular calcium homeostasis is one of the most critical elements to determine neuroadaptive changes and neuronal fate. Heroin, one of the most addictive opiates, may induce neurotoxicity potentially inducing brain impairment, especially for those chronic users who get an overdose. Here we examined changes in intracellular calcium concentration ([Ca2+]i) after repeated exposure to heroin using cultured cerebral cortical neurons. Dynamic changes in [Ca2+]i indicated by fluo-3-AM were monitored using confocal laser scan microscopy, followed by cytotoxicity assessments. It showed that the cells dissociated from heroin-dependent rats had a smaller depolarization-induced [Ca2+]i responses, and a higher elevation in [Ca2+]i when challenged with a high concentration of heroin (500 μM). The restoration ability to remove calcium after washout of these stimulants was impaired. Calcium channel blocker verapamil inhibited the heroin-induced [Ca2+]i elevations as well as the heroin-induced cell damage. The relative [Ca2+]i of the nerve cells closely correlated with the number of damaged cells induced by heroin. These results demonstrate that nerve cells from heroin-dependent rats manifest abnormal [Ca2+]i homeostasis, as well as vulnerability to heroin overdose, suggesting involvement of [Ca2+]i regulation mechanisms in heroin addiction and neurotoxicity.
Denier, Niklaus; Gerber, Hana; Vogel, Marc; Klarhöfer, Markus; Riecher-Rossler, Anita; Wiesbeck, Gerhard A; Lang, Undine E; Borgwardt, Stefan; Walter, Marc
Heroin dependence is a chronic relapsing brain disorder, characterized by the compulsion to seek and use heroin. Heroin itself has a strong potential to produce subjective experiences characterized by intense euphoria, relaxation and release from craving. The neurofunctional foundations of these perceived effects are not well known. In this study, we have used pharmacological magnetic resonance imaging (phMRI) in 15 heroin-dependent patients from a stable heroin-assisted treatment program to observe the steady state effects of heroin (60 min after administration). Patients were scanned in a cross-over and placebo controlled design. They received an injection of their regular dose of heroin or saline (placebo) before or after the scan. As phMRI method, we used a pulsed arterial spin labeling (ASL) sequence based on a flow-sensitive alternating inversion recovery (FAIR) spin labeling scheme combined with a single-shot 3D GRASE (gradient-spin echo) readout on a 3 Tesla scanner. Analysis was performed with Statistical Parametric Mapping (SPM 8), using a general linear model for whole brain comparison between the heroin and placebo conditions. We found that compared to placebo, heroin was associated with reduced perfusion in the left anterior cingulate cortex (ACC), the left medial prefrontal cortex (mPFC) and in the insula (both hemispheres). Analysis of extracted perfusion values indicate strong effect sizes and no gender related differences. Reduced perfusion in these brain areas may indicate self- and emotional regulation effects of heroin in maintenance treatment.
Boix, Fernando; Andersen, Jannike M; Mørland, Jørg
High blood-brain permeability and effective delivery of morphine to the brain have been considered as explanations for the high potency of heroin. Results from Andersen et al. indicate that 6-monoacetylmorphine (6-MAM), and not morphine, is the active metabolite responsible for the acute effects observed for heroin. Here, we use pharmacokinetic modeling on data from the aforementioned study to calculate parameters of the distribution of heroin, 6-MAM and morphine in blood and brain tissue after subcutaneous heroin administration in mice. The estimated pharmacokinetic parameters imply that the very low heroin and the high 6-MAM levels observed both in blood and brain in the original experiment are likely to be caused by a very high metabolic rate of heroin in blood. The estimated metabolic rate of heroin in brain was much lower and cannot account for the low heroin and high 6-MAM levels in the brain, which would primarily reflect the concentrations of these compounds in blood. The very different metabolic rates for heroin in blood and brain calculated by the model were confirmed by in vitro experiments. These results show that heroin's fast metabolism in blood renders high concentrations of 6-MAM which, due to its relatively good blood-brain permeability, results in high levels of this metabolite in the brain. Thus, it is the high blood metabolism rate of heroin and the blood-brain permeability to 6-MAM, and not to heroin, which could account for the highly efficient delivery of active metabolites to the brain after heroin administration.
Walter, Marc; Gerber, Hana; Kuhl, Hans Christian; Schmid, Otto; Joechle, Wolfgang; Lanz, Christian; Brenneisen, Rudolf; Schächinger, Hartmut; Riecher-Rössler, Anita; Wiesbeck, Gerhard A; Borgwardt, Stefan J
Heroin dependence is associated with a stressful environment and with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The present study examined the acute effects of intravenous heroin versus placebo on the HPA axis response in heroin-dependent patients. Twenty-eight heroin-dependent patients in heroin-assisted treatment and 20 age- and sex-matched healthy participants were included in a controlled trial in which patients were twice administered heroin or saline in a crossover design, and healthy controls were only administered saline. The HPA axis response was measured by adrenocorticotropic hormone (ACTH) levels and by cortisol levels in serum and saliva before and 20 and 60 minutes after substance administration. Craving, withdrawal, and anxiety levels were measured before and 60 minutes after substance application. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Heroin administration reduces craving, withdrawal, and anxiety levels and leads to significant decreases in ACTH and cortisol concentrations (P < 0.01). After heroin administration, cortisol concentrations did not differ from healthy controls, and ACTH levels were significantly lower (P < 0.01). In contrast, when patients receive saline, all hormone levels were significantly higher in patients than in healthy controls (P < 0.01). Heroin-dependent patients showed a normalized HPA axis response compared to healthy controls when they receive their regular heroin dose. These findings indicate that regular opioid administration protects addicts from stress and underscore the clinical significance of heroin-assisted treatment for heroin-dependent patients.
Caillé, Stéphanie; Parsons, Loren H
The present experiments tested the hypothesis that the selective CB1 receptor antagonist SR141716A alters heroin self-administration by attenuating heroin-induced increases in nucleus accumbens dopamine levels. SR141716A pretreatment dose-dependently (0.3-3 mg/kg, i.p.) reduced operant heroin self-administration by male Wistar rats under a fixed ratio schedule of reinforcement, and significantly lowered the breaking point of responding for heroin under a progressive ratio schedule of reinforcement. These observations are consistent with recent reports that CB1 receptor inactivation reduces the rewarding properties of opiates. Operant responding for water reinforcement by water-restricted rats was unaltered by these SR141716A doses. Microdialysis tests revealed that heroin self-administration significantly increases interstitial dopamine levels in the nucleus accumbens shell of vehicle-pretreated control rats. However, whereas SR141716A pretreatment dose-dependently reduced heroin self-administration, it did not alter the heroin-associated increase in nucleus accumbens dopamine. These findings suggest that the CB1 antagonist-induced attenuation of heroin reward does not involve dopaminergic mechanisms in the nucleus accumbens shell.
Gottås, A; Øiestad, E L; Boix, F; Vindenes, V; Ripel, Å; Thaulow, C H; Mørland, J
BACKGROUND AND PURPOSE Heroin, with low affinity for μ-opioid receptors, has been considered to act as a prodrug. In order to study the pharmacokinetics of heroin and its active metabolites after i.v. administration, we gave a bolus injection of heroin to rats and measured the concentration of heroin and its metabolites in blood and brain extracellular fluid (ECF). EXPERIMENTAL APPROACH After an i.v. bolus injection of heroin to freely moving Sprague–Dawley rats, the concentrations of heroin and metabolites in blood samples from the vena jugularis and in microdialysis samples from striatal brain ECF were measured by ultraperformance LC-MS/MS. KEY RESULTS Heroin levels decreased very fast, both in blood and brain ECF, and could not be detected after 18 and 10 min respectively. 6-Monoacetylmorphine (6-MAM) increased very rapidly, reaching its maximal concentrations after 2.0 and 4.3 min, respectively, and falling thereafter. Morphine increased very slowly, reaching its maximal levels, which were six times lower than the highest 6-MAM concentrations, after 12.6 and 21.3 min, with a very slow decline during the rest of the experiment and only surpassing 6-MAM levels at least 30 min after injection. CONCLUSIONS AND IMPLICATIONS After an i.v. heroin injection, 6-MAM was the predominant opioid present shortly after injection and during the first 30 min, not only in the blood but also in rat brain ECF. 6-MAM might therefore mediate most of the effects observed shortly after heroin intake, and this finding questions the general assumption that morphine is the main and most important metabolite of heroin. PMID:23865556
Pirompanich, Pattarin; Chankrachang, Siwaporn
Heroin-associated spongiform leukoencephalopathy is a rare, and sometimes fatal, condition usually caused by vapor inhalation of heroin. The authors report a 41-year-old man who was diagnosed with delayed spongiform leukoencephalopathy three weeks after injecting heroin intravenously. He had been admitted to another hospital due to acute heroin overdose, which had occurred four hours after intravenous injection of an unknown amount of heroin. His clinical condition showed progressive improvement and he was discharged 12 days after admission. Three weeks after this episode, his cognitive functioning declined. Akinetic mutism, spasticity and hyperreflexia of all extremities were observed. Electroencephalography (EEG) and imaging of the brain showed typical characteristics of spongiform leukoencephalopathy. The three and six-month follow-up of the patient showed clinical improvement and this was corroborated through EEG measures and brain imaging. The discussion summarizes eight previously reported cases of intravenous heroin associated spongiform leukoencephalopathy and compares them to the authors'case.
Liu, Cuimei; Hua, Zhendong; Bai, Yanping
The illicit manufacture of heroin results in the formation of trace levels of acidic and neutral manufacturing impurities that provide valuable information about the manufacturing process used. In this work, a new ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF) method; that features high resolution, mass accuracy and sensitivity for profiling neutral and acidic heroin manufacturing impurities was developed. After the UPLC-Q-TOF analysis, the retention times and m/z data pairs of acidic and neutral manufacturing impurities were detected, and 19 peaks were found to be evidently different between heroin samples from "Golden Triangle" and "Golden Crescent". Based on the data set of these 19 impurities in 150 authentic heroin samples, classification of heroin geographic origins was successfully achieved utilizing partial least squares discriminant analysis (PLS-DA). By analyzing another data set of 267 authentic heroin samples, the developed discrimiant model was validated and proved to be accurate and reliable.
Introduction Acute intoxication with drugs of abuse in children is often only the tip of the iceberg, actually hiding chronic exposure. Analysis using non-conventional matrices such as hair can provide long-term information about exposure to recreational drugs. Case presentation We report the case of a one-month-old Caucasian boy admitted to our pediatric emergency unit with respiratory distress and neurological abnormalities. A routine urine test was positive for opiates, suggesting an acute opiate ingestion. No other drugs of misuse, such as cocaine, cannabis, amphetamines or derivatives, were detected in the baby's urine. Subsequently, hair samples from the baby and the parents were collected to evaluate the possibility of chronic exposure to drug misuse by segmental analysis. Opiates and cocaine metabolites were detected in hair samples from the baby boy and his parents. Conclusions In light of these and previous results, we recommend hair analysis in babies and children from risky environments to detect exposure to heroin and other drug misuse, which could provide the basis for specific social and health interventions. PMID:21729296
Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A.; Riecher-Rössler, Anita; Lang, Undine E.; Borgwardt, Stefan
Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of
Zhang, Jie; Wang, Lanqiong; Zeng, Lin; Liao, Qishun; Chen, Ping
This paper summarizes the study of acupuncture for giving up heroin and treatment of withdrawal syndrome in China from 1995 to 2003, which includes the selection of acupoints, the evaluation of the therapeutic effects, studies of acupoints and application of relevant instruments, as well as treatment of the withdrawal syndromes of heroin with acupuncture. The therapeutic effect of acupuncture and moxibustion is definite and indispensable, especially at the time when there is no specific remedy for heroin addition.
Prowse, S J; Lima, T; Irion, K L; Burhan, H; Hochhegger, B; Marchiori, E
This article reports the case of a patient demonstrating acute bilateral pneumonitis almost completely confined to the upper lobes as a result of inhaling heroin. We attribute this distribution to the patient performing the Valsalva manoeuvre immediately after inhaling heroin. This pattern has not been reported before and we believe it may be seen more frequently owing to a switch amongst drug users from intravenous to inhaled heroin.
Denier, Niklaus; Schmidt, André; Gerber, Hana; Vogel, Marc; Huber, Christian G; Lang, Undine E; Riecher-Rossler, Anita; Wiesbeck, Gerhard A; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan
Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction.
Schmidt, André; Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Borgwardt, Stefan
Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of
Denier, Niklaus; Schmidt, André; Gerber, Hana; Schmid, Otto; Riecher-Rössler, Anita; Wiesbeck, Gerhard A; Huber, Christian G; Lang, Undine E; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan
Structure and function are closely related in the healthy human brain. In patients with chronic heroin exposure, brain imaging studies have identified long-lasting changes in gray matter (GM) volume. More recently, we showed that acute application of heroin in dependent patients results in hypoperfusion of fronto-temporal areas compared with the placebo condition. However, the relationship between structural and cerebral blood flow (CBF) changes in heroin addiction has not yet been investigated. Moreover, it is not known whether there is any interaction between the chronic structural changes and the short and long-term effects on perfusion caused by heroin. Using a double-blind, within-subject design, heroin or placebo (saline) was administered to 14 heroin-dependent patients from a stable heroin-assisted treatment program, in order to observe acute short-term effects. Arterial spin labeling (ASL) was used to calculate perfusion quantification maps in both treatment conditions, while Voxel-Based Morphometry (VBM) was conducted to calculate regional GM density. VBM and ASL data were used to calculate homologous correlation fields by Biological Parametric Mapping (BPM) and a whole-brain Pearson r correlation. We correlated each perfusion condition (heroin and placebo) separately with a VBM sample that was identical for the two treatment conditions. It was assumed that heroin-associated perfusion is manifested in short-term effects, while placebo-associated perfusion is more related to long-term effects. In order to restrict our analyses to fronto-temporal regions, we used an explicit mask for our analyses. Correlation analyses revealed a significant positive correlation in frontal areas between GM and both perfusion conditions (heroin and placebo). Heroin-associated perfusion was also negatively correlated with GM in the inferior temporal gyrus on both hemispheres. These findings indicate that, in heroin-dependent patients, low GM volume is positively associated with
Sun, Yan; Liu, Linwen; Feng, Jiajia; Yue, Weihua; Lu, Lin; Fan, Yong; Shi, Jie
The rs1137070 polymorphism of monoamine oxidase A (MAOA) is associated with alcoholism and smoking behavior. However, the association between rs1137070 and heroin addiction remains unclear. In this study, we examined the allelic distribution of rs1137070 in 1,035 heroin abusers and 2,553 healthy controls and investigated the interactive effects of rs1137070 and heroin addiction on gray matter volume (GMV) based on 78 heroin abusers and 79 healthy controls. The C allele frequency of rs1137070 was significantly higher in heroin abusers. Heroin addiction and the rs1137070 variant interactively altered measures of GMV in the anterior cingulate cortex, orbital frontal cortex, temporal pole, and insula, which were correlated with cognitive function. Heroin abusers with the C allele had lower measures of GMV in these regions than the healthy controls with the same allele, whereas those with the T allele displayed a different trend. The altered brain regions were connected with white matter tracts, yielding a structural network that partially overlapped with the salience network. These findings suggest that the low activity-related C allele of MAOA rs1137070 is associated with an increase in the sensitivity to heroin addiction and the damaging effects of heroin abuse on cognition and the salience network. PMID:28345608
Kuo, Shin-Chang; Yeh, Yi-Wei; Chen, Chun-Yen; Huang, Chang-Chih; Chang, Hsin-An; Yen, Che-Hung; Ho, Pei-Shen; Liang, Chih-Sung; Chou, Han-Wei; Lu, Ru-Band; Huang, San-Yuan
Dopamine D3 receptor-mediated pathways are involved in the mechanism of addiction, and genetic factors play a role in the vulnerability to heroin dependence. The aim of this study was to examine whether the corresponding gene, DRD3, is associated with the development of heroin dependence and specific personality traits in HD patients. Eight polymorphisms in DRD3 were analyzed in 1067 unrelated Han Chinese subjects (566 heroin dependence patients and 501 controls). All participants were screened using the same assessment tool and all patients met the criteria for heroin dependence. A Tridimensional Personality Questionnaire was used to assess personality traits in 276 heroin dependence patients. In addition, heroin dependence patients were divided into 4 clinical subgroups based on age-of-onset and family history of substance abuse, to reduce the clinical heterogeneity. The rs6280 and rs9825563 variants showed association with the development of early-onset heroin dependence. The GTA haplotype frequency in the block (rs324029, rs6280, rs9825563) was significantly associated with early-onset heroin dependence (p=0.003). However, these significant associations were weaker after Bonferroni's correction. In addition, these DRD3 polymorphisms did not influence novelty seeking and harm avoidance scores in HD patients. DRD3 is possibly a genetic factor in the development of early-onset heroin dependence, but is not associated with specific personality traits in these patients among the Han Chinese population.
Lex, B W
A pilot investigation was undertaken to determine whether the social relationships between men who currently used heroin with their female mates differed from those of men who formerly used heroin, but were currently abstinent, with their female mates. Six couples were selected for study via the representative case method. Men currently abstinent from heroin had begun drug use later, had a family history of affective disorders, and had initiated their conjugal relationship after cessation of heroin use. Female mates of males currently abstinent from heroin had never used heroin with their mates in conjunction with sexual activity, had significantly positive ratings of their mates' performance of social roles, and were striving to obtain formal training to improve their employment skills. In contrast, the couples including actively using heroin addicts used opiates together, especially to enhance their sexual activity. The relationships of these couples were not as mutually supportive, and the male's role was less responsible and attracted less respect than that of the abstinent male. The females were depressed and had little positive aspects to their lives. Partners in all couples experienced a large number of stressful events, but current heroin use increased stress and hampered coping efforts. Interaction analysis of dynamics in relationships of men currently abstinent from heroin revealed that participation in mates' family life served to reshape their behaviors into more socially acceptable roles.
Trusk, T.C.; Stein, E.A.
Cerebral functional activity was measured as changes in distribution of the free fatty acid (1-14C)octanoate in autoradiograms obtained from rats during brief presentation of a tone previously paired to infusions of heroin or saline. Rats were trained in groups of three consisting of one heroin self-administering animal and two animals receiving yoked infusions of heroin or saline. Behavioral experiments in separate groups of rats demonstrated that these training parameters imparts secondary reinforcing properties to the tone for animals self-administering heroin while the tone remains behaviorally neutral in yoked-infusion animals. The optical densities of thirty-seven brain regions were normalized to a relative index for comparisons between groups. Previous pairing of the tone to heroin infusions irrespective of behavior (yoked-heroin vs. yoked-saline groups) produced functional activity changes in fifteen brain areas. In addition, nineteen regional differences in octanoate labeling density were evident when comparison was made between animals previously trained to self-administer heroin to those receiving yoked-heroin infusions, while twelve differences were noted when comparisons were made between the yoked vehicle and self administration group. These functional activity changes are presumed related to the secondary reinforcing capacity of the tone acquired by association with heroin, and may identify neural substrates involved in auditory signalled conditioning of positive reinforcement to opiates.
Fishbein, Diana H.; Krupitsky, Evgeny; Flannery, Barbara A.; Langevin, Doris J.; Bobashev, Georgiy; Verbitskaya, Elena; Augustine, Cynthia B.; Bolla, Karen I.; Zvartau, Edwin; Schech, Barry; Egorova, Valentina; Bushara, Natali; Tsoy, Marina
Research on the neurocognitive characteristics of heroin addiction is sparse and studies that do exist include polydrug abusers; thus, they are unable to distinguish neurocognitive effects of heroin from those of other drugs. To identify neurocognitive correlates specific to heroin addiction, the present study was conducted in St. Petersburg, Russia where individuals typically abuse and/or become addicted to only one substance, generally alcohol or heroin. Heroin addicts were recruited from an inpatient treatment facility in St. Petersburg. Three comparison groups included alcoholics, addicts who used both alcohol and heroin, and non-abusers. Psychiatric, background, and drug history evaluations were administered after detoxification to screen for exclusion criteria and characterize the sample. Executive Cognitive Functions (ECF) that largely activate areas of the prefrontal cortex and its circuitry measured include complex visual pattern recognition (Paired Associates Learning), working memory (Delayed Matching to Sample), problem solving (Stockings of Cambridge), executive decision making (Cambridge Decision Making Task), cognitive flexibility (Stroop Color-Word Task) and response shifting (Stop Change Task). In many respects, the heroin addicts were similar to alcohol and alcohol\\heroin dependent groups in neurocognitive deficits relative to controls. The primary finding was that heroin addicts exhibited significantly more disadvantageous decision making and longer deliberation times while making risky decisions than the other groups. Because the nature and degree of recovery from drug abuse are likely a function of the type or pattern of neurocognitive impairment, differential drug effects must be considered. PMID:17382488
Craparo, Giuseppe; Gori, Alessio; Dell’Aera, Stefano; Costanzo, Giulia; Fasciano, Silvia; Tomasello, Antonia
Several investigations document altered emotion processing in opiate addiction. Nevertheless, the origin of this phenomenon remains unclear. Here we examined the role of alexithymia in the ability (i.e., number of errors—accuracy and reaction times—RTs) of thirty-one heroin addicts and thirty-one healthy controls to detect several affective expressions. Results show generally lower accuracy and higher RTs in the recognition of facial expressions of emotions for patients, compared to controls. The hierarchical multivariate regression analysis shows that alexithymia might be responsible of the between groups difference with respect to the RTs in emotion detection. Overall, we provide new insights in the clinical interpretation of affective deficits in heroin addicts suggesting a role of alexithymia in their ability to recognize emotions. PMID:27069803
Samantaray, P.K.; Ray, R.; Chandiramani, K.
One hundred and four subjects with heroin dependence, consecutive new admission to a ward were studied prospectively to assess treatment retention. All these subjects were admitted voluntarily after pre-admission counselling wherein treatment package (four week′s stay), ward routine, rules and regulation were explained. Socio-demographic parameters, drug use history, motivation as understood by “readiness to change”, reasons for seeking treatment were obtained. Reasons for non completion were noted. Thirty two subjects (31%) completed treatment. Out of 72 non-completers, 38 subjects (36%) left against medical advice and 34(33%) were discharged prematurely by the treating team for violating ward norms. Multivariate analysis showed that readiness to change (being in action stage), age of onset of heroin use (late), legal problems (high) and self confidence regarding recovery (high) in order of significance, predicted treatment completion. Therapeutic strategies to minimise drop-out. are discussed. PMID:21584093
Hoffer, Lee D; Bobashev, Georgiy; Morris, Robert J
This project applies agent-based modeling (ABM) techniques to better understand the operation, organization, and structure of a local heroin market. The simulation detailed was developed using data from an 18-month ethnographic case study. The original research, collected in Denver, CO during the 1990s, represents the historic account of users and dealers who operated in the Larimer area heroin market. Working together, the authors studied the behaviors of customers, private dealers, street-sellers, brokers, and the police, reflecting the core elements pertaining to how the market operated. After evaluating the logical consistency between the data and agent behaviors, simulations scaled-up interactions to observe their aggregated outcomes. While the concept and findings from this study remain experimental, these methods represent a novel way in which to understand illicit drug markets and the dynamic adaptations and outcomes they generate. Extensions of this research perspective, as well as its strengths and limitations, are discussed.
Chan, Yuan-Yu; Yang, Szu-Nian; Lin, Jyh-Chyang; Chang, Junn-Liang; Lin, Jaung-Geng; Lo, Wan-Yu
Opioid addiction influences many physiological functions including reactions of the immune system. The objective of this study was to investigate the immune system function in heroin addicted patients undergoing methadone maintenance treatment (MMT) compared to healthy controls. We tested the cytokine production of IL-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α from a group of heroin addicts (n=34) and healthy controls (n=20). The results show that production of IL-1β, IL-6 and IL-8 was significantly higher in the group of methadone-maintained patients than in the healthy control group. Plasma TNF-α and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1β level was significantly correlated with the duration of methadone maintenance treatment. These findings suggest that methadone maintenance treatment influences the immune system functions of opioid-dependent patients and may also induce long-term systemic inflammation.
Pickering, Lucy; Neale, Joanne; Nettleton, Sarah
There is a particular silence around the social life of defecation. Little analyzed, rarely discussed in polite conversation, it largely appears only at moments of dysfunction. For active heroin users, digestion is often characterized by such dysfunction and experienced through constipation; recovery, a welcome return to defecating 'normally.' Drawing on interviews with active and recovering heroin users in southern England, we focus on this moment of transition in order to illuminate the experiences and transitions between a dysfunctional, constipated body and 'normal' defecation. We discuss the contrast between candor in talk in active use with the silences surrounding defecation talk in recovery, and analyze these twin shifts within the context of a historical progression within Europe toward ever-increasing levels of masking defecation from social life. Located thus, this analysis of the tipping point between constipation and 'normality,' disclosure and embarrassment, provides a powerful lens through which to view the invisibility of defecation in contemporary British social life.
Mohs, M E; Watson, R R; Leonard-Green, T
Use of addictive drugs, such as cocaine, marijuana, and nicotine, affects food and liquid intake behavior, taste preference, and body weight. Changes in specific nutrient status and metabolism can also develop; heroin addiction can cause hyperkalemia and morphine use can result in calcium inhibition. Nutrition-related physiological aspects, such as impaired gastrin release, hypercholesterolemia, hypothermia, and hyperthermia, are also seen with morphine use. Nutrition-related conditions can affect sensitivity to and dependence on drugs and their effects. Diabetes decreases sensitivity to and dependence on morphine, protein deprivation produces preferential fat utilization with low cocaine use, and vitamin D deficiency decelerates morphine dependency. During use and/or withdrawal from nicotine, heroin, marijuana, and cocaine, major changes in food selection and intake occur, which result in weight gain or loss. Detailed human studies are needed to investigate the effects of drug use on the broad spectrum of nutrients and to determine the role of nutrition during drug withdrawal.
Nuttall, Ronald L.; Nuttall, Ena Vazquez
Using 1968 data collected from junior and senior high school students in Bayamon, Puerto Rico, substance usage patterns for heroin and alcohol were predicted for 1975-6. A sample of 1,000 of the initial 5,000 students were selected for re-interview; half were selected to be at high risk of substance abuse and half were selected randomly. Some 657…
Black, F W
The author presents data on the Minnesota Multiphasic Personality Inventory (MMPI) characteristics of a sample of enlisted Army men returning from Viet Nam identified as heroin abusers. Although a marked heterogeneity of MMPI profile types was found, a significant percentage of the subjects showed indications of marked psychopathology, and only a minority performed within normal limits on the MMPI. Theses military subjects showed neither greater nor less psychopathology and sociopathology than previously reported samples of civilian addicts.
Yu, Kui; Ouyang, Jianying; Zhang, Yanguang; Tung, Hsien-Tse; Lin, Shuqiong; Nagelkerke, Robbert A L; Kingston, David; Wu, Xiaohua; Leek, Donald M; Wilkinson, Diana; Li, Chunsheng; Chen, In-Gann; Tao, Ye
Homogeneously alloyed PbSe(x)S(1-x) nanocrystals (NCs) with their excitonic absorption peaks in wavelength shorter than 1200 nm were developed for photovoltaic (PV) applications. Schottky-type solar cells fabricated with our PbSe₀.₃S₀.₇ NCs as their active materials reached a high power conversion efficiency (PCE) of 3.44%, with an open circuit voltage (V(oc)) of 0.49 V, short circuit photocurrent (J(sc)) of 13.09 mA/cm², and fill factor (FF) of 0.54 under Air Mass 1.5 global (AM 1.5G) irradiation of 100 mW/cm². The syntheses of the small-sized colloidal PbSe(x)S(1-x) NCs were carried out at low temperature (60 °C) with long growth periods (such as 45 min) via a one-pot noninjection-based approach in 1-octadecene (ODE), featuring high reaction yield, high product quality, and high synthetic reproducibility. This low-temperature approach employed Pb(oleate)₂ as a Pb precursor and air-stable low-cost thioacetamide (TAA) as a S source instead of air-sensitive high-cost bis(trimethylsilyl)sulfide ((TMS)₂S), with n-tributylphosphine selenide (TBPSe) as a Se precursor instead of n-trioctylphosphine selenide (TOPSe). The reactivity difference of TOPSe made from commercial TOP 90% and TBPSe made from commercial TBP 97% and TBP 99% was addressed with in situ observation of the temporal evolution of NC absorption and with ³¹P nuclear magnetic resonance (NMR). Furthermore, the addition of a strong reducing/nucleation agent diphenylphosphine (DPP) promoted the reactivity of the Pb precursor through the formation of a Pb-P complex, which is much more reactive than Pb(oleate)₂. Thus, the reactivity of TBPSe was increased more than that of TAA. The larger the DPP-to-Pb feed molar ratio, the more the Pb-P complex, the higher the Se amount in the resulting homogeneously alloyed PbSe(x)S(1-x) NCs. Therefore, the use of DPP allowed reactivity match of the Se and S precursors and led to sizable nucleation at low temperature so that long growth periods became
Jakhar, Jitender Kumar; Dhattarwal, S K; Aggarwal, A D; Chikara, Pankaj; Khanagwal, Vijay Pal
We report a case of death due to heroin leakage in a body packer, attempting to smuggle the drug by concealing it in his gastro-intestinal tract. The body was recovered 3-5 days of incidence that was confirmed by autopsy. Fifty pellets (packages) were recovered from the body, 42 identical oval shaped "egg" packages were found in the stomach out of which two were damaged, 6 in small intestine, 2 in large intestine. The total weight of the powder was 267 g. Toxicological analysis of the powder samples from the damaged package and other 48 packages was performed and was found positive for heroin, caffeine and codeine. The main pathological findings at autopsy were pulmonary and cerebral edema. This case illustrates the challenges in postmortem evaluation of narcotic fatalities and the need to consider factors such as ante-mortem history, thorough post mortem examination, toxicology results and photography in forensic diagnosis. This case is unique in the sense that cause of death was intoxication caused by leakage of heroin from damaged packages detected at autopsy and demonstrates that body packing is an existing problem in India.
Chao, Mu-Rong; Fragou, Domniki; Zanos, Panos; Hu, Chiung-Wen; Bailey, Alexis; Kouidou, Sofia; Kovatsi, Leda
Epigenetic changes include the addition of a methyl group to the 5' carbon of the cytosine ring, known as DNA methylation, which results in the generation of the fifth DNA base, namely 5-methylcytosine. During active or passive demethylation, an intermediate modified base is formed, 5-hydroxymethylcytosine. We have currently quantified 5-methylcytosine and 5-hydroxymethylcytosine in the liver and brain of mice treated with cocaine or heroin, using liquid chromatography/tandem mass spectrometry (LC-MS/MS). Our results show that global 5-methylcytosine levels are not affected by heroin or cocaine administration, neither in the liver nor in the brain. However, 5-hydroxymethylcytosine levels are reduced in the liver following cocaine administration, while they are not affected by cocaine in the brain or by heroin administration in the liver and the brain. Elucidation of the epigenetic phenomena that takes place with respect to drug abuse and addiction, via quantitative analysis of different modified bases, may enable a better understanding of the underlying mechanisms and may lead to more personalized and effective treatment options.
Schepelern Johansen, Birgitte; Schepelern Johansen, Katrine
This article provides an anthropological analysis of the introduction of medically prescribed heroin as part of official substance abuse treatment. While anthropological inquiries of substance abuse treatment have mainly focused on providing the users perspectives on the (ab)use or unraveling the conflicts and negotiations between users and staff, the present article argues for the merits of paying attention to the spatial dimensions of substance abuse treatment. Focusing on the spatial and material ramification of the treatment can shed a nuanced light on the still vulnerable process of altering the heroin from drug to medicine, and thereby on the attempts to settle heroin in a new practical and semantic landscape. The heroin is anchored in some powerful discourses of crime, death, and pleasure, and the analysis shows how these discourses (re-)appear in the spatial textures of the clinic, contesting the attempts to medicalize the heroin. Further, the article argues that even though the treatment aims at a marginalization of the heroin in the life of the clients, the spatial arrangements and the practices within them simultaneously enforces a centralization of the heroin, making the space for treatment highly ambivalent.
Imperio, Caesar G.; Grigson, Patricia S.
Heroin addiction is a disease of chronic relapse affecting over half of its users. Therefore, modeling individual differences in addiction-like behavior is needed to better reflect the human condition. In a rodent model, avoidance of a cocaine-paired saccharin cue is associated with greater cocaine seeking and taking. Here, we tested whether rats would avoid a saccharin cue when paired with the opportunity to self-administer heroin and whether the rats that most greatly avoid the heroin-paired taste cue would exhibit the greatest drug escalation over time, the greatest willingness to work for drug, and the greatest heroin-induced relapse. Adult male Sprague-Dawley rats received 5 min access to a 0.15% saccharin solution followed by the opportunity to self-administer either saline or heroin for 3 h (short access) or 6 h (extended access). Following 16 – 18 pairings, terminal saccharin intake was used to categorize the rats into small (>200 licks/5min) or large (<200 licks/5min) suppressors and responding for drug was examined accordingly. Only 5% of the short access rats reached the criteria for large suppressors. This large suppressor did not differ from the small suppressors in drug taking behavior. Conversely, 50% of the extended access saccharin-heroin rats were large suppressors and showed the largest escalation of drug intake, drug-loading behavior, and the greatest relapse-like behaviors. Extended access small suppressors displayed drug-taking behaviors that were similar to rats in the short access heroin condition. Avoidance of a heroin-paired taste cue reliably identifies individual differences in addiction-like behavior for heroin using extended drug access. PMID:26214212
Imperio, Caesar G; Grigson, Patricia S
Heroin addiction is a disease of chronic relapse affecting over half of its users. Therefore, modeling individual differences in addiction-like behavior is needed to better reflect the human condition. In a rodent model, avoidance of a cocaine-paired saccharin cue is associated with greater cocaine seeking and taking. Here, we tested whether rats would avoid a saccharin cue when paired with the opportunity to self-administer heroin and whether the rats that most greatly avoid the heroin-paired taste cue would exhibit the greatest drug escalation over time, the greatest willingness to work for drug, and the greatest heroin-induced relapse. Adult male Sprague-Dawley rats received 5 min access to a 0.15% saccharin solution followed by the opportunity to self-administer either saline or heroin for 3 hr (short access) or 6 hr (extended access). Following 16 to 18 pairings, terminal saccharin intake was used to categorize the rats into small (>200 licks/5min) or large (<200 licks/5min) suppressors and responding for drug was examined accordingly. Only 5% of the short access rats reached the criteria for large suppressors. This large suppressor did not differ from the small suppressors in drug-taking behavior. On the other hand, 50% of the extended access saccharin-heroin rats were large suppressors and showed the largest escalation of drug intake, drug-loading behavior, and the greatest relapse-like behaviors. Extended access small suppressors displayed drug-taking behaviors that were similar to rats in the short access heroin condition. Avoidance of a heroin-paired taste cue reliably identifies individual differences in addiction-like behavior for heroin using extended drug access.
Schmidt, André; Walter, Marc; Gerber, Hana; Schmid, Otto; Smieskova, Renata; Bendfeldt, Kerstin; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Rubia, Katya; McGuire, Philip; Borgwardt, Stefan
Impairments in inhibitory control and in stimulus-driven attention are hallmarks of drug addiction and are associated with decreased activation in the right inferior frontal gyrus (IFG). Although previous studies indicate that the response inhibition function is impaired in abstinent heroin dependents, and that this is mediated by reduced IFG activity, it remains completely unknown whether and how an acute dose of heroin modulates IFG activity during cognitive control in heroin-dependent patients. This study investigates the acute effects of heroin administration on IFG activity during response inhibition and stimulus-driven attention in heroin-dependent patients. Using a cross-over, double-blind, placebo-controlled design, saline and heroin were administered to 26 heroin-dependent patients from stable heroin-assisted treatment, while performing a Go/No–Go event-related functional magnetic resonance imaging task to assess right IFG activity during motor response inhibition, as well as during oddball-driven attention allocation. Relative to saline, heroin significantly reduced right IFG activity during both successful response inhibition and oddball-driven attention allocation, whereas it did not change right IFG activity during response inhibition after correction for the effect of attention allocation. These heroin-induced effects were not related to changes in drug craving, state anxiety, behavioral performance, or co-consumption of psychostimulant drugs. This study demonstrates that heroin administration acutely impairs stimulus-driven attention allocation, as indicated by reduced IFG activity in response to infrequently presented stimuli, and does not specifically modulate IFG activity during response inhibition. PMID:23673865
Platt, D M; Rowlett, J K; Spealman, R D
Heroin has characteristic subjective effects that contribute importantly to its widespread abuse. Drug discrimination procedures in animals have proven to be useful models for investigating pharmacological mechanisms underlying the subjective effects of drugs in humans. However, surprisingly little information exists concerning the mechanisms underlying the discriminative stimulus (DS) effects of heroin. This study characterized the DS effects of heroin in rhesus monkeys trained to discriminate i.v. heroin from saline. In drug substitution experiments, heroin, its metabolites 6-monoacetylmorphine, morphine, morphine-6-glucuronide, and morphine-3-glucuronide, and the mu-agonists fentanyl and methadone engendered dose-dependent increases in heroin-lever responding, reaching average maximums of >80% (full substitution) at doses that did not appreciably suppress response rate. In contrast, the delta-agonist SNC 80, the kappa-agonist spiradoline, and the dopamine uptake blockers/releasers cocaine, methamphetamine, and GBR 12909 did not engender heroin-like DS effects regardless of dose. In antagonism studies, in vivo apparent pA2 and pK(B) values for naltrexone combined with heroin, morphine, and 6-monoacetylmorphine (8.0-8.7) were comparable with those reported previously for naltrexone antagonism of prototypical mu-agonists. The results show that the DS effects of heroin are pharmacologically specific and mediated primarily at mu-opioid receptors. Moreover, the acetylated and glucuronated metabolites of heroin appear to play significant roles in these effects. Despite previous speculation that morphine-3-glucuronide lacks significant opioid activity, it substituted fully for heroin in our study, suggesting that it can exhibit prominent mu-agonist effects in vivo.
Gottås, A; Boix, F; Øiestad, E L; Vindenes, V; Mørland, J
After injection, heroin is rapidly metabolized to 6-monoacetylmorphine (6-MAM) and further to morphine. As morphine has been shown to increase striatal dopamine, whereas 6-MAM has not been studied in this respect, we gave i.v. injections of 3 μmol 6-MAM, morphine or heroin to rats. Opioids were measured in blood, and dopamine and opioids in microdialysate from brain striatal extracellular fluid (ECF), by UPLC-MS/MS. After 6-MAM injection, 6-MAM ECF concentrations increased rapidly, and reached Cmax of 4.4 μM after 8 min. After heroin injection, 6-MAM increased rapidly in blood and reached Cmax of 6.4 μM in ECF after 8 min, while ECF Cmax for heroin was 1.2 μM after 2 min. T max for morphine in ECF was 29 and 24 min following 6-MAM and heroin administration, respectively, with corresponding Cmax levels of 1 and 2 μM. Dopamine levels peaked after 8 and 14 min following 6-MAM and heroin administration, respectively. The dopamine responses were equal, indicating no dopamine release by heroin per se. Furthermore, 6-MAM, and not morphine, appeared to mediate the early dopamine response, whereas morphine administration, giving rise to morphine ECF concentrations similar to those observed shortly after 6-MAM injection, did not increase ECF dopamine. 6-MAM appeared accordingly to be the substance responsible for the early increase in dopamine observed after heroin injection. As 6-MAM was formed rapidly from heroin in blood, and was the major substance reaching the brain after heroin administration, this also indicates that factors influencing blood 6-MAM concentrations might change the behavioural effects of heroin.
Schmidt, André; Walter, Marc; Gerber, Hana; Schmid, Otto; Smieskova, Renata; Bendfeldt, Kerstin; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Rubia, Katya; McGuire, Philip; Borgwardt, Stefan
Impairments in inhibitory control and in stimulus-driven attention are hallmarks of drug addiction and are associated with decreased activation in the right inferior frontal gyrus (IFG). Although previous studies indicate that the response inhibition function is impaired in abstinent heroin dependents, and that this is mediated by reduced IFG activity, it remains completely unknown whether and how an acute dose of heroin modulates IFG activity during cognitive control in heroin-dependent patients. This study investigates the acute effects of heroin administration on IFG activity during response inhibition and stimulus-driven attention in heroin-dependent patients. Using a cross-over, double-blind, placebo-controlled design, saline and heroin were administered to 26 heroin-dependent patients from stable heroin-assisted treatment, while performing a Go/No-Go event-related functional magnetic resonance imaging task to assess right IFG activity during motor response inhibition, as well as during oddball-driven attention allocation. Relative to saline, heroin significantly reduced right IFG activity during both successful response inhibition and oddball-driven attention allocation, whereas it did not change right IFG activity during response inhibition after correction for the effect of attention allocation. These heroin-induced effects were not related to changes in drug craving, state anxiety, behavioral performance, or co-consumption of psychostimulant drugs. This study demonstrates that heroin administration acutely impairs stimulus-driven attention allocation, as indicated by reduced IFG activity in response to infrequently presented stimuli, and does not specifically modulate IFG activity during response inhibition.
Kerr, Debra; Dietze, Paul; Kelly, Anne-Maree; Jolley, Damien
Naloxone distribution to injecting drug users (IDUs) for peer administration is a suggested strategy to prevent fatal heroin overdose. The aim of this study was to explore attitudes of IDUs to administration of naloxone to others after heroin overdose, and preferences for method of administration. A sample of 99 IDUs (median age 35 years, 72% male) recruited from needle and syringe programs in Melbourne were administered a questionnaire. Data collected included demographics, attitudes to naloxone distribution, and preferences for method of administration. The primary study outcomes were attitudes of IDUs to use of naloxone for peer administration (categorized on a five-point scale ranging from "very good idea" to "very bad idea") and preferred mode of administration (intravenous, intramuscular, and intranasal). The majority of the sample reported positive attitudes toward naloxone distribution (good to very good idea: 89%) and 92% said they were willing to participate in a related training program. Some participants raised concerns about peer administration including the competence of IDUs to administer naloxone in an emergency, victim response on wakening and legal implications. Most (74%) preferred intranasal administration in comparison to other administration methods (21%). There was no association with age, sex, or heroin practice. There appears to be strong support among Australian IDU for naloxone distribution to peers. Intranasal spray is the preferred route of administration.
Darke, Shane; Duflou, Johan; Torok, Michelle
To determine the effects of a sudden and sustained reduction in heroin purity on the toxicology of heroin overdose, 959 consecutive heroin overdose cases autopsied at the NSW Department of Forensic Medicine (1/1/1998-31/12/2006) were analysed. There was a significant reduction in blood morphine concentration across the study period (beta=-0.07), declining from a median of 0.50mg/L in the years 1998-2000 prior to 0.40mg/L in the period 2001-2006. There was no significant change in the proportion of alcohol positive cases, but the proportion of benzodiazepine positive cases increased across time (OR 1.11), as did methadone positive cases (OR 1.12). The decline in blood morphine concentrations remained significant after controlling for these factors (beta=-0.07). In determining toxic and lethal morphine concentrations, the fact that the toxicology of overdose is responsive to changes in the opioid street market needs to be borne in mind.
Koblin, Beryl A.; Bonner, Sebastian; Hoover, Donald R.; Xu, Guozhen; Lucy, Debbie; Fortin, Princess; Putnam, Sara; Latka, Mary H.
Background Limited data are available on interventions to reduce sexual risk behaviors and increase knowledge of HIV vaccine trial concepts in high risk populations eligible to participate in HIV vaccine efficacy trials. Methods The UNITY Study was a two-arm randomized trial to determine the efficacy of enhanced HIV risk reduction and vaccine trial education interventions to reduce the occurrence of unprotected vaginal sex acts and increase HIV vaccine trial knowledge among 311 HIV-negative non-injection drug using women. The enhanced vaccine education intervention using pictures along with application vignettes and enhanced risk reduction counseling consisting of three one-on-one counseling sessions were compared to standard conditions. Follow-up visits at one week and one, six and twelve months after randomization included HIV testing and assessment of outcomes. Results During follow up, the percent of women reporting sexual risk behaviors declined significantly, but did not differ significantly by study arm. Knowledge of HIV vaccine trial concepts significantly increased but did not significantly differ by study arm. Concepts about HIV vaccine trials not adequately addressed by either condition included those related to testing a vaccine for both efficacy and safety, guarantees about participation in future vaccine trials, assurances of safety, medical care, and assumptions about any protective effect of a test vaccine. Conclusions Further research is needed to boost educational efforts and strengthen risk reduction counseling among high-risk non-injection drug using women. PMID:20190585
Yarnold, B M
This analysis examines the use of heroin by 481 adolescents in Dade County, Florida public schools during 1992. Statistically significant factors which tend to increase the probability of heroin use by adolescents include: peer use of heroin and students' involvement in school clubs. Not significantly related to heroin use is their access to the drug, their ethnic background or race, and their gender. Although not statistically significant, adolescents were more likely to use heroin if they knew of the risks associated with heroin use. There are no statistically significant variables which inhibit the rise of heroin by Miami adolescents. When religion was an important part of their lives, they were at lower risk for heroin use, but this was not significant. Also not significantly related to heroin use are a number of other variables, including family-related variables (whether adolescents live with their mothers, fathers, or alone: and whether someone in the family has a problem with drugs or alcohol). Similarly, early cigarette smoking and alcohol rise did not serve as gateways to later heroin use. Academic performance, and extracurricular school activities (athletics, music, and other activities) were all unrelated to the use of heroin by adolescents, with the exception of involvement in school clubs which substantially increased the risk of heroin use.
Hser, Yih-Ing; Huang, David; Chou, Chih-Ping; Anglin, M. Douglas
This study investigates trajectories of heroin use and subsequent consequences in a sample of 471 male heroin addicts who were admitted to the California Civil Addict Program in 1964-1965 and followed over 33 years. Applying a two-part growth mixture modeling strategy to heroin use level during the first 16 years of the addiction careers since…
Rückert, Christian; Licht, Katharina; Kalinowski, Jörn; Espírito Santo, Christophe; Antwerpen, Markus; Hanczaruk, Matthias; Reischl, Udo; Holzmann, Thomas; Gessner, André; Tiemann, Carsten; Grass, Gregor
We report the draft genome sequence of Bacillus anthracis UR-1, isolated from a fatal case of injectional anthrax in a German heroin user. Analysis of the genome sequence of strain UR-1 may aid in describing phylogenetic relationships between virulent heroin-associated isolates of B. anthracis isolated in the United Kingdom, Germany, and other European countries.
Morrison, J; Thornton, V; Ranaldi, R
In a previous study we showed that chronic intermittent heroin in rats enhanced responding with conditioned reinforcement and reversal learning of a conditioned magazine approach task when tested three days after the heroin treatment. Whether or not this enhanced appetitive learning persists after a protracted withdrawal period remains unknown and constitutes the aim of the present study. Forty-eight male Long Evans rats were each exposed to positive pairings of a light stimulus and food for 4 consecutive daily sessions. Then, two groups of rats received saline and two groups received heroin (2 mg/kg) injections before placement in activity monitors for 9 consecutive daily sessions. This was followed by testing in operant conditioning chambers where one lever produced the light stimulus previously paired with food and another no stimulus. For one saline and one heroin group this testing occurred after 2 days of withdrawal while for the other saline and heroin groups it occurred after 30 days of withdrawal. The results indicate that animals treated with heroin displayed progressively and significantly greater locomotor activity across sessions while animals treated with saline displayed locomotor activity that remained low and stable across sessions. In addition, the heroin groups in each withdrawal condition displayed significantly enhanced responding with conditioned reinforcement compared to their respective saline control groups. These results demonstrate that chronic intermittent heroin enhances appetitive learning for natural reinforcers and motivational processes and that this effect persists even after 30-days of withdrawal.
Inturrisi, C E; Schultz, M; Shin, S; Umans, J G; Angel, L; Simon, E J
The relative affinity to opiate receptors of heroin, 6-acetylmorphine and morphine was estimated by determining their ability to displace specifically bound 3H-naltrexone from rat brain opiate binding sites. In vitro hydrolysis of heroin to 6-acetylmorphine was monitored in the binding assay filtrate by use of a quantitative HPLC procedure. The rate of heroin hydrolysis was significantly slower at 0 degrees C than at 37 degrees C. The displacement of 1 nM 3H-naltrexone by unlabeled ligand at concentrations ranging from 7 to 500 nM was measured at 0 degrees C for 120 minutes, yielding IC50 values of heroin = 483 nM, 6-acetylmorphine = 73 nM and morphine = 53 nM. When the binding data for heroin were recalculated to include the displacement that could be attributed to the 6-acetylmorphine derived from heroin degradation during the incubation, all of the apparent heroin binding was accounted for by the 6-acetylmorphine. These results are consistent with previous reports of the low binding affinity of morphine congeners (e.g., codeine) that lack a free phenolic 3-hydroxyl group and support the view that heroin is a prodrug which serves to determine the distribution of its intrinsically active metabolites, 6-acetylmorphine and morphine.
Li, Jun-Xu; Koek, Wouter; France, Charles P
The cannabinoid receptor agonist Δ(9)-tetrahydrocannabinol (THC) enhances the antinociceptive effects of µ-opioid receptor agonists, raising the possibility of using a combination of THC and opioids for treating pain. This study examined the effects of noncontingent and contingent administration of THC on intravenous heroin self-administration in rhesus monkeys. Self-administration of different unit doses of heroin (0.0001-0.1 mg/kg/infusion) generated a typical inverted U-shaped dose-response curve. In one experiment (n=4), noncontingent THC (0.1-1.0 mg/kg) dose dependently shifted the heroin dose-response curve downward in three monkeys and slightly leftward in one monkey. In a second experiment (n=4), monkeys could self-administer THC alone (0.0032-0.032 mg/kg/infusion), heroin alone, or a mixture of THC and heroin. THC alone did not maintain responding above that obtained with saline; however, increasing the THC dose with heroin dose dependently decreased the number of infusions received and the rate of responding, as compared with data that were obtained with heroin alone. These results indicate that THC does not significantly enhance the positive reinforcing effects of heroin, further supporting the view that combining cannabinoid and opioid receptor agonists (e.g. for treating pain) does not increase, and might decrease, the abuse liability of individual drugs.
National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.
Included in this document are selections of topic-specific articles on heroin research reprinted from the National Institute on Drug Abuses (NIDA) research newsletter, NIDA Notes. Titles include: Buprenorphine Taken Three Times Per Week Is as Effective as Daily Doses in Treating Heroin Addiction; 33-Year Study Finds Lifelong, Lethal Consequences…
Li, Jun-Xu; Koek, Wouter; France, Charles P.
The cannabinoid receptor agonist delta9-tetrahydrocannabinol (THC) enhances the antinociceptive effects of mu opioid receptor agonists, raising the possibility of using a combination of THC and opioids for treating pain. This study examined the effects of noncontingent and contingent administration of THC on i.v. heroin self-administration in rhesus monkeys. Self-administration of different unit doses of heroin (0.0001–0.1 mg/kg/infusion) generated a typical inverted U-shaped dose-response curve. In one experiment (n=4), noncontingent THC (0.1–1.0 mg/kg) dose-dependently shifted the heroin dose-response curve downward in three monkeys and slightly leftward in one monkey. In a second experiment (n=4), monkeys could self-administer THC alone (0.0032–0.032 mg/kg/infusion), heroin alone, or a mixture of THC and heroin. THC alone did not maintain responding above that obtained with saline; however, increasing the THC dose with heroin dose-dependently decreased the number of infusions received and the rate of responding, as compared to data that were obtained with heroin alone. These results indicate that THC does not significantly enhance the positive reinforcing effects of heroin, further supporting the view that combining cannabinoid and opioid receptor agonists (e.g., for treating pain) does not increase, and might decrease, the abuse liability of the individual drugs. PMID:23044830
Primary heroin abusers who remained in a voluntary drug-free treatment program for an average of nine months were carefully matched with not-retained control subjects. Marijuana was used by the retained subjects as a heroin substitute and those who used marijuana were more apt to remain in the treatment program. (Author)
Peters, Ronald J., Jr.; Yacoubian, George S., Jr.; Baumler, Elizabeth R.; Ross, Michael W.; Johnson, Regina J.
To be effective with rehabilitation counseling, counselors need to be aware of cultural patterns of drug use. This study analyzed trends in heroin use between 1990 and 1997 among the arrestee population in some parts of the South. Findings suggest geographic, ethnic, and age-related variables for heroin use. (JDM)
National Inst. on Drug Abuse (DHHS/PHS), Bethesda, MD.
Although heroin use has decreased in the general population during the last few years, a troubling new trend is emerging. Use is up among school-age children and they are now subject to a popular culture in music and films that glamorizes its use. This trend along with increased availability and purity of heroin has created a major health concern…
Bergschmidt, Viktoria B
Taking the observation of disciplining and controlling everyday practices of methadone substitution as a point of departure, this paper explores the question of what exactly is so threatening or dangerous about heroin and heroin users. Drawing on the work of Michel Foucault and Judith Butler, the main argument of this article is that the danger of heroin use is a discursive construction in accordance with bio-power. On the one hand, the juridical governance of heroin dependence is shifting from punishment to therapy, and biomedical discourses proclaim the substitution of a moral notion of heroin dependence by a disease model. Nevertheless, in the context of the anxiety associated with HIV, heroin remains the dangerous drug par excellence, and heroin users are constructed as 'abject others', unable to subordinate to certain social norms. As a reaction to such injurious ascriptions, I argue, applicants to the methadone programme in their life stories intensely narrate a desire for normalization, which I read as a desire to emerge from the realm of the abject. Both the danger and the pleasure associated with heroin use are bound to fundamental processes of subject formation, which are often ignored in biomedical and anthropological discourses.
Mars, Sarah G; Bourgois, Philippe; Karandinos, George; Montero, Fernando; Ciccarone, Daniel
This qualitative study documents the pathways to injecting heroin by users in Philadelphia and San Francisco before and during a pharmaceutical opioid pill epidemic. Data was collected through in-depth, semi-structured interviews (conducted between 2010 and 2012) that were, conducted against a background of longer-term participant-observation, ethnographic studies of street-based drug users and dealers in Philadelphia (2007-12) and San Francisco (1994-2007, 2012). Philadelphia and San Francisco were selected for their contrasting political economies, immigration patterns and source type of heroin. In Philadelphia the ethnographers found heroin injectors, usually white users, who had started their opiate using careers with prescription opioids rather than transitioning from other drugs. In both Philadelphia and San Francisco, most of the young heroin injectors interviewed began, their drug-use trajectories with opioid pills--usually Percocet (oxycodone and acetaminophen), generic short acting oxycodone or, OxyContin (long-acting oxycodone)--before transitioning to heroin, usually by nasal inhalation (sniffing) or smoking at first, followed by injecting. While most of the Philadelphia users were born in the city or its suburbs and had started using both opioid pills and heroin there, many of the San Francisco users had initiated their pill and sometimes heroin use elsewhere and had migrated to the city from around the country. Nevertheless, patterns of transition of younger injectors were similar in both cities suggesting an evolving national pattern. In contrast, older users in both Philadelphia and San Francisco were more likely to have graduated to heroin injection from non-opiate drugs such as cannabis, methamphetamine and cocaine. Pharmaceutical opioid initiates typically reported switching to heroin for reasons of cost and ease-of-access to supply after becoming physically and emotionally dependent on opioid pills. Many expressed surprise and dismay at their
Wilson, G S; McCreary, R; Kean, J; Baxter, J C
Disturbances of growth and behavior in infants and toddlers of women addicted to heroin during pregnancy have been reported in uncontrolled studies. In this study, 3- to 6-year-old children of heroin-addicted mothers were compared to three other groups matched for age, race, sex, birth weight, and socioeconomic status. Heroin-exposed children weighed less and were shorter than those in the comparison groups; 14% had a head circumference below the third percentile. Heroin-exposed children were rated by parents as less well adjusted than control children and they differed significantly in perceptual measures and on subtests of the Illinois Test of Psycholinguistic Abilities and McCarthy Scales of Children's Abilities relating to the process of organization. These findings suggest that chronic intrauterine exposure to heroin may affect growth and behavior as well as perceptual and learning processes in preschool children.
Tanda, G; Pontieri, F E; Di Chiara, G
The effects of the active ingredient of Cannabis, Delta9-tetrahydrocannabinol (Delta9-THC), and of the highly addictive drug heroin on in vivo dopamine transmission in the nucleus accumbens were compared in Sprague-Dawley rats by brain microdialysis. Delta9-THC and heroin increased extracellular dopamine concentrations selectively in the shell of the nucleus accumbens; these effects were mimicked by the synthetic cannabinoid agonist WIN55212-2. SR141716A, an antagonist of central cannabinoid receptors, prevented the effects of Delta9-THC but not those of heroin. Naloxone, a generic opioid antagonist, administered systemically, or naloxonazine, an antagonist of micro1 opioid receptors, infused into the ventral tegmentum, prevented the action of cannabinoids and heroin on dopamine transmission. Thus, Delta9-THC and heroin exert similar effects on mesolimbic dopamine transmission through a common mu1 opioid receptor mechanism located in the ventral mesencephalic tegmentum.
Hutson, Lee W; Szczytkowski, Jennifer L; Saurer, Timothy B; Lebonville, Christina; Fuchs, Rita A; Lysle, Donald T
Dopamine receptor stimulation is critical for heroin-conditioned immunomodulation; however, it is unclear whether the ventral tegmental area (VTA) contributes to this phenomenon. Hence, rats received repeated pairings of heroin with placement into a distinct environmental context. At test, they were re-exposed to the previously heroin-paired environment followed by systemic lipopolysaccharide treatment to induce an immune response. Bilateral GABA agonist-induced neural inactivation of the anterior, but not the posterior VTA, prior to context re-exposure inhibited the ability of the heroin-paired environment to suppress peripheral nitric oxide and tumor necrosis factor-α expression, suggesting a role for the anterior VTA in heroin-conditioned immunomodulation.
Increased densities of nitric oxide synthase expressing neurons in the temporal cortex and the hypothalamic paraventricular nucleus of polytoxicomanic heroin overdose victims: possible implications for heroin neurotoxicity.
Bernstein, Hans-Gert; Trübner, Kurt; Krebs, Philipp; Dobrowolny, Henrik; Bielau, Hendrik; Steiner, Johann; Bogerts, Bernhard
Heroin is one of the most dangerous drugs of abuse, which may exert various neurotoxic actions on the brain (such as gray matter loss, neuronal apoptosis, mitochondrial dysfunction, synaptic defects, depression of adult neurogenensis, as well as development of spongiform leucoencephalopathy). Some of these toxic effects are probably mediated by the gas nitric oxide (NO). We studied by morphometric analysis the numerical density of neurons expressing neuronal nitric oxide synthase (nNOS) in cortical and hypothalamic areas of eight heroin overdose victims and nine matched controls. Heroin addicts showed significantly increased numerical densities of nNOS immunoreactive cells in the right temporal cortex and the left paraventricular nucleus. Remarkably, in heroin abusers, but not in controls, we observed not only immunostained interneurons, but also cortical pyramidal cells. Given that increased cellular expression of nNOS was accompanied by elevated NO generation in brains of heroin addicts, these elevated levels of NO might have contributed to some of the known toxic effects of heroin (for example, reduced adult neurogenesis, mitochondrial pathology or disturbances in synaptic functioning).
Broséus, Julian; Gentile, Natacha; Esseiva, Pierre
The illicit drug cutting represents a complex problem that requires the sharing of knowledge from addiction studies, toxicology, criminology and criminalistics. Therefore, cutting is not well known by the forensic community. Thus, this review aims at deciphering the different aspects of cutting, by gathering information mainly from criminology and criminalistics. It tackles essentially specificities of cocaine and heroin cutting. The article presents the detected cutting agents (adulterants and diluents), their evolution in time and space and the analytical methodology implemented by forensic laboratories. Furthermore, it discusses when, in the history of the illicit drug, cutting may take place. Moreover, researches studying how much cutting occurs in the country of destination are analysed. Lastly, the reasons for cutting are addressed. According to the literature, adulterants are added during production of the illicit drug or at a relatively high level of its distribution chain (e.g. before the product arrives in the country of destination or just after its importation in the latter). Their addition seems hardly justified by the only desire to increase profits or to harm consumers' health. Instead, adulteration would be performed to enhance or to mimic the illicit drug effects or to facilitate administration of the drug. Nowadays, caffeine, diltiazem, hydroxyzine, levamisole, lidocaïne and phenacetin are frequently detected in cocaine specimens, while paracetamol and caffeine are almost exclusively identified in heroin specimens. This may reveal differences in the respective structures of production and/or distribution of cocaine and heroin. As the relevant information about cutting is spread across different scientific fields, a close collaboration should be set up to collect essential and unified data to improve knowledge and provide information for monitoring, control and harm reduction purposes. More research, on several areas of investigation, should be
Rook, Elisabeth J; van Ree, Jan M; van den Brink, Wim; Hillebrand, Michel J X; Huitema, Alwin D R; Hendriks, Vincent M; Beijnen, Jos H
A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon" method. In this technique, heroin base is heated on aluminium foil, and heroin vapours are inhaled into the lungs. Not much is known about the pharmacokinetics profile and bioavailability of this specific administration method. Therefore, a study was performed on pharmacokinetics and pharmacodynamics of heroin inhalation and intravenous use. Eleven patients who injected heroin and 9 patients who inhaled heroin entered the study. They were on steady-state heroin treatment for at least 12 months. For safety reasons, there was no crossing-over between heroin injection or inhalation. In a double-blind randomised study, 67-100-150% of the regular heroin maintenance dose was administered to each patient. Maximal single heroin dose was 450 mg. Plasma concentrations of heroin and its metabolites 6-monoacetylmorphine, morphine and morphine-glucuronides were analysed using LC-MS-MS. Blood pressure, heart rate, skin temperature and reaction time were assessed. Furthermore, visual analogue scales regarding craving and appreciation of heroin effect were scored by the subjects. Both in inhaling and injecting patients, the areas under curve of heroin and all measured metabolites were linearly related to heroin dose. Mean C(max) of heroin and its metabolites were 2-6 times lower after inhalation, than after intravenous injection. Bioavailability (F) of heroin inhalation was estimated as 52% (95% CI 44-61%). Heroin was rapidly cleared from plasma. Cl/F was 930 l/hr (95% CI 799-1061 l/hr) after intravenous administration, and 1939 l/hr (95% CI 1661-2217 l/hr) after inhalation. Heroin Cl and Vd were correlated to body weight (R(2) 15-19%). Morphine-glucuronides levels were inversely related to
McGill, Svena; Hjelm, Eva; Rajs, Jovan; Lindquist, Olle; Friman, Göran
A high frequency of Bartonella elizabethae seropositivity (39%) was recorded among intravenous heroin addicts in Stockholm, Sweden, who died from a lethal injection. Some of the B. elizabethae-seropositive individuals also had antibodies to B. henselae Houston-1, B. grahamii, and B. quintana, but none had antibodies to B. henselae Marseille or B. vinsonii subsp. vinsonii. Hepatitis was a frequent finding but no case had peliosis hepatitis. There was no case of endocarditis, but in three persons active subacute-to-chronic myocarditis was found; two of these cases were Bartonella-positive and HIV-negative.
Uusitalo, Susanne; Broers, Barbara
In our previous article on the question whether heroin addicts are able to give informed consent voluntarily to research on heroin-assisted treatment, we criticized the ongoing bioethical discussion of a flawed conceptualization of heroin addicts' options. As a participant in this discussion, Edmund Henden defends the conceptualization as sufficient for determining whether heroin addicts are able to give informed consent to the research on heroin-assisted treatment voluntarily. This discussion on research on heroin-assisted treatment seems to go astray in several respects. In his reply to our article Henden maintains some of the biases, such as the necessity of abstinence in recovery, that seem to prevail in addiction research on a more general level as well. These biases run the danger of having implausible ethical implications on stakeholders in addiction research and treatment. In our reply to him, we will further clarify and discuss the importance of describing the relevant issues in plausible terms that do justice to the realities of the cases of informed consent in research on heroin-assisted treatment and also raise a wider issue of the ethics of wording as well as of the narrow scope, or 'tunnel vision', in addiction research as currently conducted.
Price, Erin P; Seymour, Meagan L; Sarovich, Derek S; Latham, Jennie; Wolken, Spenser R; Mason, Joanne; Vincent, Gemma; Drees, Kevin P; Beckstrom-Sternberg, Stephen M; Phillippy, Adam M; Koren, Sergey; Okinaka, Richard T; Chung, Wai-Kwan; Schupp, James M; Wagner, David M; Vipond, Richard; Foster, Jeffrey T; Bergman, Nicholas H; Burans, James; Pearson, Talima; Brooks, Tim; Keim, Paul
In December 2009, two unusual cases of anthrax were diagnosed in heroin users in Scotland. A subsequent anthrax outbreak in heroin users emerged throughout Scotland and expanded into England and Germany, sparking concern of nefarious introduction of anthrax spores into the heroin supply. To better understand the outbreak origin, we used established genetic signatures that provided insights about strain origin. Next, we sequenced the whole genome of a representative Bacillus anthracis strain from a heroin user (Ba4599), developed Ba4599-specific single-nucleotide polymorphism assays, and genotyped all available material from other heroin users with anthrax. Of 34 case-patients with B. anthracis-positive PCR results, all shared the Ba4599 single-nucleotide polymorphism genotype. Phylogeographic analysis demonstrated that Ba4599 was closely related to strains from Turkey and not to previously identified isolates from Scotland or Afghanistan, the presumed origin of the heroin. Our results suggest accidental contamination along the drug trafficking route through a cutting agent or animal hides used to smuggle heroin into Europe.
Yan, Biao; Hu, Zhaoyang; Yao, Wenqing; Le, Qiumin; Xu, Bo; Liu, Xing; Ma, Lan
MicroRNAs (miRNAs) are a class of evolutionarily conserved, 18–25 nucleotide non-coding sequences that post-transcriptionally regulate gene expression. Recent studies implicated their roles in the regulation of neuronal functions, such as learning, cognition and memory formation. Here we report that miR-218 inhibits heroin-induced behavioral plasticity. First, network propagation-based method was used to predict candidate miRNAs that played potential key roles in regulating drug addiction-related genes. Microarray screening was also carried out to identify miRNAs responding to chronic heroin administration in the nucleus accumbens (NAc). Among the collapsed miRNAs, top-ranked miR-218 was decreased after chronic exposure to heroin. Lentiviral overexpression of miR-218 in NAc could inhibit heroin-induced reinforcement in both conditioned place preference (CPP) test and heroin self-administration experiments. Luciferase activity assay indicated that miR-218 could regulate 3′ untranslated regions (3′ UTR) of multiple neuroplasticity-related genes and directly target methyl CpG binding protein 2 (Mecp2). Consistently, Mecp2308/y mice exhibited reduced heroin seeking behavior in CPP test. These data reveal a functional role of miR-218 and its target, MeCP2, in the regulation of heroin-induced behavioral plasticity. PMID:28074855
Longo, Marie C; Henry-Edwards, Susan M; Humeniuk, Rachel E; Christie, Paul; Ali, Robert L
Since late 2000, anecdotal reports from drug users and health professionals have suggested that there was a reduction in the supply of heroin in Adelaide in the first half of 2001, referred to as a heroin 'drought'. The aim of this paper was to critically review evidence for this, using data obtained from 100 injecting drug users surveyed for the 2001 Illicit Drug Reporting System (IDRS). This project is carried out annually in all Australian jurisdictions, and collects up-to-date information on the markets for heroin, methamphetamine, cocaine and cannabis. This paper also investigates the possible implications of this 'drought' on patterns of drug use and drug-related harms. The 2001 IDRS found consistent reports by users of an increase in the price of heroin, together with decreases in purity and availability. These factors resulted in a decrease in the frequency of self-reported heroin use among those surveyed in 2001, and a concomitant increase in the use of other drugs, in particular methamphetamine and morphine. The heroin 'drought' appears to have had a substantial impact on several indices of drug-related harm. There was a marked decrease in the number of opioid-related fatalities, and hospital data also showed reductions in heroin-related presentations. Treatment service data showed an increase in the number of admissions related to amphetamines. There is a need for health promotion and education on the adverse effects of methamphetamine use, and the development of improved treatment protocols for methamphetamine abuse and dependence.
Ciccarone, Daniel; Harris, Magdalena
The loss of functioning veins (venous sclerosis) is a root cause of suffering for long-term heroin injectors. In addition to perpetual frustration and loss of pleasure/esteem, venous sclerosis leads to myriad medical consequences including skin infections, for example, abscess, and possibly elevated HIV/HCV risks due to injection into larger jugular and femoral veins. The etiology of venous sclerosis is unknown and users’ perceptions of cause/meaning unexplored. This commentary stems from our hypothesis that venous sclerosis is causally related to heroin acidity, which varies by heroin source-form and preparation. We report pilot study data on first ever in vivo measurements of heroin pH and as well as qualitative data on users’ concerns and perceptions regarding the caustic nature of heroin and its effects. Heroin pH testing in natural settings is feasible and a useful tool for further research. Our preliminary findings, for example, that different heroin source-forms and preparations have a two log difference in acidity, have potentially broad, vital and readily implementable harm reduction implications. PMID:26077143
Díaz-Flores, José F; Sañudo, Ricardo I; Rodríguez, Elena M; Romero, Carlos Díaz
Na, K, Ca, Mg, P, Fe, Cu, Zn and Se concentrations were determined in the serum of 106 heroin addicts and were compared with the concentrations obtained in a control group formed of 186 apparently healthy individuals. Heroin addicts displayed K and Se mean concentrations lower (p < 0.05), and Na, Mg, P mean concentrations and a Cu/Zn ratio higher (p < 0.05) than those mean values observed in the control group. The Mg and P concentrations in the serum of heroin addicts tended to normalize when age increased. The heroin addicts included in the methadone maintenance treatment program had higher serum mean concentrations of K and Mg than the heroin addicts in the detoxification process. The Na, K and Mg concentrations displayed highly significant correlations, with a different behavior for the heroin addicts group and the control group. When applying factor analysis and representing the scores of the first and second factors, the heroin addicts tended to differentiation from the control group. However, methadone substitution treatment was not able to normalize these concentrations.
Ciccarone, Daniel; Harris, Magdalena
The loss of functioning veins (venous sclerosis) is a root cause of suffering for long-term heroin injectors. In addition to perpetual frustration and loss of pleasure/esteem, venous sclerosis leads to myriad medical consequences including skin infections, for example, abscess, and possibly elevated HIV/HCV risks due to injection into larger jugular and femoral veins. The etiology of venous sclerosis is unknown and users' perceptions of cause/meaning unexplored. This commentary stems from our hypothesis that venous sclerosis is causally related to heroin acidity, which varies by heroin source-form and preparation. We report pilot study data on first ever in vivo measurements of heroin pH and as well as qualitative data on users' concerns and perceptions regarding the caustic nature of heroin and its effects. Heroin pH testing in natural settings is feasible and a useful tool for further research. Our preliminary findings, for example, that different heroin source-forms and preparations have a two log difference in acidity, have potentially broad, vital and readily implementable harm reduction implications.
Pandria, Niki; Kovatsi, Leda; Vivas, Ana B; Bamidis, Panagiotis D
Drug addiction is a major health problem worldwide. Recent neuroimaging studies have shed light into the underlying mechanisms of drug addiction as well as its consequences to the human brain. The most vulnerable, to heroin addiction, brain regions have been reported to be specific prefrontal, parietal, occipital, and temporal regions, as well as, some subcortical regions. The brain regions involved are usually linked with reward, motivation/drive, memory/learning, inhibition as well as emotional control and seem to form circuits that interact with each other. So, along with neuroimaging studies, recent advances in resting-state dynamics might allow further assessments upon the multilayer complexity of addiction. In the current manuscript, we comprehensively review and discuss existing resting-state neuroimaging findings classified into three overlapping and interconnected groups: functional connectivity alterations, structural deficits and abnormal topological properties. Moreover, behavioral traits of heroin-addicted individuals as well as the limitations of the currently available studies are also reviewed. Finally, in need of a contemporary therapy a multimodal therapeutic approach is suggested using classical treatment practices along with current neurotechonologies, such as neurofeedback and goal-oriented video-games.
Darke, Shane; Duflou, Johan; Torok, Michelle
The demographic and toxicological characteristics of deliberate (SUI, n = 50) and accidental (ACC, n = 927) fatal heroin overdose cases were examined. SUI cases were more likely to be female, had lower body mass indices, were more likely to be enrolled in treatment and less likely to have hepatic pathology. The median blood morphine concentration of SUI cases was significantly higher than that of ACC cases (0.70 vs. 0.40 mg/L, p < 0.001). Blood morphine concentrations of >1 mg/L were seen among 38.0% of SUI cases compared to 13.9% of ACC cases. Being a member of the SUI group remained a significant independent predictor of higher morphine concentrations after controlling for the effects of potential confounders (p < 0.001), other significant predictors being the absence of alcohol (p < 0.001), the presence of methadone (p < 0.05), and the presence of cocaine (p < 0.05). The current data are consistent with the view that suicide forms a small, but distinct, category of heroin overdose cases, rather than overdose being a parasuicidal phenomenon per se.
Dettmeyer, R; Friedrich, K; Schmidt, P; Madea, B
Well-known complications related to drug abuse are myocardial insufficiency, myocardial infarction, endocarditis, myocarditis, aortic dissection, neurologic damages, ischemic colitis, thrombotic phenomenons, renal infarction and acute liver failure. Furthermore, microfocal fibrosis of the myocardium is found in stimulant abuse. The origin of myocardial fibrosis associated with opiate abuse (endocarditis, myocarditis, embolism) is still unclear. This question shall be investigated using immunohistochemical staining for early diagnosis of myocarditis. A quantification of myocardial interstitial leucocytic infiltrates was accomplished in 21 chronic drug abusers who died of heroin/morphine intoxication and compared to 15 normal subjects who died suddenly due to non-cardiac causes of death without intoxication (e.g. traffic accidents, head trauma). Toxicological investigations were performed and in addition, blood samples were checked to clarify the status of HIV, hepatitis A, B and C in both groups. To verify signs of inflammation, myocardial specimen from different locations were investigated with conventional histological stainings and immunohistochemical techniques for characterization and quantification of interstitial myocardial leucocytes, T-lymphocytes and macrophages. The number of cells were found up to fivefold increased in heroin addicts compared to the control group without reaching the cut-off values for immunohistochemically based diagnosis of myocarditis.
Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M
Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy. PMID:25803496
Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M
Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.
Ornoy, A; Michailevskaya, V; Lukashov, I; Bar-Hamburger, R; Harel, S
In the present investigation we were interested to study the possible role of in-utero exposure to heroin and of the home environmental in the etiology of long-term developmental problems in children born to heroin-dependent parents in comparison to matched controls. The children were examined at .5-6 years of age by a developmental pediatrician and a developmental psychologist using, for the children up to 2.5 years of age, the Bayley Developmental Scales, and for children aged 3-6 years the McCarthy Scales for Children's Abilities. We examined 83 children born to heroin-dependent mothers, and compared the results to those of 76 children born to heroin-dependent fathers and to three control groups; 50 children with environmental deprivation, 50 normal children from families of moderate or high socioeconomic class, without environmental deprivation, and 80 healthy children from kindergartens in Jerusalem. There were five children (6.0%) with significant neurological damage among the children born to heroin-dependent mothers and six (7.9%) children among those born to heroin-dependent fathers. The children born to heroin-dependent mothers had a lower birth weight and a lower head circumference at examination when compared to controls. The children born to heroin-dependent parents also had a high incidence of hyperactivity, inattention, and behavioral problems. The lowest DQ or IQ among the children with cognitive levels above 70 was found in the children with environmental deprivation, next was the DQ or IQ of children born to heroin-dependent fathers, then the DQ or IQ of the children born to heroin-dependent mothers. When the children born to heroin-dependent mothers were divided to those that were adopted at a very young age and to those raised at home, the adopted children were found to function similarly to the controls while those not adopted functioned significantly lower. Our results show that the developmental delay and behavioral disorders observed among
Darke, Shane; Ross, Joanne; Teesson, Maree
Opioids make the single largest contribution to illicit drug-related mortality and morbidity worldwide In this paper we reflect upon what has been learnt regarding treatment outcome and the natural history of heroin use from the Australian Treatment Outcome Study (ATOS). We focus on what we knew prior to ATOS, what ATOS revealed that is novel, and the implications for research, practice and policy. ATOS provided strong evidence for sustained improvement attributable to treatment across the three years of the study. It is argued that treatment for heroin dependence is money well spent, and leads to clear and sustained benefits to both heroin users and society.
Farrell, Michael; Hall, Wayne
This editorial considers the findings of the systematic review of heroin-assisted treatment, with six different studies from six different countries, published in this issue. The meta-analysis focuses on supervised injected heroin and reports significant crime reduction and an overall cost-effectiveness of treatment. Despite this body of evidence, policy makers remain reluctant to develop this treatment further. The question remains, what else is required to convince policy makers of the value of such treatment for severe and refractory heroin dependence?
Musshoff, F; Trafkowski, J; Madea, B
A fully validated procedure for the simultaneous determination of morphine (MOR), morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), 6-acetylmorphine (6AM), codeine (COD), codeine-6-glucuronide (C6G), acetylcodeine (AC), noscapine (NOS) and papaverine (PAP) based on liquid chromatography followed by electrospray mass spectrometry applying multiple reaction monitoring (LC-ESI-MS/MS) in urine samples is described. The extraction was carried out on a Zymark Rapid Trace Workstation using C18 solid-phase extraction cartridges. The separation was performed in 19 min on an Agilent 1100 HPLC system, using a Phenomenex C18 AQUA column (4 microm, 150 mm x 2 mm), which is coupled with an Applied Biosystems API 2000 mass spectrometer. Deuterated analogues were used as internal standards. The limits of detection were in the range of 0.1 ng/ml (PAP) to 7.4 ng/ml (M6G), the coefficients of correlation were higher than 0.996, the precisions ranged from 3% to 12% and the absolute recoveries were between 45% (M3G) and 98% (MOR). Analyses of samples from patients of a heroin prescription program demonstrated the usefulness of the procedure for the analytical differentiation between prescribed synthetic heroin (diamorphine) use and non-prescription heroin abuse on the basis of urine analysis. After the ingestion of pharmaceutical heroin only general markers for heroin use were detected, which are MOR, M3G, M6G and 6AM, respectively. When illicit heroin was abused, additionally to further general markers (COD, C6G) specific markers for non-prescription heroin abuse (AC, NOS, PAP) were found. However, it must be kept in mind that only AC may be regarded as absolute specific marker of non-prescription heroin, because all other compounds may appear in urine after ingestion of opiate alkaloids containing medicines or foods (e.g. poppy seeds). Therefore, patients of a heroin prescription program should be advised not to ingest such products.
Polettini, A; Groppi, A; Montagna, M
In order to evaluate pharmacokinetic interactions between heroin and alcohol and their role in the etiology of heroin-related deaths (HRD), the alcohol concentration in blood (BAC), the free (FM) and total morphine (TM) concentrations in blood (determined by DPC Coat-A-Count radioimmunoassay before and after enzymatic hydrolysis), and the TM concentration in urine and bile (DPC Coat-A-Count after enzymatic hydrolysis) in a population of 39 lethal cases included in the records of the Department of Legal Medicine and Public Health at the University of Pavia from the period January 1997-April 1998 were examined. The cause of death in each case was attributed to either heroin or associated heroin-ethanol intoxication. Cases were arbitrarily divided into two groups according to BAC (low-ethanol group, LE, BAC < or = 1000 mg/L and high-ethanol group, HE, BAC > 1000 mg/L). The differences in the FM and TM concentrations in blood, bile, and urine and in the FM/TM ratios between the two . groups were statistically evaluated (Mann-Whitney U test). A similar statistical evaluation was carried out on data from a previously published study concerning the disposition of heroin and its metabolites (6-acetylmorphine and morphine) in blood and urine in 23 lethal cases attributed to either heroin or heroin and alcohol intoxication. The values of the following variables in the LE and HE groups were compared: FM, TM, and 6-acetylmorphine concentrations in blood (6-AM); the FM/ (FM + 6-AM) ratio; the FM/TM ratio; and the urinary concentrations of heroin, 6-acetylmorphine, and free morphine. Statistical analyses of data indicated that high BACs are associated with reduced hydrolysis of 6-AM to morphine (FM/[FM + 6-AM], p = 0.0022) and that a good inverse correlation exists between BAC and hydrolysis of 6-AM to morphine (r2 = 0.67). High BACs were also found to be associated with an increased FM/TM ratio and with reduced excretion of free and total morphine. These results suggest the
Cadoni, Cristina; Simola, Nicola; Espa, Elena; Fenu, Sandro; Di Chiara, Gaetano
Adolescent Cannabis exposure has been hypothesized to act as a gateway to opiate abuse. In order to investigate the role of genetic background in cannabinoid-opiate interactions, we studied the effect of Δ(9) -tetrahydrocannabinol (THC) exposure of adolescent Lewis and Fischer 344 rats on the responsiveness of accumbens shell and core dopamine (DA), as monitored by microdialysis, to THC and heroin at adulthood. Heroin reward and reinstatement by heroin priming were studied by conditioned place preference (CPP) and cognitive and emotional functions by object recognition, Y maze and elevated plus maze paradigms. THC stimulated shell DA in Lewis but not in Fischer 344 rats. Adolescent THC exposure potentiated DA stimulant effects of heroin in the shell and core of Lewis and only in the core of Fischer 344 rats. Control Lewis rats developed stronger CPP to heroin and resistance to extinction compared with Fischer 344 strain. In Lewis rats, THC exposure did not affect heroin CPP but potentiated the effect of heroin priming. In Fischer 344 rats, THC exposure increased heroin CPP and made it resistant to extinction. Lewis rats showed seeking reactions during extinction and hedonic reactions in response to heroin priming. Moreover, adolescent THC exposure affected emotional function only in Lewis rats. These observations suggest that long-term effects of Cannabis exposure on heroin addictive liability and emotionality are dependent on individual genetic background.
Kvello, Anne Marte Sjursen; Andersen, Jannike Mørch; Øiestad, Elisabeth Leere; Mørland, Jørg; Bogen, Inger Lise
Immunotherapy can provide a supplemental treatment strategy against heroin use on the principle of sequestering the active drug in the bloodstream, thereby reducing its distribution to the brain. Previous studies have shown that heroin's first metabolite, 6-monoacetylmorphine (6-MAM), is the main mediator of acute heroin effects. The objective of the present study was to characterize the pharmacological potential of a monoclonal antibody against 6-MAM (anti-6-MAM mAb) to counteract the heroin response. The individual contributions from heroin and 6-MAM to heroin effects were also examined by pretreating mice with anti-6-MAM mAb (10-100 mg/kg) prior to either heroin or 6-MAM injection (1.25-2.5 μmol/kg). The opioid-induced behavioral response was assessed in a locomotor activity test, followed by opioid and antibody quantification in blood and brain tissue. Pretreatment with mAb caused a profound reduction of heroin- and 6-MAM-induced behavior, accompanied by correspondingly decreased levels of 6-MAM in brain tissue. mAb pretreatment was more efficient against 6-MAM injection than against heroin, leading to an almost complete blockade of 6-MAM-induced effects. mAb pretreatment was unable to block the immediate (5-minute) transport of active metabolites across the blood-brain barrier after heroin injection, indicating that heroin itself appears to enhance the immediate delivery of 6-MAM to the brain. The current study provides additional evidence that 6-MAM sequestration is crucial for counteracting the acute heroin response, and demonstrates the pharmacological potential of immunotherapy against heroin use.
Gerra, G; Di Petta, G; D'Amore, A; Iannotta, P; Bardicchia, F; Falorni, F; Coacci, A; Strepparola, G; Campione, G; Lucchini, A; Vedda, G; Serio, G; Manzato, E; Antonioni, M; Bertacca, S; Moi, G; Zaimovic, A
This study compared the anti-aggressiveness effects of the atypical anti-psychotic olanzapine with that of selective serotonin reuptake inhibitors (SSRI) and benzodiazepines (BZD) among patients with heroin dependence submitted to opioid-agonists substitution treatment. Sixty-seven (67) patients who met the DSM-IV criteria for heroin dependence and showed aggressive personality traits, not affected by comorbid schizophrenia or bipolar disorder, accepted to participate in a 12-week prospective, observational trial. Patients were included into two subgroups in relationship with treatment, for the evaluation of the endpoints at week 12: group 1: substitution treatment in combination with OLA (32 patients); group 2: substitution treatment in combination with fluoxetine/paroxetine and clonazepam (35 patients). Efficacy measures were Buss Durkee Hostility Inventory (BDHI), Symptoms Check List-90 (SCL 90) anger--hostility scores, incidence rates of aggressive incidents and attacks. The rates of patients who remained in treatment at week 12 in group 1, treated with OLA, and group 2, treated with SSRI and BDZ, were not significantly different (17 = 53.1% vs 16 = 45.7%). BDHI total, direct aggressiveness, verbal aggressiveness scores, SCL 90 aggressiveness scores and aggressive incidents rates showed a significantly more consistent decrease from baseline in group 1 than in group 2 subjects, in the patients who completed the treatment (p < 0.001; p < 0.01; p < 0.05; p < 0.01; p < 0.001). Among the completers, 69.3% achieved early full substance abuse remission, while 30.7% achieved partial substance abuse remission, with no significant difference between 1 and 2 treatment subgroups. Although obtained by an observational--open clinical study, with multiple limitations, our findings suggest that OLA may be useful as an adjunctive agent in reducing aggressive/hostile behaviour in heroin addicted individuals during maintenance substitution treatment. Otherwise, atypical anti
Wilson, Geraldine S.; And Others
Disturbances of growth and behavior in children of heroin-addicted mothers was studied in 77 preschool children. Arthur Retlaw and Associates, Inc., Suite 2080, 1603 Orrington Avenue, Evanston, Illinois 60201. (Author/DLS)
Maremmani, Angelo Giovanni Icro; Rovai, Luca; Rugani, Fabio; Pacini, Matteo; Lamanna, Francesco; Bacciardi, Silvia; Perugi, Giulio; Deltito, Joseph; Dell’Osso, Liliana; Maremmani, Icro
In a group of 1066 heroin addicts, who were seeking treatment for opioid agonist treatment, we looked for differences in historical, demographic, and clinical characteristics, between patients with different levels of awareness of illness (insight). The results showed that, in the cohort studied, a majority of subjects lacked insight into their heroin-use behavior. Compared with the impaired-insight group, those who possessed insight into their illness showed significantly greater awareness of past social, somatic, and psychopathological impairments, and had a greater number of past treatment-seeking events for heroin addiction. In contrast with other psychiatric illnesses, the presence of awareness appears to be related to the passing of time and to the worsening of the illness. Methodologies to improve the insight of patients should, therefore, be targeted more directly on patients early in their history of heroin dependence, because the risk of lack of insight is greatest during this period. PMID:22787450
Vereczkei, Andrea; Sasvári-Székely, Mária; Barta, Csaba
Heroin dependence is a disorder with complex inheritance. It is influenced by multiple genetic and environmental factors. This paper gives an overview on the specific risk factors in the background of heroin addiction, especially within the dopaminergic system, which is one of the most important components of the brain's reward system. In connection with the development of heroin addiction the role of the dopamine D2 and D4 receptors, the dopamine transporter and the catechol-O-methyltransferase genes is discussed. Certain polymorphisms of the most extensively studied dopamine D2 receptor gene show strong association with heroin dependence. Dopamine D4 receptor and catechol-O-methyltransferase genes are also associated with the disease, but some results are still controversial. Only few studies have been done in association with the dopamine transporter gene and substance misuse and no convincing results have been found. To unravel the contradictions and better understand the pathogenesis of the disease more research needs to be conducted.
Trenz, Rebecca C; Harrell, Paul; Scherer, Michael; Mancha, Brent E; Latimer, William W
The current study uses structural equation modeling to investigate factors associated with alcohol initiation and injection heroin use. Baseline data from the NEURO-HIV Epidemiologic Study in Baltimore, Maryland, were used. Participants were 404 injection heroin users (M(age) = 32.72) with a history of regular injection in their lifetime. Latent variables were created for self-reported school problems and academic failure. The final model indicated that greater school problems were associated with earlier alcohol initiation (ß = -0.22, p < .001) and earlier alcohol initiation was associated with greater frequency of recent heroin use (ß = -0.12, p < .05). Academic failure was directly related to greater frequency of recent heroin injection (ß = 0.15, p < .01). The results expand research investigating the relationship between adolescent behavior and illicit drug use in adulthood.
Bolz, Jan; Meves, Saskia H; Kara, Kaffer; Reinacher-Schick, Anke; Gold, Ralf; Krogias, Christos
Hypereosinophilic syndrome represents a rare cause for cerebral infarctions and inflammatory neurological disorders. Various possible pathogenic mechanisms for cerebral infarctions have already been discussed. Complex mechanisms including a local hypercoagulability by eosinophilic granules as well as a direct damage to endothelial cells, leading to alterations of the microcirculation seem to be involved. The changing pattern of heroin use to inhalation/sniffing leading to an increasing abuse may cause a rise in the prevalence of Heroin induced eosinophilia, as it has been reported in a case of eosinophilic pneumonia associated with heroin inhalation. To our knowledge, the present case report displays the first description of stroke in the setting of heroin induced hypereosinophilia. Thus, besides usual vasoconstriction, HES should be considered in drug-induced cerebral infarctions.
Rabin, Richard L.
Background Acute comitant esotropia secondary to heroin withdrawal is a rarely reported phenomenon that has never been described with nystagmus. Adverse effects of heroin on eye alignment were first reported in soldiers returning from Vietnam, yet no theory is generally accepted as the cause of these abnormalities. Method We present a case of a 22-year-old female who developed 40 prism diopters of alternating comitant esotropia with nystagmus 8 days after abrupt heroin cessation, review the existing literature, and propose a novel hypothesis for this phenomenon. Results After 76 days, her esotropia resolved, and she was left with 7 prism diopters of esophoria. Conclusion This case demonstrates that acquired nystagmus can present in addition to acute-onset esotropia after abrupt heroin cessation. We compare and contrast the theories of this mechanism and review the literature. PMID:26483678
Boeri, Miriam Williams; Sterk, Claire E.; Elifson, Kirk W.
Purpose Our knowledge regarding older users of illicit drugs is limited despite their increasing numbers. In this paper we apply a life course perspective to gain a further understanding of older adult drug use, specifically contrasting early- and late-onset heroin users. Design and Methods Qualitative data were collected from 29 older heroin users. Life course analysis focused on the users’ experiences across the life span. Results The findings suggest that those aging-into heroin use (late-onset) are disadvantaged compared to those who are maturing-in (early-onset) except in areas of health. Implications We propose that conceptualizing the use of heroin and other illicit drugs among older adults based on their life course trajectory will provide insights for social and health services, including drug treatment. PMID:18981280
Lazzeri, Davide; Castello, Manuel Francisco; Lippi, Donatella; Weisz, George M.
Judith was a legendary Hebrew heroine who beheaded the general Holofernes and saved the children of Israel from destruction by the Assyrian army. In the Book of Judith, which is still present in the Catholic and Orthodox Christian Bibles, Judith is presented as an illustrious woman who defeated the enemy using her virtue and fortitude. The present investigation has revealed 24 portraits in which Judith has been depicted with variable grades of thyroid gland enlargement on the scene where she decapitates Holofernes. There is no doubt that the integration of a slight thyroid enlargement in the paintings is a stylistic hallmark that portrays an idealized female beauty with a balanced neck and graceful body. The large extended goiter was probably depicted by the artists as a symbol of a powerful masculine body and her courage, and at the same time, it probably also reflects better anatomic accuracy and knowledge of artists from that period. PMID:26904480
Cooper, Jamie G; Spilke, Cord E; Denton, Miles; Jamieson, Stuart
Wound botulism is a rare infectious disease due to neurotoxin release from the anaerobic, spore-forming bacterium Clostridium botulinum that is becoming an ever more frequent complication of parenteral drug abuse in the Western world. Before the year 2000, no such cases had been reported in the UK and Ireland, but since then the number of proven and suspected cases of wound botulism occurring in parenteral drug users has increased markedly. The diagnosis is often difficult, based on a high degree of clinical suspicion and if not considered in the initial differential diagnosis, then considerable delays in treatment may result. This is the case report of a male heroin user who presented three times to an Emergency Department in the UK before a diagnosis of wound botulism was made and treatment commenced. It is important that emergency clinicians are aware of the possibility of wound botulism in parenteral drug users that present with unusual neurological or respiratory symptomatology.
Reed, J L; Ghodse, A H
Tests on 12 heroin addicts showed that their response to a glucose load differed from that in normal controls. Though the fasting blood sugar was normal, the rise in blood glucose after a standard 50-g oral glucose tolerance test was delayed and the rise smaller than in the controls. The heroin addicts had high resting insulin levels and a delayed peak response to an oral glucose load, and their growth hormone response was also abnormal.
Klous, Marjolein G; Van den Brink, Wim; Van Ree, Jan M; Beijnen, Jos H
Presently, there is a considerable interest in heroin-assisted treatment: co-prescription of heroin to certain subgroups of chronic, treatment-resistant, opioid dependent patients. In 2002, nine countries had planned (Australia, Belgium, Canada, France, Spain) or ongoing (Germany, The Netherlands, Switzerland, United Kingdom) clinical trials on this subject. These trials (and the routine heroin-assisted treatment programs that might result) will need pharmaceutical heroin (diacetylmorphine) to prescribe to the patients. Research into the development of pharmaceutical forms of heroin for prescription to addicts can benefit from the large amount of knowledge that already exists regarding this substance. Therefore, in this paper we review the physicochemical and pharmaceutical properties of diacetylmorphine and the clinically investigated routes of administration, as well as routes of administration utilised on the street in the context of developing pharmaceutical heroin formulations for prescription to addicts. Patient acceptability of the formulation is essential, because heroin-assisted treatment is aimed at treatment-resistant addicts, who often have to be encouraged to participate (or to maintain participation) in a treatment program. This means that the most suitable products would have pharmacokinetic profiles mimicking that of diacetylmorphine for injection, with rapid peak concentrations of diacetylmorphine and 6-acetylmorphine, ensuring the 'rush effect' and the sustained presence of morphine(-6-glucuronide) creating the prolonged euphoria. Diacetylmorphine for inhalation after volatilisation (via 'chasing the dragon') seems to be a suitable candidate, while intranasal and oral diacetylmorphine are currently thought to be unsuitable. However, oral and intranasal delivery systems might be improved and become suitable for use by heroin dependent patients.
Lin, Lan; Liao, Lin-chuan; Yan, You-yi
Heroin can be metabolized easily in body and the mail metabolites are 6-MAM, morphine and so on. At present, there are urine, blood, hair and so on as specimens for detection, while the analytical technology conclude TLC, GC, HPLC, GC/MS, LC/MS, IA, CE etc. In this paper, these technologies used for heroin's metabolites were viewed in order to provide some reference to the study in relative field.
Lin, I-Mei; Ko, Jiun-Min; Fan, Sheng-Yu; Yen, Cheng-Fang
Objective Low heart rate variability (HRV) has been confirmed in heroin users, but the effects of heart-rate-variability–biofeedback in heroin users remain unknown. This study examined (1) correlations between depression and HRV indices; (2) group differences in HRV indices among a heroin-user group, a group with major depressive disorder but no heroin use, and healthy controls; and (3) the effects of heart-rate-variability–biofeedback on depressive symptoms, HRV indices, and respiratory rates within the heroin group. Methods All participants completed a depression questionnaire and underwent electrocardiogram measurements, and group differences in baseline HRV indices were examined. The heroin group underwent electrocardiogram and respiration rate measurements at baseline, during a depressive condition, and during a happiness condition, before and after which they took part in the heart-rate-variability–biofeedback program. The effects of heart-rate-variability–biofeedback on depressive symptoms, HRV indices, and respiration rates were examined. Results There was a negative correlation between depression and high frequency of HRV, and a positive correlation between depression and low frequency to high frequency ratio of HRV. The heroin group had a lower overall and high frequency of HRV, and a higher low frequency/high frequency ratio than healthy controls. The heart-rate-variability–biofeedback intervention increased HRV indices and decreased respiratory rates from pre-intervention to post-intervention. Conclusion Reduced parasympathetic and increased sympathetic activations were found in heroin users. Heart-rate-variability–biofeedback was an effective non-pharmacological intervention to restore autonomic balance. PMID:27121428
Lin, Huang-Chi; Wang, Peng-Wei; Yang, Yi-Hsin; Tsai, Jih-Jin; Yen, Cheng-Fang
Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p < .001) and had ever received methadone maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p < .01) were more likely to enter methadone maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may
Cunha-Oliveira, Teresa; Rego, A Cristina; Garrido, Jorge; Borges, Fernanda; Macedo, Tice; Oliveira, Catarina R
Cocaine and heroin are frequently co-abused by humans, in a combination known as speedball. Recently, chemical interactions between heroin (Her) or its metabolite morphine (Mor) and cocaine (Coc) were described, resulting in the formation of strong adducts. In this work, we evaluated whether combinations of Coc and Her affect the neurotoxicity of these drugs, using rat cortical neurons incubated with Coc, Her, Her followed by Coc (Her+Coc) and Her plus Coc (Her:Coc, 1:1). Neurons exposed to Her, Her+Coc and Her:Coc exhibited a decrease in cell viability, which was more pronounced in neurons exposed to Her and Her+Coc, in comparison with neurons exposed to the mixture (Her:Coc). Cells exposed to the mixture showed increased intracellular calcium and mitochondrial dysfunction, as determined by a decrease in intracellular ATP levels and in mitochondrial membrane potential, displaying both apoptotic and necrotic characteristics. Conversely, a major increase in cytochrome c release, caspase 3-dependent apoptosis, and decreased metabolic neuronal viability were observed upon sequential exposure to Her and Coc. The data show that drug combinations potentiate cortical neurotoxicity and that the mode of co-exposure changes cellular death pathways activated by the drugs, strongly suggesting that chemical interactions occurring in Her:Coc, such as adduct formation, shift cell death mechanisms towards necrosis. Since impairment of the prefrontal cortex is involved in the loss of impulse control observed in drug addicts, the data presented here may contribute to explain the increase in treatment failure observed in speedball abusers.
Banna, Kelly M; Back, Sudie E; Do, Phong; See, Ronald E
Stress and drug-associated cues can trigger craving and relapse in abstinent drug-dependent individuals. Although the role of these two critical factors in relapse has been extensively studied, the interaction between stress and drug-associated cues in relapse has been less well characterized. Using an animal model of relapse, we assessed the effects of the pharmacological stressor, yohimbine (1.25 or 2.5mg/kg), on reinstatement of extinguished heroin-seeking in rats either in the presence or absence of heroin-associated cues. Yohimbine, in the absence of heroin-associated cues, and cues by themselves reliably reinstated heroin-seeking over extinction levels. Notably, animals showed significantly potentiated responding when yohimbine preceded cue-induced reinstatement (3-4x higher over cues or yohimbine alone). These results demonstrate that exposure to heroin-paired cues during yohimbine-induced stress greatly potentiates heroin-seeking, and support the simultaneous targeting of both stress and cue activation during relapse intervention.
Wang, Xu; Ma, Tong-Cui; Li, Jie-Liang; Zhou, Yu; Geller, Ellen B.; Adler, Martin W.; Peng, Jin-Song; Zhou, Wang; Zhou, Dun-Jin; Ho, Wen-Zhe
Although opioids have been extensively studied for their impact on the immune system, limited information is available about the specific actions of opioids on intracellular antiviral innate immunity against HIV infection. Thus, we investigated whether heroin, one of the most abused drugs, inhibits the expression of intracellular HIV restriction microRNA (miRNA) and facilitates HIV replication in macrophages. Heroin treatment of macrophages enhanced HIV replication, which was associated with the downregulation of several HIV restriction miRNAs. These heroin-mediated actions on the miRNAs and HIV could be antagonized by naltrexone, an opioid receptor antagonist. Furthermore, the in vitro negative impact of heroin on HIV-associated miRNAs was confirmed by the in vivo observation that heroin addicts had significantly lower levels of macrophage-derived HIV restriction miRNAs than those in the control subjects. These in vitro and in vivo findings indicate that heroin use compromises intracellular anti-HIV innate immunity, providing a favorable microenvironment for HIV survival in the target cells. PMID:26583016
Walter, Marc; Degen, Bigna; Treugut, Constanze; Albrich, Jürgen; Oppel, Monika; Schulz, André; Schächinger, Hartmut; Dürsteler-Macfarland, Kenneth M; Wiesbeck, Gerhard A
The Antisocial personality disorder (ASPD), one of the most common co-morbid psychiatric disorders in heroin-dependent patients, is associated with a lack of affective modulation. The present study aimed to compare the affect-modulated startle responses of opioid-maintained heroin-dependent patients with and without ASPD relative to those of healthy controls. Sixty participants (20 heroin-dependent patients with ASPD, 20 heroin-dependent patients without ASPD, 20 healthy controls) were investigated in an affect-modulated startle experiment. Participants viewed neutral, pleasant, unpleasant, and drug-related stimuli while eye-blink responses to randomly delivered startling noises were recorded continuously. Both groups of heroin-dependent patients exhibited significantly smaller startle responses (raw values) than healthy controls. However, they showed a normal affective modulation: higher startle responses to unpleasant, lower startle responses to pleasant stimuli and no difference to drug-related stimuli compared to neutral stimuli. These findings indicate a normally modulated affective reactivity in heroin-dependent patients with ASPD.
Buxton, Jane A; Sebastian, Renee; Clearsky, Lorne; Angus, Natalie; Shah, Lena; Lem, Marcus; Spacey, Sian D
An association between leukoencephalopathy, a disease of the white matter of the brain, and smoking heroin is well recognized. This paper describes 27 cases of leukoencephalopathy identified in two cities in British Columbia, Canada 2001-2006; the largest number of geographically and temporally defined reported cases in North America.Twenty cases of leukoencephalopathy were identified in and around Vancouver with onset dates December 2001 to July 2003; seven further cases were identified in Victoria September 2005-August 2006. Twenty (74%) of all cases were male, two couples were reported and eleven cases (55%) had Asian ethnicity. One case reported smoking heroin on a single occasion and developed mild symptoms; all other cases were hospitalized. Thirteen (48%) cases died; all had smoked heroin for a minimum of 3 years. Testing of one available heroin sample identified no substance other than common cutting agents.Although a specific etiology was not identified our study supports the theory of an intermittent exposure to a toxic agent added to the heroin or a combustion by-product. It also suggests a dose response effect rather than genetic predisposition. Collaboration with public health, health professionals, law enforcement and persons who use illegal drugs, will facilitate the early identification of cases to enable timely and complete follow-up including obtaining samples. Testing of implicated heroin samples may allow identification of the contaminant and therefore prevent further cases. It is therefore important to ensure key stakeholders are aware of our findings.
Nettleton, Sarah; Neale, Joanne; Pickering, Lucy
This paper seeks to make sense of the sleeping practices of people who are recovering from heroin use. It brings together two hitherto unrelated literatures: the sociology of sleep and studies on heroin use and recovery. Conceptual resources developed within the sociology of sleep are deployed to facilitate the analysis of interview data generated as part of a qualitative investigation into the everyday lives of recovering heroin users living in England. Twenty one men and 19 women were interviewed with 37 of the 40 being interviewed twice, giving a corpus of 77 interviews. Without exception all the participants in the research experienced extensive sleeping problems that were not only exacerbated by the pharmacological effects of heroin, but were made worse by the way of life that accompanied their using. Irregular and anarchic sleeping practices mirrored the study participants' disrupted and difficult lives. Attempts to establish sleep routines, and normative sleeping patterns, constitutes an important marker of recovery, but after years, and for some decades, of chaotic, intermittent and irregular sleeping, cultivating sleep presents a series of difficult challenges. Their embodied biographies of heroin use constrain the promotion of sleep, and attempts to develop rituals and routines to restore sleeping patterns are confounded by the involuntary aspects of sleep and their recalcitrant bodies. These findings are significant because not only is the quality of sleep critical to health outcomes but it also forms an important but hitherto relatively overlooked aspect of recovery from heroin use.
B Gadžurić, Slobodan; O Podunavac Kuzmanović, Sanja; B Vraneš, Milan; Petrin, Marija; Bugarski, Tatjana; Kovačević, Strahinja Z
The purpose of this work is to promote and facilitate forensic profiling and chemical analysis of illicit drug samples in order to determine their origin, methods of production and transfer through the country. The article is based on the gas chromatography analysis of heroin samples seized from three different locations in Serbia. Chemometric approach with appropriate statistical tools (multiple-linear regression (MLR), hierarchical cluster analysis (HCA) and Wald-Wolfowitz run (WWR) test) were applied on chromatographic data of heroin samples in order to correlate and examine the geographic origin of seized heroin samples. The best MLR models were further validated by leave-one-out technique as well as by the calculation of basic statistical parameters for the established models. To confirm the predictive power of the models, external set of heroin samples was used. High agreement between experimental and predicted values of acetyl thebaol and diacetyl morphine peak ratio, obtained in the validation procedure, indicated the good quality of derived MLR models. WWR test showed which examined heroin samples come from the same population, and HCA was applied in order to overview the similarities among the studied heroine samples.
Scofield, Michael D.; Boger, Heather; Hensley, Megan; Kalivas, Peter W.
Reducing the enduring vulnerability to relapse is a therapeutic goal in treating drug addiction. Studies with animal models of drug addiction show a marked increase in extrasynaptic glutamate in the core subcompartment of the nucleus accumbens (NAcore) during reinstated drug seeking. However, the synaptic mechanisms linking drug-induced changes in extrasynaptic glutamate to relapse are poorly understood. Here, we discovered impaired glutamate elimination in rats extinguished from heroin self-administration that leads to spillover of synaptically released glutamate into the nonsynaptic extracellular space in NAcore and investigated whether restoration of glutamate transport prevented reinstated heroin seeking. Through multiple functional assays of glutamate uptake and analyzing NMDA receptor-mediated currents, we show that heroin self-administration produced long-lasting downregulation of glutamate uptake and surface expression of the transporter GLT-1. This downregulation was associated with spillover of synaptic glutamate to extrasynaptic NMDA receptors within the NAcore. Ceftriaxone restored glutamate uptake and prevented synaptic glutamate spillover and cue-induced heroin seeking. Ceftriaxone-induced inhibition of reinstated heroin seeking was blocked by morpholino-antisense targeting GLT-1 synthesis. These data reveal that the synaptic glutamate spillover in the NAcore results from reduced glutamate transport and is a critical pathophysiological mechanism underling reinstated drug seeking in rats extinguished from heroin self-administration. PMID:24741055
B. Gadžurić, Slobodan; O. Podunavac Kuzmanović, Sanja; B. Vraneš, Milan; Petrin, Marija; Bugarski, Tatjana; Kovačević, Strahinja Z.
The purpose of this work is to promote and facilitate forensic profiling and chemical analysis of illicit drug samples in order to determine their origin, methods of production and transfer through the country. The article is based on the gas chromatography analysis of heroin samples seized from three different locations in Serbia. Chemometric approach with appropriate statistical tools (multiple-linear regression (MLR), hierarchical cluster analysis (HCA) and Wald-Wolfowitz run (WWR) test) were applied on chromatographic data of heroin samples in order to correlate and examine the geographic origin of seized heroin samples. The best MLR models were further validated by leave-one-out technique as well as by the calculation of basic statistical parameters for the established models. To confirm the predictive power of the models, external set of heroin samples was used. High agreement between experimental and predicted values of acetyl thebaol and diacetyl morphine peak ratio, obtained in the validation procedure, indicated the good quality of derived MLR models. WWR test showed which examined heroin samples come from the same population, and HCA was applied in order to overview the similarities among the studied heroine samples. PMID:28243268
Fragou, Domniki; Zanos, Panos; Kouidou, Sofia; Njau, Samuel; Kitchen, Ian; Bailey, Alexis; Kovatsi, Leda
Drug abuse is associated with epigenetic changes, such as histone modifications and DNA methylation. The purpose of the present study was to examine the effect of chronic cocaine and heroin administration on global DNA methylation in brain and liver. Male, 8 week old, C57BL/6J mice received heroin in a chronic 'intermittent' escalating dose paradigm, or cocaine in a chronic escalating dose 'binge' paradigm, which mimic the human pattern of opioid or cocaine abuse respectively. Following sacrifice, livers and brains were removed and DNA was extracted from them. The extracted DNA was hydrolyzed and 2'-deoxycytidine and 5-methyl-2'-deoxycytidine were determined by HPLC-UV. The % 5-methyl-2'-deoxycytidine content of DNA was significantly higher in the brain compared to the liver. There were no differences between the control animals and the cocaine or heroin treated animals in neither of the tissues examined, which is surprising since cocaine administration induced gross morphological changes in the liver. Moreover, there was no difference in the % 5-methyl-2'-deoxycytidine content of DNA between the cocaine and the heroin treated animals. The global DNA methylation status in the brain and liver of mice chronically treated with cocaine or heroin remains unaffected, but this finding cannot exclude the existence of anatomical region or gene-specific methylation differences. This is the first time that global DNA methylation in the liver and whole brain has been studied following chronic cocaine or heroin treatment.
Shen, Hao-wei; Scofield, Michael D; Boger, Heather; Hensley, Megan; Kalivas, Peter W
Reducing the enduring vulnerability to relapse is a therapeutic goal in treating drug addiction. Studies with animal models of drug addiction show a marked increase in extrasynaptic glutamate in the core subcompartment of the nucleus accumbens (NAcore) during reinstated drug seeking. However, the synaptic mechanisms linking drug-induced changes in extrasynaptic glutamate to relapse are poorly understood. Here, we discovered impaired glutamate elimination in rats extinguished from heroin self-administration that leads to spillover of synaptically released glutamate into the nonsynaptic extracellular space in NAcore and investigated whether restoration of glutamate transport prevented reinstated heroin seeking. Through multiple functional assays of glutamate uptake and analyzing NMDA receptor-mediated currents, we show that heroin self-administration produced long-lasting downregulation of glutamate uptake and surface expression of the transporter GLT-1. This downregulation was associated with spillover of synaptic glutamate to extrasynaptic NMDA receptors within the NAcore. Ceftriaxone restored glutamate uptake and prevented synaptic glutamate spillover and cue-induced heroin seeking. Ceftriaxone-induced inhibition of reinstated heroin seeking was blocked by morpholino-antisense targeting GLT-1 synthesis. These data reveal that the synaptic glutamate spillover in the NAcore results from reduced glutamate transport and is a critical pathophysiological mechanism underling reinstated drug seeking in rats extinguished from heroin self-administration.
Brenneisen, Rudolf; Hasler, Felix
The inhalation of heroin vapors after heating on aluminium foil ("chasing the dragon") is gaining popularity nowadays among heroin users seeking to avoid the risks of parenteral drug administration. The heroin-smoking procedure was simulated under laboratory conditions by heating the samples on aluminium foil at 250 to 400 degrees C and collecting the vapors in a condenser trap. A total of 72 pyrolysis products of diacetylmorphine, street heroin, residues from aluminium foils used to smoke street heroin, typical by-products, and adulterants were detected by gas chromatography/mass spectrometry (GC/MS). About half of these compounds could be identified. Diacetylmorphine (base and salt) undergoes substantial to complete degradation. Some typical street heroin constituents, like morphine, codeine, acetylcodeine, papaverine, and caffeine, are rather heat-stable. Other compounds, like noscapine and paracetamol, are pyrolyzed to a greater extent. The principal chemical reactions leading to the formation of pyrolysis products are desacetylation, transacetylation, N-demethylation, O-methylation, ring cleavage and oxydation.
Cousins, P; Bentall, R P
To date few studies have compared heroin users who smoke heroin with those who inject it. In the present study a sample of 38 heroin users, half smokers and half injectors, was investigated using several drugs career indices. Results showed that users display preferences, with the use of some drugs being favoured over time. Injectors used all drugs more frequently than smokers. Although there was much variability in frequency of use the trend over the initial 3 years of use showed no increase in heroin use for either smokers or injectors. Although the majority of smokers had injected heroin there was no evidence that this group favoured injecting over time; rather the data suggested that smoking became the increasingly preferred method of consumption. Smokers were more likely than injectors to use other drugs post-heroin. Contrary to expectation, few periods of abstinence were reported by the subjects in either group.
Anton, Benito; Salazar, Alberto; Flores, Anabel; Matus, Maura; Marin, Rodrigo; Hernandez, Jorge-Alberto; Leff, Philippe
Current pharmacotherapies for treating morphine/heroin dependence are designed to substitute or block addiction by targeting the drug itself rather than the brain. The heroin addict is still being exposed to addictive opiates, and consequently may develop tolerance to and experience withdrawal and drug's toxic effects from the treatment with high incidence of relapse to addictive drug consumption. As for other drugs of abuse, an alternative approach for morphine/heroin addiction is an antibody-based antagonism of heroin's brain entry. This review summarizes the literature examining important aspects of neurobiological and pharmacological processes involved in opiate dependence. Thereafter, classical pharmacological interventions for opiate dependence treatment and its major clinical limitations are reviewed. Finally, relevant preclinical studies are examined for comparisons in the design, use, immunogenic profile and efficacy of several models of morphine/heroin vaccine as immunologic interventions on the pharmacokinetics and behavioral of morphine/heroin in the rat as animal model.
Bammer, Gabriele; van den Brink, Wim; Gschwend, Patrick; Hendriks, Vincent; Rehm, Jürgen
Following on from last edition's Harm Reduction Digest on drug consumption facilities this Digest investigates what can be learnt from the Swiss and Dutch trials of heroin prescribing about the unintended consequences of this controversial intervention to reduce heroin-related harm. The authors of the paper bring considerable experience in the implementation and evaluation of such schemes in Europe and their consideration in Australia. The paper systematically addresses concerns about heroin prescribing and suggests further research to respond to some unanswered questions.
Karsinti, Emily; Fortias, Maeva; Dupuy, Gaël; Ksouda, Kamilia; Laqueille, Xavier; Simonpoli, Anne-Marie; Touzeau, Didier; Avril, Elisabeth; Orizet, Cyrille; Belforte, Beatriz; Coeuru, Philippe; Polomeni, Pierre; Icick, Romain; Jarroir, Marine; Bloch, Vanessa; Scott, Jan; Lépine, Jean-Pierre; Bellivier, Frank; Vorspan, Florence
Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.
Xie, Xiaohu; Xu, Limin; Liu, Huifen; Chen, Weisheng; Zhuang, Dingding; Zhang, Jianbing; Duan, Shiwei; Zhou, Wenhua
By balancing the ratios of dopamine and norepinephrine, dopamine beta hydroxylase (DBH) plays an important role in brain reward circuit that is involved with behavioral effects of heroin addiction. DBH -1021C/T (rs1611115) is a functional variant with strong correlation with plasma DBH activity and several nerval and psychic disorders. In the present study, we have collected 333 male cases with heroin addiction and 200 male healthy controls to explore the role of -1021C/T in heroin addiction. There is no evidence of association between -1021C/T and heroin addiction on both genotype and allele levels (P>0.05). In the injection subgroup of cases, -1021TT carriers have longer heroin addiction time (P<0.001) and higher dosage of self-administered heroin (P=0.045) than carriers with -1021CC or -1021CT, suggesting that patients with TT genotype are likely to have more progressive style of heroin users with injection route. In conclusion, our results support -1021TT genotype may be implicated with a more progressive nature of heroin addiction, although DBH -1021C/T is unlikely to be involved in the risk of heroin addiction.
Rosenblum, Daniel; Unick, Jay; Ciccarone, Daniel
There have been large structural changes in the US heroin market over the past 20 years. Colombian-sourced heroin entered the market in the mid-1990s, followed by a large fall in the price per pure gram and the exit of Asian heroin. By the 2000s, Colombian-sourced heroin had become a monopoly on the east coast and Mexican-sourced heroin a monopoly on the west coast with competition between the two in the middle. We estimate the relationship between these changes in competitive market structure on retail-level heroin price and purity. We find that the entry of Colombian-sourced heroin is associated with less competition and a lower price per pure gram of heroin at the national level. However, there is wide variation in changes in market concentration across the US. Controlling for the national fall in the heroin price, more competition in a region or city is associated with a lower price per pure gram. PMID:24211155
Meade, Christina S; McDonald, Leah J; Weiss, Roger D
Heroin users are at high risk for HIV infection, but little is known about HIV risk in oxycodone users. This study examined HIV risk behaviors in heroin (n = 27) and oxycodone (n = 23) users seeking inpatient detoxification at a private psychiatric hospital. Drug use histories were similar, except oxycodone users used marijuana more frequently. Injection drug risk occurred exclusively among heroin users. The rates of sexual activity (66%), unprotected intercourse (69%), sex while intoxicated (74%), and sex with strangers (24%) were similar, but more oxycodone users had multiple partners (39% vs. 6%, p < .05). HIV prevention efforts should target both heroin and oxycodone users.
Rosenblum, Daniel; Unick, George Jay; Ciccarone, Daniel
There have been large structural changes in the US heroin market over the past 20 years. Colombian-sourced heroin entered the market in the mid-1990s, followed by a large fall in the price per pure gram and the exit of Asian heroin. By the 2000s, Colombian-sourced heroin had become a monopoly on the east coast and Mexican-sourced heroin a monopoly on the west coast with competition between the two in the middle. We estimate the relationship between these changes in competitive market structure on retail-level heroin price and purity. We find that the entry of Colombian-sourced heroin is associated with less competition and a lower price per pure gram of heroin at the national level. However, there is wide variation in changes in market concentration across the US. Controlling for the national fall in the heroin price, more competition in a region or city is associated with a lower price per pure gram.
Flores, David V; Torres, Luis R; Torres-Vigil, Isabel; Bordnick, Patrick S; Ren, Yi; Torres, Melissa I M; Deleon, Freddie; Pericot-Valverde, Irene; Lopez, Tenee
Drug use among older adults is a growing concern, particularly for the burgeoning Hispanic population. Older adults seeking drug treatment will double over the next decade to almost 6 million. Cultural factors influence drug use, and more specifically, Hispanic cultural values influence heroin use. This study explored Mexican-American injection drug users' adherence to traditional Hispanic cultural values and their impact on cessation. Ethnographic interviews endorsed contextualized influences of values on heroin use. Cultural values functioned dichotomously, influencing both initiation and cessation. Understanding the impact of cultural values on substance abuse is critical given the changing demographics in American society.
Risser, Daniele; Uhl, Alfred; Oberndorfer, Felicitas; Hönigschnabl, Selma; Stichenwirth, Martin; Hirz, Robert; Sebald, Dieter
This study examines the quality of street heroin seized in Vienna in 1999 and whether there was a relationship between the purity of street heroin and the number of heroin-related emergencies as well as the number of heroin-related deaths. Street heroin confiscated by the Viennese police, run-sheets of drug-related emergencies, and postmortem reports of drug-related deaths in Vienna in 1999 were analyzed. A total of 415 retail samples with a total weight of 128.02 g contained a median percentage of 6.5% diacetylmorphine (range: 0.0-47.0%). All the samples contained a diluent, mainly lactose, as well as adulterants, such as caffeine and/or paracetamol. During the study period, 75 heroin-related deaths and 387 heroin-related emergencies were registered in Vienna. Time-series analysis revealed no statistically significant relationship between the rate of heroin-related incidents and the diacetylmorphine concentration of street heroin samples confiscated in Vienna in 1999. The widely held belief that the number of heroin-related deaths could be explained simply through fluctuations in the purity of street heroin could not be substantiated, even though the results of this study do not rule out an association between the purity of heroin and heroin-related deaths/emergencies.
Small, Dan; Drucker, Ernest
A decade of research in Switzerland, The Netherlands, Germany, and Spain now constitutes a massive body of work supporting the use of heroin treatment for the most difficult patients addicted to opiates. These trials concur on this method's safety and efficacy and are now serving as a prelude to the institution of heroin treatment in clinical practice throughout Europe. While the different sampling and research protocols for heroin treatment in these studies were important to the academic claims about specific results and conclusions that could be drawn from each study, the overall outcomes were quite clear – and uniformly positive. They all find that the use of prescribed pharmaceutical heroin does exactly what it is intended to do: it reaches a treatment refractory group of addicts by engaging them in a positive healthcare relationship with a physician, it reduces their criminal activity, improves their health status, and increases their social tenure through more stable housing, employment, and contact with family. The Canadian trial (NAOMI), now underway for over a year, but not yet completed, now faces a dilemma about what to do with its patients who have successfully completed 12 months of heroin and must be withdrawn from heroin and transferred to other treatments in accordance with the research protocol approved by Government of Canada, federal granting body and host institutions. The problem is that the principal criterion for acceptance to NAOMI was their history of repeated failure in these very same treatment programs to which they will now be referred. The existence of the results from abroad (some of which were not yet available when NAOMI was designed and initiated) now raises a very important question for Canada: is it ethical to continue to prohibit the medical use of heroin treatment that has already been shown to be feasible and effective in numerous medical studies throughout the world? And while this is being worked out, is it acceptable to
Maguire, David R.; France, Charles P.
Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Poly-drug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated co-administration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ9-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32–32 μg/kg/infusion, i.v.) generated an inverted U-shaped dose–effect curve. Administered acutely, Δ9-THC (0.01–0.32 mg/kg, s.c.) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ9-THC (0.01–0.1 mg/kg/12hr, s.c.) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ9-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist. PMID:26397756
Imperio, Caesar G; McFalls, Ashley J; Colechio, Elizabeth M; Masser, Dustin R; Vrana, Kent E; Grigson, Patricia S; Freeman, Willard M
Heroin addiction is a disease of chronic relapse that harms the individual through devaluation of personal responsibilities in favor of finding and using drugs. Only some recreational heroin users devolve into addiction but the basis of these individual differences is not known. We have shown in rats that avoidance of a heroin-paired taste cue reliably identifies individual animals with greater addiction-like behavior for heroin. Here rats received 5min access to a 0.15% saccharin solution followed by the opportunity to self-administer either saline or heroin for 6h. Large Suppressors of the heroin-paired taste cue displayed increased drug escalation, motivation for drug, and drug loading behavior compared with Small Suppressors. Little is known about the molecular mechanisms of these individual differences in addiction-like behavior. We examined the individual differences in mRNA expression in the nucleus accumbens (NAc) of rats that were behaviorally stratified by addiction-like behavior using next-generation sequencing. We hypothesized that based on the avoidance of the drug-paired cue there will be a unique mRNA profile in the NAc. Analysis of strand-specific whole genome RNA-Seq data revealed a number of genes differentially regulated in NAc based on the suppression of the natural saccharine reward. Large Suppressors exhibited a unique mRNA prolife compared to Saline controls and Small Suppressors. Genes related to immunity, neuronal activity, and behavior were differentially expressed among the 3 groups. In total, individual differences in avoidance of a heroin-paired taste cue are associated with addiction-like behavior along with differential NAc gene expression.
Idoine, Fay A; Carter, James F; Sleeman, Richard
Comparative analysis involves various but complementary methods and can be used for forensic intelligence purposes to group seizures of heroin into batches. Much forensic analysis now combines expertise in the traditional area of drugs investigation with a detailed understanding of supply, packaging, distribution, and drugs intelligence. It was the intention of this research to determine whether illicit heroin seizures and packaging material can be grouped according to isotopic compositions, and to explore factors that affect the isotopic compositions. In order to achieve these aims, 14 samples of seized heroin, thirteen provided by Avon and Somerset Constabulary (UK), were analysed by elemental analysis/isotope ratio mass spectrometry (EA/IRMS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) for carbon and hydrogen isotopes. These tests elucidated that a combination of the delta13C, delta15N, delta18O and delta2H results from EA/IRMS is able to distinguish between most samples of bulk heroin. We speculate that the delta13C values of the alkaloids, obtained by GC/C/IRMS, give indications of different geographical or temporal origins of some of the heroin samples. GC/C/IRMS of the cutting agent, caffeine, provides a means to link dilution events. Fifteen retail cling film samples and seven cling film samples from heroin seizures were analysed by EA/IRMS. A multivariate comparison of the carbon, hydrogen and oxygen isotope ratios was able to distinguish between most of the samples. This technique enabled the cling films from the heroin to be grouped according to seizure. Three solvents were tested on two samples of cling film of known composition. Methanol and chloroform were both found to extract material from PVC and from non-PVC cling films. Water-treated PVC was indistinguishable from the untreated PVC and thus water was found to be the most suitable solvent when washing cling film prior to IRMS analysis.
Lin, Pao-Yen; Wu, Yi-Shan
Background Studies have examined the association between heroin dependence and serotonin transporter gene polymorphisms but yielded inconsistent results. The purpose of current study is to determine the overall effect of these polymorphisms on the risk for heroin dependence through a meta-analytic method. Methods A meta-analysis was conducted to examine the association of heroin dependence with two common polymorphisms of serotonin transporter gene, in the promoter (5-hydroxytryptamine transporter-linked promotor region [5-httlpr]) and intron 2 (a various number tandem repeat in serotonin transporter intron 2 [STin2]). Data from studies with 5-httlpr (6 studies) and STin2 (8 studies) were synthesized by random effects model. Results In the analysis, heroin dependence was found to be significantly associated with the S allele of 5-httlpr (odds ratio [OR] =1.22, 95% confidence interval [CI] =1.08–1.41, P=0.002). The association between the S allele of 5-httlpr and heroin dependence was significant in Caucasian subjects (OR =1.37, 95% CI =1.12–1.68, P=0.003), but not in non-Caucasian subjects. On the other hand, no association with STin2 polymorphism was found (OR =1.14, 95% CI =0.91–1.42, P=0.242). Conclusion The results suggest an ethnic-specific effect of the 5-httlpr polymorphism on the risk for heroin dependence, but the influence of the genetic variance in the patients with comorbidities or intermediate phenotypes of heroin dependence needs to be further examined. PMID:27942217
Gottås, André; Arnestad, Marianne; Halvorsen, Per Steinar; Bachs, Liliana C; Høiseth, Gudrun
Vitreous humor (VH) is an alternative matrix for drug analysis in forensic toxicology. However, little is known about the distribution of xenobiotics, such as opioids, into VH in living organisms. The aim of this study was to simultaneously measure heroin and metabolite concentrations in blood and VH after injection of heroin in a living pig model. Six pigs were under non-opioid anesthesia during the surgical operation and experiment. Ocular microdialysis was used to acquire dialysate from VH, and a venous catheter was used for blood sampling. Twenty milligrams of heroin was injected intravenously with subsequent sampling of blood and dialysate for 6 h. The samples were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Heroin was not detected in VH; 6-monoacetylmorphine (6-MAM) and morphine were first detected in VH after 60 min. The morphine concentration in VH thereafter increased throughout the experimental period. For 6-MAM, Cmax was reached after 230 min in VH. In blood, 6-MAM reached Cmax after 0.5 min, with a subsequent biphasic elimination phase. The blood and VH 6-MAM concentrations reached equilibrium after 2 h. In blood, morphine reached Cmax after 4.3 min, with a subsequent slower elimination than 6-MAM. The blood and VH morphine concentrations were in equilibrium about 6 h after injection of heroin. In conclusion, both 6-MAM and morphine showed slow transport into VH; detection of 6-MAM in VH did not necessarily reflect a recent intake of heroin. Because postmortem changes are expected to be small in VH, these experimental results could assist the interpretation of heroin deaths.
Pacifici, R; di Carlo, S; Bacosi, A; Pichini, S; Zuccaro, P
The parallelism between serum levels of heroin and morphine (M) metabolites and the production of interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), and interferon-gamma (IFN-gamma) from murine splenocyte cultures following s.c. injection with 20 mg/kg heroin or M in C57/BL mice is described. The pharmacokinetic profiles of M and inactive morphine-3-glucuronide (M3G) in morphine-treated mice nearly overlapped those in heroin-treated mice, with the only difference being the presence of 6-monoacetylmorphine (AM) in profiles of the latter group. Heroin and M significantly increased production of IL-1beta, IL-2, TNF-alpha and IFN-gamma at 3, 20 and 40 min from treatment, peaking at 20 min, though the effect was very brief. At 24 h production was greatly inhibited, and this depressive effect lasted longer than the stimulatory effect. At 48 h only a partial recovery was observed. Heroin and M also had a highly stimulatory effect on the release of anti-inflammatory cytokines such as TGF-beta1 and IL-10, though this effect was observed after 120 min, peaking at 24 h and then somewhat decreasing at 48 h. This study demonstrates that the more rapid and pronounced immune response to heroin treatment was due to the presence of AM. Both heroin and M produced a biphasic effect on cytokine production: the central opioid or non-opioid receptors are involved in exogenous opiod-induced stimulatory effects, whereas peripheral opioid or non-opioid receptors are involved in depressive effects. Deficient or excess expression of these key mediators may predispose the host to aberrant defence mechanisms.
Malek, Antoine; Obrist, Cristina; Wenzinger, Silvana; von Mandach, Ursula
Background Methadone is the therapeutic agent of choice for the treatment of opiate addiction in pregnancy. The co-consumption (heroin, cocaine) which may influence the effects of methadone is frequent. Therefore, the impact of cocaine and heroin on the placental transfer of methadone and the placental tissue was investigated under in vitro conditions. Methods Placentae (n = 24) were ex-vivo perfused with medium (m) (control, n = 6), m plus methadone (n = 6), m plus methadone and cocaine (n = 6) or m plus methadone and heroin (n = 6). Placental functionality parameters like antipyrine permeability, glucose consumption, lactate production, hormone production (hCG and leptin), microparticles release and the expression of P-glycoprotein were analysed. Results Methadone accumulated in placental tissue. Methadone alone decreased the transfer of antipyrine from 0.60 +/- 0.07 to 0.50 +/- 0.06 (fetal/maternal ratio, mean +/- SD, P < 0.01), whereas the combination with cocaine or heroin increased it (0.56 +/- 0.08 to 0.68 +/- 0.13, P = 0.03 and 0.58 +/- 0.21 to 0.71 +/- 0.24; P = 0.18). Microparticles (MPs) released from syncytiotrophoblast into maternal circuit increased by 30% after cocaine or heroin (P < 0.05) and the expression of P-glycoprotein in the tissue increased by ≥ 49% after any drug (P < 0.05). All other measured parameters did not show any significant effect when methadone was combined with cocaine or heroine. Conclusion The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast. PMID:19519880
Maguire, David R; France, Charles P
Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Polydrug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated coadministration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32-32 μg/kg/infusion, intravenously) generated an inverted U-shaped dose-effect curve. Administered acutely, Δ-THC (0.01-0.32 mg/kg, subcutaneously) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ-THC (0.01-0.1 mg/kg/12 h, subcutaneously) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist.
Marinetti, Laureen J; Ehlers, Brooke J
The Montgomery County Coroner's Office Toxicology Section and the Miami Valley Regional Crime Lab (MVRCL) Drug Chemistry Section have been receiving case work in drug seizures, death cases and human performance cases involving products marketed as heroin or as illicit fentanyl. Upon analysis by the Drug Chemistry Section, these products were found to contain various drug(s) including illicit fentanyl only, illicit fentanyl and heroin, illicit fentanyl and cocaine and illicit fentanyl, heroin and cocaine. Both the Chemistry and Toxicology Sections began seeing these combinations starting in late October 2013. The percentage of the combinations encountered by the MVRCL as well as the physical appearance of the product, and the results of presumptive screening tests will be discussed. The demographics of the users and the results of toxicology and autopsy findings on the decedents will also be discussed. According to regional drug task force undercover agents, there is evidence that some of the products are being sold as illicit fentanyl and not just as a heroin product. Also, there is no evidence to support that the fentanyl source is being diverted from pharmaceutical grade fentanyl. The chemistry section currently has over 109 confirmed cases, and the toxicology section currently has 81 confirmed drug deaths, 8 driving under the influence of drugs and 1 suicidal hanging. Both sections are continuing to see these cases at the present time.
Mars, Sarah G; Fessel, Jason N; Bourgois, Philippe; Montero, Fernando; Karandinos, George; Ciccarone, Daniel
Heroin overdose, more accurately termed 'heroin-related overdose' due to the frequent involvement of other drugs, is the leading cause of mortality among regular heroin users. (Degenhardt et al., 2010) Heroin injectors are at greater risk of hospital admission for heroin-related overdose (HOD) in the eastern United States where Colombian-sourced powder heroin is sold than in the western US where black 'tar' heroin predominates. (Unick et al., 2014) This paper examines under-researched influences on HOD, both fatal and non-fatal, using data from a qualitative study of injecting drug users of black tar heroin in San Francisco and powder heroin in Philadelphia Data were collected through in-depth, semi-structured interviews carried out in 2012 that were conducted against a background of longer-term participant-observation, ethnographic studies of drug users and dealers in Philadelphia (2007-12) and of users in San Francisco (1994-2007, 2012). Our findings suggest three types of previously unconsidered influences on overdose risk that arise both from structural socio-economic factors and from the physical properties of the heroin source-types: 1) retail market structure including information flow between users; 2) marketing techniques such as branding, free samples and pricing and 3) differences in the physical characteristics of the two major heroin source forms and how they affect injecting techniques and vascular health. Although chosen for their contrasting source-forms, we found that the two cities have contrasting dominant models of drug retailing: San Francisco respondents tended to buy through private dealers and Philadelphia respondents frequented an open-air street market where heroin is branded and free samples are distributed, although each city included both types of drug sales. These market structures and marketing techniques shape the availability of information regarding heroin potency and its dissemination among users who tend to seek out the
Mars, Sarah G.; Fessel, Jason N.; Bourgois, Philippe; Montero, Fernando; Karandinos, George; Ciccarone, Daniel
Heroin overdose, more accurately termed ‘heroin-related overdose’ due to the frequent involvement of other drugs, is the leading cause of mortality among regular heroin users. (Degenhardt et al., 2010) Heroin injectors are at greater risk of hospital admission for heroin-related overdose (HOD) in the eastern United States where Colombian-sourced powder heroin is sold than in the western US where black ‘tar’ heroin predominates. (Unick et al., 2014) This paper examines under-researched influences on HOD, both fatal and non-fatal, using data from a qualitative study of injecting drug users of black tar heroin in San Francisco and powder heroin in Philadelphia Data were collected through in-depth, semi-structured interviews carried out in 2012 that were conducted against a background of longer-term participant-observation, ethnographic studies of drug users and dealers in Philadelphia (2007–12) and of users in San Francisco (1994–2007, 2012). Our findings suggest three types of previously unconsidered influences on overdose risk that arise both from structural socio-economic factors and from the physical properties of the heroin source-types: 1) retail market structure including information flow between users; 2) marketing techniques such as branding, free samples and pricing and 3) differences in the physical characteristics of the two major heroin source forms and how they affect injecting techniques and vascular health. Although chosen for their contrasting source-forms, we found that the two cities have contrasting dominant models of drug retailing: San Francisco respondents tended to buy through private dealers and Philadelphia respondents frequented an open-air street market where heroin is branded and free samples are distributed, although each city included both types of drug sales. These market structures and marketing techniques shape the availability of information regarding heroin potency and its dissemination among users who tend to seek out
Haghpanah, Tahereh; Afarinesh, Mohammadreza; Divsalar, Kouros
Background: Long-term use of opioids has acute effects on homeostasis of the body. Discovering the impacts of opioids on hematological parameters of narcotics withdrawal and dependents blood may be helpful in recognizing the homeostasis condition of their body for the useful treatment. Methods: In this study a cross-sectional method was applied. The abusers of opium and heroin for more than two consecutive years were considered as opium and heroin dependent groups, respectively. The dependent people, who passed the 1-month withdrawal period, entered the study as opium and heroin withdrawal groups. In this study, hematological factors of heroin and opium dependent and withdrawal groups were investigated. Findings: The RBC count remained unchanged in all groups. The WBC count had a significant increase in opium dependent group but in heroin dependent group and withdrawal group there was no significant difference. HGB level had a significant increase only in opium and heroin withdrawal groups. The percentage of HCT had a significant increase in all groups. The MCV increased in heroin and opium dependent groups. MCH level increased significantly in heroin and opium withdrawal groups. MCHC level had a significant increase in all groups. Neutrophil and lymphocyte counts in heroin and opium addicted groups significantly decreased. Platelet, neutrophil and monocyte counts significantly increased in opium dependent group. Monocyte countshowed a significant reduction in heroin withdrawal group. Eosinophil count showed no difference in any of the groups. Conclusion: The current study indicated that not only the chronic and long-term use of opium and heroin, also withdrawal of addicted people could change hematological parameters related to human serum. PMID:24494095
Holler, Justin M; Bosy, Thomas Z; Klette, Kevin L; Wiegand, Russel; Jemionek, John; Jacobs, Aaron
Current Department of Defense (DoD) and Department of Health and Human Services (HHS) procedures for the detection of heroin abuse by testing urine utilize an initial opiate (codeine/morphine) immunoassay (IA) screen followed by gas chromatography-mass spectrometry (GC-MS) confirmation of 6-acetylmorphine (6-AM), if the morphine concentration is above established cutoff. An alternative to the current opiates screen for heroin abuse is the direct IA for the metabolite of heroin, 6-acetylmorphine. In this regard, the performance of the Microgenics CEDIA heroin metabolite (6-AM) screening reagent was assessed. This evaluation was conducted on the P module of a Hitachi Modular automated IA analyzer calibrated using 6-AM at 10 ng/mL. Reproducibility, linearity, accuracy, sensitivity, and interferences associated with use of the 6-AM IA reagent were evaluated. The IA reagent precision (percent coefficient of variation (%CV)) around each of seven standards was less than 0.63%, with a linearity (r(2)) value of 0.9951. A total of 37,713 active duty service members' urine samples were analyzed simultaneously using the CEDIA heroin metabolite (6-AM) reagent and the Roche Abuscreen ONLINE opiate reagent to evaluate both the prevalence rate of 6-AM in the demographic group and the sensitivity and specificity of the reagents for the detection of heroin use. Of the 37,713 samples tested using the CEDIA heroin metabolite (6-AM) reagent, three samples screened positive at the DoD and HHS cutoff of 10 ng/mL. One of the three samples confirmed positive for 6-AM by GC-MS above the cutoff of 10 ng/mL, the two remaining samples confirmed negative for 6-AM at a GC-MS limit of detection (LOD) of 2.1 ng/mL. In contrast, the Roche Abuscreen ONLINE opiate IA produced 74 opiate-positive results for codeine/morphine, with 6 of the 74 specimens confirming positive for morphine above the DoD cutoff concentration of 4000 ng/mL (8% DoD morphine confirmation rate), only one of the 74 opiate
Peng, Jin-Song; Wang, Xu; Liu, Man-Qing; Zhou, Dun-Jin; Gong, Jie; Xu, Han-Ming; Chen, Jian-Ping; Zhu, Hong-Hao; Zhou, Wang; Ho, Wen-Zhe
Since the majority of heroin abusers use injection as the primary route of admission, heroin abuse contributes significantly to the transmission of hepatitis C virus (HCV). We determined HCV infection and its genotype distribution among injection heroin users in Wuhan, the largest city in the central China. Eight hundred seventy-eight (84%) out of 1046 serum specimens from the injection drug users were positive for HCV antibody. Out of randomly selected 122 specimens positive for HCV antibody, seventy-eight (64%) had detectable HCV RNA with genotype 6a as the predominant strain (50%), followed by 3b (32.2%), 1a (8.1%), 1b (6.5%), and 3a (3.2%). HCV RNA levels in male heroin users were significantly higher (P=0.013) than those in the female subjects. Although there was no significant difference in HCV RNA levels among the specimens positive for HCV 6a and 1a/1b, the samples with 6a or 1a/1b contained higher levels of HCV RNA than the specimens positive for HCV 3b (P=0.019, P=0.012, respectively). These findings indicate that there is a high prevalence of HCV infection with genotypes 6a and 3b as predominated strains among injection heroin users in Wuhan, China.
Levran, O.; Londono, D.; O’Hara, K.; Nielsen, D. A.; Peles, E.; Rotrosen, J.; Casadonte, P.; Linzy, S.; Randesi, M.; Ott, J.; Adelson, M.; Kreek, M. J.
Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify genetic variants that are associated with susceptibility to develop heroin addiction, by analyzing 1350 variants in 130 candidate genes. All subjects had Caucasian ancestry. The sample consisted of 412 former severe heroin addicts in methadone treatment, and 184 healthy controls with no history of drug abuse. Nine variants, in six genes, showed the lowest nominal P values in the association tests (P < 0.01). These variants were in non-coding regions of the genes encoding the mu (OPRM1; rs510769, rs3778151), kappa (OPRK1; rs6473797), and delta opioid receptors, (OPRD1; rs2236861, rs2236857 and rs3766951), the neuropeptide galanin (GAL; rs694066), the serotonin receptor subtype 3B (HTR3B; rs3758987) and the casein kinase 1 isoform epsilon (CSNK1E; rs1534891). Several haplotypes and multi-locus genotype patterns showed nominally significant associations (e.g. OPRM1; P = 0.0006 and CSNK1E; P = 0.0007). Analysis of a combined effect of OPRM1 and OPRD1 showed that rs510769 and rs2236861 increase the risk of heroin addiction (P = 0.0005). None of these associations remained significant after adjustment for multiple testing. This study suggests the involvement of several genes and variants in heroin addiction that is worthy of future study. PMID:18518925
Mertz, Kristen J; Janssen, Jennifer K; Williams, Karl E
Drugs contributing to overdose deaths are listed on death certificates, but their validity is rarely studied. To assess the accuracy of "morphine" and "codeine" listings on death certificates for unintentional overdose deaths in Allegheny County, PA, investigative and laboratory reports were reviewed. Deaths were reclassified as heroin-related if documentation showed 6-monoacetylmorphine in blood or urine, "stamp bags" or drug paraphernalia at scene, history of heroin use, or track marks. Deaths were considered morphine-related if notes indicated morphine use, prescription, or morphine at scene, or codeine-related if the codeine blood level exceeded morphine. Of 112 deaths with morphine but not heroin listed on the death certificate, 74 met heroin criteria and 21 morphine criteria. Of 20 deaths with both morphine and heroin listed, only one met morphine criteria. Of 34 deaths with codeine listed, only five were attributed to codeine. Consideration of patient history, death scene evidence, and expanded toxicology testing may improve the accuracy of death certificate drug listings.
Schmeichel, Brooke E; Barbier, Estelle; Misra, Kaushik K; Contet, Candice; Schlosburg, Joel E; Grigoriadis, Dimitri; Williams, John P; Karlsson, Camilla; Pitcairn, Caleb; Heilig, Markus; Koob, George F; Vendruscolo, Leandro F
The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1 h; ShA) or long- (12 h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence.
Hoglund, David E.; Lucero, Daniel P.
This paper discusses the preparation to assess the performance of heroin and cocaine vapor/particle detection systems. Equipment available commercially and field prototype system equipment will be assessed. Breadboard or brassboard devices or prototype modules will not be assessed. The assessment comprises a performance specifications verification and target response and a controlled field test for equipment available commercially only. Special purpose test procedures, tools, and detection targets were developed to ensure the reproducibility and control of all assessment tests. The sampling equipment parameters and their relative importance and the test procedures and objectives were defined and designed to maximize the information obtained within the test constraints. Test results will be obtained for standardized fundamental representative targets, independent of detection strategy, which can be correlated to a wide range of applications by the potential users. United States Customs Service will not form conclusions regarding the equipment performance for specific applications. It is anticipated the utility of the assessment program will be in availing equipment standardized test results to law enforcement agencies to examine the compatibility of the equipment performance with their requirements, applications, and detection strategy.
Szöcs, Levente; Orgován, Gábor; Tóth, Gergő; Kraszni, Márta; Gergó, Lajos; Hosztafi, Sándor; Noszál, Béla
The hydroxide-catalyzed non-enzymatic, simultaneous and consecutive hydrolyses of diacetylmorphine (DAM, heroin) are quantified in terms of 10 site- and species-specific rate constants in connection with also 10 site- and species-specific acid-base equilibrium constants, comprising all the 12 coexisting species in solution. This characterization involves the major and minor decomposition pathways via 6-acetylmorphine and 3-acetylmorphine, respectively, and morphine, the final product. Hydrolysis has been found to be 18-120 times faster at site 3 than at site 6, depending on the status of the amino group and the rest of the molecule. Nitrogen protonation accelerates the hydrolysis 5-6 times at site 3 and slightly less at site 6. Hydrolysis rate constants are interpreted in terms of intramolecular inductive effects and the concomitant local electron densities. Hydrolysis fraction, a new physico-chemical parameter is introduced and determined to quantify the contribution of the individual microspecies to the overall hydrolysis. Hydrolysis fractions are depicted as a function of pH.
This paper addresses the use of drugs, specifically heroin, by women. While women's rate of incarceration in the nation have dramatically increased, tripling in the last decade, prisons have not kept pace with the growth of the number of women in prison and the need for drug treatment and recovery for this population. This paper examines one programmatic effort to provide services to this most vulnerable population in the state of Illinois. The continuum of care model is considered in light of the challenges of high recidivism rates, particularly in the state of Illinois. It identifies a need for more effective evidence-based services at the state level for prison inmates before and after discharge. Effective program evaluation has not been a priority in some states, and perhaps Illinois correction is prototypical. More effective intervention may require more community involvement post-release for ex-offenders. Barriers to healthcare, employment and housing, are just as evident with female drug offenders as in the male population.
Cai, Xi-lan; Wu, Guo-ping
In the present paper, using Fourier transform infrared (FTIR) absorption spectrometry, the characteristic peaks of fingerprint infrared spectra of heroin samples from different routes were identified with clustering analysis successfully. It is a very fast, simple and reliable method. That is to say, a new method for the discrimination of heroin seizured from different routes is provided.
Wang, Qing-Liang; Liu, Zhi-Min
The objective of this study was to explore the characteristics of comorbid psychiatric symptoms and the relationship between different routes of drug administration and psychiatric symptoms. Five hundred and nine heroin addicts were studied in Drug Detoxification and Rehabilitation Centers in Yunnan and Heilongjiang provinces of China. The measure instrument, including demographic characteristics, history of drug abuse, and the Symptom Checklist-90 (SCL-90) scale (Chinese version), was administered to eligible heroin addicts. Among the subjects, comorbid psychopathology conditions were more severe on all dimensions of SCL-90 comparing with normal adults and the average score of Depression was highest among the 9 dimensions in heroin addicts; psychiatric symptoms were more severe in heroin injecting group than in "chasing the dragon" group and only the difference in Obsessive-Compulsive was significant, but more significant differences were found between snorting heroin addicts and chasing or injecting heroin addicts, and the average score of each dimension of SCL-90 was higher in the snorting group than in the other 2 groups. The reasons of the results and meaning for the present study are discussed. In summary, comorbid psychiatric symptoms in the heroin addicts were very common and severe and their severity varied with different routes of drug administration, suggesting that routes of drug administration should be considered as an important risk factor to mental health of heroin addicts.
Vosburg, Suzanne K.; Eaton, Thomas A.; Sokolowska, Marta; Osgood, Eric D.; Ashworth, Judy B.; Trudeau, Jeremiah J.; Muffett-Lipinski, Michelle; Katz, Nathaniel P.
The progression from prescription opioid (RXO) abuse to RXO addiction is not well understood in adolescents, nor is the progression from RXO addiction to heroin abuse. The purpose of this pilot study was to characterize the development of RXO drug abuse, RXO drug addiction, and heroin abuse in a small cohort of adolescents recovering from opioid…
Bu, Jun; Zhan, Changshu; Huang, Yi; Shen, Baohua; Zhuo, Xianyi
Heroin is a highly addictive drug, and heroin abuse is considered to be a serious criminal act. The major metabolite of heroin, morphine, can usually be detected as evidence of heroin abuse. However, it is difficult to determine heroin use when morphine and codeine are both detected, because codeine use will also result in the presence of morphine in urine. Therefore, it is important to distinguish heroin abuse from codeine administration. In this study, urine samples from 21 volunteers with various ingestion patterns of a compound codeine phosphate oral solution were used as negative controls, and urine samples from 89 alleged heroin users were used as positive controls. Urine from single and multiple doses of codeine administration were collected at different time points for a systematic comparison. After protein precipitation, the urine samples were analyzed for the presence of free morphine, free codeine and their metabolites by ultra-performance liquid chromatography-tandem mass spectrometry. The method of percentiles, with median and standard interquartile ranges, was used to describe and analyze the data based on the normality of the distribution. The ratios of concentration of morphine and morphine to codeine were found to be the possible criteria to distinguish heroin users from codeine users in Chinese people.
Klous, Marjolein G; Huitema, Alwin D R; Rook, Elisabeth J; Hillebrand, Michel J X; Hendriks, Vincent M; Van den Brink, Wim; Beijnen, Jos H; Van Ree, Jan M
In preparation for a trial on co-prescription of inhalable heroin and methadone, two methods for inhalation of heroin/caffeine tablets were compared: the commonly used method of 'chasing the dragon' and a standardised procedure for inhalation of volatilised heroin, using a heating device. Five male addicts inhaled a tablet of smokable heroin daily for 5 days, alternating the inhalation method. Plasma concentrations of heroin, 6-acetylmorphine, morphine and morphine-3- and -6-glucuronide were determined using a liquid chromatography method with tandem mass spectrometric detection. The exposure to heroin and its metabolites (expressed as areas under the concentration-time curve) was significantly lower after smoking via the heating device than after 'chasing the dragon': heroin 80% and 6-acetylmorphine 73% lower (p < 0.05). Maximal concentrations of heroin and 6-acetylmorphine were also 80% and 70% lower (p < 0.05) after using the heating device. 'Chasing the dragon' is a more efficient inhalation method than inhalation via the heating device.
Lin, Shih-Hsien; Chen, Kao Chin; Lee, Sheng-Yu; Chiu, Nan Tsing; Lee, I Hui; Chen, Po See; Yeh, Tzung Lieh; Lu, Ru-Band; Chen, Chia-Chieh; Liao, Mei-Hsiu; Yang, Yen Kuang
One of the consequences of heroin dependency is a huge expenditure on drugs. This underlying economic expense may be a grave burden for heroin users and may lead to criminal behavior, which is a huge cost to society. The neuropsychological mechanism related to heroin purchase remains unclear. Based on recent findings and the established dopamine hypothesis of addiction, we speculated that expenditure on heroin and central dopamine activity may be associated. A total of 21 heroin users were enrolled in this study. The annual expenditure on heroin was assessed, and the availability of the dopamine transporter (DAT) was assessed by single-photon emission computed tomography (SPECT) using [(99m)TC]TRODAT-1. Parametric and nonparametric correlation analyses indicated that annual expenditure on heroin was significantly and negatively correlated with the availability of striatal DAT. After adjustment for potential confounders, the predictive power of DAT availability was significant. Striatal dopamine function may be associated with opioid purchasing behavior among heroin users, and the cycle of spiraling dysfunction in the dopamine reward system could play a role in this association.
Ma, Baomiao; Yue, Kai; Chen, Lin; Tian, Xiang; Ru, Qin; Gan, Yongping; Wang, Daisong; Jin, Guozhang; Li, Chaoying
L-Stepholidine (l-SPD), an alkaloid extract of the Chinese herb Stephania intermedia, is the first compound known to exhibit mixed dopamine D1 receptor agonist/D2 antagonist properties and is a potential medication for the treatment of opiate addiction. The aim of the present study was to investigate the effects of pretreatment with L-SPD on heroin-seeking behavior induced by heroin priming. Male Sprague-Dawley rats were trained to self-administer heroin (0.05mg/kg per infusion) under a fixed ratio 1 schedule for 12 consecutive days and nose-poke responding was extinguished for 12 days, after which reinstatement of drug seeking was induced by heroin priming. Pretreatment with L-SPD (2.5, 5.0 and 10.0mg/kg, i.p.) inhibited the heroin-induced reinstatement of heroin-seeking behavior. Importantly, L-SPD did not affect locomotion, indicating that the observed effects of L-SPD on reinstatement are not the result of motor impairments. The present data suggested that l-SPD inhibits heroin-induced reinstatement and its potential for the treatment of heroin relapse.
Feng, Gang; Luo, Qiancheng; Guo, Enwei; Yao, Yulan; Yang, Feng; Zhang, Bingyu; Li, Longxuan
Multiple organ dysfunction syndrome (MODS) has rarely been described in patients with heroin intoxication. Here, we report a rare case of MODS involving six organs, due to heroin intoxication. The patient was a 32-year-old Chinese man with severe heroin intoxication complicated by acute pulmonary edema and respiratory insufficiency, shock, myocardial damage and cardiac insufficiency, rhabdomyolysis and acute renal insufficiency, acute liver injury and hepatic insufficiency, toxic leukoencephalopathy, and hypoglycemia. He managed to survive and was discharged after 10 weeks of intensive care. The possible pathogenesis and therapeutic measures of MODS induced by heroin intoxication and some suggestions for preventing and treating severe complications of heroin intoxication, based on clinical evidence and the pertinent literature, are discussed in this report.
Brambilla, F; Nobile, P; Zanoboni, A; Zanoboni-Muciaccia, W; Meroni, P L
Pituitary-thyroid function has been studied in heroin addicts. Data have been obtained in 10 male addicts, aged 18-24 years, with histories of addiction to heroin alone lasting from 8 months to 4 years, and in 9 controls matched for sex and age. Basal plasma levels of TSH, T4 and T3 were measured. A TRH stimulation test was done, injecting 500 micrograms of TRH iv as a bolus and assaying TSH levels before the injection and at 30 min intervals up to 2 h afterwards. The results revealed no difference between addicts and controls in basal levels of TSH, T4 and T3. The TRH stimulation test induced a blunted TSH rise in 50% of the cases. The possible mechanism of action of heroin on pituitary-thyroid axis is discussed.
Balayssac, Stéphane; Retailleau, Emmanuel; Bertrand, Geneviève; Escot, Marie-Pierre; Martino, Robert; Malet-Martino, Myriam; Gilard, Véronique
Twenty-four samples of heroin from different illicit drug seizures were analyzed using proton Nuclear Magnetic Resonance ((1)H NMR) and two-dimensional diffusion-ordered spectroscopy (2D DOSY) (1)H NMR. A careful assignment and quantification of (1)H signals enabled a comprehensive characterization of the substances present in the samples investigated: heroin, its main related impurities (6-acetylmorphine, acetylcodeine, morphine, noscapine and papaverine) and cutting agents (caffeine and acetaminophen in nearly all samples as well as lactose, lidocaine, mannitol, piracetam in one sample only), and hence to establish their spectral signatures. The good agreement between the amounts of heroin, noscapine, caffeine and acetaminophen determined by (1)H NMR and gas chromatography, the reference method in forensic laboratories, demonstrates the validity of the (1)H NMR technique. In this paper, 2D DOSY (1)H NMR offers a new approach for a whole characterization of the various components of these complex mixtures.
This paper estimates the empirical relationship between cocaine and heroin prices and drug-related hospital ED admissions for 21 U.S. cities. These outcomes bypass some of the problems with self-reports and directly measure a component of healthcare costs associated with heavy drug usage. The price elasticity of the probability of a cocaine and heroin episode is estimated at -0.27 and -0.10, respectively. A 10% increase in prices can prevent 10,723 cocaine and heroin-related ED visits, with cost savings between 21 million dollars and 47 million dollars. These low magnitudes of the drug outcome-price response have implications for the cost-effectiveness of enforcement-driven price increases.
Mayock, Paula; Cronly, Jennifer; Clatts, Michael C
This paper examines young women's initiation to heroin use in the context of an intimate relationship based on data from a small-scale ethno-epidemiology of heroin use in Ireland, 2007-2009. The epidemiological sample included 120 young people, and life history interviews were conducted with a sub-sample of 40 youth aged 16-25 years. A detailed analysis of the "risk environment" of young women's heroin initiation highlights a complex interplay between women's agency and intimate partner influence. It is argued that dichotomous representations of women as victims or emancipated consumers do not adequately capture the complexity of women's initiation journeys. The study's limitations are noted and implications for drug use prevention and harm reduction strategies are discussed.
Hempstead, Katherine; Yildirim, Emel O
The inelastic price demand observations characteristic of illegal drug markets have led to the conclusion that the burden of a negative supply shock would be completely reflected to consumers. This paper argues that the increasing availability of prescription opioids may threaten heroin sellers' profit margin and force them to find alternative methods to compensate buyers in the event of a supply shock. We investigate the 2006 fentanyl overdose episode in New Jersey and argue that the introduction of non-pharmaceutical fentanyl, its spatial distribution, and the timing of overdose deaths may have been related to trends in heroin purity. Using medical examiner data, as well as data from the Drug Enforcement Administration, Office of Diversion Control on retail sales of prescription opioids in a negative binomial specification, we show that month-to-month fluctuations in heroin purity have a significant effect on fentanyl-related overdoses, particularly in those areas where prescription opioids are highly available.
Anticević, Vesna; Britvić, Dolores; Sodić, Lidija
The purpose of this study was to investigate differences in social characteristics (level of education, working and family status, and criminal record) between heroin addicts, cannabis users and a control group. Additional goal was to explore the possibility of discerning subjects of different addiction status (of both gender) based on their scores on Eysenck Personality Questionnaire (EPQ). In comparison to the control group, heroin addicts and cannabis users had lower level of education, were more frequently unemployed and with criminal record, and more often came from dysfunctional families. In cannabis users the frequency of these characteristics was generally lower than in heroin addicts. Proportion of correct classification of subjects in groups of different addiction status based on the EPQ scores was 23.3% for males (higher than by chance alone), and 30% for females.
Schneider, Serge; Meys, François
This article discusses drug purity, frequency of appearance and concentration ranges of adulterants of 471 illicit cocaine and 962 illicit heroin samples seized in Luxembourg from January 2005 to December 2010. For cocaine samples the mean concentration was lowest in 2009 (43.2%) and highest in 2005 (54.7%) but no clear trend could be observed during the last 6 years. 14 different adulterants have been detected in cocaine samples, from which phenacetin has been the most abundant in terms of frequency of appearance and concentration until 2009. In 2010 the veterinary antihelminthic drug levamisole has become the most abundant adulterant detected in cocaine samples, its concentrations however remained low (1.5-4.1%). The mean heroin concentration was 26.6% in 2005, a decline has been observed in 2006 and the concentrations have been relatively stable since then (15.8-17.4%). Paracetamol and caffeine were by far the most abundant adulterants detected in heroin samples.
Bencharit, Sompop; Morton, Christopher L; Xue, Yu; Potter, Philip M; Redinbo, Matthew R
We present the first crystal structures of a human protein bound to analogs of cocaine and heroin. Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that catalyzes the hydrolysis of heroin and cocaine, and the detoxification of organophosphate chemical weapons, such as sarin, soman and tabun. Crystal structures of the hCE1 glycoprotein in complex with the cocaine analog homatropine and the heroin analog naloxone provide explicit details about narcotic metabolism in humans. The hCE1 active site contains both specific and promiscuous compartments, which enable the enzyme to act on structurally distinct chemicals. A selective surface ligand-binding site regulates the trimer-hexamer equilibrium of hCE1 and allows each hCE1 monomer to bind two narcotic molecules simultaneously. The bioscavenger properties of hCE1 can likely be used to treat both narcotic overdose and chemical weapon exposure.
Gschwend, P; Eschmann, S; Güttinger, F; Hosek, M; Rehm, J; Uchtenhagen, A
In 1994, Switzerland introduced experimental heroin assisted treatment for refractory opioid addicts as last line of treatment. An evaluation research was established examining effectiveness and cost-benefit of heroin-assisted treatment for the first project phase between 1994 and 1996. The present publication intends to provide an overview for the newer results of the evaluation. In summary, the positive outcomes found at first follow-ups continued to persist regarding somatic and mental improvements, social integration including reduction of criminal behaviour, and reduction of use of illicit drugs. In future, treatment of co-morbid mental disorders, integration into the labour market and persistent consumption of cocaine in some patients still need focussed attention. Different efforts to assure quality control and development hopefully will serve towards further optimisation of heroin-assisted treatment.
Wright, Nat; Oldham, Nicola; Jones, Lesley
The aim of this study was to explore the relationship between housing status, associated social networks and risk factors for heroin-related death. We used semi-structured face-to-face qualitative interviews, recorded, transcribed and analysed thematically by framework techniques at three centres providing services to homeless people in a large cosmopolitan city. Different types of accommodation for homeless people have differing social cultures which have an impact upon the amount of heroin used, likelihood of injecting alone or likelihood of achieving abstinence. Hostel accommodation appeared to be linked with a culture of group injecting, which tends to increase the amount of heroin taken. Those with experience of rough sleeping described heroin use to ameliorate the uncomfortable realities of outdoor sleeping, although the overall amount used tended to be less due to having less money to spend on drugs. The prison setting was described as a setting where heroin use was reduced or stopped. Moving away from homelessness towards sustaining an independent tenancy appeared to be associated with a move towards solitary use. We postulate that a progression towards solitary use in a housed environment is one explanation for previous research findings showing the average age of heroin-related death to be increasing despite a decrease in the average age of initiation into heroin use. Hostel accommodation should form a priority setting for future health promotion interventions aimed to reduce heroin-related death. They appear to be linked with an increase in heroin use in the presence of a third party. Drug users sleeping rough in cold climates need to be made aware of the dangers of medicating with heroin to address problems of insomnia due to cold weather.
Kreek, M J
In 1963, Professor Vincent P. Dole at the Rockefeller University formed a small team to develop a pharmacotherapy for the management of heroin addiction. They hypothesized that heroin addiction is a disease of the brain with behavioral manifestations, and not merely a personality disorder or criminal behavior and began to address the specific question of whether a long-acting opioid agonist could be used in the long-term maintenance treatment of heroin addiction. Over the next 35 years, many studies documented the safety, efficacy and effectiveness of methadone pharmacotherapy for heroin addiction, but Federal regulations and stigmatization of heroin addiction prevented implementation of treatment. Finally, in 1999, NIH published a report unequivocally supporting methadone maintenance pharmacotherapy for heroin addiction. Two other effective opioid agonist treatments have been developed: the even longer acting opioid agonist l-alpha-acetylmethadol (LAAM) has been approved for pharmacotherapy for heroin addiction, and still under study is the opioid partial agonist-antagonist buprenorphine-naloxone combination. A variety of studies, both laboratory based and clinical, have revealed the mechanisms of action of long-acting opioid agonists in treatment, including prevention of disruption of molecular, cellular and physiologic events and, in fact, allowing normalization of those functions disrupted by chronic heroin use. Recent molecular biological studies have revealed single nucleotide polymorphisms of the human mu opioid receptor gene; the mu opioid receptor is the site of action of heroin, the major opiate drug of abuse, analgesic agents such as morphine, and the major treatment agents for heroin addiction. These findings support the early hypotheses of our laboratory that addiction may be due to a combination of genetic, drug-induced and environmental (including behavioral) factors and also, that atypical stress responsivity may contribute to the acquisition and
Gerra, G; Garofano, L; Santoro, G; Bosari, S; Pellegrini, C; Zaimovic, A; Moi, G; Bussandri, M; Moi, A; Brambilla, F; Donnini, C
In previous studies, serotonin (5-HT) system disturbance was found involved in a variety of behavioral disorders, psychopathologies, and substance use disorders. A functional polymorphism in the promoter region of the human serotonin transporter gene (5-HTTLPR) was recently identified and the presence of the short (S) allele found to be associated with a lower level of expression of the gene, lower levels of 5-HT uptake, type 2 alcoholism, violence and suicidal behavior. In the present study, 101 heroin addicts (males, West European, Caucasians) and 101 healthy control subjects matched for race and gender, with no history of substance use disorder, have been genotyped. Aggressiveness levels were measured in both heroin addicts and controls utilizing Buss-Durkee-Hostility-Inventory (BDHI). Data about suicide attempt and violent criminal behavior in subject history have been collected. The short-short (SS) genotype frequency was significantly higher among heroin dependent individuals compared with control subjects (P = 0.025). The odds ratio for the SS genotype versus the long-long (LL) genotype frequency was 0.69, 95% Cl (0.49-0.97), when heroin addicts were compared with healthy controls. The SS genotype frequency was significantly higher among violent heroin dependent individuals compared with addicted individuals without aggressive behavior (P = 0.02). BDHI mean total scores and suspiciousness and negativism subscales scores were significantly higher in SS individuals, in comparison with LL subjects, among heroin addicts. No association was found between SS genotype and suicide history. Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with an increased risk for substance use disorders, particularly in the subjects with more consistent aggressiveness and impulsiveness.
Arnold-Reed, Diane E; Hulse, Gary K; Hansson, Robert C; Murray, Sean D; O'Neil, George; Basso, Maria R; Holman, C D'Arcy J
The aim of this study was to investigate the association between prior exposure to naltrexone and increased risk of fatal heroin overdose using a review of toxicology reports for heroin-related fatalities between July 1997 to August 1999 for two groups: those treated with oral naltrexone and those who were not treated. Additional information for the oral naltrexone group was obtained from clinic files. Naltrexone-treated deaths were identified from the patient database at the Australian Medical Procedures Research Foundation (AMPRF), Perth, Western Australia (WA) through the Western Australian Department of Health, Data Linkage Project. Non-treated cases were identified from the database at the Forensic Science Laboratory, State Chemistry Centre (WA). We identified and investigated blood morphine concentrations following 21 fatal heroin overdoses with prior exposure to naltrexone and in 71 non-naltrexone-exposed cases over the same time period. The proportion of deaths where heroin use was a major contributing factor was little different in the non-naltrexone compared to the naltrexone-exposed group. Furthermore, in 'acute opiate toxicity' deaths, blood morphine levels were lower in non-naltrexone-exposed compared with naltrexone-exposed cases. Although there was a higher number of deaths designated as rapid (i.e. occurring within 20 minutes) in the naltrexone-exposed (89%) compared with the non-exposed group (72%) this was not statistically significant. Other drug use in relation to heroin-related fatalities is discussed. Findings do not support the hypothesis that prior exposure to naltrexone increases sensitivity to heroin toxicity.
Hausken, A M; Skurtveit, S; Christophersen, A S
An increasing number of heroin and ecstasy seizures were recorded by the Norwegian police and customs authorities in the 1990s. The number of apprehended drivers in whom heroin and ecstasy were detected also rose in the same period (Heroin, 1991: n = 17, 1999: n = 320. Ecstasy, 1995: n = 6, 1999: n = 123). Drivers who tested positive for heroin (detected in urine as the metabolite 6-monoacetyl-morphine, 6-MAM) or ecstasy (3,4-methylenedioxy-metamphetamine, MDMA, detected in blood) were characterized with regard to age distribution, drug use pattern, and earlier arrests. In 1998-1999, the police apprehended 9013 drivers on suspicion of being under the influence of drugs other than alcohol. Blood and urine samples from the drivers were sent to the Norwegian Institute of Public Health, Division of Forensic Toxicology and Drug Abuse and analyzed for the most commonly abused drugs. 6-MAM was detected in urine in 7% of the cases (n = 637), representing 542 different drivers (male: 85%, n = 463, female: 15%, n = 79) as some drivers were rearrested several times during the selection period. MDMA was detected in 2% of the cases (n = 190), representing 177 drivers (male: 90%, n = 160, female: 10%, n = 17). The median ages of drivers who tested positive for 6-MAM or MDMA were 32 and 24 years, respectively. Multi-drug use was very common in both groups (83% and 98% for the heroin and ecstasy group, respectively). Drivers in both groups were followed back to 1985 to detect earlier arrests for the same offence. Of the heroin group, 78% (n = 417) had earlier been arrested for drunken or drugged driving. Alcohol was the drug most frequently detected on first arrest. Of the ecstasy group, 47% (n = 83) had earlier been arrested, and amphetamine was most frequently found on first arrest.
Wyman, John; Bultman, Steve
The presence of 6-monoacetylmorphine (6-MAM) is often used to distinguish between heroin (diacetylmorphine) and morphine exposures. 6-MAM, however, is rapidly metabolized to morphine and may not be present in detectable quantities in blood following heroin exposure. Recent studies have shown that 6-MAM may persist in cerebrospinal fluid (CSF) and this specimen may be preferable for establishing heroin exposure. This study reports postmortem distribution of 6-MAM, unconjugated morphine, and codeine in different tissues from 25 deceased individuals. In all cases, 6-MAM was detected in vitreous humor, and in CSF in 16 of the 25 cases (64%). When 6-MAM was detected in blood (13 of 25 cases), the level of 6-MAM in vitreous humor and CSF was higher than in blood, with a mean concentration ratio of 11.3 (range: 1.7-27) for vitreous humor and 6.6 (range: 2.6-17.3) for CSF. 6-MAM was not detected in liver in any of the cases examined. Free morphine levels were highest in liver, followed by blood, CSF, and vitreous humor. The concentration ratios (mean +/- standard deviation) for free morphine in vitreous humor, CSF, and liver to that in blood were 0.36 +/- 0.18, 0.64 +/- 0.27, and 2.99 +/- 2.12, respectively. The liver/blood ratio was consistent with previously reported values for morphine in heart and femoral blood. Codeine levels following heroin overdose were consistently low relative to the morphine concentration. For blood, liver, and CSF, the ratio of codeine to morphine was essentially the same (0.06), whereas the vitreous codeine/morphine concentration ratio was slightly higher (0.19). These results characterize the distribution of heroin metabolites in postmortem tissues. Vitreous humor appears to be a useful specimen for determining 6-MAM and establishing the morphine was derived from heroin.
Zilkha, Noga; Feigin, Eugene; Barnea-Ygael, Noam; Zangen, Abraham
The effect of psychoactive drugs on depression has usually been studied in cases of prolonged drug addiction and/or withdrawal, without much emphasis on the effects of subchronic or recreational drug use. To address this issue, we exposed laboratory rats to subchronic regimens of heroin or cocaine and tested long-term effects on (i) depressive-like behaviors, (ii) brain-derived neurotrophic factor (BDNF) levels in reward-related brain regions, and (iii) depressive-like behavior following an additional chronic mild stress procedure. The long-term effect of subchronic cocaine exposure was a general reduction in locomotor activity whereas heroin exposure induced a more specific increase in immobility during the forced swim test. Both cocaine and heroin exposure induced alterations in BDNF levels that are similar to those observed in several animal models of depression. Finally, both cocaine and heroin exposure significantly enhanced the anhedonic effect of chronic mild stress. These results suggest that subchronic drug exposure induces depressive-like behavior which is accompanied by modifications in BDNF expression and increases the vulnerability to develop depressive-like behavior following chronic stress. Implications for recreational and small-scale drug users are discussed. In the present study, we examined the long-term effects of limited subchronic drug exposure on depressive-like symptoms. Our results demonstrate that short-term, subchronic administration of either cocaine or heroin promotes some depressive-like behaviors, while inducing alterations in BDNF protein levels similar to alterations observed in several animal models of depression. In addition, subchronic cocaine or heroin enhanced the anhedonic effect of chronic stress.
Meyer, Andrew C.; Patrick, Mollie E.; Sigmon, Stacey C.
Background While research suggests primary prescription opioid (PO) abusers may exhibit less severe demographic and drug use characteristics than primary heroin abusers, less is known about whether a lifetime history of heroin use confers greater severity among PO abusers. Objective In this secondary analysis, we examined demographic and drug use characteristics as a function of lifetime heroin use among 89 PO-dependent adults screened for a trial evaluating the relative efficacy of buprenorphine taper durations. Exploratory analyses also examined contribution of lifetime heroin use to treatment response among a subset of participants who received a uniform set of study procedures. Methods Baseline characteristics were compared between participants reporting lifetime heroin use ≥5 (H+; n=41) vs. <5 (H−; n=48) times. Treatment response (i.e., illicit opioid abstinence and treatment retention at end of study) was examined in the subset of H+ and H− participants randomized to receive the 4-week taper condition (N=22). Results H+ participants were significantly older and more likely to be male. They reported longer durations of illicit opioid use, greater alcohol-related problems, more past-month cocaine use, greater lifetime IV drug use, and greater lifetime use of cigarettes, amphetamines and hallucinogens. H+ participants also had lower scores on the Positive Symptom Distress and Depression subscales of the Brief Symptom Inventory. Finally, there was a trend toward poorer treatment outcomes among H+ participants. Conclusion A lifetime history of heroin use may be associated with elevated drug severity and unique treatment needs among treatment-seeking PO abusers. PMID:25481453
Macchia, Marco; Bertini, Simone; Mori, Claudio; Orlando, Caterina; Papi, Chiara; Placanica, Giorgio
In this paper, an HPLC method is proposed for a routine, rapid and simple analysis of heroin samples confiscated from the illicit market, based on a new type of packing for HPLC columns (monolithic silica). Acetonitrile and pH 3.5 phosphate buffer solution were used under both isocratic and gradient conditions. Under our analytical conditions, all the components of a typical mixture of an illicit heroin sample proved to be fully separated into well-resolved peaks in 7 min. Analytical linearity and accuracy of the method were also studied for all analytes using tetracaine hydrochloride as the internal standard.
Wu, Zhong-cheng; Chen, Wen-ge; Wang, Lian-chao; Ge, Yu; Yu, Cheng-duan; Fang, Ting-jian
A simple technique for sensitive detection of heroin based on surface-plasmon-resonance has been theoretically and experimentally investigated. The experiment was realized by using an anti-MO monoclonal antibody and a morphine (MO)-bovine serum albumin (MO-BSA) conjugate (antigen). The reason for using MO-BSA in the detection of heroine was also discussed. MO-BSA was immobilized on a gold thin film of SPR sensor chip by physical adsorption. The configuration of the device is allowed to be further miniaturized, which is required for the construction of a portable SPR device in the application of in-situ analysis.
Schwartz, Robert P; Kelly, Sharon M; Gryczynski, Jan; Mitchell, Shannon Gwin; O'Grady, Kevin E; Jaffe, Jerome H
This article reviews research conducted in Baltimore over the past 15 years, examining the following: (1) What factors differentiate heroin-addicted individuals who enter methadone treatment from those who do not? (2) How difficult is gaining access to methadone treatment? (3) What are effective ways to overcome barriers to treatment entry? (4) Why do so many methadone patients drop out of treatment prematurely? (5) What are the added benefits of counseling when coupled with methadone or buprenorphine treatment? (6) Does increasing access to treatment have an impact on overdose deaths? Specific recommendations are made for policymakers concerned with addressing heroin addiction.
Flores, David V.; Torres, Luis R.; Torres-Vigil, Isabel; Bordnick, Patrick S.; Ren, Yi; Torres, Melissa I. M.; DeLeon, Freddy; Pericot-Valverde, Irene; Lopez, Tenee
Drug use among older adults is a growing concern, particularly for the burgeoning Hispanic population. Older adults seeking drug treatment will double over the next decade to almost 6 million. Cultural factors influence drug use, and more specifically, Hispanic cultural values influence heroin use. This study explored Mexican-American injection drug users' adherence to traditional Hispanic cultural values and their impact on cessation. Ethnographic interviews endorsed contextualized influences of values on heroin use. Cultural values functioned dichotomously, influencing both initiation and cessation. Understanding the impact of cultural values on substance abuse is critical given the changing demographics in American society. PMID:24779493
MacMaster, Samuel A.; Jones, Jenny L.; Rasch, Randolph F. R.; Crawford, Sharon L.; Thompson, Stephanie; Sanders, Edwin C., II
Objective: This article provides an evaluation of a federally funded faith-based program that serves African Americans who use heroin and cocaine and are at risk for HIV/AIDS in Nashville, Tennessee. Methods: Data were collected from 163 individuals at baseline and 6- and 12-month follow-up interviews. A subset of participants (n = 51) completed…
Paterson, Sue; Cordero, Rosa
In this study the use of the various opiate alkaloid contaminants as potential markers for illicit heroin ingestion were investigated. Urine samples (n = 227) taken from prisoners for routine drug screen, which were positive for opiates by immunoassay screening, were analyzed for contaminants in illicit heroin. A previously described method was used for the analysis; urines were extracted using mixed-mode solid-phase extraction; the extracts were derivatized using N-methyl-bistrifluoroacetamide and N-methyl-N-trimethylsilyltrifluoroactamide/trimethylchlorosilane. The derivatized extracts were subjected to electron impact gas chromatography-mass spectrometry. The extracts were injected in full scan mode followed by selected ion monitoring mode for target opiate alkaloids found as contaminants in illicit heroin. The opiate alkaloids and their metabolites specifically targeted included meconine, desmethylmeconine, hydrocotarnine, acetylcodeine, codeine, morphine, 6-monacetylmorphine (6-mam), papaverine, hydroxypapaverine, and dihydroxypapaverine. Of the 227 samples positive for opiates by immunoassay, using a cut-off of 300 ng/mL, 199 were confirmed positive for morphine and using a cut-off of 10 ng/mL, 28 were confirmed positive for 6-mam. Using the screening method described in the study, the following numbers of positives were found: 199 for morphine, 103 for codeine, 5 for meconine, 46 for desmethylmeconine, 18 for 6-mam, 136 for hydroxypapaverine, and 139 for dihydroxypapaverine. Acetylcodeine, hydrocotarnine, and papaverine were not detected in any of the samples. The results of this study show that analysis for papaverine metabolites is more sensitive than 6-mam as a way of demonstrating illicit heroin use.
Liao, Yanhui; Tang, Jinsong; Liu, Tieqiao; Chen, Xiaogang; Liu, Xuebing; Hao, Wei
An understanding of the relationship among life events, anxiety, depression, and heroin abuse may benefit the prevention and early treatment of heroin dependence. The objective of this study was to assess self-reported life events, anxiety, and depression in patients with heroin dependence. In this survey, Chinese heroin-dependent patients (n = 139) were asked to conduct a battery of self-reported questionnaires. A total of 76.26% of heroin-dependent patients reported the occurrence of major lifestyle pattern (dietary and sleep) changes as negative life events. Financial problems from family, unemployment, and poor interpersonal relationships were also frequently reported as negative events. Heroin-dependent patients experienced overwhelmingly more negative life events than positive life events. Those negative life events positively correlated with depression and anxiety. They also exhibited high levels of anxiety (Self-Rating Anxiety Scale, mean 44.42 ± 8.27) and depression (Self-Rating Depression Scale, mean 47.28 ± 8.54). Although preliminary, findings from this study suggest the need for further investigation of life events, anxiety, and depression in a generalized large sample, which may benefit community-based psychosocial intervention and prevention of relapse in heroin-dependent subjects.
Zhong, H J; Huo, Z H; Dang, J; Chen, J; Zhu, Y S; Liu, J H
Heroin dependence is a debilitating psychiatric disorder with a complex inheritance mechanism. Genetic polymorphisms in functional regions of the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene, which encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor, may modulate the risk of heroin addiction. We investigated the potential association between 8 single nucleotide polymorphisms (SNPs) of the GRIN2A gene (SNPs rs3219790, rs1014531, rs8044472, rs8045712, rs9933624, rs9940680, rs1420040, and rs767749) and heroin addiction using the MassARRAY system and GeneScan. A total of 405 heroin-addicted patients and 397 healthy control subjects were recruited for this study. Statistically significant differences were observed for rs3219790 in the promoter region of the GRIN2A gene. The frequency of the (GT)26 repeats in the heroin addiction group was significantly higher than that in the control group [X(2) = 5.475, P = 0.019, odds ratio (OR) = 1.367, 95% confidence interval (CI) = 1.051-1.776]. Strong linkage disequilibrium was observed in block 1 (D' > 0.9). However, significant evidence of linkage disequilibrium was not observed between the 7 SNPs in our sample population. These data suggest that GRIN2A gene polymorphisms confer susceptibility to heroin addiction and support the hypothesis that dysfunction of GRIN2A is involved in the pathophysiological process of heroin addiction.
Chen, Weisheng; Wang, Yiqi; Sun, Anna; Zhou, Linyi; Xu, Wenjin; Zhu, Huaqiang; Zhuang, Dingding; Lai, Miaojun; Zhang, Fuqiang; Zhou, Wenhua; Liu, Huifen
Infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction, but whether the IL regulates the extinction and reinstatement of heroin-seeking behavior is unknown. To address this issue, the male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, then the rats underwent 7 daily 2h extinction session in the operant chamber. The activation of IL by microinjection PEPA, an allosteric AMPA receptor potentiator into IL before each of extinction session facilitated the extinction responding after heroin self-administration, but did not alter the locomotor activity in an open field testing environment. Other rats were first trained under a FR1 schedule for heroin self-administration for 14 days, followed by 14 days of extinction training, and reinstatement of heroin-seeking induced by cues was measured for 2h. Intra-IL microinjecting of PEPA at 15min prior to test inhibited the reinstatement of heroin-seeking induced by cues. Moreover, the expression of GluR1 in the IL and NAc remarkably increased after treatment with PEPA during the reinstatement. These finding suggested that activation of glutamatergic projection from IL to NAc shell may be involved in the extinction and reinstatement of heroin-seeking.
Objective(s): Previous studies demonstrated a functional similarity between vertebrate and honey bee nervous systems. The aim of the present study was to compare the effects of heroin and Iranian street Kerack, a combination of heroin and caffeine, on sensory threshold and locomotor activity in honey bees. Materials and Methods: All drugs were given orally to honey bees 30 min before each experiment. The levels of these drugs and their metabolites in brain samples of honey bees were determined by GC/MS. The sucrose sensitivity test was used for evaluation of changes in honey bees’ sensory threshold. Following the administration of both drugs, the honey bees’ locomotor activity changes were evaluated in open fields. Results: 6-acetylmorphine had a higher concentration in comparison with other heroin metabolites in honey bees’ brains. Concentration of the compound in the brain was directly proportional to the amount ingested. Heroin reduced the sensory threshold of honey bees, but Kerack increased it in the same doses. Locomotor activity of honey bee in open field was enhanced after the administration of both drugs. However, immobility time of honey bees was only affected by high doses of heroin. Conclusion: Acute effects of heroin andKerack on the sensory and motor functions of honey bees were different. Findings of this research suggest that these differences originated from the activation of different neurotransmitter systems by caffeine together with activation of opioid receptors by heroin. PMID:26019799
Grass, Gregor; Ahrens, Bjoern; Schleenbecker, Uwe; Dobrzykowski, Linda; Wagner, Matthias; Krüger, Christian; Wölfel, Roman
We describe a culture-based method suitable for isolating Bacillus anthracis and other live bacteria from heroin. This protocol was developed as a consequence of the bioforensic need to retrieve bacteria from batches of the drug associated with cases of injectional anthrax among heroin-consumers in Europe. This uncommon manifestation of infection with the notorious pathogen B. anthracis has resulted in 26 deaths between the years 2000 to 2013. Thus far, no life disease agent has been isolated from heroin during forensic investigations surrounding these incidences. Because of the conjectured very small number of disease-causing endospores in the contaminated drug it is likely that too few target sequences are available for molecular genetic analysis. Therefore, a direct culture-based approach was chosen here. Endospores of attenuated B. anthracis artificially spiked into heroin were successfully retrieved at 84-98% recovery rates using a wash solution consisting of 0.5% Tween 20 in water. Using this approach, 82 samples of un-cut heroin originating from the German Federal Criminal Police Office's heroin analysis program seized during the period between 2000 and 2014 were tested and found to be surprisingly poor in retrievable bacteria. Notably, while no B. anthracis was isolated from the drug batches, other bacteria were successfully cultured. The resulting methodical protocol is therefore suitable for analyzing un-cut heroin which can be anticipated to comprise the original microbiota from the drug's original source without interference from contaminations introduced by cutting.
Doherty, James M; Cooke, Bradley M; Frantz, Kyle J
Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir(+) and Fos-ir(-) neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir(+) neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration.
Liu, J H; Zhong, H J; Dang, J; Peng, L; Zhu, Y S
Previous studies suggested that dopamine receptors may be associated with drug dependence and impulsive behavior. In this study, we examined whether dopamine receptor D1 (DRD1) is associated with heroin dependence and the impulsive behavior in patients with heroin dependence. The participants included 367 patients with heroin dependence and 372 healthy controls from a Chinese Han population. We examined the potential association between heroin dependence and 8 single-nucleotide polymorphisms (rs686, rs4867798, rs1799914, rs4532, rs5326, rs265981, rs10078714, rs10078866) of DRD1, and the associations between single single-nucleotide polymorphism, haplotypes, and impulsive behavior. Compared with the healthy controls, heroin dependence patients showed a significantly lower frequency of GG homozygotes of rs5326 (P = 0.027), significantly lower frequency of the G allele of rs5326 (P = 0.007, odds ratio = 0.718, 95% confidence interval = 0.565-0.913), and higher frequency of the rs265981 G allele (P = 0.0002, odds ratio = 1.711, 95% confidence interval = 1.281-2.287). Furthermore, strong linkage disequilibrium was observed in 2 blocks (D' > 0.9). However, no association was observed between haplotypes and heroin dependence in the 2 blocks. This genetic behavior correlation study showed that the 2 single-nucleotide polymorphisms, rs5326 and rs265981, were not associated with the impulsive behavior in patients with heroin dependence. These findings indicate that DRD1 gene polymorphisms are related to heroin dependence in a Chinese Han population and may be informative for future genetic or biological studies on heroin dependence.
Topp, Libby; Day, Carolyn; Degenhardt, Louisa
Between 1996 and 2000, heroin was the drug most frequently injected in Australia, and viable heroin markets existed in six of Australia's eight jurisdictions. In 2001, there was a dramatic and sustained reduction in the availability of heroin that was accompanied by a substantial increase in its price, and a 14% decline in the average purity of seizures analysed by forensic laboratories. The shortage of heroin constitutes a unique natural experiment within which to examine the impact of supply reduction. This paper reviews one important correlate of the shortage, namely changes in patterns of illicit drug injection. A number of studies have consistently suggested that between 2000 and 2001, there was a sizeable decrease in both prevalence and frequency of heroin injection among injecting drug users. These changes were accompanied by increased prevalence and frequency of stimulant injection. Cocaine was favoured in NSW, the sole jurisdiction in which a cocaine market was established prior to the heroin shortage; whereas methamphetamine predominated in other jurisdictions. Some data suggest that, at least in the short-term, some drug injectors left the market altogether subsequent to the reduced heroin availability. However, the findings that (1) some former heroin users switched their drug preference to a stimulant; and (2) subsequently attributed this change to the reduced availability of heroin, suggests that reducing the supply of one drug may serve to increase the use of others. Given the differential harms associated with the use of stimulants and opiates, this possibility has grave implications for Australia, where the intervention and treatment system is designed primarily to accommodate opiate use and dependence.
Page, Richard C.; Kubiak, Larry
Apparent success of the marathon groups in altering the perceptions of Black female heroin addicts toward the future, counseling, and themselves offers preliminary evidence that marathons may have potential as a counseling strategy with these clients. Future research needs to be performed to substantiate or reject these findings. (Author/PD)
Navaee, Aso; Salimi, Abdollah; Teymourian, Hazhir
In the present study, the graphene nanosheets (GNSs) modified glassy carbon (GC) electrode is employed for simultaneous determination of morphine, noscapine and heroin. To the best of our knowledge this is the first report of the simultaneous determination of these three important opiate drugs based on their direct electrochemical oxidation. Field emission scanning electron microscopy (FESEM) technique is utilized in order to study the surface morphology of the modified electrode. The modified electrode shows excellent electrocatalytic activity toward oxidation of morphine, noscapine and heroin at reduced overpotentials in wide pH range. In the performed experiments, differential pulse voltammetric determination of morphine, noscapine and heroin yields calibration curves with the following characteristics; linear dynamic range up to 65, 40 and 100 μM, sensitivity of 275, 500 and 217 nA μM(-1) cm(-2), and detection limits of 0.4, 0.2 and 0.5 μM at 3S(B), respectively. Fast response time, signal stability, high sensitivity, low cost and ease of preparation method without using any specific electron-transfer mediator or specific reagent are the advantageous of the proposed sensor. The modified electrode can be used for simultaneous or individual detection of three major narcotic components, heroin, noscapine and morphine at micromolar concentration without any separation or pretreatment steps.
Lai, S; Liu, W; Chen, J; Yang, J; Li, Z J; Li, R J; Liang, F X; Liang, S L; Zhu, Q Y; Yu, X F
Guangxi Province, China recently experienced an outbreak of HIV-1 infection among heroin users. We studied HIV-1 incidence rates and associated risk factors for HIV-1 infection among heroin users residing in Pingxiang City. A total of 318 heroin users were followed from February 1998 through January 1999 (median follow-up: 8.1 months). Of these, 130 were prospectively followed from January through September 1999 (median follow-up: 8.3 months). HIV-1 and hepatitis C virus (HCV) incidence rates for each period were calculated. A generalized estimating equation approach was implemented to identify independent risk factors associated with HIV-1 infection across both periods. Among 318 study participants, 97.2% were men. The median age was 22 years. Approximately 60% reported sharing needles. HIV-1 prevalence at baseline was 15.4%. During the first follow-up period, HIV-1 incidence was 2.38 per 100 person years (py), and HCV incidence was 26.8 per 100 py. During the second follow-up period, HIV-1 incidence was 6.86 per 100 py, and HCV incidence was 28.9 per 100 py. After controlling for age and other factors, HCV seropositivity, history of sexually transmitted diseases, and sharing needles were independently associated with HIV-1 infection. These data suggest that HIV-1 incidence was rising over time in Pingxiang City, Guangxi Province. The high incidence of HCV heightens the importance of enhanced prevention programs to reduce injection and needle sharing among heroin users.
Grunow, R; Klee, S R; Beyer, W; George, M; Grunow, D; Barduhn, A; Klar, S; Jacob, D; Elschner, M; Sandven, P; Kjerulf, A; Jensen, J S; Cai, W; Zimmermann, R; Schaade, L
Injection anthrax was described first in 2000 in a heroin-injecting drug user in Norway. New anthrax cases among heroin consumers were detected in the United Kingdom (52 cases) and Germany (3 cases) in 2009-10. In June 2012, a fatal case occurred in Regensburg, Bavaria. As of December 2012, 13 cases had been reported in this new outbreak from Germany, Denmark, France and the United Kingdom. We analysed isolates from 2009-10 and 2012 as well as from the first injection anthrax case in Norway in 2000 by comparative molecular typing using a high resolution 31 marker multilocus variable-number tandem repeat analysis (MLVA) and a broad single nucleotide polymorphism (SNP) analysis. Our results show that all cases may be traced back to the same outbreak strain. They also indicate the probability of a single source contaminating heroin and that the outbreak could have lasted for at least a decade. However, an additional serological pilot study in two German regions conducted in 2011 failed to discover additional anthrax cases among 288 heroin users.
Akyar, Eda; Seneca, Kathleen H; Akyar, Serra; Schofield, Neal; Schwartz, Mark P; Nahass, Ronald G
We identified a 41.4% prevalence of hepatitis C virus, absence of HIV, and unexpectedly high frequency of hepatitis C virus genotype 3 among suburban New Jersey heroin users 17-35 years of age during 2014-2015. Despite 2 clinicians prepared to engage these users, few were successfully linked to care and treated.
The portrayal of the working girl in the silent films of the 1920s ignored the fact that in reality women worked to help support their families, to be financially independent, or to supplement their family's income. A study of movie heroines from that era reveals that these characterizations reinforce the image of the traditionally dependent woman…
In the fast paced, fluid contemporary world, and in a headlong rush to invent the future, there is a tendency to jettison aspects of the past as flotsam and jetsam, unworthy of a place in steerage into the future. This paper argues that is some respects the ordinary heroes and heroines who enact school leaderships, and from their practice…
Seneca, Kathleen H.; Akyar, Serra; Schofield, Neal; Schwartz, Mark P.; Nahass, Ronald G.
We identified a 41.4% prevalence of hepatitis C virus, absence of HIV, and unexpectedly high frequency of hepatitis C virus genotype 3 among suburban New Jersey heroin users 17–35 years of age during 2014–2015. Despite 2 clinicians prepared to engage these users, few were successfully linked to care and treated. PMID:27089172
Klous, Marjolein G; Bronner, Gaby M; Nuijen, Bastiaan; van Ree, Jan M; Beijnen, Jos H
Pharmaceutical heroin for inhalation was developed for a clinical trial on co-prescription of heroin and methadone to chronic treatment-resistant heroin addicts. Diacetylmorphine base was selected as the active pharmaceutical ingredient for this product with caffeine anhydrate added as an excipient. Differential scanning calorimetry and thermogravimetric analysis showed that addition of caffeine resulted in a lower melting temperature and a higher volatilisation rate for the mixture than for diacetylmorphine base alone. Recovery experiments showed that 40.8+/-5.3% of diacetylmorphine base could be found in smoke condensate after volatilisation of diacetylmorphine-caffeine tablets. All of the caffeine from each tablet was recovered unchanged in the fumes, while 85.6% of the diacetylmorphine from each tablet was recovered, either unchanged in the fumes or as non-volatilised residue. Recovery was found to be reproducible and only small differences were found between the tablet types. The experimental set-up was found to efficiently collect the vapours resulting from heating the powder. Under the tested experimental conditions, no evidence was found that degradation products of diacetylmorphine or caffeine, other than 6-acetylmorphine (5.9%) had volatilised, even though a decomposed residue was present after heating diacetylmorphine-caffeine samples. Diacetylmorphine-caffeine was found to be a suitable basis for pharmaceutical heroin to be used by 'chasing the dragon'.
Shand, Fiona L; Degenhardt, Louisa; Slade, Tim; Nelson, Elliot C
Introduction and aims To examine differences in the characteristics and histories of male and female dependent heroin users, and in the clinical characteristics associated with multiple substance dependence diagnoses. Design and methods 1513 heroin dependent participants underwent an interview covering substance use and dependence, psychiatric history, child maltreatment, family background, adult violence and criminal history. Family background, demographic and clinical characteristics were analysed by sex. Ordinal regression was used to test for a relationship between number of substance dependence diagnoses and other clinical variables. Results Women were more likely to experience most forms of child maltreatment, to first use heroin with a boyfriend or partner, to experience ongoing adult violence at the hands of a partner, and to have a poorer psychiatric history than men. Males had more prevalent lifetime substance dependence diagnoses and criminal histories and were more likely to meet criteria for ASPD. Predictors of multiple substance dependence diagnoses for both sexes were mental health variables, antisocial behaviour, childhood sexual abuse, victim of adult violence, younger age at first cannabis use and overdose. As the number of dependence diagnoses increased, clinical and behavioural problems increased. Childhood emotional neglect was related to increasing dependence diagnoses for females but not males, whereas PTSD was a significant predictor for males but not females. Discussion and conclusions Mental health problems, other substance dependence, childhood and adult trauma were common in this sample, with sex differences indicating different treatment needs and possible different pathways to heroin dependence for men and women. PMID:20833480
McFalls, Ashley J; Imperio, Caesar G; Bixler, Georgina; Freeman, Willard M; Grigson, Patricia Sue; Vrana, Kent E
One of the most damaging aspects of drug addiction is the degree to which natural rewards (family, friends, employment) are devalued in favor of seeking, obtaining and taking drugs. We have utilized an animal model of reward devaluation and heroin self-administration to explore the role of the coricotropin releasing factor (CRF) pathway. Given access to a saccharin cue followed by the opportunity to self-administer heroin, animals will parse into distinct phenotypes that suppress their saccharin intake (in favor of escalating heroin self-administration) or vice versa. We find that large saccharin suppressors (large heroin takers) demonstrate increased mRNA expression for elements of the CRF signaling pathway (CRF, CRF receptors and CRF binding protein) within the hippocampus, medial prefrontal cortex and the ventral tegmental area. Moreover, there were no gene expression changes of these components in the nucleus accumbens. Use of bisulfite conversion sequencing suggests that changes in CRF binding protein and CRF receptor gene expression may be mediated by differential promoter methylation.
Housová, J; Wilczek, H; Haluzík, M M; Kremen, J; Krízová, J; Haluzík, M
Heroin addiction markedly affects the nutritional and metabolic status and frequently leads to malnutrition. The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts were significantly decreased (3.4+/-0.4 vs. 4.5+/-0.6 ng/ml and 18.9+/-3.3 vs. 33.9+/-3.1 ng/microl, respectively; p 0.05) while serum resistin concentrations were increased compared to healthy subjects (10.1+/-1.2 vs. 4.6+/-0.3 ng/ml; p 0.05). Moreover, positive correlation of serum leptin levels with body mass index was lost in the addicts in contrast to control group. One year of methadone maintenance treatment normalized serum leptin, but not serum adiponectin and resistin concentrations. In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction. These alterations appear to be relatively independent of nutritional status and insulin sensitivity.
Ghitza, Udi E.; Epstein, David H.; Schmittner, John; Vahabzadeh, Massoud; Lin, Jia-Ling; Preston, Kenzie L.
To examine the effect of reinforcer density in prize-based abstinence reinforcement, heroin/cocaine users (N = 116) in methadone maintenance (100 mg/day) were randomly assigned to a noncontingent control group (NonC) or to 1 of 3 groups that earned prize draws for abstinence: manual drawing with standard prize density (MS) or computerized drawing…
An examination of America's attempts to cope with the problem of heroin (and other drug) addiction must proceed through an analysis of the basic responses to the problem--penal, behavioral and medical--from two quite different, and frequently conflicting, vantage points: that of the individual addict and that of the society as a whole. (Author/NQ)
Gutierres, Sara E.; And Others
Reviewed the literature on female drug use/abuse and derived descriptions of the female heroin abuser and the female prescription drug abuser. Researchers suggest that problems of female drug abusers should be viewed in terms of the feminine role as well as the role of drug abuser. (BH)
Platt, J J; Labate, C
An investigation was made of the association between the postrelease circumstances and behavior of 79 youthful heroin offenders and parole outcome. The data suggest that steady employment and the absence of drug use on parole are significantly related to parole success and to each other.
Dujourdy, L; Besacier, F
This article aims at exploiting the statistical data of the qualitative and quantitative analyses of heroin circulating in France over more than 20 years. This information, systematically recorded by the Forensic Laboratories from Institut national de police scientifique is a good source of knowledge of this product at both the chemical and sanitary levels (street level, wholesalers, imports, etc.).
Gabadadze, G D; Kinle, A F
The examination of the activity of serum amilase and cholinesterase in the blood from subjects who had died of heroin poisoning showed significant elevation of such activity. These findings allow experts to use the activity of the above enzymes as effective markers in detection of narcotic drugs in cadaveric blood, opiate narcotics, in particular.
As part of an ongoing ethnographic study, this paper aims to consider the practice of poetry, "sher-o-shayari", as naturalistic peer learning among a group of heroin addicts in Yamuna Bazaar, New Delhi. By examining meanings given to "sher-o-shayari" and experiences of participating in the practice, this article makes the claim…
Furst, R. Terry; Balletto, Rebecca
Ethnographic and qualitative research were utilized to examine how the effects of geographic place can be related to heroin abuse and collective identity in non-metropolitan areas (NMAs) in the mid-Hudson region of New York State, U.S. The socio-geographic consequences of this interrelationship are explored. In-depth interviews were conducted with…
Park, Paula E; Schlosburg, Joel E; Vendruscolo, Leandro F; Schulteis, Gery; Edwards, Scott; Koob, George F
Opioids represent effective drugs for the relief of pain, yet chronic opioid use often leads to a state of increased sensitivity to pain that is exacerbated during withdrawal. A sensitization of pain-related negative affect has been hypothesized to closely interact with addiction mechanisms. Neuro-adaptive changes occur as a consequence of excessive opioid exposure, including a recruitment of corticotropin-releasing factor (CRF) and norepinephrine (NE) brain stress systems. To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia-like behavior during heroin withdrawal utilizing models of both acute and chronic dependence. We found that passive or self-administered heroin produced a significant mechanical hypersensitivity. During acute opioid dependence, systemic administration of the CRF1 receptor antagonist MPZP (20 mg/kg) alleviated withdrawal-induced mechanical hypersensitivity. In contrast, several functional adrenergic system antagonists (clonidine, prazosin, propranolol) failed to alter mechanical hypersensitivity in this state. We then determined the effects of chronic MPZP or clonidine treatment on extended access heroin self-administration and found that MPZP, but not clonidine, attenuated escalation of heroin intake, whereas both drugs alleviated chronic dependence-associated hyperalgesia. These findings suggest that an early potentiation of CRF signaling occurs following opioid exposure that begins to drive both opioid-induced hyperalgesia and eventually intake escalation.
Tull, Matthew T.; Schulzinger, David; Schmidt, Norman B.; Zvolensky, Michael J.; Lejuez, C. W.
Anxiety sensitivity (AS) recently has been identified as a potential cognitive vulnerability underlying substance use problems, with some evidence specifically indicating its relevance to heroin. Focusing on the potential utility of interventions centered on increasing willingness to have anxiety-related sensations reduce vulnerability for relapse…
Phillips, Peter; Glover, Chris; Allan, Teresa; Khoo, Mary Ellen
Aims: This study used group psycho-education methods to assist injecting heroin users in preventing, and responding to overdose. Methods: An "OD Prevention" group was advertised in a London prescribing service and associated primary care unit. The intervention took place in a small group over one afternoon (3.5 hours), and trained…
Street "doctory" is a form of peer-based medical care performed in street settings among a group of heroin addicts in Yamuna Bazaar, New Delhi. Using participant observation and semi-structured interviews, this study describes three components of the practice, and suggests that each contained peer learning processes. First, participants…
Boeri, Miriam Williams; Sterk, Claire E.; Elifson, Kirk W.
Purpose: Researchers' knowledge regarding older users of illicit drugs is limited despite the increasing numbers of users. In this article, we apply a life course perspective to gain a further understanding of older adult drug use, specifically contrasting early- and late-onset heroin users. Design and Methods: We collected qualitative data from…
Todd, Ross J.
Reports on a study of a small group of girls in Australia that investigated how older adolescents cognitively utilize information on heroin. The study sought to establish the perceived effects of exposures to information and to establish how the perceived effects are associated with changes to the girls' knowledge structures. (Author/LRW)
Krupitsky, Evgeny M; Burakov, Andrei M; Dunaevsky, Igor V; Romanova, Tatyana N; Slavina, Tatyana Y; Grinenko, Alexander Y
A prior study found that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified inpatients with heroin dependence received a ketamine-assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the first group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction.
Steffen, T; Kaufmann, B; Blättler, R; Dobler-Mikola, A; Gutzwiller, F; Uchtenhagen, A
Heroin-assisted treatment has been examined broadly in Switzerland since 1994 within the context of scientific studies. The goal was to clarify the suitability of this treatment for opiate addicts whom previous therapy had failed to reach. Results of the initial research phase show that the target group could be reached for treatment extending 18 months with a satisfactory retention rate of 69%. The patients could improve their health and social situation during treatment and reduce illegal consumption of narcotics. Studies during the initial years primarily examined the viability of heroin-assisted treatment and its effects on the patients' psychosocial and somatic development. A second study phase ongoing since 1998 pursues the specific importance of medical and psychosocial treatment for patients' health and social development in heroin-assisted treatment. The focal point is the effort to optimise treatment of patients with comorbidity of psychiatric disorders and severe somatic diseases, particularly AIDS. Investigations carried out in Switzerland have been discussed broadly at an international level. Studies on heroin-assisted treatment are also being conducted at present in various countries. In future, co-operation should be further intensified with researchers on an international scale.
Xie, Chunming; Shao, Yongcong; Ma, Lin; Zhai, Tianye; Ye, Enmao; Fu, Liping; Bi, Guohua; Chen, Gang; Cohen, Alex; Li, Wenjun; Chen, Guangyu; Yang, Zheng; Li, Shi-Jiang
Using neuroeconomic approaches, our findings demonstrate that the underlying duality of the β-δ discounting networks that jointly influence valuation is impaired to a pathogenic state in abstinent heroin dependents. The imbalanced functional link between the β-δ networks for valuation may orchestrate the irrational choice in drug addiction. PMID:23207652
Wallenstein, S L; Houde, R W; Portenoy, R; Lapin, J; Rogers, A; Foley, K M
A direct comparison of the analgesic activities of heroin and hydromorphone was carried out in cancer patients with postsurgical pain. Intramuscular doses of 5 and 10 mg of heroin were compared with 1 and 2 mg of hydromorphone in a randomized, double-blind, 4-point parallel group assay. Design innovations in the study provided that about half the patients would receive prior repeated doses of the same drug as the test medication, and half would receive the alternate medication. Both test drugs were found to be potent, relatively short acting analgesics with similar profiles of action. Hydromorphone was about 5 times as potent as heroin on a milligram basis. The comparison of those patients who had repeated doses of the same treatment prior to the test dose and those who had repeated doses of the alternate drug demonstrated no significant effect on the relative potency estimates. Side effect occurrence was similar for both drugs, with sleepiness the most prominent effect. The study supports the view that hydromorphone and heroin produce similar clinical effects, and that either drug may adequately substitute for the other. Covariate analysis indicated that time since last analgesic was positively related to analgesia, and amount of prior opioid had a negative relationship. To a lesser extent, increase in patient age was associated with an increase in analgesic scores. Taking these covariates into account served to increase the sensitivity of the analysis.
Zhao, Li-Yan; Shi, Jie; Zhang, Xiao-Li; Lu, Lin
Stress exposure in addicted individuals is known to provoke drug craving, presumably through a memory-like process, but less is known about the effects of stress on non-drug-related affective memory retrieval per se in such individuals, which is likely to provide important insights into therapy for relapse. In present study, we explored the effect of stress on retrieval of neutral and emotionally valenced (positive and negative) words in abstinent heroin addicts. In present study, 28 male inpatient abstinent heroin addicts and 20 sex-, age-, education- and economic status-matched healthy control participants were assessed for 24h delayed recall of valenced and neutral word lists on two occasions 4 weeks apart-once in a nonstress control condition, once after exposure to the Trier Social Stress Test in a counterbalanced design. In addition, attention, working memory, blood pressure, heart rate and salivary cortisol were assessed. We found acute stress at the time of word list recall enhanced retrieval of positively valenced words, but no effect on negative and neutral word retrieval in abstinent heroin addicts was observed. No changes were detected for attention and working memory. The stressor induced a significant increase in salivary free cortisol, blood pressure and heart rate. Stress can enhance non-drug-related positive memory in abstinent heroin addicts. Our findings will provide richer information in understanding dysregulation of their emotional memory processing under stress and hopefully provide insight into designing improved treatments for drug addiction.
Potter, Jennifer S; Prather, Kristi; Kropp, Frankie; Byrne, Mimmie; Sullivan, C Rollynn; Mohamedi, Nadia; Copersino, Marc L; Weiss, Roger D
Treatment research with opioid-dependent populations has not traditionally distinguished between those dependent on prescription opioids versus dependent upon heroin. Evidence suggests there is a substantial subpopulation of individuals with opioid dependence resulting largely or exclusively from prescription opioid use. Because this subpopulation may respond to treatment differently from heroin users, a method for discriminating DSM-IV opioid dependence due to prescription opioid use would provide more precision when examining this population. This paper describes an innovative method using a currently available diagnostic instrument, to diagnose DSM-IV opioid dependence and distinguish between dependence resulting from prescription opioids versus dependence upon heroin.
Lenoir, Magalie; Guillem, Karyn; Koob, George F; Ahmed, Serge H
Increased drug availability can precipitate a rapid escalation of drug consumption in both vulnerable humans and laboratory animals. Drug intake escalation is observed across a broad spectrum of drugs of abuse, including stimulants, opiates, ethanol and phencyclidine. Whether and to what extent the processes underlying escalated levels of drug intake vary across different substances is poorly understood. The present study sought to address this question in rats self-administering both cocaine and heroin-two addictive drugs with both common and different neurobiological effects. In experiment 1, we determined how cocaine intake is initially related to heroin intake in non-escalated rats with a limited access to both drugs. In experiment 2, two groups of rats were initially allowed to self-administer either cocaine or heroin for 1 hour per day and then after behavioral stabilization, for 6 hours per day to precipitate drug intake escalation. In each group, dose-injection functions for cocaine and heroin self-administration were generated. In experiment 1, regardless of the dose, rats with a high intake of one drug did not necessarily have a high intake of the alternate drug. In experiment 2, escalated levels of heroin or cocaine self-administration did not generalize to the other drug. This outcome was confirmed in a third drug substitution experiment following different access lengths to cocaine self-administration (i.e. 1, 4 and 8 hours). The processes underlying spontaneous and escalated drug overconsumption appear thus to vary across different drugs of abuse. More research should be devoted in the future to these differences.
Gerra, G; Somaini, L; Manfredini, M; Raggi, M A; Saracino, M A; Amore, M; Leonardi, C; Cortese, E; Donnini, C
The aim of this paper was to investigate the subjective responses of abstinent heroin users to both neutral and negative stimuli and the related hypothalamus-pituitary-adrenal reactions to emotional experience in relationship to their perception of childhood adverse experiences. Thirty male abstinent heroin dependents were included in the study. Emotional responses and childhood neglect perception were measured utilizing the State-Trait Anxiety Inventory Y-1 and the Child Experience of Care and Abuse Questionnaire. Neutral and unpleasant pictures selected from the International Affective Picture System and the Self-Assessment Manikin procedure have been used to determine ratings of pleasure and arousal. These ratings were compared with normative values obtained from healthy volunteers used as control. Blood samples were collected before and after the experimental sessions to determine both adrenocorticotropic hormone and cortisol plasma levels. Basal anxiety scores, cortisol and adrenocorticotropic hormone levels were higher in abstinent heroin users than in controls. Tests showed that anxiety scores did not change in controls after the vision of neutral slides, whilst they did in abstinent heroin addicts, increasing significantly; and increased less significantly after the unpleasant task, in comparison to controls. Abstinent heroin users showed significantly higher levels of parent antipathy and childhood emotional neglect perception than controls for both the father and the mother. Plasma adrenocorticotropic hormone and cortisol levels did not significantly increase after unpleasant slide set viewing among addicted individuals, because of the significantly higher basal levels characterizing the addicted subjects in comparison with controls. Multiple regression correlation showed a significant relationship between childhood neglect perception, arousal reaction, impaired hypothalamus-pituitary-adrenal axis response and addiction severity. Early adverse experiences
Lurie, Ira S; Toske, Steven G
The applicability of ultra- performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) for heroin profiling is described. The coupling of the high separation power of UPLC with the highly selective and sensitive detection of MS/MS is well suited for heroin profiling. An Acquity UPLC BEH C18 1.7 microm particle column (100 mm x 2.1mm) with binary gradients containing 1% formic acid (pH 2.0) or 10 mM ammonium bicarbonate (pH 10.0)/acetonitrile mixtures was investigated for the profiling. For MS/MS detection, an atmospheric pressure positive electrospray source was employed with multiple reaction monitoring (MRM). MRMs for individual basic impurities were generated for heroin profiling using low and high pH mobile phases, while MRMs for neutral impurities were generated using a high pH mobile phase. Compared to a pH 2.2 mobile phase, the use of a pH 10 mobile phase allowed for significantly greater sample loading, major selectivity differences, and lower MRM sensitivity. UPLC-MS/MS allowed for the highly selective and sensitive detection of many of the targeted solutes in seized heroin exhibits. Basic impurities detected included morphine, codeine, noscapine, papaverine and the previously unreported solutes reticuline, reticuline monoacetate (2 products), reticuline diacetate, narceine, codamine, laudanidine, cryptopine, laudanosine, and norlaudanosine. Neutral impurities found included N,3,6-triacetylnormorphine, N-acetylnorcodeine, N-acetylnornarcotine, 3,6-dimethoxy-4-acetyloxy-5-[2-(N-methylacetamido)]-ethylphenanthrene, and cis-n-acetylanhydronornarceine. The detection of these impurities, at levels as low as 10(-6)% w/w should allow for greatly enhanced heroin profiles.
Mateu-Gelabert, Pedro; Harris, Shana; Berbesi, Dedsy; Segura Cardona, Ángela María; Montoya Vélez, Liliana Patricia; Mejía Motta, Inés Elvira; Jessell, Lauren; Guarino, Honoria; Friedman, Samuel R.
Background Heroin production in Colombia has increased dramatically in recent decades, and some studies point to an increase in local heroin use since the mid-1990s. Despite this rapid increase, little is known about the effects of these activities on heroin injection within Colombia. One of the biggest concerns surrounding heroin injection is the potential spread of HIV through drug user networks. Objectives This article examines injection risk behaviors among heroin injectors in the Colombian cities of Medellín and Pereira to explore the implications for possible increased HIV transmission within this group. Methods A cross-sectional study used respondent-driving sampling to recruit a sample of 540 people who inject drugs (PWID) over 18 years of age (Medellín: n = 242, Pereira: n = 298). Structured interviews with each participant were conducted using the World Health Organization Drug Injection Study Phase II Survey. An HIV test was also administered. Results Information regarding the socio-demographics, injection drug use, HIV risk and transmission behaviors, injection risk management, and HIV knowledge and prevalence of participants are reported. The study identified many young, newly initiated injectors who engage in risky injection practices. The study also found that HIV prevalence is fairly low among participants (2.7%). Conclusions/Importance Findings indicate a potential risk for the spread of HIV among PWID in Colombia given their widespread sharing practices, high rate of new injector initiation, and unsafe syringe cleaning practices. Colombia has a possibly time-limited opportunity to prevent an HIV epidemic by implementing harm reduction interventions among young, newly initiated PWID. PMID:26800352
Albertson, Dawn N; Schmidt, Carl J; Kapatos, Gregory; Bannon, Michael J
Drug abuse is thought to induce long-term cellular and behavioral adaptations as a result of alterations in gene expression. Understanding the molecular consequences of addiction may contribute to the development of better treatment strategies. This study utilized highthroughput Affymetrix microarrays to identify gene expression changes in the post-mortem nucleus accumbens of chronic heroin abusers. These data were analyzed independently and in relation to our previously reported data involving human cocaine abusers, in order to determine which expression changes were drug specific and which may be common to the phenomenon of addiction. A significant decrease in the expression of numerous genes encoding proteins involved in presynaptic release of neurotransmitter was seen in heroin abusers, a finding not seen in the cocaine-abusing cohort. Conversely, the striking decrease in myelin-related genes observed in cocaine abusers was not evident in our cohort of heroin subjects. Overall, little overlap in gene expression profiles was seen between the two drug-abusing cohorts: out of the approximately 39 000 transcripts investigated, the abundance of only 25 was significantly changed in both cocaine and heroin abusers, with nearly one-half of these being altered in opposite directions. These data suggest that the profiles of nucleus accumbens gene expression associated with chronic heroin or cocaine abuse are largely unique, despite what are thought to be common effects of these drugs on dopamine neurotransmission in this brain region. A re-examination of our current assumptions about the commonality of molecular mechanisms associated with substance abuse seems warranted. PMID:16710320
Andersson, Maria; Björkhem-Bergman, Linda; Beck, Olof
Heroin is de-acetylated in the body to morphine in two steps. The intermediate 6-acetylmorphine (6-AM) is formed rapidly and is considered important for the pharmacological effect of heroin. In urine drug testing, an atypical pattern of morphine and 6-AM is known to occur in low frequency. The aim of this study was to investigate this atypical pattern in more detail and to identify responsible substances for a possible inhibition of the conversion from 6-AM to morphine. Urine samples were selected from a routine flow of samples sent for drug testing. Out of 695 samples containing morphine and 6-acetylmorphine, 11.5% had the atypical pattern of a 6-AM to morphine ratio above 0.26 as derived from a bimodal frequency distribution. An in vitro study of the conversion of 6-acetylmorphine to morphine in human liver homogenates demonstrated that a number of known carboxylesterase inhibitors were able to inhibit the reaction mimicking the situation in vivo. Compound 3 (3,6-Dimethoxy-4-acetoxy-5-[2-(N-methylacetamido)ethyl]phenanthrene) a substance formed from thebaine during the production of heroin was found to be a strong inhibitor. Liquid chromatography-mass spectrometry was used to identify possible inhibitors present in vivo. This part of the investigation demonstrated that several components may contribute to the effect. It is concluded that inhibition of liver carboxylesterase activity is a possible mechanism causing the atypical pattern and that one candidate compound is the result of the heroin production process. An inhibition of 6-AM metabolism is likely to increase the pharmacological effect of heroin and may be related to a higher risk of lethal toxicity.
Lee, Sooyeun; Cordero, Rosa; Paterson, Sue
There is limited published data to aid interpretation of analytical findings from hair analysis. The aim of the study was to collate 6-monoacetylmorphine (6-AM) and morphine concentrations in head and pubic hair from heroin users and to propose reference ranges and relate these to the amount of heroin used. The ratio of morphine-to-6-AM was also investigated. A total of 82 head hair samples divided into 173 segments of various lengths and 15 pubic hair samples were collected at postmortem from heroin users. The hair was analysed using a previously published method. A statistical evaluation demonstrated that in head hair, the lower, middle and upper concentration ranges of 6-AM were 0.1-0.9, 0.9-12.5 and 12.5-154.1 ng/mg and those of morphine were 0.1-0.8, 0.8-6.0 and 6.0-36.3 ng/mg. In pubic hair, the lower, middle and upper concentration ranges of 6-AM were 0.2-0.5, 0.5-2.3 and 2.3-18.2 ng/mg and those of morphine were 0.2-0.4, 0.4-2.4 and 2.4-13.3 ng/mg. The morphine-to-6-AM ratio showed a large variation. The ratio tended to decrease from proximal to distal segments. The statistical results suggest low, middle and high concentration ranges which we propose can be used for estimating the amount of heroin consumed into corresponding low or occasional, regular or habitual and heavy or excessive drug use. The ratio of morphine-to-6-AM showed great variation and did not support the proposal that a ratio less than 0.77 is needed to prove ingestion of heroin.
Pattison, Lindsey P; McIntosh, Scot; Sexton, Tammy; Childers, Steven R; Hemby, Scott E
Concurrent use of cocaine and heroin (speedball) has been shown to exert synergistic effects on dopamine neurotransmission in the nucleus accumbens (NAc), as observed by significant increases in extracellular dopamine levels and compensatory elevations in the maximal reuptake rate of dopamine. The present studies were undertaken to determine whether chronic self-administration of cocaine, heroin or a combination of cocaine:heroin led to compensatory changes in the abundance and/or affinity of high- and low-affinity DAT binding sites. Saturation binding of the cocaine analog [(125) I] 3β-(4-iodophenyl)tropan-2β-carboxylic acid methyl ester ([(125) I]RTI-55) in rat NAc membranes resulted in binding curves that were best fit to two-site binding models, allowing calculation of dissociation constant (Kd ) and binding density (Bmax ) values corresponding to high- and low-affinity DAT binding sites. Scatchard analysis of the saturation binding curves clearly demonstrate the presence of high- and low- affinity binding sites in the NAc, with low-affinity sites comprising 85 to 94% of the binding sites. DAT binding analyses revealed that self-administration of cocaine and a cocaine:heroin combination increased the affinity of the low-affinity site for the cocaine congener RTI-55 compared to saline. These results indicate that the alterations observed following chronic speedball self-administration are likely due to the cocaine component alone; thus further studies are necessary to elaborate upon the synergistic effect of cocaine:heroin combinations on the dopamine system in the NAc.
Active immunization is an effective means of blocking the pharmacodynamic effects of drugs and holds promise as a treatment for heroin addiction. Previously, we demonstrated the efficacy of our first-generation vaccine in blocking heroin self-administration in rats, however, many vaccine components can be modified to further improve performance. Herein we examine the effects of varying heroin vaccine injection route and adjuvant formulation. Mice immunized via subcutaneous (sc) injection exhibited inferior anti-heroin titers compared to intraperitoneal (ip) and sc/ip coadministration injection routes. Addition of TLR9 agonist cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) to the original alum adjuvant elicited superior antibody titers and opioid affinities compared to alum alone. To thoroughly assess vaccine efficacy, full dose–response curves were generated for heroin-induced analgesia in both hot plate and tail immersion tests. Mice treated with CpG ODN 1826 exhibited greatly shifted dose–response curves (10–13-fold vs unvaccinated controls) while non-CpG ODN vaccine groups did not exhibit the same robust effect (2–7-fold shift for ip and combo, 2–3-fold shift for sc). Our results suggest that CpG ODN 1826 is a highly potent adjuvant, and injection routes should be considered for development of small molecule–protein conjugate vaccines. Lastly, this study has established a new standard for assessing drugs of abuse vaccines, wherein a full dose–response curve should be performed in an appropriate behavioral task. PMID:24517171
Wu, Xian; Pang, Gang; Zhang, Yong-Mei; Li, Guangwu; Xu, Shengchun; Dong, Liuyi; Stackman, Robert W; Zhang, Gongliang
Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction.
Abbara, Aula; Brooks, Tim; Taylor, Graham P; Nolan, Marianne; Donaldson, Hugo; Manikon, Maribel; Holmes, Alison
Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) occur intermittently and require vigilance and rapid reporting of individual cases. Here, we give a firsthand account of the cases in London during an outbreak of heroin-associated anthrax during 2009-2010 in the United Kingdom. This new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. During 2012-13, additional cases of heroin-associated anthrax among PWIDs in England and other European countries were reported, suggesting that anthrax-contaminated heroin remains in circulation. Antibacterial drugs used for serious soft tissue infection are effective against anthrax, which may lead to substantial underrecognition of this novel illness. The outbreak in London provides a strong case for ongoing vigilance and the use of serologic testing in diagnosis and serologic surveillance schemes to determine and monitor the prevalence of anthrax exposure in the PWID community.
Abbara, Aula; Brooks, Tim; Taylor, Graham P.; Nolan, Marianne; Donaldson, Hugo; Manikon, Maribel
Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) occur intermittently and require vigilance and rapid reporting of individual cases. Here, we give a firsthand account of the cases in London during an outbreak of heroin-associated anthrax during 2009–2010 in the United Kingdom. This new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. During 2012–13, additional cases of heroin-associated anthrax among PWIDs in England and other European countries were reported, suggesting that anthrax-contaminated heroin remains in circulation. Antibacterial drugs used for serious soft tissue infection are effective against anthrax, which may lead to substantial underrecognition of this novel illness. The outbreak in London provides a strong case for ongoing vigilance and the use of serologic testing in diagnosis and serologic surveillance schemes to determine and monitor the prevalence of anthrax exposure in the PWID community. PMID:24959910
Darke, Shane; Williamson, Anna; Ross, Joanne; Mills, Katherine L; Havard, Alys; Teesson, Maree
To determine annual patterns and correlates of nonfatal heroin overdose across 3 years, data were analyzed on 387 heroin users recruited for the Australian Treatment Outcome Study (ATOS), interviewed at 12, 24, and 36 months. A heroin overdose across follow-up was reported by 18.6%, and naloxone had been administered to 11.9%. Annual rates of overdose declined between baseline and 12 months and then remained stable. Previous overdose experience was strongly related to subsequent overdose. Those with a history of overdose before ATOS were significantly more likely to overdose during the study period. In particular, there was a strong association between overdose experience in any 1 year and increased overdose risk in the subsequent year. This is the first study to examine long-term annual trends in nonfatal heroin overdose. While overdose rates declined after extensive treatment, substantial proportions continued to overdose in each year, and this was strongly associated with overdose history.
Cousins, Sarah J; Radfar, Seyed Ramin; Crèvecoeur-MacPhail, Desirée; Ang, Alfonso; Darfler, Kendall; Rawson, Richard A
Extended-release naltrexone (XR-NTX) is associated with an increased number of opioid-free days, improved adherence rates in substance use disorder treatment programs, and reduced cravings and drug-seeking behaviors. There is little evidence on the predictive associations between baseline characteristics of opioid-dependent patients and XR-NTX utilization. Some studies have demonstrated better pharmacotherapy adherence and/or retention rates among non-heroin opioid users compared to heroin users. This study examines predictive associations between characteristics of patients and XR-NTX utilization, as well as participants' urge to use opiates. Our findings suggest that XR-NTX may contribute to decreases in urges to use among both heroin and non-heroin opioid users. Non-heroin opioid users and heroin users were retained in XR-NTX treatment for comparable periods of time. However, those who identified as homeless, injected opioids (regardless of opioid-type), or were diagnosed with a mental illness were less likely to be retained in treatment with XR-NTX.
Klous, M G; Nuijen, B; van den Brink, W; van Ree, J M; Beijnen, J H
In 1998, two clinical trials were started in The Netherlands to evaluate the effect of coprescription of heroin and methadone on the mental and physical health and social functioning of chronic, treatment-resistant, heroin-dependent patients. Since 75-85% of the heroin addicts in The Netherlands use their heroin by "chasing the dragon," one of the two study arms concerned the coprescription of inhalable heroin. A pharmaceutical dosage form for inhalable heroin was developed for this trial, consisting of a 3:1 powder mixture of diacetylmorphine base and caffeine anhydrate. We describe the manufacturing process that was developed for filling sachets with this mixture in four dosages using a micro dose auger filler. In order to control product quality, in-process controls were developed to monitor the filling process and quality control tests were performed on the finished product. In-process control results have shown the filling process to be accurate and precise. The diacetylmorphine/caffeine sachets were shown to comply with the specifications for content and uniformity of mass. The finished product was found to be stable for 2 years when stored at 25 degrees C, 60% relative humidity and for 6 months when stored at 40 degrees C, 75% relative humidity.
Peavy, K Michelle; Banta-Green, Caleb J; Kingston, Susan; Hanrahan, Michael; Merrill, Joseph O; Coffin, Phillip O
The availability and diversion of prescription-type opioids increased dramatically in the first decade of the twenty-first century. One possible consequence of increased prescription opioid use and accessibility is the associated rise in opioid dependence, potentially resulting in heroin addiction. This study aimed to determine how common initial dependence on prescription-type opioids is among heroin injectors; associations with demographic and drug-using characteristics were also examined. Interview data were collected at syringe exchanges in King County, Washington in 2009. Among the respondents who had used heroin in the prior four months, 39% reported being "hooked on" prescription-type opioids first. Regression analysis indicated that younger age, sedative use and no recent crack use were independently associated with self-report of being hooked on prescription-type opioids prior to using heroin. These data quantify the phenomenon of being hooked on prescription-type opioids prior to initiating heroin use. Further research is needed to characterize the epidemiology, etiology and trajectory of prescription-type opioid and heroin use in the context of continuing widespread availability of prescription-type opioids.
Periodic public concern about heroin use has been a major driver of Australian drug policy in the four decades since heroin use was first reported. The number of heroin-dependent people in Australia has increased from several hundreds in the late 1960s to around 100,000 by the end of the 1990s. In this paper I do the following: (1) describe collaborative research on heroin dependence that was undertaken between 1991 and 2001 by researchers at the National Drug and Alcohol Research Centre; (2) discuss the contribution that this research may have made to the formulation of policies towards the treatment of heroin dependence during a period when the policy debate crystallized around the issue of whether or not Australia should conduct a controlled trial of heroin prescription; and (3) reflect on the relationships between research and policy-making in the addictions field, specifically on the roles of investigator-initiated and commissioned research, the interface between researchers, funders and policy-makers; and the need to be realistic about the likely impact of research on policy and practice.
Bogusz, M J; Maier, R D; Erkens, M; Kohls, U
The planned introduction of a prescription heroin program in Germany created a need for differentiation between non-prescription and prescribed diamorphine use. The following substances were chosen as markers of non-prescription heroin: acetylcodeine (AC); its metabolites codeine (C) and codeine 6-glucuronide (C6G); papaverine (P); and noscapine (N). Typical heroin markers diamorphine (DAM) and its metabolites monoacetylmorphine (MAM) and morphine (M) were also determined. The drugs were extracted from urine samples with solid-phase extraction (C18) using standard 200-mg columns and 96-well microplates (100 mg). The extracts were examined with liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (positive ionization) in two isocratic systems. Selected ion monitoring procedures were applied for protonated molecular masses and characteristic fragments of drugs involved. The limits of detection were in the range of 0.5-1 ng/mL urine. The occurrence of selected heroin markers was investigated in 25 urine samples collected from heroin abusers (road traffic offenders and overdosed patients). C6G was found in all samples, C in 24 samples, N in 22 samples, MAM in 16 samples, P in 14 samples, DAM in 12 samples, and AC in 4 samples. The appearance of these compounds in urine reflects their pharmacokinetic properties and the composition of non-prescription heroin.
Lutz, Pierre-Eric; Ayranci, Gulebru; Chu-Sin-Chung, Paul; Matifas, Audrey; Koebel, Pascale; Filliol, Dominique; Befort, Katia; Ouagazzal, Abdel-Mouttalib; Kieffer, Brigitte L
Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse. PMID:24874714
Zhou, Yan; Leri, Francesco; Cummins, Erin; Kreek, Mary Jeanne
Individual vulnerability to stress-induced relapse during abstinence from chronic heroin exposure is a key feature of opiate addiction, with limited studies on this topic. Arginine vasopressin (AVP) and its V1b receptor, components of the brain stress responsive systems, play a role in heroin-seeking behavior triggered by foot shock (FS) stress in rats. In this study, we tested whether individual differences in the FS-induced heroin-seeking were associated with alterations of AVP and V1b, as well as other stress responsive systems, including pro-opiomelanocortin (POMC), orexin, plasma ACTH and corticosterone, as well as dopamine D2 receptor (D2) and plasma prolactin. Sprague-Dawley rats were subjected to 3-hour intravenous heroin self-administration (SA) and then tested in extinction, and FS-induced and heroin priming-induced reinstatements. The rats that self-administered heroin were divided into high and low reinstatement responders induced by FS (H-RI; L-RI). Over SA sessions, both the H-RI and L-RI displayed similar active lever responding, heroin infusion and total heroin intake. Compared to the L-RI, however, the H-RI showed greater active lever responses during stress-induced reinstatement, with higher AVP mRNA levels in medial/basolateral amygdala and lower D2 mRNA levels in caudate putamen. However, heroin priming resulted in similar reinstatement in both groups and produced similarly low POMC and high orexin mRNA levels in hypothalamus. Our results indicate that: 1) enhanced amygdalar AVP and reduced striatal D2 expression may be related to individual vulnerability to stress-induced reinstatement of heroin- seeking; and 2) heroin abstinence-associated alterations of hypothalamic orexin and POMC expression may be involved in drug priming-induced heroin-seeking.
See, Ronald E
In brain regions that have been implicated in the reinstatement of drug-seeking, the prelimbic cortex has emerged as a critical regulator of relapse behaviours. Here, the effects of prelimbic cortex dopamine (DA) D(1) receptor antagonism on drug-seeking produced by heroin-paired cues, or by a single priming dose of heroin are examined. Rats lever-pressed daily for i.v. heroin discretely paired with a conditioned stimulus during 3-h sessions for a period of 2 wk, followed by extinction and reinstatement of drug-seeking by previously heroin-paired cues (tone+light) or heroin-priming injections (0.25 mg/kg) in the absence of heroin reinforcement. Intracranial infusion of the DA D(1) receptor antagonist, SCH 23390 (0.02-2.0 microg/side), into the prelimbic cortex potently and dose dependently attenuated heroin-seeking in response to either cue presentations or a priming dose of heroin. These results suggest that DA D1 receptors regulate prefrontal cortex pathways necessary for the reinstatement of heroin-seeking.
Odell, Luke R; Skopec, Jana; McCluskey, Adam
Tasmanian opium accounts for 25% of the world's legal supply of opium straw, and in 1998-99 sufficient numbers of flower pods (66,013) to manufacture ca 500 kg of heroin were stolen. Whilst the heroin signature program has been developed to determine the origin of heroin from other key producers, no such signature currently exists for Tasmanian derived heroin. Tasmanian poppies contain a unique alkaloid, oripavine, which is the source of 'marker' impurities in illicit heroin produced from Tasmanian poppy straw. Treatment of oripavine (500mg) under Thiboumery and Mohr heroin processing conditions, followed by simple evaporative workup afforded 613 mg of a dark orange residue, which upon extensive chromatographic purification yielded oripavine 3-acetate (2) 22 mg; 3-acetyl-N-acetyldesthebaine (3) 35 mg; 3-acetyl-6-methoxy-4,5-epoxyphenanthrene (4) 5.8 mg; 3,4-diacetyl-6-methoxyphenanthrene (5) 27 mg; and 3,4,6-methoxy-5-[2(N-methylacetamido)]ethylphenanthrene (6) 52 mg. Compounds (2-6) are derived from oripavine and are unique to heroin derived from the Tasmanian poppy Papaver somniferum N. Analysis of illicit heroin samples seized from Turkey, Pakistan, Columbia and Myanmar did not reveal any of the aforementioned marker compounds. We have, however, identified four of these marker compounds (3-6) in seized heroin samples from Australia suggesting that they are of Tasmanian origin. Complete details of the isolation and identification of these compounds are provided.
Xie, Pu; Wang, Tie-jie; Yin, Guo; Yan, Yan; Xiao, Li-he; Li, Qing; Bi, Kai-shun
Hair analysis is with the advantage of non-invasive collection and long surveillance window. The present study employed a sensitive and reliable liquid chromatography coupled with ion trap-time of flight mass spectrometry method to study the metabonomic characters in the hair of 58 heroin abusers and 72 non-heroin abusers. Results indicated that certain endogenous metabolites, such as sorbitol and cortisol, were accelerated, and the level of arachidonic acid, glutathione, linoleic acid, and myristic acid was decreased in hair of heroin abusers. The metabonomic study is helpful for further understanding of heroin addiction and clinical diagnosis.
Andersen, H S; Sestoft, D M; Lillebaek, T; Gabrielsen, G
Two groups of Danish prisoners on remand (in solitary confinement and not in solitary confinement) were examined by interview on reception (n = 133 & n = 95) in order to evaluate the prevalence and form of administration of opioid abuse/dependence. About 50% had abused opioids during their lifetime; one third were dependent at the time of reception. Twenty percent of opioid dependent prisoners administered opioids by smoking. More intravenous users were treated with methadone before and during imprisonment than those who were dependent on smoking opioids. Few were objectively suffering from withdrawal symptoms. The psycho-social impact of dependence on smoking heroin and intravenous heroin one month prior to imprisonment was at the same level and substantial as measured by the Global Assessment Scale.
Fischer, Benedikt; Oviedo-Joekes, Eugenia; Blanken, Peter; Haasen, Christian; Rehm, Jürgen; Schechter, Martin T; Strang, John; van den Brink, Wim
Since the initial Swiss heroin-assisted treatment (HAT) study conducted in the mid-1990s, several other jurisdictions in Europe and North America have implemented HAT trials. All of these studies embrace the same goal-investigating the utility of medical heroin prescribing for problematic opioid users-yet are distinct in various key details. This paper briefly reviews (initiated or completed) studies and their main parameters, including primary research objectives, design, target populations, outcome measures, current status and-where available-key results. We conclude this overview with some final observations on a decade of intensive HAT research in the jurisdictions examined, including the suggestion that there is a mounting onus on the realm of politics to translate the-largely positive-data from completed HAT science into corresponding policy and programming in order to expand effective treatment options for the high-risk population of illicit opioid users.
Maguet, Olivier; Majeed, Murtaza
Afghanistan has suffered decades of war, occupation and unrest. It is also the world's greatest producer of opium and drug production and trafficking account for a third of the total Afghan economy. Currently alongside the "War on Terrorism", the control and eradication of opium production and related trafficking is a main concern of the international community. However, this focus on supply reduction has meant scant attention has been paid to increasing drug use problems within the country; it is estimated there are up to 25,000 opium users and 20,000 heroin users in Kabul city. Drug use is often a response to war, poverty and under-development, however, street opium and heroin manufactured in the country are widely available, affordable and of high purity. This paper documents the efforts of non-governmental organisations to promote and develop harm reduction and treatment services for problem drug users in Afghanistan in this difficult context.
Arzumanov, Iu L; Abakumova, A A; Borisova, E V; Adamova, A V
Eighty patients with heroin addiction, aged from 15 to 20 years (most of them over the age of 16), were examined. The duration of illness was from 6 months to 3 years. The examination was conducted 2-3 weeks after arresting of withdrawal syndrome. In that period, patients had different mental disorders: depressive-dysphoric, neurosis-like, anxiety-hypochondriac, hysteriform and others. The aim of the examination was to find peculiarities of functioning of different cortical regions in the process of appraisal of conscious and unconscious stimuli using the method of visual evoked potentials with P300 recording. Stimuli were words highlighted on the screen--indifferent and potentially significant for a patient (e.g. heroin). The stimulus related to the dominating motivation caused in patients the higher diffuse cortical activation on the unconscious level compared to non-targeted stimuli.
Blanken, Peter; van den Brink, Wim; Hendriks, Vincent M; Huijsman, Ineke A; Klous, Marjolein G; Rook, Elisabeth J; Wakelin, Jennifer S; Barendrecht, Cas; Beijnen, Jos H; van Ree, Jan M
This monograph describes the history, findings and international context of heroin-assisted treatment (HAT) in the Netherlands. The monograph consists of (1) a short introduction and seven paragraphs describing the following aspects of HAT in the Netherlands: (2) history of HAT studies and implementation of routine HAT in the Netherlands; (3) main findings on efficacy, safety and cost-effectiveness from the two randomized controlled HAT trials in the Netherlands; (4) new findings from a large cohort study on the effectiveness of HAT in routine clinical practice in the Netherlands; (5) unique data on the patient's perspective of HAT; (6) data on the pharmacological and pharmaceutical basis for HAT in the Netherlands; (7) description of the registration process; and (8) account of the international context of HAT. Together, these data show that HAT can now be considered a safe and proven-effective intervention for the treatment of chronic, treatment-resistant heroin dependent patients.
Sedki, Firas; D'Cunha, Tracey; Shalev, Uri
In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during abstinence. Moreover, various environmental challenges can exacerbate this effect, as well as increase ongoing drug intake. The procedure we describe here highlights the impact of a common environmental challenge, food restriction, on drug craving that is expressed as an augmentation of drug seeking in abstinent rats. Rats are implanted with chronic intravenous i.v. catheters, and then trained to press a lever for i.v. heroin over a period of 10-12 days. Following the heroin self-administration phase the rats are removed from the operant conditioning chambers and housed in the animal care facility for a period of at least 14 days. While one group is maintained under unrestricted access to food (sated group), a second group (FDR group) is exposed to a mild food restriction regimen that results in their body weights maintained at 90% of their nonrestricted body weight. On day 14 of food restriction the rats are transferred back to the drug-training environment, and a drug-seeking test is run under extinction conditions (i.e. lever presses do not result in heroin delivery). The procedure presented here results in a highly robust augmentation of heroin seeking on test day in the food restricted rats. In addition, compared to the acute food deprivation manipulations we have used before, the current procedure is a more clinically relevant model for the impact of caloric restriction on drug seeking. Moreover, it might be closer to the human condition as the rats are not required to go through an extinction-training phase before the drug-seeking test, which is an integral component of the popular reinstatement procedure.
Holzmann, T; Frangoulidis, D; Simon, M; Noll, P; Schmoldt, S; Hanczaruk, M; Grass, G; Pregler, M; Sing, A; Hörmansdorfer, S; Bernard, H; Grunow, R; Zimmermann, R; Schneider-Brachert, W; Gessner, A; Reischl, U
Blood cultures from a heroin user who died in June 2012, a few hours after hospital admission, due to acute septic disease, revealed the presence of Bacillus anthracis. This report describes the extended diagnosis by MALDI-TOF and real-time PCR and rapid confirmation of the anthrax infection through reference laboratories. Physicians and diagnostic laboratories were informed and alerted efficiently through the reporting channels of German public health institutions, which is essential for the prevention of further cases.
Liu, Ting-ting; Epstein, David H.; Bao, Yan-Ping
Chinese herbal medicine has shown promise for heroin detoxification. This review extends a prior meta-analysis of Chinese herbal medicine for heroin detoxification, with particular attention to the time course of symptoms. Both English and Chinese databases were searched for randomized trials comparing Chinese herbal medicine to either α2-adrenergic agonists or opioid agonists for heroin detoxification. The methodological quality of each study was assessed with Jadad’s scale (1–2 = low; 3–5 = high). Meta-analysis was performed with fixed- or random-effect models in RevMan software; outcome measures assessed were withdrawal-symptoms score, anxiety, and adverse effects of treatment. Twenty-one studies (2,949 participants) were included. For withdrawal-symptoms score relieving during the 10-day observation, Chinese herbal medicine was superior to α2-adrenergic agonists in relieving opioid-withdrawal symptoms during 4–10 days (except D8) and no difference was found within the first 3 days. Compared with opioid agonists, Chinese herbal medicine was inferior during the first 3 days, but the difference became non-significant during days 4–9. Chinese herbal medicine has better effect on anxiety relieving at late stage of intervention than α2-adrenergic agonists, and no difference with opioid agonists. The incidence of some adverse effects (fatigue, dizziness) was significantly lower for Chinese herbal medicine than for α2-adrenergic agonists (sufficient data for comparison with opioid agonists were not available). Findings were robust to file-drawer effects. Our meta-analysis suggests that Chinese herbal medicine is an effective and safety treatment for heroin detoxification. And more work is needed to determine the specific effects of specific forms of Chinese herbal medicine. PMID:18584321
Morrow, R; Wong, B; Finkelstein, W E; Sternberg, S S; Armstrong, D
Aspergillosis of the cerebral ventricles developed in a 36-year-old heroin abuser who died during the sixth week of illness. The diagnosis was not made during life. A review of our case and of four previous cases from the literature indicates that aspergillosis should be considered in parenteral drug abusers with the syndrome of chronic meningitis or ventriculitis. The diagnosis is difficult to establish, but serologic tests may be helpful. This form of CNS aspergillosis can be cured with antifungal drugs.
Forty-four heroin dependence patients took detoxification treatment in Fukko-kai Tarumi Hospital from October 1998 to April 2008 (total of 80 admissions). Injectable formulation of buprenorphine (0.2 mg) was used intramuscularly to relieve withdrawal symptoms from October 2002. In the initial phase, small dosage of buprenorphine (0.4 mg per day) was dispensed but obvious effects were not confirmed. Therefore, the dosage was increased to 0.6 mg (3 ampoules), possibly more for 27 patients (total of 53 admissions) from October 2005. While treatment was interrupted by various reasons in 6 patients (total of 10 admissions), the rest completed detoxification. Dosage of buprenorphine given to the patients varied from 0.6 mg (3 ampoules) to 1.6 mg (8 ampoules) per day, and only 4 patients required over 1.0 mg. While duration of administration ranged from 5 days to 15 days, it was between 7 days and 10 days in over the half cases. When sufficient amount of buprenorphine was administered, severity and duration of heroin withdrawal symptoms was distinctly reduced. Since the introduction of heroin detoxification with buprenorphine, number of patients who request the treatment voluntarily increased including those who relapsed, but the length of hospital stay was shortened. One patient rejected buprenorphine injection for unknown reason and one patient left the hospital because of insufficient effect due to insufficient amount of buprenorphine dose, serious adverse effect was not observed. Detoxification treatment with buprenorphine cannot ensure sustained abstinence but can motivate heroin-using patients to receive treatment and strive for abstinence.
Lopez-Longo, F.J.; Monteagudo, I.; Vaquero, F.J.; Martinez Moreno, J.L.; Carreno, L.
A 20-year-old heroin user developed staphylococcus septic arthritis of the manubrium joint. The diagnosis was established by a culture of the infected tissue and blood culture. The clinical impression was aided by 99mTc radionuclide scintimetry. Early diagnosis localized the infection. Immediate antibiotic therapy solved a problem in the sternum that seems not to have been reported in the English literature.
Giugliano, D; Quatraro, A; Consoli, G; Stante, A; Simeone, V; Ceriello, A; Paolisso, G; Torella, R
Plasma glucose, insulin, C-peptide, glucagon and growth hormone responses to intravenous glucose were evaluated in 10 heroin addicts in the basal state and during an infusion of sodium salicylate, an inhibitor of endogenous prostaglandin synthesis. Ten normal subjects, matched for age, sex and weight served as controls. In the basal state, the heroin addicts had markedly reduced insulin responses to intravenous glucose and low glucose disappearance rates (p less than 0.01 vs controls). The infusion of sodium salicylate caused a striking increase of the acute insulin response to intravenous glucose (from 14.5 +/- 4 microU/ml to 88 +/- 11 microU/ml, p less than 0.001) and restored to normal the reduced glucose tolerance (KG from 1.10 +/- 0.1% min-1 to 2.04 +/- 0.19% min-1). Hypoglycemic values were found in all addicts at the end of the test during salicylate infusion. Indomethacin pretreatment in five additional addicts also caused normalization of the impaired insulin responses to the intravenous glucose challenge and restored to normal the reduced glucose disappearance rate. Plasma glucagon and growth hormone levels were normally suppressed by glucose in addicts in basal conditions; sodium salicylate infusion completely overturned these hormonal responses which became positive in the first 15 min following the glucose challenge. These results demonstrate that the two prostaglandin synthesis inhibitors can restore the impaired B-cell response to glucose in heroin addicts to normal, indicating that this response is not lost but is inhibited by heroin itself or by other substances, perhaps by the endogenous prostaglandins.
112. 17 D. C. Kay, R. B. Eisenstein and D. R. Jasinski, Morphine effects on human REM state, waking state, and NREM sleep . Psychopharmacologia, 14...recording days. The EEG state data showed an increase in waking and decrease in both slow wave and REM sleep during acute heroin withdrawal. Total sleep ...was maximally suppressed on withdrawal days 2 and 3 and was still below normal control values on with- drawal days 5 - 7. REM sleep was more
Weiss, Linda; Gass, Jonathon; Egan, James E.; Ompad, Danielle C.; Trezza, Claudia; Vlahov, David
Background There is abundant literature describing heroin initiation, co-morbidities, and treatment. Few studies focus on cessation, examining the factors that motivate and facilitate it. Methods The CHANGE study utilized mixed methods to investigate heroin cessation among low-income New York City participants. This paper describes findings from qualitative interviews with 20 former and 11 current heroin users. Interviews focused on background and current activities, supports, drug history, cessation attempts, and motivators and facilitators to cessation. Results Participants found motivation for cessation in improved quality of life; combination of treatment, strategic avoidance of triggers, and engagement in alternative activities, including support groups, exercise, and faith-based practice. Several reported that progress toward goals served as motivators that increased confidence and facilitated cessation. Ultimatums were key motivators for some participants. Beyond that, they could not articulate factors that distinguished successful from unsuccessful cessation attempts, although data suggest that those who were successful could describe more individualized and concrete—rather than general—motivators and strategies. Conclusions Our findings indicate that cessation may be facilitated by multifaceted and individualized strategies, suggesting a need for personal and comprehensive approaches to treatment. PMID:25052788
Nettleton, Sarah; Neale, Joanne; Pickering, Lucy
Research that has explored the lives of men and women recovering from heroin addiction has reported that users often claim that they 'just want to be normal'. Working within a Foucauldian tradition, we argue in this article that the notions of 'governmentality' and the 'norm' are especially apposite to understanding the ubiquity of this aspiration. Here we focus not on the formal institutions of governance that encourage individuals to adhere to social, cultural and political norms, but rather seek to explore recovering users' accounts of normality as they are envisaged and expressed. The reported empirical data were generated from interviews with 40 men and women in England at various stages of recovery from heroin use. The analytic focus is upon the accounts of normality articulated during the interviews in order to identify the ways in which being normal is presented by the participants. In keeping with the methodological tradition of discourse analysis we identify six discursive repertoires of 'normality talk' that transcend the accounts. It is concluded that the negotiation of normality is a precarious route for this social group. Articulations of a desire to be normal are replete with tensions; there are expressions of both resistance and resignation. Despite claims by some contemporary social theorists that diversity is the 'new normality', the accepted bounds of 'difference' are limited for those who have been addicted to heroin.
Grigson, P S; Twining, R C; Carelli, R M
Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with an aversive unconditioned stimulus such as lithium chloride. This phenomenon is referred to as a conditioned taste aversion (CTA). Rats also suppress intake of a saccharin CS when paired with a rewarding sucrose solution and when paired with a drug of abuse. Although the suppressive effects of drugs of abuse have long been interpreted as CTAs, evidence suggests that rats may suppress intake of the saccharin CS following taste-drug pairings because they are anticipating the rewarding rather than the aversive properties of the drug. Oddly, however, while all other drugs of abuse tested suppress intake of a gustatory CS, the highly reinforcing drug, heroin, is reportedly ineffective. The present study reexamined this issue in both water-deprived and water-replete rats using procedures that sustain both morphine- and cocaine-induced suppression of CS intake. The results showed that heroin greatly reduced CS intake following saccharin-heroin pairings and that this effect was less variable when assessed in water-replete subjects. When taken with other reports, these data suggest that rats suppress intake of a saccharin CS in anticipation of the availability of all drugs of abuse tested.
Qiao, Xiaomeng; Yin, Fangyuan; Guo, Hao; Huang, Xin; Lai, Jianghua; Wei, Shuguang
Recent studies have shown that variants in FAT atypical cadherin 3 (FAT3), kinectin 1 (KTN1), discs large homolog2 (DLG2) and deleted in colorectal cancer (DCC) genes influence the structure of the human mesolimbic reward system. We conducted a systematic analysis of the potential functional single nucleotide polymorphisms (SNPs) in these genes associated with heroin addiction. We scanned the functional regions of these genes and identified 20 SNPs for genotyping by using the SNaPshot method. A total of 1080 samples, comprising 523 cases and 557 controls, were analyzed. We observed that DCC rs16956878, rs12607853, and rs2292043 were associated with heroin addiction. The T alleles of rs16956878 (p = 0.0004) and rs12607853 (p = 0.002) were significantly enriched in the case group compared with the controls. A lower incidence of the C allele of rs2292043 (p = 0.002) was observed in the case group. In block 2 of DCC (rs2292043-rs12607853-rs16956878), the frequency of the T-T-T haplotype was significantly higher in the case group than in the control group (p = 0.024), and fewer C-C-C haplotypes (p = 0.006) were detected in the case group. DCC may be an important candidate gene in heroin addiction, and rs16956878, rs12607853, and rs2292043 may be risk factors, thereby providing a basis for further genetic and biological research. PMID:27676367
Li, Fuying; Cheng, Kejun; Antoline, Joshua F. G.; Iyer, Malliga R.; Matyas, Gary R.; Torres, Oscar B.; Jalah, Rashmi; Beck, Zoltan; Alving, Carl R.; Parrish, Damon A.; Deschamps, Jeffrey R.; Jacobson, Arthur E.; Rice, Kenner C.
Three haptens have been synthesized with linkers for attachment to carrier macromolecules at either the piperidino-nitrogen or via an introduced 3-amino group. Two of the haptens, with a 2-oxopropyl functionality at either C6, or at both the C3 and C6 positions on the 4,5-epoxymorphinan framework, as well as the third hapten (DiAmHap) with diamido moieties at both the C3 and C6 positions, should be much more stable in solution, or in vivo in a vaccine, than a hapten with an ester in one of those positions, as found in many heroin-based haptens. A “classical” opioid synthetic scheme enabled the formation of a 3-amino-4,5-epoxymorphinan which could not be obtained using palladium chemistry. Our vaccines are aimed at the reduction of the abuse of heroin and, as well, at the reduction of the effects of its predominant metabolites, 6-acteylmorphine and morphine. One of the haptens, DiAmHap, has given interesting results in a heroin vaccine and is clearly more suited for the purpose than the other two haptens. PMID:24995943
Kellogg, Scott; Melia, Dorothy; Khuri, Elizabeth; Lin, Amy; Ho, Ann; Kreek, Mary Jeanne
This study examined the impact of methadone maintenance treatment on an inclusive group of adolescent and young adult opiate-dependent patients, ages 15-23, admitted over a 6-year period, during their first year in the program. Retention in treatment was the primary outcome variable, and at 12 months, 48% were still in treatment. The findings were: (a) a stepwise discriminant function analysis revealed that patients who consistently used heroin were at a greater risk of leaving treatment within the first 12 months; (b) the use of cocaine was an indicator of higher levels of heroin use in those who reached the one-year mark; (c) among patients who stayed in treatment for one year, there was a significant reduction in heroin use, a trend toward a reduction in cocaine use, and no significant impact on benzodiazepine use; and (d) the group that stayed in treatment was slightly younger than the group that left before the first year ended. There were no gender or ethnic differences between the two groups. Suggestions for interventions that might improve treatment outcome are presented.
Klous, Marjolein G; Lee, WeiChing; Hillebrand, Michel J X; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H
Pharmaceutical smokable heroin was developed for a clinical trial on medical co-prescription of heroin and methadone. This product, consisting of 75% w/w diacetylmorphine base and 25% w/w caffeine anhydrate, was intended for use via "chasing the dragon", that is, inhalation after volatilization. This procedure involves heating the powder mixture, which may lead to formation of degradation products that could subsequently be inhaled. We developed a method that used a high-performance liquid chromatography system that was compatible with photodiode-array detection and mass spectrometric detection to separate diacetylmorphine- and caffeine-related compounds in a wide polarity range for analysis of the vapor. This method was used to analyze the contents of the plastic drinking straws that were used by patients to inhale the vapors from pharmaceutical heroin used via chasing the dragon, which were considered to be representative of the vapors the patients inhaled. They contained primarily unchanged diacetylmorphine, its main metabolite 6-acetylmorphine, caffeine, and some morphine. Several unidentified peaks were observed in the straw chromatograms. Chemical structures were proposed for nine degradation products: morphine derivatives with different substitution patterns of the C(3), C(6), and/or N(17) positions, which comprised 0.4-9.7% of the straw sample residue weight. Activity and toxicity of most of these compounds are unknown and require further investigation.
Vatury, Ori; Barg, Jacob; Slotkin, Theodore A; Yanai, Joseph
Prenatal heroin exposure disrupts hippocampal cholinergic synaptic function and related behaviors. Biochemical studies indicate an increase in the number of presynaptic high-affinity choline transporter (HACT) sites, as assessed by [3H]hemicholinium-3 (HC-3) binding. The present study was designed to assess whether this effect involves global upregulation of the transporter, or whether disruption occurs with a specific tempero-spatial distribution. Pregnant mice were given 10mg/kg per day of heroin subcutaneously on gestational days (GD) 9-18. Autoradiographic distribution of HC-3 binding sites was evaluated in the hippocampus of the offspring at postnatal days 15, 25, and 53. These results, suggestive of hippocampal "miswiring," are likely to explain the net impairment of cholinergic synaptic function after prenatal heroin exposure, despite the simultaneous upregulation of both presynaptic cholinergic activity and postsynaptic receptors. Understanding the subregional selectivity of hippocampal defects can lead to the development of strategies that may potentially enable therapeutic interventions to offset or reverse the neurobehavioral defects.
Doran, C M; Shanahan, M; Bell, J; Gibson, A
The purpose of this study was to conduct a cost-effectiveness analysis of detoxification from heroin using buprenorphine in a specialist clinic versus a shared care setting. A randomized controlled trial was conducted with a total of 115 heroin-dependent patients receiving a 5-day treatment regime of buprenorphine. The specialist clinic was a community-based treatment agency in inner-city Sydney. Shared care involved treatment by a general practitioner supplemented by weekend dispensing and some concurrent counselling at the specialist clinic. Quantification of resource use was limited to inputs for treatment provision. The primary outcome measure used in the economic analysis was the proportion of each group that completed detoxification and achieved an initial 7-day period of abstinence. Buprenorphine detoxification in the shared care setting was estimated to be 24 dollars more expensive per patient than treatment at the clinic, which had an average treatment cost of 332 dollars per patient. Twenty-three per cent of the shared care patients and 22% of the clinic patients reported no opiate use during the withdrawal period. These results suggest that the provision of buprenorphine treatment for heroin dependence in shared care and clinic appear to be equally cost-effective.
Gerasimov, M R; Ashby, C R; Gardner, E L; Mills, M J; Brodie, J D; Dewey, S L
We examined the acute effect of the irreversible GABA-transaminase inhibitor, gamma-vinyl GABA (GVG, Sabril((R)), Vigabatrin((R))) on increases in nucleus accumbens (NAc) dopamine (DA) following acute administration of methamphetamine, heroin, or ethanol. Methamphetamine (2.5 mg/kg) produced a dose-dependent increase (2, 700%) in NAc DA. GVG preadministration (300 or 600 mg/kg), however, inhibited this response by approximately 39 and 61%, respectively. The lower dose of methamphetamine (1.25 mg/kg), increased DA by 1, 700%. This response was inhibited to a similar extent (44%) regardless of the GVG dose preadministered (300 or 600 mg/kg). In addition, heroin-induced increases in NAc DA (0.5 mg/kg, 170%) were inhibited or completely abolished by GVG (150 or 300 mg/kg, 65 and 100%, respectively). Finally, at half the dose necessary for heroin, GVG (150 mg/kg) also completely abolished ethanol-induced increases in NAc DA following a 0.25 g/kg challenge dose (140%). Taken with our previous findings using nicotine or cocaine as the challenge drug, these results indicate that GVG attenuates increases in NAc DA by a mechanism common to many drugs of abuse. However, it appears unlikely that an acute dose of GVG can completely inhibit increases in NAc DA following challenges with a drug whose mechanism of action is mediated primarily through the DA reuptake site.
Xu, Limin; Hong, Qingxiao; Chen, Xiaoying; Xu, Xuting; Liu, Huifen; Zhou, Wenhua; Duan, Shiwei
Diacetylmorphine hydrochloride (heroin) addiction is a chronic relapsing brain disorder that is a heavy public health burden worldwide. Brm/SWI2-related gene-1 (BRG1) is a tumor suppressor gene that can influence embryogenesis and the development of the cerebellum. The current study aimed to investigate the effect of histone H4 lysine 5 (H4K5) modifications on the BRG1 gene in brain tissue of the ventral tegmental area (VTA) of heroin-addicted rats. A total of 21 male Sprague Dawley rats were raised in a standard manner and underwent heroin self-administration training. Rats were randomly divided into three equal groups: Group A, self-administered delivery of heroin; group B, yoked delivery of heroin; and group C, yoked delivery of saline. The VTA was harvested and subjected to chromatin immunoprecipitation (ChIP) analysis. Gene expression was evaluated by quantitative polymerase chain reaction. We calculated the recovery rate, which indicated the percentage of the total input BRG1 recovered by ChIP. Our results showed that BRG1 was less associated with H4K5 histone modification in the group of rats that underwent heroin self-administration than in the other two groups (A vs. B, P=0.031; A vs. C, P=0.067). The recovery fold changes of the self-administration group and the passive-administration group were significantly different from those of the group with yoked saline (A vs. C, P=0.013; B vs. C, P=0.009; A vs. B, P=0.731). The results of the current study demonstrated that H4K5 histone acetylation of BRG1 in the VTA may be associated with heroin administration, but not addiction.
Xu, Limin; Hong, Qingxiao; Chen, Xiaoying; Xu, Xuting; Liu, Huifen; Zhou, Wenhua; Duan, Shiwei
Diacetylmorphine hydrochloride (heroin) addiction is a chronic relapsing brain disorder that is a heavy public health burden worldwide. Brm/SWI2-related gene-1 (BRG1) is a tumor suppressor gene that can influence embryogenesis and the development of the cerebellum. The current study aimed to investigate the effect of histone H4 lysine 5 (H4K5) modifications on the BRG1 gene in brain tissue of the ventral tegmental area (VTA) of heroin-addicted rats. A total of 21 male Sprague Dawley rats were raised in a standard manner and underwent heroin self-administration training. Rats were randomly divided into three equal groups: Group A, self-administered delivery of heroin; group B, yoked delivery of heroin; and group C, yoked delivery of saline. The VTA was harvested and subjected to chromatin immunoprecipitation (ChIP) analysis. Gene expression was evaluated by quantitative polymerase chain reaction. We calculated the recovery rate, which indicated the percentage of the total input BRG1 recovered by ChIP. Our results showed that BRG1 was less associated with H4K5 histone modification in the group of rats that underwent heroin self-administration than in the other two groups (A vs. B, P=0.031; A vs. C, P=0.067). The recovery fold changes of the self-administration group and the passive-administration group were significantly different from those of the group with yoked saline (A vs. C, P=0.013; B vs. C, P=0.009; A vs. B, P=0.731). The results of the current study demonstrated that H4K5 histone acetylation of BRG1 in the VTA may be associated with heroin administration, but not addiction. PMID:27588112
Perez de Los Cobos, Jose; Trujols, Joan; Siñol, Núria; Duran-Sindreu, Santiago; Batlle, Francesca
Methadone maintenance treatment (MMT) has long been used to treat heroin-dependent patients. However, satisfaction with methadone in this patient population is unknown. The aim of this cross-sectional case-control study was to evaluate satisfaction with methadone in heroin-dependent patients with current substance use disorders (SUDs). Cases included 152 methadone-maintained patients with current SUD, requiring inpatient detoxification treatment, and controls included 33 methadone-maintained patients in sustained full remission for SUD. Satisfaction with methadone as a medication to treat heroin addiction was measured by using the Scale to Assess Satisfaction with Medications for Addiction Treatment-methadone for heroin addiction (SASMAT-METHER). The SASMAT-METHER subscales assess the following domains: personal functioning and well-being, antiaddictive effect on heroin, and antiaddictive effect on other substances. Compared with patients with remitted SUD, patients with current SUD scored lower on all SASMAT-METHER assessments. In such patients, overall SASMAT-METHER scores were independently and negatively associated with downward desired adjustment of methadone dose and days of heroin use during last month; although various sets of factors were independently associated with each of the SASMAT-METHER subscales, the only determinant of dissatisfaction on all subscales was the desire for downward adjustment of methadone dose. In summary, MMT patients with current SUD are less satisfied with methadone than MMT patients with remitted SUD. In patients with current SUD, downward desired adjustment of methadone dose and days of heroin use during last month are independently associated with overall dissatisfaction with methadone.
Hemby, S E; Co, C; Dworkin, S I; Smith, J E
The abuse of cocaine/opiate combinations (speedball) represents a growing trend in illicit drug use. Delineation of neurobiological substrates mediating the reinforcing effects of the combination may increase our knowledge of reinforcement mechanisms and provide useful new information for the development of pharmacotherapies. Several studies suggest dopaminergic innervations of the nucleus accumbens (NAc) have a central role in the brain processes underlying drug reinforcement. The present study was undertaken to determine the relationship between the self-administration of cocaine/heroin combinations and NAc extracellular dopamine concentrations ([DA]e) using in vivo microdialysis and microbore high-pressure liquid chromatography. Rats were assigned randomly to one of three groups to self-administer i.v. cocaine (125, 250, and 500 micrograms/infusion; n = 5), heroin (4.5, 9, and 18 micrograms/infusion; n = 5), or cocaine/heroin combinations (125/4.5; 250/9, and 500/18 micrograms/infusion; n = 4) under a fixed ratio (FR) 10: 20-s time-out schedule of reinforcement/multicomponent dosing session. After stable rates of responding were engendered and maintained, microdialysis samples were collected in 10-min intervals during the self-administration session. Self-administration of cocaine/heroin combinations produced synergisitic elevations in NAc [DA]e (1000% baseline) compared with cocaine (400% baseline) and heroin (not significantly different from baseline levels). Neither the number of infusions nor the interinfusion intervals was significantly different between the groups across the self-administration session. Moreover, cocaine concentrations were not significantly different between the cocaine and cocaine/heroin groups. These results demonstrate that heroin interacts with cocaine to produce synergistic elevations in [DA]e, providing a neurochemical basis for understanding the abuse liability of cocaine/opiate combinations.
Zhang, Yong; Picetti, Roberto; Butelman, Eduardo R; Ho, Ann; Blendy, Julie A; Kreek, Mary Jeanne
Mu-opioid receptors (MOPRs) are the target of heroin and other prescription opioids, which are currently responsible for massive addiction morbidity in the US. The gene coding for the human MOPR (OPRM1) has an important functional single nucleotide polymorphism (SNP), A118G. The OPRM1 A118G genotype results in substantially increased risk of heroin addiction in humans; however, the neurobiological mechanism for this increased risk is not fully understood. This study examined heroin self-administration (SA) behavior in A112G (G/G) mice, harboring a functionally equivalent SNP in Oprm1 with a similar amino acid substitution, in extended (4 h) SA sessions. Adult male and female G/G mice and 'wild-type' litter mates (A/A) were allowed to self-administer heroin (0.25 mg/kg/unit dose, FR1 with a nose poke response) for 4 h/day, for 10 consecutive days. Half of the mice then continued in a heroin dose-response study, while extinction from heroin SA was studied in the other half. In vivo microdialysis was used to measure acute heroin-induced increases of striatal dopamine in the GG vs AA genotypes. Male and female G/G mice responded for heroin significantly more (and thus had greater intake) than A/A mice, in the initial 10 days of heroin SA, and in the subsequent dose-response study. There were no significant differences in extinction of SA between the A/A and G/G mice. Heroin-induced increases in striatal dopamine levels are higher in the GG mice than in the AA mice. Both male and female G/G mice self-administered more heroin than did A/A mice over a 10-day period, possibly because of the greater increases of heroin-induced striatal dopamine in the GG mice. Furthermore, G/G male mice escalated the amount of heroin self-administration across 10 extended-access sessions more than A/A male mice did. These are the first studies to examine the acquisition of heroin SA in this mouse model. These studies may lead to a better understanding of the neurobiological and behavioral
Pan, Ying-Xian; Xu, Jin; Xu, Mingming; Rossi, Grace C; Matulonis, Joshua E; Pasternak, Gavril W
Heroin remains a major drug of abuse and is preferred by addicts over morphine. Like morphine, heroin has high affinity and selectivity for mu-receptors, but its residual analgesia in exon 1 MOR-1 knockout mice that do not respond to morphine suggests a different mechanism of action. MOR-1 splice variants lacking exon 1 have been observed in mice, humans, and rats, raising the possibility that they might be responsible for the residual heroin and morphine-6beta-glucuronide (M6G) analgesia in the exon 1 knockout mice. To test this possibility, we disrupted exon 11 of MOR-1, which eliminates all of the variants that do not contain exon 1. Morphine and methadone analgesia in the exon 11 knockout mouse was normal, but the analgesic actions of heroin, M6G, and fentanyl were markedly diminished in the radiant heat tail-flick and hot-plate assays. Similarly, the ability of M6G to inhibit gastrointestinal transit was greatly diminished in these exon 11 knockout mice, whereas the ability of morphine was unchanged. These findings identify receptors selectively involved with heroin and M6G actions and confirm the relevance of the exon 11-associated variants and raise important issues regarding the importance of atypical truncated G-protein-coupled receptors.
Dubois, Nathalie; Hallet, Claude; Seidel, Laurence; Demaret, Isabelle; Luppens, David; Ansseau, Marc; Rozet, Eric; Albert, Adelin; Hubert, Philippe; Charlier, Corinne
To develop a model for estimating the time delay between last heroin consumption and blood sampling in chronic drug users. Eleven patients, all heroin inhalers undergoing detoxification, were included in the study. Several plasma samples were collected during the detoxification procedure and analyzed for the heroin metabolites 6-acetylmorphine (6AM), morphine (MOR), morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), according to a UHPLC/MSMS method. The general linear mixed model was applied to time-related concentrations and a pragmatic four-step delay estimation approach was proposed based on the simultaneous presence of metabolites in plasma. Validation of the model was carried out using the jackknife technique on the 11 patients, and on a group of 7 test patients. Quadratic equations were derived for all metabolites except 6AM. The interval delay estimation was 2-4 days when only M3G present in plasma, 1-2 days when M6G and M3G were both present, 0-1 day when MOR, M6G and M3G were present and <2 h for all metabolites present. The 'jackknife' correlation between declared and actual estimated delays was 0.90. The overall precision of the delay estimates was 8-9 h. The delay between last heroin consumption and blood sampling in chronic drug users can be satisfactorily predicted from plasma heroin metabolites.
Zou, Feng; Wu, Xinhuai; Zhai, Tianye; Lei, Yu; Shao, Yongcong; Jin, Xiao; Tan, Shuwen; Wu, Bing; Wang, Lubin; Yang, Zheng
Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross-sectional study, whole-brain resting-state functional magnetic resonance images (8 min) were collected from 30 heroin-addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting-state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse-related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin-dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long-term-abstinent heroin-dependent individuals.
Nielsen, Suzanne; Hillhouse, Maureen; Mooney, Larissa; Ang, Alfonso; Ling, Walter
Most research examining buprenorphine has been conducted with heroin users. Few studies have examined buprenorphine pharmacotherapy for prescription opioid users. Data were from a randomized controlled trial of behavioral treatment provided for 16weeks on a platform of buprenorphine pharmacotherapy and medication management. We compared heroin (H, n=54), prescription opioid (PO, n=54) and combination heroin+prescription opioid (POH, n=71) users to test the hypothesis that PO users will have better treatment outcomes compared with heroin users. The PO group provided more opioid-negative urine drug screens over the combined treatment period (PO:70%, POH:40%, H:38%, p<0.001) and at the end of the combined treatment period (PO:65%, POH:31%, H:33%, p<0.001). Retention was lowest in the H group (PO:80%, POH:65%, H:57%, p=0.039). There was no significant difference in buprenorphine dose between the groups. PO users appear to have better outcomes in buprenorphine pharmacotherapy compared to those reporting any heroin use, confirming that buprenorphine pharmacotherapy is effective in PO users.
Hu, Airong; Lai, Miaojun; Wei, Jianzi; Wang, Lina; Mao, Huijuan; Zhou, Wenhua; Liu, Sheng
Augmentation of extinction with learning enhancing therapy may offer an effective strategy to combat heroin relapse. Our lab previously found that electroacupuncture (EA) not only significantly reduced cue-induced reinstatement of heroin seeking but also exhibited a promoting effect on the ability of learning and memory. In the present study, we further investigated the effects of EA on the extinction of heroin-seeking behavior in rats with a history of intravenous heroin self-administration. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4h or 25 infusions for 14 consecutive days; then the rats underwent 7 daily 3h extinction sessions in the operant chamber. To assess EA's effects on the extinction response of heroin-associated cues, 2Hz EA was administered 1h before each of the 7 extinction sessions. We also applied immunohistochemistry to detect FosB-positive nuclei in the nucleus accumbens core. We found that EA treatment facilitated the extinction response of heroin seeking but did not alter the locomotor activity in an open field testing environment. EA stimulation attenuated the FosB expression in the core of the nucleus accumbens, a brain region involved in the learning and execution of motor responses. Altogether, these results suggest that EA may provide a novel nonpharmacological approach to enhance extinction learning when combined with extinction therapy for the treatment of heroin addiction.
Andersen, Jannike M; Haugen, Karianne S; Ripel, Ase; Mørland, Jørg
It has been suggested that the potentiating effect observed in human beings when combining alcohol and heroin may be due to an interference of ethanol with the pharmacokinetics of heroin, leading to accumulation of the biologically active metabolites, 6-monoacetylmorphine (6MAM) and morphine. However, experimental evidence for this hypothesis is lacking. In this study, we used mice and examined the effect of ethanol on the metabolism of heroin by combining a locomotor activity test, which is a behaviour model representative of psychomotor stimulation, with pharmacokinetic studies in blood and brain tissue. Pre-treatment with ethanol (1 and 2.5 g/kg, po) affected heroin-stimulated (2.5 and 15 μmol/kg, sc) locomotor activation significantly, resulting in a dose-dependent reduction in run distance. However, the change in the activity profiles did not indicate any increase in the concentration of active metabolites. Pharmacokinetic studies in blood and brain supported the behavioural findings, showing no change in the time-versus-concentration curves of either 6MAM or morphine after administration of heroin (15 μmol/kg, sc) to mice pre-treated with ethanol (2.5 g/kg, po). The concentration of heroin itself was elevated, but is probably of minor importance because heroin has low biological activity by itself. The in vivo pharmacokinetic findings were supported by experiments in vitro. In conclusion, studies in mice do not support the hypothesis from epidemiological studies of a pharmacokinetic interaction between alcohol and heroin.
Patrick, Julie C.; Orzechowska, Grazyna E.; Poziomek, Edward J.
Technological challenges in the development and testing of illicit narcotics include assuring safety of researchers and operations personnel from drug exposure, assessing the efficiency of sampling and sample handling, checking for artifacts introduced by field procedures, and maintaining quality control/quality assurance. The dye methylene blue was chosen as a simulant for cocaine HCl and heroin HCl. The similarities include the presence of fused ring systems, molecular weights over 300 g/mol, and melting points between 200 and 300 degrees C. A significant difference is that methylene blue has a much lower solubility in water than cocaine HCl and heroin HCl. Experiments have been conducted to successfully increase the solubility of the simulant to match those of cocaine HCl and heroin HCl by adding solidum methyl sulfate.
Behnam, Behnaz; Semnani, Vahid; Saghafi, Nadia; Ghorbani, Raheb; Dianak Shori, Mina; Ghooshchian Choobmasjedi, Samaneh
Gabapentin seems to be a safe and well tolerated medication for treating heroine dependence. This study examined the efficacy of gabapentin for relieving withdrawal-related pain due to heroin use. Sixty men were recruited from an inpatient psychiatric ward of Fatemieh hospital in Semnan and randomized to receive either placebo (n = 30) or gabapentin (1800 mg/day) (n = 30) for 7 days. Subjective Opioid Withdrawal Scale (SOWS) was measured as a self-administered scale for grading body pain at baseline, and on days 1, 2, 3, 4, 6, and 7. Mean of pain score had a significant decrease trend in both gabapentin and placebo groups. Pain severity during the most of detoxification duration was significantly lower in gabapentin group compared with the placebo group. It is suggested that gabapentin may have an effective role in removing heroin withdrawal-related pain.
Gerra, G; Maremmani, I; Capovani, B; Somaini, L; Berterame, S; Tomas-Rossello, J; Saenz, E; Busse, A; Kleber, H
Many studies have documented the safety, efficacy, and effectiveness of long-acting opioids (L-AOs), such as methadone and buprenorphine, in the treatment of heroin addiction. This article reviews the pharmacological differences between L-AO medications and short-acting opioids (heroin) in terms of reinforcing properties, pharmacokinetics, effects on the endocrine and immune systems. Given their specific pharmacological profile, L-AOs contribute to control addictive behavior, reduce craving, and restore the balance of disrupted endocrine function. The use of the term "substitution," referring to the fact that methadone or buprenorphine replace heroin in binding to brain opioid receptors, has been generalized to consider L-AOs as simple replacement of street drugs, thus contributing to the widespread misunderstanding of this treatment approach.
Su, Hang; Li, Zhibin; Du, Jiang; Jiang, Haifeng; Chen, Zhikang; Sun, Haiming; Zhao, Min
Relapse is a typical feature of heroin addiction and rooted in genetic and psychological determinants. The aim of this study was to evaluate the effect of personality traits, impulsivity, and COMT gene polymorphism (rs4680) on relapse to heroin use during 5-year follow up. 564 heroin dependent patients were enrolled in compulsory drug rehabilitation center. 12 months prior to their release, personality traits were measured by BIS-11 (Barratt Impulsiveness Scale-11) and Temperament and Character Inventory (TCI). The COMT gene rs4680 polymorphism was genotyped using a DNA sequence detection system. The heroin use status was evaluated for 5 years after discharged. Among the 564 heroin-dependent patients, 500 were followed for 5 years after discharge and 53.0% (n = 265) were considered as relapsed to heroin use according to a strict monitor system. Univariate analysis showed that age, having ever been in methadone maintenance treatment (MMT), the total scores and non-planning scores of BIS-11, and the COMT rs4680 gene variants were different between relapse and abstinent groups. Logistic regression analysis showed higher BIS total score, having ever been in MMT and younger first heroin use age are the predictors of relapse to heroin use during 5 years follow-up, and the COMT rs4680 gene had an interaction with BIS scores. Our findings indicated that the impulsive personality traits, methadone use history, and onset age could predict relapse in heroin-dependent patients during 5 year's follow up. The COMT gene showed a moderational effect in part the relationship of impulsivity with heroin relapse.
Lopez-Quintero, Catalina; Roth, Kimberly B.; Eaton, William W.; Wu, Li-Tzy; Cottler, Linda B.; Bruce, Martha; Anthony, James C.
Background In contrast to research on more restricted samples of drug users, epidemiological studies open up a view of death rates and survivorship of those who have tried heroin a few times, with no acceleration toward sustained use patterns often seen in treatment and criminal justice samples. At their best, epidemiological estimates of heroin effects on risk of dying are not subject to serious selection biases faced with more restricted samples. Methods Data are from 7207 adult participants aged 18–48 years in United States Epidemiologic Catchment Area Program field surveys, launched in 1980–1984. US National Death Index (NDI) records through 2007 disclosed 723 deaths. NDI enabled estimation of heroin-associated risk of dying as well as survivorship. Results Estimated cumulative mortality for all 18–48 year old participants is 3.9 deaths per 1000 person-years (95% confidence interval, CI = 3.7, 4.2), relative to 12.4 deaths per 1000 person-years for heroin users (95% CI = 8.7, 17.9). Heroin use, even when non-sustained, predicted a 3–4 fold excess of risk of dying prematurely. Post-estimation record review showed trauma and infections as top-ranked causes of these deaths. Conclusions Drawing strengths from epidemiological sampling, standardized baseline heroin history assessments, and very long-term NDI follow-up, this study of community-dwelling heroin users may help clinicians and public health officials who need facts about heroin when they seek to prevent and control heroin outbreaks. Heroin use, even when sporadic or non-sustained, is predictive of premature death in the US, with expected causes of death such as trauma and infections. PMID:26386826
Li, Qiang; Li, Wei; Wang, Hanyue; Wang, Yarong; Zhang, Yi; Zhu, Jia; Zheng, Ying; Zhang, Dongsheng; Wang, Lina; Li, Yongbin; Yan, Xuejiao; Chang, Haifeng; Fan, Min; Li, Zhe; Tian, Jie; Gold, Mark S; Wang, Wei; Liu, Yijun
Abnormal salience attribution is implicated in heroin addiction. Previously, combining functional magnetic resonance imaging (fMRI) and a drug cue-reactivity task, we demonstrated abnormal patterns of subjective response and brain reactivity in heroin-dependent individuals. However, whether the changes in cue-induced brain response were related to relapse was unknown. In a prospective study, we recruited 49 heroin-dependent patients under methadone maintenance treatment, a gold standard treatment (average daily dose 41.8 ± 16.0 mg), and 20 healthy subjects to perform the heroin cue-reactivity task during fMRI. The patients' subjective craving was evaluated. They participated in a follow-up assessment for 3 months, during which heroin use was assessed and relapse was confirmed by self-reported relapse or urine toxicology. Differences between relapsers and non-relapsers were analyzed with respect to the results from heroin-cue responses. Compared with healthy subjects, relapsers and non-relapsers commonly demonstrated significantly increased brain responses during the processing of heroin cues in the mesolimbic system, prefrontal regions and visuospatial-attention regions. However, compared with non-relapsers, relapsers demonstrated significantly greater cue-induced craving and the brain response mainly in the bilateral nucleus accumbens/subcallosal cortex and cerebellum. Although the cue-induced heroin craving was low in absolute measures, the change in craving positively correlated with the activation of the nucleus accumbens/subcallosal cortex among the patients. These findings suggest that in treatment-seeking heroin-dependent individuals, greater cue-induced craving and greater specific regional activations might be related to reward/craving and memory retrieval processes. These responses may predict relapse and represent important targets for the development of new treatment for heroin addiction.
Smith, M L; Shimomura, E T; Summers, J; Paul, B D; Jenkins, A J; Darwin, W D; Cone, E J
Heroin is one of the major target drugs in workplace drug-testing programs because of its history of abuse, liability, and continued negative social impact. This study was a comprehensive examination of pharmacokinetics, pharmacodynamics, detection times, opiate immunoassay performance, and urine excretion profiles following single doses of heroin administered to human subjects via smoking and intravenous routes. Studies of the first four components of this investigation were previously published. This article describes the urine excretion profiles. Total morphine (Tmor), free morphine (Fmor), and 6-acetylmorphine (6-AM) were measured by gas chromatography-mass spectrometry (GC-MS) in 920 urine samples collected from 11 male human subjects following single doses of heroin. Eight received intravenous doses of 3, 6, and 12 mg heroin HCI and four smoked 3.5-, 5.2-, 7-, 10.5-, or 13.9-mg doses of heroin (base). In addition, 183 urine-based blind quality-control samples were added to the study set to assess assay performance. Creatinine was also measured in each sample by a colorimetric technique. The parameters studied were not significantly dependent on route of administration. Excretion half-life mean +/- SD for Tmor was 3.11 +/- 0.30 h. Range (median) of peak urine concentrations, time to peak, time to last positive sample for low cutoff (300 ng/mL) and high cutoff (2000 ng/mL) for Tmor following lower doses (< or = 7 mg) were, respectively, 1392-9250 (3620) ng/mL, 1.2-6.2 (2.3) h, 7.4-31.9 (7.4) h, and 0-10.1 (4.3) h. Following higher doses (> 10 mg) they were 2065-29,030 (16,470) ng/mL, 2.3-9.3 (4.5) h, 10.7-53.5 (34.4) h, 2.3-22.3 (8.3) h. Fmor peaked in the same sample as Tmor. Range (median) of peak Fmor concentrations and time to last positive using a cutoff of 100 ng/mL for low and high doses were, respectively, 117-1160 (415) ng/mL, 1.2-10.1 (4.5) h and 150-2580 (1400) ng/mL, 2.3-29.1 (9.3) h. The range (median) of peak urine concentrations for 6-AM was 6
Xie, Xiaohu; Liu, Huifen; Zhang, Jianbing; Chen, Weisheng; Zhuang, Dingding; Duan, Shiwei; Zhou, Wenhua
Growing amounts of evidence suggest that N-Methyl-d-aspartate (NMDA) receptor mediated glutamate neurotransmission may be involved in the pathophysiology of drug dependence. The NMDA receptor consists of three subfamilies (NR1, NR2, and NR3). The ability of subunit NR3 to negatively modulate the NMDA receptor function makes it an attractive candidate gene of heroin addiction. The purpose of this study is to explore the association between four single nucleotide polymorphisms (SNPs) of NR3 gene and heroin addiction. Genotyping of two SNPs (rs3739722 and rs17189632) in GRIN3A and two SNPs (rs4807399 and rs2240158) in GRIN3B was performed using TaqMan SNP genotyping method. The association between heroin addiction and these SNPs was assessed among 332 male heroin dependent patients and 400 male normal control subjects. The results showed the genotype and allele frequencies of rs17189632 and rs2240158 were significantly different between the cases and the controls (nominal P values were 0.0284, 0.0136 for rs17189632; 0.0048, 0.0013 for rs2240158, respectively). After Bonferroni correction, rs2240158 of GRIN3B was still found to be associated with heroin addiction. The frequencies of haplotype C-A at GRIN3A (rs3739722-rs17189632) and of C-C and C-T at GRIN3B (rs4807399-rs2240158) differed significantly between the cases and the controls. The genotype and allele distributions of rs3739722 and rs4807399 were not significantly different between in the cases and in the controls (P>0.05). These results suggest that GRIN3A rs17189632 and GRIN3B rs2240158 may contribute to the susceptibility of heroin addiction.
Martin, Thomas J.; Buechler, Nancy L.; Kim, Susy A.; Ewan, Eric E; Xiao, Ruoyu; Childers, Steven R.
Background Neuropathic pain alters opioid self-administration in rats. The brain regions altered in the presence of neuropathic pain mediating these differences have not been identified, but likely involve ascending pain pathways interacting with the limbic system. The amygdala is a brain region that integrates noxious stimulation with limbic activity. Methods μ-opioid receptors were blocked in the amygdala using the irreversible antagonist β-funaltrexamine and the antiallodynic and reinforcing effects of heroin were determined in spinal nerve ligated rats. Additionally, the effect of β-funaltrexamine was determined on heroin self-administration in sham-operated rats. Results β-funaltrexamine decreased functional activity of μ-opioid receptors by 60 ± 5% (mean ± SD) Irreversible inhibition of μ-opioid receptors in the amygdala significantly attenuated the ability of doses of heroin up to 100 μg/kg to reverse hypersensitivity following spinal nerve ligation. Heroin intake by self-administration in spinal nerve ligated rats was increased from 5.0 ± 0.3 to 9.9 ± 2.1 infusions/h following administration of 2.5 nmol of β-funaltrexamine in the lateral amygdala, while having no effect in sham-operated animals (5.8 ± 1.6 before, 6.7 ± 0.9 after). The antiallodynic effects of 60 μg/kg of heroin was decreased up to 4 days, but self-administration was affected for up to 14 days. Conclusions μ-opioid receptors in the lateral amygdala partially meditate heroin’s antiallodynic effects and self-administration following peripheral nerve injury. The lack of effect of β-funaltrexamine on heroin self-administration in sham-operated subjects suggests that opioids maintain self-administration through a distinct mechanism in the presence of pain. PMID:21293255
Kamali-Sarvestani, Fahimeh; Motiallah, Tahereh; Ghaffarinejad, Farahnaz
Background Heroin is an extremely addictive narcotic drug derived from morphine. Its continued use requires increased amounts of the drug to achieve the same effect, resulting in tolerance and addiction. This study was done in order to determine the prevalence of musculoskeletal pain and forward head posture among heroin users during their withdrawal. Methods This research was a cross-sectional study that was done on 90 heroin users (83 males, 7 females) aged between 20 to 40 years (32.5 ± 3.81) during their withdrawal in Shiraz, Iran. They were selected by simple randomized sampling. Data were collected by a form regarding age, sex, the duration of heroin use, and musculoskeletal pain. Pain was measured by VAS (visual analog scale) and forward head posture was evaluated by plumb line. Pearson correlation technique and chi-square were used for analyzing the data. Findings The results revealed that the majority of heroin users suffered from musculoskeletal pain during their withdrawal. At the end of withdrawal 53.4% had severe pain, 38.8% had moderate pain, and 7.8% of them had mild pain. Pain in the lower extremities and low back was more common than the upper extremities. The intensity of pain before withdrawal was mild, during withdrawal was moderate, and at the end was sever, but there was no significant correlation between them. The results also showed 43.3% of subjects had normal posture and 56.7% had forward posture. Conclusion According to the results, the intensity of pain increased during the withdrawal period; therefore, more attention must be paid to this complication in heroin users for better evaluation and a successful withdrawal. PMID:25140215
Eriksen, Guro Søe; Andersen, Jannike Mørch; Boix, Fernando; Mørland, Jørg
The opioid receptor antagonist 3-methoxynaltrexone (3-MeONtx) has previously been shown in rodents to selectively reverse the analgesic actions of heroin and its metabolites 6-monoacetylmorphine (6-MAM), and morphine-6-glucuronide (M6G), but not that of morphine. Based on these and other results, a heroin/6-MAM/M6G μ-opioid receptor binding site or subreceptor mediating their analgesic activity has been proposed. It is however unknown whether this also accounts for the acute psychomotor stimulating properties of these opioids. The aim of the present study was therefore to explore if the acute psychomotor stimulating effects of heroin, 6-MAM, and morphine are mediated by distinct μ-opioid receptor binding sites or subreceptors. To address this aim, we examined how pretreatment with 3-MeONtx or naltrexone (NTX) affected the acute increase in locomotor activity induced by heroin, 6-MAM, or morphine in mice. The pharmacokinetic profiles of 3-MeONtx and NTX were also assessed in mouse brain. We found that 3-MeONtx similarly antagonized the acute increase in locomotor activity induced by equipotent doses of heroin, 6-MAM, or morphine. This antagonistic effect was comparable to the one observed following administration of NTX, and both antagonists gave similar pharmacokinetic profiles in mouse brain. Our findings do not support that different μ-opioid receptor subtypes or a distinct binding site at the μ-opioid receptor is involved in morphine-induced versus heroin/6-MAM-induced psychomotor activation. This might suggest that the opioid-induced psychomotor stimulation is mediated by different μ-opioid subreceptors than those responsible for their analgesic effects.
Güttinger, Franziska; Gschwend, Patrick; Schulte, Bernd; Rehm, Jürgen; Uchtenhagen, Ambros
Since January 1994, heroin-assisted treatment for opiate addicts has been available in Switzerland. This is the first report of the long-term effects of this form of treatment. The report examines subjects who entered a study involving medical prescription of opiates (Projekt zur ärztlichen Verschreibung von Betäubungsmitteln; PROVE) in Switzerland between January 1994 and March 1995 (n = 366). Opiates were dispensed in eight treatment centres. A follow-up was conducted 6 years after treatment entry. Two groups were assessed: clients who have continuously been on heroin-assisted treatment since entry into the PROVE study or who re-entered this treatment, and ex-clients who had discontinued heroin-assisted treatment at the time of follow-up. Two kinds of comparisons were conducted. Firstly, conditions at treatment entry were compared to 6-year follow-up outcomes, and secondly, outcomes were compared between clients still on heroin-assisted treatment and those who had been discharged. It was found that 46% of the clients still alive were on heroin-assisted treatment at the time of follow-up. A comparison of the present living conditions showed very little difference between those in treatment and those who had terminated treatment. Compared to the situation at entry, the results of the follow-up showed a significant decrease in the use of illegal substances, illegal income and most other variables concerning social conditions, but they also showed an increase in unemployment and reliance on social benefits. Heroin-assisted treatment is thus efficacious in the long-term course of treatment and is still effective after termination of treatment with respect to living conditions and use of illicit substances.
Barrio, Gregorio; Brugal, M. Teresa; de la Fuente, Luis; Ballesta, Rosario; Bravo, María J.; Silva, Teresa C.; Rodríguez-Martos, Alicia
To identify the self-perceived reasons for unintentional opioid overdose of young heroin users in three Spanish cities and their agreement with objective risk factors for overdose. Computer-Assisted Personal Interviews (CAPI) were held with 991 street-recruited current heroin users aged 18–30. The general reasons for overdose and the reasons for the last overdose suffered were explored with open-ended (OEQs) and pre-coded questions (PCQs). Limited knowledge of overdose risk factors was defined as mention of fewer than two objective risk factors for unintentional overdose in the OEQ. Univariate, bivariate, and logistic regression methods were used. 77.8% (Seville), 64.9% (Madrid) and 57.2% (Barcelona) of participants have limited knowledge of overdose risk factors. Residence in Seville and not having attended courses or meetings on overdoses were significantly associated with limited knowledge, after adjusting for other factors. The most frequently identified general reasons in OEQ or PCQ were using heroin in large amounts (66.8%), together with tranquilizers (62.0%), adulterated (60.7%), or purer than usual (57.6%). Most reasons were selected more frequently in PCQ than in OEQ, especially rapid injection of the entire dose and using heroin shortly after using tranquilizers or alcohol, by injection, or after a period of abstinence. The results were similar for overdoses suffered by participants. Most young heroin users do not have sufficient knowledge of overdose risk factors, especially the use of heroin by injection, after a period of abstinence, or together with alcohol or methadone. Specific informational or educational programs adapted to the local context are critically needed. PMID:16739049
Cooper, Chad; Bilbao, Jorge E.; Said, Sarmad; Alkhateeb, Haider; Bizet, Jorge; Elfar, Ahmed; Davalos, Olinamyr; Meza, Ana T.; Hernandez, German T.
Background: Systemic AA amyloidosis is a long-term complication of several chronic inflammatory disorders. Organ damage results from the extracellular deposition of proteolytic fragments of the acute-phase reactant serum amyloid A (SAA) as amyloid fibrils. Drug users that inject drug by a subcutaneous route (“skin popping”) have a higher chance of developing secondary amyloidosis. The kidneys, liver, and spleen are the main target organs of AA amyloid deposits. More than 90% of patients with renal amyloidosis will present with proteinuria, nephrotic syndrome, or renal function. Case presentation: A 37 year-old female presented to the hospital with a one-week history of pain and redness in her right axilla. Her relevant medical history included multiple skin abscesses secondary to “skin popping”, heroin abuse for 18 years, and hepatitis C. The physical examination revealed “skin popping” lesions, bilateral costovertebral angle tenderness, and bilateral knee swelling. The laboratory workup was significant for renal insufficiency with a serum creatinine of 5 mg/dL and 14.8 grams of urine protein per 1 gram of urine creatinine. The renal biopsy findings were consistent with a diagno