Decrease of cocaine, but not heroin, self-administration and relapse by the tyrosine kinase inhibitor masitinib in male Sprague Dawley rats.

PubMed

Belin-Rauscent, A; Lacoste, J; Hermine, O; Moussy, A; Everitt, B J; Belin, David

2018-05-01

Accumulating evidence shows that cocaine, and also heroin, influence several tyrosine kinases, expressed in neurons and in non-neuronal populations such as microglia, astrocytes and mast-cells. Drug-induced activation of mast cells both triggers inflammatory processes in the brain mediated by the glial cells they activate, and facilitates histamine release which may directly influence the dopamine system. Thus, by triggering the activation and degranulation of mast cells dependent on the tyrosine kinase c-kit and Fyn, the latter being also involved in NMDA-dependent synaptic plasticity, cocaine and heroin may indirectly influence the neural mechanisms that mediate their reinforcing properties. Masitinib, a novel tyrosine kinase inhibitor with high selectivity for c-Kit, Fyn and Lyn, may alter the aberrant consequences of the activation of these tyrosine kinases by cocaine and heroin. We investigated in rats the effect of a chronic oral treatment with masitinib (20 mg/kg) on the reinforcing and motivational properties of self-administered cocaine (250 μg/infusion) and heroin (40 μg/infusion). Three different cohorts of rats were trained instrumentally to respond for cocaine, heroin or food under continuous reinforcement. In each group, we assessed the influence of chronic daily treatment with masitinib on the maintenance of instrumental responding and intake and the motivation for the reinforcer. Thus, masitinib and vehicle-treated rats were challenged to adapt to high behavioural demand, to respond under a progressive ratio schedule of reinforcement and to reinstate instrumental responding after extinction and/or abstinence. Masitinib selectively decreased cocaine intake, the motivation for cocaine and the subsequent propensity to respond for cocaine under extinction, while having no effect on instrumental responding for heroin or food. The present findings suggest masitinib, a drug with proven efficacy in CNS disorders, could represent a novel treatment for

IS THE U.S. EXPERIENCING AN INCIPIENT EPIDEMIC OF HALLUCINOGEN USE?

PubMed Central

Golub, Andrew; Johnson, Bruce D.; Sifaneck, Stephen J.; Chesluk, Benjamin; Parker, Howard

2008-01-01

NHSDA and MTF survey data indicate “epidemic”-like growth in hallucinogen use from 1992-1996 and associated increases in cocaine, crack, heroin and amphetamine use. These trends might have resulted from a proliferation of raves and dance clubs in the U.S. as occurred in Europe and elsewhere, although in contrast to evidence regarding European experiences the American epidemic involves primarily teens as opposed to persons in their twenties and involves primarily use of LSD as opposed to MDMA. This analysis highlights the need for further research into the context, significance, and consequences of these recently popular American drug use practices. PMID:11758819

Classification and Short-Term Course of DSM-IV Cannabis, Hallucinogen, Cocaine, and Opioid Disorders in Treated Adolescents

ERIC Educational Resources Information Center

Chung, Tammy; Martin, Christoper S.

2005-01-01

This study examined the latent class structure of Diagnostic and Statistical Manual of Mental Disorders (text rev.; DSM-IV; American Psychiatric Association, 2000) symptoms used to diagnose cannabis, hallucinogen, cocaine, and opiate disorders among 501 adolescents recruited from addictions treatment. Latent class results were compared with the…

Is Slow-Onset Long-Acting Monoamine Transport Blockade to Cocaine as Methadone is to Heroin? Implication for Anti-Addiction Medications

PubMed Central

Peng, Xiao-Qing; Xi, Zheng-Xiong; Li, Xia; Spiller, Krista; Li, Jie; Chun, Lauren; Wu, Kuo-Ming; Froimowitz, Mark; Gardner, Eliot L

2010-01-01

The success of methadone in treating opiate addiction has suggested that long-acting agonist therapies may be similarly useful for treating cocaine addiction. Here, we examined this hypothesis, using the slow-onset long-acting monoamine reuptake inhibitor 31,345, a trans-aminotetralin analog, in a variety of addiction-related animal models, and compared it with methadone's effects on heroin's actions in the same animal models. Systemic administration of 31,345 produced long-lasting enhancement of electrical brain-stimulation reward (BSR) and extracellular nucleus accumbens (NAc) dopamine (DA). Pretreatment with 31,345 augmented cocaine-enhanced BSR, prolonged cocaine-enhanced NAc DA, and produced a long-term (24-48 h) reduction in cocaine self-administration rate without obvious extinction pattern, suggesting an additive effect of 31,345 with cocaine. In contrast, methadone pretreatment not only dose-dependently inhibited heroin self-administration with an extinction pattern but also dose-dependently inhibited heroin-enhanced BSR and NAc DA, suggesting functional antagonism by methadone of heroin's actions. In addition, 31,345 appears to possess significant abuse liability, as it produces dose-dependent enhancement of BSR and NAc DA, maintains a low rate of self-administration behavior, and dose-dependently reinstates drug-seeking behavior. In contrast, methadone only partially maintains self-administration with an extinction pattern, and fails to induce reinstatement of drug-seeking behavior. These findings suggest that 31,345 is a cocaine-like slow-onset long-acting monoamine transporter inhibitor that may act as an agonist therapy for cocaine addiction. However, its pattern of action appears to be significantly different from that of methadone. Ideal agonist substitutes for cocaine should fully emulate methadone's actions, that is, functionally antagonizing cocaine's action while blocking monoamine transporters to augment synaptic DA. PMID:20827272

Proximity to the US-Mexico border: a key to explaining geographic variation in US methamphetamine, cocaine and heroin purity.

PubMed

Cunningham, James K; Maxwell, Jane Carlisle; Campollo, Octavio; Cunningham, Kathryn I; Liu, Lon-Mu; Lin, Hui-Lin

2010-10-01

Although illicit drug purity is a widely discussed health risk, research explaining its geographic variation within a country is rare. This study examines whether proximity to the US-Mexico border, the United States' primary drug import portal, is associated with geographic variation in US methamphetamine, heroin and cocaine purity. Distances (proximity) between the US-Mexico border and locations of methamphetamine, cocaine and heroin seizures/acquisitions (n = 239,070) recorded in STRIDE (System to Retrieve Information from Drug Evidence) were calculated for the period of 1990-2004. The association of drug purity with these distances and other variables, including time and seizure/acquisition size, was examined using hierarchical multivariate linear modeling (HMLM). Coterminous United States. Methamphetamine, cocaine and heroin purity generally decreased with distance from the US-Mexico border. Heroin purity, however, after initially declining with distance, turned upwards-a U-shaped association. During 2000-04, methamphetamine purity also had a U-shaped association with distance. For each of the three drugs, temporal changes in the purity of small acquisitions (<10 g) were typically more dynamic in areas closer to the US-Mexico border. Geographic variance in methamphetamine, cocaine and heroin purity throughout the coterminous United States was associated with US-Mexico border proximity. The U-shaped associations between border-distance and purity for heroin and methamphetamine may be due to imports of those drugs via the eastern United States and southeast Canada, respectively. That said, areas closer to the US-Mexico border generally had relatively high illicit drug purity, as well as more dynamic change in the purity of small ('retail level') drug amounts. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine.

PubMed

Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah; Ettenberg, Aaron

2011-04-01

Evidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers. The current study was therefore devised to test the hypothesis that differences in the animals' responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of prior cocaine and heroin runway self-administration. Rats ran a straight alley for single intravenous injections of either heroin (0.1 mg/kg/inj) or cocaine (1.0 mg/kg/inj) each paired with a distinct olfactory cue. Animals experienced 15 trials with each drug reinforcer in a counterbalanced manner. Start latencies, run times, and retreat behaviors (a form of approach-avoidance conflict) provided behavioral indices of the subjects' motivation to seek the reinforcer on each trial. Responsiveness to each drug-paired cue was assessed after 7, 14, or 21 days of non-reinforced extinction trials. Other animals underwent conditioned place preference (CPP) testing to ensure that the two drug reinforcers were capable of producing drug-cue associations. While both drugs produced comparable CPPs, heroin served as a stronger incentive stimulus in the runway as evidenced by faster start and run times and fewer retreats. In contrast, cocaine- but not heroin-paired cues produced increases in drug-seeking behavior during subsequent extinction trials. The subjects' responsiveness to drug-paired cues during extinction was not predicted by differences in the motivation to seek heroin versus cocaine during prior drug self-administration.

Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats.

PubMed

Steidl, Stephan; Wang, Huiling; Wise, Roy A

2014-01-01

Cholinergic input to the ventral tegmental area (VTA) is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg) provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII), the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65)% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.

Temperament and character traits associated with the use of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens: evidence from a large Brazilian web survey.

PubMed

Schneider, Ricardo; Ottoni, Gustavo L; de Carvalho, Hudson W; Elisabetsky, Elaine; Lara, Diogo R

2015-01-01

To evaluate how personality traits are associated with occasional use, abuse, and dependence of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens in a large availability sample of adults via online questionnaires. The sample consisted of 8,646 individuals (24.7% men and 75.3% women) who completed an anonymous web survey. Involvement with drugs and temperament/character traits were assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Temperament and Character Inventory - Revised (TCI-R), respectively. Interactions among variables were analyzed using MANOVA with Bonferroni adjustment. Novelty seeking was the trait most associated with increased involvement with alcohol, cannabis, and cocaine. There was a significant association between harm avoidance and benzodiazepine use. Persistence was lower in cannabis-, benzodiazepine-, and cocaine-dependent subjects, as well as in hallucinogen abusers. Self-directedness was reduced in dependents of all drug classes. No strong relationships were found between other temperament or character dimensions and the severity of drug use. Novelty seeking was associated with increased involvement with all drugs studied in this sample, although to a lesser extent with benzodiazepines and hallucinogens. The temperament and character profile for benzodiazepine use was different from that of other drugs due to the relationship with higher harm avoidance and self-transcendence and lower self-directedness.

Characteristics of Hidden Status Among Users of Crack, Powder Cocaine, and Heroin in Central Harlem

PubMed Central

Davis, W. Rees; Johnson, Bruce D.; Liberty, Hilary James; Randolph, Doris D.

2007-01-01

This article analyzes hidden status among crack, powder cocaine, and heroin users and setters, in contrast to more accessible users/sellers. Several sampling strategies acquired 657 users (N=559) and sellers (N=98). Indicators of hidden status were those who (1) paid rent in full in the last 30 days, (2) used nonstreet drug procurement. (3) had legal jobs, and (4) earned $1,000 or more in legal income in the last 30 days. Nearly half had at least one indicator: approximately 16% of users/sellers had two to four indicators. In logistic regression analyses, those who had not panhandled in the last 30 days, those who had used powder cocaine in the last 30 days, and those never arrested were the most likely to have hidden status, whether the analysis predicted those having any indicators or those having two to four indicators. The four indicators begin to operationally define hidden status among users of cocaine and heroin. PMID:17710217

The drug use behaviour of cocaine users.

PubMed

Moosburger, R; Plant, A J; Pierce, J P

1990-01-01

We interviewed 50 current cocaine users with the aim of providing insights into cocaine use in Sydney. The study sample was obtained by one researcher using a chain referral technique. Appointments were made for interview and the interview aimed to determine the quantity, frequency, pattern and circumstances of drug use in the respondents. The study sample included people with a wide range of incomes and occupations; all but one person were employed. Extensive current drug use was reported; 78% smoked tobacco, 98% drank alcohol with 36% having more than two drinks per day, 96% used marijuana with 40% smoking marijuana at least 5 times per week, 65% used amphetamines, 36% used hallucinogens and 10% used heroin. Ten per cent were unable to name one health risk of cocaine. When asked about the image of a cocaine user, 42% thought of a rock star, film industry worker or someone involved in the arts and entertainment world. The information obtained from a study such as this provides important data for targeting of people in anti-drug campaigns.

Heroin

MedlinePlus

... an illegal narcotic because it has dangerous side effects and is very addictive. Sometimes Called: horse, smack, big H, black tar, caballo (Spanish), 8-ball (heroin mixed with crack cocaine), junk, TNT How It's Used: Heroin is usually ...

Dysregulated post-synaptic density and endocytic zone in the amygdala of human heroin and cocaine abusers

PubMed Central

Ökvist, Anna; Fagergren, Pernilla; Whittard, John; Garcia-Osta, Ana; Drakenberg, Katarina; Horvath, Monika Cs.; Schmidt, Carl J.; Keller, Eva; Bannon, Michael J.; Hurd, Yasmin L.

2010-01-01

Background Glutamatergic transmission in the amygdala is hypothesized as an important mediator of stimulus-reward associations contributing to drug-seeking behavior and relapse. Insight is, however, lacking regarding the amygdala glutamatergic system in human drug abusers. Methods We examined glutamate receptors and scaffolding proteins associated with the post-synaptic density (PSD) of excitatory synapses in the human post-mortem amygdala. mRNA or protein levels were studied in a multi-drug (7 heroin, 8 cocaine, 7 heroin/cocaine and 7 control) or predominant heroin (29 heroin and 15 control) population of subjects. Results The amygdala of drug abusers was characterized by a striking positive correlation (r > 0.8) between AMPA GluA1 and post-synaptic protein-95 (PSD-95) mRNA levels, which was not evident in controls. Structural equation multi-group analysis of protein correlations also identified the relationship between GluA1 and PSD-95 protein levels as the distinguishing feature of abusers. In line with the GluA1—PSD-95 implications of enhanced synaptic plasticity, Homer 1b/c protein expression was significantly increased in both heroin and cocaine users as was its binding partner dynamin-3, localized to the endocytic zone. Furthermore, there was a positive relationship between Homer 1b/c and dynamin-3 in drug abusers that reflected an increase in the direct physical coupling between the proteins. A noted age-related decline of Homer 1b/c—dynamin-3 interactions, as well as GluA1 levels, was blunted in abusers. Conclusions Impairment of key components of the amygdala PSD and coupling to the endocytic zone, critical for the regulation of glutamate receptor cycling, may underlie heightened synaptic plasticity in human drug abusers. PMID:21126734

Cocaine-related deaths.

PubMed

Lora-Tamayo, C; Tena, T; Rodriguez, A

1994-07-15

Cocaine availability has been increasing in Spain in the past few years. A review of all the toxicological analyses carried out at the Madrid Department of the Instituto Nacional de Toxicología, with subjects who had died of drugs from 1990 to 1992, found 533 persons who had cocaine in their blood and/or tissues; 450 (84%) deaths involved cocaine and heroin together whereas 83 (16%) deaths involved cocaine with an absence of heroin. This paper reports the circumstances, cocaine and benzoylecgonine concentrations in the blood and other toxicological findings for the two major groups of deaths where cocaine was found with an absence of heroin, i.e., possible overdose cases (35 cases) and traffic accidents (23 cases).

Genetic variants associated with addictive behavior in Colombian addicted and non-addicted to heroin or cocaine.

PubMed

Isaza, Carlos; Henao, Julieta; Beltrán, Leonardo; Porras, Liliana; Gonzalez, Martha; Cruz, Raquel; Carracedo, Angel

2013-01-01

Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age and ethnicity. A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 polymorphism of the OPRM1, DRD2, DRD4, SLC6A3, SLC6A4, ABCB1, DβH and CYP2B6 genes. For the identification of alleles markers were used mini-sequencing and fragment multiplex PCR techniques; ethnicity of cases and controls was analyzed with 61 AIMs. The age of onset use of heroin or coca derivatives (cocaine/crack) was 16.5±6 years and 99.2% of them consume several illicit drugs. It showed that controls and addicts belong to the same ethnic group. Significant differences between addicts and controls in relation to schooling, marital status, social security family history of substance abuse (p <0.001), Int8-VNTR SLC6A3 gene (p= 0.015) and SNP 3435C>T ABCB1 gene (p= 0.001) were found. The present results indicate that the VNTR- 6R polymorphism of the gene SLC6A3 and the genotype 3435CC in the ABCB1 gene, are both associated with addictive behavior to heroin or cocaine.

Excess mortality among people who report lifetime use of illegal drugs in the United States: A 20-year follow-up of a nationally representative survey.

PubMed

Walker, Elizabeth Reisinger; Pratt, Laura A; Schoenborn, Charlotte A; Druss, Benjamin G

2017-02-01

The purpose of this study was to determine the mortality risks, over 20 years of follow-up in a nationally representative sample, associated with illegal drug use and to describe risk factors for mortality. We analyzed data from the 1991 National Health Interview Survey, which is a nationally representative household survey in the United States, linked to the National Death Index through 2011. This study included 20,498 adults, aged 18-44 years in 1991, with 1047 subsequent deaths. A composite variable of self-reported lifetime illegal drug use was created (hierarchical categories of heroin, cocaine, hallucinogens/inhalants, and marijuana use). Mortality risk was significantly elevated among individuals who reported lifetime use of heroin (HR=2.40, 95% CI: 1.65-3.48) and cocaine (HR=1.27, 95% CI: 1.04-1.55), but not for those who used hallucinogens/inhalants or marijuana, when adjusting for demographic characteristics. Baseline health risk factors (smoking, alcohol use, physical activity, and BMI) explained the greatest amount of this mortality risk. After adjusting for all baseline covariates, the association between heroin or cocaine use and mortality approached significance. In models adjusted for demographics, people who reported lifetime use of heroin or cocaine had an elevated mortality risk due to external causes (poisoning, suicide, homicide, and unintentional injury). People who had used heroin, cocaine, or hallucinogens/inhalants had an elevated mortality risk due to infectious diseases. Heroin and cocaine are associated with considerable excess mortality, particularly due to external causes and infectious diseases. This association can be explained mainly by health risk behaviors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Heroin Use Is Associated with Ruptured Saccular Aneurysms.

PubMed

Can, Anil; Castro, Victor M; Ozdemir, Yildirim H; Dagen, Sarajune; Dligach, Dmitriy; Finan, Sean; Yu, Sheng; Gainer, Vivian; Shadick, Nancy A; Savova, Guergana; Murphy, Shawn; Cai, Tianxi; Weiss, Scott T; Du, Rose

2017-11-04

While cocaine use is thought to be associated with aneurysmal rupture, it is not known whether heroin use increases the risk of rupture in patients with non-mycotic saccular aneurysms. Our goal was to investigate the association between heroin and cocaine use and the rupture of saccular non-mycotic aneurysms. The medical records of 4701 patients with 6411 intracranial aneurysms, including 1201 prospective patients, diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and non-ruptured groups. Univariable and multivariable logistic regression analyses were performed to determine the association between heroin, cocaine, and methadone use and the presence of ruptured intracranial aneurysms. In multivariable analysis, current heroin use was significantly associated with rupture status (OR 3.23, 95% CI 1.33-7.83) whereas former heroin use (with and without methadone replacement therapy), and current and former cocaine use were not significantly associated with intracranial aneurysm rupture. In the present study, heroin rather than cocaine use is significantly associated with intracranial aneurysm rupture in patients with non-mycotic saccular cerebral aneurysms, emphasizing the possible role of heroin in the pathophysiology of aneurysm rupture and the importance of heroin cessation in patients harboring unruptured intracranial aneurysms.

Effects of prior cocaine versus morphine or heroin self-administration on extinction learning driven by overexpectation versus omission of reward.

PubMed

Lucantonio, Federica; Kambhampati, Sarita; Haney, Richard Z; Atalayer, Deniz; Rowland, Neil E; Shaham, Yavin; Schoenbaum, Geoffrey

2015-05-15

Addiction is characterized by an inability to stop using drugs, despite adverse consequences. One contributing factor to this compulsive drug taking could be the impact of drug use on the ability to extinguish drug seeking after changes in expected outcomes. Here, we compared effects of cocaine, morphine, and heroin self-administration on two forms of extinction learning: standard extinction driven by reward omission and extinction driven by reward overexpectation. In experiment 1, we trained rats to self-administer cocaine, morphine, or sucrose for 3 hours per day (limited access). In experiment 2, we trained rats to self-administer heroin or sucrose for 12 hours per day (extended access). Three weeks later, we trained the rats to associate several cues with palatable food reward, after which we assessed extinction of the learned Pavlovian response, first by pairing two cues together in the overexpectation procedure and later by omitting the food reward. Rats trained under limited access conditions to self-administer sucrose or morphine demonstrated normal extinction in response to both overexpectation and reward omission, whereas cocaine-experienced rats or rats trained to self-administer heroin under extended access conditions exhibited normal extinction in response to reward omission but failed to show extinction in response to overexpectation. Here we show that cocaine and heroin can induce long-lasting deficits in the ability to extinguish reward seeking. These deficits were not observed in a standard extinction procedure but instead only affected extinction learning driven by a more complex phenomenon of overexpectation. Published by Elsevier Inc.

Heroin and cocaine abusers have higher discount rates for delayed rewards than alcoholics or non-drug-using controls.

PubMed

Kirby, Kris N; Petry, Nancy M

2004-04-01

To test a prediction of the discounting model of impulsiveness that discount rates would be positively associated with addiction. The delay-discount rate refers to the rate of reduction in the present value of a future reward as the delay to that reward increases. We estimated participants' discount rates on the basis of their pattern of choices between smaller immediate rewards ($11-80) and larger, delayed rewards ($25-85; at delays from 1 week to 6 months) in a questionnaire format. Participants had a one-in-six chance of winning a reward that they chose on one randomly selected trial. Heroin (n = 27), cocaine (n = 41) and alcohol (n = 33) abusers and non-drug-using controls (n = 44) were recruited from advertisements. They were tested in a drug abuse research clinic at a medical school. On average, the cocaine and heroin groups had higher rates than controls (both P < 0.001), but alcoholics did not (P = 0.44). Abstinence was associated with lower rates for heroin abusers (P = 0.03), but not for cocaine or alcohol abusers (both P > 0.50). These data suggest that discount rates vary with the preferred drug of abuse, and that high discount rates should be considered in the development of substance abuse prevention and treatment efforts.

Randomized Trial of Prize-Based Reinforcement Density for Simultaneous Abstinence from Cocaine and Heroin

ERIC Educational Resources Information Center

Ghitza, Udi E.; Epstein, David H.; Schmittner, John; Vahabzadeh, Massoud; Lin, Jia-Ling; Preston, Kenzie L.

2007-01-01

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…

Acute heroin intoxication in a baby chronically exposed to cocaine and heroin: a case report

PubMed Central

2011-01-01

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

Profile of executive deficits in cocaine and heroin polysubstance users: common and differential effects on separate executive components.

PubMed

Verdejo-García, Antonio; Pérez-García, Miguel

2007-03-01

Structure of executive function was examined and we contrasted performance of substance dependent individuals (polysubstance users) and control participants on neuropsychological measures assessing the different executive components obtained. Additionally, we contrasted performance of polysubstance users with preference for cocaine vs heroin and controls to explore possible differential effects of the main substance abused on executive impairment. Two groups of participants were recruited: abstinent polysubstance users and controls. Polysubstance users were further subdivided based on their drug of choice (cocaine vs heroin). We administered to all participants a comprehensive protocol of executive measures, including tests of fluency, working memory, reasoning, inhibitory control, flexibility, and decision making. Consistent with previous models, the principal component analysis showed that executive functions are organized into four separate components, three of them previously described: updating, inhibition, and shifting; and a fourth component of decision making. Abstinent polysubstance users had clinically significant impairments on measures assessing these four executive components (with effect sizes ranging from 0.5 to 2.2). Cocaine polysubstance users had more severe impairments than heroin users and controls on measures of inhibition (Stroop) and shifting (go/no go and category test). Greater severity of drug use predicted poorer performance on updating measures. Executive functions can be fractionated into four relatively independent components. Chronic drug use is associated with widespread impairment of these four executive components, with cocaine use inducing more severe deficits on inhibition and shifting. These findings show both common and differential effects of two widely used drugs on different executive components.

Research Reports: Inhalants

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... are appropriately concerned about illicit drugs such as marijuana, cocaine, and LSD, they often ignore the dangers ...

Cannabinoids and hallucinogens for headache.

PubMed

McGeeney, Brian E

2013-03-01

Hallucinogens and most cannabinoids are classified under schedule 1 of the Federal Controlled Substances Act 1970, along with heroin and ecstacy. Hence they cannot be prescribed by physicians, and by implication, have no accepted medical use with a high abuse potential. Despite their legal status, hallucinogens and cannabinoids are used by patients for relief of headache, helped by the growing number of American states that have legalized medical marijuana. Cannabinoids in particular have a long history of use in the abortive and prophylactic treatment of migraine before prohibition and are still used by patients as a migraine abortive in particular. Most practitioners are unaware of the prominence cannabis or "marijuana" once held in medical practice. Hallucinogens are being increasingly used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and maintain quiescence for which there is considerable anecdotal success. The legal status of cannabinoids and hallucinogens has for a long time severely inhibited medical research, and there are still no blinded studies on headache subjects, from which we could assess true efficacy. © 2012 American Headache Society.

Characterizing longitudinal health state transitions among heroin, cocaine, and methamphetamine users

PubMed Central

Nosyk, B; Li, L; Evans, E; Huang, D; Min, J; Kerr, T; Brecht, ML; Hser, YI

2014-01-01

Aims Characterize longitudinal patterns of drug use careers and identify determinants of drug use frequency across cohorts of primary heroin, methamphetamine (MA) and cocaine users. Design Pooled analysis of prospective cohort studies. Settings Illicit drug users recruited from community, criminal justice and drug treatment settings in California, USA. Participants We used longitudinal data on from five observational cohort studies featuring primary users of heroin (N=629), cocaine (N=694) and methamphetamine (N=474). The mean duration of follow-up was 20.9 years. Measurements Monthly longitudinal data was arranged according to five health states (incarceration, drug treatment, abstinence, non-daily and daily use). We fitted proportional hazards (PH) frailty models to determine independent differences in successive episode durations. We then executed multi-state Markov (MSM) models to estimate probabilities of transitioning between health states, and the determinants of these transitions. Findings Across primary drug use types, PH frailty models demonstrated durations of daily use diminished in successive episodes over time. MSM models revealed primary stimulant users had more erratic longitudinal patterns of drug use, transitioning more rapidly between periods of treatment, abstinence, non-daily and daily use. MA users exhibited relatively longer durations of high-frequency use. Criminal engagement had a destabilizing effect on health state durations across drug types. Longer incarceration histories were associated with delayed transitions towards cessation. Conclusions PH frailty and MSM modeling techniques provided complementary information on longitudinal patterns of drug abuse. This information can inform clinical practice and policy, and otherwise be used in health economic simulation models, designed to inform resource allocation decisions. PMID:24837584

The epidemiology of cocaine use in Spain.

PubMed

Barrio Anta, G; Vicente Orta, J; Bravo Portela, M J; de la Fuente de Hoz, L

1993-12-01

Trends and patterns of cocaine use in Spain are described with the aid of different information sources such as population surveys, the State Information System on Drug Abuse, and anthropological studies. In recent years the magnitude of cocaine supply indicators has increased greatly. High levels of last-month prevalence of cocaine use have been detected among the general population--consistently higher than those for heroin-- and cocaine consumption among heroin users has increased. Although the frequency of some health problems related to cocaine use--treatment admissions, hospital emergency admissions--has increased, it is still 30 times less than for heroin. Various hypotheses to explain these discrepancies are discussed.

Development and validation of a solid-phase extraction gas chromatography–mass spectrometry method for the simultaneous quantification of methadone, heroin, cocaine and metabolites in sweat

PubMed Central

Brunet, Bertrand R.; Barnes, Allan J.; Scheidweiler, Karl B.; Mura, Patrick

2009-01-01

A sensitive and specific method is presented to simultaneously quantify methadone, heroin, cocaine and metabolites in sweat. Drugs were eluted from sweat patches with sodium acetate buffer, followed by SPE and quantification by GC/MS with electron impact ionization and selected ion monitoring. Daily calibration for anhydroecgonine methyl ester, ecgonine methyl ester, cocaine, benzoylecgonine (BE), codeine, morphine, 6-acetylcodeine, 6-acetylmorphine (6AM), heroin (5–1000 ng/patch) and methadone (10–1000 ng/patch) achieved determination coefficients of >0.995, and calibrators quantified to within ±20% of the target concentrations. Extended calibration curves (1000–10,000 ng/patch) were constructed for methadone, cocaine, BE and 6AM by modifying injection techniques. Within (N=5) and between-run (N=20) imprecisions were calculated at six control levels across the dynamic ranges with coefficients of variation of <6.5%. Accuracies at these concentrations were ±11.9% of target. Heroin hydrolysis during specimen processing was <11%. This novel assay offers effective monitoring of drug exposure during drug treatment, workplace and criminal justice monitoring programs. PMID:18607576

Wheel running decreases the positive reinforcing effects of heroin.

PubMed

Smith, Mark A; Pitts, Elizabeth G

2012-01-01

The purpose of this study was to examine the effects of voluntary wheel running on the positive reinforcing effects of heroin in rats with an established history of drug self-administration. Rats were assigned to sedentary (no wheel) and exercise (wheel) conditions and trained to self-administer cocaine under positive reinforcement contingencies. Rats acquiring cocaine self-administration were then tested with various doses of heroin during daily test sessions. Sedentary rats self-administered more heroin than exercising rats, and this effect was greatest at low and moderate doses of heroin. These data suggest that voluntary wheel running decreases the positive reinforcing effects of heroin.

Heroin purchasing is income and price sensitive.

PubMed

Roddy, Juliette; Steinmiller, Caren L; Greenwald, Mark K

2011-06-01

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. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

The Textures of Heroin: User Perspectives on "Black Tar" and Powder Heroin in Two U.S. Cities.

PubMed

Mars, Sarah G; Bourgois, Philippe; Karandinos, George; Montero, Fernando; Ciccarone, Daniel

2016-01-01

Since the 1990s, U.S. heroin consumers have been divided from the full range of available products: east of the Mississippi River, Colombian-sourced powder heroin (PH) dominates the market while, to the west, Mexican-sourced "black tar" (BTH) is the main heroin available. By conducting qualitative research in two exemplar cities, Philadelphia (PH) and San Francisco (BTH), we compare users' experiences of heroin source-types, markets, health consequences, and consumption preferences. The strict division of heroin markets may be changing with novel forms of powder heroin appearing in San Francisco. Our researchers and interviewees perceived vein loss stemming from the injection of heroin alone to be a particular problem of BTH while, among the Philadelphia sample, those who avoided the temptations of nearby cocaine sales displayed healthier injecting sites and reported few vein problems. Abscesses were common across both sites, the Philadelphia sample generally blaming missing a vein when injecting cocaine and the San Francisco group finding several explanations, including the properties of BTH. Consumption preferences revealed a "connoisseurship of potency," with knowledge amassed and deployed to obtain the strongest heroin available. We discuss the reasons that their tastes take this narrow form and its relationship to the structural constraints of the heroin market.

The Textures of Heroin: User Perspectives on “Black Tar” and Powder Heroin in Two US Cities

PubMed Central

Mars, Sarah G.; Bourgois, Philippe; Karandinos, George; Montero, Fernando; Ciccarone, Daniel

2016-01-01

Since the 1990s, US heroin consumers have been divided from the full range of available products: east of the Mississippi River, Colombian-sourced powder heroin (PH) dominates the market, while to the west, Mexican-sourced “black tar” (BTH) is the main heroin available. By conducting qualitative research in two exemplar cities, Philadelphia (PH) and San Francisco (BTH), we compare users’ experiences of heroin source-types, markets, health consequences and consumption preferences. The strict division of heroin markets may be changing with novel forms of powder heroin appearing in San Francisco. Our researchers and interviewees perceived vein loss stemming from the injection of heroin alone to be a particular problem of BTH while among the Philadelphia sample, those who avoided the temptations of nearby cocaine sales displayed healthier injecting sites and reported few vein problems. Abscesses were common across both sites, the Philadelphia sample generally blaming missing a vein when injecting cocaine and the San Francisco group finding several explanations, including the properties of BTH. Consumption preferences revealed a ‘connoisseurship of potency’, with knowledge amassed and deployed to obtain the strongest heroin available. We discuss the reasons that their tastes take this narrow form and its relationship to the structural constraints of the heroin market. PMID:27440088

Neural correlates of the severity of cocaine, heroin, alcohol, MDMA and cannabis use in polysubstance abusers: a resting-PET brain metabolism study.

PubMed

Moreno-López, Laura; Stamatakis, Emmanuel A; Fernández-Serrano, Maria José; Gómez-Río, Manuel; Rodríguez-Fernández, Antonio; Pérez-García, Miguel; Verdejo-García, Antonio

2012-01-01

Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients.

The cocaine and heroin markets in the era of globalisation and drug reduction policies.

PubMed

Costa Storti, Cláudia; De Grauwe, Paul

2009-11-01

Despite the large volume of public effort devoted to restrain drug supply and the growing attention given to drug demand reduction policies, the use of cocaine and heroin remains steady. Furthermore, retail drug prices have fallen significantly in Europe and the US. This puzzling evidence leads us to develop a model aiming at systematically analysing illicit drug markets. We model the markets of cocaine and heroin from production to the final retail markets. One novelty of the analysis consists in characterising the retail market as a monopolistic competitive one. Then, upper level dealers have some market power in the retail market. This allows them to charge a markup and to earn extra profits. These extra profits attract newcomers so that profits tend to fall over time. Theoretical model was used to analyse the effect of supply containment policies on the retail market, the producer market and the export-import business. This introduces the discussion of the impact of demand reduction policies on the high level traffickers' profit. Finally, globalisation enters in the model. Law enforcement measures increase the risk premia received by the lower and higher level traffickers. Consequently, trafficking intermediation margins tend to increase. However, globalisation has the opposite effect. It lowers intermediation margins and, then, pushes retail prices down, thereby stimulating consumption. In doing so, globalisation offsets the effects of supply containment policies. Finally, we discuss how the effectiveness of supply containment policies can be enhanced by combining them with demand reduction policies.

A social network perspective on heroin and cocaine use among adults: evidence of bidirectional influences.

PubMed

Bohnert, Amy S B; Bradshaw, Catherine P; Latkin, Carl A

2009-07-01

While several studies have documented a relationship between initiation of drug use and social network drug use in youth, the direction of this association is not well understood, particularly among adults or for stages of drug involvement beyond initiation. The present study sought to examine two competing theories (social selection and social influence) in the longitudinal relationship between drug use (heroin and/or cocaine) and social network drug use among drug-experienced adults. Three waves of data came from a cohort of 1108 adults reporting a life-time history of heroin and/or cocaine use. Low-income neighborhoods with high rates of drug use in Baltimore, Maryland. Participants had weekly contact with drug users and were 18 years of age or older. Drug use data were self-report. Network drug use was assessed through a social network inventory. Close friends were individuals whom the participant reported seeing daily or rated as having the highest level of trust. Findings Structural equation modeling indicated significant bidirectional influences. The majority of change in network drug use over time was due to change in the composition of the network rather than change in friends' behavior. Drug use by close peers did not influence participant drug use beyond the total network. There is evidence of both social selection and social influence processes in the association between drug use and network drug use among drug-experienced adults.

Family Checkup: Positive Parenting Prevents Drug Abuse

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Comorbidity

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Patterns of Cognitive Impairments among Heroin and Cocaine Users: The Association with Self-Reported Learning Disabilities and Infectious Disease

ERIC Educational Resources Information Center

Severtson, Stevan G.; Hedden, Sarra L.; Martins, Silvia S.; Latimer, William W.

2012-01-01

This study used data from six neuropsychological measures of executive function (EF) and general intellectual functioning (GIF) administered to 303 regular users of heroin and/or cocaine as indicators in a latent profile analysis (LPA). Results indicated the presence of three profiles: impaired GIF and EF profile (30.8%), intact GIF and EF profile…

Solid phase microextraction and gas chromatography-mass spectrometry methods for residual solvent assessment in seized cocaine and heroin.

PubMed

Cabarcos, Pamela; Herbello-Hermelo, Paloma; Álvarez-Freire, Iván; Moreda-Piñeiro, Antonio; Tabernero, María Jesús; Bermejo, Ana María; Bermejo-Barrera, Pilar

2016-09-01

A simple sample pre-treatment method based on solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) has been optimized and validated for the assessment of 15 residual solvents (2-propanol, 2-methylpentane, 3-methylpentane, acetone, ethyl acetate, benzene, hexane, methylcyclohexane, methylcyclopentane, m-xylene, propyl acetate, toluene, 1,2,4-trimethylbenzene, dichloromethane, and ethylbenzene) in seized illicit cocaine and heroin. DMSO and DMF as sample diluents were found to offer the best residual solvent transference to the head space for further adsorption onto the SPME fiber, and the developed method therefore showed high sensitivity and analytical recovery. Variables affecting SPME were fully evaluated by applying an experimental design approach. Best conditions were found when using an equilibration time of 5 min at 70 °C and headspace sampling of residual solvents at the same temperature for 15 min. Method validation, performed within the requirements of international guidelines, showed excellent sensitivity, as well as intra- and inter-day precision and accuracy. The proposed methodology was applied to 96 cocaine samples and 14 heroin samples seized in Galicia (northwestern Spain) within 2013 and 2014.

Inhalants

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Notes Articles Adolescent Cigarette, Alcohol Use Declines as Marijuana Use Rises ( February 2013 ) Program Helps Troubled Boys ...

NIDA Notes

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... were more likely to misuse opioid analgesics. Why Marijuana Displeases Basic Science , Published March 2018 This study ...

Drugged Driving

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... in the past year. Middle Figure: Driving after marijuana use is more common than driving after alcohol ...

Teens Mix Prescription Opioids with Other Substances

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... least one other substance in the past year. Marijuana and alcohol were the most common (58.5% ...

Substance Use in Women and Men

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Text Description of Infographic Figure 1: Differences in Marijuana Use Disorder Women: develop disorder more quickly 1 ...

How Can Prescription Drug Addiction Be Treated?

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Principles of Substance Abuse Prevention for Early Chil... Marijuana: Facts Parents Need to Know Marijuana: Facts for ...

Polydrug Use and HIV Risk Among People Who Inject Heroin in Tijuana, Mexico: A Latent Class Analysis.

PubMed

Meacham, Meredith C; Rudolph, Abby E; Strathdee, Steffanie A; Rusch, Melanie L; Brouwer, Kimberly C; Patterson, Thomas L; Vera, Alicia; Rangel, Gudelia; Roesch, Scott C

2015-01-01

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. Participants were PWID residing in Tijuana, aged ≥18 years who reported heroin injection in the past six months and were recruited through respondent-driven sampling (n = 1,025). Latent class analysis was conducted to assign individuals to classes on a probabilistic basis, using four indicators of past six-month polydrug and polyroute use: cocaine injecting, cocaine smoking or snorting, methamphetamine injecting, and methamphetamine smoking or snorting. Latent class membership was regressed onto covariates in a multinomial logistic regression. 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. 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.

Polydrug use and HIV risk among people who inject heroin in Tijuana, Mexico: A Latent class analysis

PubMed Central

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.

2016-01-01

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

Brief Intervention Helps Adolescents Curb Substance Use

MedlinePlus

... Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines ... Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids Other Drugs Over-the-Counter ...

Treat Jail Detainees' Drug Abuse to Lower HIV Transmission

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Illegal Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids Other Drugs Over-the- ...

Expanded HIV Screening Projected to Decrease Spread of the Virus

MedlinePlus

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Illegal Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids Other Drugs Over-the- ...

What You Need to Know About Drugs: Heroin

MedlinePlus

... illegal narcotic because it is has dangerous side effects and is very addictive. Sometimes Called: horse, smack, big H, black tar, caballo (Spanish), 8-ball (heroin mixed with crack cocaine), junk, TNT How It's Used: Heroin is usually ...

Application of ToFSIMS to Studying Surface Diffusion: Do cocaine and heroin form a two-dimensional gas on surfaces?

NASA Astrophysics Data System (ADS)

Avci, Recep; Maccagnano, Sara; Bohannan, Gary; Gresham, Gary; Groenewold, Gary

2001-03-01

Imaging time-of-flight secondary ion mass spectroscopy ( ToFSIMS) is a practical tool for studying the movement of molecules on material surfaces as a function of time. The high detection sensitivity, rapid data acquisition and reasonable spatial resolution present ideal conditions for such studies. An application of ToFSIMS is presented characterizing the diffusion of large molecules on gold-coated Si wafers. Polydimethylsiloxane (PDMS) was selected for study because it contaminates material surfaces and can be detected easily. Also, the temperature dependent diffusion properties of hydrochlorinated heroin and cocaine are presented as part of a forensic application. While the PDMS diffusion could be explained by a two-dimensional ( 2-D) Brownian motion with a Gaussian probability distribution function (pdf) with a diffusion coefficient of 1.6 μ m^2/sec, the cocaine and to a lesser extent heroin were observed to move nearly freely on the surfaces as though they were part of a 2-D gas evaporating in 2-D from a condensed phase. The results could be described reasonably well using an extreme Lévi pdf with an index of stability α<= 0.01.

Substance Use and Mental Health Trends among U.S. Military Active Duty Personnel: Key Findings from the 2008 DoD Health Behavior Survey

DTIC Science & Technology

2010-06-01

marijuana or hashish, cocaine. LSD, PCP. MDMA , other hallucino- gens, methamphetamine, heroin, GHB/GBL, and inhalants. Prescription drugs included...dayB. Any Illinit Dmg LJsp inRluning Prèsf.nptinn Drug K îsiLsa = »sa nt manjuana cocaine (including crackl, hallucinogens (PCP WDA MDMA and othet...S. bartnlurates/sedaiivas. orpain wlievers Illiril nn [Isp. F^i:lnili = use o( marijuana, cocaine ¡including Crack), hallucinpgens (PCP. MDA, MDMA

Days of heroin use predict poor self-reported health in hospitalized heroin users

PubMed Central

Meshesha, Lidia Z.; Tsui, Judith I.; Liebschutz, Jane M.; Crooks, Denise; Anderson, Bradley J.; Herman, Debra S.; Stein, Michael D.

2013-01-01

This study examined associations between substance use behaviors and self-reported health among hospitalized heroin users. Of the 112 participants, 53 (47%) reported good or better health. In multivariable logistic regression models, each day of heroin use in the last month was associated with an 8% lower odds of reporting health as good or better (OR=.92; 95%CI 0.87, 0.97, p < .05). Cocaine, cannabis, cigarettes, alcohol use, unintentional overdose, nor injection drug use were associated with health status. PMID:24045030

Cognitive-behavioural therapy for heroin and cocaine use: Ecological momentary assessment of homework simplification and compliance.

PubMed

Willner-Reid, Jessica; Whitaker, Damiya; Epstein, David H; Phillips, Karran A; Pulaski, Amber R; Preston, Kenzie L; Willner, Paul

2016-09-01

The purpose of this study was to evaluate the effects of homework-task difficulty and electronic-diary reminders on written homework completion during cognitive-behavioural therapy (CBT) for addiction. Completion of homework is an important element in CBT that may affect outcome. All participants received all combinations of our two interventions in a factorial 2 × 2 counterbalanced Latin-square design. Methadone-maintained cocaine and heroin users were given homework between each of 12 weekly CBT sessions and carried electronic diaries that collected ecological momentary assessment (EMA) data on craving and exposure to drug-use triggers in four 3-week blocks assessing two levels of homework difficulty and prompted and unprompted homework. Neither simplified (picture-based) homework nor electronic reminders increased homework completion. In EMA reports, standard but not simplified homework seemed to buffer the craving that followed environmental exposure to drug cues. EMA recordings before and after the CBT intervention confirmed a decrease over time in craving for cocaine and heroin. These findings demonstrate the utility of EMA to assess treatment effects. However, the hypothesis that simplified homework would increase compliance was not supported. Our simplifications of homework assignments for cognitive-behavioural therapy were mostly ineffective, or even counterproductive, perhaps because they did not engage sufficient depth of processing or because they were perceived as too simplistic. Our reminder beeps for homework were mostly ineffective, or even counterproductive, suggesting that mobile electronic interventions for substance-use disorders may need to be more interactive. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball'-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers

PubMed Central

Greenwald, Mark K; Lundahl, Leslie H; Steinmiller, Caren L

2010-01-01

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball' (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy. PMID:20881947

Sexually transmitted infections among pregnant heroin or cocaine addicted women in treatment: The significance of psychiatric comorbidity and sex trade

PubMed Central

Cavanaugh, Courtenay E.; Hedden, Sarra L.; Latimer, William W.

2010-01-01

Summary Psychiatric comorbidity and sex trade were tested as correlates of sexually transmitted infections (STIs) among 76 pregnant heroin or cocaine dependent women. Participants were recruited from a drug treatment program and attended a clinician-administered assessment including the Structured Clinical Interview for DSM-IV (SCID-IV-TR) and self report questionnaires about lifetime histories of sex trade and STIs (i.e. gonorrhea, syphilis, chlamydia, herpes, genital warts, or trichomonas). Lifetime and six month rates of STIs were 53.9% and 18.4% respectively. The majority of women also had lifetime histories of psychiatric comorbidity (61.8%) and/or sex trade (60.5%). Participants with psychiatric comorbidity (AOR 3.9; 95% CI 1.3–11.6) and/or sex trade (AOR 3.2; 95% CI 1.1–9.5) were more likely to report STIs during their lifetime compared to those without such histories while controlling for age, education, and race/ethnicity. Results suggest that as many as one-in-five pregnant heroin or cocaine dependent women in treatment have one or more STIs that are concurrent with their pregnancy and may contribute to risk for contracting HIV and pregnancy complications; psychiatric comorbidity and/or sex trade were associated with greater STI risk. Findings underscore the importance of identifying and addressing comorbid psychiatric disorders and sex trade behavior in this population. PMID:20090001

Neuronal representation of individual heroin choices in the orbitofrontal cortex.

PubMed

Guillem, Karine; Brenot, Viridiana; Durand, Audrey; Ahmed, Serge H

2018-05-01

Drug addiction is a harmful preference for drug use over and at the expense of other non-drug-related activities. We previously identified in the rat orbitofrontal cortex (OFC) a mechanism that influences individual preferences between cocaine use and an alternative action rewarded by a non-drug reward (i.e. sweet water). Here, we sought to test the generality of this mechanism to a different addictive drug, heroin. OFC neuronal activity was recorded while rats responded for heroin or the alternative non-drug reward separately or while they chose between the two. First, we found that heroin-rewarded and sweet water-rewarded actions were encoded by two non-overlapping OFC neuronal populations and that the relative size of the heroin population represented individual drug choices. Second, OFC neurons encoding the preferred action-which was the non-drug action in the large majority of individuals-progressively fired more than non-preferred action-coding neurons 1 second after the onset of choice trials and around 1 second before the preferred action was actually chosen, suggesting a pre-choice neuronal competition for action selection. Together with a previous study on cocaine choice, the present study on heroin choice reveals important commonalities in how OFC neurons encode individual drug choices and preferences across different classes of drugs. It also reveals some drug-specific differences in OFC encoding activity. Notably, the proportion of neurons that non-selectively encode both the drug and the non-drug reward was higher when the drug was heroin (present study) than when it was cocaine (previous study). We will discuss the potential functional significance of these commonalities and differences in OFC neuronal activity across different drugs for understanding drug choice. © 2017 Society for the Study of Addiction.

[Hallucinogens].

PubMed

Morita, Nobuaki; Shimane, Takuya

2010-08-01

Hallucinogens are drugs that cause hallucinations, which is distortions in a person s perceptions of reality. Historically they were found in some plants and mushrooms and had been used mostly during religious rituals. Various hallucinogens came to be compounded chemically in the 20th century, and have spread among the young men in West European countries. Also in Japan, use of MDMA, or other hallucinogens is increasing in the young adult and minors. In recent years, Japanese medicine-related law were revised and most hallucinogens came to be treated as illegal drugs, but even now Japanese young men have got hallucinogens through the Internet and dance clubs, and medical and educational staffs and caregivers need to implement early intervention.

Differences in Mortality among Heroin, Cocaine, and Methamphetamine Users: A Hierarchical Bayesian Approach

PubMed Central

Liang, Li-Jung; Huang, David; Brecht, Mary-Lynn; Hser, Yih-ing

2010-01-01

Studies examining differences in mortality among long-term drug users have been limited. In this paper, we introduce a Bayesian framework that jointly models survival data using a Weibull proportional hazard model with frailty, and substance and alcohol data using mixed-effects models, to examine differences in mortality among heroin, cocaine, and methamphetamine users from five long-term follow-up studies. The traditional approach to analyzing combined survival data from numerous studies assumes that the studies are homogeneous, thus the estimates may be biased due to unobserved heterogeneity among studies. Our approach allows us to structurally combine the data from different studies while accounting for correlation among subjects within each study. Markov chain Monte Carlo facilitates the implementation of Bayesian analyses. Despite the complexity of the model, our approach is relatively straightforward to implement using WinBUGS. We demonstrate our joint modeling approach to the combined data and discuss the results from both approaches. PMID:21052518

Modeling the structure and operation of drug supply chains: The case of cocaine and heroin in Italy and Slovenia.

PubMed

Caulkins, Jonathan P; Disley, Emma; Tzvetkova, Marina; Pardal, Mafalda; Shah, Hemali; Zhang, Xiaoke

2016-05-01

Multiple layers of dealers connect international drug traffickers to users. The fundamental activity of these dealers is buying from higher-level dealers and re-selling in smaller quantities at the next lower market level. Each instance of this can be viewed as completing a drug dealing "cycle". This paper introduces an approach for combining isolated accounts of such cycles into a coherent model of the structure, span, and profitability of the various layers of the domestic supply chain for illegal drugs. The approach is illustrated by synthesizing data from interviews with 116 incarcerated dealers to elucidate the structure and operation of distribution networks for cocaine and heroin in Italy and Slovenia. Inmates' descriptions of cycles in the Italian cocaine market suggest fairly orderly networks, with reasonably well-defined market levels. The Italian heroin market appears to have more "level-jumpers" who skip a market level by making a larger number of sales per cycle, with each sale being of a considerably smaller weight. Slovenian data are sparser, but broadly consistent. Incorporating prices allows calculation of how much of the revenue from retail sales is retained by dealers at each market level. In the Italian cocaine market, both retail sellers and the international supply chain outside of Italy each appear to receive about 30-40% of what users spend, with the remaining 30% going to higher-level dealers operating in Italy (roughly 10% to those at the multi-kilo level and 20% to lower level wholesale dealers). Factoring in cycle frequencies permits rough estimation of the number of organizations at each market level per billion euros in retail sales, and of annual net revenues for organizations at each level. These analyses provide an approach to gaining insight into the structure and operation of the supply chain for illegal drugs. They also illustrate the value of two new graphical tools for describing illicit drug supply chains and hint at possible

Drug Use among American High School Students, College Students, and Other Young Adults. National Trends Through 1985.

ERIC Educational Resources Information Center

Johnston, Lloyd D.; And Others

Drug use and related attitudes of U.S. high school seniors from the graduating classes of 1975-1985 and young adults in their late teens and early- to mid-twenties were studied, as part of an ongoing research project. Eleven classes of drugs were assessed: marijuana (including hashish), inhalants, hallucinogens, cocaine, heroin, other natural and…

[Hallucinogenic mushrooms].

PubMed

Reingardiene, Dagmara; Vilcinskaite, Jolita; Lazauskas, Robertas

2005-01-01

The group of hallucinogenic mushrooms (species of the genera Conocybe, Gymnopilus, Panaeolus, Pluteus, Psilocybe, and Stropharia) is psilocybin-containing mushrooms. These "magic", psychoactive fungi have the serotonergic hallucinogen psilocybin. Toxicity of these mushrooms is substantial because of the popularity of hallucinogens. Psilocybin and its active metabolite psilocin are similar to lysergic acid diethylamide. These hallucinogens affect the central nervous system rapidly (within 0.5-1 hour after ingestion), producing ataxia, hyperkinesis, and hallucinations. In this review article there are discussed about history of use of hallucinogenic mushrooms and epidemiology; pharmacology, pharmacodynamics, somatic effects and pharmacokinetics of psilocybin, the clinical effects of psilocybin and psilocin, signs and symptoms of ingestion of hallucinogenic mushrooms, treatment and prognosis.

Do painkillers serve as "hillbilly heroin" for rural adults with high levels of psychosocial stress?

PubMed

Black, Pamela; Hendy, Helen M

2017-07-05

Nonmedical use of painkillers has increased in recent years, with some authors suggesting that painkillers serve as "hillbilly heroin": a drug chosen by rural adults to cope with psychosocial stresses in their lives. The present study compared rural and urban adults for their reported use of 5 drugs during the past year (painkillers, marijuana, cocaine, methamphetamine, heroin) and for associations between these 5 drugs and their reported psychosocial stressors. This study conducted secondary analyses of anonymous survey data provided by the 2014 National Survey on Drug Use and Health with responses from 8,699 rural and 18,481 urban adults. The survey included demographics (gender, age, race, education, marital status, family income), reports of whether participants had used each of 5 illicit drugs during the past year, and measures of psychological distress and social functioning problems. Controlling for demographics, rural adults showed no greater prevalence of painkiller use than urban adults, but rural adults were more likely than urban adults to use methamphetamine and less likely to use marijuana, cocaine, and heroin. Controlling for demographics, rural adults showed no associations between psychological or social stressors and the use of painkillers, but such stressors were significantly associated with the use of marijuana, methamphetamine, and heroin. Urban adults showed significant associations of psychological and social stressors with the use of painkillers, as well as with the use of marijuana, cocaine, and heroin. Results suggest that painkillers are unlikely to serve as "hillbilly heroin" for rural adults, but they may serve as "big-city heroin" for urban adults.

Hallucinogen Use Disorders Among Adult Users of MDMA and Other Hallucinogens

PubMed Central

Wu, Li-Tzy; Ringwalt, Christopher L.; Mannelli, Paolo; Patkar, Ashwin A.

2008-01-01

We investigated the prevalence, patterns, and correlates of past-year DSM-IV hallucinogen use disorders (HUDs) among past-year users of MDMA and other hallucinogens from a sample of Americans 18 or older (n = 37,227). Users were categorized as MDMA users and other hallucinogen users. Overall, one in five (20%) MDMA users and about one in six (16%) other hallucinogen users reported at least one clinical feature of HUDs. Among MDMA users, prevalence of hallucinogen abuse, subthreshold dependence, and dependence was 4.9%, 11.9%, and 3.6%, respectively. The majority with hallucinogen abuse displayed subthreshold dependence. Most with hallucinogen dependence exhibited abuse. Subthreshold hallucinogen dependence is relatively prevalent and represents a clinically important subgroup that warrants future research and consideration in a major diagnostic classification system. PMID:18770077

Demand Curves for Hypothetical Cocaine in Cocaine-Dependent Individuals

PubMed Central

Bruner, Natalie R.; Johnson, Matthew W.

2013-01-01

Rationale Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. Objectives This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Methods Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Results Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and Omax (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, Pmax, were significantly correlated with real-world cocaine use. Conclusions Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use. PMID:24217899

Demand curves for hypothetical cocaine in cocaine-dependent individuals.

PubMed

Bruner, Natalie R; Johnson, Matthew W

2014-03-01

Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use.

Drug Intoxicated Irregular Fighters: Complications, Dangers, and Responses

DTIC Science & Technology

2008-03-01

manufactured . The result is the use of marijuana, khat, hallucinogenic mush- rooms, cocaine, heroin, methamphetamine, and looted pharmaceuticals to...drugs in today’s wars falls into at least one of four categories: traditional, transshipped, looted, and manufactured . These categories are not...also be attained by looting them from pharmacies, clinics, and hospitals. These are prescrip- tion drugs manufactured by pharmaceutical companies 10

Opponent process properties of self-administered cocaine.

PubMed

Ettenberg, Aaron

2004-01-01

Over the past decade, data collected in our laboratory have demonstrated that self-administered cocaine produces Opponent-Process-like behavioral effects. Animals running a straight alley once each day for IV cocaine develop over trials an approach-avoidance conflict about re-entering the goal box. This conflict behavior is characterized by a stop in forward locomotion (usually at the very mouth of the goal box) followed by a turn and 'retreat' back toward the goal box. The results of a series of studies conducted over the past decade collectively suggest that the behavioral ambivalence exemplified by rats running the alley for IV cocaine stems from concurrent and opponent positive (rewarding) and negative (anxiogenic) properties of the drug--both of which are associated with the goal box. These opponent properties of cocaine have been shown to result from temporally distinct affective states. Using a conditioned place preference test, we have been able to demonstrate that while the initial immediate effects of IV cocaine are reinforcing, the state present 15 min post-injection is aversive. In our most recent work, the co-administration of IV cocaine with either oral ethanol or IV heroin was found to greatly diminish the development and occurrence of retreat behaviors in the runway. It may therefore be that the high incidence of co-abuse of cocaine with either ethanol or heroin, stems from the users' motivation to alleviate some of the negative side effects of cocaine. It would seem then that the Opponent Process Theory has provided a useful conceptual framework for the study of the behavioral consequences of self-administered cocaine including the notion that both positive and negative reinforcement mechanisms are involved in the development and maintenance of cocaine abuse.

Acute morphine and cocaine related death after trimethoprim-adultered cocaine abuse.

PubMed

Fucci, Nadia; Pascali, Vincenzo L

2014-01-01

Over the last few decades, cocaine and morphine (heroin) have been among the primary causes of deaths related to drug abuse. Cocaine is frequently altered by dilution, substitution, contamination, and adulteration. Trimethoprim has never been identified in the powders of cocaine, making this the first post-mortem case report in which the presence of this compound is described. The case reported here is that of a 46-year-old woman with a history of cocaine and morphine abuse who was found dead inside her bathroom. The police found the corpse next to a syringe, with a telephone card containing trace of cocaine on the sink. Toxicological analysis was performed, and drug levels were measured by means of gas chromatography/mass spectrometry. In addition to the presence of cocaine and smaller alkaloids, trimethoprim was also detected on the syringe and telephone card and in the woman's nasal mucosa. Trimethoprim analysis is very quick and easy and can be added to the routine analysis of drugs of abuse seized on the illicit market to obtain more information. © 2014 by the Association of Clinical Scientists, Inc.

Oral Fluid as an Alternative Matrix to Monitor Opiate and Cocaine Use in Substance-Abuse Treatment Patients

PubMed Central

Dams, Riet; Choo, Robin E.; Lambert, Willy E.; Jones, Hendree; Huestis, Marilyn A.

2007-01-01

Interest in oral fluid as an alternative matrix for monitoring drug use is due to its ease-of-collection and non-invasiveness; however, limited data are available on the disposition of drugs into oral fluid. The objective of this research was to provide data on the presence and concentrations of heroin, cocaine and multiple metabolites in oral fluid after illicit opioid and cocaine use. Thrice weekly oral fluid specimens (N=403) from 16 pregnant opiate-dependent women were obtained with the Salivette® oral fluid collection device. Evidence of heroin (N=62) and cocaine (N=130) use was detected in oral fluid by LC-APCI-MS/MS. 6-Acetylmorphine (6-AM), heroin and morphine were the major opiates detected, with median concentrations of 5.2, 2.3, and 7.5 μg/L, respectively. Cocaine and benzoylecgonine (BE) had median concentrations of 6.4 and 3.4 μg/L. Application of the Substance Abuse Mental Health Services Administration (SAMHSA) recommended cutoffs for morphine and codeine (40 μg/L), 6-AM (4 μg/L) and cocaine and BE (8 μg/L), yielded 28 opiate- and 50 cocaine-positive specimens. Oral fluid is a promising alternative matrix to monitor opiate and cocaine use in drug testing programs. These data guide interpretation of oral fluid test results and evaluate currently proposed SAMHSA oral fluid testing cutoffs. PMID:17008030

Recent Increases in Cocaine-Related Overdose Deaths and the Role of Opioids.

PubMed

McCall Jones, Christopher; Baldwin, Grant T; Compton, Wilson M

2017-03-01

To assess trends in cocaine overdose deaths and examine the role opioids play in these deaths. We used data on drug overdose deaths in the United States from 2000 to 2015 collected in the National Vital Statistics System to calculate annual rates and numbers of cocaine-related overdose deaths overall and deaths both involving and not involving opioids. We assessed statistically significant changes in trends with joinpoint regression. Rates of cocaine-related overdose deaths increased significantly from 1.26 to 2.50 per 100 000 population from 2000 to 2006, declined to 1.35 in 2010, and increased to 2.13 in 2015. Cocaine-related overdose deaths involving opioids increased from 0.37 to 0.91 from 2000 to 2006, declined to 0.57 in 2010, and then increased to 1.36 in 2015. Cocaine-related overdose deaths not involving opioids increased from 0.89 to 1.59 from 2000 to 2006 and then declined to 0.78 in 2015. Opioids, primarily heroin and synthetic opioids, have been driving the recent increase in cocaine-related overdose deaths. This corresponds to the growing supply and use of heroin and illicitly manufactured fentanyl in the United States.

Cocaine behavioral economics: From the naturalistic environment to the controlled laboratory setting

PubMed Central

Greenwald, Mark K.; Steinmiller, Caren L.

2017-01-01

Background We previously observed that behavioral economic factors predict naturalistic heroin seeking behavior that correlates with opioid seeking in the experimental laboratory. The present study sought to replicate and extend these prior findings with regular cocaine users. Methods Participants (N = 83) completed a semi-structured interview to establish income-generating and cocaine-purchasing/use repertoire during the past month. Questions addressed sources/amounts of income and expenditures; price (money and time) per purchase; and frequency/amounts of cocaine purchased and consumed. Naturalistic cocaine purchasing and use patterns were: (1) analyzed as a function of income quartile, (2) perturbed by hypothetical changes in cost factors to assess changes in purchasing/use habits, and (3) correlated with experimental cocaine seeking. Results Income was positively related to naturalistic cocaine seeking/use pattern (i.e., income elastic), and behaviors were cost-efficient and sensitive to supply chain. Income was unrelated to proportional expenditure on cocaine (≈55%) but inversely related to food expenditure. In all hypothetical scenarios (changes in income or dealer, loss of income assistance from government or family/friends, and increasing arrest risk when purchasing), the high-income group reported they would continue to use more cocaine daily than other groups. Number of laboratory cocaine choices significantly correlated with cocaine purchase time (positively) and purity of cocaine (negatively) in the naturalistic setting. Conclusions These results replicate and extend findings with regular heroin users, demonstrate the importance of income, cost-efficiency and supply-mindedness in cocaine seeking/use, and suggest that this interview-based approach has good external validity. PMID:24878248

Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose

PubMed Central

Griswold, Matthew K.; Chai, Peter R.; Krotulski, Alex J.; Friscia, Melissa; Chapman, Brittany; Boyer, Edward W.; Logan, Barry K.; Babu, Kavita M.

2018-01-01

Objective To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. Methods This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and non-pharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. Results Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. Conclusions Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700). PMID:28681615

Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose.

PubMed

Griswold, Matthew K; Chai, Peter R; Krotulski, Alex J; Friscia, Melissa; Chapman, Brittany; Boyer, Edward W; Logan, Barry K; Babu, Kavita M

2018-01-01

To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and nonpharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700).

The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens.

PubMed

Canal, Clinton E; Murnane, Kevin S

2017-01-01

Classic hallucinogens share pharmacology as serotonin 5-HT 2A , 5-HT 2B , and 5-HT 2C receptor agonists. Unique among most other Schedule 1 drugs, they are generally non-addictive and can be effective tools in the treatment of addiction. Mechanisms underlying these attributes are largely unknown. However, many preclinical studies show that 5-HT 2C agonists counteract the addictive effects of drugs from several classes, suggesting this pharmacological property of classic hallucinogens may be significant. Drawing from a comprehensive analysis of preclinical behavior, neuroanatomy, and neurochemistry studies, this review builds rationale for this hypothesis, and also proposes a testable, neurobiological framework. 5-HT 2C agonists work, in part, by modulating dopamine neuron activity in the ventral tegmental area-nucleus accumbens (NAc) reward pathway. We argue that activation of 5-HT 2C receptors on NAc shell, GABAergic, medium spiny neurons inhibits potassium Kv1.x channels, thereby enhancing inhibitory activity via intrinsic mechanisms. Together with experiments that show that addictive drugs, such as cocaine, potentiate Kv1.x channels, thereby suppressing NAc shell GABAergic activity, this hypothesis provides a mechanism by which classic hallucinogen-mediated stimulation of 5-HT 2C receptors could thwart addiction. It also provides a potential reason for the non-addictive nature of classic hallucinogens.

Simultaneous Liquid Chromatography–Mass Spectrometry Quantification of Urinary Opiates, Cocaine, and Metabolites in Opiate-Dependent Pregnant Women in Methadone-Maintenance Treatment

PubMed Central

Shakleya, Diaa M.; Dams, Riet; Choo, Robin E.; Jones, Hendree; Huestis, Marilyn A.

2011-01-01

Opiates, cocaine, and metabolites were quantified by liquid chromatography–mass spectrometry (LC–MS) in 284 urine specimens, collected thrice weekly, to monitor possible drug relapse in 15 pregnant heroin-dependent women. Opiates were detected in 149 urine specimens (52%) with limits of quantification (LOQ) of 10–50 μg/L. Morphine, morphine-3-glucuronide, and/or morphine-6-glucuronide were positive in 121 specimens; 6-acetylmorphine, a biomarker of heroin ingestion, was quantifiable in only 7. No heroin, 6-acetylcodeine, papaverine, or noscapine were detected. One hundred and sixty-five urine specimens (58%) from all 15 participants were positive for one or more cocaine analytes (LOQ 10–100 μg/L). Ecgonine methylester (EME) and/or benzoylecgonine were the major cocaine biomarkers in 142. Anhydroecgonine methylester, a biomarker of smoked cocaine, was positive in six; cocaethylene and/or ecgonine ethylester, biomarkers of cocaine and ethanol co-ingestion, were found in 25. At the current Substance Abuse Mental Health Services Administration cutoffs for total morphine (2000 μg/L), codeine (2000 μg/L), 6-acetylmorphine (10 μg/L), and benzoylecgonine (100 μg/L), 16 opiate- and 29 cocaine-positive specimens were identified. Considering 100 μg/L EME as an additional urinary cocaine biomarker would identify 51 more positive cocaine specimens. Of interest is the differential pattern of opiate and cocaine biomarkers observed after LC–MS as compared to gas chromatography–mass spectrometry analysis. PMID:20109298

Drug Abuse: The Crack Cocaine Epidemic Health Consequences and Treatment.

DTIC Science & Technology

1991-01-01

addicts . Buackground Once considered to be nonaddictive, recent studies show that cocaine is one of the most potent drugs of abuse. Cocaine is a...responsibility for addiction prevention and treatment programs. The agencies we contacted include NIDA, the Alcohol, Drug Abuse, and Mental Health Administration...heroin addicts for Treating Crack are being used to treat many crack addicts . Meanwhile, drug treatment Addicts researchers are experimenting with new

Disrupted white matter integrity in heroin dependence: a controlled study utilizing diffusion tensor imaging.

PubMed

Liu, Haihong; Li, Lin; Hao, Yihui; Cao, Dong; Xu, Lin; Rohrbaugh, Robert; Xue, Zhimin; Hao, Wei; Shan, Baoci; Liu, Zhening

2008-01-01

Fractional anisotropy (FA) via diffusion tensor imaging (DTI) can quantify the white matter integrity. Exposure to addictive drugs, such as alcohol, cocaine, methamphetamine, marijuana, and nicotine has been shown to alter FA. White matter abnormalities have been shown, but it remains unclear whether the white matter FA is altered in heroin dependence. Utilizing DTI, we investigated the FA difference between heroin-dependent and control subjects by a voxel-based strategy. The FA values of the identified regions were calculated from the FA image of each subject and were correlated with clinical features including months of heroin use, age, education, and dose of methadone. Reduced FA among 16 heroin dependent subjects was located in the bilateral frontal sub-gyral regions, right precentral and left cingulate gyrus. FA in the right frontal sub-gyral was negatively correlated with duration of heroin use. The disrupted white matter integrity in right frontal white matter may occur in continuous heroin abuse.

The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens

PubMed Central

Canal, Clinton E; Murnane, Kevin S

2017-01-01

Classic hallucinogens share pharmacology as serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonists. Unique among most other Schedule 1 drugs, they are generally non-addictive and can be effective tools in the treatment of addiction. Mechanisms underlying these attributes are largely unknown. However, many preclinical studies show that 5-HT2C agonists counteract the addictive effects of drugs from several classes, suggesting this pharmacological property of classic hallucinogens may be significant. Drawing from a comprehensive analysis of preclinical behavior, neuroanatomy, and neurochemistry studies, this review builds rationale for this hypothesis, and also proposes a testable, neurobiological framework. 5-HT2C agonists work, in part, by modulating dopamine neuron activity in the ventral tegmental area—nucleus accumbens (NAc) reward pathway. We argue that activation of 5-HT2C receptors on NAc shell, GABAergic, medium spiny neurons inhibits potassium Kv1.x channels, thereby enhancing inhibitory activity via intrinsic mechanisms. Together with experiments that show that addictive drugs, such as cocaine, potentiate Kv1.x channels, thereby suppressing NAc shell GABAergic activity, this hypothesis provides a mechanism by which classic hallucinogen-mediated stimulation of 5-HT2C receptors could thwart addiction. It also provides a potential reason for the non-addictive nature of classic hallucinogens. PMID:27903793

Youth, Heroin, Crack: A Review of Recent British Trends

ERIC Educational Resources Information Center

Seddon, Toby

2008-01-01

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…

A survey of hallucinogenic mushroom use, factors related to usage, and perceptions of use among college students.

PubMed

Hallock, Robert M; Dean, Andrew; Knecht, Zachary A; Spencer, Jared; Taverna, Elise C

2013-06-01

Recreational usage and attitudes toward psilocybin-containing hallucinogenic mushrooms among college students are seldom explored. We surveyed 882 randomly selected undergraduates at Skidmore College in upstate New York and quantified whether participants had ever used psilocybin mushrooms, their attitudes toward the drug, and polydrug use. There were 409 responses and 29.5% of the sample reported psilocybin use. Among users, the mean number of times they reported using mushrooms was 3.4 (mode=1). The top factors cited that influenced their decisions to try hallucinogenic mushrooms for the first time were 'curiosity', 'to achieve a mystical experience', and 'introspection'. Users and non-users had significantly different perceptions of mushrooms: non-users were more likely to say that hallucinogenic mushrooms were addictive and had the potential for abuse than users. Users did not believe that psilocybin negatively impacts their academics, mental health, or physical health, while non-users did. Both users and non-users of psilocybin reported high life-time use of alcohol (97% vs 96%, respectively), marijuana (98% vs 73%, respectively) and tobacco (82% vs 54%, respectively). Psilocybin users were significantly more likely to use other drugs such as cocaine, ecstasy, opiates, non-prescribed prescription drugs, opiates, and lysergic acid diethylamide (LSD) than non-users of psilocybin. This study uncovers important insights into hallucinogenic mushroom use by college students. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria: implications for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition.

PubMed

Kerridge, Bradley T; Saha, Tulshi D; Smith, Sharon; Chou, Patricia S; Pickering, Roger P; Huang, Boji; Ruan, June W; Pulay, Attila J

2011-09-01

Prior research has demonstrated the dimensionality of Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria. The purpose of this study was to examine the dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria. In addition, we assessed the impact of elimination of the legal problems abuse criterion on the information value of the aggregate abuse and dependence criteria, another proposed change for DSM-IV currently lacking empirical justification. Factor analyses and item response theory (IRT) analyses were used to explore the unidimisionality and psychometric properties of hallucinogen and inhalant/solvent abuse and dependence criteria using a large representative sample of the United States (U.S.) general population. Hallucinogen and inhalant/solvent abuse and dependence criteria formed unidimensional latent traits. For both substances, IRT models without the legal problems abuse criterion demonstrated better fit than the corresponding model with the legal problem abuse criterion. Further, there were no differences in the information value of the IRT models with and without the legal problems abuse criterion, supporting the elimination of that criterion. No bias in the new diagnoses was observed by sex, age and race-ethnicity. Consistent with findings for alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria, hallucinogen and inhalant/solvent criteria reflect underlying dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the DSM-V Substance and Related Disorders Workgroup, that is, combining DSM-IV abuse and dependence criteria and eliminating the legal problems abuse

The selective dopamine D3 receptor antagonist, SR 21502, reduces cue-induced reinstatement of heroin seeking and heroin conditioned place preference in rats.

PubMed

Galaj, Ewa; Manuszak, Monica; Babic, Sandra; Ananthan, Subramaniam; Ranaldi, Robert

2015-11-01

Because the role of dopamine (DA) D3 receptors has been investigated primarily in relation to cocaine-related behaviors little is known of the role of these receptors in heroin seeking. To investigate the effect of the selective DA D3 receptor antagonist, SR 21502, on cue-induced reinstatement of heroin seeking and heroin conditioned place preference (CPP). In experiment 1, rats were trained to self-administer intravenous heroin for 15 days followed by extinction. Following extinction animals were treated with one of several SR 21502 doses (0, 7.5, 10 or 15mg/kg) and a cue-induced reinstatement test was conducted. In experiment 2, animals were conditioned to experience heroin in one compartment of a CPP apparatus and saline in the other. On the test day animals were treated with 0, 3.75, 7.5, 10 or 15mg/kg of SR 21502 and tested for their CPP. The results from experiment 1 showed a significant dose-related reduction in cue-induced reinstatement of active lever pressing in the 7.5 and 10mg groups and an absence of the reinstatement effect in the 15mg group. In experiment 2, animals treated with vehicle or 3.75mg of SR 21502 showed significant heroin place preferences but those treated with the higher doses showed no CPP. Our findings suggest that DA D3 receptors play a significant role in heroin approach behaviors driven by conditioned stimuli. As such, we propose that SR 21502 holds potential as an effective pharmacotherapeutic agent for relapse prevention and should be studied further. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Risks associated with crack cocaine smoking among exotic dancers in Baltimore, MD.

PubMed

Sherman, Susan G; Reuben, Jacqueline; Chapman, Chris Serio; Lilleston, Pamela

2011-04-01

There is a dearth of research focusing on sex work in exotic dance clubs. We conducted a cross-sectional study to examine the prevalence and correlates of crack cocaine smoking among a sample of exotic dancers. The "block," a historical red-light district in downtown Baltimore, MD, is comprised of 30 adult-entertainment establishments. Between 01/09 and 08/09, we conducted a survey with exotic dancers (N=98). The survey explored demographic, and drug and sexual/drug risk behaviors. Bivariate and multivariate analysis was conducted using Poisson regression with robust variance estimates to examine correlates of current crack smoking. Crack cocaine smokers compared to non-crack cocaine smokers were significantly more likely to report: older age (29 vs. 23 years, respectively, p<0.0001); being White (79% vs. 50%, respectively, p=0.008); having been arrested (93% vs. 67%, respectively, p=0.008); daily alcohol consumption (36% vs. 17%, p=0.047); current heroin injection (57% vs. 13%, p<0.001); and current sex exchange (79% vs. 30%, p<0.001). In the presence of other variables, crack cocaine smokers compared to non-crack cocaine smokers were significantly older, more likely to report current heroin injection, and more likely to report current sex exchange. We found high levels of drug use and sexual risk behaviors as well as a number of risks behaviors associated with crack cocaine smoking among this very under-studied population. Targeted interventions are greatly needed. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Dimensionality of Hallucinogen and Inhalant/Solvent Abuse and Dependence Criteria: Implications for the Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition

PubMed Central

Kerridge, Bradley T.; Saha, Tulshi D.; Smith, Sharon; Chou, Patricia S.; Pickering, Roger P.; Huang, Boji; Ruan, June W.; Pulay, Attila J.

2012-01-01

Background Prior research has demonstrated the dimensionality of Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria. The purpose of this study was to examine the dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria. In addition, we assessed the impact of elimination of the legal problems abuse criterion on the information value of the aggregate abuse and dependence criteria, another proposed change for DSM- IV currently lacking empirical justification. Methods Factor analyses and item response theory (IRT) analyses were used to explore the unidimisionality and psychometric properties of hallucinogen and inhalant/solvent abuse and dependence criteria using a large representative sample of the United States (U.S.) general population. Results Hallucinogen and inhalant/solvent abuse and dependence criteria formed unidimensional latent traits. For both substances, IRT models without the legal problems abuse criterion demonstrated better fit than the corresponding model with the legal problem abuse criterion. Further, there were no differences in the information value of the IRT models with and without the legal problems abuse criterion, supporting the elimination of that criterion. No bias in the new diagnoses was observed by sex, age and race-ethnicity. Conclusion Consistent with findings for alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria, hallucinogen and inhalant/solvent criteria reflect underlying dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the DSM-V Substance and Related Disorders Workgroup, that is, combining DSM-IV abuse and dependence criteria

Hallucinogens

MedlinePlus

... perception responses to the environment emotion learning and memory Short-Term Effects The effects of hallucinogens can begin within 20 to 90 minutes and can last as long as 6 to 12 hours. Salvia's effects are ...

[Hallucinogens, amphetamines and entactogens].

PubMed

Vollenweider, F X; Vollenweider-Scherpenhuyzen, M F

2003-06-01

MDMA ("Ecstasy") and its analogues such as MDE and MDA are amphetamine derivatives reported to produce an altered state with emotional overtones. Since more than ten years, ecstasy is after cannabis the most frequently used recreational drug by young adults, particularly in the so-called techno-scene. However, according to a recent survey there is an increasing trend for a revival of classic amphetamine and hallucinogen abuse, possibly due to the concern about the potential neurotoxicity and somatic risks associated with ecstasy use. Of the hallucinogens consumed, psilocybin containing mushroom ("magic mushrooms"), but also LSD are at the forefront. The present contribution summarizes the psychological and somatic effects of hallucinogens, amphetamines, and entactogens.

Monitoring Pregnant Women’s Illicit Opiate and Cocaine Use With Sweat Testing

PubMed Central

Brunet, Bertrand R.; Barnes, Allan J.; Choo, Robin E.; Mura, Patrick; Jones, Hendrée E.; Huestis, Marilyn A.

2011-01-01

Dependence on illicit drugs during pregnancy is a major public health concern as there may be associated adverse maternal, fetal, and neonatal consequences. Sweat patches (n = 389) were collected from 39 pregnant volunteers who provided written informed consent for this Institutional Review Board-approved protocol and wore patches, replaced approximately weekly, from study entry until delivery. Patches were analyzed for opiates (heroin, 6-acetylmor-phine, 6-acetylcodeine, morphine and codeine) and cocaine (cocaine, benzoylecgonine, ecgonine methyl ester, anhydroecgonine methyl ester) by solid phase extraction and gas chromatography mass spectrometry. Seventy-one percent (276) of collected sweat patches were ≥5 ng per patch (limit of quantification) for one or more analytes. Cocaine was present in 254 (65.3%) patches in concentrations ranging from 5.2 to 11,835 ng per patch with 154 of these high enough to satisfy the proposed Substance Abuse and Mental Health Services Administration guidelines for a confirmatory drug test (25 ng per patch). Interestingly, 6-acetylmorphine was the most prominent opiate analyte documented in 134 patches (34.4%) with 11.3% exceeding the proposed opiate Substance Abuse and Mental Health Services Administration cut-off (25 ng per patch). Heroin was identified in fewer patches (77), but in a similar concentration range (5.3–345.4 ng per patch). Polydrug use was evident by the presence of both cocaine and opiate metabolites in 136 (35.0%) patches. Sweat testing is an effective method for monitoring abstinence or illicit drug use relapse in this high-risk population of pregnant opiate- and/or cocaine-dependent women. PMID:19927046

The behavioral pharmacology of hallucinogens

PubMed Central

Fantegrossi, William E.; Murnane, Aeneas C.; Reissig, Chad J.

2008-01-01

Until very recently, comparatively few scientists were studying hallucinogenic drugs. Nevertheless, selective antagonists are available for relevant serotonergic receptors, the majority of which have now been cloned, allowing for reasonably thorough pharmacological investigation. Animal models sensitive to the behavioral effects of the hallucinogens have been established and exploited. Sophisticated genetic techniques have enabled the development of mutant mice, which have proven useful in the study of hallucinogens. The capacity to study post-receptor signaling events has lead to the proposal of a plausible mechanism of action for these compounds. The tools currently available to study the hallucinogens are thus more plentiful and scientifically advanced than were those accessible to earlier researchers studying the opioids, benzodiazepines, cholinergics, or other centrally active compounds. The behavioral pharmacology of phenethylamine, tryptamine, and ergoline hallucinogens are described in this review, paying particular attention to important structure activity relationships which have emerged, receptors involved in their various actions, effects on conditioned and unconditioned behaviors, and in some cases, human psychopharmacology. As clinical interest in the therapeutic potential of these compounds is once again beginning to emerge, it is important to recognize the wealth of data derived from controlled preclinical studies on these compounds. PMID:17977517

Therapeutic Applications of Classic Hallucinogens.

PubMed

Bogenschutz, Michael P; Ross, Stephen

2018-01-01

This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. A survey of possible mechanisms of clinically relevant effects is provided. The well-established safety of classic hallucinogens is reviewed. To provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. The studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including

Extensive Necrotic Purpura in Levamisole-Adulterated Cocaine Abuse - A Case Report.

PubMed

Le Garff, Erwan; Tournel, Gilles; Becquart, Coralie; Cottencin, Olivier; Dupin, Nicolas; Delaporte, Emmanuel; Hedouin, Valéry

2016-11-01

Levamisole, which is used as an adulterated compound of cocaine, is currently being seen year after year in cocaine intoxication. For a few cases in the last decade, necrotic purpura and neutropenia after levamisole/cocaine intoxication have been described in the medical community. Herein, we present an original case of levamisole intoxication of a 40-year-old woman who smoked heroin and cocaine few during a month. She rapidly presented an extensive necrotic purpura of the nose, cheeks and extremities (lower and upper), and immunologic reactions (positive anti-MPO and anti-HNE). Levamisole was detected on hairs with ultra-high performance liquid chromatography and tandem mass spectrometry. The case reports also a probable cocaine supplier deceit, which bring pure drug for hospital investigation after the intoxication of his client. The intoxicated woman had survived with several skin and chronic pain complications. That case recalls the knowledge about levamisole with a short review of the forensic literature. © 2016 American Academy of Forensic Sciences.

Human Hallucinogen Research: Guidelines for Safety

PubMed Central

Johnson, Matthew W.; Richards, William A.; Griffiths, Roland R.

2010-01-01

There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action (“bad trip”), which could lead to potentially dangerous behavior such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment, and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science. PMID:18593734

Cocaine and Instability in Africa: Lessons from Latin America and the Caribbean (Africa Security Brief, Number 5, July 2010)

DTIC Science & Technology

2010-07-01

however, that instability in East Africa is attracting heroin traffic (contributing to an esti- Davin O’Regan is a Research Associate at the Africa...Narcotics trafficking is not intrinsically violent. Violence within the international trade in cannabis and Ecstasy , a popular hallucinogen...70 people were killed in clashes and gun battles. Trafficking- associated violence can reach even more dangerous levels. In Mexico, traffickers fre

Discriminative Stimulus Effects of Psychostimulants and Hallucinogens in S(+)-3,4-Methylenedioxymethamphetamine (MDMA) and R(−)-MDMA Trained Mice

PubMed Central

Murnane, K. S.; Murai, N.; Howell, L. L.

2009-01-01

3,4-Methylenedioxymethamphetamine (MDMA) is a substituted phenethylamine more commonly known as the drug of abuse “ecstasy.” The acute and persistent neurochemical effects of MDMA in the mice are distinct from those in other species. MDMA shares biological effects with both amphetamine-type stimulants and mescaline-type hallucinogens, which may be attributable to distinct effects of its two enantiomers, both of which are active in vivo. In this regard, among the substituted phenethylamines, R(−)-enantiomers tend to have hallucinogen-like effects, whereas S(+)-enantiomers tend to have stimulant-like effects. In the present study, mice were trained to discriminate S(+)- or R(−)-MDMA from vehicle. Drug substitution tests were then undertaken with the structurally similar phenethylamine dopamine/norepinephrine releaser S(+)-amphetamine, the structurally dissimilar tropane nonselective monoamine reuptake inhibitor cocaine, the structurally similar phenethylamine 5-hydroxytryptamine (5-HT)2A agonist 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), and the structurally dissimilar mixed action tryptamine 5-HT2A agonist/monoamine reuptake inhibitor N,N-dipropyltryptamine (DPT). S(+)-amphetamine fully substituted in the S(+)-MDMA-treated animals but did not substitute for the R(−)-MDMA cue. 2C-T-7 fully substituted in the R(−)-MDMA-trained animals but did not substitute for the S(+)-MDMA cue. Cocaine and DPT substituted for both training drugs, but whereas cocaine was more potent in S(+)-MDMA-trained mice, DPT was more potent in R(−)-MDMA-trained mice. These data suggest that qualitative differences in the discriminative stimulus effects of each stereoisomer of MDMA exist in mice and further our understanding of the complex nature of the interoceptive effects of MDMA. PMID:19684254

Acute effects of heroin on emotions in heroin-dependent patients.

PubMed

Blum, Julia; Gerber, Hana; Gerhard, Urs; Schmid, Otto; Petitjean, Sylvie; Riecher-Rössler, Anita; Wiesbeck, Gerhard A; Borgwardt, Stefan J; Walter, Marc

2013-01-01

Euphoria has been described in heroin-dependent individuals after heroin administration. However, affective disturbances and disorders are common in heroin dependence. The present study examined the acute effects of heroin on emotions in heroin-dependent patients. This randomized controlled crossover trial included 28 heroin-dependent patients (67.9% male, n = 19) in stable heroin-assisted treatment and 20 healthy controls. The patients were administered heroin or saline (placebo), the controls were administered saline. Data measuring mood, affects and heroin craving (BDI, AMRS, STAI, STAXI, and HCQ) were assessed before and 60 minutes after substance injection. Before substance injection, heroin-dependent patients showed significantly higher levels of anxiety and depression than healthy controls (p < .0001). Heroin administration-but not placebo administration-was associated with a significant decrease in all negative emotions, including craving, and a significant increase in emotional well-being (p < .0001), irrespective of perceived intoxication and sedation. After the experiment, the patients did not differ from healthy controls in their emotions, once they had received heroin. Heroin dampens craving, negative emotions, and increases positive emotions. These findings indicate that heroin regulates emotions and underscore the clinical benefit of opioid substitution treatment for heroin-dependent patients. Copyright © American Academy of Addiction Psychiatry.

Activation of AMPA receptor in the infralimbic cortex facilitates extinction and attenuates the heroin-seeking behavior in rats.

PubMed

Chen, Weisheng; Wang, Yiqi; Sun, Anna; Zhou, Linyi; Xu, Wenjin; Zhu, Huaqiang; Zhuang, Dingding; Lai, Miaojun; Zhang, Fuqiang; Zhou, Wenhua; Liu, Huifen

2016-01-26

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Patterns of drug use and HIV infection among adults in a nationally representative sample

PubMed Central

Shiau, Stephanie; Arpadi, Stephen M.; Yin, Michael T.; Martins, Silvia S.

2017-01-01

Background Little is known about drug use patterns among people living with HIV in comparison to an uninfected group in the general population. The aim of this study was to investigate the association between legal and illegal drug use and HIV infection in a nationally representative sample of adults in the United States. Methods Public use data files (2005–2014) from the National Survey on Drug Use and Health (NSDUH) were used. Respondents were asked whether a medical professional had ever told them that they had HIV/AIDS. Ever (lifetime), past-year, and past month use of cigarettes, alcohol, marijuana, cocaine, heroin, hallucinogens, inhalants, and nonmedical use of psychotherapeutics was assessed. Logistic regression was used to estimate adjusted odds ratios (aOR) of the relationship between drug use and HIV infection, adjusting for demographics. Results Of 377,787 respondents age 18 and older, 548 (0.19%) were categorized as HIV-infected. Ever use of cigarettes, tobacco, marijuana, cocaine, heroin, hallucinogens, inhalants, and psychotherapeutics was higher in HIV-infected individuals compared to HIV-uninfected individuals after adjustment for sex, age, race/ethnicity, education, total family income, and marital status. Past year and past month use was also higher for HIV-infected individuals for all substances aside from alcohol. Conclusions In a nationally representative sample, there are higher levels of drug use and DSM-IV dependence among the HIV-infected population compared to the HIV-uninfected population. This is of concern because drug use and dependence can impede engagement in HIV care and adherence to antiretroviral therapy. PMID:28088742

Do hallucinogens cause residual neuropsychological toxicity?

PubMed

Halpern, J H; Pope, H G

1999-02-01

We collected and reviewed studies in which neuropsychological tests were administered to users of LSD or other hallucinogens. Interpretation of the studies is limited by various confounding variables, such as subjects' premorbid cognitive and personality function and prior use of other substances. At present, the literature tentatively suggests that there are few, if any, long-term neuropsychological deficits attributable to hallucinogen use. To better resolve this issue, however, it will be important to study larger samples of chronic, frequent hallucinogen users who have not often used other types of drugs.

Association between cholesterol plasma levels and craving among heroin users.

PubMed

Lin, Shih-Hsien; Yang, Yen Kuang; Lee, Sheng-Yu; Hsieh, Pei Chun; Chen, Po See; Lu, Ru-Band; Chen, Kao Chin

2012-12-01

Lipids may play some roles in the central nervous system functions that are associated with drug addiction. To date, cholesterol is known to influence relapse of cocaine use. However, the relationship between cholesterol and heroin craving is unclear. This study examined the concurrent association between cholesterol and craving. The serum lipid levels of 70 heroin users who were undergoing or had undergone a methadone maintenance therapy were measured. Their craving and demographic data were assessed. Total cholesterol and low-density lipoprotein cholesterol are negatively associated with craving before (r = -0.33, P < 0.01, and r = -0.36, P < 0.01, respectively) and after controlling for the effects of potential confounders (β = -0.38, P < 0.01, and β = -0.42, P < 0.01, respectively). Cholesterol could be associated with the cognitive aspect of craving and may be a potential marker to predict risk of drug relapse.

Simultaneous determination of opiates, cocaine and major metabolites of cocaine in human hair by gas chromotography/mass spectrometry (GC/MS).

PubMed

Kintz, P; Mangin, P

1995-05-22

A procedure is presented for the simultaneous identification and quantification of morphine (MOR), codeine (COD), ethylmorphine (EM), 6-monoacetylmorphine (6-MAM), cocaine (COC), benzoylecgonine (BZE), ecgonine methylester (EME) and cocaethylene (CE), contained in the hair of opiates and cocaine addicts. The method involves decontamination in dichloromethane, pulverization in a ball mill, heat-acid hydrolysis, addition of deuterated internal standards, liquid-liquid extraction and gas chromatography/mass spectrometry (GC/MS) after silylation. The limit of detection (LOD) was approximately 0.1-0.8 ng/mg for each drug, using a 30-mg hair sample. The method is reproductible, with a coefficient of variation (CV) of approximately 8-17%. Cocaine and 6-monoacetylmorphine were the major compounds detected in cases of cocaine (14 cases) and heroin (68 cases) intake. Concentrations were in the range 0.4-78.4 ng/mg (COC), 0.0-36.3 ng/mg (BZE), 0.0-1.6 ng/mg (EME), 0.0-2.1 ng/mg (CE), 0.0-84.3 ng/mg (6-MAM), 0.2-27.1 ng/mg (MOR) and 0.1-19.6 ng/mg (COD). An application in forensic sciences, involving multi-sectional analysis, is given.

Brain mechanisms of hallucinogens and entactogens

PubMed Central

Vollenweider, Franz X.

2001-01-01

This review focuses on recent brain imaging and behavioral studies of sensory gating functions, which assess similarities between the effects of classic hallucinogens (eg, psilocybin), dissociative anesthetics (eg, ketamine), and entactogens (eg, 3,4-methylenedioxymethamphetamine [MDMA]) in humans. Serotonergic hallucinogens and psychotomimetic anesthetics produce overlapping psychotic syndromes associated with a marked activation of the prefrontal cortex (hyperfrontality) and other overlapping changes in temporoparietal, striatal, and thalamic regions, suggesting that both classes of drugs act upon a common final pathway. Together with the observation that both hallucinogens and N-methyl-oaspartate (NMDA) antagonists disrupt sensory gating in rats by acting on 5-hydroxytryptamine (serotonin) 5-HT2 receptors located in cortico-striato-thalamic circuitry these findings suggest that disruption of cortico-subcortical processing leading to sensory overload of the cortex is a communality of these psychoses. In contrast to hallucinogens, the entactogen MDMA produces an emotional state of positive mood, concomitant with an activation of prefrontolimbiclparalimbic structures and a deactivation of amygdala and thalamus. PMID:22033605

Hallucinogens and cannabinoids for headache.

PubMed

McGeeney, Brian E

2012-10-01

Most hallucinogens and cannabinoids fall into Federal Controlled Substances schedule 1, meaning they cannot be prescribed by practitioners, allegedly have no accepted medical use, and have a high abuse potential. The legal and regulatory status has inhibited clinical research on these substances such that there are no blinded studies from which to assess true efficacy. Despite such classification, hallucinogens and cannabinoids are used by patients with headache on occasion. Cannabinoids in particular have a long history of use for headache and migraine before prohibition and are still used by patients as a migraine abortive. Hallucinogens are being increasing used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and to maintain quiescence for which there is considerable anecdotal success. © 2012 American Headache Society.

Heroin uncertainties: Exploring users' perceptions of fentanyl-adulterated and -substituted 'heroin'.

PubMed

Ciccarone, Daniel; Ondocsin, Jeff; Mars, Sarah G

2017-08-01

The US is experiencing an unprecedented opioid overdose epidemic fostered in recent years by regional contamination of the heroin supply with the fentanyl family of synthetic opioids. Since 2011 opioid-related overdose deaths in the East Coast state of Massachusetts have more than tripled, with 75% of the 1374 deaths with an available toxicology positive for fentanyl. Fentanyl is 30-50X more potent than heroin and its presence makes heroin use more unpredictable. A rapid ethnographic assessment was undertaken to understand the perceptions and experiences of people who inject drugs sold as 'heroin' and to observe the drugs and their use. A team of ethnographers conducted research in northeast Massachusetts and Nashua, New Hampshire in June 2016, performing (n=38) qualitative interviews with persons who use heroin. (1) The composition and appearance of heroin changed in the last four years; (2) heroin is cheaper and more widely available than before; and (3) heroin 'types' have proliferated with several products being sold as 'heroin'. These consisted of two types of heroin (alone), fentanyl (alone), and heroin-fentanyl combinations. In the absence of available toxicological information on retail-level heroin, our research noted a hierarchy of fentanyl discernment methods, with embodied effects considered most reliable in determining fentanyl's presence, followed by taste, solution appearance and powder color. This paper presents a new 'heroin' typology based on users' reports. Massachusetts' heroin has new appearances and is widely adulterated by fentanyl. Persons who use heroin are trying to discern the substances sold as heroin and their preferences for each form vary. The heroin typology presented is inexact but can be validated by correlating users' discernment with drug toxicological testing. If validated, this typology would be a valuable harm reduction tool. Further research on adaptations to heroin adulteration could reduce risks of using heroin and

Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens.

PubMed

Halberstadt, Adam L

2017-01-01

Serotonergic hallucinogens induce profound changes in perception and cognition. The characteristic effects of hallucinogens are mediated by 5-HT 2A receptor activation. One class of hallucinogens are 2,5-dimethoxy-substituted phenethylamines, such as the so-called 2C-X compounds 2,5-dimethoxy-4-bromophenethylamine (2C-B) and 2,5-dimethoxy-4-iodophenethylamine (2C-I). Addition of an N-benzyl group to phenethylamine hallucinogens produces a marked increase in 5-HT 2A -binding affinity and hallucinogenic potency. N-benzylphenethylamines ("NBOMes") such as N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (25I-NBOMe) show subnanomolar affinity for the 5-HT 2A receptor and are reportedly highly potent in humans. Several NBOMEs have been available from online vendors since 2010, resulting in numerous cases of toxicity and multiple fatalities. This chapter reviews the structure-activity relationships, behavioral pharmacology, metabolism, and toxicity of members of the NBOMe hallucinogen class. Based on a review of 51 cases of NBOMe toxicity reported in the literature, it appears that rhabdomyolysis is a relatively common complication of severe NBOMe toxicity, an effect that may be linked to NBOMe-induced seizures, hyperthermia, and vasoconstriction.

A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats.

PubMed

Li, Qian-Qian; Luo, Yi-Xiao; Sun, Cheng-Yu; Xue, Yan-Xue; Zhu, Wei-Li; Shi, Hai-Shui; Zhai, Hai-Feng; Shi, Jie; Lu, Lin

2011-12-01

Heroin use has seriously threatened public heath in many countries, but the existing therapies continue to have many limitations. Recently, immunotherapy has shown efficacy in some clinical studies, including vaccines against nicotine and cocaine, but no opioid vaccines have been introduced in clinical studies. The development of a novel opioid antigen designed specifically for the prevention of heroin addiction is necessary. A morphine-keyhole limpet hemocyanin conjugate was prepared and administered subcutaneously in rats. Antibody titers in plasma were measured using an enzyme-linked immunosorbent assay (ELISA). Competitive ELISA was used to assess the selectivity of the antibodies. Dopamine concentrations in the nucleus accumbens in rats after vaccine administration were determined by high-performance liquid chromatography with electrochemical detection. The effects of the vaccine on the heroin-primed restatement of self-administration and locomotor sensitization were evaluated. A novel hapten, 6-glutarylmorphine, was produced, and the vaccine generated a high antibody titer response. This vaccine displayed specificity for both morphine and heroin, but the anti-morphine antibodies could not recognize dissimilar therapeutic opioid compounds, such as buprenorphine, methadone, naloxone, naltrexone, codeine, and nalorphine. The morphine antibody significantly decreased morphine-induced locomotor activity in rats after immunization. Importantly, rats immunized with this vaccine did not exhibit heroin-primed reinstatement of heroin seeking when antibody levels were sufficiently high. The vaccine reduced dopamine levels in the nucleus accumbens after morphine administration, which is consistent with its behavioral effects. These results suggest that immunization with a novel vaccine is an effective means of inducing a morphine-specific antibody response that is able to attenuate the behavioral and psychoactive effects of heroin. © 2011 The Authors. Journal of

Recent Advances in the Neuropsychopharmacology of Serotonergic Hallucinogens

PubMed Central

Halberstadt, Adam L.

2014-01-01

Serotonergic hallucinogens, such as (+)-lysergic acid diethylamide, psilocybin, and mescaline, are somewhat enigmatic substances. Although these drugs are derived from multiple chemical families, they all produce remarkably similar effects in animals and humans, and they show cross-tolerance. This article reviews the evidence demonstrating the serotonin 5-HT2A receptor is the primary site of hallucinogen action. The 5-HT2A receptor is responsible for mediating the effects of hallucinogens in human subjects, as well as in animal behavioral paradigms such as drug discrimination, head twitch response, prepulse inhibition of startle, exploratory behavior, and interval timing. Many recent clinical trials have yielded important new findings regarding the psychopharmacology of these substances. Furthermore, the use of modern imaging and electrophysiological techniques is beginning to help unravel how hallucinogens work in the brain. Evidence is also emerging that hallucinogens may possess therapeutic efficacy. PMID:25036425

Is the New Heroin Epidemic Really New? Racializing Heroin.

PubMed

Bowser, Benjamin; Fullilove, Robert; Word, Carl

2017-01-01

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. Copyright © 2016 National Medical Association. Published by Elsevier Inc. All rights reserved.

Serotonergic hallucinogens as translational models relevant to schizophrenia.

PubMed

Halberstadt, Adam L; Geyer, Mark A

2013-11-01

One of the oldest models of schizophrenia is based on the effects of serotonergic hallucinogens such as mescaline, psilocybin, and (+)-lysergic acid diethylamide (LSD), which act through the serotonin 5-HT(2A) receptor. These compounds produce a 'model psychosis' in normal individuals that resembles at least some of the positive symptoms of schizophrenia. Based on these similarities, and because evidence has emerged that the serotonergic system plays a role in the pathogenesis of schizophrenia in some patients, animal models relevant to schizophrenia have been developed based on hallucinogen effects. Here we review the behavioural effects of hallucinogens in four of those models, the receptor and neurochemical mechanisms for the effects and their translational relevance. Despite the difficulty of modelling hallucinogen effects in nonverbal species, animal models of schizophrenia based on hallucinogens have yielded important insights into the linkage between 5-HT and schizophrenia and have helped to identify receptor targets and interactions that could be exploited in the development of new therapeutic agents.

Serotonergic Hallucinogens as Translational Models Relevant to Schizophrenia

PubMed Central

Halberstadt, Adam L.; Geyer, Mark A.

2014-01-01

One of the oldest models of schizophrenia is based on the effects of serotonergic hallucinogens such as mescaline, psilocybin, and (+)-lysergic acid diethylamide (LSD), which act through the serotonin 5-HT2A receptor. These compounds produce a “model psychosis” in normal individuals that resembles at least some of the positive symptoms of schizophrenia. Based on these similarities, and because evidence has emerged that the serotonergic system plays a role in the pathogenesis of schizophrenia in some patients, animal models relevant to schizophrenia have been developed based on hallucinogen effects. Here we review the behavioral effects of hallucinogens in four of those models, the receptor and neurochemical mechanisms for the effects, and their translational relevance. Despite the difficulty of modeling hallucinogen effects in nonverbal species, animal models of schizophrenia based on hallucinogens have yielded important insights into the linkage between 5-HT and schizophrenia and have helped to identify receptor targets and interactions that could be exploited in the development of new therapeutic agents. PMID:23942028

Recent advances in the neuropsychopharmacology of serotonergic hallucinogens.

PubMed

Halberstadt, Adam L

2015-01-15

Serotonergic hallucinogens, such as (+)-lysergic acid diethylamide, psilocybin, and mescaline, are somewhat enigmatic substances. Although these drugs are derived from multiple chemical families, they all produce remarkably similar effects in animals and humans, and they show cross-tolerance. This article reviews the evidence demonstrating the serotonin 5-HT2A receptor is the primary site of hallucinogen action. The 5-HT2A receptor is responsible for mediating the effects of hallucinogens in human subjects, as well as in animal behavioral paradigms such as drug discrimination, head twitch response, prepulse inhibition of startle, exploratory behavior, and interval timing. Many recent clinical trials have yielded important new findings regarding the psychopharmacology of these substances. Furthermore, the use of modern imaging and electrophysiological techniques is beginning to help unravel how hallucinogens work in the brain. Evidence is also emerging that hallucinogens may possess therapeutic efficacy. Copyright © 2014 Elsevier B.V. All rights reserved.

Heroin and Pregnancy

MedlinePlus

... Home > Pregnancy > Is it safe? > Heroin and pregnancy Heroin and pregnancy E-mail to a friend Please ... way that’s safe for your baby. What is heroin? Heroin (also called smack or junk) is an ...

Association of time-dependent changes in mu opioid receptor mRNA, but not BDNF, TrkB, or MeCP2 mRNA and protein expression in the rat nucleus accumbens with incubation of heroin craving.

PubMed

Theberge, Florence R M; Pickens, Charles L; Goldart, Evan; Fanous, Sanya; Hope, Bruce T; Liu, Qing-Rong; Shaham, Yavin

2012-12-01

Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC). We also investigated the effect of the preferential MOR antagonist naloxone on cue-induced heroin seeking during abstinence. We trained rats to self-administer heroin or saline for 9-10 days and then dissected the NAc, DS, and mPFC at different abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as well as MOR mRNA (Oprm1). In other groups, we assessed cue-induced heroin seeking in extinction tests after 1, 11, and 30 abstinence days, and naloxone's (0-1.0 mg/kg) effect on extinction responding after 1 and 15 days. Cue-induced heroin seeking progressively increased or incubated during abstinence. This incubation was not associated with changes in BDNF, TrkB, or MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular changes were observed after extinction tests on day 11. In NAc, but not DS or mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over time. Naloxone significantly decreased cue-induced heroin seeking after 15 abstinence days but not 1 day. Results suggest a role of MOR in incubation of heroin craving. As previous studies implicated NAc BDNF in incubation of cocaine craving, our data suggest that different mechanisms contribute to incubation of heroin versus cocaine craving.

Association of time-dependent changes in mu opioid receptor mRNA, but not BDNF, TrkB, or MeCP2 mRNA and protein expression in the rat nucleus accumbens with incubation of heroin craving

PubMed Central

Theberge, Florence R. M.; Pickens, Charles L.; Goldart, Evan; Fanous, Sanya; Hope, Bruce T.; Liu, Qing-Rong

2013-01-01

Rationale and objectives Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), dorsal striatum (DS), and medial pre-frontal cortex (mPFC). We also investigated the effect of the preferential MOR antagonist naloxone on cue-induced heroin seeking during abstinence. Methods We trained rats to self-administer heroin or saline for 9–10 days and then dissected the NAc, DS, and mPFC at different abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as well as MOR mRNA (Oprm1). In other groups, we assessed cue-induced heroin seeking in extinction tests after 1, 11, and 30 abstinence days, and naloxone’s (0–1.0 mg/kg) effect on extinction responding after 1 and 15 days. Results Cue-induced heroin seeking progressively increased or incubated during abstinence. This incubation was not associated with changes in BDNF, TrkB, or MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular changes were observed after extinction tests on day 11. In NAc, but not DS or mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over time. Naloxone significantly decreased cue-induced heroin seeking after 15 abstinence days but not 1 day. Conclusions Results suggest a role of MOR in incubation of heroin craving. As previous studies implicated NAc BDNF in incubation of cocaine craving, our data suggest that different mechanisms contribute to incubation of heroin versus cocaine craving. PMID:22790874

Impact of South American heroin on the US heroin market 1993-2004.

PubMed

Ciccarone, Daniel; Unick, George J; Kraus, Allison

2009-09-01

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. 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. 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. 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.

Heroin Addicts Reporting Previous Heroin Overdoses Also Report Suicide Attempts

ERIC Educational Resources Information Center

Bradvik, Louise; Frank, Arne; Hulenvik, Per; Medvedeo, Alvaro; Berglund, Mats

2007-01-01

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…

Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.

PubMed

Oliveto, A H; Feingold, A; Schottenfeld, R; Jatlow, P; Kosten, T R

1999-09-01

Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10. In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence. Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Heroin

MedlinePlus

... DEA Museum and Visitors' Center National Prevention Week Heroin Last Updated: Wednesday, December 27, 2017 What is ... from morphine and extracted from certain poppy plants. Heroin comes in a white or brownish powder, or ...

Classical hallucinogens and neuroimaging: A systematic review of human studies: Hallucinogens and neuroimaging.

PubMed

Dos Santos, Rafael G; Osório, Flávia L; Crippa, José Alexandre S; Hallak, Jaime E C

2016-12-01

Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have anxiolytic, antidepressant, and antiaddictive properties. These drugs act as agonists of frontocortical 5-HT 2A receptors, but the neural basis of their effects are not well understood. Thus, we conducted a systematic review of neuroimaging studies analyzing the effects of serotonergic hallucinogens in man. Studies published in the PubMed, Lilacs, and SciELO databases until 12 April 2016 were included using the following keywords: "ayahuasca", "DMT", "psilocybin", "LSD", "mescaline" crossed one by one with the terms "mri", "fmri", "pet", "spect", "imaging" and "neuroimaging". Of 279 studies identified, 25 were included. Acute effects included excitation of frontolateral/frontomedial cortex, medial temporal lobe, and occipital cortex, and inhibition of the default mode network. Long-term use was associated with thinning of the posterior cingulate cortex, thickening of the anterior cingulate cortex, and decreased neocortical 5-HT 2A receptor binding. Despite the high methodological heterogeneity and the small sample sizes, the results suggest that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parieto-occipital cortex. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association of testosterone levels and heroin usage characteristics in male heroin users.

PubMed

Wang, Zhuo; Zhou, Xiao-Bo; Yang, Xiao-Rong; Song, Hui; Cao, Bing-Rong; Yin, Fei; Kang, Lin; An, Zhen-Mei; Li, Jing

2017-05-01

Previous studies have shown that heroin abuse can alter the gonadal functions. Few studies examined the association between testosterone levels and heroin use in the existing literature. We aimed to determine the association between gonadal hormones and heroin usage characteristics over 12 weeks of abstinence in heroin users. We collected data on patient demographics and heroin use patterns for 65 men aged 18 to 45 and for 29 age-matched healthy controls. Serum levels of total testosterone, estradiol, and prolactin were assessed at 5 time points. Testosterone levels gradually increased and prolactin levels decreased in heroin users in this study. In heroin users, a significant positive correlation was observed between the way of using drug and the testosterone levels, the way of using drug and the estradiol levels, between the duration of heroin dependence and the testosterone levels, between the duration of heroin dependence and the estradiol levels on D0, and between relapse time and testosterone levels on D84. Our data reveal testosterone might promote injection drug use and repeated relapse in male heroin users.

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

PubMed Central

Halberstadt, Adam L.; Geyer, Mark A.

2011-01-01

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT2 receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT2A receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT2 and non-5-HT2 receptors. PMID:21256140

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens.

PubMed

Halberstadt, Adam L; Geyer, Mark A

2011-09-01

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT(2) receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT(2A) receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT(2) and non-5-HT(2) receptors. Copyright © 2011 Elsevier Ltd. All rights reserved.

"Every 'never' I ever said came true": transitions from opioid pills to heroin injecting.

PubMed

Mars, Sarah G; Bourgois, Philippe; Karandinos, George; Montero, Fernando; Ciccarone, Daniel

2014-03-01

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

The relationship between US heroin market dynamics and heroin-related overdose, 1992-2008.

PubMed

Unick, George; Rosenblum, Daniel; Mars, Sarah; Ciccarone, Daniel

2014-11-01

Heroin-related overdose is linked to polydrug use, changes in physiological tolerance and social factors. Individual risk can also be influenced by the structural risk environment including the illicit drug market. We hypothesized that components of the US illicit drug market, specifically heroin source/type, price and purity, will have independent effects on the number of heroin-related overdose hospital admissions. Yearly, from 1992 to 2008, Metropolitan Statistical Area (MSA) price and purity series were estimated from the US Drug Enforcement Administration data. Yearly heroin overdose hospitalizations were constructed from the Nationwide Inpatient Sample. Socio-demographic variables were constructed using several databases. Negative binomial models were used to estimate the effect of price, purity and source region of heroin on yearly hospital counts of heroin overdoses controlling for poverty, unemployment, crime, MSA socio-demographic characteristics and population size. Purity was not associated with heroin overdose, but each $100 decrease in the price per pure gram of heroin resulted in a 2.9% [95% confidence interval (CI) = 4.8%, 1.0%] increase in the number of heroin overdose hospitalizations (P = 0.003). Each 10% increase in the market share of Colombian-sourced heroin was associated with a 4.1% (95% CI = 1.7%, 6.6%) increase in number of overdoses reported in hospitals (P = 0.001) independent of heroin quality. Decreases in the price of pure heroin in the United States are associated with increased heroin-related overdose hospital admissions. Increases in market concentration of Colombian-source/type heroin is also associated with an increase in heroin-related overdose hospital admissions. Increases in US heroin-related overdose admissions appear to be related to structural changes in the US heroin market. © 2014 Society for the Study of Addiction.

Impact of South American heroin on the US heroin market 1993–2004

PubMed Central

Ciccarone, Daniel; Unick, George J; Kraus, Allison

2008-01-01

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

Classic hallucinogens in the treatment of addictions.

PubMed

Bogenschutz, Michael P; Johnson, Matthew W

2016-01-04

Addictive disorders are very common and have devastating individual and social consequences. Currently available treatment is moderately effective at best. After many years of neglect, there is renewed interest in potential clinical uses for classic hallucinogens in the treatment of addictions and other behavioral health conditions. In this paper we provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review other relevant research concerning hallucinogens, and suggest directions for future research. Clinical trial data are very limited except for the use of LSD in the treatment of alcoholism, where a meta-analysis of controlled trials has demonstrated a consistent and clinically significant beneficial effect of high-dose LSD. Recent pilot studies of psilocybin-assisted treatment of nicotine and alcohol dependence had strikingly positive outcomes, but controlled trials will be necessary to evaluate the efficacy of these treatments. Although plausible biological mechanisms have been proposed, currently the strongest evidence is for the role of mystical or other meaningful experiences as mediators of therapeutic effects. Classic hallucinogens have an excellent record of safety in the context of clinical research. Given our limited understanding of the clinically relevant effects of classic hallucinogens, there is a wealth of opportunities for research that could contribute important new knowledge and potentially lead to valuable new treatments for addiction. Copyright © 2015 Elsevier Inc. All rights reserved.

US federal cocaine essential (‘precursor’) chemical regulation impacts on US cocaine availability: an intervention time–series analysis with temporal replication

PubMed Central

Callaghan, Russell C.; Liu, Lon‐Mu

2015-01-01

Abstract Background and Aims Research shows that essential/precursor chemical controls have had substantial impacts on US methamphetamine and heroin availability. This study examines whether US federal essential chemical regulations have impacted US cocaine seizure amount, price and purity—indicators of cocaine availability. Design Autoregressive integrated moving average (ARIMA)‐intervention time–series analysis was used to assess the impacts of four US regulations targeting cocaine manufacturing chemicals: potassium permanganate/selected solvents, implemented October 1989 sulfuric acid/hydrochloric acid, implemented October 1992; methyl isobutyl ketone, implemented May 1995; and sodium permanganate, implemented December 2006. Of these chemicals, potassium permanganate and sodium permanganate are the most critical to cocaine production. Setting Conterminous United States (January 1987—April 2011). Measurements Monthly time–series: purity‐adjusted cocaine seizure amount (in gross weight seizures < 6000 grams), purity‐adjusted price (all available seizures), and purity (all available seizures). Data source: System to Retrieve Information from Drug Evidence. Findings The 1989 potassium permanganate/solvents regulation was associated with a seizure amount decrease (change in series level) of 28% (P < 0.05), a 36% increase in price (P < 0.05) and a 4% decrease in purity (P < 0.05). Availability recovered in 1–2 years. The 2006 potassium permanganate regulation was associated with a 22% seizure amount decrease (P < 0.05), 100% price increase (P < 0.05) and 35% purity decrease (P < 0.05). Following the 2006 regulation, essentially no recovery occurred to April 2011. The other two chemical regulations were associated with statistically significant but lesser declines in indicated availability. Conclusions In the United States, essential chemical controls from 1989 to 2006 were associated with pronounced downturns in cocaine availability. PMID:25559418

Cue-induced activation of implicit affective associations with heroin use in abstinent heroin abusers.

PubMed

Chen, Jianyong; Wang, Xuan; Zhang, Meng; Zhang, Feng; Shen, Mowei

2015-06-01

While drug-related contexts have been shown to influence drug users' implicit and explicit drug-related cognitions, this has been minimally explored in heroin abusers. This study examined the effect of heroin-related cue exposure on implicit and explicit valence and arousal-sedation associations with heroin use for abstinent heroin abusers. In Experiment 1, 39 male abstinent heroin abusers were exposed to heroin-related words and reported cravings before and after cue exposure. They subsequently performed two Extrinsic Affective Simon Tasks (EASTs), which were used to assess implicit valence and arousal-sedation associations with heroin use. Thirty-six male abstinent heroin abusers (controls) only performed the two EASTs. All participants completed measures of explicit expectancy regarding heroin use. In Experiment 2, twenty-eight newly recruited abstinent heroin abusers were exposed to heroin-related pictures, and completed the same implicit and explicit measures used in Experiment 1. A non-significant increase in craving after cue exposure was observed. While participants exposed to heroin-related words or pictures exhibited more positive implicit heroin use associations (relative to negative associations), and such trend was not observed in controls, this difference was not significant across groups. Participants still indicated negative explicit associations with heroin use after cue exposure. Exposure to cues significantly accelerated arousal and sedation responses. Whether cue exposure could change self-reported craving requires further study in abstinent heroin abusers. The exclusively male sample limits generalization of the results. The present findings extend the evidence on whether implicit and explicit heroin-related cognitions are susceptible to context. Copyright © 2014 Elsevier Ltd. All rights reserved.

Heroin (Smack, Junk) Facts

MedlinePlus

... That People Abuse » Heroin (Smack, Junk) Facts Heroin (Smack, Junk) Facts Listen ©istock.com/ Bestfotostudio Heroin ... 301.56 KB) (301.56 KB) "I needed heroin just to get by." ©istock.com/ pixelheadphoto Deon ...

Anticonvulsants for cocaine dependence.

PubMed

Minozzi, Silvia; Cinquini, Michela; Amato, Laura; Davoli, Marina; Farrell, Michael F; Pani, Pier Paolo; Vecchi, Simona

2015-04-17

Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles. All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence. We used the standard methodological procedures expected by The Cochrane Collaboration. We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95

Risks for HIV infection among users and sellers of crack, powder cocaine and heroin in central Harlem: Implications for interventions

PubMed Central

DAVIS, W. REES; JOHNSON, B. D.; RANDOLPH, D.; LIBERTY, H. J.

2007-01-01

This article investigates behaviours that may be associated HIV infection among users and sellers of crack, powder cocaine and heroin in central Harlem. Chain referral sampling and other strategies were combined to acquire a sample of 637 (Users = 546; Sellers = 91) who provided urine specimens that were tested for the presence of drugs and HIV. Nearly a quarter (23.9%) of all respondents were HIV positive. Drug injectors were more than 2.5 times more likely to have HIV infections than other respondents (OR = 2.66; 95% CI 1.66–4.26). Those involved in frauds/cons were almost as likely to be HIV positive (OR = 2.58; 95% CI 1.64–4.06). Those with a marital status of being separated, divorced or widowed were twice as likely to be HIV infected (OR 2.16; 95% CI 1.43–3.25). Respondents currently having multiple partner sex (OR = 1.66; 95% CI 1.1–2.51) or who were female (OR = 1.66; 95% CI 1.12–2.45) were more than 1.5 times more likely to be HIV positive. Thus, controlling for lifetime drug injection and current multiple partner sex, other factors, such as participating in frauds/cons, as well as relationship status and being female, were also associated with HIV infection. PMID:16338774

The relationship between US heroin market dynamics and heroin-related overdose, 1992–2008

PubMed Central

Unick, George; Rosenblum, Daniel; Mars, Sarah; Ciccarone, Daniel

2017-01-01

Background and Aims Heroin-related overdose is linked to polydrug use, changes in physiological tolerance and social factors. Individual risk can also be influenced by the structural risk environment including the illicit drug market. We hypothesized that components of the US illicit drug market, specifically heroin source/type, price and purity, will have independent effects on the number of heroin-related overdose hospital admissions. Methods Yearly, from 1992 to 2008, Metropolitan Statistical Area (MSA) price and purity series were estimated from the US Drug Enforcement Administration data. Yearly heroin overdose hospitalizations were constructed from the Nationwide Inpatient Sample. Socio-demographic variables were constructed using several databases. Negative binomial models were used to estimate the effect of price, purity and source region of heroin on yearly hospital counts of heroin overdoses controlling for poverty, unemployment, crime, MSA socio-demographic characteristics and population size. Results Purity was not associated with heroin overdose, but each $100 decrease in the price per pure gram of heroin resulted in a 2.9% [95% confidence interval (CI) = 4.8%, 1.0%] increase in the number of heroin overdose hospitalizations (P = 0.003). Each 10% increase in the market share of Colombian-sourced heroin was associated with a 4.1% (95% CI = 1.7%, 6.6%) increase in number of overdoses reported in hospitals (P = 0.001) independent of heroin quality. Conclusions Decreases in the price of pure heroin in the United States are associated with increased heroin-related overdose hospital admissions. Increases in market concentration of Colombian-source/type heroin is also associated with an increase in heroin-related overdose hospital admissions. Increases in US heroin-related overdose admissions appear to be related to structural changes in the US heroin market. PMID:24938727

Effects of incentives for naltrexone adherence on opiate abstinence in heroin-dependent adults

PubMed Central

Jarvis, Brantley P.; Holtyn, August F.; DeFulio, Anthony; Dunn, Kelly E.; Everly, Jeffrey J.; Leoutsakos, Jeannie-Marie S.; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E.; Silverman, Kenneth

2017-01-01

Aim To test whether an incentive-based intervention that increased adherence to naltrexone also increased opiate abstinence. Design Post-hoc combined analysis of three earlier randomized controlled trials that individually showed that incentives for adherence to oral and to extended-release injection naltrexone dosing schedules increased naltrexone adherence but not opiate abstinence. Setting Outpatient therapeutic workplace in Baltimore, MD, USA. Participants 140 unemployed heroin-dependent adults participating from 2006–2010. Interventions Participants were hired in a model workplace for 26 weeks and randomized to a Contingency (n=72) or Prescription (n=68) group. Both groups were offered naltrexone. Contingency participants were required to take scheduled doses of naltrexone in order to work and earn wages. Prescription participants could earn wages independent of naltrexone adherence. Measures Thrice-weekly and monthly urine samples tested for opiates and cocaine and measures of naltrexone adherence (percentage of monthly urine samples positive for naltrexone or percentage of scheduled injections received). All analyses included prerandomization attendance, opiate use, and cocaine use as covariates. Additional analyses controlled for cocaine use and naltrexone adherence during the intervention. Findings Contingency participants had more opiate abstinence than Prescription participants (68.1% vs. 52.9% opiate-negative thrice-weekly urine samples, respectively; and 71.9% vs. 61.7% opiate-negative monthly urine samples, respectively) based on initial analyses (thrice-weekly samples, OR = 3.3, 95% CI = 1.7–6.5, p < .01; monthly samples, OR = 2.6, 95% CI = 1.0–7.1, p = .06) and on analyses that controlled for cocaine use (thrice-weekly samples, OR = 3.9, 95% CI = 3.3–4.5, p < .01; monthly samples, OR = 3.4, 95% CI = 1.1–11.1, p =.04), which was high and associated with opiate use. The difference in opiate abstinence rates between Contingency participants

US federal cocaine essential ('precursor') chemical regulation impacts on US cocaine availability: an intervention time-series analysis with temporal replication.

PubMed

Cunningham, James K; Callaghan, Russell C; Liu, Lon-Mu

2015-05-01

Research shows that essential/precursor chemical controls have had substantial impacts on US methamphetamine and heroin availability. This study examines whether US federal essential chemical regulations have impacted US cocaine seizure amount, price and purity-indicators of cocaine availability. Autoregressive integrated moving average (ARIMA)-intervention time-series analysis was used to assess the impacts of four US regulations targeting cocaine manufacturing chemicals: potassium permanganate/selected solvents, implemented October 1989 sulfuric acid/hydrochloric acid, implemented October 1992; methyl isobutyl ketone, implemented May 1995; and sodium permanganate, implemented December 2006. Of these chemicals, potassium permanganate and sodium permanganate are the most critical to cocaine production. Conterminous United States (January 1987-April 2011). Monthly time-series: purity-adjusted cocaine seizure amount (in gross weight seizures < 6000 grams), purity-adjusted price (all available seizures), and purity (all available seizures). System to Retrieve Information from Drug Evidence. The 1989 potassium permanganate/solvents regulation was associated with a seizure amount decrease (change in series level) of 28% (P < 0.05), a 36% increase in price (P < 0.05) and a 4% decrease in purity (P < 0.05). Availability recovered in 1-2 years. The 2006 potassium permanganate regulation was associated with a 22% seizure amount decrease (P < 0.05), 100% price increase (P < 0.05) and 35% purity decrease (P < 0.05). Following the 2006 regulation, essentially no recovery occurred to April 2011. The other two chemical regulations were associated with statistically significant but lesser declines in indicated availability. In the United States, essential chemical controls from 1989 to 2006 were associated with pronounced downturns in cocaine availability. © 2015 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Perspectives on zebrafish models of hallucinogenic drugs and related psychotropic compounds.

PubMed

Neelkantan, Nikhil; Mikhaylova, Alina; Stewart, Adam Michael; Arnold, Raymond; Gjeloshi, Visar; Kondaveeti, Divya; Poudel, Manoj K; Kalueff, Allan V

2013-08-21

Among different classes of psychotropic drugs, hallucinogenic agents exert one of the most prominent effects on human and animal behaviors, markedly altering sensory, motor, affective, and cognitive responses. The growing clinical and preclinical interest in psychedelic, dissociative, and deliriant hallucinogens necessitates novel translational, sensitive, and high-throughput in vivo models and screens. Primate and rodent models have been traditionally used to study cellular mechanisms and neural circuits of hallucinogenic drugs' action. The utility of zebrafish ( Danio rerio ) in neuroscience research is rapidly growing due to their high physiological and genetic homology to humans, ease of genetic manipulation, robust behaviors, and cost effectiveness. Possessing a fully characterized genome, both adult and larval zebrafish are currently widely used for in vivo screening of various psychotropic compounds, including hallucinogens and related drugs. Recognizing the growing importance of hallucinogens in biological psychiatry, here we discuss hallucinogenic-induced phenotypes in zebrafish and evaluate their potential as efficient preclinical models of drug-induced states in humans.

Perspectives on Zebrafish Models of Hallucinogenic Drugs and Related Psychotropic Compounds

PubMed Central

2013-01-01

Among different classes of psychotropic drugs, hallucinogenic agents exert one of the most prominent effects on human and animal behaviors, markedly altering sensory, motor, affective, and cognitive responses. The growing clinical and preclinical interest in psychedelic, dissociative, and deliriant hallucinogens necessitates novel translational, sensitive, and high-throughput in vivo models and screens. Primate and rodent models have been traditionally used to study cellular mechanisms and neural circuits of hallucinogenic drugs’ action. The utility of zebrafish (Danio rerio) in neuroscience research is rapidly growing due to their high physiological and genetic homology to humans, ease of genetic manipulation, robust behaviors, and cost effectiveness. Possessing a fully characterized genome, both adult and larval zebrafish are currently widely used for in vivo screening of various psychotropic compounds, including hallucinogens and related drugs. Recognizing the growing importance of hallucinogens in biological psychiatry, here we discuss hallucinogenic-induced phenotypes in zebrafish and evaluate their potential as efficient preclinical models of drug-induced states in humans. PMID:23883191

The effect of central nervous system depressant, stimulant and hallucinogenic drugs on injury severity in patients admitted for trauma.

PubMed

Cordovilla-Guardia, Sergio; Lardelli-Claret, Pablo; Vilar-López, Raquel; López-Espuela, Fidel; Guerrero-López, Francisco; Fernández-Mondéjar, Enrique

2017-08-04

The effect of drugs other than alcohol on severity of trauma remains unclear. Pooled data analyses in previous studies that grouped substances with opposite effects on the central nervous system (CNS) may have masked the influence of substances on injury severity. The aim was to analyze the effect of stimulant, hallucinogenic and depressant drugs other than alcohol on injury severity in trauma patients. The presence of alcohol, stimulant drugs (cocaine, amphetamines and methamphetamines), depressant drugs (benzodiazepines, opiates, methadone and barbiturates) and hallucinogenic drugs (THC and PCP) was analyzed in 1187 patients between 16 and 70 years old admitted to a trauma hospital between November 2012 and June 2015. Injury severity was determined prospectively as the Injury Severity Score. A multivariate analysis was used to quantify the strength of association between exposure to substances and trauma severity, using the presence of alcohol as a stratification variable. Drugs other than alcohol were found in 371 patients (31.3%): 32 (2.7%) stimulants, 186 (15.3%) depressants, 78 (6.6%) hallucinogenics and 75 (5.6%) polydrug use. The presence of CNS depressant substances was associated with increased injury severity only in patients also exposed to alcohol, with an adjusted odds ratio of 4.63 (1.37-15.60) for moderate injuries and 7.83 (2.53-24.21) for severe. CNS depressant drugs had a strong influence on injury severity in patients who screened positive for alcohol consumption. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Pharmacokinetic Correlates of the Effects of a Heroin Vaccine on Heroin Self-Administration in Rats

PubMed Central

Raleigh, Michael D.; Pentel, Paul R.; LeSage, Mark G.

2014-01-01

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

Gender Differences and Correlated Factors of Heroin Use Among Heroin Users.

PubMed

Zhou, Xiaobo; Yi, Zhihua; Yang, Xiaorong; Wang, Zhuo; Lyu, Xianxiang; Li, Jing

2017-01-02

Gender differences in illicit drug use are becoming increasingly recognized. However, there are few studies concerning differences between male and female heroin users in China. The study aimed to explore gender differences in terms of socio-demographic characteristics, drug-related behaviors, and treatment history among a heroin-using population in China. A cross-sectional study was conducted in four cities in December 2013. A total of 788 participants were recruited from several types of sites in each city: compulsory detoxification centers, methadone maintenance treatment clinics, and detention facilities. The data were collected via a self-administered questionnaire. Analysis of variance, chi-square test, and multivariate logistic regression analyses were conducted to examine gender differences in socio-demographic characteristics, drug-related behaviors, and treatment history. Female heroin users were more likely to be unemployed, have more education, and use heroin with their spouse/companion (p <.05). Male heroin users were more likely to be in detention facilities and MMT clinics, and relapse when they felt hopeless (p <.05). Conclusions/Importance: Although there were some similarities between male and female heroin users, significant gender differences do exist in some aspects of socio-demographic characteristics and heroin use. The data provide evidence that interventions aimed at preventing the initiation of heroin use and reducing relapse should take gender into account.

Heroin overdose deaths and heroin purity between 1990 and 2000 in Istanbul, Turkey*.

PubMed

Toprak, Sadik; Cetin, Ilhan

2009-09-01

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.

Detecting cocaine use? The autobiographical implicit association test (aIAT) produces false positives in a real-world setting

PubMed Central

2013-01-01

Background The autobiographical Implicit Association Test (aIAT) is a novel application of the implicit association concept for detecting life events. It has been used to reveal concealed knowledge in clinical and forensic settings, including detecting drug use. In this study, we aimed to explore the functionality of the aIAT to identify drug use in real-world settings. Methods The study used mixed methodology with known groups of drug users and nonusers. Recreational cocaine users (n = 23) and non-users (n = 23) were recruited through ethnographic methodology and assessed using a bespoke brief aIAT for cocaine use. An identical aIAT test for heroin detection was also administered to a sub-sample of 10 cocaine users and 13 nonusers. The accuracy of the cocaine aIAT was measured through ROC analysis. Paradoxical aIAT results were explored by integrating craving, consumption measures and life-story interviews into the analysis. Results Whilst the two brief aIATs showed good concurrent validity for cocaine users by accurately detecting drug using status for 18 of the 23 users (78.3%), the test falsely reported 61% cocaine users in the non-user comparison group. The average D-scores were 0.257±0.246 for the cocaine users and 0.134±0.367 for the non-users, showing no discriminatory power (t(44) = 1.339, p = 0.187; AUC = 0.605, p = 0.223). Results were independent from craving and recent cocaine use. The comparison group’s cocaine and heroin aIAT scores correlated significantly (r(13) = 0.776, p = 0.002) whilst an accurate absence of such relationship was evidenced in the cocaine using sample (r(10) = 0.061, p = 0.866). Triangulation with life-story interviews suggests that in the absence of an autobiographical event, this test may measure an alternative cognitive construct linked to the Self-concept. Conclusion The aIAT is a variant of an attitude measure and can be better rationalized if propositional thinking is implied to explain outcomes. The Relational Frame

Heroin. Specialized Information Service.

ERIC Educational Resources Information Center

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…

Clinical applications of hallucinogens: A review.

PubMed

Garcia-Romeu, Albert; Kersgaard, Brennan; Addy, Peter H

2016-08-01

Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Clinical Applications of Hallucinogens: A Review

PubMed Central

Garcia-Romeu, Albert; Kersgaard, Brennan; Addy, Peter H.

2016-01-01

Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value. PMID:27454674

Heroin in brown, black and white: structural factors and medical consequences in the US heroin market.

PubMed

Ciccarone, Daniel

2009-05-01

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. 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. 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 HIV prevalence. BTH is

Heroin in brown, black and white: Structural factors and medical consequences in the US heroin market

PubMed Central

Ciccarone, Daniel

2009-01-01

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

Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines.

PubMed

Winter, J C

2009-04-01

Although man's first encounters with hallucinogens predate written history, it was not until the rise of the sister disciplines of organic chemistry and pharmacology in the nineteenth century that scientific studies became possible. Mescaline was the first to be isolated and its chemical structure determined. Since then, additional drugs have been recovered from their natural sources and synthetic chemists have contributed many more. Given their profound effects upon human behavior and the need for verbal communication to access many of these effects, some see humans as ideal subjects for study of hallucinogens. However, if we are to determine the mechanisms of action of these agents, establish hypotheses testable in human subjects, and explore the mechanistic links between hallucinogens and such apparently disparate topics as idiopathic psychosis, transcendental states, drug abuse, stress disorders, and cognitive dysfunction, studies in animals are essential. Stimulus control by hallucinogens has provided an intuitively attractive approach to the study of these agents in nonverbal species. The intent of this review is to provide a brief account of events from the time of the first demonstration of hallucinogen-induced stimulus control to the present. In general, the review is limited to lysergic acid diethylamide (LSD) and the hallucinogenic derivatives of phenethylamine and tryptamine. The pharmacological basis for stimulus control by LSD and hallucinogenic phenethylamines and tryptamines is serotonergic in nature. The 5-HT(2A) receptor appears to be the primary site of action with significant modulation by other serotonergic sites including 5-HT(2C) and 5-HT(1A) receptors. Interactions with other neurotransmitters, especially glutamate and dopamine, are under active investigation. Most studies to date have been conducted in the rat but transgenic mice offer interesting possibilities. Hallucinogen-induced stimulus control provides a unique behavioral tool for the

A follow-up study of heroin addicts (VEdeTTE2): study design and protocol

PubMed Central

Vigna-Taglianti, Federica D; Mathis, Federica; Diecidue, Roberto; Burroni, Paola; Iannaccone, Antonio; Lampis, Fabio; Zuccaro, Piergiorgio; Pacifici, Roberta; Versino, Elisabetta; Davoli, Marina; Faggiano, Fabrizio

2007-01-01

Background In Italy, a large cohort study (VEdeTTE1) was conducted between 1998–2001 to evaluate the effectiveness of treatments in reducing mortality and increasing treatment retention among heroin addicts. The follow-up of this cohort (VEdeTTE2) was designed to evaluate the effectiveness of treatments on long-term outcomes, such as rehabilitation and social re-integration. The purpose of this paper is to describe the protocol of the VEdeTTE2 study, and to present the results of the pilot study carried out to assess the feasibility of the study and to improve study procedures. Methods The source population for the VEdeTTE2 study was the VEdeTTE1 cohort, from which a sample of 2,200 patients, traced two or more years after enrolment in the cohort, were asked to participate. An interview investigates drug use; overdose; family and social re-integration. Illegal activity are investigated separately in a questionnaire completed by the patient. Patients are also asked to provide a hair sample to test for heroin and cocaine use. Information on treatments and HIV, HBV and HCV morbidity are obtained from clinical records. A pilot phase was planned and carried out on 60 patients. Results The results of the pilot phase pointed out the validity of the procedures designed to limit attrition: the number of traced subjects was satisfactory (88%). Moreover, the pilot phase was very useful in identifying possible causes of delays and attrition, and flaws in the instruments. Improvements to the procedures and the instruments were subsequently implemented. Sensitivity of the biological test was quite good for heroin (78%) but lower for cocaine (42.3%), highlighting the need to obtain a hair sample from all patients. Conclusion In drug addiction research, studies investigating health status and social re-integration of subjects at long-term follow-up are lacking. The VEdeTTE2 study aims to investigate these outcomes at long-term follow-up. Results of the pilot phase underline the

Lifetime history of insomnia and hypersomnia symptoms as correlates of alcohol, cocaine, and heroin use and relapse among adults seeking substance use treatment in the United States from 1991 to 1994

PubMed Central

Dolsen, Michael R.; Harvey, Allison G.

2017-01-01

Aims To examine the association between a lifetime history of insomnia and hypersomnia compared with no sleep disturbance and substance use patterns and amounts before and after a substance use treatment episode. Design Secondary analysis of data from the Drug Abuse Treatment Outcome Studies conducted from 1991 to 1994. Setting Data were collected at 96 substance use treatment programs in 11 United States cities including short-term in-patient, long-term residential, methadone maintenance, and outpatient drug-free treatment modalities. Participants Study samples included 7,168 adults at treatment entry and 2,965 at 12 months post-treatment entry whose primary substance use at entry was alcohol (14.7%), cocaine (62.7%), or heroin (22.6%). Measurements Lifetime history of insomnia and hypersomnia was assessed via self-report. Type and frequency of substance use were assessed at treatment entry. Substance use was also assessed 12 months following treatment completion. Associations were examined using linear and logistic regression with age, sex, race, education level, depression history, treatment modality, and in-treatment substance use as covariates. Findings Lifetime history of insomnia, hypersomnia, both or neither was reported by 26.3%, 9.5%, 28.0% and 36.2% of participants, respectively. Compared with no sleep disturbance, lifetime insomnia and hypersomnia were associated at treatment entry with unique substance use patterns and a higher frequency of any substance use (p < .001). All types of sleep disturbance were associated with higher rates of cocaine use at 12-month post-entry (ORs: 1.30–1.57). Conclusions There is evidence of an adverse association between substance use and sleep disturbance including higher frequency of all substance use before substance abuse treatment and higher rates of cocaine use after a treatment episode. PMID:28127809

N-acetylaspartylglutamate Inhibits Heroin Self-Administration and Heroin-Seeking Behaviors Induced by Cue or Priming in Rats.

PubMed

Zhu, Huaqiang; Lai, Miaojun; Chen, Weisheng; Mei, Disen; Zhang, Fuqiang; Liu, Huifeng; Zhou, Wenhua

2017-08-01

Activation of presynaptic group II metabotropic glutamate receptors (mGluR2/3) inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate (NAAG), an agonist of endogenous mGluR2/3, in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroin-seeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1 (FR1) schedule for 10 days, then received NAAG (50 or 100 μg/10 μL in each nostril) in the absence or presence of LY341495 (1 mg/kg, i.p.), an antagonist of mGluR2/3, on day 11 and the effects of NAAG on heroin self-administration under FR1 were recorded for 3 consecutive days. Motivation was assessed in heroin self-administration under a progressive ratio schedule on day 11 in another 5 groups with the same doses of NAAG. Additional rats were withdrawn for 14 days after 14 days of heroin self-administration, then received the same pharmacological pretreatment and were tested for heroin-seeking behaviors induced by heroin priming or cues. The results showed that intranasal administration of NAAG significantly decreased intravenous heroin self-administration on day 12, but not on day 11. Pretreatment with LY341495 prior to testing on day 12 prevented the inhibitory effect of NAAG on heroin reinforcement. The break-point for reward motivation was significantly reduced by NAAG. Moreover, NAAG also significantly inhibited the heroin-seeking behaviors induced by heroin priming or cues and these were restored by pretreatment with LY341495. These results demonstrated that NAAG, via activation of presynaptic mGluR2/3, attenuated the heroin reinforcement, heroin motivational value, and heroin-seeking behavior, suggesting that it may be used as an adjunct treatment for heroin addiction.

From gold-medal glory to prohibition: the early evolution of cocaine in the United Kingdom and the United States

PubMed Central

Gilchrist, Dawna

2013-01-01

As reported in the 2011 World Drug Report, cocaine is likely to be the most problematic drug worldwide in terms of trafficking-related violence and second only to heroin in terms of negative health consequences and drug deaths. Over a period of 60 years, cocaine evolved from the celebrated panacea of the 1860s to outlawed street drug of the 1920s. As demonstrated by the evolution of cocaine use and abuse in the United Kingdom and United States during this time period, cultural attitudes influenced both the acceptance of cocaine into the medical field and the reaction to the harmful effects of cocaine. Our review of articles on cocaine use in the United Kingdom and the United States from 1860 to 1920 reveals an attitude of caution in the United Kingdom compared with an attitude of progressivism in the United States. When the trends in medical literature are viewed in the context of the development of drug regulations, our analysis provides insight into the relationship between cultural attitudes and drug policy, supporting the premise that it is cultural and social factors which shape drug policy, rather than drug regulations changing culture. PMID:23772315

Hallucinogenic drugs in pre-Columbian Mesoamerican cultures.

PubMed

Carod-Artal, F J

2015-01-01

The American continent is very rich in psychoactive plants and fungi, and many pre-Columbian Mesoamerican cultures used them for magical, therapeutic and religious purposes. The archaeological, ethno-historical and ethnographic evidence of the use of hallucinogenic substances in Mesoamerica is reviewed. Hallucinogenic cactus, plants and mushrooms were used to induce altered states of consciousness in healing rituals and religious ceremonies. The Maya drank balché (a mixture of honey and extracts of Lonchocarpus) in group ceremonies to achieve intoxication. Ritual enemas and other psychoactive substances were also used to induce states of trance. Olmec, Zapotec, Maya and Aztec used peyote, hallucinogenic mushrooms (teonanacatl: Psilocybe spp) and the seeds of ololiuhqui (Turbina corymbosa), that contain mescaline, psilocybin and lysergic acid amide, respectively. The skin of the toad Bufo spp contains bufotoxins with hallucinogenic properties, and was used since the Olmec period. Jimson weed (Datura stramonium), wild tobacco (Nicotiana rustica), water lily (Nymphaea ampla) and Salvia divinorum were used for their psychoactive effects. Mushroom stones dating from 3000 BC have been found in ritual contexts in Mesoamerica. Archaeological evidence of peyote use dates back to over 5000 years. Several chroniclers, mainly Fray Bernardino de Sahagún, described their effects in the sixteenth century. The use of psychoactive substances was common in pre-Columbian Mesoamerican societies. Today, local shamans and healers still use them in ritual ceremonies in Mesoamerica. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

HIV seroprevalence among street-recruited injection drug and crack cocaine users in 16 US municipalities.

PubMed Central

Kral, A H; Bluthenthal, R N; Booth, R E; Watters, J K

1998-01-01

OBJECTIVES: This study deter- mined human immunodeficiency virus (HIV) seroprevalence and factors associated with HIV infection among street-recruited injection drug users and crack cocaine smokers. METHODS: An analysis was performed on HIV serologies and risk behaviors of 6402 injection drug users and 3383 crack smokers in 16 US municipalities in 1992 and 1993. RESULTS: HIV seroprevalence was 12.7% among injection drug users and 7.5% among crack smokers. Most high-seroprevalence municipalities (>25%) were located along the eastern seaboard of the United States. In high-seroprevalence municipalities, but not in others, HIV seroprevalence was higher for injection drug users than for crack smokers. Among injection drug users, cocaine injection, use of speedballs (cocaine or amphetamines with heroin), and sexual risk behaviors were independently associated with HIV infection. Among crack smokers, sexual risk behaviors were associated with HIV infection. CONCLUSIONS: Injection drug users and crack smokers are at high risk for HIV infection. PMID:9584014

The hallucinogenic world of tryptamines: an updated review.

PubMed

Araújo, Ana Margarida; Carvalho, Félix; Bastos, Maria de Lourdes; Guedes de Pinho, Paula; Carvalho, Márcia

2015-08-01

In the area of psychotropic drugs, tryptamines are known to be a broad class of classical or serotonergic hallucinogens. These drugs are capable of producing profound changes in sensory perception, mood and thought in humans and act primarily as agonists of the 5-HT2A receptor. Well-known tryptamines such as psilocybin contained in Aztec sacred mushrooms and N,N-dimethyltryptamine (DMT), present in South American psychoactive beverage ayahuasca, have been restrictedly used since ancient times in sociocultural and ritual contexts. However, with the discovery of hallucinogenic properties of lysergic acid diethylamide (LSD) in mid-1900s, tryptamines began to be used recreationally among young people. More recently, new synthetically produced tryptamine hallucinogens, such as alpha-methyltryptamine (AMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), emerged in the recreational drug market, which have been claimed as the next-generation designer drugs to replace LSD ('legal' alternatives to LSD). Tryptamine derivatives are widely accessible over the Internet through companies selling them as 'research chemicals', but can also be sold in 'headshops' and street dealers. Reports of intoxication and deaths related to the use of new tryptamines have been described over the last years, raising international concern over tryptamines. However, the lack of literature pertaining to pharmacological and toxicological properties of new tryptamine hallucinogens hampers the assessment of their actual potential harm to general public health. This review provides a comprehensive update on tryptamine hallucinogens, concerning their historical background, prevalence, patterns of use and legal status, chemistry, toxicokinetics, toxicodynamics and their physiological and toxicological effects on animals and humans.

The discriminative effects of the kappa-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects.

PubMed

Butelman, Eduardo R; Rus, Szymon; Prisinzano, Thomas E; Kreek, Mary Jeanne

2010-06-01

The widely available hallucinogen salvinorin A is a unique example of a plant-derived compound selective for kappa-opioid receptors and may produce effects distinct from those of other compounds with classic hallucinogenic or dissociative properties which are also abused in humans. The objective of this study is to characterize the salvinorin A discriminative cue in nonhuman primates with high kappa-receptor genetic homology to humans. Adult rhesus monkeys (n = 3) were trained to discriminate salvinorin A (0.015 mg/kg, s.c.) from vehicle, in a food-reinforced operant discrimination assay. Parallel studies, using unconditioned behavioral endpoints (facial relaxation and ptosis) also evaluated the kappa-opioid receptor mediation of salvinorin A in vivo function. Monkeys trained to discriminate salvinorin A generalized structurally diverse, centrally penetrating kappa-agonists (bremazocine, U69,593, and U50,488). By contrast, mu- and delta-opioid agonists (fentanyl and SNC80, respectively) were not generalized, nor were the serotonergic 5HT2 hallucinogen psilocybin or the dissociative N-methyl-D-aspartic acid antagonist, ketamine. The discriminative effects of salvinorin A were blocked by the opioid antagonist quadazocine (0.32 mg/kg), but not by the 5HT2 antagonist ketanserin (0.1 mg/kg). Consistent with these findings, salvinorin and kappa-agonists (e.g., U69,593) produce effects in the unconditioned endpoints (e.g., ptosis), whereas psilocybin was inactive. These findings support the conclusion that the interoceptive/discriminative cue produced by salvinorin A is mediated by agonism at kappa-receptors and is mechanistically distinct from that produced by a classic serotonergic hallucinogen.

Heroin: MedlinePlus Health Topic

MedlinePlus

... flashes with goose bumps. NIH: National Institute on Drug Abuse Start Here DrugFacts: Heroin (National Institute on Drug Abuse) Also in Spanish Heroin (Drug Enforcement Administration) Heroin ( ...

DrugFacts: Heroin

MedlinePlus

... White matter impairment in chronic heroin dependence: a quantitative DTI study. Brain Res . 2013;1531:58-64. ... Minneapolis/St.Paul, Minn." Watch video (1:08) Research Report Heroin Offers the latest scientific information on ...

Research Reports: Heroin

MedlinePlus

... 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- ...

CDC Vital Signs: Today's Heroin Epidemic

MedlinePlus

... is increasing, and so are heroin-related overdose deaths. How is heroin harmful? Heroin is an illegal, ... can cause slow and shallow breathing, coma, and death. People often use heroin along with other drugs ...

Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives

PubMed Central

Martinotti, Giovanni; Spano, Maria Chiara; Lorusso, Marco; di Giannantonio, Massimo; Lerner, Arturo G.

2018-01-01

Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, but it can arise in anyone, even after a single exposure to triggering drugs. The aims of the present study are to review all the original studies about HPPD in order to evaluate the following: (1) the possible suggested etiologies; (2) the possible hallucinogens involved in HPPD induction; (3) the clinical features of both HPPD I and II; (4) the possible psychiatric comorbidities; and (5) the available and potential therapeutic strategies. We searched PubMed to identify original studies about psychedelics and Hallucinogen Persisting Perception Disorder (HPPD). Our research yielded a total of 45 papers, which have been analyzed and tabled to provide readers with the most updated and comprehensive literature review about the clinical features and treatment options for HPPD. PMID:29547576

Main mental disorders in crack-cocaine users treated at Psychosocial Care Centers for Alcohol and Drugs in the city of Recife, Brazil.

PubMed

Castro, Antonio Gomes de; Silva, Diego César Nunes da; Figueiroa, Magda da Silva

2016-01-01

Brazil's Northeast region has the highest crack-cocaine consumption in the country. Crack-cocaine has more intense effects than cocaine powder and can cause greater chemical dependence. Psychosocial Care Centers for Alcohol and Drugs (CAPSad) are public health services that provide treatment for drug dependence. It is common for drug users, and particularly crack-cocaine users, to develop mental disorders. Objective: To evaluate the most common mental disorders in crack-cocaine dependents in treatment at CAPSad in the city of Recife, Brazil. The research database "Between rocks and shots: user profiles, consumption strategies, and social impact of crack cocaine" (CEP/CCS/UFPE no. 206/11) was consulted to establish the areas of crack cocaine consumption in the city of Recife. There were 885 patients in treatment for crack-cocaine use, with a mean age of 29.8±9.4 years. The mean duration of drug use was 6.1±4.6 years. Most of the patients were males (80.3%), had left school at some point between the 1st and 9th grades (45.6%), were unemployed and/or seeking employment (52%) and used drugs daily (56.4%). Cocaine chemical dependence was more significant when correlated with use of crack-cocaine and other drugs such as medications and hallucinogens (p = 0.01). Data from this study showed strong associations between crack-cocaine uses and development of mental disorders, particularly when abuse of multiple substances occurs. Based on these data, there is a clear need for coordination of related public policies for support and social reintegration to provide these people with comprehensive care.

Signs of Heroin Abuse and Addiction

MedlinePlus

... Signs of Heroin Use and Addiction Signs of Heroin Use and Addiction Listen Heroin can give you ... Previous Index Next Español English Español "I needed heroin just to get by." ©istock.com/ pixelheadphoto Deon ...

Carrier-mediated cocaine transport at the blood-brain barrier as a putative mechanism in addiction liability.

PubMed

Chapy, Hélène; Smirnova, Maria; André, Pascal; Schlatter, Joël; Chiadmi, Fouad; Couraud, Pierre-Olivier; Scherrmann, Jean-Michel; Declèves, Xavier; Cisternino, Salvatore

2014-10-31

The rate of entry of cocaine into the brain is a critical factor that influences neuronal plasticity and the development of cocaine addiction. Until now, passive diffusion has been considered the unique mechanism known by which cocaine crosses the blood-brain barrier. We reassessed mechanisms of transport of cocaine at the blood-brain barrier using a human cerebral capillary endothelial cell line (hCMEC/D3) and in situ mouse carotid perfusion. Both in vivo and in vitro cocaine transport studies demonstrated the coexistence of a carrier-mediated process with passive diffusion. At pharmacological exposure level, passive diffusion of cocaine accounted for only 22.5% of the total cocaine influx in mice and 5.9% in hCMEC/D3 cells, whereas the carrier-mediated influx rate was 3.4 times greater than its passive diffusion rate in vivo. The functional identification of this carrier-mediated transport demonstrated the involvement of a proton antiporter that shared the properties of the previously characterized clonidine and nicotine transporter. The functionnal characterization suggests that the solute carrier (SLC) transporters Oct (Slc22a1-3), Mate (Slc47a1) and Octn (Slc22a4-5) are not involved in the cocaine transport in vivo and in vitro. Diphenhydramine, heroin, tramadol, cocaethylene, and norcocaine all strongly inhibited cocaine transport, unlike benzoylecgonine. Trans-stimulation studies indicated that diphenhydramine, nicotine, 3,4-methylenedioxyamphetamine (ecstasy) and the cathinone compound 3,4-methylenedioxypyrovalerone (MDPV) were also substrates of the cocaine transporter. Cocaine transport at the BBB involves a proton-antiporter flux that is quantitatively much more important than its passive diffusion. The molecular identification and characterization of this transporter will provide new tools to understand its role in addictive mechanisms. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e

Carrier-Mediated Cocaine Transport at the Blood-Brain Barrier as a Putative Mechanism in Addiction Liability

PubMed Central

Chapy, Hélène; Smirnova, Maria; André, Pascal; Schlatter, Joël; Chiadmi, Fouad; Couraud, Pierre-Olivier; Scherrmann, Jean-Michel; Declèves, Xavier

2015-01-01

Background: The rate of entry of cocaine into the brain is a critical factor that influences neuronal plasticity and the development of cocaine addiction. Until now, passive diffusion has been considered the unique mechanism known by which cocaine crosses the blood-brain barrier. Methods: We reassessed mechanisms of transport of cocaine at the blood-brain barrier using a human cerebral capillary endothelial cell line (hCMEC/D3) and in situ mouse carotid perfusion. Results: Both in vivo and in vitro cocaine transport studies demonstrated the coexistence of a carrier-mediated process with passive diffusion. At pharmacological exposure level, passive diffusion of cocaine accounted for only 22.5% of the total cocaine influx in mice and 5.9% in hCMEC/D3 cells, whereas the carrier-mediated influx rate was 3.4 times greater than its passive diffusion rate in vivo. The functional identification of this carrier-mediated transport demonstrated the involvement of a proton antiporter that shared the properties of the previously characterized clonidine and nicotine transporter. The functionnal characterization suggests that the solute carrier (SLC) transporters Oct (Slc22a1-3), Mate (Slc47a1) and Octn (Slc22a4-5) are not involved in the cocaine transport in vivo and in vitro. Diphenhydramine, heroin, tramadol, cocaethylene, and norcocaine all strongly inhibited cocaine transport, unlike benzoylecgonine. Trans-stimulation studies indicated that diphenhydramine, nicotine, 3,4-methylenedioxyamphetamine (ecstasy) and the cathinone compound 3,4-methylenedioxypyrovalerone (MDPV) were also substrates of the cocaine transporter. Conclusions: Cocaine transport at the BBB involves a proton-antiporter flux that is quantitatively much more important than its passive diffusion. The molecular identification and characterization of this transporter will provide new tools to understand its role in addictive mechanisms. PMID:25539501

Measuring the incentive value of escalating doses of heroin in heroin-dependent Fischer rats during acute spontaneous withdrawal

PubMed Central

Reed, Brian; Ho, Ann; Kreek, Mary Jeanne

2011-01-01

Rationale/objectives Although continued heroin use and relapse are thought to be motivated, in part, by the positive incentive-motivational value attributed to heroin, little is understood about heroin’s incentive value during the relapse-prone state of withdrawal. This study uses place preference to measure the incentive value attributed to escalating-dose heroin in the context of heroin dependence. Methods Male Fischer rats were exposed chronically to escalating doses of heroin in the homecage and during place preference conditioning sessions. Conditioned preference for the context paired with escalating-dose heroin was tested after homecage exposure was discontinued and rats entered acute spontaneous withdrawal. Individuals’ behavioral and locomotor responses to heroin and somatic withdrawal signs were recorded. Results Conditioned preference for the heroin-paired context was strong in rats that received chronic homecage exposure to escalating-dose heroin and were tested in acute withdrawal. Behavioral responses to heroin (e.g., stereotypy) varied widely across individuals, with rats that expressed stronger heroin preference also expressing stronger behavioral activation in response to heroin. Individual differences in preference were also related to locomotor responses to heroin but not to overt somatic withdrawal signs. Conclusions Escalating doses of heroin evoked place preference in rats, suggesting that positive incentive-motivational value is attributed to this clinically relevant pattern of drug exposure. This study offers an improved preclinical model for studying dependence and withdrawal and provides insight into individual vulnerabilities to addiction-like behavior. PMID:21748254

Pharmacokinetics and pharmacodynamics of smoked heroin.

PubMed

Jenkins, A J; Keenan, R M; Henningfield, J E; Cone, E J

1994-10-01

Despite the current popularity of smoking as a route of drug self-administration, there have been few human studies characterizing the pharmacokinetics and pharmacodynamics of smoked drugs of abuse. A variety of technological difficulties are encountered in the design of smoking studies, such as delivering reproducible doses and limiting the amount of pyrolysis of parent drug. As part of a concerted research effort to deliver precise, smoked doses of drug, a computer-assisted smoking device was utilized that delivered single puffs of heroin vapor to human subjects under controlled clinical conditions. Recovery studies indicated that the smoking device delivered approximately 89% of parent heroin to subjects. Although only two qualified heroin smokers could be identified as eligible volunteers, their participation provided the unique opportunity to study the pharmacokinetics and pharmacodynamics of smoked heroin. The two subjects were administered four smoked heroin doses in ascending order. In addition, four intravenous doses of heroin were administered for comparison of effects and estimation of bioavailability. Concurrent physiological, behavioral, and performance measures were collected along with blood samples. Blood was analyzed for heroin, 6-acetylmorphine, and morphine by solid-phase extraction gas chromatography-mass spectrometry. Heroin appeared rapidly in blood after administration and peaked 1-5 minutes after smoking, which is similar to that observed following intravenous administration. Heroin concentrations declined rapidly to the limit of detection (1.0 ng/mL) by 30 minutes. 6-Acetylmorphine blood concentrations also peaked and declined rapidly after smoked heroin with peak concentrations occurring at 1-2 minutes after smoking. Morphine levels rose and decayed more slowly. Mean elimination half-lives for heroin, 6-acetylmorphine, and morphine were 3.3 min, 5.4 min, and 18.8 min, respectively, by the smoked route. The bioavailability of smoked heroin

High-throughput simultaneous analysis of buprenorphine, methadone, cocaine, opiates, nicotine, and metabolites in oral fluid by liquid chromatography tandem mass spectrometry

PubMed Central

Concheiro, Marta; Gray, Teresa R.; Shakleya, Diaa M.

2011-01-01

A method for simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), anhydroecgonine methyl ester (AEME), morphine, codeine, 6-acetylmorphine (6AM), heroin, 6-acetylcodeine (6AC), nicotine, cotinine, and trans-3′-hydroxycotinine (OH-cotinine) by liquid chromatography tandem mass spectrometry in oral fluid (OF) was developed and extensively validated. Acetonitrile (800 μL) and OF (250 μL) were added to a 96-well Isolute-PPT+protein precipitation plate. Reverse-phase separation was achieved in 16 min and quantification was performed by multiple reaction monitoring. The assay was linear from 0.5 or 1 to 500 μg/L. Intraday, interday, and total imprecision were less than 13% (n=20), analytical recovery was 92–114% (n= 20), extraction efficiencies were more than 77% (n=5), and process efficiencies were more than 45% (n=5). Although ion suppression was detected for EME, cocaine, morphine, 6AC, and heroin (less than 56%) and enhancement was detected for BE and nicotine (less than 316%), deuterated internal standards compensated for these effects. The method was sensitive (limit of detection 0.2–0.8 μg/L) and specific (no interferences) except that 3-hydroxy-4-methoxyamphetamine interfered with AEME. No carryover was detected, and all analytes were stable for 24 h at 22 °C, for 72 h at 4 °C, and after three freeze–thaw cycles, except cocaine, 6AC, and heroin (22–97% loss). The method was applied to 41 OF specimens collected throughout pregnancy with a Salivette® OF collection device from an opioid-dependent BUP-maintained pregnant woman. BUP ranged from 0 to 7,400 μg/L, NBUP from 0 to 71 μg/L, methadone from 0 to 3 μg/L, nicotine from 32 to 5,020 μg/L, cotinine from 125 to 508 μg/L, OH-cotinine from 11 to 51 μg/L, cocaine from 0 to 419 μg/L, BE from 0 to 351 μg/L, EME from 0 to 286 μg/L, AEME from 0 to

Neural correlates of adherence to extended-release naltrexone pharmacotherapy in heroin dependence

PubMed Central

Wang, A-L; Elman, I; Lowen, S B; Blady, S J; Lynch, K G; Hyatt, J M; O'Brien, C P; Langleben, D D

2015-01-01

Injectable extended-release naltrexone (XRNTX) presents an effective therapeutic strategy for opioid addiction, however its utility could be hampered by poor adherence. To gain a better insight into this phenomenon, we utilized blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) in conjunction with a validated cue-induced craving procedure to examine neural correlates of XRNTX adherence. We operationalized treatment adherence as the number of monthly XRNTX injections (range: 0–3) administered to a group of fully detoxified heroin-dependent subjects (n=32). Additional outcomes included urine toxicology screening and self-reported tobacco use. The presented heroin-related visual cues reliably elicited heroin craving in all tested subjects. Nine, five, three and 15 of the participants, respectively, received zero, one, two and three XRNTX injections, predicted by the individual baseline fMRI signal change in response to the cues in the medial prefrontal cortex, a brain region involved in inhibitory self-control and emotional appraisal. The incidence of opioid-positive urines during the XRNTX therapy was low and remained about half the pre-treatment rate after the XRNTX ended. During the treatment, cigarette smoking behaviors followed patterns of opioid use, while cocaine consumption was increased with reductions in opioid use. The present data support the hypothesis that medial prefrontal cortex functions are involved in adherence to opioid antagonist therapy. A potential role of concurrent non-opioid addictive substances consumption during the XRNTX pharmacotherapy warrants further investigation. Our findings set the stage for further bio-behavioral investigations of the mechanisms of relapse prevention in opioid dependence. PMID:25781230

Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments.

PubMed

Kreek, Mary Jeanne; Bart, Gavin; Lilly, Charles; LaForge, K Steven; Nielsen, David A

2005-03-01

Opiate and cocaine addictions are major social and medical problems that impose a significant burden on society. Despite the size and scope of these problems, there are few effective treatments for these addictions. Methadone maintenance is an effective and most widely used treatment for opiate addiction, allowing normalization of many physiological abnormalities caused by chronic use of short-acting opiates. There are no pharmacological treatments for cocaine addiction. Epidemiological, linkage, and association studies have demonstrated a significant contribution of genetic factors to the addictive diseases. This article reviews the molecular genetics and pharmacogenetics of opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems that have been associated with or have evidence for linkage to opiate or cocaine addiction. This evidence has been marshalled either through identification of variant alleles that lead to functional alterations of gene products, altered gene expression, or findings of linkage or association studies. Studies of polymorphisms in the mu opioid receptor gene, which encodes the receptor target of some endogenous opioids, heroin, morphine, and synthetic opioids, have contributed substantially to knowledge of genetic influences on opiate and cocaine addiction. Other genes of the endogenous opioid and monoaminergic systems, particularly genes encoding dopamine beta-hydroxylase, and the dopamine, serotonin, and norepinephrine transporters have also been implicated. Variants in genes encoding proteins involved in metabolism or biotransformation of drugs of abuse and also of treatment agents are reviewed.

[Methods of use and behavior of cocaine addicts consulting medical-legal emergency units in Paris. Clinical aspects and urinary toxicology profile].

PubMed

Bécour, Bertrand; Menet, Marie-Claude; Questel, Frank; Guyon, François; Diamant-Berger, Odile

2003-03-01

Establish the epidemiological characteristics and urinary toxicological profiles of a population of cocaine addicts under police custody. A series of 60 cocaine addicts consulting the medico-legal emergency unit of the Hôtel-Dieu hospital in Paris was studied prospectively on the following elements: clinical characteristics, method of cocaine administration and association with other licit or illicit substances. Urinary toxicological analysis, using immuno-chemistry and chromatography linked to a mass spectrometer was systematically proposed to each patient. Half of the 17 to 26 year-old patients declared having consumed cocaine for the past 2 to 5 years. Inhalation of the vapours and the intravenous route were used more than the cigarette or nasal route. The majority of 26 to 35 year-olds were multi-drug addicted, generally associating cocaine, heroine and tobacco. Analysis of the urine provided an objective assessment of the cocaine consumption of these persons under police custody in Paris. Screening for urinary toxicity gives better knowledge on the consumption of addictive products by the person in whom urine was sampled. This study was conducted in cocaine addicts under police custody, and for the majority were social misfits. In this population, the consumption of crack by inhalation predominated.

The relationship between initial route of heroin administration and speed of transition to daily heroin use.

PubMed

Hines, Lindsey A; Lynskey, Michael; Morley, Katherine I; Griffiths, Paul; Gossop, Michael; Powis, Beverly; Strang, John

2017-09-01

The effect of heroin administration route on speed of transition to regular use is unknown. This paper aims to determine whether the speed of transition from initiation of heroin use to daily heroin use differs by route of administration (injecting, chasing/inhaling or snorting). Privileged access interviewer survey of purposively selected sample of 395 current people who use heroin (both in and not in treatment) in London, UK (historical sample from 1991). Data on age and year of initiation, time from initiation to daily use and routes of administration were collected by means of a structured questionnaire. Generalised ordered logistic models were used to test the relationship between route of initial administration of heroin and speed of transition to daily heroin use. Analyses were adjusted for gender, ethnicity, daily use of other drug(s) at time of initiation, year of initiation and treatment status at interview. After adjustment, participants whose initial administration route was injecting had a 4.71 (95% confidence interval 1.34-16.5) increase in likelihood of progressing to daily use within 1-3 weeks of initiation, compared to those whose initial administration route was non-injecting. The speed of transition from first use to daily heroin use is faster if the individual injects heroin at initiation of use. Those who initiate heroin use through injecting have a shorter time frame for intervention before drug use escalation. [Hines LA, Lynskey M, Morley KI, Griffiths P, Gossop M, Powis B, Strang J. The relationship between initial route of heroin administration and speed of transition to daily heroin use. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Heroin crystal nephropathy

PubMed Central

Bautista, Josef Edrik Keith; Merhi, Basma; Gregory, Oliver; Hu, Susie; Henriksen, Kammi; Gohh, Reginald

2015-01-01

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. PMID:26034599

[Fatal toxic leukoencephalopathy associated with consumption of pasta base of cocaine: Report of three cases].

PubMed

Cartier R, Luis; González L, Daniela; Harán D, Jorge

2015-11-01

The prevalence of drug-associated toxic encephalopathy is unknown, but it is an uncommon condition. Toxic leukoencephalopathy was described associated with heroin consumption, it has been less commonly described with the use of cocaine and there are no reports of its association with consumption pasta base of cocaine (PBC). We report two females aged 31 years and a male aged 19 years, consumers of PBC who developed a fatal toxic leukoencephalopathy. They initiated their disease with severe and persistent headache, sequential focal neurologic deficits and a progressive impairment of consciousness that culminated with their death. Laboratory parameters such as blood count, cerebrospinal fluid analyses or infectious biological indices were normal. MRI showed multifocal lesions in brain white matter of both hemispheres confirming the leukoencephalopathy. There was no response to the use of methylprednisolone.

Adverse Reactions to Hallucinogenic Drugs.

ERIC Educational Resources Information Center

Meyer, Roger E. , Ed.

This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

Hallucinogenic plant poisoning in children.

PubMed

Al-Shaikh, Adnan M; Sablay, Zakira M

2005-01-01

Datura is a hallucinogenic plant found in urban or rural areas in the Kingdom of Saudi Arabia KSA. It grows wildly in many parts of the country. Its taste and shape makes it unattractive to both man and animals, though deliberate use by young adults for its hallucinogenic effects have been widely reported for the past 30 years. Datura contains 3 main toxic alkaloids: atropine, scopolamine and hyoscamine. Consumption of any part of the plant can result in severe anticholinergic toxicity. Clinical symptoms are those seen in atropine poisoning, particularly mydriasis and hallucinations. Children have a special susceptibility to atropine toxicity; even small amount may produce central nervous system manifestations. Hospitalization is required for agitation and combative behavior although symptomatic treatment is usually sufficient. We report a case of acute Datura stramonium intoxication in a 6-year-old boy from Khamis Mushayt, KSA, who presented with restlessness, hallucinations and mydriasis 8 hours after ingesting the seeds of Datura plant.

PCP and hallucinogens.

PubMed

Carroll, M E

1990-01-01

In this review phencyclidine and related arylcyclohexylamines and hallucinogens, using LSD as the prototype, are considered as two distinct classes of abused drugs. Within these classes drugs that are found on the street are discussed, and a current epidemiological summary is provided. The abuse liability and dependence potential of these drugs are evaluated by considering four major determinants of their abuse. First, is the ability of a drug to function as a positive reinforcer and increase the probability of operant behavior leading to its delivery. Animal data describing the reinforcing effects of PCP are reviewed with respect to the influence of variables controlling drug-reinforced behavior; however, there are no animal models of hallucinogen-reinforced behavior. Several methods of quantifying reinforcing efficacy are discussed. A second determinant is the subjective effects of the respective drugs. These effects are described and compared across drugs based on clinical reports in humans and drug discrimination studies in animals. A third determinant is the behavioral and physiological toxicity that results from acute and chronic use of these drugs. Clinical reports and results of sensitive tests that have been developed for laboratory animals are reviewed. A fourth determinant is the dependence potential that exists with these drugs, measured by tolerance development and the extent to which behavioral and physiological disturbances occur when drug use is terminated.

Implicit processing of heroin and emotional cues in abstinent heroin users: early and late event-related potential effects.

PubMed

Yang, Ling; Zhang, Jianxun; Zhao, Xin

2015-05-01

The abnormal cognitive processing of drug cues is a core characteristic of drug dependence. Previous research has suggested that the late positive potential (LPP) of heroin users is increased by heroin-related stimuli because of the attention-grabbing nature of such stimuli. The present research used a modified emotional Stroop (eStroop) task to examine whether there was an early posterior negativity (EPN) modulation to heroin cues compared with emotional or neutral stimuli in heroin dependent subjects. Fifteen former heroin users and 15 matched controls performed the eStroop task, which was composed of positive, negative, heroin-related, and neutral pictures with superimposed color squares. Participants responded to the color of the square and not to the picture while behavioral data and event-related potentials were recorded. There were no significant differences of EPN amplitudes to emotional and neutral stimuli between heroin users and controls. However, heroin users displayed increased EPN modulation for heroin cues, whereas this modulation was absent in controls. Drug-related cues acquire motivational salience and automatically capture the attention of heroin users at early processing stages, even when engaged in a non-drug-related task. The EPN to heroin cues could represent a novel electrophysiological index with clinical implications for selecting abstinent drug users who are at increased risk of relapse or to evaluate treatment interventions.

Heroin - Multiple Languages

MedlinePlus

... Spanish) PDF The basics - Opioids, part 1 - English MP3 The basics - Opioids, part 1 - español (Spanish) MP3 The basics - Opioids, part 1 - English MP4 The ... Spanish) PDF Heroin - Opioid addiction, part 7 - English MP3 Heroin - Opioid addiction, part 7 - español (Spanish) MP3 ...

Illicit Drug Use and Treatment in South Africa

PubMed Central

Peltzer, Karl; Ramlagan, Shandir; Johnson, Bruce D.; Phaswana-Mafuya, Nancy

2008-01-01

This review synthesizes available epidemiological data on current drug use and substance abuse treatment admissions in south africa since 1994, and how changes in the political, economic and social structures within south africa both before and after apartheid make the country more vulnerable to drug use. based on national surveys current use of cannabis ranged among adolescents from 2% to 9% and among adults 2%, cocaine/crack (0.3%), mandrax/sedatives (0.3%), club drugs/amphetamine-type stimulants (0.2%), opiates (0.1%) and hallucinogens (0.1%). The primary illicit substance at admission to South African drug treatment centers was cannabis 16.9%, methamphetamine (Tik) 12.8%, crack/cocaine 9.6%, cannabis and mandrax 3.4%, heroin/opiates 9.2%, and prescription and OTC 2.6%. An increase in substance abuse treatment admissions has occurred. While the prevalence of illicit drug use in South Africa is relatively low compared to the USA and Australia, prevention and intervention policies need to be designed to reduce these levels by targeting the more risky subpopulations identified from this review. PMID:21039113

31 CFR 91.8 - Alcoholic beverages, narcotics, hallucinogenic and dangerous drugs.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., hallucinogenic and dangerous drugs. 91.8 Section 91.8 Money and Finance: Treasury Regulations Relating to Money... dangerous drugs. Entering or being on the property, or operating a motor vehicle thereon by a person under the influence of alcoholic beverages, narcotics, hallucinogenic or dangerous drugs is prohibited. The...

31 CFR 91.8 - Alcoholic beverages, narcotics, hallucinogenic and dangerous drugs.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., hallucinogenic and dangerous drugs. 91.8 Section 91.8 Money and Finance: Treasury Regulations Relating to Money... dangerous drugs. Entering or being on the property, or operating a motor vehicle thereon by a person under the influence of alcoholic beverages, narcotics, hallucinogenic or dangerous drugs is prohibited. The...

31 CFR 91.8 - Alcoholic beverages, narcotics, hallucinogenic and dangerous drugs.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., hallucinogenic and dangerous drugs. 91.8 Section 91.8 Money and Finance: Treasury Regulations Relating to Money... dangerous drugs. Entering or being on the property, or operating a motor vehicle thereon by a person under the influence of alcoholic beverages, narcotics, hallucinogenic or dangerous drugs is prohibited. The...

31 CFR 91.8 - Alcoholic beverages, narcotics, hallucinogenic and dangerous drugs.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., hallucinogenic and dangerous drugs. 91.8 Section 91.8 Money and Finance: Treasury Regulations Relating to Money... dangerous drugs. Entering or being on the property, or operating a motor vehicle thereon by a person under the influence of alcoholic beverages, narcotics, hallucinogenic or dangerous drugs is prohibited. The...

The North American Opiate Medication Initiative (NAOMI): Profile of Participants in North America’s First Trial of Heroin-Assisted Treatment

PubMed Central

Nosyk, Bohdan; Brissette, Suzanne; Chettiar, Jill; Schneeberger, Pascal; Marsh, David C.; Krausz, Michael; Anis, Aslam; Schechter, Martin T.

2008-01-01

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. PMID:18758964

Prevalence and correlates of fentanyl-contaminated heroin exposure among young adults who use prescription opioids non-medically.

PubMed

Macmadu, Alexandria; Carroll, Jennifer J; Hadland, Scott E; Green, Traci C; Marshall, Brandon D L

2017-05-01

The rate of overdose deaths caused by fentanyl-contaminated heroin (FCH) use is increasing rapidly in the United States. We examined risk factors for exposure to FCH and experiences with FCH use among young adult non-medical prescription opioids (NMPO) users. We analyzed data from the Rhode Island Young Adult Prescription Drug Study (RAPiDS), which enrolled young adults aged 18 to 29 reporting prior 30day NMPO use between January 2015 and February 2016. Participants completed questionnaires ascertaining drug use patterns and risk behaviors, including FCH exposure. Logistic regression was used to assess factors associated with known or suspected FCH exposure. Of 199 participants, the median age was 25 (IQR: 22, 27), 130 (65.3%) were male, and 122 (61.3%) were of White, non-Hispanic race/ethnicity. In total, 22 (11%) reported known or suspected FCH exposure in the prior six months. Several drug use patterns and risk behaviors were associated with FCH exposure, including: regular heroin and cocaine use; diverted pharmaceutical fentanyl use in the prior six months; NMPO use to avoid withdrawal symptoms; longer duration of NMPO use; regular injection drug use; and prior overdose (all p<0.001). Among participants who reported FCH exposure, 59% were unaware that their heroin was contaminated with fentanyl prior to last use, 59% reported that FCH provides a better high, and all recognized that fentanyl increases overdose risk. Exposure to fentanyl-contaminated heroin is an emerging trend among young adult NMPO users in Rhode Island. Overdose prevention programs addressing FCH use are urgently needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heroin shortage in Coastal Kenya: A rapid assessment and qualitative analysis of heroin users’ experiences

PubMed Central

Mital, Sasha; Miles, Gillian; McLellan-Lemal, Eleanor; Muthui, Mercy; Needle, Richard

2016-01-01

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

Heroin shortage in Coastal Kenya: A rapid assessment and qualitative analysis of heroin users' experiences.

PubMed

Mital, Sasha; Miles, Gillian; McLellan-Lemal, Eleanor; Muthui, Mercy; Needle, Richard

2016-04-01

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. 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. 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. 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. Published by Elsevier B.V.

Reasons for recent marijuana use in relation to use of other illicit drugs among high school seniors in the United States.

PubMed

Palamar, Joseph J; Griffin-Tomas, Marybec; Kamboukos, Dimitra

2015-01-01

Studies show that illicit cannabis (marijuana) use is related to use of other illicit drugs and that reasons for use are related to frequency of marijuana use. However, research is needed to examine whether specific reasons for marijuana use are associated with use of other illicit drugs. Data from recent marijuana-using high school seniors were examined from 12 cohorts of Monitoring the Future (Weighted n = 6481) to examine whether reasons for recent marijuana use are associated with use of eight other illicit drugs. Using "to experiment" decreased odds of reporting use of each drug and using to decrease effects of other drugs increased odds of reporting use of each drug. In multivariable models, using marijuana "to experiment" decreased the odds for reporting use of hallucinogens other than LSD and narcotics other than heroin. Using marijuana for "insight" increased the odds for use of hallucinogens other than LSD, and use due to "boredom" increased the odds for reporting use of powder cocaine and hallucinogens other than LSD. Using marijuana to increase effects of other drugs increased odds of reporting use of each of the eight drugs, and using it to decrease other drug effects increased odds of reporting use of crack, hallucinogens other than LSD, and amphetamine/stimulants. This study helped identify illicit marijuana users who are more likely to report use of other illicit drugs. Prevention efforts need to focus on students who report certain reasons for marijuana use as they may be at risk for use of other illicit drugs.

Reasons for Recent Marijuana Use in Relation to Use of Other Illicit Drugs among High School Seniors in the United States

PubMed Central

Palamar, Joseph J.; Griffin-Tomas, Marybec; Kamboukos, Dimita

2015-01-01

Objectives Studies show that illicit cannabis (marijuana) use is related to use of other illicit drugs and that reasons for use are related to frequency of marijuana use. However, research is needed to examine whether specific reasons for marijuana use are associated with use of other illicit drugs. Methods Data from recent-marijuana-using high school seniors were examined from 12 cohorts of Monitoring the Future (Weighted N=6,481) to examine whether reasons for recent marijuana use are associated with use of eight other illicit drugs. Results Using “to experiment” decreased odds of reporting use of each drug and using to decrease effects of other drugs increased odds of reporting use of each drug. In multivariable models, using marijuana “to experiment” decreased the odds for reporting use of hallucinogens other than LSD and narcotics other than heroin. Using marijuana for “insight” increased the odds for use of hallucinogens other than LSD, and use due to “boredom” increased the odds for reporting use of powder cocaine and hallucinogens other than LSD. Using marijuana to increase effects of other drugs increased odds of reporting each of the eight drugs, and using it to decrease other drug effects increased odds of reporting use of crack, hallucinogens other than LSD, and amphetamine/stimulants. Conclusions This study helped identify illicit marijuana users who are more likely to report use of other illicit drugs. Prevention efforts need to focus on students who report certain reasons for marijuana use as they may be at risk for use of other illicit drugs. PMID:26115351

Heroin overdose.

PubMed

Darke, Shane

2016-11-01

This narrative review aims to provide a brief history of the development of the heroin overdose field by discussing a selection of major 'classics' from the latter part of the 20th century. Papers considered landmarks were selected from 1972, 1977, 1983, 1984 and 1999. Findings of earlier works suggest much of what later research was to demonstrate. These include arguing that overdoses occurred primarily among tolerant older users, that most 'overdose' deaths involved low morphine concentrations, that most overdoses involve polypharmacy, that drug purity has only a moderate influence on overdose rates and that instant death following heroin administration is rare. Landmark studies of heroin overdose from the 1970s, 1980s and 1990s laid the foundations for subsequent overdose research, mainly by identifying the major demographic characteristics of overdose cases, risk factors, survival times and behaviours at overdose events. © 2016 Society for the Study of Addiction.

Selective Effects of a Morphine Conjugate Vaccine on Heroin and Metabolite Distribution and Heroin-Induced Behaviors in Rats

PubMed Central

Pravetoni, M.; Harris, A.C.; Birnbaum, A.K.; Pentel, P.R.

2013-01-01

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

African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction.

PubMed

Levran, Orna; Randesi, Matthew; Peles, Einat; Correa da Rosa, Joel; Ott, Jurg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne

2016-06-01

This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence. The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed. Of the 20 SNPs that showed nominally significant associations, the association of the African-specific CHRM4 SNP rs2229163 (Asn417=) with cocaine dependence survived correction for multiple testing (Pcorrected = 0.047). CHRM4 is located in a region of strong linkage disequilibrium on chromosome 11 that includes genes associated with schizophrenia. CHRM4 SNP rs2229163 is in strong linkage disequilibrium with several African-specific SNPs in DGKZ and AMBRA1. Cholinergic receptors' variants may contribute to drug addiction and have a potential role as pharmacogenetic markers.

rsfMRI effects of KB220Z™ on Neural Pathways in Reward Circuitry of Abstinent Genotyped Heroin Addicts

PubMed Central

Blum, Kenneth; Liu, Yijun; Wang, Wei; Wang, Yarong; Zhang, Yi; Oscar-Berman, Marlene; Smolen, Andrew; Febo, Marcelo; Han, David; Simpatico, Thomas; Cronjé, Frans J; Demetrovics, Zsolt; Gold, Mark S.

2016-01-01

Recently Willuhn et al. reported that cocaine use and even non-substance related addictive behavior, increases, as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors, also associated with lower activation to cues in occipital cortex and cerebellum in a recent PET study from Volkow’s group. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of ten heroin addicts undergoing protracted abstinence, an average 16.9 months. In a randomized placebo-controlled crossover study of KB220Z™ five subjects completed a triple blinded–experiment in which the subject, the person administering the treatment and the person evaluating the response to treatment were blinded as to which treatment any particular subject was receiving. In addition, nine subjects total were genotyped utilizing the GARSRX™ test. We preliminarily report that KB220Z ™ induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following one-hour acute administration. Furthermore, KB220Z™ also reduced resting state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all ten abstinent heroin-dependent subjects, three brain regions of interest (ROIs) we observed to be significantly activated from resting state by KB220Z compared to placebo (P < 0.05). Increased functional connectivity was observed in a putative network that included the dorsal anterior cingulate, medial frontal gyrus, nucleus accumbens, posterior cingulate, occipital cortical areas and cerebellum. These results and other qEEG study results suggest a putative anti-craving/anti-relapse role for KB220Z in addiction by direct or indirect dopaminergic interaction. Due to

Pavlovian conditioned approach, extinction, and spontaneous recovery to an audiovisual cue paired with an intravenous heroin infusion.

PubMed

Peters, Jamie; De Vries, Taco J

2014-01-01

Novel stimuli paired with exposure to addictive drugs can elicit approach through Pavlovian learning. While such approach behavior, or sign tracking, has been documented for cocaine and alcohol, it has not been shown to occur with opiate drugs like heroin. Most Pavlovian conditioned approach paradigms use an operandum as the sign, so that sign tracking can be easily automated. We were interested in assessing whether approach behavior occurs to an audiovisual cue paired with an intravenous heroin infusion. If so, would this behavior exhibit characteristics of other Pavlovian conditioned behaviors, such as extinction and spontaneous recovery? Rats were repeatedly exposed to an audiovisual cue, similar to that used in standard self-administration models, along with an intravenous heroin infusion. Sign tracking was measured in an automated fashion by analyzing motion pixels within the cue zone during each cue presentation. We were able to observe significant sign tracking after only five pairings of the conditioned stimulus (CS) with the unconditioned stimulus (US). This behavior rapidly extinguished over 2 days, but exhibited pronounced spontaneous recovery 3 weeks later. We conclude that sign tracking measured by these methods exhibits all the characteristics of a classically conditioned behavior. This model can be used to examine the Pavlovian component of drug memories, alone, or in combination with self-administration methods.

Pathways between Ecstasy Initiation and Other Drug Use

PubMed Central

Martins, Silvia S.; Ghandour, Lilian A.; Chilcoat, Howard D.

2007-01-01

This study aims to shed light on drug use pathways associated with ecstasy use initiation. Data from 54,573 respondents aged 12-21 years old from the 2002-2003 National Survey on Drug Use and Health (NSDUH) public use data files were analyzed via Cox proportional hazards models with time-dependent covariates. Our findings showed that marijuana, cocaine, and heroin were significant independent predictors of subsequent ecstasy use. Earlier ecstasy initiation was significantly associated with subsequent other illegal drug initiation (marijuana, cocaine and heroin). The strength of the association was greater for the pathway from earlier marijuana initiation to subsequent ecstasy initiation as compared to the pathway in the opposite direction. The pathway from earlier ecstasy initiation to subsequent cocaine and heroin initiation was also stronger as compared to pathways in the opposite directions. Pathways between ecstasy initiation and marijuana, cocaine and heroin initiation seem to be independent of the association between drug use and psychiatric symptoms/deviant behaviors. Ecstasy initiation seems to play a role in the subsequent initiation of cocaine and heroin. PMID:17174036

Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population.

PubMed

Poling, James; Oliveto, Alison; Petry, Nancy; Sofuoglu, Mehmet; Gonsai, Kishorchandra; Gonzalez, Gerardo; Martell, Bridget; Kosten, Thomas R

2006-02-01

No effective pharmacotherapies exist for cocaine dependence, although contingency management (CM) has demonstrated efficacy. To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals. This 25-week, placebo-controlled, double-blind trial randomly assigned participants to 1 of 4 treatment conditions: CM and placebo (CMP), CM and 300 mg/d of bupropion hydrochloride (CMB), voucher control and placebo (VCP), or voucher control and bupropion (VCB). Outpatient clinic at the Veterans Affairs Connecticut Healthcare System. A total of 106 opiate-dependent, cocaine-abusing individuals. All study participants received methadone hydrochloride (range, 60-120 mg). Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3. In the CM conditions, each urine sample negative for both opioids and cocaine resulted in a monetary-based voucher that increased for consecutively drug-free urine samples during weeks 1 to 13. Completion of abstinence-related activities also resulted in a voucher. During weeks 14 to 25, only completion of activities was reinforced in the CM group, regardless of sample results. The voucher control groups received vouchers for submitting urine samples, regardless of results, throughout the study. Thrice-weekly urine toxicologic test results for cocaine and heroin. Groups did not differ in baseline characteristics or retention rates. Opiate use decreased significantly, with all treatment groups attaining equivalent amounts of opiate use at the end of the study. In the CMB group, the proportion of cocaine-positive samples significantly decreased during weeks 3 to 13 (P<.001) relative to week 3 and remained low during weeks 14 to 25. In the CMP group, cocaine use significantly increased during weeks 3 to 13 (P<.001) relative to week 3, but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 (P<.001). In contrast, by

Cocaine

MedlinePlus

... confidencial Press Room » Multi-Media Library » Image Gallery » Cocaine COCAINE To Save Images: First click on the thumbnail ... your Save in directory and then click Save. Cocaine Crack Cocaine RESOURCE CENTER Controlled Substances Act DEA ...

Heroin and saccharin demand and preference in rats.

PubMed

Schwartz, Lindsay P; Kim, Jung S; Silberberg, Alan; Kearns, David N

2017-09-01

Several recent studies have investigated the choice between heroin and a non-drug alternative reinforcer in rats. A common finding in these studies is that there are large individual differences in preference, with some rats preferring heroin and some preferring the non-drug alternative. The primary goal of the present study was to determine whether individual differences in how heroin or saccharin is valued, based on demand analysis, predicts choice. Rats lever-pressed for heroin infusions and saccharin reinforcers on fixed-ratio schedules. The essential value of each reinforcer was obtained from resulting demand curves. Rats were then trained on a mutually exclusive choice procedure where pressing one lever resulted in heroin and pressing another resulted in saccharin. After seven sessions of increased access to heroin or saccharin, rats were reexposed to the demand and choice procedures. Demand for heroin was more elastic than demand for saccharin (i.e., heroin had lower essential value than saccharin). When allowed to choose, most rats preferred saccharin. The essential value of heroin, but not saccharin, predicted preference. The essential value of both heroin and saccharin increased following a week of increased access to heroin, but similar saccharin exposure had no effect on essential value. Preference was unchanged after increased access to either reinforcer. Heroin-preferring rats differed from saccharin-preferring rats in how they valued heroin, but not saccharin. To the extent that choice models addiction-related behavior, these results suggest that overvaluation of opioids specifically, rather than undervaluation of non-drug alternatives, could identify susceptible individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions.

PubMed

Lundqvist, Thomas

2005-06-01

This review aims to compare cognitive consequence between cannabis, and stimulants and heroin with regards to attention, memory and executive functions. The available studies using brain imaging techniques and neuropsychological tests show that acutely, all drugs create a disharmony in the neuropsychological network, causing a decrease of activity in areas responsible for short-term memory and attention, with the possible exception of heroin. Cannabis induces loss of internal control and cognitive impairment, especially of attention and memory, for the duration of intoxication. Heavy cannabis use is associated with reduced function of the attentional/executive system, as exhibited by decreased mental flexibility, increased perserveration, and reduced learning, to shift and/or sustain attention. Recent investigations on amphetamine/methamphetamine have documented deficits in learning, delayed recall, processing speed, and working memory. MDMA users exhibit difficulties in coding information into long-term memory, display impaired verbal learning, are more easily distracted, and are less efficient at focusing attention on complex tasks. The degree of executive impairment increases with the severity of use, and the impairments are relatively lasting over time. Chronic cocaine users display impaired attention, learning, memory, reaction time and cognitive flexibility. Heroin addiction may have a negative effect on impulse control, and selective processing.

Painkiller (Oxy, Vike) Facts

MedlinePlus

... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... these pills just like they sell heroin or cocaine. Some people borrow or steal these pills from ...

Use of Preclinical Drug vs. Food Choice Procedures to Evaluate Candidate Medications for Cocaine Addiction.

PubMed

Banks, Matthew L; Hutsell, Blake A; Schwienteck, Kathryn L; Negus, S Stevens

2015-06-01

Drug addiction is a disease that manifests as an inappropriate allocation of behavior towards the procurement and use of the abused substance and away from other behaviors that produce more adaptive reinforcers (e.g. exercise, work, family and social relationships). The goal of treating drug addiction is not only to decrease drug-maintained behaviors, but also to promote a reallocation of behavior towards alternative, nondrug reinforcers. Experimental procedures that offer concurrent access to both a drug reinforcer and an alternative, nondrug reinforcer provide a research tool for assessment of medication effects on drug choice and behavioral allocation. Choice procedures are currently the standard in human laboratory research on medications development. Preclinical choice procedures have been utilized in biomedical research since the early 1940's, and during the last 10-15 years, their use for evaluation of medications to treat drug addiction has increased. We propose here that parallel use of choice procedures in preclinical and clinical studies will facilitate translational research on development of medications to treat cocaine addiction. In support of this proposition, a review of the literature suggests strong concordance between preclinical effectiveness of candidate medications to modify cocaine choice in nonhuman primates and rodents and clinical effectiveness of these medications to modify either cocaine choice in human laboratory studies or metrics of cocaine abuse in patients with cocaine use disorder. The strongest evidence for medication effectiveness in preclinical choice studies has been obtained with maintenance on the monoamine releaser d -amphetamine, a candidate agonist medication for cocaine use analogous to use of methadone to treat heroin abuse or nicotine formulations to treat tobacco dependence.

Use of Preclinical Drug vs. Food Choice Procedures to Evaluate Candidate Medications for Cocaine Addiction

PubMed Central

Banks, Matthew L; Hutsell, Blake A; Schwienteck, Kathryn L; Negus, S. Stevens

2015-01-01

Opinion Statement Drug addiction is a disease that manifests as an inappropriate allocation of behavior towards the procurement and use of the abused substance and away from other behaviors that produce more adaptive reinforcers (e.g. exercise, work, family and social relationships). The goal of treating drug addiction is not only to decrease drug-maintained behaviors, but also to promote a reallocation of behavior towards alternative, nondrug reinforcers. Experimental procedures that offer concurrent access to both a drug reinforcer and an alternative, nondrug reinforcer provide a research tool for assessment of medication effects on drug choice and behavioral allocation. Choice procedures are currently the standard in human laboratory research on medications development. Preclinical choice procedures have been utilized in biomedical research since the early 1940’s, and during the last 10–15 years, their use for evaluation of medications to treat drug addiction has increased. We propose here that parallel use of choice procedures in preclinical and clinical studies will facilitate translational research on development of medications to treat cocaine addiction. In support of this proposition, a review of the literature suggests strong concordance between preclinical effectiveness of candidate medications to modify cocaine choice in nonhuman primates and rodents and clinical effectiveness of these medications to modify either cocaine choice in human laboratory studies or metrics of cocaine abuse in patients with cocaine use disorder. The strongest evidence for medication effectiveness in preclinical choice studies has been obtained with maintenance on the monoamine releaser d-amphetamine, a candidate agonist medication for cocaine use analogous to use of methadone to treat heroin abuse or nicotine formulations to treat tobacco dependence. PMID:26009706

Cocaine abuse versus cocaine dependence: cocaine self-administration and pharmacodynamic response in the human laboratory.

PubMed

Walsh, Sharon L; Donny, Eric C; Nuzzo, Paul A; Umbricht, Annie; Bigelow, George E

2010-01-01

Cocaine has high abuse liability but only a subset of individuals who experiment with it develop dependence. The DSM-IV (APA. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-R. American Psychiatric Association, Washington, DC, 2000) provides criteria for diagnosing cocaine abuse and cocaine dependence as distinct disorders- the latter characterized by additional symptoms related to loss of control over drug use. In this study, two groups of cocaine users (n=8/group), matched on demographic factors and length of cocaine use history and meeting criteria for either cocaine abuse (CocAb) or cocaine dependence (CocDep), were compared on (1) measures related to impulsivity and sensation seeking, (2) response to experimenter-administered cocaine (0, 12.5, 25 and 50mg/70 kg, i.v.), and (3) cocaine self-administration using a Relapse Choice and a Progressive Ratio Procedure (0, 12.5 and 25mg/70 kg, i.v.). Groups did not differ on impulsivity or sensation seeking scores. After experimenter-administered cocaine, the CocAb group reported feeling more suspicious and observers rated them significantly higher on unpleasant effects (e.g., irritability, difficulty concentrating). In contrast, the CocDep group reported significantly greater desire for cocaine, which was sustained over the course of the study, and gave higher street value estimates for cocaine (p<0.05). While cocaine self-administration was dose-related and generally comparable across the two procedures, the CocDep users chose to take significantly more cocaine than the CocAb users. These data suggest that, while regular long-term users of cocaine with cocaine abuse or dependence diagnoses cannot be distinguished by trait measures related to impulsivity, they do exhibit significant differences with regard to cocaine-directed behavior and response to cocaine administration. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Hallucinogen persisting perception disorder after psilocybin consumption: a case study.

PubMed

Espiard, Marie-Laure; Lecardeur, Laurent; Abadie, Pascale; Halbecq, Isabelle; Dollfus, Sonia

2005-08-01

The recurrence of flashbacks without acute or chronic hallucinogen consumption has been recognized in the DSM IV criteria as the hallucinogen persisting perception disorder (HPPD). Perceptual disturbances may last for 5 years or more and represent a real psychosocial distress. We reported here a case of a 18-year-old young man presenting HPPD after a mixed intoxication with psylocibin and cannabis. This report shows symptomatic recurrences persisting more than 8 months. Various differential diagnoses were evoked and our therapeutic strategies were described.

Cocaine withdrawal

MedlinePlus

... Substance use - cocaine withdrawal; Substance abuse - cocaine withdrawal; Drug abuse - cocaine withdrawal; Detox - cocaine ... Elsevier Saunders; 2016:chap 50. National Institute on Drug Abuse. What is cocaine? Updated May 2016. www.drugabuse. ...

Environmental enrichment as a potential intervention for heroin seeking.

PubMed

Galaj, E; Manuszak, M; Ranaldi, R

2016-06-01

Heroin-related cues can trigger craving and relapse in addicts or heroin seeking in rats. In the present study we investigated whether environmental enrichment (EE) implemented after heroin exposure can reduce cue-induced reinstatement of heroin seeking and expression of heroin conditioned place preference. In Experiment 1, male Long Evans rats that already acquired a heroin self-administration habit, were housed in enriched or non-enriched environments, underwent extinction training and later were tested for cue-induced reinstatement of heroin seeking. In Experiment 2, rats were conditioned with heroin in one compartment of a CPP apparatus and saline in the other, exposed to 30days of enrichment or no enrichment and were later tested for heroin CPP. The results showed that exposure to EE significantly reduced responding during the reinstatement test (Experiment 1) and prevented the expression of heroin CPP (Experiment 2). Our findings suggest that EE can be an effective behavioral approach to diminish the effects of conditioned cues on heroin seeking. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nonmedical prescription opioids and pathways of drug involvement in the US: Generational differences.

PubMed

Wall, Melanie; Cheslack-Postava, Keely; Hu, Mei-Chen; Feng, Tianshu; Griesler, Pamela; Kandel, Denise B

2018-01-01

This study sought to specify (1) the position of nonmedical prescription opioids (NMPO) in drug initiation sequences among Millennials (1979-96), Generation X (1964-79), and Baby Boomers (1949-64) and (2) gender and racial/ethnic differences in sequences among Millennials. Data are from the 2013-2014 National Surveys on Drug Use and Health (n = 73,026). We identified statistically significant drug initiation sequences involving alcohol/cigarettes, marijuana, NMPO, cocaine, and heroin using a novel method distinguishing significant sequences from patterns expected only due to correlations induced by common liability among drugs. Alcohol/cigarettes followed by marijuana was the most common sequence. NMPO or cocaine use after marijuana, and heroin use after NMPO or cocaine, differed by generation. Among successively younger generations, NMPO after marijuana and heroin after NMPO increased. Millennials were more likely to initiate NMPO than cocaine after marijuana; Generation X and Baby Boomers were less likely (odds ratios = 1.4;0.3;0.2). Millennials were more likely than Generation X and Baby Boomers to use heroin after NMPO (hazards ratios = 7.1;3.4;2.5). In each generation, heroin users were far more likely to start heroin after both NMPO and cocaine than either alone. Sequences were similar by gender. Fewer paths were significant among African-Americans. NMPOs play a more prominent role in drug initiation sequences among Millennials than prior generations. Among Millennials, NMPO use is more likely than cocaine to follow marijuana use. In all generations, transition to heroin from NMPO significantly occurs only when both NMPO and cocaine have been used. Delineation of drug sequences suggests optimal points in development for prevention and treatment efforts. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute eosinophilic pneumonia secondary to heroin inhalation.

PubMed

Eyüpoğlu, Damla; Ortaç Ersoy, Ebru; Rollas, Kazım; Topeli, Arzu

2017-06-01

Smoking heroin (chasing the dragon), is a method of inhaling heroin via heating the drug on a tin-foil above a flame. It also has been associated both with the indirect effects of heroin overdose and with direct pulmonary toxicity. We describe a case of acute eosinophilic pneumonia secondary to heroin inhalation in our medical intensive care unit. She presented with fever, cough, dyspnea and pleuritic chest pain. Chest radiograph showed bilateral infiltrations. Examination of bronchoalveolar lavage fluid revealed significant eosinophilia. She was diagnosed with acute eosinophilic pneumonia. After heroin abstinence and corticosteroid therapy, remission was achieved rapidly and the patient was discharge on the fourth day of her hospital stay.

Attitudes towards drug legalization among drug users.

PubMed

Trevino, Roberto A; Richard, Alan J

2002-01-01

Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

Combined Cocaine Hydrolase Gene Transfer and Anti-Cocaine Vaccine Synergistically Block Cocaine-Induced Locomotion

PubMed Central

Carroll, Marilyn E.; Zlebnik, Natalie E.; Anker, Justin J.; Kosten, Thomas R.; Orson, Frank M.; Shen, Xiaoyun; Kinsey, Berma; Parks, Robin J.; Gao, Yang; Brimijoin, Stephen

2012-01-01

Mice and rats were tested for reduced sensitivity to cocaine-induced hyper-locomotion after pretreatment with anti-cocaine antibody or cocaine hydrolase (CocH) derived from human butyrylcholinesterase (BChE). In Balb/c mice, direct i.p. injection of CocH protein (1 mg/kg) had no effect on spontaneous locomotion, but it suppressed responses to i.p. cocaine up to 80 mg/kg. When CocH was injected i.p. along with a murine cocaine antiserum that also did not affect spontaneous locomotion, there was no response to any cocaine dose. This suppression of locomotor activity required active enzyme, as it was lost after pretreatment with iso-OMPA, a selective BChE inhibitor. Comparable results were obtained in rats that developed high levels of CocH by gene transfer with helper-dependent adenoviral vector, and/or high levels of anti-cocaine antibody by vaccination with norcocaine hapten conjugated to keyhole limpet hemocyanin (KLH). After these treatments, rats were subjected to a locomotor sensitization paradigm involving a “training phase" with an initial i.p. saline injection on day 1 followed by 8 days of repeated cocaine injections (10 mg/kg, i.p.). A 15-day rest period then ensued, followed by a final “challenge" cocaine injection. As in mice, the individual treatment interventions reduced cocaine-stimulated hyperactivity to a modest extent, while combined treatment produced a greater reduction during all phases of testing compared to control rats (with only saline pretreatment). Overall, the present results strongly support the view that anti-cocaine vaccine and cocaine hydrolase vector treatments together provide enhanced protection against the stimulatory actions of cocaine in rodents. A similar combination therapy in human cocaine users might provide a robust therapy to help maintain abstinence. PMID:22912888

[Hallucinogenic fungi (psilocybe). Part II. Identification of Psilocybe semilanceata by PCR].

PubMed

Adamczyk, Aldona; Sadakierska-Chudy, Anna; Janoszka, Jerzy; Rymkiewicz, Apoloniusz; Dobosz, Tadeusz

2007-01-01

Psilocybe semilanceata belongs to the genus of Psilocybe; it is a hallucinogenic fungus, frequently found in regions with high rainfall, in the grass and moss. There are estimated to be as many as eight Psilocybe hallucinogenic species containing psychoactive alkaloids, such as psilocybin and psilocin, which may cause visual, auditory and other hallucinations, as well as profound changes in the perception of time and space. Since identification of P semilanceata in a form different than a fresh mushroom is almost impossible, the authors made an attempt at developing a method of fungi identification based on the PCR technique, which could be helpful in a fight against dangerous consumption of these hallucinogens by the youth. Detection of the specific DNA sequence for P semilanceata brought good results; the test may be commonly employed in forensic practice in the future.

Suppression of hypothalamic-pituitary-adrenal axis by acute heroin challenge in rats during acute and chronic withdrawal from chronic heroin administration

PubMed Central

Zhou, Yan; Leri, Francesco; Ho, Ann; Kreek, Mary Jeanne

2013-01-01

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

Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens.

PubMed

Goda, Sailaja A; Piasecka, Joanna; Olszewski, Maciej; Kasicki, Stefan; Hunt, Mark J

2013-07-01

The nucleus accumbens (NAc) is a site critical for the actions of many drugs of abuse. Psychoactive compounds, such as N-methyl-D-aspartate receptor (NMDAR) antagonists, modify gamma (40-90) and high frequency oscillations (HFO, 130-180 Hz) in local field potentials (LFPs) recorded in the NAc. Lysergic acid diethylamide (LSD) and 2,5-dimethoxy-4-iodoamphetamine (DOI) are serotonergic hallucinogens and activation of 5HT2A receptors likely underlies their hallucinogenic effects. Whether these compounds can also modulate LFP oscillations in the NAc is unclear. This study aims to examine the effect of serotonergic hallucinogens on gamma and HFO recorded in the NAc and to test whether 5HT2A receptors mediate the effects observed. LFPs were recorded from the NAc of freely moving rats. Drugs were administered intraperitoneally. LSD (0.03-0.3 mg/kg) and DOI (0.5-2.0 mg/kg) increased the power and reduced the frequency of HFO. In contrast, the hallucinogens produced a robust reduction in the power of low (40-60 Hz), but not high gamma oscillations (70-90 Hz). MDL 11939 (1.0 mg/kg), a 5HT2A receptor antagonist, fully reversed the changes induced by DOI on HFO but only partially for the low gamma band. Equivalent increases in HFO power were observed after TCB-2 (5HT2A receptor agonist, 0.1-1.5 mg/kg), but not CP 809101 (5H2C receptor agonist, 0.1-3 mg/kg). Notably, hallucinogen-induced increases in HFO power were smaller than those produced by ketamine (25 mg/kg). Serotonergic hallucinogen-induced changes in HFO and gamma are mediated, at least in part, by stimulation of 5HT2A receptors. Comparison of the oscillatory changes produced by serotonergic hallucinogens and NMDAR antagonists are also discussed.

Cardiovascular manifestations of substance abuse: part 2: alcohol, amphetamines, heroin, cannabis, and caffeine.

PubMed

Frishman, William H; Del Vecchio, Alexander; Sanal, Shirin; Ismail, Anjum

2003-01-01

The abuse of alcohol is associated with chronic cardiomyopathy, hypertension, and arrhythmia. Abstinence or using alcohol in moderation can reverse these cardiovascular problems. Alcohol is also distinguished among the substances of abuse by having possible protective effects against coronary artery disease and stroke when used in moderate amounts. Amphetamines (eg, speed, ice, ecstasy) have many of the cardiovascular toxicities seen with cocaine, including acute and chronic cardiovascular diseases. Heroin and other opiates can cause arrhythmias and noncardiac pulmonary edema, and may reduce cardiac output. Cardiovascular problems are less common with cannabis (marijuana) than with opiates, but major cognitive disorders may be seen with its chronic use. It is still controversial whether caffeine can cause hypertension and coronary artery disease, and questions have been raised about its safety in patients with heart failure and arrhythmia.

Cocaine.

ERIC Educational Resources Information Center

Piazza, Nick J.; Yeager, Rebecca D.

Cocaine was first used by Europeans in the nineteenth century when extract from the coca leaf was combined with various beverages. Cocaine comes as a white crystalline powder. However, a product called crack cocaine may come as an opaque crystal similar in size and shape to rock salt. A third form of cocaine is known as coca paste, which is an…

User’s Guide for the Longitudinal Scalogram Analysis Program

DTIC Science & Technology

1991-01-01

cannabis, pills, psychedelics , cocaine, and heroin. The LSA analysis was restricted to these respondents (n = 791), because complete information about...Total n = 791. 0 = not passed, I = passed. Items am legal drugs, cannabis, pills, psychedelics , cocaine, and heroin. Asterisks denote longitudinal

Acupuncture inhibits cue-induced heroin craving and brain activation★

PubMed Central

Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

2012-01-01

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving. PMID:25368637

Acupuncture inhibits cue-induced heroin craving and brain activation.

PubMed

Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

2012-11-25

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving.

Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine

PubMed Central

Fitzgerald, Paul J.

2013-01-01

A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general. PMID:24151426

Illicit drug use and treatment in South Africa: a review.

PubMed

Peltzer, Karl; Ramlagan, Shandir; Johnson, Bruce D; Phaswana-Mafuya, Nancy

2010-11-01

This review synthesizes available epidemiological data on current drug use and substance user treatment admissions in South Africa since 1994, and how changes in the political, economic, and social structures within South Africa, both before and after Apartheid, has made the country more vulnerable to drug use. Based on national surveys, current use of cannabis ranged among adolescents from 2% to 9% and among adults it was 2%, cocaine/crack (0.3%), mandrax/sedatives (0.3%), club drugs/amphetamine-type stimulants (0.2%), opiates (0.1%), and hallucinogens (0.1%). The use of primary illicit substance at admission to South African drug user treatment centers was cannabis 16.9%, methamphetamine (tik) 12.8%, crack/cocaine 9.6%, cannabis and mandrax 3.4%, heroin/opiates 9.2%, and prescription and OTC drugs 2.6%. An increase in substance user treatment admissions has increased. While the prevalence of illicit drug use in South Africa is relatively low compared to the United States and Australia, prevention and intervention policies need to be designed to reduce these levels by targeting the more risky subpopulations identified from this review.

Childhood maltreatment and substance use disorders among men and women in a nationally representative sample.

PubMed

Afifi, Tracie O; Henriksen, Christine A; Asmundson, Gordon J G; Sareen, Jitender

2012-11-01

To examine the association between a history of 5 types of childhood maltreatment (that is, physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional neglect) and several substance use disorders (SUDs), including alcohol, sedatives, tranquilizers, opioids, amphetamines, cannabis, cocaine, hallucinogens, heroin, and nicotine, in a nationally representative US adult sex-stratified sample. Data were drawn from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a nationally representative US sample of adults aged 20 years and older (n = 34 653). Logistic regression models were conducted to understand the relations between 5 types of childhood maltreatment and SUDs separately among men and women after adjusting for sociodemographic variables and Diagnostic and Statistical Manual of Mental Disorders (DSM) Axis I and II mental disorders. All 5 types of childhood maltreatment were associated with increased odds of all individual SUDs among men and women after adjusting for sociodemographic variables, with the exception of physical neglect and heroin abuse or dependence, emotional neglect, and amphetamines and cocaine abuse or dependence among men (adjusted odds ratio range 1.3 to 4.7). After further adjustment for other DSM Axis I and II mental disorders, the relations between childhood maltreatment and SUDs were attenuated, but many remained statistically significant. Differences in the patterns of findings were noted for men and women for sexual abuse and emotional neglect. This research provides evidence of the robust nature of the relations between many types of childhood maltreatment and many individual SUDs. The prevention of childhood maltreatment may help to reduce SUDs in the general population.

[The ethnopharmacology of hallucinogens: from "primitive rites" to their "presence" on TV. Proposals for the year 2000].

PubMed

Cugurra, F

1996-11-01

Hallucinogens are the chemicals which in nontoxic doses produce changes in perception, mental confusion, memory loss, or disorientation for person, place and time, with organic brain reactions. Mescaline and LSD are historically the most interesting hallucinogens. Today the cannabis is very important, socially. Traditional hallucinogens survive everywhere in the world. A dramatic increase in use of cartoons in drug education and prevention programs prove great damages: in comics and films often have stimulated the appetite for drug experimentation (seduction of innocent, R. K. Siegel). Cartoons and comics are instruments for correcting perceptions and behaviour of youth and youthful drug abusers. As the hallucinogens.

Cocaine adulteration.

PubMed

Kudlacek, Oliver; Hofmaier, Tina; Luf, Anton; Mayer, Felix P; Stockner, Thomas; Nagy, Constanze; Holy, Marion; Freissmuth, Michael; Schmid, Rainer; Sitte, Harald H

2017-10-01

Cocaine is a naturally occurring and illicitly used psychostimulant drug. Cocaine acts at monoaminergic neurotransmitter transporters to block uptake of the monoamines, dopamine, serotonin and norepinephrine. The resulting increase of monoamines in the extracellular space underlies the positively reinforcing effects that cocaine users seek. In turn, this increase in monoamines underlies the development of addiction, and can also result in a number of severe side effects. Currently, cocaine is one of the most common illicit drugs available on the European market. However, cocaine is increasingly sold in impure forms. This trend is driven by cocaine dealers seeking to increase their profit margin by mixing ("cutting") cocaine with numerous other compounds ("adulterants"). Importantly, these undeclared compounds put cocaine consumers at risk, because consumers are not aware of the additional potential threats to their health. This review describes adulterants that have been identified in cocaine sold on the street market. Their typical pharmacological profile and possible reasons why these compounds can be used as cutting agents will be discussed. Since a subset of these adulterants has been found to exert effects similar to cocaine itself, we will discuss levamisole, the most frequently used cocaine cutting agent today, and its metabolite aminorex. Copyright © 2017. Published by Elsevier B.V.

Disrupted white matter structural connectivity in heroin abusers.

PubMed

Sun, Yan; Wang, Gui-Bin; Lin, Qi-Xiang; Lu, Lin; Shu, Ni; Meng, Shi-Qiu; Wang, Jun; Han, Hong-Bin; He, Yong; Shi, Jie

2017-01-01

Neurocognitive impairment is one of the factors that put heroin abusers at greater risk for relapse, and deficits in related functional brain connections have been found. However, the alterations in structural brain connections that may underlie these functional and neurocognitive impairments remain largely unknown. In the present study, we investigated topological organization alterations in the structural network of white matter in heroin abusers and examined the relationships between the network changes and clinical measures. We acquired diffusion tensor imaging datasets from 76 heroin abusers and 78 healthy controls. Network-based statistic was applied to identify alterations in interregional white matter connectivity, and graph theory methods were used to analyze the properties of global networks. The participants also completed a battery of neurocognitive measures. One increased subnetwork characterizing widespread abnormalities in structural connectivity was present in heroin users, which mainly composed of default-mode, attentional and visual systems. The connection strength was positively correlated with increases in fractional anisotropy in heroin abusers. Intriguingly, the changes in within-frontal and within-temporal connections in heroin abusers were significantly correlated with daily heroin dosage and impulsivity scores, respectively. These findings suggest that heroin abusers have extensive abnormal white matter connectivity, which may mediate the relationship between heroin dependence and clinical measures. The increase in white matter connectivity may be attributable to the inefficient microstructure integrity of white matter. The present findings extend our understanding of cerebral structural disruptions that underlie neurocognitive and functional deficits in heroin addiction and provide circuit-level markers for this chronic disorder. © 2015 Society for the Study of Addiction.

The Dynamics of a Heroin Addiction Epidemic

ERIC Educational Resources Information Center

DuPont, Robert L.; Greene, Mark H.

1973-01-01

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)

Drug specificity in drug versus food choice in male rats.

PubMed

Tunstall, Brendan J; Riley, Anthony L; Kearns, David N

2014-08-01

Although different classes of drug differ in their mechanisms of reinforcement and effects on behavior, little research has focused on differences in self-administration behaviors maintained by users of these drugs. Persistent drug choice despite available reinforcement alternatives has been proposed to model behavior relevant to addiction. The present study used a within-subjects procedure, where male rats (Long-Evans, N = 16) were given a choice between cocaine (1.0 mg/kg/infusion) and food (a single 45-mg grain pellet) or between heroin (0.02 mg/kg/infusion) and food in separate phases (drug order counterbalanced). All rats were initially trained to self-administer each drug, and the doses used were based on previous studies showing that small subsets of rats tend to prefer drug over food reinforcement. The goal of the present study was to determine whether rats that prefer cocaine would also prefer heroin. Choice sessions consisted of 2 forced-choice trials with each reinforcer, followed by 14 free-choice trials (all trials separated by 10-min intertrial interval). Replicating previous results, small subsets of rats preferred either cocaine (5 of the 16 rats) or heroin (2 of the 16 rats) to the food alternative. Although 1 of the 16 rats demonstrated a preference for both cocaine and heroin to the food alternative, there was no relationship between degree of cocaine and heroin preference in individual rats. The substance-specific pattern of drug preference observed suggests that at least in this animal model, the tendencies to prefer cocaine or heroin in preference to a nondrug alternative are distinct behavioral phenomena.

Dynamic vaccine blocks relapse to compulsive intake of heroin

PubMed Central

Schlosburg, Joel E.; Vendruscolo, Leandro F.; Bremer, Paul T.; Lockner, Jonathan W.; Wade, Carrie L.; Nunes, Ashlee A. K.; Stowe, G. Neil; Edwards, Scott; Janda, Kim D.; Koob, George F.

2013-01-01

Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin’s rapid metabolism to 6-acetylmorphine and morphine. We recently developed a “dynamic” vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin’s metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin’s psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance. PMID:23650354

Buprenorphine from detox and beyond: preliminary evaluation of a pilot program to increase heroin dependent individuals' engagement in a full continuum of care.

PubMed

Donovan, Dennis M; Knox, Patricia C; Skytta, Jenny A F; Blayney, Jessica A; DiCenzo, Jessica

2013-04-01

Absence of successful transition to post-detoxification treatment leads to high rates of relapse among detoxified heroin users. The present study evaluated a pilot buprenorphine treatment program (BTP). Heroin dependent individuals were inducted onto buprenorphine/naloxone in detox, maintained while transitioning through an intensive inpatient program (IIP), and gradually tapered off medication over 5 months of outpatient (OP) treatment. Compared to programmatic indicators of treatment engagement in the year prior to BTP implementation, referrals from detox to IIP, entry into and completion of IIP and subsequent OP, and days in OP treatment increased substantially. BTP completers, compared to non-completers, viewed abstinence as more difficult and as requiring more assistance to achieve, were less likely to be current cocaine and alcohol users or to have relapsed during the course of treatment. Although preliminary and in need of replication, initial adjunctive use of buprenorphine in an abstinence-based continuum of care may improve post-detoxification treatment entry, engagement, and completion. Copyright © 2013 Elsevier Inc. All rights reserved.

Facial recognition of heroin vaccine opiates: type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine.

PubMed

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

2014-03-14

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. Copyright © 2014. Published by Elsevier Ltd.

Facial recognition of heroin vaccine opiates: Type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine

PubMed Central

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; Alving, Carl R.

2014-01-01

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. PMID:24486371

Characteristics of primary amphetamine users in Sweden: a criminal justice population examined with the Addiction Severity Index.

PubMed

Hakansson, A; Schlyter, F; Berglund, M

2009-01-01

Characteristics of primary amphetamine, heroin and cocaine users were compared in a criminal justice population. 7,085 clients with suspected or reported substance use were studied using the Addiction Severity Index. Variables separating amphetamine, heroin and cocaine users were analyzed in stepwise logistic regression. There were considerably more primary amphetamine users (n = 1,396) than heroin (n = 392) and cocaine (n = 119) users. Amphetamine users were older, a more rural population, and less likely to be non-Nordic immigrants. Compared with heroin, amphetamine use was associated with older age, Nordic origin, nonurban residence, memory/concentration problems, parental alcohol problems, and less history of other opioid use, overdose and detoxification. Compared with cocaine, amphetamine use was associated with older age, Nordic origin, nonurban residence, injecting, tobacco and institution treatment. Overlap of drug use between groups was relatively uncommon. This pattern of amphetamine use, common among Swedish criminals, has relatively distinct boundaries from heroin and cocaine use, commonly involves injecting, and differs from other countries. Psychiatric problems and alcohol heredity were common, and evidence-based treatment for amphetamine users is needed. The connection between amphetamine use and criminal behavior is insufficiently understood and should be further addressed. Copyright 2008 S. Karger AG, Basel.

A bacterial cocaine esterase protects against cocaine-induced epileptogenic activity and lethality.

PubMed

Jutkiewicz, Emily M; Baladi, Michelle G; Cooper, Ziva D; Narasimhan, Diwahar; Sunahara, Roger K; Woods, James H

2009-09-01

Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (-)-2beta-carbomethoxy-3beta-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted.

Detection of drugs in the urine of body-packers.

PubMed

Gherardi, R K; Baud, F J; Leporc, P; Marc, B; Dupeyron, J P; Diamant-Berger, O

1988-05-14

The presence of opiates and benzoylecgonine, the major metabolite of cocaine, in the urine was detected by means of enzyme immunoassay in a series of 120 smugglers who had either ingested or inserted into their rectum cocaine or heroin packaged for transportation. There was a striking relation between the presence of drugs in the urine and swallowing of drug-filled bundles (cocaine 49 of 50 cases, heroin 9 of 10). The proportion of positive results was also high in cases of rectal insertion (cocaine 2 of 2, heroin 35 of 58). In 30 cases of cocaine-packet ingestion, serial measurements showed that the accuracy of the test progressively decreased with respect to the detection of residual packets in the body. Drug detection in the urine of suspected body-packers seems to be a useful test, positive results justifying subsequent radiological investigations.

Researchers Explore New Visions for Hallucinogens

ERIC Educational Resources Information Center

Brown, Susan

2006-01-01

Recently, 36 people who had never taken hallucinogens before gave them a try. The pill they took launched a daylong psychedelic journey, sometimes fantastic, sometimes frightening. When it was over, a few who took the drug said it was the most meaningful experience of their lives, as momentous as the birth of a first child or the death of a…

Cocaine

MedlinePlus

Cocaine is a white powder. It can be snorted up the nose or mixed with water and injected with a needle. Cocaine can also be made into small white rocks, ... Crack is smoked in a small glass pipe. Cocaine speeds up your whole body. You may feel ...

10 CFR 712.37 - Evaluation for hallucinogen use.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Evaluation for hallucinogen use. 712.37 Section 712.37 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.37 Evaluation for... performance and observed behavior. ...

10 CFR 712.37 - Evaluation for hallucinogen use.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Evaluation for hallucinogen use. 712.37 Section 712.37 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.37 Evaluation for... performance and observed behavior. ...

10 CFR 712.37 - Evaluation for hallucinogen use.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Evaluation for hallucinogen use. 712.37 Section 712.37 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.37 Evaluation for... performance and observed behavior. ...

10 CFR 712.37 - Evaluation for hallucinogen use.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Evaluation for hallucinogen use. 712.37 Section 712.37 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.37 Evaluation for... performance and observed behavior. ...

10 CFR 712.37 - Evaluation for hallucinogen use.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Evaluation for hallucinogen use. 712.37 Section 712.37 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.37 Evaluation for... performance and observed behavior. ...

Do drug seizures predict drug-related emergency department presentations or arrests for drug use and possession?

PubMed

Wan, Wai-Yin; Weatherburn, Don; Wardlaw, Grant; Sarafidis, Vasilis; Sara, Grant

2016-01-01

Direct evidence of the effect of drug seizures on drug use and drug-related harm is fairly sparse. The aim of this study was to see whether seizures of heroin, cocaine and ATS predict the number of people arrested for use and possession of these drugs and the number overdosing on them. We examined the effect of seizure frequency and seizure weight on arrests for drug use and possession and on the frequency of drug overdose with autoregressive distributed lag (ARDL) models. Granger causality tests were used to test for simultaneity. Over the short term (i.e. up to 4 months), increases in the intensity of high-level drug law enforcement (as measured by seizure weight and frequency) directed at ATS, cocaine and heroin did not appear to have any suppression effect on emergency department (ED) presentations relating to ATS, cocaine and heroin, or on arrests for use and/or possession of these drugs. A significant negative contemporaneous relationship was found between the heroin seizure weight and arrests for use and/or possession of heroin. However no evidence emerged of a contemporaneous or lagged relationship between heroin seizures and heroin ED presentations. The balance of evidence suggests that, in the Australian context, increases in the monthly seizure frequency and quantity of ATS, cocaine and heroin are signals of increased rather than reduced supply. Copyright © 2015 Elsevier B.V. All rights reserved.

A Bacterial Cocaine Esterase Protects Against Cocaine-Induced Epileptogenic Activity and Lethality

PubMed Central

Jutkiewicz, Emily M.; Baladi, Michelle G.; Cooper, Ziva D.; Narasimhan, Diwahar; Sunahara, Roger K.; Woods, James H.

2012-01-01

Study objective Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Methods Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. Results The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (−)-2β-carbomethoxy-3β-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. Conclusion The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted. PMID:19013687

The risk of adolescent suicide across patterns of drug use: a nationally representative study of high school students in the United States from 1999 to 2009.

PubMed

Wong, Shane Shucheng; Zhou, Bo; Goebert, Deborah; Hishinuma, Earl S

2013-10-01

Substance use is associated with suicidal ideation, planning and attempts among adolescents, but it is unclear how this association varies across different types and number of substances. This study examined the association between patterns of substance use and suicidality among a nationally representative sample of high school students in the United States during the last decade. Data from the 2001 to 2009 Youth Risk Behavior Survey including 73,183 high school students were analyzed. Logistic regression analyses examined the association between lifetime use of ten common substances of abuse (alcohol, cocaine, ecstasy, hallucinogens, heroin, inhalants, marijuana, methamphetamines, steroids, and tobacco) and four measures of suicidality over the last year (suicidal ideation, suicide plan, suicide attempt, and severe suicide attempt requiring medical attention), controlling for potential confounders (socio-demographic variables, interpersonal violence, sexual intercourse, and symptoms of depression and eating disorder). Among the ten substances, univariate analysis demonstrates that adolescents reporting a history of heroin use have the strongest association with suicidal ideation, suicide plan, suicide attempts and severe suicide attempts in the last year (odds ratio = 5.0, 5.9, 12.0, and 23.6 compared to non-users), followed by users of methamphetamines (OR = 4.3-13.1) and steroids (OR = 3.7-11.8). Cocaine, ecstasy, hallucinogens and inhalants had a moderate association with suicidality (OR = 3.1-10.8). Users of marijuana, alcohol and tobacco also had an increased odds ratio of suicidality (OR = 1.9-5.2). The association between each of ten substances and the four measures of suicidality remained significant with multivariate analysis controlling for multiple confounders (p < 0.05), except for the association between alcohol use and severe suicide attempts. The seven illicit substances had a stronger association with severe suicide attempts as compared to all

Levels of heroin and its metabolites in blood and brain extracellular fluid after i.v. heroin administration to freely moving rats

PubMed Central

Gottås, A; Øiestad, E L; Boix, F; Vindenes, V; Ripel, Å; Thaulow, C H; Mørland, J

2013-01-01

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

A System Description of the Heroin Trade

DTIC Science & Technology

1994-01-01

19 3.3. Estimated Distribution of Heroin Smuggling by U.S. Entry Region ............................................. 20 4.1...14. Distribution of Incoming Heroin Among U.S. Entry Regions (Cells A351 to R418) .................................... 84 C-15. Distribution of...Transportation Modes into U.S. Entry Regions (Cells A419 to P472) .................................... 86 C.16. Seizures of Heroin (Cells A473 to P498

North American Indian rock art and hallucinogenic drugs.

PubMed

Wellmann, K F

1978-04-14

It is proposed that the aboriginal rock paintings in two areas of North America may have been produced by shamans while they were under the influence of hallucinogenic agents derived from plants. The first of these areas is the Chumash and Yokuts Indian region of California, where polychrome paintings show designs similar to those visualized during the trance induced by decoctions of jimsonweed (Datura species). The second area is the lower Pecos River region of Texas, where shamanistic figures display traits considered to be conceptual analogues of the mescal bean (Sophora secundiflora) cult as practiced during historic times by Great Plains Indians. Although the evidence is only circumstantial, the proposed connections between these rock drawings and mind-expanding pharmacologic compounds fit well into the documented relationship that encompasses hallucinogenic drugs and certain movable objects of pre-Columbian American art.

An item response theory analysis of DSM-IV criteria for hallucinogen abuse and dependence in adolescents

PubMed Central

Wu, Li-Tzy; Pan, Jeng-Jong; Yang, Chongming; Reeve, Bryce B.; Blazer, Dan G.

2009-01-01

Aim This study applied both item response theory (IRT) and multiple indicators–multiple causes (MIMIC) methods to evaluate item-level psychometric properties of diagnostic questions for hallucinogen use disorders (HUDs), differential item functioning (DIF), and predictors of latent HUD. Methods Data were drawn from 2004–2006 National Surveys on Drug Use and Health. Analyses were based on 1548 past-year hallucinogen users aged 12–17 years. Substance use and symptoms were assessed by audio computer-assisted self-interviewing methods. Results Abuse and dependence criteria empirically were arrayed along a single continuum of severity. All abuse criteria indicated middle-to-high severity on the IRT-defined HUD continuum, while dependence criteria captured a wider range from the lowest (tolerance and time spent) to the highest (taking larger amounts and inability to cut down) severity levels. There was indication of DIF by hallucinogen users’ age, gender, race/ethnicity, and ecstasy use status. Adjusting for DIF, ecstasy users (vs. non-ecstasy hallucinogen users), females (vs. males), and whites (vs. Hispanics) exhibited increased odds of HUD. Conclusions Symptoms of hallucinogen abuse and dependence empirically do not reflect two discrete conditions in adolescents. Trends and problems related to hallucinogen use among girls and whites should be examined further to inform the designs of effective gender-appropriate and culturally sensitive prevention programs. PMID:19896773

Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moeller, S.J.; Goldstein, R.; Moeller, S.J.

Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures-under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)-was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences thatmore » were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.« less

The impact of law enforcement activity on a heroin market.

PubMed

Weatherburn, D; Lind, B

1997-05-01

It may be argued that seizing large quantities of heroin being imported into the country should decrease its supply and hence increase its price, resulting in a reduction in the quantity of the drug being purchased or consumed. To date, however, there has been no empirical evidence that heroin seizures in Australia have any effect on the price of heroin at street level. This article describes a 2-year research study during which the price and purity of street-level heroin were regularly monitored. It was found that heroin seizures had no effect on the price, purity or perceived availability of heroin at street level. It was further found that admissions to methadone treatment were not affected by the price or perceived availability of heroin or by local arrests for heroin use/possession, nor was any relationship found between these arrests and the price of street-level heroin. Nevertheless, two-thirds of those who sought entry to local methadone programmes indicated the price as a reason for stopping using heroin. This paper argues that supply-side law enforcement should only be used as a strategy for maintaining high heroin prices if the demand for heroin can be shown to be price-elastic and, further, that the costs of such a strategy need to be weighted against the benefits.

Novel C-1 Substituted Cocaine Analogs Unlike Cocaine or Benztropine

PubMed Central

Ali, Solav; Hashim, Audrey; Sheikh, Imran S.; Theddu, Naresh; Gaddiraju, Narendra V.; Mehrotra, Suneet; Schmitt, Kyle C.; Murray, Thomas F.; Sershen, Henry; Unterwald, Ellen M.; Davis, Franklin A.

2012-01-01

Despite a wealth of information on cocaine-like compounds, there is no information on cocaine analogs with substitutions at C-1. Here, we report on (R)-(−)-cocaine analogs with various C-1 substituents: methyl (2), ethyl (3), n-propyl (4), n-pentyl (5), and phenyl (6). Analog 2 was equipotent to cocaine as an inhibitor of the dopamine transporter (DAT), whereas 3 and 6 were 3- and 10-fold more potent, respectively. None of the analogs, however, stimulated mouse locomotor activity, in contrast to cocaine. Pharmacokinetic assays showed compound 2 occupied mouse brain rapidly, as cocaine itself; moreover, 2 and 6 were behaviorally active in mice in the forced-swim test model of depression and the conditioned place preference test. Analog 2 was a weaker inhibitor of voltage-dependent Na+ channels than cocaine, although 6 was more potent than cocaine, highlighting the need to assay future C-1 analogs for this activity. Receptorome screening indicated few significant binding targets other than the monoamine transporters. Benztropine-like “atypical” DAT inhibitors are known to display reduced cocaine-like locomotor stimulation, presumably by their propensity to interact with an inward-facing transporter conformation. However, 2 and 6, like cocaine, but unlike benztropine, exhibited preferential interaction with an outward-facing conformation upon docking in our DAT homology model. In summary, C-1 cocaine analogs are not cocaine-like in that they are not stimulatory in vivo. However, they are not benztropine-like in binding mechanism and seem to interact with the DAT similarly to cocaine. The present data warrant further consideration of these novel cocaine analogs for antidepressant or cocaine substitution potential. PMID:22895898

Acute progressive paraplegia in heroin-associated myelopathy.

PubMed

Mahoney, Kyle W; Romba, Meghan; Gailloud, Philippe; Izbudak, Izlem; Saylor, Deanna

2018-05-01

As the opioid epidemic continues, understanding manifestations of abuse, including heroin-associated myelopathy remains essential. Here we describe a young man with a past medical history significant for polysubstance abuse who developed acute-onset, rapidly progressive myelopathy after resumption of intravenous heroin use. He had significant spinal cord involvement with findings suggestive of heroin-associated myelopathy. The salient features of this case include diffusion imaging of the spine and spinal angiography supporting a possible vasculopathy as the pathophysiologic mechanism underlying heroin-associated myelopathy. Additionally, CSF studies showed the transition from a neutrophilic pleocytosis to a lymphocytic pleocytosis suggesting an inflammatory component. Copyright © 2018 Elsevier Ltd. All rights reserved.

Differential effect of opioid and cannabinoid receptor blockade on heroin-seeking reinstatement and cannabinoid substitution in heroin-abstinent rats

PubMed Central

Fattore, L; Spano, MS; Melis, V; Fadda, P; Fratta, W

2011-01-01

BACKGROUND AND PURPOSE Opioids and cannabinoids interact in drug addiction and relapse. We investigated the effect of the opioid receptor antagonist naloxone and/or the cannabinoid CB1 receptor antagonist rimonabant on cannabinoid-induced reinstatement of heroin seeking and on cannabinoid substitution in heroin-abstinent rats. EXPERIMENTAL APPROACH Rats were trained to self-administer heroin (30 µg·kg−1 per infusion) under a fixed-ratio 1 reinforcement schedule. After extinction of self-administration (SA) behaviour, we confirmed the effect of naloxone (0.1–1 mg·kg−1) and rimonabant (0.3–3 mg·kg−1) on the reinstatement of heroin seeking induced by priming with the CB1 receptor agonist WIN55,212-2 (WIN, 0.15–0.3 mg·kg−1). Then, in a parallel set of heroin-trained rats, we evaluated whether WIN (12.5 µg·kg−1 per infusion) SA substituted for heroin SA after different periods of extinction. In groups of rats in which substitution occurred, we studied the effect of both antagonists on cannabinoid intake. KEY RESULTS Cannabinoid-induced reinstatement of heroin seeking was significantly attenuated by naloxone (1 mg·kg−1) and rimonabant (3 mg·kg−1) and fully blocked by co-administration of sub-threshold doses of the two antagonists. Moreover, contrary to immediate (1 day) or delayed (90 days) drug substitution, rats readily self-administered WIN when access was given after 7, 14 or 21 days of extinction from heroin, and showed a response rate that was positively correlated with the extinction period. In these animals, cannabinoid intake was increased by naloxone (1 mg·kg−1) and decreased by rimonabant (3 mg·kg−1). CONCLUSIONS AND IMPLICATIONS Our findings extend previous research on the crosstalk between cannabinoid and opioid receptors in relapse mechanisms, which suggests a differential role in heroin-seeking reinstatement and cannabinoid substitution in heroin-abstinent rats. LINKED ARTICLES This article is part of a themed issue on

Emergence of cocaine and methamphetamine injection among HIV-positive injection drug users in Northern and Western India

PubMed Central

Mehta, Shruti H.; Srikrishnan, Aylur K; Noble, Eva; Vasudevan, Canjeevaram K; Solomon, Suniti; Kumar, M Suresh; Solomon, Sunil S

2014-01-01

Background Little is known regarding the epidemiology of drug injection and risk behaviors among injection drug users (IDUs) across India. In particular, there is limited data on the prevalence of stimulant injection. Methods We sampled 801 HIV positive IDUs from 14 locations throughout India to represent the geography of India as well as the diversity in IDU epidemic stage (established epidemics, emerging epidemics and large cities). All participants underwent a behavioral survey and blood draw. Given prior associations with stimulant injection and HIV risk, we compared stimulant injectors (cocaine and/or methamphetamine) to those who injected opiates and/or pharmaceuticals only. Results The median age was 33; 86% were male. The primary drugs injected were heroin, buprenorphine and other pharmaceuticals. In all but four sites, >50% of those actively injecting reported needle sharing. Stimulant injection was most common in emerging epidemics. Compared to exclusive opiate injectors, stimulant injectors were significantly younger, more likely to be educated and employed, more likely to report non-injection use of heroin, crack/cocaine and amphetamines, heavy alcohol use, recent needle sharing (71% vs. 57%), sex with a casual partner (57% vs. 31%) and men having sex with other men (33% vs. 9%; p<0.01 for all). Conclusions Emerging IDU epidemics have a drug/sexual risk profile not previously been observed in India. Given the high prevalence of stimulant injection in these populations, HIV prevention/treatment programs may need to be redesigned to maximize effectiveness. The high levels of injection sharing overall reinforce the need to ensure access to harm-reduction services for all. PMID:24382362

Trends and characteristics of heroin overdoses in Wisconsin, 2003-2012.

PubMed

Meiman, Jon; Tomasallo, Carrie; Paulozzi, Leonard

2015-07-01

Heroin abuse has increased substantially during the past decade in the United States. This study describes trends and demographic shifts of heroin overdoses and heroin-related fatalities in Wisconsin and contrasts these with prescription opioid overdoses. This study was cross-sectional using databases of emergency department (ED) visits, hospital admissions, and death certificates in Wisconsin, United States, during 2003-2012. Cases were Wisconsin residents treated for heroin or prescription opioid overdose, and residents who died of heroin-related drug poisoning. Primary measurements were rates over time and by geographic region, and rates and rate ratios for selected demographic characteristics. During 2003-2012, age-adjusted rates of heroin overdoses treated in EDs increased from 1.0 to 7.9/100,000 persons; hospitalized heroin overdoses increased from 0.7 to 3.5/100,000. Whites accounted for 68% of hospitalized heroin overdoses during 2003-2007 but 80% during 2008-2012. Heroin-related deaths were predominantly among urban residents; however, rural fatalities accounted for zero deaths in 2003 but 31 (17%) deaths in 2012. Among patients aged 18-34 years, those hospitalized with heroin overdose were more often men (73.0% versus 54.9%), uninsured (44.2% versus 29.9%), and urban (84.3% versus 73.2%) than those with prescription opioid overdose. Rates of ED visits for heroin overdose in this age group exceeded rates for prescription opioid overdose in 2012 (26.1/100,000 versus 12.6/100,000 persons, respectively). An epidemic of heroin abuse is characterized by demographic shifts toward whites and rural residents. Rates of heroin overdose in younger persons now exceed rates of prescription opioid overdose. Published by Elsevier Ireland Ltd.

Hapten Optimization for Cocaine Vaccine with Improved Cocaine Recognition

PubMed Central

Ramakrishnan, Muthu; Kinsey, Berma M.; Singh, Rana A.; Kosten, Thomas R.; Orson, Frank M.

2014-01-01

In the absence of any effective pharmacotherapy for cocaine addiction, immunotherapy is being actively pursued as a therapeutic intervention. While several different cocaine haptens have been explored to develop anti-cocaine antibodies, none of the hapten was successfully designed which had a protonated tropane nitrogen as is found in native cocaine under physiological conditions, including the succinyl norcocaine (SNC) hapten that has been tested in phase II clinical trials. Herein, we discuss three different cocaine haptens: hexyl-norcocaine (HNC), bromoacetamido butyl- norcocaine (BNC), and succinyl-butyl- norcocaine (SBNC), each with a tertiary nitrogen structure mimicking that of native cocaine which could optimize the specificity of anti-cocaine antibodies for better cocaine recognition. Mice immunized with these haptens conjugated to immunogenic proteins produced high titer anti-cocaine antibodies. However, during chemical conjugation of HNC and BNC haptens to carrier proteins, the 2β methyl ester group is hydrolyzed and immunizing mice with these conjugate vaccines in mice produced antibodies that bound both cocaine and the inactive benzoylecgonine metabolite. While in the case of the SBNC conjugate vaccine hydrolysis of the methyl ester did not appear to occur, leading to antibodies with high specificity to cocaine over BE. Though we observed similar specificity with a SNC hapten, the striking difference is that SBNC carries a positive charge on the tropane nitrogen atom, and therefore it is expected to have better binding of cocaine. The 50% cocaine inhibitory concentration (IC50) value for SBNC antibodies (2.8 μM) was significantly better than the SNC antibodies (9.4 μM) when respective hapten-BSA was used as a substrate. In addition, antibodies from both sera had no inhibitory effect from BE. In contrast to BNC and HNC, the SBNC conjugate was also found to be highly stable without any noticeable hydrolysis for several months at 4°C and 2-3 days in p

Prenatal and postnatal cocaine exposure predict teen cocaine use

PubMed Central

Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

2015-01-01

Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

Temporal correlation between opiate seizures in East/Southeast Asia and B.C. heroin deaths: a transoceanic model of heroin death risk.

PubMed

McLean, Mark E

2003-01-01

Because heroin supply changes cannot be measured directly, their impact on populations is poorly understood. British Columbia has experienced an injection drug use epidemic since the 1980s that resulted in 2,590 illicit drug deaths from 1990-1999. Since previous work indicates heroin seizures can correlate with supply and B.C. receives heroin only from Southeast Asia, this study examined B.C. heroin deaths against opiate seizures in East/Southeast Asia. Opiate seizures in East/Southeast Asia and data from two B.C. mortality datasets containing heroin deaths were examined. The Pearson correlation coefficient for seizures against each mortality dataset was determined. Opiate seizures, all illicit drug deaths and all opiate deaths concurrently increased twice and decreased twice from 1989-1999, and all reached new peak values in 1993. Three B.C. sub-regions exhibited illicit drug deaths rate trends concurrent with the three principal datasets studied. The Pearson correlation coefficient for opiate-induced deaths against opiate seizures from 1980-1999 was R=0.915 (p<0.0001), and for illicit drug deaths against opiate seizures from 1987-1999 was R=0.896 (p<0.0001). From 1980-1999, opiate seizures in East/Southeast Asia were very strongly correlated with B.C. opiate and illicit drug deaths. The number of B.C. heroin-related deaths may be strongly linked to heroin supply. Enforcement services are not effective in preventing harm caused by heroin in B.C.; therefore, Canada should examine other methods to prevent harm. The case for harm reduction is strengthened by the ineffectiveness of enforcement and the unlikelihood of imminent eradication of heroin production in Southeast Asia.

What caused the recent reduction in heroin supply in Australia?

PubMed

Wodak, Alex

2008-08-01

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

Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine

PubMed Central

Siciliano, Cody A.; Fordahl, Steve C.

2016-01-01

Cocaine addiction is a debilitating neuropsychiatric disorder characterized by uncontrolled cocaine intake, which is thought to be driven, at least in part, by cocaine-induced deficits in dopamine system function. A decreased ability of cocaine to elevate dopamine levels has been repeatedly observed as a consequence of cocaine use in humans, and preclinical work has highlighted tolerance to cocaine's effects as a primary determinant in the development of aberrant cocaine taking behaviors. Here we determined that cocaine self-administration in rats produced tolerance to the dopamine transporter-inhibiting effects of cocaine in the nucleus accumbens core, which was normalized following a 14 or 60 d abstinence period; however, although these rats appeared to be similar to controls, a single self-administered infusion of cocaine at the end of abstinence, even after 60 d, fully reinstated tolerance to cocaine's effects. A single cocaine infusion in a naive rat had no effect on cocaine potency, demonstrating that cocaine self-administration leaves the dopamine transporter in a “primed” state, which allows for cocaine-induced plasticity to be reinstated by a subthreshold cocaine exposure. Further, reinstatement of cocaine tolerance was accompanied by decreased cocaine-induced locomotion and escalated cocaine intake despite extended abstinence from cocaine. These data demonstrate that cocaine leaves a long-lasting imprint on the dopamine system that is activated by re-exposure to cocaine. Further, these results provide a potential mechanism for severe cocaine binge episodes, which occur even after sustained abstinence from cocaine, and suggest that treatments aimed at transporter sites may be efficacious in promoting binge termination following relapse. SIGNIFICANCE STATEMENT Tolerance is a DSM-V criterion for substance abuse disorders. Abusers consistently show reduced subjective effects of cocaine concomitant with reduced effects of cocaine at its main site of action

Leucoencephalopathy following abuse of sniffed heroin.

PubMed

Lefaucheur, Romain; Lebas, Axel; Gérardin, Emmanuel; Grangeon, Lou; Ozkul-Wermester, Ozlem; Aubier-Girard, Carole; Martinaud, Olivier; Maltête, David

2017-01-01

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prenatal and postnatal cocaine exposure predict teen cocaine use.

PubMed

Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

2011-01-01

Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

Substance use -- cocaine

MedlinePlus

... Charlie, coca, coke, flake, rock, snow, speedball, toot. Cocaine's Effects on Your Brain Cocaine is a strong stimulant. ... injecting, and last 15 to 30 minutes. Harmful Effects of Cocaine Cocaine can harm the body in many ways ...

Polysubstance Use and Heroin Relapse among Adolescents following Residential Treatment

ERIC Educational Resources Information Center

Branson, Christopher E.; Clemmey, Philip; Harrell, Paul; Subramaniam, Geetha; Fishman, Marc

2012-01-01

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…

[Forensic Analysis of 20 Dead Cases Related to Heroin Abuse].

PubMed

Huang, W Q; Li, L H; Li, Z; Hong, S J

2016-08-01

To perform retrospective analysis on 20 dead cases related to heroin abuse, and to provide references for the forensic assessment of correlative cases. Among 20 dead cases related to heroin abuse, general situation, using method of drug, cause of death and result of forensic examination were analyzed by statistical analysis for summarizing the cause of death and pathologic changes. The dead were mostly young adults, with more male than female. The results of histopathological examinations showed non-specific pathological changes. There were four leading causes of death, including acute poisoning of heroin abuse or leakage （13 cases, 65%）, concurrent diseases caused by heroin abuse （3 cases, 15%）, inspiratory asphyxia caused by taking heroin （2 cases, 10%）, and heroin withdrawal syndrome （2 cases, 10%）. The forensic identification on dead related to heroin abuse must base on the comprehensive autopsy, and combine with the qualitative and quantitative analysis of heroin and its metabolites in death and the case information, as well as the scene investigation. Copyright© by the Editorial Department of Journal of Forensic Medicine

ZNF804A variants confer risk for heroin addiction and affect decision making and gray matter volume in heroin abusers.

PubMed

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

2016-05-01

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. © 2015 Society for the Study of Addiction.

[CNS metabolism in high-risk drug abuse, German version : Insights gained from 1H- and 31P MRS and PET].

PubMed

Bodea, S V

2017-06-01

High-risk drug consumption is a considerable problem for public health actors in industrialised countries. The latest trends show a market tendency towards diversification and increasing demand for high-purity synthetic drugs. Whilst most consumers seek medical help after cannabis use, it is high-risk drugs like cocaine, heroin and amphetamines that account for most of the 1000 drug-related deaths that occur in Germany every year. This article presents the most prominent in vivo cerebral metabolic information in cocaine, heroin and methamphetamine users provided by MRI spectroscopy and PET imaging. We reviewed the literature reporting neuroimaging studies of in vivo metabolic data for methamphetamine, cocaine and heroin consumption published up to March 2017. The search was conducted using PubMed with the following key words: methamphetamine, cocaine, heroin, MR spectroscopy, PET. MRI and PET are indispensable tools in gauging brain metabolic response to illegal drug abuse. Future breakthroughs in this field will most likely come from the investigation of novel neurotransmitter systems in PET and imaging phosphorus and carbon metabolites in MRI.

Differential effects of the metabotropic glutamate 2/3 receptor agonist LY379268 on nicotine versus cocaine self-administration and relapse in squirrel monkeys.

PubMed

Justinova, Zuzana; Le Foll, Bernard; Redhi, Godfrey H; Markou, Athina; Goldberg, Steven R

2016-05-01

Group II metabotropic glutamate receptors (mGluR2 and mGluR3) have been suggested to play an important role in mediation of drug-reinforced behaviors, as well as in the mechanisms underlying relapse in abstinent subjects. The prototypical mGluR2/3 agonist, LY379268, has been shown to attenuate nicotine reinforcement and cue-induced reinstatement of drug seeking in rats, as well as reinstatement induced by drug-associated stimuli and contexts across different drugs of abuse (i.e., cocaine, heroin, and methamphetamine). However, in primates, LY379268 has been shown to produce conflicting results on abuse-related effects of cocaine, and there are no data available for nicotine. To explore the therapeutic potential of mGluR2/3 agonists, we compared the effects of LY379268 (0.03-1.0 mg/kg) on nicotine, cocaine, and food self-administration under a fixed-ratio (FR10) schedule in three separate groups of squirrel monkeys. Moreover, we studied the effects of LY379268 on nicotine/cocaine priming-induced and cue-induced reinstatement of drug-seeking behavior in nicotine- and cocaine-experienced groups of animals. LY379268 blocked nicotine, but not cocaine, self-administration in monkeys. There was a partial overlap between doses that affected nicotine and food self-administration. In abstinent monkeys, LY379268 dose-dependently blocked nicotine, but not cocaine, priming-induced reinstatement of drug seeking. In both cocaine-experienced and nicotine-experienced groups of animals, LY379268 potently reduced cue-induced reinstatement of drug-seeking behavior. The present findings provide strong support for the potential utility of mGlu2/3 receptor agonists for the treatment of nicotine dependence and suggest their utility for prevention of relapse induced by environmental cues associated with drug taking.

A proposal to evaluate mechanistic efficacy of hallucinogens in addiction treatment.

PubMed

Burdick, Brittany Vasae; Adinoff, Bryon

2013-09-01

Current treatments for addiction are frequently ineffective. Hallucinogenic therapy has been indicated as helpful for a range of substance use disorders, yet this approach remains understudied and publicly unavailable. It is nonetheless a promising treatment, which has significant, long-term beneficial effects with single doses and a profile characterized by general safety, low toxicity, and non-addictiveness. However, pharmacological interventions, such as hallucinogens, should not be offered if the same effects (e.g. psychological insights/mystical experiences) and outcomes (e.g. decreased drug use) could be achieved absent pharmacological intervention. To date, there have been no clinical comparisons of drug-induced altered states with non-drug-induced states for addiction treatment. We propose and then outline a clinical trial to address this gap in knowledge. The proposed design would evaluate abstinence outcomes in a population of prescription opioid abusers after exposure to one of three conditions: a drug-induced altered state using psilocybin, a non-drug-induced altered state via hyperventilation (Holotropic Breathwork), and an active placebo with niacin. The outcomes of such a study would reveal important differences in therapeutic potential by discriminating hallucinogen-dependent effects from those psychological effects resulting from altered states.

Therapeutic mechanisms of classic hallucinogens in the treatment of addictions: from indirect evidence to testable hypotheses.

PubMed

Bogenschutz, Michael P; Pommy, Jessica M

2012-01-01

Alcohol and drug addiction are major public health problems, and existing treatments are only moderately effective. Although there has been interest for over half a century in the therapeutic use of classic hallucinogens to treat addictions, clinical research with these drugs was halted at an early stage in the early 1970s, leaving many fundamental questions unanswered. In the past two decades, clinical research on classic hallucinogens has resumed, although addiction treatment trials are only now beginning. The purpose of this paper is to provide a targeted review of the research most relevant to the therapeutic potential of hallucinogens, and to integrate this information with current thinking about addiction and recovery. On the basis of this information, we present a heuristic model which organizes a number of hypotheses that may be tested in future research. We conclude that existing evidence provides a convincing rationale for further research on the effects of classic hallucinogens in the treatment of addiction. Copyright © 2012 John Wiley & Sons, Ltd.

Prescription naloxone: a novel approach to heroin overdose prevention.

PubMed

Sporer, Karl A; Kral, Alex H

2007-02-01

The mortality and morbidity from heroin overdose have increased in the United States and internationally in the last decade. The lipid solubility allows the rapid deposition of heroin and its metabolites into the central nervous system and accounts for the "rush" experienced by users and for the toxicity. Risk factors for fatal and nonfatal heroin overdoses such as recent abstinence, decreased opiate tolerance, and polydrug use have been identified. Opiate substitution treatment such as methadone or buprenorphine is the only proven method of heroin overdose prevention. Death from a heroin overdose most commonly occurs 1 to 3 hours after injection at home in the company of other people. Numerous communities have taken advantage of this opportunity for treatment by implementing overdose prevention education to active heroin users, as well as prescribing naloxone for home use. Naloxone is a specific opiate antagonist without agonist properties or potential for abuse. It is inexpensive and nonscheduled and readily reverses the respiratory depression and sedation caused by heroin, as well as causing transient withdrawal symptoms. Program implementation considerations, legal ramifications, and research needs for prescription naloxone are discussed.

Cigarette Cue Attentional Bias in Cocaine-Smoking and Non-Cocaine-Using Cigarette Smokers.

PubMed

Marks, Katherine R; Alcorn, Joseph L; Stoops, William W; Rush, Craig R

2016-09-01

Cigarette smoking in cocaine users is nearly four times higher than the national prevalence and cocaine use increases cigarette smoking. The mechanisms underlying cigarette smoking in cocaine-using individuals need to be identified to promote cigarette and cocaine abstinence. Previous studies have examined the salience of cigarette and cocaine cues separately. The present aim was to determine whether cigarette attentional bias (AB) is higher in cigarettes smokers who smoke cocaine relative to individuals who only smoke cigarettes. Twenty cigarette smokers who smoke cocaine and 20 non-cocaine-using cigarette smokers completed a visual probe task with eye-tracking technology. During this task, the magnitude of cigarette and cocaine AB was assessed through orienting bias, fixation time, and response time. Cocaine users displayed an orienting bias towards cigarette cues. Cocaine users also endorsed a more urgent desire to smoke to relieve negative affect associated with cigarette craving than non-cocaine users (g = 0.6). Neither group displayed a cigarette AB, as measured by fixation time. Cocaine users, but not non-cocaine users, displayed a cocaine AB as measured by orienting bias (g = 2.0) and fixation time (g = 1.2). There were no significant effects for response time data. Cocaine-smoking cigarettes smokers display an initial orienting bias toward cigarette cues, but not sustained cigarette AB. The incentive motivation underlying cigarette smoking also differs. Cocaine smokers report more urgent desire to smoke to relieve negative affect. Identifying differences in motivation to smoke cigarettes may provide new treatment targets for cigarette and cocaine use disorders. These results suggest that cocaine-smoking cigarette smokers display an initial orienting bias towards cigarette cues, but not sustained attention towards cigarette cues, relative to non-cocaine-using smokers. Smoked cocaine users also report a more urgent desire to smoke to relieve negative affect

Resistance exercise decreases heroin self-administration and alters gene expression in the nucleus accumbens of heroin-exposed rats.

PubMed

Smith, Mark A; Fronk, Gaylen E; Abel, Jean M; Lacy, Ryan T; Bills, Sarah E; Lynch, Wendy J

2018-04-01

Preclinical studies consistently report that aerobic exercise decreases drug self-administration and other forms of drug-seeking behavior; however, relatively few studies have examined other types of physical activity. The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration and mRNA expression of genes known to mediate opioid reinforcement and addictive behavior in the nucleus accumbens (NAc) of heroin-exposed rats. Female rats were obtained during late adolescence and divided into two groups. Resistance exercise rats were trained to climb a vertical ladder wearing a weighted vest; sedentary control rats were placed repeatedly on the ladder oriented horizontally on its side. All rats were implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. mRNA expression in the NAc core and shell was examined following behavioral testing. Resistance exercise significantly decreased heroin self-administration, resulting in a downward shift in the dose-effect curve. Resistance exercise also reduced mRNA expression for mu opioid receptors and dopamine D1, D2, and D3 receptors in the NAc core. Resistance exercise increased mRNA expression of dopamine D5 receptors in the NAc shell and increased mRNA expression of brain-derived neurotrophic factor (exons I, IIB, IIC, IV, VI, IX) in the NAc core. These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and produces changes in opioid and dopamine systems in the NAc of heroin-exposed rats.

Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

PubMed Central

Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

2015-01-01

Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin’s attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin’s effect on cocaine seeking may be mediated by different mechanisms in male and females. PMID:26523890

A Primer on Heroin and Fentanyl.

PubMed

Worley, Julie

2017-06-01

Heroin and fentanyl use have reached epidemic proportions in the United States and are now blamed for the majority of drug-related overdose deaths. Both drugs are produced primarily in South America and Asia and enter the United States illegally. One result of smoking or injecting heroin or fentanyl is the development of a substance use disorder (SUD), which causes changes in brain chemistry and function. These changes result in negative behaviors and an inability to stop use. Yet, treatments are available and recovery is possible. Nurses have the potential to impact the heroin and fentanyl epidemic through developing therapeutic relationships with patients who are at risk or already have a SUD. Strategies for effective communication include maintaining a supportive, nonjudgmental attitude and incorporating motivational interviewing. All patients should be screened for opioid use and referred for treatment if indicated. It is important for nurses to be knowledgeable about heroin and fentanyl and available treatments. [Journal of Psychosocial Nursing and Mental Health Services, 55(6), 16-20.]. Copyright 2017, SLACK Incorporated.

The price elasticity of demand for heroin: Matched longitudinal and experimental evidence.

PubMed

Olmstead, Todd A; Alessi, Sheila M; Kline, Brendan; Pacula, Rosalie Liccardo; Petry, Nancy M

2015-05-01

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. Copyright © 2015 Elsevier B.V. All rights reserved.

The price elasticity of demand for heroin: matched longitudinal and experimental evidence#

PubMed Central

Olmstead, Todd A.; Alessi, Sheila M.; Kline, Brendan; Pacula, Rosalie Liccardo; Petry, Nancy M.

2015-01-01

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

The cocaine cutting agent levamisole is frequently detected in cocaine users.

PubMed

Pope, Jeffrey D; Drummer, Olaf H; Schneider, Hans G

2018-06-21

Cocaine use in Australia is increasing, with approximately 2.5% of the surveyed population having used cocaine. In the USA, levamisole, a widely used anti-helminthic veterinary drug has been increasingly detected as a cutting agent in cocaine seizures. Levamisole is known to cause agranulocytosis in humans. We ascertained the prevalence of levamisole-adulterated cocaine, detectable in the urine from patients that had undergone a pathology request for a urine drug screen. We assayed routinely requested urines that were positive for cocaine on immunoassay with liquid chromatography high resolution quadrupole time of flight mass spectrometry (LC-QToF). We investigated available urine samples from a period of 2 years that had a positive result for cocaine. In addition, we examined samples that were below the cut-off for cocaine on immunoassay. Specimens were analysed for the presence of levamisole and other 'unknown' drugs. In the period under investigation the laboratory examined 3665 urine samples for cocaine: 1.4% (n = 51) of the samples were positive for cocaine by immunoassay and half of these (n = 26, 51%) were further examined by LC-QToF. In addition, we examined 10 samples that were negative by immunoassay (as defined by AS/NZS 4308:2008). Levamisole was detected in the urine of cocaine users in approximately 75% of cases. Other illicit drugs were also frequently found in this cohort. The most common illicit drugs detected were methamphetamine, ecstasy and cannabis. Australian cocaine is widely adulterated with levamisole. Cocaine users are at risk of levamisole related health problems in addition to the problems related to cocaine. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

The NK1 Receptor Antagonist L822429 Reduces Heroin Reinforcement

PubMed Central

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

2013-01-01

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. PMID:23303056

Hallucinogenic Drug Research: Impact on Science and Society.

ERIC Educational Resources Information Center

Gamage, James R.; Zerkin, Edmund L., Ed.

This book, authored by experienced researchers in the hallucinogenic drug field, is intended to fill the gap created by most previously published work, which tends to be either highly technical or emotional and partisan. The authors range from ardent proponents to skeptics, but they share a commitment to scientific evidence and the clear…

Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus

PubMed Central

Koob, George; Hicks, Martin J.; Wee, Sunmee; Rosenberg, Jonathan B.; De, Bishnu P.; Kaminksy, Stephen M.; Moreno, Amira; Janda, Kim D.; Crystal, Ronald G.

2012-01-01

The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. Based on these concepts, we developed dAd5GNE, a disrupted E1−E3− serotype 5 Ad with GNE, a stable cocaine analog, covalently linked to the Ad capsid proteins. In pre-clinical studies, dAd5GNE evoked persistent, high titer, high affinity IgG anti-cocaine antibodies, and was highly effective in blocking cocaine-induced hyperactivity and cocaine self-administration behavior in rats. Future studies will be designed to expand the efficacy studies, carry out relevant toxicology studies, and test dAd5GNE in human cocaine addicts. PMID:22229312

Electroencephalographic activity and mood in cocaine-dependent outpatients: effects of cocaine cue exposure.

PubMed

Bauer, L O; Kranzler, H R

1994-08-01

Electroencephalographic (EEG) and subjective reactions to cocaine cues were evaluated in 18 cocaine-dependent outpatients, after 14 or fewer days of abstinence, and 16 noncocaine-dependent controls. EEG activity and desire for cocaine were recorded while subjects viewed three 5-min films that featured either cocaine-associated, erotic, or neutral stimuli. Other measures of mood state and cocaine craving, derived from the Mood Adjective Checklist and the Cocaine Craving Questionnaire, respectively, were recorded immediately after each film. Analyses of absolute EEG power within six frequency bands (delta, theta, slow and fast alpha, slow and fast beta) revealed no EEG abnormalities in the cocaine-dependent group under any condition. In both subject groups, the cocaine-associated and erotic films produced a similar reduction in total EEG power. The cocaine-associated and erotic films also produced a similar increase in the self-rated desire for cocaine, but this change only occurred in the cocaine-dependent group.

Children's Heroes and Heroines: Developing Values Manifested through Artwork.

ERIC Educational Resources Information Center

McCrary, Judy H.

This study assessed the personal values of a group of 17 kindergarten-age children. Children participated in a classroom discussion of heroes and heroines, then drew a picture of their heroes or heroines. The researcher analyzed each child's artwork and determined the outstanding values represented by the hero or heroine. A parallel was drawn…

The heroin addict! A personal view.

PubMed

Cyngler, Charles

2002-04-01

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.

Hapten optimization for cocaine vaccine with improved cocaine recognition.

PubMed

Ramakrishnan, Muthu; Kinsey, Berma M; Singh, Rana A; Kosten, Thomas R; Orson, Frank M

2014-09-01

In the absence of any effective pharmacotherapy for cocaine addiction, immunotherapy is being actively pursued as a therapeutic intervention. While several different cocaine haptens have been explored to develop anticocaine antibodies, none of the hapten was successfully designed, which had a protonated tropane nitrogen as is found in native cocaine under physiological conditions, including the succinyl norcocaine (SNC) hapten that has been tested in phase II clinical trials. Herein, we discuss three different cocaine haptens: hexyl norcocaine (HNC), bromoacetamido butyl norcocaine (BNC), and succinyl butyl norcocaine (SBNC), each with a tertiary nitrogen structure mimicking that of native cocaine which could optimize the specificity of anticocaine antibodies for better cocaine recognition. Mice immunized with these haptens conjugated to immunogenic proteins produced high titre anticocaine antibodies. However, during chemical conjugation of HNC and BNC haptens to carrier proteins, the 2β methyl ester group is hydrolyzed, and immunizing mice with these conjugate vaccines in mice produced antibodies that bound both cocaine and the inactive benzoylecgonine metabolite. While in the case of the SBNC conjugate, vaccine hydrolysis of the methyl ester did not appear to occur, leading to antibodies with high specificity to cocaine over BE. Although we observed similar specificity with a SNC hapten, the striking difference is that SBNC carries a positive charge on the tropane nitrogen atom, and therefore, it is expected to have better binding of cocaine. The 50% cocaine inhibitory concentration (IC50 ) value for SBNC antibodies (2.8 μm) was significantly better than the SNC antibodies (9.4 μm) when respective hapten-BSA was used as a substrate. In addition, antibodies from both sera had no inhibitory effect from BE. In contrast to BNC and HNC, the SBNC conjugate was also found to be highly stable without any noticeable hydrolysis for several months at 4 °C and 2-3�

Cold Preparation of Heroin in a Black Tar Market.

PubMed

Roth, Alexis M; Armenta, Richard F; Wagner, Karla D; Strathdee, Steffanie A; Goldshear, Jesse L; Cuevas-Mota, Jazmine; Garfein, Richard S

2017-07-29

Black tar heroin is typically prepared for injection with heat which decreases the risk of HIV transmission by inactivating the virus. We received reports that persons who inject drugs (PWID) in Tijuana, Baja California, Mexico, a black tar heroin market, were using only water to dissolve heroin. Because Tijuana abuts San Diego County, CA, United States, we undertook the present analyses to determine the prevalence of this practice among PWID in San Diego, California. PWID completed quarterly behavioral assessments and serological testing for blood-borne viruses. Bivariate and multivariable logistic regression models were constructed to assess for individual, social, and structural correlates of preparing heroin without heat within the preceding 6 months. Nearly half of black tar heroin users (149/305) reported they had prepared heroin without heat within 6 months. In multivariable analysis, cold preparation was independently associated with younger age (10 year decrease; AOR = 1.25; 95% CI 1.03, 1.53), more drug injecting acquaintances (per 5 acquaintance increase; AOR = 1.05; 95% CI 1.01, 1.09) and prefilled syringe use (injecting drugs from syringes that are already filled with drugs before purchase; AOR = 1.86; 95% CI 1.14, 3.02). Conclusions/Importance: To our knowledge, this is the first paper to report that PWID living in a black tar heroin market are preparing heroin without heat. Additional research is needed to determine whether this is an endemic practice or PWID are engaging in new forms of drug preparation in response to changes in the environment.

Oral Fluid Cocaine and Benzoylecgonine Concentrations Following Controlled Intravenous Cocaine Administration

PubMed Central

Ellefsen, Kayla N.; Concheiro, Marta; Pirard, Sandrine; Gorelick, David A.; Huestis, Marilyn A.

2016-01-01

Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze® (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25 mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE median observed Cmax (range) was 932 (394–1,574) μg/L for cocaine and 248 (96.9–953) μg/L for BE. SS median (range) observed cocaine and BE Cmax trended lower at 732 (83.3–1,892) μg/L and 360 (77.2–836) μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5 h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs. PMID:26851651

Metabotropic Glutamate 7 (mGlu7) Receptor: A Target for Medication Development for the Treatment of Cocaine Dependence

PubMed Central

Li, Xia; Xi, Zheng-Xiong; Markou, Athina

2013-01-01

Brain glutamate has been shown to play an important role in reinstatement to drug seeking, a behavior considered to be of relevance to relapse to drug taking in humans. Therefore, glutamate receptors, in particular metabotropic glutamate (mGlu) receptors, have become important targets for medication development for the treatment of drug dependence. In this review article, we focus on the mGlu7 receptor subtype, and discuss recent findings with AMN082, a selective mGlu7 receptor allosteric agonist, in animal models with relevance to drug dependence. Systemic or local administration of AMN082 into the nucleus accumbens (NAc), a critical brain region involved in reward and drug dependence processes, inhibited the reinforcing and motivational effects of cocaine, heroin and ethanol, as assessed by the intravenous drug self-administration procedure. In addition, AMN082 inhibited the reward-enhancing effects induced by cocaine, as assessed in the intracranial self-stimulation procedure, and cocaine- or cue-induced reinstatement of drug-seeking behavior. In vivo microdialysis studies indicated that systemic or intra-NAc administration of AMN082 significantly decreased extracellular γ-aminobutyric acid (GABA) and elevated extracellular glutamate, but had no effect on extracellular dopamine in the NAc, suggesting that a non-dopaminergic mechanism underlies the effects of AMN082 on the actions of cocaine. Further, data indicated that AMN082-induced changes in glutamate were the net effect of two actions: one is the direct inhibition of glutamate release by activation of mGlu7 receptors on glutamatergic neurons; another is the indirect increases of glutamate release mediated by decreases in GABA transmission. These increases in extracellular glutamate functionally antagonized cocaine-induced inhibition of NAc-ventral pallidum GABAergic neurotransmission, and therefore, the rewarding effects of cocaine. In addition, elevated extracellular glutamate activated presynaptic mGlu2

Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

PubMed Central

Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A.; Riecher-Rössler, Anita; Lang, Undine E.; Borgwardt, Stefan

2015-01-01

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

Monitoring cocaine use and abstinence among cocaine users for contingency management interventions.

PubMed

Holtyn, August F; Knealing, Todd W; Jarvis, Brantley P; Subramaniam, Shrinidhi; Silverman, Kenneth

2017-06-01

During contingency management interventions, reinforcement of cocaine abstinence is arranged by delivering an incentive when a urine sample tests cocaine-negative. The use of qualitative versus quantitative urinalysis testing may have important implications for effects on cocaine abstinence. Qualitative testing (i.e., testing that solely identifies whether a particular substance is present or absent) may not detect short-term cocaine abstinence because a single instance of cocaine use can result in cocaine-positive urine over many days. Quantitative testing (i.e., testing that identifies how much of a substance is present) may be more sensitive to short-term cocaine abstinence; however, the selection of a criterion for distinguishing new use versus carryover from previous use is an important consideration. The present study examined benzoylecgonine concentrations, the primary metabolite of cocaine, in urine samples collected three times per week for 30 weeks from 28 cocaine users who were exposed to a cocaine abstinence contingency. Of the positive urine samples (benzoylecgonine concentration >300 ng/ml), 29%, 21%, 14%, and 5% of the samples decreased in benzoylecgonine concentration by more than 20%, 40%, 60%, and 80% per day, respectively. As the size of the decrease increased, the likelihood of that sample occurring during a period leading to a cocaine-negative urine sample (benzoylecgonine concentration ≤300 ng/ml) also increased. The number of days required to produce a cocaine-negative sample following a positive sample ranged from 1 to 10 days and was significantly correlated with the starting benzoylecgonine level ( r = 0.43, p < 0.001). The present analyses may aid in the development of procedures that allow for the precise reinforcement of recent cocaine abstinence during contingency management interventions.

Hopelessness in Alcohol- and Heroin-Dependent Women.

ERIC Educational Resources Information Center

Beck, Aaron T.; And Others

1984-01-01

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)

Hallucinogen use and intimate partner violence: Prospective evidence consistent with protective effects among men with histories of problematic substance use.

PubMed

Walsh, Zach; Hendricks, Peter S; Smith, Stephanie; Kosson, David S; Thiessen, Michelle S; Lucas, Philippe; Swogger, Marc T

2016-07-01

Evidence suggests that hallucinogens may have therapeutic potential for addressing a variety of problem behaviors related to the externalizing spectrum of psychopathology, such as substance misuse and criminality. Intimate partner violence (IPV) is a prevalent form of criminal violence that is related to externalizing pathology. However, the association between hallucinogen use and IPV has not been comprehensively examined. In this prospective study, we examined the association between IPV and naturalistic hallucinogen use among 302 inmates at a US county jail. Cox regression analyses indicated that hallucinogen use predicted reduced arrest for IPV independently (β=-0.54, SE=0.20, χ(2)=7.19, exp(B)=0.58, p<0.01) and after accounting for covariates (β=-0.48, SE=0.23, χ(2)=4.44, exp(B)=0.62, p<0.05). These results add to a growing literature suggesting distinct therapeutic potential for hallucinogens to assist in the attenuation of problematic behavior. © The Author(s) 2016.

Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice.

PubMed

Moreno, José L; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C; González-Maeso, Javier

2013-03-01

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice

PubMed Central

Moreno, José L.; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C.; González-Maeso, Javier

2013-01-01

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT2A receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24 mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5 mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [3H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT2A agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT2A receptor-dependent hallucinogenic effects of LSD. PMID:23333599

Cocaine-specific Antibodies Blunt the Subjective Effects of Smoked Cocaine in Humans

PubMed Central

Haney, Margaret; Gunderson, Erik W.; Jiang, Huiping; Collins, Eric D.; Foltin, Richard W.

2012-01-01

Background Rates of relapse among cocaine-dependent patients are high, and new treatment approaches are needed. Clinical data demonstrate that a cocaine vaccine (TA-CD: Celtic Pharmaceutical) produces selective anti-cocaine antibodies, yet the impact of these antibodies on cocaine’s direct effects is unknown. The objective of this human laboratory study was to measure the relationship between antibody titers and the effects of smoked cocaine on ratings of intoxication, craving and cardiovascular effects. Methods Ten cocaine-dependent men not seeking drug treatment spent 2 nights per week for 13 weeks inpatient where the effects of cocaine (0, 25, 50 mg) were determined prior to vaccination and at weekly intervals thereafter. Two doses of TA-CD (82 µg, n=4; 360 µg, n=6) were administered at weeks 1, 3, 5 and 9. Results Peak plasma antibody levels, which were highly variable, significantly predicted cocaine’s effects. Those individuals in the upper half of antibody production had an immediate (within 4 minutes of cocaine smoking) and robust (55–81%) reduction in ratings of Good Drug Effect and Cocaine Quality, while those in the lower half showed only a nonsignificant attenuation (6–26%). Self-reported cocaine use while participants were outpatient tended to decrease as a function of antibody titer (p < 0.12). By contrast, higher antibody levels predicted significantly greater cocaine-induced tachycardia. Conclusions The TA-CD vaccine substantially decreased smoked cocaine’s intoxicating effects in those generating sufficient antibody. These data support further testing of cocaine immunotherapy as a treatment for cocaine dependence. PMID:19846066

Metabolomic profiling of brain tissues of mice chronically exposed to heroin.

PubMed

Li, Ren-Shi; Takeda, Tomoki; Ohshima, Takashi; Yamada, Hideyuki; Ishii, Yuji

2017-02-01

The chronic neurotoxicity of heroin on the nervous system is poorly understood. To address this issue, we comprehensively assessed the alteration of brain metabolomics caused by chronic heroin exposure and the withdrawal of heroin. Male C57BL/6J mice (n = 10) were given heroin (15 μmol/kg, i.p., twice a day) for 12 days while the withdrawal group received saline-treatment instead of heroin for the last two days. The control group received saline. We developed an UPLC-TOF/MS-based metabolomic approach to analyze the metabolites and carry out a metabolic pathway analysis in the brain. The major metabolites contributing to the discrimination were identified as amino acids, tricarboxylic-acid cycle intermediates, neurotransmitters, nucleotides and other compounds. A marked reduction in histidine and a slight but significant increase in phenylalanine and tryptophan were observed after heroin was withdrawn while the increased level of catecholamines was restored to baseline. Interestingly, N-acetylserotonin - a precursor of melatonin - was increased with the withdrawal of heroin while melatonin was markedly reduced along with the sub-chronic exposure to heroin. This shows that heroin disrupts not only the energy metabolism but also the biosynthesis of both catecholamines and melatonin in the mouse brain. Therefore, these substances are candidate biomarkers for chronic heroin-abuse. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo.

PubMed

Tallarida, Christopher S; Egan, Erin; Alejo, Gissel D; Raffa, Robert; Tallarida, Ronald J; Rawls, Scott M

2014-04-01

Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effects of heroin administration and drug cues on impulsivity.

PubMed

Jones, Jermaine D; Vadhan, Nehal P; Luba, Rachel R; Comer, Sandra D

2016-08-01

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.

Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey.

PubMed

Schindler, Emmanuelle A D; Gottschalk, Christopher H; Weil, Marsha J; Shapiro, Robert E; Wright, Douglas A; Sewell, Richard Andrew

2015-01-01

Cluster headache is one of the most debilitating pain syndromes. A significant number of patients are refractory to conventional therapies. The Clusterbusters.org medication use survey sought to characterize the effects of both conventional and alternative medications used in cluster headache. Participants were recruited from cluster headache websites and headache clinics. The final analysis included responses from 496 participants. The survey was modeled after previously published surveys and was available online. Most responses were chosen from a list, though others were free-texted. Conventional abortive and preventative medications were identified and their efficacies agreed with those previously published. The indoleamine hallucinogens, psilocybin, lysergic acid diethylamide, and lysergic acid amide, were comparable to or more efficacious than most conventional medications. These agents were also perceived to shorten/abort a cluster period and bring chronic cluster headache into remission more so than conventional medications. Furthermore, infrequent and non-hallucinogenic doses were reported to be efficacious. Findings provide additional evidence that several indoleamine hallucinogens are rated as effective in treating cluster headache. These data reinforce the need for further investigation of the effects of these and related compounds in cluster headache under experimentally controlled settings.

A regulatory perspective on the evaluation of hallucinogen drugs for human use.

PubMed

Calderon, Silvia N; Hunt, Joshua; Klein, Michael

2017-11-24

In recent years, there is renewed interest in the study of various hallucinogens for their potential therapeutic effects. In the United States of America (USA), the abuse potential assessment of a drug is carried out as part of the general safety and efficacy evaluation of a drug. Additionally, the abuse potential assessment is taken under consideration in determining if a drug needs to be subject to controls to minimize the abuse of the drug once on the market. This assessment is conducted for all new drugs with central nervous system (CNS) activity, that are chemically or pharmacologically similar to other drugs with known abuse potential, or drugs that produce psychoactive effects predictive of abuse, such as euphoria and hallucinations. This paper describes the regulatory framework for evaluating the abuse potential of new drugs, with emphasis on hallucinogens. The paper discusses the role of the United States Food and Drug Administration (FDA) in the evaluation of the abuse potential of drugs and its role in drug control, and provides an overview of the controlled status of hallucinogens and the requirements to conduct research with Schedule I substances in the USA. Published by Elsevier Ltd.

The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.

PubMed

Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L

2005-09-01

We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.

Quinine-induced thrombocytopenia following intravenous use of heroin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christie, D.J.; Walker, R.H.; Kolins, M.D.

1983-06-01

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 themore » first to confirm that quinine used as an adulterant can induce immunologic thrombocytopenia following an injection of heroin.« less

Cocaine (Coke, Crack) Facts

MedlinePlus

... That People Abuse » Cocaine (Coke, Crack) Facts Cocaine (Coke, Crack) Facts Listen Cocaine is a white ... 69 KB) "My life was built around getting cocaine and getting high." ©istock.com/ Marjot Stacey is ...

Crack Cocaine Injection Practices and HIV Risk: Findings From New York and Bridgeport

PubMed Central

Lankenau, Stephen E.; Clatts, Michael C.; Goldsamt, Lloyd A.; Welle, Dorinda L.

2007-01-01

This article examines the behavioral practices and health risks associated with preparing crack cocaine for injection. Using an ethno-epidemiological approach, injection drug users (n=38) were recruited between 1999 and 2000 from public settings in New York City and Bridgeport, Connecticut and responded to a semistructured interview focusing on crack injection initiation and their most recent crack injection. Study findings indicate that methods of preparing crack for injection were impacted by a transforming agent, heat applied to the “cooker,” heroin use, age of the injector, and geographic location of the injector. The findings suggest that crack injectors use a variety of methods to prepare crack, which may carry different risks for the transmission of bloodborne pathogens. In particular, crack injection may be an important factor in the current HIV epidemic. PMID:18079990

The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration, reinstatement of cocaine-seeking and cocaine induced locomotor activity.

PubMed

Harvey-Lewis, Colin; Li, Zhaoxia; Higgins, Guy A; Fletcher, Paul J

2016-02-01

Lorcaserin (Lorqess, Belviq(®)) is a selective 5-HT(2C) receptor agonist that has received FDA approval for the treatment of obesity. 5-HT(2C) receptor agonists are also efficacious in decreasing multiple aspects of cocaine motivation and reward in preclinical models. This would suggest that lorcaserin is a clinically available therapeutic with the potential to treat cocaine addiction. Here we report the effects of lorcaserin (0.1 mg/kg-1.0 mg/kg) on multiple aspects of cocaine-related behaviours in rats. We find that lorcaserin dose-dependently decreases cocaine self-administration on progressive and fixed ratio schedules of reinforcement. Lorcaserin also reduces reinstatement of cocaine-seeking behaviour in response to priming injections of cocaine and/or reintroduction of cocaine-associated cues. Finally, lorcaserin dose-dependently decreases cocaine-induced hyperlocomotion. Our results, when considered in concert with similar emergent findings in non-human primates, strongly support continued research into the potential of lorcaserin as a clinical treatment for cocaine addiction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Choosing Under the Influence: A Drug-Specific Mechanism by Which the Setting Controls Drug Choices in Rats

PubMed Central

Vandaele, Youna; Cantin, Lauriane; Serre, Fuschia; Vouillac-Mendoza, Caroline; Ahmed, Serge H

2016-01-01

Ample evidence shows that the setting can control drug choices in both humans and animals. Here we reveal in rats that a major mechanism of this control involves a regulation of the drug influence on other competing options at the time of choice. Briefly, rats were offered a choice between a drug dose (cocaine or heroin) and a brief access to water sweetened with saccharin in two different settings. In one setting, choosing under the influence was not possible and rats largely preferred saccharin over either cocaine or heroin. In contrast, when the same rats were shifted to a setting where choosing under the influence was possible, they chose the drug either nonexclusively or exclusively depending on whether the drug enhanced or suppressed sweet reward, respectively. Thus, when rats were under the orexigenic influence of heroin at the time of choice, they more frequently chose saccharin in alternation with heroin. In contrast, when rats were under the anorexic influence of cocaine, they stopped choosing saccharin and continued taking cocaine exclusively. These setting- and drug-specific changes in preference were rapid and reversible, and could be induced by passively administering cocaine or heroin before choice. Finally, rats behaved as if they were oblivious to the drug influence on their choices. This behavior could explain why rats are vulnerable to harm themselves, sometimes to the point of death, in settings where choices are made under the drug influence, notably if this influence excludes other important options or, conversely, enhances harmful ones. PMID:26129679

Choosing Under the Influence: A Drug-Specific Mechanism by Which the Setting Controls Drug Choices in Rats.

PubMed

Vandaele, Youna; Cantin, Lauriane; Serre, Fuschia; Vouillac-Mendoza, Caroline; Ahmed, Serge H

2016-01-01

Ample evidence shows that the setting can control drug choices in both humans and animals. Here we reveal in rats that a major mechanism of this control involves a regulation of the drug influence on other competing options at the time of choice. Briefly, rats were offered a choice between a drug dose (cocaine or heroin) and a brief access to water sweetened with saccharin in two different settings. In one setting, choosing under the influence was not possible and rats largely preferred saccharin over either cocaine or heroin. In contrast, when the same rats were shifted to a setting where choosing under the influence was possible, they chose the drug either nonexclusively or exclusively depending on whether the drug enhanced or suppressed sweet reward, respectively. Thus, when rats were under the orexigenic influence of heroin at the time of choice, they more frequently chose saccharin in alternation with heroin. In contrast, when rats were under the anorexic influence of cocaine, they stopped choosing saccharin and continued taking cocaine exclusively. These setting- and drug-specific changes in preference were rapid and reversible, and could be induced by passively administering cocaine or heroin before choice. Finally, rats behaved as if they were oblivious to the drug influence on their choices. This behavior could explain why rats are vulnerable to harm themselves, sometimes to the point of death, in settings where choices are made under the drug influence, notably if this influence excludes other important options or, conversely, enhances harmful ones.

Heroin and Methamphetamine Injection: An Emerging Drug Use Pattern.

PubMed

Al-Tayyib, Alia; Koester, Stephen; Langegger, Sig; Raville, Lisa

2017-07-03

We sought to describe an emerging drug use pattern characterized by injection of both methamphetamine and heroin. We examined differences in drug injection patterns by demographics, injection behaviors, HIV and HCV status, and overdose. Persons who inject drugs (PWID) were recruited as part of the National HIV Behavioral Surveillance (NHBS) system in Denver, Colorado. We used chi-square statistics to assess differences between those who reported only heroin injection, only methamphetamine injection, and combined heroin and methamphetamine injection. We used generalized linear models to estimate unadjusted and adjusted prevalence ratios to describe the association between drug injection pattern and reported nonfatal overdose in 2015. We also examined changes in the drug reported as most frequently injected across previous NHBS cycles from 2005, 2009, and 2012. Of 592 participants who completed the survey in 2015, 173 (29.2%) reported only injecting heroin, 123 (20.8%) reported only injecting methamphetamine, and 296 (50.0%) reported injecting both drugs during the past 12 months. Injecting both heroin and methamphetamine was associated with a 2.8 (95% confidence interval: 1.7, 4.5) fold increase in reported overdose in the past 12 months compared with only injecting heroin. The proportion of those reporting methamphetamine as the most frequently injected drug increased from 2.1% in 2005 to 29.6% in 2015 (p < 0.001). The rapid increase in methamphetamine injection, and the emergence of combining methamphetamine with heroin, may have serious public health implications.

Reward and Toxicity of Cocaine Metabolites Generated by Cocaine Hydrolase.

PubMed

Murthy, Vishakantha; Geng, Liyi; Gao, Yang; Zhang, Bin; Miller, Jordan D; Reyes, Santiago; Brimijoin, Stephen

2015-08-01

Butyrylcholinesterase (BChE) gene therapy is emerging as a promising concept for treatment of cocaine addiction. BChE levels after gene transfer can rise 1000-fold above those in untreated mice, making this enzyme the second most abundant plasma protein. For months or years, gene transfer of a BChE mutated into a cocaine hydrolase (CocH) can maintain enzyme levels that destroy cocaine within seconds after appearance in the blood stream, allowing little to reach the brain. Rapid enzyme action causes a sharp rise in plasma levels of two cocaine metabolites, benzoic acid (BA) and ecgonine methyl ester (EME), a smooth muscle relaxant that is mildly hypotensive and, at best, only weakly rewarding. The present study, utilizing Balb/c mice, tested reward effects and cardiovascular effects of administering EME and BA together at molar levels equivalent to those generated by a given dose of cocaine. Reward was evaluated by conditioned place preference. In this paradigm, cocaine (20 mg/kg) induced a robust positive response but the equivalent combined dose of EME + BA failed to induce either place preference or aversion. Likewise, mice that had undergone gene transfer with mouse CocH (mCocH) showed no place preference or aversion after repeated treatments with a near-lethal 80 mg/kg cocaine dose. Furthermore, a single administration of that same high cocaine dose failed to affect blood pressure as measured using the noninvasive tail-cuff method. These observations confirm that the drug metabolites generated after CocH gene transfer therapy are safe even after a dose of cocaine that would ordinarily be lethal.

Examining the Rise in Mexican Drug Cartel Related Violence

DTIC Science & Technology

2016-06-10

funneling money and weapons south to be used by the cartels.5 3 Mexican DTOs supply American consumers with marijuana , methamphetamines and heroin...Tijuana and Juarez. The Sinaloa Cartel is highly diversified and able to smuggle the drugs heroine, marijuana , cocaine, and methamphetamines via all...counter the corruption throughout government, the Mexican Congress passed a law in August 2009 decriminalizing small amounts of cocaine, marijuana and

Heroin and pharmaceutical opioid overdose events: Emergency medical response characteristics.

PubMed

Banta-Green, Caleb J; Coffin, Phillip O; Schoeppe, Jennie A; Merrill, Joseph O; Whiteside, Lauren K; Ebersol, Abigail K

2017-09-01

Emergency Medical Services (EMS) data may provide insight into opioid overdose incidence, clinical characteristics, and medical response. This analysis describes patient characteristics, clinical features, and EMS response to opioid overdoses, comparing heroin and pharmaceutical opioid (PO) overdoses, using a structured opioid overdose case criteria definition. A case series study was conducted. EMS medical staff screened cases for possible overdoses and study staff categorized the likelihood of opioid overdose. Medical form data were abstracted. Patient characteristics, clinical presentation, and medical response to heroin and PO-involved overdoses were compared with bi-variate test statistics. We identified 229 definite or probable opioid overdose cases over six months: heroin in 98 (43%) cases (10 also involved PO), PO without heroin in 85 (37%) cases, and 46 (20%) that could not be categorized and were excluded from analyses. Heroin overdose patients were younger than PO (median age 33 v 41 (p<0.05)), more often male (80% v 61% (p=<0.01)), intubated less (8% v 22%, p<0.01) and more likely to be administered naloxone (72% v 51%, p<0.01). No significant differences were found between heroin and PO overdoses for initial respiratory rate, Glasgow Coma Scale score, or co-ingestants, but heroin users were more likely to have miotic pupils (p<0.01). While heroin and PO events presented similarly, heroin-involved cases were more likely to receive naloxone and less likely to be intubated. Standardized case definitions and data documentation could aid opioid overdose surveillance as well as provide data for measuring the impact of professional and lay interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

Essential/precursor chemicals and drug consumption: impacts of US sodium permanganate and Mexico pseudoephedrine controls on the numbers of US cocaine and methamphetamine users.

PubMed

Cunningham, James K; Liu, Lon-Mu; Callaghan, Russell C

2016-11-01

In December 2006 the United States regulated sodium permanganate, a cocaine essential chemical. In March 2007 Mexico, the United States' primary source for methamphetamine, closed a chemical company accused of illicitly importing 60+ tons of pseudoephedrine, a methamphetamine precursor chemical. US cocaine availability and methamphetamine availability, respectively, decreased in association. This study tested whether the controls had impacts upon the numbers of US cocaine users and methamphetamine users. Auto-regressive integrated moving average (ARIMA) intervention time-series analysis. Comparison series-heroin and marijuana users-were used. United States, 2002-14. The National Survey on Drug Use and Health (n = 723 283), a complex sample survey of the US civilian, non-institutionalized population. Estimates of the numbers of (1) past-year users and (2) past-month users were constructed for each calendar quarter from 2002 to 2014, providing each series with 52 time-periods. Downward shifts in cocaine users started at the time of the cocaine regulation. Past-year and past-month cocaine users series levels decreased by approximately 1 946 271 (-32%) (P < 0.05) and 694 770 (-29%) (P < 0.01), respectively-no apparent recovery occurred through 2014. Downward shifts in methamphetamine users started at the time of the chemical company closure. Past-year and past-month methamphetamine series levels decreased by 494 440 (-35%) [P < 0.01; 95% confidence interval (CI) = -771 897, -216 982] and 277 380 (-45%) (P < 0.05; CI = -554 073, -686), respectively-partial recovery possibly occurred in 2013. The comparison series changed little at the intervention times. Essential/precursor chemical controls in the United States (2006) and Mexico (2007) were associated with large, extended (7+ years) reductions in cocaine users and methamphetamine users in the United States. © 2016 Society for the Study of Addiction.

(-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine self-administration in rats.

PubMed

Manuszak, M; Harding, W; Gadhiya, S; Ranaldi, R

2018-05-31

Dopamine receptors are implicated in cocaine reward and seeking. We hypothesize that (-)-stepholidine, a dopamine D1/D2/D3 multi-receptor agent, would be effective in reducing cocaine reward and seeking in an animal model. We investigated the effects of (-)-stepholidine in cue-induced reinstatement of cocaine seeking and cocaine self-administration (reward). Cue-induced reinstatement experiment: Rats were trained to press a lever reinforced by cocaine (1 mg/kg/injection) for 15 consecutive daily sessions, after which the response was extinguished by withholding cocaine and cocaine-paired cues (light and pump activation). This was followed by a cue-induced reinstatement test where subjects were exposed to two cocaine cue presentations and presses on the active lever produced cues. Subjects were treated with one of four (-)-stepholidine doses prior to the reinstatement test. Cocaine self-administration (reward) experiment: Rats were trained to self-administer cocaine under a progressive ratio schedule of reinforcement. After stable breakpoints were established, rats were injected with four doses of (-)-stepholidine prior to testing; each dose was injected prior to a separate test session with no-treatment sessions intervening to re-establish break points. (-)-Stepholidine significantly reduced cue-induced reinstatement of cocaine seeking in a dose-related manner. Additionally, (-)-stepholidine significantly reduced break points for cocaine reward. (-)-Stepholidine did not significantly affect locomotor activity. (-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine reward, suggesting that it may be useful in treating relapse in cocaine addiction. Copyright © 2018 Elsevier B.V. All rights reserved.

Anhydroecgonine methyl ester, a cocaine pyrolysis product, may contribute to cocaine behavioral sensitization.

PubMed

Garcia, Raphael Caio Tamborelli; Torres, Larissa Helena; Balestrin, Natália Trigo; Andrioli, Tatiana Costa; Flório, Jorge Camilo; de Oliveira, Carolina Dizioli Rodrigues; da Costa, José Luiz; Yonamine, Mauricio; Sandoval, Maria Regina Lopes; Camarini, Rosana; Marcourakis, Tania

2017-02-01

Crack cocaine has a high potential to induce cocaine addiction and its smoke contains cocaine's pyrolysis product anhydroecgonine methyl ester (AEME), a partial agonist at M 1 - and M 3 -muscarinic acetylcholine receptor and an antagonist at the remaining subtypes. No reports have assessed AEME's role in addiction. Adult male Wistar rats were intraperitoneally administered with saline, 3mg/kg AEME, 15mg/kg cocaine, or a cocaine-AEME combination on every other day during a period of 9 days. After a 7-days withdrawal period, a challenge injection of the respective drugs was performed on the 17th day. The locomotor activity was evaluated on days 1, 3, 5, 7, 9 and 17, as well as dopamine levels (9th day) and dopaminergic receptors proteins (D 1 R and D 2 R on the 17th day) in the caudate-putamen (CPu) and nucleus accumbens (NAc). AEME was not able to induce the expression of behavioral sensitization, but it substantially potentiates cocaine-effects, with cocaine-AEME combination presenting higher expression than cocaine alone. An increase in the dopamine levels in the CPu in all non-saline groups was observed, with the highest levels in the cocaine-AEME group. There was a decrease in D 1 R protein level in this brain region only for cocaine and cocaine-AEME groups. In the NAc, an increase in the dopamine levels was only observed for cocaine and cocaine-AEME groups, with no changes in both D 1 R and D 2 R protein levels. These behavioral and neurochemical data indicate that AEME alone does not elicit behavioral sensitization but it significantly potentiates cocaine effects when co-administered, resulting in dopamine increase in CPu and NAc, brain regions where dopamine release is mediated by cholinergic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Miss Heroin.

ERIC Educational Resources Information Center

Riley, Bernice

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…

Supervised Injectable Heroin: A Clinical Perspective.

PubMed

Bell, James; Waal, Rob van der; Strang, John

2017-07-01

Six recent randomised control trials (RCTs) have suggested that supervised injectable heroin (SIH) can be effective in patients who persist in street heroin use during methadone treatment. However, short-term randomised control trials have limitations in assessing the effectiveness of treatments for addictive disorders, which are chronic and relapsing disorders of motivation. These RCTs particularly fail to capture the process of the SIH treatment and the diversity of influence and change over time. This narrative review is based on the analysis of published data. Conclusions are drawn from a process of reflection informed by experience in delivering one of the published trials, subsequent experiences in varying the way SIH is delivered, and through consideration of possible mechanisms of action of SIH. Many long-term, socially marginalised and demoralised people who are addicted to heroin experience few rewards from the stability afforded by methadone treatment. Supervised injected heroin is sufficiently reinforcing for many of these individuals to attend daily and participate in highly structured treatment. With an adequate daily dose of supervised methadone to avoid withdrawal dysphoria, occasional diamorphine injections-not necessarily twice daily, or even every day-is enough to hold people in treatment. Participation was associated with reduced amounts of non-prescribed drug use, a gradual change in self-image and attitude, and for some subjects, a movement towards social reintegration and eventual withdrawal from SIH. Prescribed heroin is sufficiently motivating to hold a proportion of recidivist addicts in long-term treatment. Participation in structured treatment provides respite from compulsive drug use, and a proportion of subjects develop sufficient rewards from social reintegration to successfully withdraw from treatment. Such change, when it occurs, is slow and stuttering.

Prevalence of heroin markers in urine for pain management patients.

PubMed

Knight, Julie; Puet, Brandi L; DePriest, Anne; Heltsley, Rebecca; Hild, Cheryl; Black, David L; Robert, Timothy; Caplan, Yale H; Cone, Edward J

2014-10-01

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 (heroin-positive specimens. COD was present in 1218 (42.4%) specimens. Prevalence of combinations for specimens containing MOR were as follows: DAM only 13 (0.59%), 6AM only 1140 (52.0%), 6AC only 24 (1.1%), DAM/6AM/6AC 710 (32.4%), 6AM/6AC 188 (8.6%), DAM/6AM 113 (5.2%), DAM/6AC 6 (0.27%). Importantly, the prevalence of combinations for specimens without MOR were as follows: DAM only 161 (23.8%), 6AM only 217 (32.1%), 6AC only 92 (13.6%), DAM/6AM/6AC 50 (7.4%), 6AM/6AC 7 (1.0%), DAM/6AM 145 (21.4%), DAM/6AC 5 (0.74%). Unexpected patterns of excretion were observed, such as the presence of DAM and 6AC in the absence of 6AM and MOR; therefore, multiple heroin markers may be useful to assess for

A novel UCS memory retrieval-extinction procedure to inhibit relapse to drug seeking.

PubMed

Luo, Yi-xiao; Xue, Yan-xue; Liu, Jian-feng; Shi, Hai-shui; Jian, Min; Han, Ying; Zhu, Wei-li; Bao, Yan-ping; Wu, Ping; Ding, Zeng-bo; Shen, Hao-wei; Shi, Jie; Shaham, Yavin; Lu, Lin

2015-07-14

We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts.

A novel UCS memory retrieval-extinction procedure to inhibit relapse to drug seeking

PubMed Central

Luo, Yi-xiao; Xue, Yan-xue; Liu, Jian-feng; Shi, Hai-shui; Jian, Min; Han, Ying; Zhu, Wei-li; Bao, Yan-ping; Wu, Ping; Ding, Zeng-bo; Shen, Hao-wei; Shi, Jie; Shaham, Yavin; Lu, Lin

2015-01-01

We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts. PMID:26169171

Stigma towards Marijuana Users and Heroin Users.

PubMed

Brown, Seth A

2015-01-01

Despite high levels of stigmatizing attitudes and behaviors toward individuals with substance use problems, there is surprisingly limited research on understanding the contributors to such high levels. College students with no history of marijuana or heroin use (N=250) completed self-report measures to examine the level of substance use stigma towards individuals using two illicit substances (marijuana and heroin) and the contribution of three perceiver characteristics (sex, previous contact with substance users, and five beliefs about substance use) to three dimensions of stigma (social distance, negative emotions, and forcing treatment). Greater levels of internalized stigma were noted towards individuals who use heroin (versus marijuana). For marijuana use, those who had less previous contact and higher endorsement of certain beliefs (rarity, severity, and less controllability) were associated with greater stigmatizing attitudes. For heroin use, the associations were weak or non-existent. The findings strengthen the argument that substance use stigma needs to be examined and perhaps addressed substance by substance, rather than as a group. Further, contact interventions may be a particularly effective strategy for altering substance use stigma.

The cocaine-abused heart.

PubMed

Keller, Kathryn Buchanan; Lemberg, Louis

2003-11-01

Recreational use of cocaine dates back to the Incas in South America 5000 years ago. Cocaine is derived from the leaves of Erythroxylon coca, a shrub native to South America. In the late 1800s, Sigmund Freud popularized the drug in Europe. He used cocaine to treat depression, asthma, cachexia, and for overcoming morphine addiction. Also in this period cocaine rapidly gained acceptance in surgical procedures as a local anesthetic and vasoconstrictor. Cocaine reached the United States in the early 1900s, and its popularity led President Taft to declare it public enemy number one in 1910. Cocaine became popular again in the 1980s. Currently cocaine use is responsible for more ED visits then any of the other illicit drugs. Because most cocaine users are young, they are at a lower risk for coronary artery atherosclerotic disease. An estimated 25 million people between the ages of 26 and 34 years have used cocaine at least once, 20% were women and 30% men. Habitual users of cocaine are estimated to number 1.5 million. Most cocaine-induced chest pains do not progress to MI, and in fact many originate in the chest wall. The chest pains due to cocaine, however, are induced by myocardial ischemia, a result of vasospasm and not a thrombotic occlusion of a coronary artery that has a ruptured atheromatous plaque. ECG findings can be misleading in the diagnosis because the early repolarization syndrome, a normal variant, is a frequent finding in young African American men. Measurement of cardiac troponin levels is the most reliable diagnostic test. Percutaneous coronary intervention and angioplasty, rather than thrombolysis, is the treatment of choice because intense coronary vasospasm is the primary pathophysiology in cocaine-induced MI.

Birth Order and Polydrug Abuse Among Heroin Addicts

ERIC Educational Resources Information Center

Lerner, Steven E.; Linder, Ronald L.

1975-01-01

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)

Repeated Administration of a Mutant Cocaine Esterase: Effects on Plasma Cocaine Levels, Cocaine-Induced Cardiovascular Activity, and Immune Responses in Rhesus Monkeys

PubMed Central

Collins, Gregory T.; Brim, Remy L.; Noon, Kathleen R.; Narasimhan, Diwahar; Lukacs, Nicholas W.; Sunahara, Roger K.; Woods, James H.

2012-01-01

Previous studies have demonstrated the capacity of a long-acting mutant form of a naturally occurring bacterial double mutant cocaine esterase (DM CocE) to antagonize the reinforcing, discriminative, convulsant, and lethal effects of cocaine in rodents and reverse the increases in mean arterial pressure (MAP) and heart rate (HR) produced by cocaine in rhesus monkeys. This study was aimed at characterizing the immunologic responses to repeated dosing with DM CocE and determining whether the development of anti-CocE antibodies altered the capacity of DM CocE to reduce plasma cocaine levels and ameliorate the cardiovascular effects of cocaine in rhesus monkeys. Under control conditions, intravenous administration of cocaine (3 mg/kg) resulted in a rapid increase in the plasma concentration of cocaine (n = 2) and long-lasting increases in MAP and HR (n = 3). Administration of DM CocE (0.32 mg/kg i.v.) 10 min after cocaine resulted in a rapid hydrolysis of cocaine with plasma levels below detection limits within 5 to 8 min. Elevations in MAP and HR were significantly reduced within 25 and 50 min of DM CocE administration, respectively. Although slight (10-fold) increases in anti-CocE antibodies were observed after the fourth administration of DM CocE, these antibodies did not alter the capacity of DM CocE to reduce plasma cocaine levels or ameliorate cocaine's cardiovascular effects. Anti-CocE titers were transient and generally dissipated within 8 weeks. Together, these results suggest that highly efficient cocaine esterases, such as DM CocE, may provide a novel and effective therapeutic for the treatment of acute cocaine intoxication in humans. PMID:22518021

Incubation of Cue-Induced Craving in Adults Addicted to Cocaine Measured by Electroencephalography.

PubMed

Parvaz, Muhammad A; Moeller, Scott J; Goldstein, Rita Z

2016-11-01

A common trigger for relapse in drug addiction is the experience of craving via exposure to cues previously associated with drug use. Preclinical studies have consistently demonstrated incubation of cue-induced drug-seeking during the initial phase of abstinence, followed by a decline over time. In humans, the incubation effect has been shown for alcohol, nicotine, and methamphetamine addictions, but not for heroin or cocaine addiction. Understanding the trajectory of cue-induced craving during abstinence in humans is of importance for addiction medicine. To assess cue-induced craving for cocaine in humans using both subjective and objective indices of cue-elicited responses. Seventy-six individuals addicted to cocaine with varying durations of abstinence (ie, 2 days, 1 week, 1 month, 6 months, and 1 year) participated in this laboratory-based cross-sectional study from June 19, 2007, to November 26, 2012. The late positive potential component of electroencephalography, a recognized marker of incentive salience, was used to track motivated attention to drug cues across these self-selected groups. Participants also completed subjective ratings of craving for cocaine before presentation of a cue, and ratings of cocaine "liking" (hedonic feelings toward cocaine) and "wanting" (craving for cocaine) after presentation of cocaine-related pictures. Data analysis was conducted from June 5, 2015, to March 30, 2016. The late positive potential amplitudes and ratings of liking and wanting cocaine in response to cocaine-related pictures were quantified and compared across groups. Among the 76 individuals addicted to cocaine, 19 (25%) were abstinent for 2 days, 20 (26%) were abstinent for 1 week, 15 (20%) were abstinent for 1 month, 12 (16%) were abstinent for 6 months, and 10 (13%) were abstinent for 1 year. In response to drug cues, the mean (SD) late positive potential amplitudes showed a parabolic trajectory that was higher at 1 (1.26 [1.36] µV) and 6 (1.17 [1.19] µ

Quantitative Phosphoproteomics Unravels Biased Phosphorylation of Serotonin 2A Receptor at Ser280 by Hallucinogenic versus Nonhallucinogenic Agonists*

PubMed Central

Karaki, Samah; Becamel, Carine; Murat, Samy; Mannoury la Cour, Clotilde; Millan, Mark J.; Prézeau, Laurent; Bockaert, Joël; Marin, Philippe; Vandermoere, Franck

2014-01-01

The serotonin 5-HT2A receptor is a primary target of psychedelic hallucinogens such as lysergic acid diethylamine, mescaline, and psilocybin, which reproduce some of the core symptoms of schizophrenia. An incompletely resolved paradox is that only some 5-HT2A receptor agonists exhibit hallucinogenic activity, whereas structurally related agonists with comparable affinity and activity lack such a psychoactive activity. Using a strategy combining stable isotope labeling by amino acids in cell culture with enrichment in phosphorylated peptides by means of hydrophilic interaction liquid chromatography followed by immobilized metal affinity chromatography, we compared the phosphoproteome in HEK-293 cells transiently expressing the 5-HT2A receptor and exposed to either vehicle or the synthetic hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) or the nonhallucinogenic 5-HT2A agonist lisuride. Among the 5995 identified phosphorylated peptides, 16 sites were differentially phosphorylated upon exposure of cells to DOI versus lisuride. These include a serine (Ser280) located in the third intracellular loop of the 5-HT2A receptor, a region important for its desensitization. The specific phosphorylation of Ser280 by hallucinogens was further validated by quantitative mass spectrometry analysis of immunopurified receptor digests and by Western blotting using a phosphosite specific antibody. The administration of DOI, but not of lisuride, to mice, enhanced the phosphorylation of 5-HT2A receptors at Ser280 in the prefrontal cortex. Moreover, hallucinogens induced a less pronounced desensitization of receptor-operated signaling in HEK-293 cells and neurons than did nonhallucinogenic agonists. The mutation of Ser280 to aspartic acid (to mimic phosphorylation) reduced receptor desensitization by nonhallucinogenic agonists, whereas its mutation to alanine increased the ability of hallucinogens to desensitize the receptor. This study reveals a biased phosphorylation of

Dopamine D3 receptor antagonism inhibits cocaine-seeking and cocaine-enhanced brain reward in rats.

PubMed

Vorel, Stanislav R; Ashby, Charles R; Paul, Mousumi; Liu, Xinhe; Hayes, Robert; Hagan, Jim J; Middlemiss, Derek N; Stemp, Geoffrey; Gardner, Eliot L

2002-11-01

dopamine D3 receptor is preferentially localized to the mesocorticolimbic dopaminergic system and has been hypothesized to play a role in cocaine addiction. To study the involvement of the D3 receptor in brain mechanisms and behaviors commonly assumed to be involved in the addicting properties of cocaine, the potent and selective D3 receptor antagonist trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl] cyclohexyl]-4-quinolininecarboxamide (SB-277011-A) was administered to laboratory rats, and the following measures were assessed: (1) cocaine-enhanced electrical brain-stimulation reward, (2) cocaine-induced conditioned place preference, and (3) cocaine-triggered reinstatement of cocaine seeking behavior. Systemic injections of SB-277011-A were found to (1) block enhancement of electrical brain stimulation reward by cocaine, (2) dose-dependently attenuate cocaine-induced conditioned place preference, and (3) dose-dependently attenuate cocaine-triggered reinstatement of cocaine seeking behavior. Thus, D3 receptor blockade attenuates both the rewarding effects of cocaine and cocaine-induced drug-seeking behavior. These data suggest an important role for D3 receptors in mediating the addictive properties of cocaine and suggest that blockade of dopamine D3 receptors may constitute a new and useful target for prospective pharmacotherapies for cocaine addiction.

Although Relatively Few, "Doctor Shoppers" Skew Opioid Prescribing

MedlinePlus

... Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine and E- ... Fentanyl GHB Hallucinogens Heroin Illegal Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids ...

Prenatal Methamphetamine Exposure Linked with Problems

MedlinePlus

... Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine and E- ... Fentanyl GHB Hallucinogens Heroin Illegal Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids ...

Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour

PubMed Central

Maloney, Thomas; Parvaz, Muhammad A.; Alia-Klein, Nelly; Woicik, Patricia A.; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D.; Goldstein, Rita Z.

2010-01-01

Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects’ self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes. PMID:20395264

Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moeller, S.J.; Moeller, S.J.; Maloney, T.

Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessedmore » objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes.« less

Levamisole: a Common Adulterant in Cocaine Street Samples Hindering Electrochemical Detection of Cocaine.

PubMed

de Jong, Mats; Florea, Anca; Vries, Anne-Mare de; van Nuijs, Alexander L N; Covaci, Adrian; Van Durme, Filip; Martins, José C; Samyn, Nele; De Wael, Karolien

2018-04-17

The present work investigates the electrochemical determination of cocaine in the presence of levamisole, one of the most common adulterants found in cocaine street samples. Levamisole misleads cocaine color tests, giving a blue color (positive test) even in the absence of cocaine. Moreover, the electrochemical detection of cocaine is also affected by the presence of levamisole, with a suppression of the oxidation signal of cocaine. When levamisole is present in the sample in ratios higher than 1:1, the cocaine signal is no longer detected, thus leading to false negative results. Mass spectrometry and nuclear magnetic resonance were used to investigate if the signal suppression is due to the formation of a complex between cocaine and levamisole in bulk solution. Strategies to eliminate this suppressing effect are further suggested in this manuscript. In a first approach, the increase of the pH of the sample solution from pH 7 to pH 12 allowed the voltammetric determination of cocaine in the presence of levamisole in a concentration range from 10 to 5000 μM at nonmodified graphite disposable electrodes with a detection limit of 5 μM. In a second approach, the graphite electrode was cathodically pretreated, resulting in the presence of oxidation peaks of both cocaine and levamisole, with a detection limit for cocaine of 3 μM over the linear range of concentrations from 10 to 2500 μM. Both these strategies have been successfully applied for the simultaneous detection of cocaine and levamisole in three street samples on unmodified graphite disposable electrodes.

Passive inhalation of cocaine.

PubMed

Cone, E J; Yousefnejad, D; Hillsgrove, M J; Holicky, B; Darwin, W D

1995-10-01

Six healthy male volunteers were exposed to the vapor of 100 and 200 mg freebase cocaine heated to a temperature of 200 degrees C in an unventilated room (12,600-L volume) for a period of 1 h. No pharmacological effects were detected as a result of the exposure. Blood specimens collected immediately following exposure were negative for cocaine and metabolites. Urine specimens analyzed by gas chromatography-mass spectrometry contained peak concentrations of benzoylecgonine that ranged from 22 to 123 ng/mL. The peak excretion time for benzoylecgonine following passive exposure was approximately 5 h. The amount of cocaine inhaled by the subjects during passive exposure was estimated from room air measurements of cocaine to be approximately 0.25 mg. The total amount of cocaine (cocaine plus metabolites) excreted in urine by the six subjects ranged from 0.04 to 0.21 mg. For comparison, the six subjects also received an intravenous injection of 1 mg cocaine hydrochloride. Four of six subjects screened positive (300-ng/mL cutoff concentration) following the injection, indicating that the minimum amount of cocaine in these subjects necessary to produce positive results was approximately 1 mg. A second passive inhalation study was undertaken in which specimens were collected from research staff who assisted in a series of experimental studies with "crack" (freebase cocaine) smokers. The research staff remained in close vicinity while the crack smokers smoked three doses of freebase cocaine (12.5, 25, and 50 mg) over a period of 4 h. As a result, staff members were passively exposed to sidestream smoke from crack pipes and to breath exhalation from the crack smokers. Urine specimens from the staff members contained a maximum of 6 ng/mL benzoylecgonine. Only traces (less than 1 ng/mL) of cocaine were detected in any specimen. Overall, these studies demonstrated that individuals exposed to cocaine smoke under naturalistic or artificial conditions absorbed small amounts of

Role of orbitofrontal cortex neuronal ensembles in the expression of incubation of heroin craving

PubMed Central

Fanous, Sanya; Goldart, Evan M.; Theberge, Florence R.M.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.

2012-01-01

In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin-seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving. We trained rats to self-administer heroin (6-h/d for 10 d) and assessed cue-induced heroin-seeking in extinction tests after 1 or 14 withdrawal days. Cue-induced heroin-seeking increased from 1 day to 14 days and was accompanied by increased Fos expression in ~12% of OFC neurons. Non-selective inactivation of OFC neurons with the GABA agonists baclofen+muscimol decreased cue-induced heroin-seeking on withdrawal day 14 but not day 1. We then used the Daun02 inactivation procedure to assess a causal role of the minority of selectively activated Fos-expressing OFC neurons (that presumably form cue-encoding neuronal ensembles) in cue-induced heroin-seeking after 14 withdrawal days. We trained cfos-lacZ transgenic rats to self-administer heroin and 11 days later re-exposed them to heroin-associated cues or novel cues for 15 min (induction day) followed by OFC Daun02 or vehicle injections 90 min later; we then tested the rats in extinction tests 3 days later. Daun02 selectively decreased cue-induced heroin-seeking in rats previously re-exposed to the heroin-associated cues on induction day, but not in rats previously exposed to novel cues. Results suggest that heroin-cue-activated OFC neuronal ensembles contribute to the expression of incubation of heroin craving. PMID:22915104

Ethical issues in using a cocaine vaccine to treat and prevent cocaine abuse and dependence.

PubMed

Hall, W; Carter, L

2004-08-01

A "cocaine vaccine" is a promising immunotherapeutic approach to treating cocaine dependence which induces the immune system to form antibodies that prevent cocaine from crossing the blood brain barrier to act on receptor sites in the brain. Studies in rats show that cocaine antibodies block cocaine from reaching the brain and prevent the reinstatement of cocaine self administration. A successful phase 1 trial of a human cocaine vaccine has been reported. The most promising application of a cocaine vaccine is to prevent relapse to dependence in abstinent users who voluntarily enter treatment. Any use of a vaccine to treat cocaine addicts under legal coercion raises major ethical issues. If this is done at all, it should be carefully trialled first, and only after considerable clinical experience has been obtained in using the vaccine to treat voluntary patients. There will need to be an informed community debate about what role, if any, a cocaine vaccine may have as a way of preventing cocaine addiction in children and adolescents.

Identification of hallucinogenic fungi from the genera Psilocybe and Panaeolus by amplified fragment length polymorphism.

PubMed

Lee, J C; Cole, M; Linacre, A

2000-05-01

Unambiguous identification of the hallucinogenic fungi of the genera Psilocybe and Panaeolus is required by national and international drug control legislation. We report on a DNA-based test using the technique of amplified fragment length polymorphism (AFLP). AFLP can differentiate species of the two genera Psilocybe and Panaeolus by using different primer sets. The identification of hallucinogenic fungi using a DNA-based test, which can be used in conjunction with morphological features, will assist in forensic investigations.

An Economic Analysis of Income and Expenditures by Heroin-Using Research Volunteers

PubMed Central

RODDY, JULIETTE; GREENWALD, MARK

2015-01-01

At a Detroit research program from 2004 to 2005, out-of-treatment chronic daily heroin users (N = 100) were interviewed to evaluate relationships between past 30-day income and factors influencing heroin price, expenditures, and consumption. Weekly heroin purchasing frequency was positively related to income and number of suppliers, and negatively related to time cost (min) from primary supplier. Daily heroin consumption was positively related to income and injection heroin use, and negatively related to unit cost of heroin. Implications and limitations are noted. Simulations are underway to assess within-subject changes in drug demand. Supported by NIH/NIDA R01 DA15462 and Joe Young, Sr. Funds (State of Michigan). PMID:19938929

“Hallucinations” Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs

PubMed Central

Barrett, Frederick S.; Schlienz, Nicolas J.; Lembeck, Natalie; Waqas, Muhammad; Vandrey, Ryan

2018-01-01

Abstract Introduction: Cannabis has been historically classified as a hallucinogen. However, subjective cannabis effects do not typically include hallucinogen-like effects. Empirical reports of hallucinogen-like effects produced by cannabis in controlled settings, particularly among healthy research volunteers, are rare and have mostly occurred after administration of purified Δ-9 tetrahydrocannabinol (THC) rather than whole plant cannabis. Methods: The case of a healthy 30-year-old male who experienced auditory and visual hallucinations in a controlled laboratory study after inhaling vaporized cannabis that contained 25 mg THC (case dose) is presented. Ratings on the Hallucinogen Rating Scale (HRS) following the case dose are compared with HRS ratings obtained from the participant after other doses of cannabis and with archival HRS data from laboratory studies involving acute doses of cannabis, psilocybin, dextromethorphan (DXM), and salvinorin A. Results: Scores on the Volition subscale of the HRS were greater for the case dose than for the maximum dose administered in any other comparison study. Scores on the Intensity and Perception subscales were greater for the case dose than for the maximum dose of cannabis, psilocybin, or salvinorin A. Scores on the Somaesthesia subscale were greater for the case dose than for the maximum dose of DXM, salvinorin A, or cannabis. Scores on the Affect and Cognition subscales for the case dose were significantly lower than for the maximum doses of psilocybin and DXM. Conclusion: Acute cannabis exposure in a healthy adult male resulted in self-reported hallucinations that rated high in magnitude on several subscales of the HRS. However, the hallucinatory experience in this case was qualitatively different than that typically experienced by participants receiving classic and atypical hallucinogens, suggesting that the hallucinatory effects of cannabis may have a unique pharmacological mechanism of action. This type of adverse

Cocaine self-administration disrupts mesolimbic dopamine circuit function and attenuates dopaminergic responsiveness to cocaine.

PubMed

Siciliano, Cody A; Ferris, Mark J; Jones, Sara R

2015-08-01

Dopaminergic projections from the ventral midbrain to the nucleus accumbens (NAc) have long been implicated in encoding associations between reward availability and environmental stimuli. As such, this circuit is instrumental in guiding behaviors towards obtaining maximal rewards based on previous experience. Cocaine acts on the dopamine system to exert its reinforcing effects and it is thought that cocaine-induced dysregulation of dopamine neurotransmission contributes to the difficulty that cocaine addicts exhibit in selecting environmentally appropriate behaviors. Here we used cocaine self-administration combined with in vivo fast scan cyclic voltammetry in anesthetised rats to examine the function of the ventral tegmental area to NAc projection neurons. Over 5 days of cocaine self-administration (fixed-ratio 1; 1.5 mg/kg/injection; 40 injections/day), animals increased their rate of intake. Following cocaine self-administration, there was a marked reduction in ventral tegmental area-stimulated NAc dopamine release. Additionally, there was a decreased augmentation of stimulated dopamine overflow in response to a cocaine challenge. These findings demonstrate that cocaine induces a hypodopaminergic state, which may contribute to the inflexible drug-taking and drug-seeking behaviors observed in cocaine abusers. Additionally, tolerance to the ability of cocaine to elevate dopamine may lead to increased cocaine intake in order to overcome decreased effects, another hallmark of cocaine abuse. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Preclinical Assessment of Lisdexamfetamine as an Agonist Medication Candidate for Cocaine Addiction: Effects in Rhesus Monkeys Trained to Discriminate Cocaine or to Self-Administer Cocaine in a Cocaine Versus Food Choice Procedure

PubMed Central

Hutsell, Blake A.; Blough, Bruce E.; Poklis, Justin L.; Negus, S. Stevens

2015-01-01

Background: Chronic amphetamine treatment decreases cocaine consumption in preclinical and human laboratory studies and in clinical trials. Lisdexamfetamine is an amphetamine prodrug in which L-lysine is conjugated to the terminal nitrogen of d-amphetamine. Prodrugs may be advantageous relative to their active metabolites due to slower onsets and longer durations of action; however, lisdexamfetamine treatment’s efficacy in decreasing cocaine consumption is unknown. Methods: This study compared lisdexamfetamine and d-amphetamine effects in rhesus monkeys using two behavioral procedures: (1) a cocaine discrimination procedure (training dose = 0.32mg/kg cocaine, i.m.); and (2) a cocaine-versus-food choice self-administration procedure. Results: In the cocaine-discrimination procedure, lisdexamfetamine (0.32–3.2mg/kg, i.m.) substituted for cocaine with lower potency, slower onset, and longer duration of action than d-amphetamine (0.032–0.32mg/kg, i.m.). Consistent with the function of lisdexamfetamine as an inactive prodrug for amphetamine, the time course of lisdexamfetamine effects was related to d-amphetamine plasma levels by a counter-clockwise hysteresis loop. In the choice procedure, cocaine (0–0.1mg/kg/injection, i.v.) and food (1g banana-flavored pellets) were concurrently available, and cocaine maintained a dose-dependent increase in cocaine choice under baseline conditions. Treatment for 7 consecutive days with lisdexamfetamine (0.32–3.2mg/kg/day, i.m.) or d-amphetamine (0.032–0.1mg/kg/h, i.v.) produced similar dose-dependent rightward shifts in cocaine dose-effect curves and decreases in preference for 0.032mg/kg/injection cocaine. Conclusions: Lisdexamfetamine has a slower onset and longer duration of action than amphetamine but retains amphetamine’s efficacy to reduce the choice of cocaine in rhesus monkeys. These results support further consideration of lisdexamfetamine as an agonist-based medication candidate for cocaine addiction. PMID

Heroin-associated anthrax with minimal morbidity.

PubMed

Black, Heather; Chapman, Ann; Inverarity, Donald; Sinha, Satyajit

2017-03-08

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. 2017 BMJ Publishing Group Ltd.

The Problem of Heroin

ERIC Educational Resources Information Center

Wilson, James Q.; And Others

1972-01-01

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)

Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volkow, N.D.; Wang, G.; Volkow, N.D.

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and {sup 18}FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo andmore » once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue

Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Tomasi, Dardo; Telang, Frank; Fowler, Joanna S.; Pradhan, Kith; Jayne, Millard; Logan, Jean; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher

2010-01-01

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2–5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

A 50-Year-Old Woman Addicted to Heroin

PubMed Central

O’Brien, Charles P.

2011-01-01

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

Effects of a cocaine hydrolase engineered from human butyrylcholinesterase on metabolic profile of cocaine in rats.

PubMed

Chen, Xiabin; Zheng, Xirong; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

2016-11-25

Accelerating cocaine metabolism through enzymatic hydrolysis at cocaine benzoyl ester is recognized as a promising therapeutic approach for cocaine abuse treatment. Our more recently designed A199S/F227A/S287G/A328W/Y332G mutant of human BChE, denoted as cocaine hydrolase-3 (CocH3), has a considerably improved catalytic efficiency against cocaine and has been proven active in blocking cocaine-induced toxicity and physiological effects. In the present study, we have further characterized the effects of CocH3 on the detailed metabolic profile of cocaine in rats administrated intravenously (IV) with 5 mg/kg cocaine, demonstrating that IV administration of 0.15 mg/kg CocH3 dramatically changed the metabolic profile of cocaine. Without CocH3 administration, the dominant cocaine-metabolizing pathway in rats was cocaine methyl ester hydrolysis to benzoylecgonine (BZE). With the CocH3 administration, the dominant cocaine-metabolizing pathway in rats became cocaine benzoyl ester hydrolysis to ecgonine methyl ester (EME), and the other two metabolic pathways (i.e. cocaine methyl ester hydrolysis to BZE and cocaine oxidation to norcocaine) became insignificant. The CocH3-catalyzed cocaine benzoyl ester hydrolysis to EME was so efficient such that the measured maximum blood cocaine concentration (∼38 ng/ml) was significantly lower than the threshold blood cocaine concentration (∼72 ng/ml) required to produce any measurable physiological effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Heroin: Challenge for the 21st Century.

ERIC Educational Resources Information Center

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…

Subtypes of cocaine abusers.

PubMed

Weiss, R D; Mirin, S M

1986-09-01

We have characterized five subtypes of cocaine abusers on the basis of clinical presentation, family history data, and response to specific treatment interventions. These include depressed patients who value the euphorigenic effects of the drug, patients with bipolar or cyclothymic disorder who use cocaine to augment manic or hypomanic symptoms or to alleviate depression, adults with ADD, residual type, who find that cocaine has a paradoxical effect of increasing attention span and decreasing motor restlessness, patients with narcissistic and borderline personality disorders who use cocaine for its social prestige and because it bolsters self-esteem, and patients with antisocial personality disorder who use cocaine as part of an overall pattern of antisocial behavior. Although not all cocaine abusers fit neatly into these categories, careful psychiatric evaluation and subtyping is essential in designing a specific treatment program for these patients. As the prevalence rate of cocaine abuse increases, studies that examine the efficacy of various treatment approaches for specific subtypes of cocaine abusers will be essential. It is hoped that our work will be a step in that direction.

High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens

PubMed Central

Carter, Lawrence P.; Johnson, Matthew W.; Mintzer, Miriam Z.; Klinedinst, Margaret A.; Griffiths, Roland R.

2013-01-01

Rationale Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. Objective This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Methods Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70kg), and placebo were administered to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hours. Results Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis, increases in observer-rated effects typical of classic hallucinogens (e.g. distance from reality, visual effects with eyes open and closed, joy, anxiety), and participant ratings of stimulation (e.g. jittery, nervous), somatic effects (e.g. tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g. psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow up volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. Conclusions High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin. PMID:22526529

Exploration of the telescoping effect among not-in-treatment, intensive heroin-using research volunteers.

PubMed

Stoltman, Jonathan J K; Woodcock, Eric A; Lister, Jamey J; Greenwald, Mark K; Lundahl, Leslie H

2015-03-01

Addiction research literature suggests some demographic groups exhibit a later age of substance use initiation, more rapid escalation to dependence, and worse substance use-related outcomes. This 'telescoping' effect has been observed more often in females but has not yet been examined in not-in-treatment heroin users or racial subgroups. Not-in-treatment, intensive heroin-using adults screened for laboratory-based research studies (N=554; range 18-55 yr; mean age: 42.5 yr; 60.5% African American [AA]; 70.2% male) were included in this secondary analysis. A comprehensive drug history questionnaire assessed heroin-use characteristics and lifetime adverse consequences. We examined telescoping effects by racial and gender groups: Caucasian males and females; AA males and females. Caucasian males initiated heroin use significantly later than AA males but this difference was not observed for age at intensive heroin use (≥3 times weekly). Caucasian males reported significantly more lifetime heroin use-related consequences, were more likely to inject heroin, and reported more-frequent past-month heroin use, but did not differ from AA males in lifetime heroin quit attempts or prior heroin treatment. Females, compared to males, reported later onset of initial and intensive use, but there was no gender-telescoping effect from initial to intensive heroin-use. In this not-in-treatment sample, Caucasian males exhibited more rapid heroin-use progression and adverse consequences than AA males, i.e., within-gender, racial-group telescoping. Despite later-onset heroin use among females, there was no evidence of gender-related telescoping. Given the resurgence of heroin use, differential heroin-use trajectories across demographic groups may be helpful in planning interventions. Copyright © 2015. Published by Elsevier Ireland Ltd.

Cocaine intoxication

MedlinePlus

... head, if head injury or bleeding is suspected ECG (electrocardiogram, to measure electrical activity in the heart) ... to amputation Alternative Names Intoxication - cocaine Images Electrocardiogram (ECG) References Aronson JK. Cocaine. In: Aronson JK, ed. ...

Discriminative and Reinforcing Stimulus Effects of Nicotine, Cocaine, and Cocaine + Nicotine Combinations in Rhesus Monkeys

PubMed Central

Mello, Nancy K.; Newman, Jennifer L.

2011-01-01

Concurrent cigarette smoking and cocaine use is well documented. However, the behavioral pharmacology of cocaine and nicotine combinations is poorly understood, and there is a need for animal models to examine this form of polydrug abuse. The purpose of this study was two-fold: first to assess the effects of nicotine on the discriminative stimulus effects of cocaine, and second, to study self-administration of nicotine/cocaine combinations in a novel polydrug abuse model. In drug discrimination experiments, nicotine increased the discriminative stimulus effects of low cocaine doses in two of three monkeys, but nicotine did not substitute for cocaine in any monkey. Self-administration of cocaine and nicotine alone, and cocaine + nicotine combinations was studied under a second-order fixed ratio 2, variable ratio 16 (FR2[VR16:S]) schedule of reinforcement. Cocaine and nicotine alone were self-administered in a dose-dependent manner. The combination of marginally reinforcing doses of cocaine and nicotine increased drug self-administration behavior above levels observed with the same dose of either cocaine or nicotine alone. These findings indicate that nicotine may increase cocaine’s discriminative stimulus and reinforcing effects in rhesus monkeys, and illustrate the feasibility of combining cocaine and nicotine in a preclinical model of polydrug abuse. Further studies of the behavioral effects of nicotine + cocaine combinations will contribute to our understanding the pharmacology of dual nicotine and cocaine dependence, and will be useful for evaluation of new treatment medications. PMID:21480727

Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent nicotine+cocaine self-administration.

PubMed

Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Carroll, F Ivy

2014-04-01

Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce both cigarette smoking and cocaine abuse. Varenicline is a clinically available, partial agonist at α4β2* and α6β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist at α7 nAChRs. Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus in preclinical studies. The present study examined the effects of chronic varenicline treatment on self-administration of IV nicotine, IV cocaine, IV nicotine+cocaine combinations, and concurrent food-maintained responding by five cocaine- and nicotine-experienced adult rhesus monkeys (Macaca mulatta). Varenicline (0.004-0.04 mg/kg/h) was administered intravenously every 20 min for 23 h each day for 7-10 consecutive days. Each varenicline treatment was followed by saline-control treatment until food- and drug-maintained responding returned to baseline. During control treatment, nicotine+cocaine combinations maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05-0.001). Varenicline dose-dependently reduced responding maintained by nicotine alone (0.0032 mg/kg/inj) (P<0.05), and in combination with cocaine (0.0032 mg/kg/inj) (P<0.05) with no significant effects on food-maintained responding. However, varenicline did not significantly decrease self-administration of a low dose of nicotine (0.001 mg/kg), cocaine alone (0.0032 and 0.01 mg/kg/inj), or 0.01 mg/kg cocaine combined with the same doses of nicotine. We conclude that varenicline selectively attenuates the reinforcing effects of nicotine alone but not cocaine alone, and its effects on nicotine+cocaine combinations are dependent on the dose of cocaine.

Effects of Chronic Varenicline Treatment on Nicotine, Cocaine, and Concurrent Nicotine+Cocaine Self-Administration

PubMed Central

Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Carroll, F Ivy

2014-01-01

Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce both cigarette smoking and cocaine abuse. Varenicline is a clinically available, partial agonist at α4β2* and α6β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist at α7 nAChRs. Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus in preclinical studies. The present study examined the effects of chronic varenicline treatment on self-administration of IV nicotine, IV cocaine, IV nicotine+cocaine combinations, and concurrent food-maintained responding by five cocaine- and nicotine-experienced adult rhesus monkeys (Macaca mulatta). Varenicline (0.004–0.04 mg/kg/h) was administered intravenously every 20 min for 23 h each day for 7–10 consecutive days. Each varenicline treatment was followed by saline-control treatment until food- and drug-maintained responding returned to baseline. During control treatment, nicotine+cocaine combinations maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05–0.001). Varenicline dose-dependently reduced responding maintained by nicotine alone (0.0032 mg/kg/inj) (P<0.05), and in combination with cocaine (0.0032 mg/kg/inj) (P<0.05) with no significant effects on food-maintained responding. However, varenicline did not significantly decrease self-administration of a low dose of nicotine (0.001 mg/kg), cocaine alone (0.0032 and 0.01 mg/kg/inj), or 0.01 mg/kg cocaine combined with the same doses of nicotine. We conclude that varenicline selectively attenuates the reinforcing effects of nicotine alone but not cocaine alone, and its effects on nicotine+cocaine combinations are dependent on the dose of cocaine. PMID:24304823

Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity

PubMed Central

Schindler, Charles W; Goldberg, Steven R

2012-01-01

One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans. PMID:22300096

Heroin and fentanyl overdoses in Kentucky: Epidemiology and surveillance.

PubMed

Slavova, Svetla; Costich, Julia F; Bunn, Terry L; Luu, Huong; Singleton, Michael; Hargrove, Sarah L; Triplett, Jeremy S; Quesinberry, Dana; Ralston, William; Ingram, Van

2017-08-01

The study aims to describe recent changes in Kentucky's drug overdose trends related to increased heroin and fentanyl involvement, and to discuss future directions for improved drug overdose surveillance. The study used multiple data sources (death certificates, postmortem toxicology results, emergency department [ED] records, law enforcement drug submissions, and prescription drug monitoring records) to describe temporal, geographic, and demographic changes in drug overdoses in Kentucky. Fentanyl- and heroin-related overdose death rates increased across all age groups from years 2011 to 2015 with the highest rates consistently among 25-34-year-olds. The majority of the heroin and fentanyl overdose decedents had histories of substantial exposures to legally acquired prescription opioids. Law enforcement drug submission data were strongly correlated with drug overdose ED and mortality data. The 2016 crude rate of heroin-related overdose ED visits was 104/100,000, a 68% increase from 2015 (62/100,000). More fentanyl-related overdose deaths were reported between October, 2015, and September, 2016, than ED visits, in striking contrast with the observed ratio of >10 to 1 heroin-related overdose ED visits to deaths. Many fatal fentanyl overdoses were associated with heroin adulterated with fentanyl; <40% of the heroin overdose ED discharge records listed procedure codes for drug screening. The lack of routine ED drug testing likely resulted in underreporting of non-fatal overdoses involving fentanyl and other synthetic drugs. In order to inform coordinated public health and safety responses, drug overdose surveillance must move from a reactive to a proactive mode, utilizing the infrastructure for electronic health records. Copyright © 2017 Elsevier B.V. All rights reserved.

HEROIN DEPENDENCE : THE NEW DELHI EXPERIENCE

PubMed Central

Adityanjee; Mohan, D.; Saxena, S.

1984-01-01

SUMMARY Socio-demographic and clinical profile of the first one hundred and five patients attending a de-addiction clinic of New Delhi for heroin dependence is presented. It reveals a sudden rise of Heroin use in young educated males, probably because of its easy availability and its decreasing prices in the last few years. This trend is likely to be observed in the other metropolitan cities of India as well. Need for strengthening of preventive, curative and rehabilitative services is emphasized. PMID:21966005

Effect of heroin-conditioned auditory stimuli on cerebral functional activity in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trusk, T.C.; Stein, E.A.

1988-08-01

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 amore » 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.« less

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens.

PubMed

Rickli, Anna; Moning, Olivier D; Hoener, Marius C; Liechti, Matthias E

2016-08-01

The present study investigated interactions between the novel psychoactive tryptamines DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT at monoamine receptors and transporters compared with the classic hallucinogens lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), and mescaline. We investigated binding affinities at human monoamine receptors and determined functional serotonin (5-hydroxytryptamine [5-HT]) 5-HT2A and 5-HT2B receptor activation. Binding at and the inhibition of human monoamine uptake transporters and transporter-mediated monoamine release were also determined. All of the novel tryptamines interacted with 5-HT2A receptors and were partial or full 5-HT2A agonists. Binding affinity to the 5-HT2A receptor was lower for all of the tryptamines, including psilocin and DMT, compared with LSD and correlated with the reported psychoactive doses in humans. Several tryptamines, including psilocin, DMT, DiPT, 4-OH-DiPT, and 4-OH-MET, interacted with the serotonin transporter and partially the norepinephrine transporter, similar to 3,4-methylenedioxymethamphetamine but in contrast to LSD and mescaline. LSD but not the tryptamines interacted with adrenergic and dopaminergic receptors. In conclusion, the receptor interaction profiles of the tryptamines predict hallucinogenic effects that are similar to classic serotonergic hallucinogens but also MDMA-like psychoactive properties. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Inferior Frontal Cortex Modulation with an Acute Dose of Heroin During Cognitive Control

PubMed Central

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

2013-01-01

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

College students' use of cocaine.

PubMed

Williams, Jenny; Pacula, Rosalie Liccardo; Chaloupka, Frank J; Wechsler, Henry

2006-01-01

After experiencing a period of rapid decline between 1986 and 1994, cocaine use is once again on the rise in the United States. The increased prevalence of use among college students is particularly troubling because of its potential impact on human capital acquisition and long-term labor market success. Merging information on the price of cocaine and marijuana from the U.S. Drug Enforcement Agency with data on cocaine use from the College Alcohol Study, we investigate the demand for cocaine in the college population. We find evidence that participation in cocaine use by college students is responsive to changes in the price of cocaine and marijuana and that cocaine and marijuana are economic complements for this population. Further investigation revealed significant differences in the demand for cocaine by those less than age 21 and those at least age 21, years, with the younger age group being more responsive to changes in the price of cocaine. No difference is found, however, in the demand for cocaine across gender.

Wound botulism from heroin skin popping.

PubMed

Davis, Larry E; King, Molly K

2008-11-01

Following the introduction of black tar heroin mainly from Mexico in the 1980s, cases of wound botulism dramatically increased in the western United States. Contamination with spores of Clostridium botulinum of black tar heroin occurs along the distribution line. The heating of heroin powder to solubilize it for subcutaneous injection ("skin popping") does not kill the spores. The spores germinate in an anaerobic tissue environment and release botulinum toxin type A or B. Unless skin abscesses are found in the patient, the clinical diagnosis is often challenging. Facilitation of the compound muscle action potential by repetitive nerve stimulation at 20 to 50 Hz is an important and rapid diagnostic test. Definite diagnosis is made by detection of botulinum toxin in serum or isolation of C botulinum from the abscess. Early treatment with equine ABE botulinum antitoxin obtained from the Centers for Disease Control and Prevention often shortens the time on a ventilator.

Hair analysis for opiates: hydromorphone and hydrocodone as indicators of heroin use.

PubMed

Madry, Milena M; Bosshard, Mona M; Kraemer, Thomas; Baumgartner, Markus R

2016-05-01

Identification of external contamination is a challenge in hair analysis. This study investigates metabolite ratios of hydromorphone to morphine and hydrocodone to codeine as indicators to distinguish contamination from heroin use provided that hydromorphone/hydrocodone intake is excluded. Hair samples after external contamination with street heroin proved to be negative for hydromorphone/hydrocodone. Hair samples from individuals with suspected street heroin use/contamination or opiate medication were analyzed for 6-monoacetylmorphine, morphine, acetylcodeine, codeine, hydromorphone and hydrocodone, and metabolite ratios of hydromorphone to morphine and hydrocodone to codeine were assessed. Hair samples from individuals with medicinal heroin/morphine/codeine use displayed significantly higher metabolite ratios than those with suspected street heroin use/contamination. Hydromorphone/hydrocodone are solely formed during body passage. Thus, metabolite ratios can be used to distinguish morphine/heroin use from external contamination.

Candida endophthalmitis after heroin abuse.

PubMed

Malecaze, F; Arne, J L; Bec, P; Séguéla, J P; Linas, M D; Recco, P; Béssières, M H

1985-11-01

Three cases of ocular candidosis involving heroin abusers have been observed in 1983 in Toulouse department of ophthalmology. These three patients had used iranian brown heroin. Twenty similar cases have been published in these last years. This new pathology can be explained on two reasons. The first is that the drug abusers have some immunity pertubation; however, immunity exploration in these patients does not reveal any immunodeficiency. The second reason, certainly more important, is the method of using heroin. The diagnosis of Candida endophthalmitis of course based on clinical context must be proved by biological tests. Candida albicans is never identified in aqueous humor. For this reason, it seems very interesting to detect anti-candida antibodies in aqueous humor. It has been used as methods of dosage laser Nephelemetry for IgG and immunofluorescence for candidosis antibodies. The criterion used is similar to the toxoplasmosis coefficient established by Desmonts (3). In two cases, this test was the only way that permits us to have certitude of candidosis ocular diagnosis. Otherwise the observations show that anterior chamber punction is more significant when there is an anterior uveitis.

Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants - United States, 2015-2016.

PubMed

Seth, Puja; Scholl, Lawrence; Rudd, Rose A; Bacon, Sarah

2018-03-30

During 1999‒2015, 568,699 persons died from drug overdoses in the United States.* Drug overdose deaths in the United States increased 11.4% from 2014 to 2015 resulting in 52,404 deaths in 2015, including 33,091 (63.1%) that involved an opioid. The largest rate increases from 2014 to 2015 occurred among deaths involving synthetic opioids other than methadone (synthetic opioids) (72.2%) (1). Because of demographic and geographic variations in overdose deaths involving different drugs (2,3), † CDC examined age-adjusted death rates for overdoses involving all opioids, opioid subcategories (i.e., prescription opioids, heroin, and synthetic opioids), § cocaine, and psychostimulants with abuse potential (psychostimulants) by demographics, urbanization levels, and in 31 states and the District of Columbia (DC). There were 63,632 drug overdose deaths in 2016; 42,249 (66.4%) involved an opioid. ¶ From 2015 to 2016, deaths increased across all drug categories examined. The largest overall rate increases occurred among deaths involving cocaine (52.4%) and synthetic opioids (100%), likely driven by illicitly manufactured fentanyl (IMF) (2,3). Increases were observed across demographics, urbanization levels, and states and DC. The opioid overdose epidemic in the United States continues to worsen. A multifaceted approach, with faster and more comprehensive surveillance, is needed to track emerging threats to prevent and respond to the overdose epidemic through naloxone availability, safe prescribing practices, harm-reduction services, linkage into treatment, and more collaboration between public health and public safety agencies.

Role of the 5-HT₂A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice.

PubMed

Halberstadt, Adam L; Powell, Susan B; Geyer, Mark A

2013-07-01

The 5-HT₂A receptor mediates the effects of serotonergic hallucinogens and may play a role in the pathophysiology of certain psychiatric disorders, including schizophrenia. Given these findings, there is a need for animal models to assess the behavioral effects of 5-HT₂A receptor activation. Our previous studies demonstrated that the phenylalkylamine hallucinogen and 5-HT₂A/₂C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) produces dose-dependent effects on locomotor activity in C57BL/6J mice, increasing activity at low to moderate doses and reducing activity at high doses. DOI did not increase locomotor activity in 5-HT₂A knockout mice, indicating the effect is a consequence of 5-HT₂A receptor activation. Here, we tested a series of phenylalkylamine hallucinogens in C57BL/6J mice using the Behavioral Pattern Monitor (BPM) to determine whether these compounds increase locomotor activity by activating the 5-HT₂A receptor. Low doses of mescaline, 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-propylamphetamine (DOPR), 2,4,5-trimethoxyamphetamine (TMA-2), and the conformationally restricted phenethylamine (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine (TCB-2) increased locomotor activity. By contrast, the non-hallucinogenic phenylalkylamine 2,5-dimethoxy-4-tert-butylamphetamine (DOTB) did not alter locomotor activity at any dose tested (0.1-10 mg/kg i.p.). The selective 5-HT₂A antagonist M100907 blocked the locomotor hyperactivity induced by mescaline and TCB-2. Similarly, mescaline and TCB-2 did not increase locomotor activity in 5-HT₂A knockout mice. These results confirm that phenylalkylamine hallucinogens increase locomotor activity in mice and demonstrate that this effect is mediated by 5-HT₂A receptor activation. Thus, locomotor hyperactivity in mice can be used to assess phenylalkylamines for 5-HT₂A agonist activity and hallucinogen-like behavioral effects. These studies provide additional support for the link between 5

Familiar companions diminish cocaine conditioning and attenuate cocaine-stimulated dopamine release in the nucleus accumbens.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Wang, Shyi-Wu; Yu, Lung

2016-06-01

This study aimed to assess the impact of companions on the rewarding effects of cocaine. Three cage mates, serving as companions, were housed with each experimental mouse throughout cocaine-place conditioning in a cocaine-induced conditioned place preference (CPP) paradigm using conditioning doses of 10 and 20mg/kg. The presence of companions decreased the magnitude of the CPP. At 20mg/kg, cocaine stimulated dopamine (DA) release in the nucleus accumbens as evidenced by a significant decrease in total (spontaneous and electrical stimulation-provoked) DA release in accumbal superfusate samples. The presence of companions prevented this cocaine-stimulated DA release; such a reduction in cocaine-induced DA release may account for the reduction in the magnitude of the CPP in the presence of the companions. Furthermore, cocaine pretreatment (2.5mg/kg) was found to prevent the companion-produced decreases in cocaine (10mg/kg/conditioning)-induced CPP as well as the cocaine (10mg/kg)-stimulated DA release. Moreover, the presence of methamphetamine (MA) (1mg/kg)-treated companions decreased cocaine (20mg/kg/conditioning)-induced CPP and prevented the cocaine (20mg/kg)-stimulated DA release. Finally, the presence of companions decreased the magnitude of the CPP could not seem to be accounted for by cocaine-stimulated corticosterone (CORT) release. Taken together, these results indicate that familiar companions, regardless of their pharmacological status, may exert dampening effects on CPP induced by moderate to high conditioning doses of cocaine, at least in part, by preventing cocaine-stimulated DA release in the nucleus accumbens. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased intra-individual reaction time variability in cocaine-dependent subjects: role of cocaine-related cues.

PubMed

Liu, Shijing; Lane, Scott D; Schmitz, Joy M; Green, Charles E; Cunningham, Kathryn A; Moeller, F Gerard

2012-02-01

Neuroimaging data suggest that impaired performance on response inhibition and information processing tests in cocaine-dependent subjects is related to prefrontal and frontal cortical dysfunction and that dysfunction in these brain areas may underlie some aspects of cocaine addiction. In subjects with attention-deficit hyperactivity disorder and other psychiatric disorders, the Intra-Individual Reaction Time Variability (IIRTV) has been associated with frontal cortical dysfunction. In the present study, we evaluated IIRTV parameters in cocaine-dependent subjects vs. controls using a cocaine Stroop task. Fifty control and 123 cocaine-dependent subjects compiled from three studies completed a cocaine Stroop task. Standard deviation (SD) and coefficient of variation (CV) for reaction times (RT) were calculated for both trials with neutral and trials with cocaine-related words. The parameters mu, sigma, and tau were calculated using an ex-Gaussian analysis employed to characterize variability in RTs. The ex-Gaussian analysis divides the RTs into normal (mu, sigma) and exponential (tau) components. Using robust regression analysis, cocaine-dependent subjects showed greater SD, CV and Tau on trials with cocaine-related words compared to controls (p<0.05). However, in trials with neutral words, there was no evidence of group differences in any IIRTV parameters (p>0.05). The Wilcoxon matched-pairs signed-rank test showed that for cocaine-dependent subjects, both SD and tau were larger in trials with cocaine-related words than in trials with neutral words (p<0.05). The observation that only cocaine-related words increased IIRTV in cocaine-dependent subjects suggests that cocaine-related stimuli might disrupt information processing subserved by prefrontal and frontal cortical circuits. Copyright © 2011 Elsevier Ltd. All rights reserved.

Environmental enrichment reduces cocaine neurotoxicity during cocaine-conditioned place preference in male rats.

PubMed

Freese, Luana; Almeida, Felipe Borges; Heidrich, Nubia; Hansen, Alana Witt; Steffens, Luiza; Steinmetz, Aline; Moura, Dinara Jaqueline; Gomez, Rosane; Barros, Helena Maria Tannhauser

2018-06-01

Environmental enrichment (EE) has a neuroprotective role and prevents the development of cocaine addiction behavior in rats. Studies showing the role of EE in cocaine toxicity are nonexistent. We hypothesized that rats exposed to EE are protected from cocaine-induced changes in the redox profile and DNA damage after undergoing conditioned place preference (CPP). Ten male Wistar rats were placed in EE cages equipped with toys, a ladder and tunnels, and ten were provided clean, standard laboratory housing (non-EE). EE and non-EE rats were randomly allocated to the classical CPP cocaine vs. saline (COC/Saline) group, where cocaine (15 mg/kg; i.p.) was tested alternately with saline. Afterwards, intracellular reactive species and antioxidant enzymes were evaluated and the comet essay was performed in the prefrontal cortex and hippocampus of rats. As expected, EE rats spent less time in the cocaine-paired chamber, and as a new result, less cocaine-induced DNA damage was observed in the two brain structures. Altogether, our results demonstrate that EE decreases neurotoxicity in brain regions linked to cocaine addiction but does not extinguish it completely. Copyright © 2018. Published by Elsevier Inc.

Heroin Contaminated with Fentanyl Dramatically Enhances Brain Hypoxia and Induces Brain Hypothermia.

PubMed

Solis, Ernesto; Cameron-Burr, Keaton T; Kiyatkin, Eugene A

2017-01-01

While opioid abuse is an established medical and public health issue, the increased availability of highly potent synthetic opioids, such as fentanyl, has given rise to acute health complications, including a comatose state and death during drug overdose. Since respiratory depression that leads to acute hypoxia is the most dangerous complication of opioid drug use, we examined the effects of intravenous heroin and heroin contaminated with 10% fentanyl on oxygen levels in the nucleus accumbens (NAc) monitored using high-speed amperometry in freely moving rats. Additionally, we examined the effects of heroin, fentanyl, and their mixture on locomotion and temperatures in the NAc, temporal muscle, and skin. Both fentanyl and heroin at human-relevant doses (400 and 40 μg/kg, respectively) induced rapid, strong and transient decreases in NAc oxygen, indicative of brain hypoxia. When the heroin-fentanyl mixture was injected, the NAc hypoxic response was greatly potentiated in its duration, suggesting sustained hypoxia. In contrast to modest, monophasic brain temperature increases caused by heroin alone, the heroin-fentanyl mixture induced a biphasic temperature response, with a prominent postinjection decrease resulting from peripheral vasodilation. This hypothermic effect, albeit much smaller and more transient, was typical of fentanyl injected alone. Our findings indicate that accidental use of fentanyl instead of heroin, or even a relatively minor contamination of "street heroin" with fentanyl, poses great danger for acute health complications, including a comatose state and death.

Mortality among individuals with cannabis, cocaine, amphetamine, MDMA, and opioid use disorders: a nationwide follow-up study of Danish substance users in treatment.

PubMed

Arendt, Mikkel; Munk-Jørgensen, Povl; Sher, Leo; Jensen, Signe O W

2011-04-01

This is a register-based cohort study of 20,581 individuals in treatment for illicit substance use disorders in Denmark between 1996 and 2006. All in all, 1441 deaths were recorded during 111,445 person-years of follow-up. Standardized mortality ratios (SMRs) associated with different primary substance types were calculated and Cox-regression analyses were performed in order to establish hazard ratios (HR) associated with injection drug use and psychiatric comorbidity. SMRs for primary users of specific substances were: cannabis: 4.9 (95% confidence interval (CI): 4.2-5.8), cocaine: 6.4 (CI: 3.9-10.0), amphetamine: 6.0 (CI: 4.2-8.3), heroin: 9.1 (CI: 8.5-9.8), and other opioids 7.7 (CI: 6.6-8.9). For MDMA ('ecstasy') the crude mortality rate was 1.7/1000 person-years (CI: 0.4-7.0) and the SMR was not significantly elevated. Injection drug use was associated with significantly increased hazard ratios in users of opioids and cocaine/amphetamine. Overall, psychiatric comorbidity was not associated with increased mortality (HR: 1.1 [CI: 0.9-1.2], p=.28), but an association was found specifically among cocaine/amphetamine users (HR: 3.6 [CI: 2.1-6.4], p<.001). Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Associations between behavioral disinhibition and cocaine use history in individuals with cocaine dependence.

PubMed

Prisciandaro, James J; Korte, Jeffrey E; McRae-Clark, Aimee L; Brady, Kathleen T

2012-10-01

Behavioral disinhibition has been suggested as both a cause and consequence of substance use disorders. Many studies examining associations between behavioral disinhibition and substance use history have focused on individuals with alcohol dependence or non-dependent college students. In the present study, the relationship between behavioral disinhibition and cocaine use history in individuals with cocaine dependence is examined. Forty-six non-treatment-seeking cocaine-dependent men and women completed impulsivity (Barratt impulsiveness scale; BIS) and novelty seeking (temperament and character inventory; TCI) questionnaires at the baseline visit of an ongoing study. Unadjusted, and adjusted for gender and age, Pearson correlations were calculated between BIS, TCI, and cocaine use variables from the structured clinical interview for DSM-IV and timeline follow-back (age of onset, quantity/frequency of past 30 day cocaine use). As expected, elevated motor impulsivity and novelty seeking were each associated with younger age of dependence onset. Also, individuals with lower levels of persistence on the TCI reported more days of cocaine use over the previous month. Unexpectedly, increased novelty seeking and attentional impulsivity were associated with fewer days of cocaine use and less money spent on cocaine, respectively. Controlling for age and gender did not substantially change the pattern of observed associations. The present study provides preliminary evidence for associations between behavioral disinhibition and cocaine use history in cocaine-dependent individuals. Given our relatively small sample size and the correlational nature of our findings, further research is needed to replicate and extend our results. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of Federal drug law enforcement on the supply of heroin in Australia.

PubMed

Smithson, Michael; McFadden, Michael; Mwesigye, Sue-Ellen

2005-08-01

To conduct an empirical investigation of the efficacy of law enforcement in reducing heroin supply in Australia. Specifically, this paper addresses the question of whether heroin purity levels in the Australian Capital Territory (ACT) could be predicted by heroin seizures at the national level by the Australian Federal Police (AFP) in the preceding year. We considered two forms of evidence. First, a Bayesian Markov Chain Monte Carlo (MCMC) change-point model was used to discover (a) if there was a substantial increase in heroin seizures by the AFP, (b) when the increase began and (c) whether it occurred after increased funding to the Australian Federal Police for the purpose of drug law enforcement. Second, standard time-series methods were used to ascertain whether fluctuations in heroin seizure weights or the frequency of large-scale seizures after the aforementioned changes in seizure levels predicted fluctuations in heroin purity levels in the ACT after autocorrelation had been removed from the purity series. A Bayesian MCMC change-point model supported the hypothesis that heroin seizures rapidly increased about a year before the estimated decline in heroin purity and after the increased funding of AFP. The autoregression models suggested that 10-20% of the variance in the residuals of the heroin purity series was predicted by appropriately lagged residuals of the seizure-number and log-weight series, after autocorrelation had been removed. The overall results are consistent with the hypothesis that large-scale heroin seizures by the AFP reduce street-level heroin supply a year or so later, although the short-term dynamics suggest an 'opponent' response to residual fluctuations in seizures. To our knowledge, this is first time a connection has been identified between large-scale heroin seizures and street-level supply.

Comparative behavioral pharmacology and toxicology of cocaine and its ethanol-derived metabolite, cocaine ethyl-ester (cocaethylene)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katz, J.L.; Terry, P.; Witkin, J.M.

The present study compared the behavioral and toxic effects of cocaine and its ethanol derived metabolite, cocaine ethyl-ester (cocaethylene). Both drugs produced qualitatively similar psychomoter stimulant effects. Cocaine and cocaethylene increased locomotor activity in mice, with cocaine approximately four times more potent than cocaethylene. The durations of action of ED{sub 75} doses of each of the drugs were comparable. Each of the drugs also produced stimulation of operant responding in rats. In rats and squirrel monkeys trained to discriminate cocaine injections from saline, cocaine was approximately three to five times more potent than cocaethylene in producing these cocaine-like interoceptive effects.more » In contrast to the behavioral effects, cocaine and cocaethylene were equipotent in producing convulsions, and cocaethylene was more potent than cocaine in producing lethality. These results suggest that the conversion of cocaine to cocaethylene with simultaneous cocaine and alcohol use may produce an increased risk of toxicity due to a decrease in the potency of cocaethylene in producing psychomotor stimulant effects, and its increased potency in producing toxicity.« less

[Microscopic study of powders of hallucinogenic mushrooms--Psilocybe sp].

PubMed

Schäfer, A T

2000-01-01

The paper presents simple methods for microscopic examination and basic microchemical testing for the identification of suspect mushroom powders. The microscopic features of the most commonly cultivated and trafficked hallucinogenic genus Psilocybin are described and may serve for the decision whether any suspect material consists of such mushroom powder (and is therefore to be subjected to further analysis) or not.

Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction

PubMed Central

Narasimhan, Diwahar; Woods, James H; Sunahara, Roger K

2012-01-01

Cocaine is highly addictive and there are no pharmacotherapeutic drugs available to treat acute cocaine toxicity or chronic abuse. Antagonizing an inhibitor such as cocaine using a small molecule has proven difficult. The alternative approach is to modify cocaine’s pharmacokinetic properties by sequestering or hydrolyzing it in serum and limiting access to its sites of action. We took advantage of a bacterial esterase (CocE) that has evolved to hydrolyze cocaine and have developed it as a therapeutic that rapidly and specifically clears cocaine from the subject. Native enzyme was unstable at 37°C, thus limiting CocE’s potential. Innovative computational methods based on the protein’s structure helped elucidate its mechanism of destabilization. Novel protein engineering methodologies were applied to substantially improve its stability in vitro and in vivo. These improvements rendered CocE as a powerful and efficacious therapeutic to treat cocaine intoxication and lead the way towards developing a therapy for addiction. PMID:22300094

A cluster-analytic profiling of heroin-dependent patients based on level, clinical adequacy, and patient-desired adjustment of buprenorphine dosage during buprenorphine-naloxone maintenance treatment in sixteen Spanish centers.

PubMed

Alcaraz, Saul; González-Saiz, Francisco; Trujols, Joan; Vergara-Moragues, Esperanza; Siñol, Núria; Pérez de Los Cobos, José

2018-06-01

Buprenorphine dosage is a crucial factor influencing outcomes of buprenorphine treatment for heroin use disorders. Therefore, the aim of the present study is to identify naturally occurring profiles of heroin-dependent patients regarding individualized management of buprenorphine dosage in clinical practice of buprenorphine-naloxone maintenance treatment. 316 patients receiving buprenorphine-naloxone maintenance treatment were surveyed at 16 Spanish centers during the stabilization phase of this treatment. Patients were grouped using cluster analysis based on three key indicators of buprenorphine dosage management: dose, adequacy according to physician, and adjustment according to patient. The clusters obtained were compared regarding different facets of patient clinical condition. Four clusters were identified and labeled as follows (buprenorphine average dose and percentage of participants in each cluster are given in brackets): "Clinically Adequate and Adjusted to Patient Desired Low Dosage" (2.60 mg/d, 37.05%); "Clinically Adequate and Adjusted to Patient Desired High Dosage" (10.71 mg/d, 29.18%); "Clinically Adequate and Patient Desired Reduction of Low Dosage" (3.38 mg/d, 20.0%); and "Clinically Inadequate and Adjusted to Patient Desired Moderate Dosage" (7.55 mg/d, 13.77%). Compared to patients from the other three clusters, participants in the latter cluster reported more frequent use of heroin and cocaine during last week, lower satisfaction with buprenorphine-naloxone as a medication, higher prevalence of buprenorphine-naloxone adverse effects and poorer psychological adjustment. Our results show notable differences between clusters of heroin-dependent patients regarding buprenorphine dosage management. We also identified a group of patients receiving clinically inadequate buprenorphine dosage, which was related to poorer clinical condition. Copyright © 2018 Elsevier B.V. All rights reserved.

Prevalence, correlates and patterns of heroin use among young adults in the United States.

PubMed

Ihongbe, Timothy O; Masho, Saba W

2016-12-01

The prevalence of heroin use, abuse, and dependence has increased considerably over the past decade. This increase has largely been driven by young adults (18-25years). This study aims to improve the understanding of heroin use among young adults by determining the prevalence, correlates, patterns and attitude of heroin use among young adults in the US. The 2011-2013 National Survey on Drug Use and Health was analyzed. Study population included 55,940 young adults with valid interviews. Self-reported lifetime, past-year and past-month use of heroin were examined. Descriptive statistics and adjusted odds ratios were estimated in accordance with the complex survey design. Of the respondents, 18.4 per 1000 (95% CI=16.8-20.0) used heroin at some time in their lives, and 7.3 per 1000 (95% CI=6.3-8.3) and 3.3 per 1000 (95% CI=2.6-4.0) used heroin in the past year and past month, respectively. The single most common route of heroin use was by sniffing. Majority of young adults reported using heroin in combination with other substances. Users of non-prescribed opioid pain relievers, cigarette smokers, illicit drug users and those arrested and booked for breaking the law, had higher odds of using heroin during their lifetime, in the past-year and past-month. Fewer than 2% reported ever using heroin, and 82% of those reported no use in the past month. Majority were polysubstance users and sniffed heroin in combination with other routes of use. Comprehensive programs that target young adult heroin users and address important risk factors for heroin use are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Priming with BTCP, a dopamine reuptake blocker, reinstates cocaine-seeking and enhances cocaine cue-induced reinstatement.

PubMed

Martin-Fardon, Rémi; Lorentz, Christina U; Stuempfig, Nathan D; Weiss, Friedbert

2005-09-01

N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP), a potent dopamine reuptake inhibitor, substitutes for the reinforcing effects of cocaine and meets other criteria for possible agonist pharmacotherapeutic potential. The purpose of this study was to determine (1) whether BTCP modifies reinstatement of cocaine-seeking elicited by cocaine-related environmental stimuli and (2) whether this compound produces priming effects. Male Wistar rats were trained to associate discriminative stimuli (S(D)) with cocaine availability (0.25 mg/infusion) versus non-reward and then were subjected to repeated extinction sessions during which the reinforcer and S(D) were withheld. Subsequent presentation of the cocaine S(D) produced recovery of cocaine-seeking. BTCP (2.5-30 mg/kg; i.p.) did not attenuate the conditioned reinstatement induced by the cocaine S(D) but, rather, potentiated this effect at 10 mg/kg. To test whether BTCP, by itself, exerts priming effects, different groups of rats were trained to self-administer cocaine (0.25 mg/infusion) for 2 weeks. After a 2-week extinction period, BTCP (5, 10 and 20 mg/kg, i.p.) reinstated cocaine-seeking, showing that BTCP not only increases cocaine-seeking induced by cocaine-related stimuli but also produces priming effects following abstinence. The results suggest that, in cocaine abstinent rats, BTCP produces cocaine-like effects.

Effects of heroin on rat prosocial behavior.

PubMed

Tomek, Seven E; Stegmann, Gabriela M; Olive, M Foster

2018-05-04

Opioid use disorders are characterized in part by impairments in social functioning. Previous research indicates that laboratory rats, which are frequently used as animal models of addiction-related behaviors, are capable of prosocial behavior. For example, under normal conditions, when a 'free' rat is placed in the vicinity of rat trapped in a plastic restrainer, the rat will release or 'rescue' the other rat from confinement. The present study was conducted to determine the effects of heroin on prosocial behavior in rats. For 2 weeks, rats were given the opportunity to rescue their cagemate from confinement, and the occurrence of and latency to free the confined rat was recorded. After baseline rescuing behavior was established, rats were randomly selected to self-administer heroin (0.06 mg/kg/infusion i.v.) or sucrose pellets (orally) for 14 days. Next, rats were retested for rescuing behavior once daily for 3 days, during which they were provided with a choice between freeing the trapped cagemate and continuing to self-administer their respective reinforcer. Our results indicate that rats self-administering sucrose continued to rescue their cagemate, whereas heroin rats chose to self-administer heroin and not rescue their cagemate. These findings suggest that rats with a history of heroin self-administration show deficits in prosocial behavior, consistent with specific diagnostic criteria for opioid use disorder. Behavioral paradigms providing a choice between engaging in prosocial behavior and continuing drug use may be useful in modeling and investigating the neural basis of social functioning deficits in opioid addiction. © 2018 Society for the Study of Addiction.

Increased use of heroin as an initiating opioid of abuse.

PubMed

Cicero, Theodore J; Ellis, Matthew S; Kasper, Zachary A

2017-11-01

Given the relatively recent growth in access to heroin and a more permissive atmosphere surrounding its use, we hypothesized that an increasing number of persons with limited experience and tolerance to opioids would experiment with heroin as their first opioid rather than more common prescription opioid analgesics. Individuals entering substance abuse treatment for an opioid use disorder in the period 2010-2016 (N=5885) were asked about the specific opioid they first regularly used to get high. To limit long-term recall and survival bias, analyses was restricted to opioid initiation that occurred in the past ten years (2005-2015). In 2005, only 8.7% of opioid initiators started with heroin, but this sharply increased to 33.3% (p<0.001) in 2015, with no evidence of stabilization. The use of commonly prescribed opioids, oxycodone and hydrocodone, dropped from 42.4% and 42.3% of opioid initiators, respectively, to 24.1% and 27.8% in 2015, such that heroin as an initiating opioid was now more frequently endorsed than prescription opioid analgesics. Our data document that, as the most commonly prescribed opioids - hydrocodone and oxycodone - became less accessible due to supply-side interventions, the use of heroin as an initiating opioid has grown at an alarming rate. Given that opioid novices have limited tolerance to opioids, a slight imprecision in dosing inherent in heroin use is likely to be an important factor contributing to the growth in heroin-related over dose fatalities in recent years. Copyright © 2017. Published by Elsevier Ltd.

Cue-Induced Craving in Dependence Upon Prescription Opioids and Heroin

PubMed Central

McHugh, R. Kathryn; Park, Sara; Weiss, Roger D.

2014-01-01

Background and Objectives Cues associated with heroin use (e.g., needles, powder) elicit robust craving responses in individuals dependent upon heroin. Elevated cue-induced craving may be a risk factor for relapse and can persist after periods of drug abstinence. Despite the growing prevalence of opioid dependence involving prescription opioids, published studies have yet to examine whether cue-induced craving is also present in prescription opioid dependence. Methods A sample of 50 adults diagnosed with opioid dependence (20 prescription opioid users, 25 heroin users, and 5 mixed opioid users) completed a cue reactivity assessment. Participants were administered a series of 90 pictures, including heroin-specific, prescription opioid-specific, and neutral images, and were asked to rate craving and cue salience after each image. Results Both the prescription opioid and heroin groups experienced significantly more craving to drug than to neutral stimuli. The prescription opioid group reported significantly less craving to prescription opioid stimuli than the heroin group to heroin stimuli; however, this effect was smaller and non-significant when controlling for group differences in cue salience. Discussion and Conclusions This study found evidence for cue-induced craving in individuals dependent upon prescription opioids. Further research is needed to better understand the role of cue reactivity in the course and treatment of opioid dependence involving prescription opioid use. Scientific Significance As elevated craving reactivity to drug cues may reflect a risk factor for relapse, understanding the nature of cue-induced craving in individuals with opioid dependence is important to improving treatments for this population. PMID:24628912

The effects of piracetam on heroin-induced CPP and neuronal apoptosis in rats.

PubMed

Xu, Peng; Li, Min; Bai, Yanping; Lu, Wei; Ling, Xiaomei; Li, Weidong

2015-05-01

Piracetam is a positive allosteric modulator of the AMPA receptor that has been used in the treatment of cognitive disorders for decades. Recent surveys and drug analyses have demonstrated that a heroin mixture adulterated with piracetam has spread rapidly in heroin addicts in China, but its addictive properties and the damage it causes to the central neural system are currently unknown. The effect of piracetam on the reward properties of heroin was assessed by conditioned place preference (CPP). Electron microscopy and radioimmunoassay were used to compare the effects of heroin mixed with equivalent piracetam (HP) and heroin alone on neuronal apoptosis and the levels of beta-endorphin (β-EP) in different brain subregions within the corticolimbic system, respectively. Piracetam significantly enhanced heroin-induced CPP expression while piracetam itself didn't induce CPP. Morphological observations showed that HP-treated rats had less neuronal apoptosis than heroin-treated group. Interestingly, HP normalized the levels of β-EP in the medial prefrontal cortex (mPFC) and core of the nucleus accumbens (AcbC) subregions, in where heroin-treated rats showed decreased levels of β-EP. These results indicate that piracetam potentiate the heroin-induced CPP and protect neurons from heroin-induced apoptosis. The protective role of HP might be related to the restoration of β-EP levels by piracetam. Our findings may provide a potential interpretation for the growing trend of HP abuse in addicts in China. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Factor Analysis of the Mystical Experience Questionnaire: A Study of Experiences Occasioned by the Hallucinogen Psilocybin

PubMed Central

Maclean, Katherine A.; Leoutsakos, Jeannie-Marie S.; Johnson, Matthew W.; Griffiths, Roland R.

2012-01-01

A large body of historical evidence describes the use of hallucinogenic compounds, such as psilocybin mushrooms, for religious purposes. But few scientific studies have attempted to measure or characterize hallucinogen-occasioned spiritual experiences. The present study examined the factor structure of the Mystical Experience Questionnaire (MEQ), a self-report measure that has been used to assess the effects of hallucinogens in laboratory studies. Participants (N=1602) completed the 43-item MEQ in reference to a mystical or profound experience they had had after ingesting psilocybin. Exploratory factor analysis of the MEQ retained 30 items and revealed a 4-factor structure covering the dimensions of classic mystical experience: unity, noetic quality, sacredness (F1); positive mood (F2); transcendence of time/space (F3); and ineffability (F4). MEQ factor scores showed good internal reliability and correlated with the Hood Mysticism Scale, indicating convergent validity. Participants who endorsed having had a mystical experience on psilocybin, compared to those who did not, had significantly higher factor scores, indicating construct validity. The 4-factor structure was confirmed in a second sample (N=440) and demonstrated superior fit compared to alternative models. The results provide initial evidence of the validity, reliability, and factor structure of a 30-item scale for measuring single, hallucinogen-occasioned mystical experiences, which may be a useful tool in the scientific study of mysticism. PMID:23316089

Studying the effects of classic hallucinogens in the treatment of alcoholism: rationale, methodology, and current research with psilocybin.

PubMed

Bogenschutz, Michael P

2013-03-01

Recent developments in the study of classic hallucinogens, combined with a re-appraisal of the older literature, have led to a renewal of interest in possible therapeutic applications for these drugs, notably their application in the treatment of addictions. This article will first provide a brief review of the research literature providing direct and indirect support for the possible therapeutic effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of addictions. Having provided a rationale for clinical investigation in this area, we discuss design issues in clinical trials using classic hallucinogens, some of which are unique to this class of drug. We then discuss the current status of this field of research and design considerations in future randomized trials.

A non-rewarding, non-aversive buprenorphine/naltrexone combination attenuates drug-primed reinstatement to cocaine and morphine in rats in a conditioned place preference paradigm.

PubMed

Cordery, Sarah F; Taverner, Alistair; Ridzwan, Irna E; Guy, Richard H; Delgado-Charro, M Begoña; Husbands, Stephen M; Bailey, Christopher P

2014-07-01

Concurrent use of cocaine and heroin is a major public health issue with no effective relapse prevention treatment currently available. To this purpose, a combination of buprenorphine and naltrexone, a mixed very-low efficacy mu-opioid receptor agonist/kappa-opioid receptor antagonist/nociceptin receptor agonist, was investigated. The tail-withdrawal and the conditioned place preference (CPP) assays in adult Sprague Dawley rats were used to show that naltrexone dose-dependently blocked the mu-opioid receptor agonism of buprenorphine. Furthermore, in the CPP assay, a combination of 0.3 mg/kg buprenorphine and 3.0 mg/kg naltrexone was aversive. A combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone was neither rewarding nor aversive, but still possessed mu-opioid receptor antagonist properties. In the CPP extinction and reinstatement method, a combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone completely blocked drug-primed reinstatement in cocaine-conditioned rats (conditioned with 3 mg/kg cocaine, drug prime was 3 mg/kg cocaine) and attenuated drug-primed reinstatement in morphine-conditioned rats (conditioned with 5 mg/kg morphine, drug prime was 1.25 mg/kg morphine). These data add to the growing evidence that a buprenorphine/naltrexone combination may be protective against relapse in a polydrug abuse situation. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

The effects of the novel DA D3 receptor antagonist SR 21502 on cocaine reward, cocaine seeking and cocaine-induced locomotor activity in rats.

PubMed

Galaj, E; Ananthan, S; Saliba, M; Ranaldi, Robert

2014-02-01

There is a focus on developing D3 receptor antagonists as cocaine addiction treatments. We investigated the effects of a novel selective D3 receptor antagonist, SR 21502, on cocaine reward, cocaine-seeking, food reward, spontaneous locomotor activity and cocaine-induced locomotor activity in rats. In Experiment 1, rats were trained to self-administer cocaine under a progressive ratio (PR) schedule of reinforcement and tested with vehicle or one of three doses of SR 21502. In Experiment 2, animals were trained to self-administer cocaine under a fixed ratio schedule of reinforcement followed by extinction of the response. Then, animals were tested with vehicle or one of the SR 21502 doses on cue-induced reinstatement of responding. In Experiment 3, animals were trained to lever press for food under a PR schedule and tested with vehicle or one dose of the compound. In Experiments 4 and 5, in separate groups of animals, the vehicle and three doses of SR 21502 were tested on spontaneous or cocaine (10 mg/kg, IP)-induced locomotor activity, respectively. SR 21502 produced significant, dose-related (3.75, 7.5 and 15 mg/kg) reductions in breakpoint for cocaine self-administration, cue-induced reinstatement (3.75, 7.5 and 15 mg/kg) and cocaine-induced locomotor activity (3.75, 7.5 and 15 mg/kg) but failed to reduce food self-administration and spontaneous locomotor activity. SR 21502 decreases cocaine reward, cocaine-seeking and locomotor activity at doses that have no effect on food reward or spontaneous locomotor activity. These data suggest SR 21502 may selectively inhibit cocaine's rewarding, incentive motivational and stimulant effects.

Effects of levodopa-carbidopa-entacapone and smoked cocaine on facial affect recognition in cocaine smokers.

PubMed

Bedi, Gillinder; Shiffrin, Laura; Vadhan, Nehal P; Nunes, Edward V; Foltin, Richard W; Bisaga, Adam

2016-04-01

In addition to difficulties in daily social functioning, regular cocaine users have decrements in social processing (the cognitive and affective processes underlying social behavior) relative to non-users. Little is known, however, about the effects of clinically-relevant pharmacological agents, such as cocaine and potential treatment medications, on social processing in cocaine users. Such drug effects could potentially alleviate or compound baseline social processing decrements in cocaine abusers. Here, we assessed the individual and combined effects of smoked cocaine and a potential treatment medication, levodopa-carbidopa-entacapone (LCE), on facial emotion recognition in cocaine smokers. Healthy non-treatment-seeking cocaine smokers (N = 14; two female) completed this 11-day inpatient within-subjects study. Participants received LCE (titrated to 400mg/100mg/200mg b.i.d.) for five days with the remaining time on placebo. The order of medication administration was counterbalanced. Facial emotion recognition was measured twice during target LCE dosing and twice on placebo: once without cocaine and once after repeated cocaine doses. LCE increased the response threshold for identification of facial fear, biasing responses away from fear identification. Cocaine had no effect on facial emotion recognition. Results highlight the possibility for candidate pharmacotherapies to have unintended impacts on social processing in cocaine users, potentially exacerbating already existing difficulties in this population. © The Author(s) 2016.

Do heroin overdose patients require observation after receiving naloxone?

PubMed