Multinational Investment: Opportunity and Challenge.

ERIC Educational Resources Information Center

Perspective: Essays and Reviews of Issues in Employment Security and Employment and Training Programs, 1988

1988-01-01

This volume of an annual journal contains nine articles focusing on the internationalization of the world's economy and business and how employment security and employment and training programs can be involved. The opening article, "Foreign Investment Euphoria Hides Community Upheaval" (W. Scott Boyd), provides an overview of the volume…

The Nature of Adventure Education.

ERIC Educational Resources Information Center

Cousineau, Claude

Man answers a natural call for adventure in many ways including escape into fantasy, vertigo seeking, kinetic euphoria, and by exercising the pioneer spirit. Adventure education can help equip people to satisfy their need for adventure in meaningful, enriching ways. A reaction to unsatisfactory educational milieus, adventure education has emerged…

Factor Analysis of the Aftereffects of Drinking in Alcoholics.

ERIC Educational Resources Information Center

Watson, Charles G.; And Others

1985-01-01

Performed factor analyses of 100 alcoholics' reports of the effects that they experience after alcohol consumption. Five factors emerged: Hangover, Euphoria, Flushing, Seizures, and Sleepiness. These factors may be helpful in assessing theories on the etiology of alcoholism and in studies of ethanol's effects on subsets of alcohol abusers. (BH)

Assessing Environmental Prevention Strategies for Reducing the Prevalence and Associated Harms of Methamphetamine Use

ERIC Educational Resources Information Center

Yacoubian, George S.

2007-01-01

Developed primarily in clandestine laboratories, methamphetamine is a highly addictive synthetic drug whose physical effects include hyperactivity, euphoria, tremors, and a sense of increased energy. While the accuracy of recent accounts suggesting a methamphetamine epidemic in the United States is unclear, these reports have nevertheless…

Morrison Rebuttal to Adragna.

ERIC Educational Resources Information Center

Morrison, David C.

1985-01-01

Steven Adragna's arguments for a space-based ballistic missile defense (Georgia Social Science Journal; v16 n2 p14-16 Spr 1985) are founded on the High Frontier organization's usual distortions of the historical record, coupled with a wildly optimistic technological euphoria shared by few of even the Strategic Defense Initiative's most ardent…

Cocaine Abuse: The Evolution from Coca Leaves to Freebase.

ERIC Educational Resources Information Center

Forno, Joseph J.; And Others

1981-01-01

Describes historical and sociological patterns of cocaine use. Discusses cocaine as an example of a new drug abuse trend as users search for new ways of using old drugs in ways that produce enhanced euphoria. Describes the use of cocaine freebase and emergency treatment of cocaine toxicity. (Author)

75 FR 4400 - Draft Guidance for Industry on Assessment of Abuse Potential of Drugs; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

... comments on the draft guidance by March 29, 2010. ADDRESSES: Submit written requests for single copies of...] Draft Guidance for Industry on Assessment of Abuse Potential of Drugs; Availability AGENCY: Food and... psychoactive effects such as sedation, euphoria, or mood change. DATES: Although you can comment on any...

America's Middle Schools: Practices and Progress. A 25 Year Perspective.

ERIC Educational Resources Information Center

McEwin, C. Kenneth; And Others

The 1990s will likely be a watershed period for middle level education, as the real challenges surrounding making "second level" changes replace the euphoria that accompanied early growth of the middle school movement. Yet, zealousness still characterizes reform efforts at the middle level. This study, the most comprehensive ever…

Why Is Parkinsonism Not a Feature of Human Methamphetamine Users?

ERIC Educational Resources Information Center

Moszczynska, Anna; Fitzmaurice, Paul; Ang, Lee; Kalasinsky, Kathryn S.; Schmunk, Gregory A.; Peretti, Frank J.; Aiken, Sally S.; Wickham, Dennis J.; Kish, Stephen J.

2004-01-01

For more than 50 years, methamphetamine has been a widely used stimulant drug taken to maintain wakefulness and performance and, in high doses, to cause intense euphoria. Animal studies show that methamphetamine can cause short-term and even persistent depletion of brain levels of the neurotransmitter dopamine. However, the clinical features of…

All Aboard--Destination Unknown: A Sociological Discussion of Online Learning

ERIC Educational Resources Information Center

Goldberg, Andra K.; Riemer, Frances Julia

2006-01-01

This paper is an attempt to describe the emergence and growing popularity of online distance education over the past 30 years through changing sociological lenses. Examining the re-casting of the electronic classroom through the euphoria of techno-positivism, the power-embedded analysis of Critical Theory of Technology (CTT), and the critique of…

Using Computers in Distance Study: Results of a Survey amongst Disabled Distance Students.

ERIC Educational Resources Information Center

Ommerborn, Rainer; Schuemer, Rudolf

2002-01-01

In the euphoria about new technologies in distance education there exists the danger of not sufficiently considering how ever increasing "virtualization" may exclude some student groups. An explorative study was conducted that asked disabled students about their experiences with using computers and the Internet. Overall, those questioned…

Sudden death involving inhalation of 1,1-difluoroethane (HFC-152a) with spray cleaner: three case reports.

PubMed

Sakai, Kentaro; Maruyama-Maebashi, Kyoko; Takatsu, Akihiro; Fukui, Kenji; Nagai, Tomonori; Aoyagi, Miwako; Ochiai, Eriko; Iwadate, Kimiharu

2011-03-20

Spray cleaner is a cleaning product containing compressed 1,1-difluoroethane (HFC-152a) to blow dust off electric devices and other sensitive equipment; however, it is also inhaled to induce euphoria. This report describes three cases of death involving HFC-152a inhalation with spray cleaner under different circumstances. In case 1, death was during inhalation for euphoria with which led to having frostbite. In case 2, death may have been associated with suicidal intention. Case 3 was also considered an accidental autoerotic death. In all three cases, HFC-152a was detected at 99.2-136.2mg/l in blood samples, 94.5-191.9 mg/l in urine samples and 3.6-18.4 mg in the gastric contents according to gas chromatography with flame ionization detection. To prevent death associated with HFC-152a inhalation from spray cleaner, the danger of the sudden death should be announced to people, given the ready availability of commercial products containing HFC-152a. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Opiate Antagonists Do Not Interfere With the Clinical Benefits of Stimulants in ADHD: A Double-Blind, Placebo-Controlled Trial of the Mixed Opioid Receptor Antagonist Naltrexone.

PubMed

Spencer, Thomas J; Bhide, Pradeep; Zhu, Jinmin; Faraone, Stephen V; Fitzgerald, Maura; Yule, Amy M; Uchida, Mai; Spencer, Andrea E; Hall, Anna M; Koster, Ariana J; Biederman, Joseph

Methylphenidate activates μ-opioid receptors, which are linked to euphoria. μ-Opioid antagonists, such as naltrexone, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential. This study assessed whether the combination of naltrexone with methylphenidate is well-tolerated while preserving the clinical benefits of stimulants in subjects with attention-deficit/hyperactivity disorder (ADHD). We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate from January 2013 to July 2015. Spheroidal Oral Drug Absorption System (SODAS) methylphenidate was administered twice daily, was titrated to approximately 1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with a test dose of immediate-release methylphenidate. The primary outcome measure was the Adult ADHD Investigator Symptom Report Scale (AISRS). Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS methylphenidate and randomly assigned to naltrexone 50 mg or placebo. Thirty-one subjects completed the study through week 3, and 25 completed through week 6. Throughout 6 weeks of blinded naltrexone and open methylphenidate treatment, the coadministration of naltrexone with methylphenidate did not interfere with the clinical effectiveness of methylphenidate for ADHD symptoms. Additionally, the combination of naltrexone and methylphenidate did not produce an increase in adverse events compared with methylphenidate alone. Our findings provide support for the concept of combining opioid receptor antagonists with stimulants to provide an effective stimulant formulation with less abuse potential. ClinicalTrials.gov identifier: NCT01673594​. © Copyright 2017 Physicians Postgraduate Press, Inc.

Report from the street: elm reintroduction

Treesearch

Tom. Zetterstrom

2017-01-01

Since the introduction of Dutch elm disease (DED) to North America, heritage elm preservation was paramount, but elm restoration is held as the long-term solution. Various elm restoration efforts have been advanced and encouraged over the past half century, and all have inspired the euphoria of the "Return of the American Elm." The changing cast of characters...

Pharmacological Management of New-Onset Bipolar Disorder

ERIC Educational Resources Information Center

Kratochvil, Christopher J.; Delbello, Melissa; Upadhyaya, Himanshu; Wozniak, Janet

2005-01-01

A 12-year-old boy with no psychiatric history and no evidence of substance use presents with his first manic episode. Throughout the past 4 weeks, his family, school, and friends have noted distinct changes in his mood and behavior. His mood has oscillated between euphoria and severe irritability, with little or no provocation. He has been awake…

The Back Office of School Reform: Educational Planning Units in German-Speaking Switzerland (1960s and 1970s)

ERIC Educational Resources Information Center

Bosche, Anne

2016-01-01

The present article investigates what consequences for educational policy and/or educational administration were drawn from the upheavals of the 1960s and 1970s. A popular diagnosis in political science is that political decision-makers were pushed into a "reactive" role. In the context of a general "planning euphoria", and an…

Excitement or Anxiety? A Case Study of Indian Postgraduate Sojourners at University of Nottingham

ERIC Educational Resources Information Center

Unjore, Sanju

2014-01-01

Moving to a new country is often seen as a disturbing event in sojourners' lives. Several models of adjustment postulate that the first phase of the sojourn is either categorised by euphoria or anxiety. Using a case study of three Indian Postgraduate students, this paper investigates whether the beginning phase of these sojourners was euphoric or…

Prevention of Stimulant Induced Euphoria with an Opioid Receptor Antagonist

DTIC Science & Technology

2017-02-28

7 obtaining vital signs, a urine pregnancy and drug test, and...enlistment. This number represented 38% of all cases of drug use [9]. Further surveys indicate that 10 % of military personnel abuse stimulants during...Expected Definitely Pharmacologic + Altered Dose/Changed schedule N/A 1770601 9/17/13 Early Waking Internal Mild Expected Possible None N/A 1770601 9/17

On the (Im)Possibility of Democratic Citizenship Education in the Arab and Muslim World

ERIC Educational Resources Information Center

Waghid, Yusef; Davids, Nuraan

2014-01-01

The euphoria of the recent Arab Spring that was initiated in northern African countries such as Tunisia, Egypt and Libya and spilled over to Bahrain, Yemen and Syria brings into question as to whether democratic citizenship education or more pertinently, education for democratic citizenship can successfully be cultivated in most of the Arab and…

Prevention of Stimulant Induced Euphoria with an Opioid Receptor Antagonist

DTIC Science & Technology

2015-10-01

1993, Guilford Press: New York, NY. 2. Lomas, B. and P.S. Gartside, Attention - deficit hyperactivity disorder among homeless veterans. Psychiatr Serv...the military, deficits in impulsivity, distractibility and emotional regulation that could endanger the life of the affected soldier and his or her...peers, deficits in the interactions with peers and superiors, emotional impulsivity that could lead to low self esteem, substance abuse, criminality

Rhetoric vs. Reality: The Fundraising Messages of the United Negro College Fund in the Immediate Aftermath of the "Brown" Decision

ERIC Educational Resources Information Center

Gasman, Marybeth

2004-01-01

In spite of the euphoria of the "Brown v. Board of Education of Topeka, Kansas" decision outlawing segregation, Black leaders and presidents of the member colleges of the United Negro College Fund (UNCF) understood that this critical point in history brought both opportunities and challenges to Black higher education. The "Brown" decision…

The Military Deployment Human Exposure Assessment Study (MDHEXAS): Blood and Urine Exposure Biomarkers as Environmental Surveillance Tools for Assessing Military Personnel Exposure to Chemicals During Deployment to Camp McGovern, Bosnia

DTIC Science & Technology

2003-01-01

dysp = Dyspnea euph = euphoria excitement = excited fib = fibrosis flush face = flush face ftg = fatigue Head = Headache Gidd = giddiness inco...nausea Neck = neck ache nose = irritated nose Pallor Pulm edema= pulmonar y edema Resp sys = Respiratory System skin = irritated skin som = somnolence

Coda: The Slow Fuse of Change--Obama, the Schools, Imagination, and Convergence

ERIC Educational Resources Information Center

Greene, Maxine

2009-01-01

The author began writing this essay the day after waves of euphoria swept over what appeared to be a profoundly altered public space. Americans had seen the most diverse gathering of people coming freely together to affirm a common purpose no one could quite yet define. No one had instructed them to come out in the cold of that inauguration…

Military Review: SOF/LIC

DTIC Science & Technology

1991-06-01

ment strategic environment and concludes that the United States must "integratedly and direct- ly act.., when vital global balances are truly...recognizes no borders and underdeveloped countries. The euphoria in- respects no government. Increasingly, drug car- duced by improved relations with...respond if peaceful solu- balance far more dynamic than it has been for tions fail. more than 40 years. In addition, little has been The United States

Prevention of Stimulant-Induced Euphoria with an Opioid Receptor Antagonist

DTIC Science & Technology

2014-10-01

NY. 2. Lomas, B. and P.S. Gartside, Attention - deficit hyperactivity disorder among homeless veterans. Psychiatr Serv, 1997. 48(10): p. 1331-3. 3...demanding cognitive tasks under time constraints as required in the military, deficits in impulsivity, distractibility and emotional regulation that...could endanger the life of the affected soldier and his or her peers, deficits in the interactions with peers and superiors, emotional impulsivity

Cyberspace, Distance Learning, and Higher Education in Developing Countries: Old and Emergent Issues of Access, Pedagogy, and Knowledge Production. International Studies in Sociology and Social Anthropology, 94

ERIC Educational Resources Information Center

Assie-Lumumba, N'Dri T., Ed.

2004-01-01

Amidst the euphoria about the new frontiers of technology sometimes perceived as a panacea for expansion of higher education in developing countries, there is a need to analyze persistent and new grounds of unequal opportunity for access, learning, and the production of knowledge. This volume addresses fundamental questions about the educational…

Antecedents and consequences of binge eating episodes in women with an eating disorder.

PubMed

Kjelsås, E; Børsting, I; Gudde, C Buch

2004-03-01

The aim of this study was to explore antecedents and sequelae of binge eating episodes. A sample of eating disorders (n = 154 women) was selected from a total of 1849 female respondents (out of 2500) recruited as part of a general population-based survey. Included participants met DSM-III-R criteria for anorexia nervosa (AN), bulimia nervosa (BN) or eating disorder not otherwise specified (EDNOS) based on the Survey for Eating Disorders (SEDs). Preliminary criteria for binge eating disorder (BED) were added. Results indicated that the most frequently reported antecedents and consequences of binge eating were emotional and physiological factors. There were significant differences between the different ED subgroups in their frequency of binge eating episodes. Regarding antecedents of a binge eating episode, the SEDs-defined ED subgroups had overall differences in frequency on "stomach feeling". In particular, the BN-group reported "euphoria" more frequently than the BED and EDNOS-groups. Concerning consequences of a binge eating episode, there were overall differences between the ED subgroups on "fall asleep", and in addition a borderline significance was found for "disturbed by others" (p = 0.059). None of the eight women in the AN group reported "euphoria" as a factor that terminated a binge eating episode. The findings may have important implications with regard to prevention and treatment of ED.

Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.

PubMed

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

PubMed Central

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. PMID:23691320

Spice: A New Legal Herbal Mixture Abused by Young Active Duty Military Personnel

DTIC Science & Technology

2012-01-01

ABSTRACT. Spice is an herbal mixture smoked for euphoria and mixed with synthetic cannabinoids that are undetected on urine drug screens. Spice use has...more paranoia and hallucinations, and may differ for each brand. KEYWORDS. Cannabinoid, military, spice, substance abuse INTRODUCTION Use of synthetic ...regu- lations in an attempt to decrease the use of such synthetic psychoactive substances (1). There are few reports of Spice use and its potential

Prevention of Stimulant Induced Euphoria with an Opioid Receptor Antagonist

DTIC Science & Technology

2013-10-01

2. Lomas, B. and P.S. Gartside, Attention - deficit hyperactivity disorder among homeless veterans. Psychiatr Serv, 1997. 48(10): p. 1331-3. 3. Hoyt...References 1. Weiss, G. and L. Hechtman, Hyperactive children grown up, in ADHD in children, adolescents, and adults. 1993, Guilford Press: New York, NY...420-3. 11. Wilens, T.E., et al., Does ADHD Predict Substance-Use Disorders ? A 10-Year Follow-up Study of Young Adults With ADHD . J Am Acad Child

Space tourism: A flight of fantasy or the next major space product? Paper session 3: Products

NASA Technical Reports Server (NTRS)

Stone, Barbara A.

1994-01-01

In the euphoria of the early 1980's, a number of creative proposals for nontraditional uses of space were suggested. Taking tourists to space, possibly as early as the 1990's, was one such proposal. While it is now obvious that wherever explorers go, tourists (and hoteliers, restauranteurs, and tour guides) will someday follow. This paper discusses past and present efforts to promote space as a tourist destination.

Ethylphenidate as a selective dopaminergic agonist and methylphenidate-ethanol transesterification biomarker

PubMed Central

Patrick, Kennerly S.; Corbin, Timothy R.; Murphy, Cristina E.

2014-01-01

We review the pharmaceutical science of ethylphenidate (EPH) in the contexts of drug discovery; drug interactions; biomarker for dl-methylphenidate (MPH)-ethanol exposure; potentiation of dl-MPH abuse liability; contemporary “designer drug”; pertinence to the newer transdermal and chiral switch MPH formulations; as well as problematic internal standard. d-EPH selectively targets the dopamine transporter while d-MPH exhibits equipotent actions at dopamine and norepinephrine transporters. This selectivity carries implications for the advancement of tailored attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in the era of genome-based diagnostics. Abuse of dl-MPH often involves ethanol co-abuse. Carboxylesterase 1 enantioselectively transesterifies l-MPH with ethanol to yield l-EPH accompanied by significantly increased early exposure to d-MPH and rapid potentiation of euphoria. The pharmacokinetic component of this drug interaction can largely be avoided using dexmethylphenidate (dexMPH). This notwithstanding, maximal potentiated euphoria occurs following dexMPH-ethanol. C57BL/6 mice model dl-MPH-ethanol interactions: An otherwise depressive dose of ethanol synergistically increases dl-MPH stimulation; A sub-stimulatory dose of dl-MPH potentiates a low, stimulatory dose of ethanol; Ethanol elevates blood, brain and urinary d-MPH concentrations while forming l-EPH. Integration of EPH preclinical neuropharmacology with clinical studies of MPH-ethanol interactions provides a translational approach toward advancement of ADHD personalized medicine and management of comorbid alcohol use disorder. PMID:25303048

Ethylphenidate as a selective dopaminergic agonist and methylphenidate-ethanol transesterification biomarker.

PubMed

Patrick, Kennerly S; Corbin, Timothy R; Murphy, Cristina E

2014-12-01

We review the pharmaceutical science of ethylphenidate (EPH) in the contexts of drug discovery, drug interactions, biomarker for dl-methylphenidate (MPH)-ethanol exposure, potentiation of dl-MPH abuse liability, contemporary "designer drug," pertinence to the newer transdermal and chiral switch MPH formulations, as well as problematic internal standard. d-EPH selectively targets the dopamine transporter, whereas d-MPH exhibits equipotent actions at dopamine and norepinephrine transporters. This selectivity carries implications for the advancement of tailored attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in the era of genome-based diagnostics. Abuse of dl-MPH often involves ethanol coabuse. Carboxylesterase 1 enantioselectively transesterifies l-MPH with ethanol to yield l-EPH accompanied by significantly increased early exposure to d-MPH and rapid potentiation of euphoria. The pharmacokinetic component of this drug interaction can largely be avoided using dexmethylphenidate (dexMPH). This notwithstanding, maximal potentiated euphoria occurs following dexMPH-ethanol. C57BL/6 mice model dl-MPH-ethanol interactions: an otherwise depressive dose of ethanol synergistically increases dl-MPH stimulation; a substimulatory dose of dl-MPH potentiates a low, stimulatory dose of ethanol; ethanol elevates blood, brain, and urinary d-MPH concentrations while forming l-EPH. Integration of EPH preclinical neuropharmacology with clinical studies of MPH-ethanol interactions provides a translational approach toward advancement of ADHD personalized medicine and management of comorbid alcohol use disorder. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

[Characterisation and prevalence of the psychological and behavioural symptoms in patients with dementia].

PubMed

López-Pousa, S; Vilalta-Franch, J; Garre-Olmo, J; Pons, S; Cucurella, M G

To assess the prevalence of behavioural and psychological symptoms (BPS's) in patients with dementia in Spain and their dementia-specific characteristics. A cross-sectional and retrospective study of 1025 patients from 52 specialized dementia care units using the Neuropsychiatric Inventory (NPI). Patients with a probable diagnosis of Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease and dementia (PDD) were selected for BPS's characterisation. The global prevalence of BPS's was 66.7% (684 patients; 95% CI = 63.8-69.6%). BPS's were under-diagnosed in one third of cases. A total of 668 patients with NPI of 4 or superior and a diagnosis of AD (n = 380; 56.8%), DLB (n = 156; 23.3%) and PDD (n = 132; 19.7%) had a NPI mean of 21.1 (SD = 14.7), 25.6 (SD = 13.9) and 21.8 (SD = 14.2), respectively. Apathy, depression and anxiety were the most common BPS's. Delusions and hallucinations were significantly more prevalent in DLB. Dementia severity was correlated with the global NPI value and with all the sub-items, but anxiety and euphoria. The presence of agitation, euphoria or lability was associated with a deficient therapeutic fulfillment. A high prevalence of non-diagnosed BPS's was observed in the studied population. This has serious negative consequences for the quality of life of patients and their social environment. Therefore we propose an active search and subsequent correct treatment of BPS's in all patients with dementia.

Abuse potential of propofol used for sedation in gastric endoscopy and its correlation with subject characteristics.

PubMed

Kim, Ja Hyun; Byun, Heewon; Kim, Jun Hyun

2013-11-01

Propofol has been widely used for an induction and/or maintenance of general anesthesia, or for sedation for various procedures. Although it has many ideal aspects, there have been several cases of drug abuse and addiction. The authors investigated whether there are abuse liable groups among the general population. We surveyed 169 patients after gastric endoscopic examination, which used propofol as a sedative, with the Addiction Research Center Inventory (ARCI) questionnaire. Other characteristics of the patients, such as past history, smoking habits, depression, anxiety, alcohol abuse liability and sleep disturbance, were recorded by history taking and several questionnaires before the exam. Propofol had a high Morphine-Benzedrine Group (MBG) score (representative value for euphoria) of 6.3, which is higher than marijuana, and a Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) score (representative value of sedation) of 8.1, which is lower than most opioids. The MBG score showed no statistically significant correlation between any of the characteristics of the groups. In females, the PCAG score showed a correlation with age, and in males, it showed a correlation with a sleeping problem. Propofol had relatively high euphoria and low residual sedative effects. It had a more potent sedative effect in the female group who were young, and in the male group who had a low sleep quality index. There were differences in the abuse liability from a single exposure to propofol in the general population. Further study is needed to evaluate the abuse liability of repeated exposure.

Effects of MDMA and Intranasal Oxytocin on Social and Emotional Processing

PubMed Central

Kirkpatrick, Matthew G; Lee, Royce; Wardle, Margaret C; Jacob, Suma; de Wit, Harriet

2014-01-01

MDMA (±3,4-methylenedioxymethamphetamine, ‘ecstasy') is used recreationally, reportedly because it increases feelings of empathy, sociability, and interpersonal closeness. One line of evidence suggests that MDMA produces these effects by releasing oxytocin, a peptide involved in social bonding. In the current study, we investigated the acute effects of MDMA and oxytocin on social and emotional processing in healthy human volunteers. MDMA users (N=65) participated in a 4-session, within-between-subjects study in which they received oral MDMA (0.75, 1.5 mg/kg), intranasal oxytocin (20 or 40 IU), or placebo under double-blind conditions. The primary outcomes included measures of emotion recognition and sociability (desire to be with others). Cardiovascular and subjective effects were also assessed. As expected, MDMA dose-dependently increased heart rate and blood pressure and feelings of euphoria (eg, ‘High' and ‘Like Drug'). On measures of social function, MDMA impaired recognition of angry and fearful facial expressions, and the larger dose (1.5 mg/kg) increased desire to be with others, compared with placebo. Oxytocin produced small but significant increases in feelings of sociability and enhanced recognition of sad facial expressions. Additionally, responses to oxytocin were related to responses to MDMA with subjects on two subjective measures of sociability. Thus, MDMA increased euphoria and feelings of sociability, perhaps by reducing sensitivity to subtle signs of negative emotions in others. The present findings provide only limited support for the idea that oxytocin produces the prosocial effects of MDMA. PMID:24448644

Reasoning or reacting to others? How consumers use the rationality of other consumers.

PubMed

Pelzmann, Linda; Hudnik, Urska; Miklautz, Michaela

2005-11-15

Consumers adapt their behavior to the structure of the information available in the environment where they form expectations. One factor in people's environments is other people. "Others" are a significant source of information and means of orientating oneself. In conditions such as uncertainty, insecurity, anxiety but also euphoria, it is "the others" who provide market participants with coordinates. The purpose of this paper is to pass forward an approach that relates to consumers' other-directedness and to demonstrate in what ways consumers use the rationality of other consumers.

The role of the social worker in the in-vitro fertilization program.

PubMed

Greenfeld, D; Mazure, C; Haseltine, F; DeCherney, A

1984-01-01

The role of the clinical social worker in the In-Vitro fertilization Program is to help provide patients with an environment that includes realistic expectation and emphasizes the emotional spectrum of euphoria, anxiety and dysphoria that can accompany the demanding protocol. The literature supports the need for counseling and supportive psychotherapy in the infertility clinic but has not dealt specifically with the psychological demands of In-Vitro fertilization. This paper addresses the emotional stress of in-vitro fertilization and emphasizes the role of social worker as counselor, educator and guide.

Effects of amphetamine on reactivity to emotional stimuli

PubMed Central

Wardle, Margaret C.; de Wit, Harriet

2011-01-01

Rationale Most studies of the reinforcing effects of stimulants have focused on the drugs’ capacity to induce positive mood (i.e., euphoria). However, recent findings suggest drugs may also alter emotional reactivity to external stimuli, and that this may occur independently of direct effects on mood. Objectives We aimed to examine effects of d-amphetamine, a prototypic stimulant, on self-reported and psychophysiological reactivity to emotional stimuli as well as overall subjective mood. We predicted that amphetamine would enhance reactivity to pleasant stimuli, particularly, stimuli with social content and that these effects would be independent of the drug’s direct effects on mood. Methods Over three sessions, 36 healthy normal adults received placebo, d-amphetamine 10 and 20 mg under counterbalanced double-blind conditions. At each session, emotional reactivity to standardized positive, neutral, and negative pictures with and without social content was measured in self-reports and facial muscles sensitive to emotional state. Drug effects on cardiovascular variables and subjective mood were also measured. Results Amphetamine produced euphoria, feelings of drug effect, and increased blood pressure. Most notably, amphetamine enhanced self-reported positive reactions to all pictures and psychophysiological reactions to positive pictures. These effects were not significantly related to drug-induced mood changes. Contrary to our hypothesis, effects of amphetamine on emotional reactivity were not moderated by social content. Conclusions This study demonstrates a previously unexamined and potentially reinforcing effect of stimulant drugs in humans, distinct from more typically measured euphorigenic effects, and suggests new areas of research in stimulant abuse risk and adaptations occurring during drug dependence. PMID:21947316

Eurekas and Euphorias - The Oxford Book of Scientific Anecdotes

NASA Astrophysics Data System (ADS)

Gratzer, Walter

2002-11-01

The march of science has been marked through the years by episodes of drama and comedy, of failure as well as triumph, by outrageous strokes of luck, deserved and undeserved, and sometimes by human tragedy. In Eurekas and Euphorias , Walter Gratzer captures the human face of discovery as he relates many intriguing tales of scientific adventures spanning over two thousand years. Open this book at random and you may chance on the clumsy chemist named Sapper who broke a thermometer in a reaction vat and made the discovery that launched the modern dyestuff industry. Or the physicist who dissolved his gold Nobel Prize medal in acid to prevent it from falling into the hands of the Nazis. The book uncovers deep intellectual friendships, as well as ferocious animosities, and even acts of theft and malice, deceit, and a hoax or two. Indeed, we discover that scientists come in all shapes--the obsessive and the dilettantish, the genial, the envious, the preternaturally brilliant and the slow-witted who sometimes saw further in the end, the open-minded and the intolerant, recluses and arrivistes . We meet mathematicians and physicists in prison cells, and even in a madhouse, making important advances in their field. And we witness the careers, sometimes tragic, sometimes carefree, of the great women scientists, from Hypatia of Alexandria, to Sophie Germain and Sonia Kovalevskaya, to Marie Curie and her relentless battle with the French Academy. Told with wit and relish, here then is a glorious parade to delight the reader, with stories to astonish, to instruct, and most especially, to entertain.

Adverse drug events related to mood and emotion in paediatric patients treated for ADHD: A meta-analysis.

PubMed

Pozzi, Marco; Carnovale, Carla; Peeters, Gabriëlla G A M; Gentili, Marta; Antoniazzi, Stefania; Radice, Sonia; Clementi, Emilio; Nobile, Maria

2018-05-22

ADHD is frequently comorbid with anxiety and mood disorders, which may increase the severity of inattention and hyperactivity symptoms. Emotional symptoms (anxiety, irritability, mood lability) also affect patients without comorbidity or emerge as adverse drug events. The influence of ADHD drugs on emotional symptoms demands investigation to improve therapies. Systematic review of trials reporting adverse events in patients pharmacologically treated for ADHD. Meta-analysis of the occurrence of irritability, anxiety, apathy, reduced talk, sadness, crying, emotional lability, biting nails, staring, perseveration, euphoria. Meta-regression analysis. Forty-five trials were meta-analysed. The most frequently reported outcomes were irritability, anxiety, sadness, and apathy. Methylphenidates, especially immediate-release formulations, were most studied; amphetamines were half as studied and were predominantly mixed amphetamine salts. Reports on atomoxetine were scant. Meta-analysis showed that methylphenidates reduced the risk of irritability, anxiety, euphoria, whereas they worsened the risk of apathy and reduced talk; amphetamines worsened the risk of emotional lability. Factors influencing risks were study year and design, patients' sex and age, drug dose and release formulation. Possible discrepancy between adverse events as indicated in clinical trials and as summarised herein. Confounding due to the aggregation of drugs into groups; uninvestigated sources of bias; incomplete lists of adverse events; lack of observations on self-injury. Methylphenidates appeared safer than amphetamines, although younger patients and females may incur higher risks, especially with high-dose, immediate-release methylphenidates. Only atomoxetine holds a black-box warning, but amphetamines and methylphenidates also did not show a safe profile regarding mood and emotional symptoms. Copyright © 2018. Published by Elsevier B.V.

Addiction and Engagement: An Explorative Study Toward Classification Criteria for Internet Gaming Disorder.

PubMed

Lehenbauer-Baum, Mario; Klaps, Armin; Kovacovsky, Zuzana; Witzmann, Karolin; Zahlbruckner, Raphaela; Stetina, Birgit U

2015-06-01

The DSM-5 introduced Internet gaming disorder (IGD) as a condition needing more research. Proposed criteria include tolerance, preoccupation, deceiving, or continued excess despite psychosocial problems. However, studies suggest differences between addicted and engaged players. Therefore, this study investigated differences between engagement and addiction in a German-speaking sample of expert World of Warcraft players. Using an online-based questionnaire, 682 participants were surveyed (Mage=23.26 years; 84.9% male) from German-speaking areas. An adapted version of the "Asheron's call" questionnaire (which covers six addiction criteria, including salience, euphoria, and tolerance), the WHOQOL-BREF, the Gaming Motivation Scale, the BDI, the SPIN, and a brief version of the personality questionnaire BFI-10 were used. The average gamer in the sample played on level 87.93 and had been playing for 5.42 years. Addicted players had higher scores on the BDI and SPIN and significantly lower scores in all dimensions of quality of life. Addicted gamers played for 39.25 hours per week (engaged players: 11.93 hours per week) with significantly higher scores in items tapping achievement and immersion. There were differences regarding the BFI-10 in terms of "agreeableness," "conscientiousness," and "neuroticism." The results suggest that factors such as achievement and immersion set engaged and addicted users apart. Addiction seems to be significantly more connected to other psychopathologies such as depression and social anxiety. The results suggest that euphoria, tolerance, and cognitive salience should be handled with caution when it comes to a classification of IGD similar to (behavioral) addiction.

Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of Withdrawal.

PubMed

Diep, Jack; Chin, David Tian; Gupta, Somdatta; Syed, Faraz; Xiong, Ming; Cheng, Jianguo

2018-04-15

Kratom is an herb indigenous to Southeast Asia with psychoactive opioid compounds, often used as a treatment for chronic pain or opiate withdrawal symptoms. It is legally and readily available via Internet sales and has been identified as an emerging drug of abuse in the United States. Kratom use has been associated with psychosis, seizures, and even death. At lower doses, kratom acts as a stimulant, while at higher doses, it produces analgesia and euphoria. Here, we describe the successful management of kratom overdose and withdrawal in a young man with negative toxicology screens.

Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of Withdrawal.

PubMed

Diep, Jack; Chin, David Tian; Gupta, Somdatta; Syed, Faraz; Xiong, Ming; Cheng, Jianguo

2017-10-26

Kratom is an herb indigenous to Southeast Asia with psychoactive opioid compounds, often used as a treatment for chronic pain or opiate withdrawal symptoms. It is legally and readily available via Internet sales and has been identified as an emerging drug of abuse in the United States. Kratom use has been associated with psychosis, seizures, and even death. At lower doses, kratom acts as a stimulant, while at higher doses, it produces analgesia and euphoria. Here, we describe the successful management of kratom overdose and withdrawal in a young man with negative toxicology screens.

For women, abortion can't be the whole story.

PubMed

Beck, J

1992-04-08

A columnist for a leading newspaper in the US addresses the euphoria present at the abortion rights march in Washington, D.C. on April 5, 1992. The intergenerational crowd had hoped to convince the Congress to pass the Freedom of Choice Act that is intended to replace the Roe v. Wade decision of the Supreme Court. The Act would prevent states from prohibiting abortion once Roe v. Wade is reversed by the Supreme Court. The bill is so controversial that it gives many legislators who may be impressed with the numbers and clout of the prochoice marchers yet oppose it an excuse to not support it. Besides many legislators do not want to vote for or against it in this election year, particularly since many constituents have not yet decided when abortion should be allowed and what restrictions should be placed on abortion. President Bush is expected to veto the bill and Congress probably does not have the votes to override the President's veto. The euphoria is misplaced. It is unfortunate that the leading goal of many women's groups since the early 1970s has been to assure women the right to kill unborn children. Men do not have to face this demeaning, uncomfortable, emotionally loaded surgery as a price for their sex lives. Women should not accept or demand this burden. They should demand more money for contraception research, free contraceptives for low income women, or changes in current laws that prevent pharmaceutical companies from developing more effective and reliable contraceptives. Women should put their energy into changing the present sexual climate which allows unwanted pregnancies to occur. They should insist on men assuming equal responsibility for sexual activity and its consequences. Demanding the right to kill unborn children is not equality and is not progress.

Pain Therapy Guided by Purpose and Perspective in Light of the Opioid Epidemic

PubMed Central

Severino, Amie L.; Shadfar, Arash; Hakimian, Joshua K.; Crane, Oliver; Singh, Ganeev; Heinzerling, Keith; Walwyn, Wendy M.

2018-01-01

Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses. Understanding the history of opioid drug development, the widespread marketing campaign for opioids, the immense financial incentive behind the treatment of pain, and vulnerable socioeconomic and physical demographics for opioid misuse give perspective on the current epidemic as an American-born problem that has expanded to global significance. In light of the current worldwide opioid epidemic, it is imperative that novel opioids are developed to treat pain without inducing the euphoria that fosters physical dependence and addiction. We describe insights from preclinical findings on the properties of opioid drugs that offer insights into improving abuse-deterrent formulations. One finding is that the ability of some agonists to activate one pathway over another, or agonist bias, can predict whether several novel opioid compounds bear promise in treating pain without causing reward among other off-target effects. In addition, we outline how the pharmacokinetic profile of each opioid contributes to their potential for misuse and discuss the emergence of mixed agonists as a promising pipeline of opioid-based analgesics. These insights from preclinical findings can be used to more effectively identify opioids that treat pain without causing physical dependence and subsequent opioid abuse. PMID:29740351

[Methaemoglobinaemia induced by ingestion of alkyl nitrite, "poppers"].

PubMed

Kragsfeldt, Celina Thelberg; Nissen, Christoffer B; Brandt, Frans

2016-08-22

We present a case report of an 18-year-old male who was referred to the emergency department with evidence of methaemoglobinaemia. He presented with classic symptoms with peripheral cyanosis and hypoxia. Arterial blood gas showed a methaemoglobin level of 36%. This was caused by ingestion of alkyl nitrate, a widespread party drug called "poppers". When inhaled it causes euphoria, reduced pain and relaxation of the anal sphincter, but oral use may induce life-threatening methaemoglobinaemia. The treatment of choice is the antidote methylene blue. After treatment the patient regained full recovery and was discharged on the following day. We discuss classic symptoms, diagnosis and treatment of intoxication with methylene blue.

"It's overwhelming... everything seems to be too much:" A theory of crisis for individuals with severe persistent mental illness.

PubMed

Ball, Jeffrey S; Links, Paul S; Strike, Carol; Boydell, Katherine M

2005-01-01

Crisis in individuals with severe persistent mental illness (SPMI) is a poorly understood phenomenon for which traditional crisis models do not apply. In this study we explored the crisis experience using in-depth interviews conducted with individuals with severe persistent mental illness from two community support programs. A grounded theory of the crisis experience was developed and the results illustrate that underlying vulnerability sets the stage for crisis occurrence which involves feeling overwhelmed and lacking control and manifests as agitation/anger/aggression, being low, feeling anxious, or euphoria. Immediate responses to crises involve getting help or managing alone and numerous factors contribute to crisis resolution and prevention.

Eclectic perspectives on the psychology of aphasia.

PubMed

Tanner, Dennis C

2003-01-01

This article explores the psychological changes that occur in patients who have suffered a stroke with resulting aphasia and examines the adjustments necessary to help the patient cope. The eclectic approach described in this paper examines the psychology of aphasia from three perspectives: effects of brain injury, psychological defenses and coping styles, and responses to loss. Depression, anxiety attacks, ego restriction, crying, euphoria, denial, anger, and a host of other psychological reactions can accompany stroke, sometimes causing health care personnel to feel overwhelmed by these psychological concomitants in their patients. This paper is intended as a guide to understanding the significant psychological adjustments many patients must undergo. Current information is provided to assist in evaluating and treating these patients.

Multimodal imaging-monitored progression of stroke-like episodes in a case of MELAS syndrome.

PubMed

Namer, Izzie Jacques; Wolff, Valérie; Dietemann, Jean-Louis; Marescaux, Christian

2014-03-01

We report imaging findings during, between, and after 2 stroke-like episodes in a 45-year-old woman with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome with an A32243G mitochondrial mutation 6 years before. In November 2010, for a first episode, she showed mixed aphasia with logorrhea, disinhibition, agitation, euphoria, and a large left temporoparietal lesion. Symptomatology progressively regressed under L-arginine treatment. She was readmitted in June 2011 for a second episode with great anxiety, disorientation, impaired face recognition, worsening mixed aphasia, and a new right temporal lesion. After additional L-carnitine treatment, she remained without relapse for 14 months.

The poppers-HIV connection.

PubMed

Wilson, H

1999-03-01

Nitrite inhalants called "poppers" are receiving renewed attention by researchers regarding the drug's role in the gay community, its contribution to risky sexual behavior, and its ability to fuel the AIDS epidemic. Research shows the effects of poppers cause a euphoria that can reduce inhibitions, increase sexual drive, and intensify the sensations of orgasm. Poppers have been associated with a decrease in condom use. In addition, research has found that popper use suppresses natural killer (NK) cell function, which increases vulnerability to infectious agents, produces sustained alterations in the immune system, and may be a Kaposi's sarcoma (KS) cofactor. The combined data implicate that the use of poppers may well pose as a significant risk factor for seroconversion.

Behavioral effects of MDMA ('ecstasy') on adult zebrafish.

PubMed

Stewart, Adam; Riehl, Russell; Wong, Keith; Green, Jeremy; Cosgrove, Jessica; Vollmer, Karoly; Kyzar, Evan; Hart, Peter; Allain, Alexander; Cachat, Jonathan; Gaikwad, Siddharth; Hook, Molly; Rhymes, Kate; Newman, Alan; Utterback, Eli; Chang, Katie; Kalueff, Allan V

2011-06-01

3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') is a potent psychedelic drug inducing euphoria and hypersociability in humans, as well as hyperactivity and anxiety in rodents. Adult zebrafish (Danio rerio) have become a widely used species in neurobehavioral research. Here, we explore the effects of a wide range (0.25-120 mg/l) of acute MDMA doses on zebrafish behavior in the novel tank test. Although MDMA was inactive at lower doses (0.25-10 mg/l), higher doses reduced bottom swimming and immobility (40-120 mg/l) and impaired intrasession habituation (10-120 mg/l). MDMA also elevated brain c-fos expression, collectively confirming the usage of zebrafish models for screening of hallucinogenic compounds.

[Clinico-pathologic correlation of dementia produced by thinner and cocaine].

PubMed

Barroso Moguel, R; Méndez Armenta, M; Villeda Hernández, J

1993-01-01

Industrial solvents mixed from thinner, used in paints, leathers, rubber, varnishes, have neurotoxic action. By laboral inhalation or spontaneously these are absorbed from the lungs, transported by blood and because of this high lipophilic section are retained within the lipid rich nervous system. Euphoric effects appear accompanied with visual and additive halucinations. In chronic abusers it produce schizophrenic-paranoid consequences with encephalic and peripheral neuronal and nervous fibers destruction, accompanied of blindness and paralysis. Cocaine is another neurotoxic drug. At first it produces euphoria, arterial hypertension and symptoms suggestive of underlying psychiatric diseases. The cocaine addicts often suffer depression, paranoia, hallucinations, seizures and suicidal ideation. The morphological base of the symptomatology is the encephalic and peripheral neuronal and nerve fibers destruction.

Third International Congress on Epilepsy, Brain, and Mind: Part 2.

PubMed

Rektor, Ivan; Schachter, Steven C; Arya, Ravindra; Arzy, Shahar; Braakman, Hilde; Brodie, Martin J; Brugger, Peter; Chang, Bernard S; Guekht, Alla; Hermann, Bruce; Hesdorffer, Dale C; Jones-Gotman, Marilyn; Kanner, Andres M; Garcia-Larrea, Luis; Mareš, Pavel; Mula, Marco; Neufeld, Miri; Risse, Gail L; Ryvlin, Philippe; Seeck, Margitta; Tomson, Torbjörn; Korczyn, Amos D

2015-09-01

Epilepsy is both a disease of the brain and the mind. Here, we present the second of two papers with extended summaries of selected presentations of the Third International Congress on Epilepsy, Brain and Mind (April 3-5, 2014; Brno, Czech Republic). Humanistic, biologic, and therapeutic aspects of epilepsy, particularly those related to the mind, were discussed. The extended summaries provide current overviews of epilepsy, cognitive impairment, and treatment, including brain functional connectivity and functional organization; juvenile myoclonic epilepsy; cognitive problems in newly diagnosed epilepsy; SUDEP including studies on prevention and involvement of the serotoninergic system; aggression and antiepileptic drugs; body, mind, and brain, including pain, orientation, the "self-location", Gourmand syndrome, and obesity; euphoria, obsessions, and compulsions; and circumstantiality and psychiatric comorbidities. Copyright © 2015 Elsevier Inc. All rights reserved.

The New Kid on the Block--Incorporating Buprenorphine into a Medical Toxicology Practice.

PubMed

Wiegand, Timothy J

2016-03-01

Buprenorphine represents a safe and effective therapy for treating opioid dependence, alleviating craving and withdrawal symptoms in opioid-dependent patients. Buprenorphine has a "blocking" effect against the action of other opioids at the mu-receptor, preventing not only opioid-induced euphoria, but CNS and respiratory depressant effects as well. Buprenorphine was approved for the treatment of opioid dependence in 2002 after the passage of Drug Abuse Treatment Act 2000 (DATA 2000) which allowed clinicians to treat opioid-dependent patients with specifically named opioid agonist therapies in an office setting. Buprenorphine programs reduce the prevalence of HIV and hepatitis C and reduce criminal behaviors associated with illicit drug use. Patients stabilized on buprenorphine have increased employment, enhanced engagement with social services, and better overall health and well-being.

Morphine sulfate and naltrexone hydrochloride extended-release capsules: naltrexone release, pharmacodynamics, and tolerability.

PubMed

Johnson, Franklin; Setnik, Beatrice

2011-01-01

Morphine sulfate and naltrexone hydrochloride extended-release capsules (EMBEDA, King Pharmaceuticals, Inc., Bristol, TN), indicated for management of chronic, moderate-to-severe pain, contain pellets of extended-release morphine sulfate with a sequestered naltrexone core (MS-sNT). Taken as directed, morphine provides analgesia while naltrexone remains sequestered; if tampered with by crushing, naltrexone is released to mitigate morphine-induced euphoric effects. While it is necessary to establish that formulations intended to reduce attractiveness for abuse are successful in doing so, it is also necessary to demonstrate that product therapeutic integrity is maintained for patients. Data were reviewed from 3 studies to determine: 1) the quantity of naltrexone released when MS-sNT pellets are crushed (MS-sNTC) for at least 2 minutes with mortar and pestle); 2) the extent to which the naltrexone released upon crushing mitigated morphine-induced subjective effects; and 3) whether sequestered naltrexone precipitates opioid withdrawal when MS-sNT is taken as directed. The naltrexone bioavailability study compared naltrexone release from MS-sNTC with that from whole intact MS-sNT capsules (MS-sNTW) and an equal naltrexone solution (NS) dose. Equivalent bioavailability was established if 90% confidence intervals (CIs) for geometric mean ratios (maximum plasma naltrexone concentration [Cmax] and area under the concentration-time curve extrapolated to infinity [AUC∞]) fell between 80% and 125%. The oral pharmacodynamic study assessed drug liking and euphoria and pharmacokinetic properties of MS-sNTC and MS-sNTW compared with morphine sulfate solution (MSS) and placebo. The 12-month, open-label (OL) safety study evaluated safety of MS-sNT administered orally as directed in patients with chronic, moderate-to-severe pain. Safety assessments included withdrawal symptoms based on the Clinical Opiate Withdrawal Scale (COWS). Naltrexone from MS-sNTC met criteria for equivalent bioavailability to NS. Although morphine relative bioavailability was similar for MS-sNTC and MSS, mean peak (Emax) visual analog scale (VAS) scores for drug liking and Cole/Addiction Research Center Inventory Stimulation-Euphoria were significantly reduced for MS-sNTC vs MSS (p < 0.001). In these 2 studies, a total of 6 participants had one measurement of plasma naltrexone after MS-sNTW that was above the lower limit of quantification. In the OL safety study, 72/93 participants (77%) had no quantifiable naltrexone concentrations. There was neither evidence of naltrexone accumulation for any participant nor any significant correlation with MS-sNT dose, age, or sex. Of 4 participants with the highest naltrexone concentrations, none had COWS scores consistent with moderate opioid withdrawal symptoms. Only 5 participants had COWS scores consistent with moderate opioid withdrawal; all 5 had not taken MS-sNT as directed. Study populations may not be fully representative of patients receiving opioid therapy for the management of chronic, moderate-to-severe pain and of opioid abusers. When MS-sNT capsules are crushed, all of the sequestered naltrexone (relative to oral NS) is released and immediately available to mitigate morphine-induced effects. When MS-sNT was crushed, the naltrexone released abated drug liking and euphoria relative to that from an equal dose of immediate-release morphine from MSS administration in a majority of participants. Naltrexone concentrations were low over a period of 12 months without evidence of accumulation, and there were no observable opioid withdrawal symptoms when MS-sNT was taken as directed.

Aviators intoxicated by inhalation of JP-5 fuel vapors.

PubMed

Porter, H O

1990-07-01

This case of intoxication of two aviators by inhalation of JP-5 fuel vapors emphasizes a dangerous safety hazard. One or both aviators experienced burning eyes, nausea, fatigue, impairment of eye-hand coordination, euphoria, and memory defects when their cockpit became overwhelmed with the odor of JP-5 fuel. Physical and laboratory examinations were normal except for their ill appearance, conjunctivitis, and mild hypertension, which resolved without sequelae. Exposure to JP-5 fuel vapor occurs frequently, particularly after acrobatic flight in some aircraft. The neurologic effects and insidious nature of intoxication makes continued operation under such conditions extremely hazardous. The following is recommended: in the event the odor of JP-5 or any noxious or irritating substance is detected in the cockpit, serious consideration should be given to terminating the flight, using precautionary emergency landing procedures and 100% O2.

Nabilone therapy for cannabis withdrawal presenting as protracted nausea and vomiting.

PubMed

Lam, Philip W; Frost, David W

2014-09-22

Cannabis is one of the most commonly used recreational drugs worldwide. Psychoactive properties of the principal compound, δ-9-tetrahydrocannabinol include euphoria, a sense of relaxation and increased appetite. Chronic cannabis use has been associated with the development of a withdrawal syndrome on abrupt discontinuation. Withdrawal symptoms typically begin within 24 h of abstinence and manifest as irritability, nervousness, sleep disturbances and decreased appetite. There is growing evidence that supports the use of plant-derived and synthetic cannabinoids for the treatment of cannabis withdrawal. In this case report, we present 20-year-old woman who developed protracted nausea and vomiting secondary to cannabis withdrawal and was successfully treated with nabilone. Nausea and vomiting is not listed in the Diagnostic and Statistical Manual-5 diagnostic criteria for cannabis withdrawal syndrome and is an uncommon symptom presentation. 2014 BMJ Publishing Group Ltd.

Direct and retrospective assessment of factors contributing to compulsive buying.

PubMed

Miltenberger, Raymond G; Redlin, Jennifer; Crosby, Ross; Stickney, Marcella; Mitchell, Jim; Wonderlich, Stephen; Faber, Ronald; Smyth, Joshua

2003-03-01

Compulsive buying is a disorder that has begun to receive attention from researchers in recent years. The results of a handful of studies suggest that compulsive buying occurs in response to negative emotions and results in a decrease in the intensity of the negative emotions. In this investigation, we used interview and self-monitoring methods to evaluate the antecedents and consequences of compulsive buying in a sample of women who met criteria for compulsive buying on the compulsive buying scale (J. Consumer Res. 19 (1992) 459). As a group, the participants reported negative emotions as the most common antecedents to compulsive buying, and euphoria or relief from the negative emotions as the most common consequence of compulsive buying. These findings were consistent across the interview and self-monitoring assessment methods. The implications for assessment and treatment are discussed.

[News items on human papillomavirus and its vaccine in the Valencian press (2006-2011)].

PubMed

Tuells, José; Duro Torrijos, José Luis; Chilet Rosell, Elisa; Pastor Villalba, Eliseo; Portero Alonso, Antonio; Navarro Ortiz, Carmen; Galiana de la Villa, Eva María

2013-01-01

The process of introducing the human papillomavirus (HPV) vaccine aimed at teenage girls has not been entirely without controversy in Spain. This vaccine was originally hyped as a preventive measure in the fight against cervical cancer but the resulting euphoria was tempered by a message calling for evidence. During administration of the second dose of the vaccine in February 2009, an unexpected turn of events attracted vast media coverage when two teenagers experienced adverse effects after immunization in Valencia (Spain). This study analyzes the scope and content of news items on HPV, immunization and cervical cancer published between 2006 and 2011 in two widely disseminated regional newspapers in Valencia. We also discuss the extent to which the messages transmitted may have influenced acceptability of the vaccine. Copyright © 2012 SESPAS. Published by Elsevier Espana. All rights reserved.

Reviews

NASA Astrophysics Data System (ADS)

2006-11-01

WE RECOMMEND Critical mass Philip Ball explores the idea of the physics of society. Eurekas and Euphorias A humorous yet insightful collection of scientific anecdotes. Wind turbine Low-cost wind turbine produces excellent results. Science Center Nemo Hands-on science centre has some great displays for teenagers. Crocodile Physics There’s something for everyone in this lesson software package. Wireless Dynamics Sensor System A fun way to measure and record altitude and acceleration. WORTH A LOOK Climate Change Begins at Home This well researched book tackles the issue of saving our planet. The Little Doctor Datalogger Datalogger has lots of facilities but needs some manual processing. HANDLE WITH CARE The Physics of Basketball Only of interest to budding physicists obsessed with basketball. Virtual Physics This package offers nice simulations but not a lot else. WEB WATCH An eclectic mix of nuclear- and general-physics websites.

Reward, salience, and attentional networks are activated by religious experience in devout Mormons

PubMed Central

Ferguson, Michael A.; Nielsen, Jared A.; King, Jace B.; Dai, Li; Giangrasso, Danielle M.; Holman, Rachel; Korenberg, Julie R.; Anderson, Jeffrey S.

2017-01-01

High-level cognitive and emotional experience arises from brain activity, but the specific brain substrates for religious and spiritual euphoria remain unclear. We demonstrate using functional magnetic resonance imaging scans in 19 devout Mormons that a recognizable feeling central to their devotional practice was reproducibly associated with activation in nucleus accumbens, ventromedial prefrontal cortex, and frontal attentional regions. Nucleus accumbens activation preceded peak spiritual feelings by 1–3 s and was replicated in four separate tasks. Attentional activation in the anterior cingulate and frontal eye fields was greater in the right hemisphere. The association of abstract ideas and brain reward circuitry may interact with frontal attentional and emotive salience processing, suggesting a mechanism whereby doctrinal concepts may come to be intrinsically rewarding and motivate behavior in religious individuals. PMID:27834117

Nephrotoxic effects of designer drugs: synthetic is not better!

PubMed

Luciano, Randy L; Perazella, Mark A

2014-06-01

Designer drugs are synthetic, psychoactive substances with similar structures and activity to existing scheduled drugs or controlled chemical compounds. The use of these drugs is not generally considered illegal and they cannot be detected using standard toxicology tests--essentially they are considered to be 'legal highs'. Over the past several years, increasing numbers of designer drugs have become available. These drugs are classified as amphetamine derivatives, phenylpiperazine derivatives, synthetic cathinones, synthetic cannabinoids, phencyclidine derivatives and synthetic opioids. Although euphoria is the desired effect, neuropsychiatric and cardiac manifestations are frequently observed in individuals using these drugs at high doses or using drugs that are contaminated with other substances. Some designer drugs are also associated with adverse renal effects, including acute kidney injury from pigment nephropathy, acute tubular necrosis, obstructive nephropathy and hyponatraemia. The misuse of these drugs should be recognized and clinicians made aware of the potential for acute nephrotoxicity as the health burden of these compounds increases.

Psychological effects of thought acceleration.

PubMed

Pronin, Emily; Jacobs, Elana; Wegner, Daniel M

2008-10-01

Six experiments found that manipulations that increase thought speed also yield positive affect. These experiments varied in both the methods used for accelerating thought (i.e., instructions to brainstorm freely, exposure to multiple ideas, encouragement to plagiarize others' ideas, performance of easy cognitive tasks, narration of a silent video in fast-forward, and experimentally controlled reading speed) and the contents of the thoughts that were induced (from thoughts about money-making schemes to thoughts of five-letter words). The results suggested that effects of thought speed on mood are partially rooted in the subjective experience of thought speed. The results also suggested that these effects can be attributed to the joy-enhancing effects of fast thinking (rather than only to the joy-killing effects of slow thinking). This work is inspired by observations of a link between "racing thoughts" and euphoria in cases of clinical mania, and potential implications of that observed link are discussed. (c) 2008 APA, all rights reserved

Ecstasy-Associated Pneumomediastinum

PubMed Central

Marasco, Silvana F; Lim, H Kiat

2007-01-01

INTRODUCTION Ecstasy, also known as MDMA (3,4, methylenedioxymethamphetamine), is a popular illicit party drug amongst young adults. The drug induces a state of euphoria secondary to its stimulant activity in the central nervous system. PATIENTS AND METHODS A database review at two major inner city hospitals was undertaken to identify patients presenting with pneumomediastinum and their charts reviewed. A Medline review of all reported cases of pneumomediastinum associated with ecstasy abuse was undertaken. RESULTS A total of 56 patients presenting with pneumomediastinum were identified over a 5-year period. Review of the charts revealed a history of ecstasy use in the hours prior to presentation in six of these patients, representing the largest series reported to date. CONCLUSIONS Review of previously reported cases reveals the likely mechanism is due to Valsalva manoeuvre during periods of extreme physical exertion, and not a direct pharmacological effect of the drug. PMID:17535617

[Betel - the fourth most popular substance in the world].

PubMed

Zdrojewicz, Zygmunt; Kosowski, Wojciech; Królikowska, Natalia; Stebnicki, Marek; Stebnicki, Michał R

2015-09-01

Betel is a kind of substance for chewing, that is made from piper betle, areca nuts and other, additional constituents. It is the fourth most popular psychoactive substance in the world, right after caffeine, nicotine and alcohol. It is particularly famous in Asia. Betel chewing induces euphoria and it is addictive. Similarly like in other substances such as nicotine or alcohol, betel also has detrimental effects. It causes e.g. oral cancer and cancer of the oesophagus, it contributes to the development of metabolic syndrome, liver cirrhosis and chronic kidney disease. There are also positive effects of chewing betel, because is has antioxidant, anti-inflammatory, antyparasitic and antiseptic properties. The aim of this paper was to expand knowledge about betel and its both: positive and negative influence on human health. In this article original and review papers associated with the topic were used. © 2015 MEDPRESS.

Induced mood and selective attention.

PubMed

Brand, N; Verspui, L; Oving, A

1997-04-01

Subjects (N = 60) were randomly assigned to an elated, depressed, or neutral mood-induction condition to assess the effect of mood state on cognitive functioning. In the elated condition film fragments expressing happiness and euphoria were shown. In the depressed condition some frightening and distressing film fragments were presented. The neutral group watched no film. Mood states were measured using the Profile of Mood States, and a Stroop task assessed selective attention. Both were presented by computer. The induction groups differed significantly in the expected direction on the mood subscales Anger, Tension, Depression, Vigour, and Fatigue, and also in the mean scale response times, i.e., slower responses for the depressed condition and faster for the elated one. Differences between conditions were found in the errors on the Stroop: in the depressed condition were the fewest errors and significantly longer error reaction times. Speed of error was associated with self-reported fatigue.

3,4-Methylenedioxy analogues of amphetamine: defining the risks to humans.

PubMed

Hegadoren, K M; Baker, G B; Bourin, M

1999-03-01

The 3,4-methylenedioxy analogues of amphetamine [MDMA ("Ecstasy", "Adam"), MDA ("Love") and MDE ("Eve")] are recreational drugs that produce feelings of euphoria and energy and a desire to socialize, which go far to explain their current popularity as "rave drugs". In addition to these positive effects, the drugs are relatively inexpensive to purchase and have the reputation of being safe compared to other recreational drugs. Yet there is mounting evidence that these drugs do not deserve this reputation of being safe. This review examines the relevant human and animal literature to delineate the possible risks MDMA, MDA and MDE engender with oral consumption in humans. Following a summary of the behavioral and cognitive effects of MDMA, MDA and MDE, risks will be discussed in terms of toxicity, psychopathology, neurotoxicity, abuse potential and the potential for drug-drug interactions associated with acute and chronic use.

Adolescents’ Stage-Environment Fit in Middle and High School: The Relationship Between Students’ Perceptions of Their Schools and Themselves

PubMed Central

Booth, Margaret Zoller; Gerard, Jean M.

2012-01-01

This mixed-methods longitudinal project investigates the association between student perceptions of their schools and themselves. Findings from the first two waves of data analysis with 894 middle and high school students in a midsized Great Lakes city reveal similarities and differences between the grade levels (7th–10th) and their perceptions of their schools. Although 7th-grade students enter middle school with the most positive feelings about their schools, they lose this feeling of euphoria by the end of their academic year. In contrast, the 10th-grade females are the most positive of all students, recognizing school characteristics which assist with their self-efficacy. Results from quantitative analyses indicate that student attitudes toward school and a sense of school connectedness are linked to both self-esteem and academic self-efficacy. PMID:25332512

MDMA: interactions with other psychoactive drugs.

PubMed

Mohamed, Wael M Y; Ben Hamida, Sami; Cassel, Jean-Christophe; de Vasconcelos, Anne Pereira; Jones, Byron C

2011-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most widely abused illegal drugs. Some users self-report euphoria and an increased perception and feeling of closeness to others. When taken in warm environments, MDMA users may develop acute complications with potential fatal consequences. In rodents, MDMA increases locomotor activity and, depending on ambient temperature, may produce a dose-dependent, potentially lethal hyperthermia. Like most other recreational drugs, MDMA is frequently taken in combination with other substances including tobacco, EtOH, marijuana, amphetamines, cocaine and, caffeine. Although polydrug use is very common, the understanding of the effects of this multiple substance use, as well as the analysis of consequences of different drug-drug associations, received rather little attention. The purpose of this review is to summarize our current knowledge about the changes on MDMA-related behavior, pharmacology, and neurotoxicity associated with co-consumption of other drugs of abuse and psychoactive agents. Copyright © 2011 Elsevier B.V. All rights reserved.

Development of a checklist of short-term and long-term psychological symptoms associated with ketamine use.

PubMed

Fan, Ni; Xu, Ke; Ning, Yuping; Wang, Daping; Ke, Xiaoyin; Ding, Yi; Sun, Bin; Zhou, Chao; Deng, Xuefeng; Rosenheck, Robert; He, Hongbo

2015-06-25

Ketamine is an increasingly popular drug of abuse in China but there is currently no method for classifying the psychological effects of ketamine in individuals with ketamine dependence. Develop a scale that characterizes the acute and long-term psychological effects of ketamine use among persons with ketamine dependence. We developed a preliminary symptom checklist with 35 dichotomous ('yes' or 'no') items about subjective feelings immediately after ketamine use and about perceived long-term effects of ketamine use that was administered to 187 inpatients with ketamine dependence recruited from two large hospitals in Guangzhou, China. Exploratory factor analysis (EFA) was conducted on a randomly selected half of thesample to reduce the items and to identify underlying constructs. Confirmatory factor analysis (CFA) was conducted on the second half of the sample to assess the robustness of the identified factor structure. Among the 35 symptoms, the most-reported acute effects were 'floating or circling' (94%), 'euphoric when listening to rousing music' (86%), and 'feeling excited, talkative, and full of energy' (67%). The mostreported long-term symptoms were 'memory impairment' (93%), 'personality changes' (86%), and 'slowed reactions' (81%). EFA resulted in a final 22-item scale best modelled by a four-factor model: two factors representing chronic symptoms (social withdrawal and sleep disturbances), one about acute psychoticlike symptoms, and one that combined acute drug-related euphoria and longer-term decreased libido. CFA showed that these 4 factors accounted for 50% of the total variance of the final 22-item scale and that the model fit was fair (Goodness of Fit Index, GIF=83.3%; Root Mean Square Error of Approximation, RMSEA=0.072). A four-factor model including social withdrawal, sleep disturbance, psychotic-like symptoms, and euphoria at the time of drug use provides a fair description of the short-term and long-term psychological symptoms associated with ketamine use. Future work on the 22-item version of the scale with larger samples is needed to confirm the validity of this 4-factor structure, to assess the scale's test-retest reliability, and to determine whether or not it can be useful in the differential diagnosis and monitoring of treatment of individuals with ketamine dependence.

Alteration in brain-derived neurotrophic factor (BDNF) after treatment of mice with herbal mixture containing Euphoria longana, Houttuynia cordata and Dioscorea japonica.

PubMed

Jeon, Songhee; Lee, Chia-Hung; Liu, Quan Feng; Kim, Geun Woo; Koo, Byung-Soo; Pak, Sok Cheon

2014-11-28

Literature data indicate that brain-derived neurotrophic factor (BDNF), cyclic-AMP response element-binding protein (CREB) and phospho-CREB (pCREB) may have a place in depression. BDNF belongs to the neurotrophin family that plays an important role in proliferation, survival and differentiation of different cell populations in the mammalian nervous system. The herbal mixture used in the present study consists of Euphoria longana, Houttuynia cordata and Dioscorea japonica. The purpose of the present study was to determine the neuroprotective effect of herbal mixture. We also tested the hypothesis that administration of herbs reverses memory deficits and promotes the protein expression of BDNF in the mouse brain. Mice were randomized into four different treatment groups (n = 10/group). Normal and stress groups received regular lab chow without stress and under stress conditions, respectively, for 3 weeks. The animals in the stress group were immobilized for 4 hours a day for 2 weeks. Different doses of herbal mixture (206 and 618 mg/kg) were administered for 3 weeks to those mice under stress conditions. Mice were analyzed by behavioral tests and immunoblotting examination in the hippocampus and cortex. An additional in vitro investigation was performed to examine whether herbs induce neurotoxicity in a human neuroblastoma cell line, SH-SY5Y cells. No significant toxicity of herbs on human neuroblastoma cells was observed. These herbs demonstrated an inductive effect on the expression of BDNF, pCREB and pAkt. For spatial working memory test, herbal mixture fed mice exhibited an increased level of spontaneous alternation (p < 0.01) compared to those in stress conditions. Moreover, herbal mixture produced highly significant (p < 0.01) reduction in the immobility time in the tail suspension test. Mice in the herbal mixture groups demonstrated lower serum corticosterone concentration than mice in the stress group (p < 0.05). Effects of the oral administration of herbal mixture on protein levels of BDNF in the hippocampi and cortices were significant. Our study showed that herbal mixture administration has antidepressant effects in mice. It is proposed that adverse events such as stress and depression can modulate the expression of molecular players of cellular plasticity in the brain.

"Partying" hard: party style, motives for and effects of MDMA use at rave parties.

PubMed

M ter Bogt, Tom F; Engels, Rutger C M E

2005-01-01

This study examines motives for and consequences of MDMA use at different types of dance parties in the Netherlands (2001 and 2002). Participants were 490 visitors of three different types of rave parties, "club/mellow," "trance/mainstream," and "hardcore" (34% female, mean age 22.3 years, 76.5% MDMA users). Partygoers are motivated primarily by the energetic and euphoric effects they expect from MDMA. Quantity of MDMA use is associated with hardcore and trance/mainstream party style, with the motives of euphoria, sexiness, self-insight, and sociability/flirtatiousness (negative), and with gender, educational level (negative), and MDMA use by friends. Women report more (acute) negative effects--depression, confusion, loss of control, suspiciousness, edginess, nausea, dizziness--than men; and in particular, women who are motivated to cope with their problems by using MDMA are at risk. Men's polydrug use and notably their motivation to conform to friends by using MDMA are associated with negative effects.

Abuse of isobutyl nitrite inhalation (Rush) by adolescents.

PubMed

Schwartz, R H; Peary, P

1986-06-01

Isobutyl nitrite is a volatile liquid sold without a prescription as a "room odorizer" but is widely used as an inhalant to produce feelings of euphoria. Of the 173 13-22-year-olds (mean age, 16 years) clients of a long-term drug treatment facility who completed a questionnaire related to drug use, 74 (43%) admitted to having used isobutyl nitrite at least once, 22 (13%) had used the substance ten or more times, and eight (4%) used the substance 50 or more times. Inhalation of this malodorous substance leads almost universally to dizziness and lightheadedness and usually to severe symptoms of vasodilatation such as "pounding of the heart," blurred vision, and a "warm feeling." The feeling was unpleasant to 44 percent of the users in this study, and most also experienced pulsatile headache. In addition, contact dermatitis and irritation of the tracheobronchial tree and eyes occurred in some users. The primary use of this substance as an euphoric agent warrants consideration of banning its sale altogether.

Validation and Cross-Cultural Adaptation of a Chinese Version of the Emotional and Social Dysfunction Questionnaire in Stroke Patients.

PubMed

Huang, Hui-Chuan; Shyu, Meei-Ling; Lin, Mei-Feng; Hu, Chaur-Jong; Chang, Chien-Hung; Lee, Hsin-Chien; Chi, Nai-Fang; Chang, Hsiu-Ju

2017-12-01

The objectives of this study were to develop a cross-cultural Chinese version of the Emotional and Social Dysfunction Questionnaire (ESDQ-C) and test its validity and reliability among Chinese-speaking stroke patients. Various methods were used to develop the ESDQ-C. A cross-sectional study was used to examine the validity and reliability of the developed questionnaire, which consists of 28 items belonging to six factors, anger, helplessness, emotional dyscontrol, indifference, inertia and fatigue, and euphoria. Satisfactory convergence and known-group validities were confirmed by significant correlations of the ESDQ-C with the Profile of Mood States-Short Form ( p < .05) and with the Hospital Anxiety and Depression Scale ( p < .05). The internal consistency was represented by Cronbach's alpha, which was .96 and .79 to .92 for the entire scale and subscales, respectively. Appropriate application of the ESDQ-C will be helpful to identify critical adjustment-related types of distress and patients who experience difficulty coping with such distress.

Bath salts: they are not what you think.

PubMed

Wieland, Diane M; Halter, Margaret J; Levine, Ciara

2012-02-01

Psychoactive bath salts are a relatively new group of designer drugs sold as tablets, capsules, or powder and pur-chased in places such as tobacco and convenience stores, gas stations, head shops, and the Internet. Bath salts are stimulant agents that mimic cocaine,lysergic acid diethylamide, methamphetamine, or methylenedioxymethamphetamine (ecstasy). The most common bath salts are the cathinone derivatives 3,4-methylenedioxypyrovalerone(MDPV), 4-methylmethcathinone(mephedrone), and 3,4-methylenedioxy-N-methylcathinone (methylone). The drugs cause intense stimulation, eu-phoria, elevated mood, and a pleasurable "rush" Tachycardia, hypertension,peripheral constriction, chest pain, hallucinations, paranoia, erratic behavior,inattention, lack of memory of substance use, and psychosis have been observed in those who have used bath salts. The U.S. Drug Enforcement Administration recently exercised an emergency authority to name three key ingredients in bath salts as Schedule I, thereby making them illegal to possess or sell in the United States. Nursing implications related to both clinical and educational settings are discussed.

Peripherally Restricted Cannabinoids for the Treatment of Pain.

PubMed

Romero-Sandoval, E Alfonso; Asbill, Scott; Paige, Candler A; Byrd-Glover, Kiara

2015-10-01

The use of cannabinoids for the treatment of chronic diseases has increased in the United States, with 23 states having legalized the use of marijuana. Although currently available cannabinoid compounds have shown effectiveness in relieving symptoms associated with numerous diseases, the use of cannabis or cannabinoids is still controversial mostly due to their psychotropic effects (e.g., euphoria, laughter) or central nervous system (CNS)-related undesired effects (e.g., tolerance, dependence). A potential strategy to use cannabinoids for medical conditions without inducing psychotropic or CNS-related undesired effects is to avoid their actions in the CNS. This approach could be beneficial for conditions with prominent peripheral pathophysiologic mechanisms (e.g., painful diabetic neuropathy, chemotherapy-induced neuropathy). In this article, we discuss the scientific evidence to target the peripheral cannabinoid system as an alternative to cannabis use for medical purposes, and we review the available literature to determine the pros and cons of potential strategies that can be used to this end. © 2015 Pharmacotherapy Publications, Inc.

Subjective and physiological effects after controlled Sativex and oral THC administration.

PubMed

Karschner, E L; Darwin, W D; McMahon, R P; Liu, F; Wright, S; Goodwin, R S; Huestis, M A

2011-03-01

Sativex is a cannabis-plant extract delivering nearly 1:1 Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and "good drug effects" with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses.

Subjective and Physiological Effects After Controlled Sativex and Oral THC Administration

PubMed Central

Karschner, EL; Darwin, WD; McMahon, RP; Liu, F; Wright, S; Goodwin, RS; Huestis, MA

2013-01-01

Sativex is a cannabis-plant extract delivering nearly 1:1 Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and “good drug effects” with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses. PMID:21289620

Psychological and environmental determinants of relapse in crack cocaine smokers.

PubMed

Wallace, B C

1989-01-01

The paper reviews approaches to relapse in the treatment of cocaine abusers. Approaches reveal a common mechanism underlying relapse that involves drug craving, recall of euphoria, environmental cues, denial, myths of being able to sell or use drugs, and painful affect states necessitating use of a multifaceted clinical technique. Empirical validation of a common mechanism underlying relapse establishes a typology of psychological and environmental determinants of relapse for crack cocaine smokers (N = 35) who relapse after hospital detoxification and return a second time. Major findings are that relapse follows a painful emotional state (40%), failure to enter arranged aftercare treatment (37%), or encounters with conditioned environmental stimuli (34%), and involves narcissistic psychopathology and denial (28.5%) and interpersonal stress (24%); 85.7% involve multideterminants. Case examples illustrate the role of multideterminants in relapse. The paper educates clinicians to the integrated theory and multifaceted clinical technique necessary for efficacious treatment of cocaine patients, while the typology predicts probable relapse situations.

[Medical cannabis: the opportunity versus the temptation].

PubMed

Naftali, Timna

2011-12-01

The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea, and inflammation. Current research has shown cannabis to be a useful remedy for many diseases, including multiple sclerosis, dystonia, and chronic pain. Cannabinoids are used to improve food intake in anorexia of AIDS patients and to prevent vomiting due to cancer chemotherapy. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and pain and diarrhea in Crohn's disease. Cannabinoids reduce the size of brain infarct and cardiac reperfusion injury. However, cannabinoid treatment is not free of side effects including euphoria, psychosis, anxiety, paranoia, dependence and abuse. Since the cannabinoid system is involved in many physiological and pathological processes, the therapeutic potential is great. We must not be blind to the opportunity offered to us by medical cannabis just because it is an illicit drug, nor should we be temped by the quick response of patients to the central effect of cannabis. More research is warranted to explore the full potential of cannabis as medicine.

The Study of Blocking Agent on Lengkeng (Euphoria Logan Lour) Fruit Shell and Seed for Adsorption of Pb (II) from Aqueous Solution

NASA Astrophysics Data System (ADS)

Kurniawati, D.; Zein, R.; Chaidir, Z.; Aziz, H.

2018-04-01

The study focuses on the roles played by mayor functional groups(carboxyl) in the lengkeng shell for sorption of Pb (II). The biosorbent was characterized by FTIR and elemental analyses. The parameters such as pH, initial concentration, particle sizes, adsorbent dose and flow rate were also studied. The results showed that the optimum condition was at pH = 3, concentration 400 mg/l, 250 μm particle sizes, adsorbent dose 0,5 g and 2 ml/min flow rate with adsorption capacity 4,8933 mg/g(shell) and 5,2720 mg/g(seed). It is show that ion exchange play as a more important role in the sorption of Pb (II) on lengkeng shell and seed. Blocking of COOH groups by chemical esterification resulted in Pb important reduction in metal binding.The result showed that adsorption capacity of lengkeng shell uncreases until 63.67 % and lengkeng seed uncreases 98.70%.

Private Education in Poland: Breaking the Mould?

NASA Astrophysics Data System (ADS)

Klus-Stanska, Dorota; Olek, Hilary

1998-03-01

The burgeoning private sector is perhaps the most tangible of the changes in education which followed the upheavals of 1989/90 in Central and Eastern Europe. This article sets out to analyse the growth of private education in Poland and its contribution to the ongoing processes of democratisation and educational development. The authors argue that the euphoria of the period immediately following the overthrow of one-party communism encouraged unrealistic expectations of educational reform. Their analysis of private sector schooling in Poland suggests that its development has occurred in a haphazard fashion, reflecting the uncertainties of a society undergoing a painful process of transition. Symptomatic of this has been the failure to establish a clear regulatory framework for the private sector - an omission which has undermined the credibility of private schools. Nevertheless, the authors argue that the development of private sector schooling in Poland has brought diversity and a degree of innovation to a system previously almost devoid of either. There is now an urgent need for the evaluation and dissemination of private sector initiatives, which can serve as examples for future educational decision-making in Poland.

Key interindividual determinants in MDMA pharmacodynamics.

PubMed

Papaseit, E; Torrens, M; Pérez-Mañá, C; Muga, R; Farré, M

2018-02-01

MDMA, 3,4-methylenedioxymethamphetamine, is a synthetic phenethylamine derivative with structural and pharmacological similarities to both amphetamines and mescaline. MDMA produces characteristic amphetamine-like actions (euphoria, well-being), increases empathy, and induces pro-social effects that seem to motivate its recreational consumption and provide a basis for its potential therapeutic use. Areas covered: The aim of this review is to present the main interindividual determinants in MDMA pharmacodynamics. The principal sources of pharmacodynamic variability are reviewed, with special emphasis on sex-gender, race-ethnicity, genetic differences, interactions, and MDMA acute toxicity, as well as possible therapeutic use. Expert opinion: Acute MDMA effects are more pronounced in women than they are in men. Very limited data on the relationship between race-ethnicity and MDMA effects are available. MDMA metabolism includes some polymorphic enzymes that can slightly modify plasma concentrations and effects. Although a considerable number of studies exist about the acute effects of MDMA, the small number of subjects in each trial limits evaluation of the different interindividual factors and does not permit a clear conclusion about their influence. These issues should be considered when studying possible MDMA therapeutic use.

The Growth of Hydrological Understanding: Technologies, Ideas, and Societal Needs Shape the Field

NASA Astrophysics Data System (ADS)

Sivapalan, Murugesu; Blöschl, Günter

2017-10-01

Inspired by the work of Newton, Darwin, and Wegener, this paper tracks the drivers and dynamics that have shaped the growth of hydrological understanding over the last century. On the basis of an interpretation of this history, the paper then speculates about what kind of future is in store for hydrology and how we can better prepare for it. The historical narrative underpinning this analysis indicates that progress in hydrological understanding is brought about by changing societal needs and technological opportunities: new ideas are generated by hydrologists through addressing societal needs with the technologies of their time. We suggest that progress in hydrological understanding over the last century has expressed itself through repeated cycles of euphoria and disenchantment, which have served as stimuli for the progress. The progress, for it to happen, also needed inspirational leaders as well as a supportive scientific community that provided the backdrop to major advances in the field. The paper concludes that, in a similar way to how Newton, Darwin, and Wegener conducted their research, hydrology too can benefit from synthesis activities aimed at "connecting the dots."

Mephedrone: use, subjective effects and health risks.

PubMed

Winstock, Adam; Mitcheson, Luke; Ramsey, John; Davies, Susannah; Puchnarewicz, Malgorzata; Marsden, John

2011-11-01

To assess the patterns of use, subjective effect profile and dependence liability of mephedrone, supported by corroborative urine toxicology. Cross-sectional structured telephone interview. UK-based drug users associated with the dance music scene. A total of 100 mephedrone users, recruited through their involvement with the dance music scene. Assessment of pattern of use, acute and after effects, DSM dependence criteria and gas chromatography-mass spectrometry urinalysis. Mephedrone consumption results in typical stimulant-related subjective effects: euphoria, increased concentration, talkativeness, urge to move, empathy, jaw clenching, reduced appetite and insomnia. Thirty per cent of the sample potentially met criteria for DSM-IV dependence and there was evidence of a strong compulsion to use the drug (47% had used the drug for 2 or more consecutive days). Self-reported recent consumption of mephedrone was confirmed by toxicological analysis in all of the 14 participants who submitted a urine sample. Mephedrone has a high abuse and health risk liability, with increased tolerance, impaired control and a compulsion to use, the predominant reported dependence symptoms. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

[Poppers at top: alkyl nitrites use in France].

PubMed

Beck, François; Guignard, Romain; Richard, Jean-Baptiste

2014-10-01

Poppers is the usual name of various forms of alkyl nitrites. They are used as recreational drugs to intensify sexual intercourses and provoke a short euphoria just after their inhalation. In spite of several periods of ban in the 2000s, poppers' use sharply rose between 2000 and 2010. In the adult population as in teenagers, it is the second product consumed after cannabis among illicit drugs, confirming that it concerns circles wider than gays and lesbians who are sometimes depicted as emblematic users. The lifetime use of poppers concerns 5.3% of 18-64 years in 2010, men (7.2%) more than women (3.4%). At the end of the adolescence, its lifetime prevalence is 8.8% for girls and 9.2% for boys. In the general population and especially among young people, poppers is favourably considered. Nevertheless, this product is not without danger, even if the risk of dependence is extremely low. Several avenues of interventions may be outlined, mainly based on information and a regular follow-up of users which can allow to avoid an intensification of the consumption. © 2014 médecine/sciences – Inserm.

Electronic commerce: beyond the euphoria.

PubMed

Healy, J L; DeLuca, J M

2000-01-01

As the center of considerable media attention, case study articles, vendor research, and development efforts, electronic commerce technology is entering healthcare and having a profound effect. The simple truth, however, is that after the drama and excitement begins to wear off, completing a successful e-commerce implementation remains good old-fashioned hard, sometimes monotonous work. To be successful, e-commerce technologies must be planned and implemented with rigorous project standards, and incorporated with significant process and workflow reengineering to actually return significant value to the organization. This article briefs readers on the organizational issues they must consider in evaluating e-commerce readiness--cultural, executive and technological factors that either support or inhibit project and technology success. Readers will be left with the tools to conduct an electronic commerce "readiness assessment" to evaluate the immediate, mid- and long-term potential of electronic commerce; practical remediation strategies for better preparing the organization for the changes inherent in moving to an e-commerce-enabled business model; and comments from the field--advice from organizations that have successfully implemented e-commerce technologies into their ongoing operations.

Rural North Dakota's oil boom and its impact on social services.

PubMed

Weber, Bret A; Geigle, Julia; Barkdull, Carenlee

2014-01-01

Over the last five years, North Dakota has experienced an oil boom based on high oil prices and hydraulic fracturing technologies. This has brought economic expansion and population growth to rural communities that had previously experienced decades of depopulation and economic struggle. Although the state has enjoyed many benefits--especially in juxtaposition to a sluggish national economy--the boom has also meant the arrival of economic refugees and dramatic impacts on largely rural social service systems. In the midst of a rapidly changing situation, available information tends to swing between euphoria over economic success and hysteria about rising crime and shifting cultures. In response, the authors used a primary focus group with county social service directors from across the state and a followup focus group with social workers operating on the edge of oil activity. Grounded in resilience theory, qualitative analysis of the primary focus group, and triangulation of data from other sources, this study provides a more objective report of the housing and social challenges, the benefits of the boom, and the challenges to solutions.

The representation of epilepsy in popular music.

PubMed

Baxendale, Sallie

2008-01-01

Much can be learned about the contemporary stereotypes associated with epilepsy by studying the representation of the disorder in paintings, literature, and movies. Popular music is arguably the most accessible and ubiquitous of the creative art forms, touching most of us on a daily basis. Reviewed here are the ways in which epilepsy and seizures are used in the lyrics of musicians from a wide variety of musical genres, from hip-hop to rhythm and blues. Many of the ancient associations of epilepsy with madness, horror, and lunacy can be found in these lyrics. However, the language of epilepsy has also been appropriated by some musical artists to represent a state of sexual ecstasy and dance euphoria. The references to these states as "epilepsy" or a "seizure" in numerous songs suggest that this shorthand is widely recognized within some subcultures. Although epilepsy has frequently been associated with female sexual availability in other creative art forms, this novel use of the language of epilepsy represents a contemporary departure in the artistic application of epilepsy-related images and associations in the 21st century.

Huffing air conditioner fluid: a cool way to die?

PubMed

Phatak, Darshan R; Walterscheid, Jeffrey

2012-03-01

"Huffing," the form of substance abuse involving inhalants, is growing in popularity because of the ease and availability of chemical inhalants in many household products. The purpose in huffing is to achieve euphoria when the chemicals in question interact with the central nervous system in combination with oxygen displacement. The abuser is lulled into a false sense of safety despite the well-documented potential for lethal cardiac arrhythmia and the effects of chronic inhalant abuse, including multisystem organ failure, and brain damage. Huffing air conditioner fluid is a growing problem given the accessibility to outdoor units and their fluid components, such as difluorochloromethane(chlorodifluoromethane, Freon), and we have classified multiple cases of accidental death due to the toxicity of difluorochloromethane. Given the ubiquity of these devices and the vast lack of gating or security devices, they make an inviting target for inhalant abusers. Acute huffing fatalities have distinct findings that are present at the scene, given the position of the decedent and proximity to the air conditioner unit. The purpose of the autopsy in these cases is to exclude other potential causes of death and to procure specimens for toxicological analysis.

Hypoxia-related brain dysfunction in forensic medicine.

PubMed

Suslo, R; Trnka, J; Siewiera, J; Drobnik, J

2015-01-01

Blood gases levels imbalances belong to important factors triggering central nervous system (CNS) functional disturbances. Hypoxia can be illness-related, like in many COPD patients, or it may be caused by broad range of external or iatrogenic factors - including influence of drugs depressing respiration, failure to keep the patient's prosthesis-supported airways patent, or a mistake in the operation of medical equipment supporting patient's respiration. Hypoxia, especially when it is not accompanied by rapid carbon dioxide retention, can go unnoticed for prolonged times, deepening existing CNS disorders, sometimes rapidly triggering their manifestation, or evoking quite new conditions and symptoms - like anxiety, agitation, aggressive behavior, euphoria, or hallucinations. Those, in turn, often result in situations raising interest in law enforcement institutions which need forensic medicine specialist's assistance and opinion. The possibility of illness or drug-related hypoxia, especially in terminal patients, is used to raise questions about the patients' ability to properly express their will in the way demanded by law - it also must be considered as a factor limiting the patients' responsibility in case they commit crimes. The possibility of hallucinations in hypoxia patients limits their credibility as witnesses or even their ability to report crime or sexual abuse they have been subjected to.

Crystal methamphetamine and ecstasy differ in relation to unsafe sex among young gay men.

PubMed

Schilder, Arn J; Lampinen, Thomas M; Miller, Mary Lou; Hogg, Robert S

2005-01-01

Poly-substance use in gay social ('club') settings is common. Recent studies suggest a link between 'club' drug use and sexual risk behaviours. In this qualitative study, we compare and contrast two 'club' drugs: crystal methamphetamine and ecstasy (MDMA). Life history interviews were conducted with 12 HIV seroconverters and 12 age-matched controls recruited from a prospective cohort study of young gay and bisexual men in Vancouver, British Columbia. Textual data concerning illicit substance use and unsafe sex were analyzed using NUDIST software. Most men related a substantial knowledge of and experience with crystal and ecstasy. Both drugs had attributes that enhanced gay socialization and were used in the same venues. Crystal was used to remain awake and increase energy. Ecstasy was used to induce euphoria and group connectedness. However, unlike ecstasy, crystal was associated with a distinct pattern of sexual arousal that frequently included unprotected (sometimes group) sex, was more likely to be used regularly by HIV-positive men, and was reportedly highly addictive and problematic. Crystal and ecstasy are used in the same social venues but differ markedly in relation to sexual risk behaviour.

Gas sniffing as a form of substance abuse.

PubMed

Remington, G; Hoffman, B F

1984-02-01

The authors review the existing literature on inhalation of gasoline fumes, highlighting the acute and chronic physical and psychological effects. The clinical picture of gas sniffing includes visual hallucinations, changes in consciousness, euphoria, nystagmus, dizziness, weakness and tremors. There is the possibility of rapid recovery, sudden death or brain damage with chronic abuse. When leaded gasoline is abused then blood and urine lead levels and erythrocytic delta-aminolevulinic acid dehydrase (ALAD) levels may be helpful. Although the treatment of acute and chronic gas sniffing syndromes is often supportive and non-specific, when lead levels are high chelated therapy is indicated including British anti-lewisite, calcium disodium versenate or D-penicillamine. We also report our findings on an isolated native Indian population where intentional gas sniffing has reached epidemic proportions. Ten percent of the total population and 25% of the children between 5 and 15 years of age had been identified as gasoline inhalation abusers. In this population, the most important etiological factors included environmental, family and cultural components. The authors emphasize the need to correct the family and social deficiencies in such communities if the incidence of gas sniffing is to be decreased.

Looking on the east: Transformation of the sleeping colossus

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

Khazanet, V.L.

1995-06-01

The initial wave of euphoria that followed the collapse of the Soviet Union has given way to the mixed blessings of a transitional period. Changing from a managed economy to a market economy is a difficult process. To understand why the transitional period is so difficult, the influence of more than 70 years of communist education, mentality, and lifestyle has to be taken into account. The results of the past are deeply felt by each ex-Soviet citizen, and the still-powerful old influences can slow down market development. The business environment is changing incredibly fast; the possibility of US construction companiesmore » working in the Former Soviet States (FSS) was unthinkable only a few years ago. Foreign companies may find it hard to do business in the FSS due to their limited knowledge of how the construction industry works there. Differences in the business mentality and in the decision-making process must be understood. To avoid failure and to successfully implement construction projects in the FSS, investors must be familiar with the history of the Soviet construction industry, its current status, and its likely future. 2 figs.« less

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.

Bipolar Disorder and Heart Transplantation: A Case Report.

PubMed

Ramírez-Giraldo, Ana María; Restrepo, Diana

Bipolar disorder is a chronic and recurrent mood disease that includes symptoms that fluctuate from euphoria to depression. As a mood disorder, itis one of the main contraindications for transplantation procedures. The case is presented of a patient with bipolar disorder who had a heart transplant after a cardiac arrest. Heart transplantation is the treatment of choice in patients with heart failure and arrhythmias that do not respond to conventional treatment. Case report and narrative review of literature. A 34-year-old woman with bipolar disorder diagnosed when she was 13, treated with lithium and aripiprazole. She required a heart transplant as the only therapeutic option, after presenting with ventricular tachycardia refractory to conventional treatment. The patient did not suffer an emotional decompensation with the removal of the lithium and aripiprazole that were associated with prolonged QTc interval, and remained eurhythmic throughout the process. Heart transplantation can be performed safely and successfully in patients with bipolar disorder, when suitably followed-up by a liaison psychiatry group. Bipolar disorder should not be considered as an absolute contraindication for heart transplantation. Copyright © 2017 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

[Methaemoglobinaemia and respiratory tract irritation connected with poppers inhalation].

PubMed

Łukasik-Głebocka, Magdalena; Matuszkiewicz, Eryk

2010-01-01

"Poppers" is the street name for volatile nitrites offered by online shops and sex-shops for their aphrodisiac and euphoric properties. Although nitrites have been abused since the late 1960s, recently they became popular in Poland. Recreational poppers using was associated with homosexual men at first. Currently they are commonly reported among heterosexual men and regular dicso participants. Advertisements of these substances tempt potential buyers with the promise of a legal narcotic high. Easy access and the sense of safety make these products the reason of acute toxicity. Volatile nitrites relaxes smooth muscle, the consequent intense peripheral vasodilatation produces flushing, a fall in blood pressure, and reflex increase in heart rate. These effects are accompanied by feeling of warmth, euphoria and intensifying of sexual pleasure. Serious poisoning results in severe methaemoglobinaemia, coma, respiratory and cardiovascular failure, and even death. Skin and mucous contact with poppers can produce a crusty lesion at the site. This article presents the case of 44-years old male hospitalized three times in Toxicology Department after history of poppers abusing. Methaemoglobinaemia (26.4%) and tracheobronchial irritation were the main symptoms observed. Patient was given specific therapy with methylene blue.

Abuse potential and psychoactive effects of δ-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine.

PubMed

Robson, Philip

2011-09-01

There is a growing consensus that cannabis dependence is a substantial and underappreciated problem. The key component responsible for the euphoric effects of cannabis and its dependence potential is δ-9-tetrahydrocannabinol (THC). THC-containing cannabinoid medicines theoretically pose a risk of abuse and dependence. In order to evaluate the potential of Sativex to cause cannabis-like psychoactivity, abuse or dependence relevant data from all published papers have been reviewed along with the integrated safety analysis for Sativex use in multiple sclerosis (MS) patients on file at GW Pharmaceuticals. In clinical trials, intoxication scores have been low and euphoria reported by only 2.2% of patients. Tolerance has not occurred, abrupt withdrawal has not resulted in a formal withdrawal syndrome, and no cases of abuse or diversion have been reported to date. A formal abuse liability study of Sativex in experienced cannabis smokers showed some abuse potential in comparison with placebo at higher doses, but scores were consistently lower than equivalent doses of THC. Evidence to date suggests that abuse or dependence on Sativex is likely to occur in only a very small proportion of recipients.

A Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans

PubMed Central

Nahler, Gerhard; Grotenhermen, Franjo; Zuardi, Antonio Waldo; Crippa, José A.S.

2017-01-01

Abstract Cannabidiol (CBD), a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. Under acidic conditions, CBD can be transformed to delta9-tetrahydrocannabinol (THC) and other cannabinoids. It has been argued that this may occur also after oral administration in humans. However, the experimental conversion of CBD to THC and delta8-THC in simulated gastric fluid (SGF) is a highly artificial approach that deviates significantly from physiological conditions in the stomach; therefore, SGF does not allow an extrapolation to in vivo conditions. Unsurprisingly, the conversion of oral CBD to THC and its metabolites has not been observed to occur in vivo, even after high doses of oral CBD. In addition, the typical spectrum of side effects of THC, or of the very similar synthetic cannabinoid nabilone, as listed in the official Summary of Product Characteristics (e.g., dizziness, euphoria/high, thinking abnormal/concentration difficulties, nausea, tachycardia) has not been observed after treatment with CBD in double-blind, randomized, controlled clinical trials. In conclusion, the conversion of CBD to THC in SGF seems to be an in vitro artifact. PMID:28861507

Intersaccadic drift velocity is sensitive to short-term hypobaric hypoxia.

PubMed

Di Stasi, Leandro L; Cabestrero, Raúl; McCamy, Michael B; Ríos, Francisco; Catena, Andrés; Quirós, Pilar; Lopez, Jose A; Saez, Carolina; Macknik, Stephen L; Martinez-Conde, Susana

2014-04-01

Hypoxia, defined as decreased availability of oxygen in the body's tissues, can lead to dyspnea, rapid pulse, syncope, visual dysfunction, mental disturbances such as delirium or euphoria, and even death. It is considered to be one of the most serious hazards during flight. Thus, early and objective detection of the physiological effects of hypoxia is critical to prevent catastrophes in civil and military aviation. The few studies that have addressed the effects of hypoxia on objective oculomotor metrics have had inconsistent results, however. Thus, the question of whether hypoxia modulates eye movement behavior remains open. Here we examined the effects of short-term hypobaric hypoxia on the velocity of saccadic eye movements and intersaccadic drift of Spanish Air Force pilots and flight engineers, compared with a control group that did not experience hypoxia. Saccadic velocity decreased with time-on-duty in both groups, in correlation with subjective fatigue. Intersaccadic drift velocity increased in the hypoxia group only, suggesting that acute hypoxia diminishes eye stability, independently of fatigue. Our results suggest that intersaccadic drift velocity could serve as a biomarker of acute hypoxia. These findings may also contribute to our understanding of the relationship between hypoxia episodes and central nervous system impairments.

An integrated telemedicine platform for the assessment of affective physiological states

PubMed Central

Katsis, Christos D; Ganiatsas, George; Fotiadis, Dimitrios I

2006-01-01

AUBADE is an integrated platform built for the affective assessment of individuals. The system performs evaluation of the emotional state by classifying vectors of features extracted from: facial Electromyogram, Respiration, Electrodermal Activity and Electrocardiogram. The AUBADE system consists of: (a) a multisensorial wearable, (b) a data acquisition and wireless communication module, (c) a feature extraction module, (d) a 3D facial animation module which is used for the projection of the obtained data through a generic 3D face model; whereas the end-user will be able to view the facial expression of the subject in real time, (e) an intelligent emotion recognition module, and (f) the AUBADE databases where the acquired signals along with the subject's animation videos are saved. The system is designed to be applied to human subjects operating under extreme stress conditions, in particular car racing drivers, and also to patients suffering from neurological and psychological disorders. AUBADE's classification accuracy into five predefined emotional classes (high stress, low stress, disappointment, euphoria and neutral face) is 86.0%. The pilot system applications and components are being tested and evaluated on Maserati's car. racing drivers. PMID:16879757

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.

Mood state dependency of dysfunctional attitudes in bipolar affective disorder.

PubMed

Babakhani, Anet; Startup, Mike

2012-01-01

Studies of cognitive styles among euthymic people with bipolar affective disorder (BAD) without use of mood induction techniques to access those cognitive styles give misleading impressions of normality of those cognitions. The aim of this study was to assess dysfunctional attitudes of participants with BAD, and control participants with no previous psychiatric histories, after mood inductions. Sad and happy moods were induced within 49 BAD and 37 controls. Dysfunctional attitudes were measured following mood inductions using the Dysfunctional Attitude Scale-short form (DAS-24), which has three subscales of achievement, interpersonal, and goal attainment. It was hypothesised that within BAD the sad mood induction would help in accessing dysfunctional attitudes in all three domains relative to the happy mood induction. This was supported. It was also hypothesised that the mood inductions would not affect dysfunctional attitudes within controls. This was supported. When diagnosis was entered as a between group variable, achievement dysfunctional attitudes were significantly higher in BAD compared to controls after a happy induction. Both sad and happy moods provoked higher levels of dysfunctional attitudes within BAD. Euphoria may be related to elevated achievement dysfunctional attitudes, raising risk for mania.

A study investigating the association between compulsive buying with measures of anxiety and obsessive-compulsive behavior among internet shoppers.

PubMed

Weinstein, A; Mezig, Hila; Mizrachi, S; Lejoyeux, M

2015-02-01

Compulsive buying is a chronic, repetitive behavior that becomes a primary response to negative events and feelings. Compulsive buyers are obsessed by buying and their behavior occurs in response to negative emotions and results in a decrease in the intensity of negative emotions. Euphoria or relief from negative emotions is the most common consequence of compulsive buying. A large number of studies have investigated the association between compulsive buying and anxiety, and some studies have used the Spielberger trait-state anxiety inventory. Compulsive buying, state and trait anxiety and general obsessive-compulsive measures were assessed among 120 habitual internet shoppers (2+ times a week, 70 men and 50 women). Results showed that Edwards Compulsive Buying scale measures were associated with Spielberger trait and not state anxiety measures. Spielberger Trait anxiety measures were also correlated with measures of Yale-Brown Obsessive-Compulsive scale (Y-Bocs). Finally, there were no sex differences in this sample. The results of this study support existing evidence for an association between compulsive buying and anxiety and they will be discussed in view of current research on comorbidity of behavioural addiction. Copyright © 2014 Elsevier Inc. All rights reserved.

Affective disorders and functional (non-epileptic) seizures in persons with epilepsy.

PubMed

Johnson, Keith A; Macfarlane, Matthew D; Looi, Jeffrey Cl

2016-12-01

This paper aims to describe the prevalence, assessment and management of affective disorders as well as functional (non-epileptic) seizures in people with epilepsy. This paper comprises a selective review of the literature of the common affective manifestations of epilepsy. Affective disorders are the most common psychiatric comorbidity seen in people with epilepsy and assessment and management parallels that of the general population. Additionally, people with epilepsy may experience higher rates of mood instability, irritability and euphoria, classified together as a group, interictal dysphoric disorder and resembling an unstable bipolar Type II disorder. Functional seizures present unique challenges in terms of identification of the disorder and a lack of specific management. Given their high prevalence, it is important to be able to recognise affective disorders in people with epilepsy. Management principles parallel those in the general population with specific caution exercised regarding the potential interactions between antidepressant medications and antiepileptic drugs. Functional seizures are more complex and require a coordinated approach involving neurologists, psychiatrists, general practitioners, nursing and allied health. There is very limited evidence to guide psychological and behavioural interventions for neurotic disorders in epilepsy and much more research is needed. © The Royal Australian and New Zealand College of Psychiatrists 2016.

Patterns of Use, Acute Subjective Experiences, and Motivations for Using Synthetic Cathinones ("Bath Salts") in Recreational Users.

PubMed

Ashrafioun, Lisham; Bonadio, Francis A; Baik, Kyoung Deok; Bradbury, Stacey L; Carhart, Victoria L; Cross, Nicole A; Davis, Alan K; Feuille, Margaret; Harper, Anna R; Lackey, Jennifer H; Lang, Brent; Lauritsen, Kirstin J; Leith, Jaclyn; Osborn, Lawrence A; Rosenberg, Harold; Stock, Jacob; Zaturenskaya, Mariya

2016-01-01

Given the variety and potential toxicity of synthetic cathinones, clinicians and educators would benefit from information about patterns of and motivations for use, frequency of psychosocial consequences, and experience of acute subjective effects. We administered a comprehensive, web-based survey to 104 recreational users of synthetic cathinones. Sixty percent of respondents consumed synthetic cathinones once or more per month, usually snorting or swallowing these drugs, typically at home, usually with others, customarily during the evening and nighttime hours, and often in combination with another drug such as alcohol or marijuana. Acute subjective effects attributed to synthetic cathinones were similar to those of other psychostimulants, including increased energy, rapid heartbeat, racing thoughts, difficulty sleeping, euphoria, decreased appetite, open-mindedness, and increased sex drive. Reported reasons for using synthetic cathinones included its stimulating effects, curiosity, substitution for another drug, and being at a party/music event. Respondents had experienced an average of six negative consequences of using synthetic cathinones during the previous year (e.g., tolerance, neglecting responsibilities, personality change). In combination with previously published investigations, these findings increase our understanding of the reported rationales and outcomes of recreational use of synthetic cathinones.

German suffering in the Franco–German War, 1870/71.

PubMed

Krüger, Christine G

2011-01-01

Suffering during the Franco–Prussian War of 1870/71 has to be interpreted in the context of three developments: the willingness to alleviate wartime suffering, which had led to the foundation of the International Red Cross and the Geneva Convention a few years earlier, the industrialization of war, which had enormously increased the efficiency of the weaponry, and the nationalization of war. For many Germans, the outcome of the war justified the wartime suffering, which was often trivialized in the media. The small number of authors who saw the high casualty numbers and the pain of the victims as a warning about the consequences of modern warfare usually belonged to the anti-Prussian opposition. Nationalist euphoria in the face of victory and German unification drowned out such critics, whose patriotism was in doubt. Finally, the remembrance of the war during the Kaiserreich aimed largely at celebrating the triumph of the German army and the foundation of the national state. The glorification of the military was hardly compatible with a detailed description of the misery of the battlefield and the pain of war victims. In 1870/71 and in the subsequent decades, nationalism overwhelmed and eventually excluded a humanitarian narrative.

Cannabis Use, Lung Cancer, and Related Issues.

PubMed

Jett, James; Stone, Emily; Warren, Graham; Cummings, K Michael

2018-04-01

The cannabis plant and its derivatives have been exploited for centuries for recreational and medicinal purposes, with millions of regular users around the world. The recreational use of cannabis is reflective of its neuropsychiatric effects, such as anxiolysis and euphoria. However, cannabis appears to have an emerging therapeutic role, especially in chronic disease and as an adjunct to cancer treatment. Increasing evidence supports cannabis in the management of chemotherapy-induced nausea and vomiting (CINV) and for pain management; however, studies are limited, particularly by difficulties associated with standardized dosing estimates and inability to accurately assess biologic activities of compounds in cannabis and derivative products. Smoking cannabis has not been proved to be a risk factor in the development of lung cancer, but the data are limited by small studies, misclassification due to self-reporting of use, small numbers of heavy cannabis smokers, and confounding of the risk associated with known causative agents for lung cancer (such as parallel chronic tobacco use). Cannabis and its biologically effective derivatives warrant additional research, ideally, controlled trials in which the cannabidiol and the delta-9-tetrahydrocabinol strength and use are controlled and documented. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

A Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans.

PubMed

Nahler, Gerhard; Grotenhermen, Franjo; Zuardi, Antonio Waldo; Crippa, José A S

2017-01-01

Cannabidiol (CBD), a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. Under acidic conditions, CBD can be transformed to delta9-tetrahydrocannabinol (THC) and other cannabinoids. It has been argued that this may occur also after oral administration in humans. However, the experimental conversion of CBD to THC and delta8-THC in simulated gastric fluid (SGF) is a highly artificial approach that deviates significantly from physiological conditions in the stomach; therefore, SGF does not allow an extrapolation to in vivo conditions. Unsurprisingly, the conversion of oral CBD to THC and its metabolites has not been observed to occur in vivo , even after high doses of oral CBD. In addition, the typical spectrum of side effects of THC, or of the very similar synthetic cannabinoid nabilone, as listed in the official Summary of Product Characteristics (e.g., dizziness, euphoria/high, thinking abnormal/concentration difficulties, nausea, tachycardia) has not been observed after treatment with CBD in double-blind, randomized, controlled clinical trials. In conclusion, the conversion of CBD to THC in SGF seems to be an in vitro artifact.

AEC to Referee, Not Promote, Industry.

PubMed

1971-10-29

A major turnabout in the attitude of the Atomic Energy Commission toward the nuclear power industry was signaled last week by the ntew AEC chairman James R. Schlesinger. With patrician froideur, Schlesinger informed a mass gathering of the nuclear power industry at Bal Harbour, Florida, that from henceforth the AEC woLuld act as the referee of nuclear power, not its promoter. Saying he would dispense with the "anecdotes and clumsy jests" customary on such occasions, Schlesinger served notice on the nuclear banqueters that their cozy relationship with the AEC was at an end. The industry should not expect the AEC to fight its battles: it should take its own case to the public-as the Sierra Club does. Nor did the AEC intend to bend the rules in industry's favor. "We have had a fair amount of advice on how to evade the clear mandate of the federal courts. It is advice we did not think proper to accept," Schlesinger said. Even on matters of engineering quality, the diners were told they knew full well they had "reason to blush." Roused out of any postprandial euphoria by this glacial disdain, the industry representatives heard the new chairman announce the following radical upheavals in official AEC philosophy.

Neuro-chemical activation of brain reward meso-limbic circuitry is associated with relapse prevention and drug hunger: a hypothesis.

PubMed

Blum, Kenneth; Gold, Mark S

2011-04-01

It is no surprise that it has taken over four decades to confirm and extend the crucial role of dopamine and related genes and gene deficits in the etiology of risk for drug dependence. Hundreds of studies, enabled by neuroscience neuroimaging and genetic advances, have been reported. While dopamine theories have been reported, confirmed, replicated and replicated again, changes have been slow to move from the bench to the bedside. Unlike penicillin used to target certain infections, addiction requires the consent, motivation and enthusiastic participation of the patient. Clearly, current treatment has not caught up with advances in the science. In-patient and out-patient treatment still relies on detoxification, abstinence and 12 step programs. Addiction is a chronic and relapsing disease. Addiction treatment can be reported as cures at 3 or 6 weeks, only to be clearly failures at 1 or 5 years. The logical standard of care should focus on detoxifying, stabilizing and returning the patient to the pre-loss of control or pre-addiction neurochemical state. Pre-clinical and clinical data on neurochemistry and neurogenetics of Substance Use Disorder (SUD) as it relates to both relapse and drug hunger has been reviewed. We are proposing herein that efforts to physiologically integrate known neural mechanisms with other psychotherapeutic treatment options to combat relapse should be encouraged. It is well known that after prolonged abstinence, recovered addicts are particularly vulnerable to relapse. Individuals who use their drug of choice after abstinence experience a powerful euphoria that can quickly precipitate a full-blown relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed "supersensitivity" might be the result of pre-morbid or state genetic hypodopaminergic polymorphisms. We are proposing that recent studies have indicated that genetic, personality and environmental factors are predictors of drug use in adolescents. Exploration of various treatment approaches for the most part reveal poor outcomes in terms of relapse prevention and continued drug hunger. The authors are proposing a new paradigm shift in residential, non-residential and aftercare involving the incorporation of genetic testing to identify risk alleles coupled with D2 receptor stimulation using neuroadatogen amino acid precursor enkephlinase--catecholamine-methyltransferase (COMT) inhibition therapy. A natural but therapeutic nutraceutical formulation potentially induces DA release could cause the induction of D2-directed mRNA and proliferation of D2 receptors in the human. We further hypothesize that this proliferation of D2 receptors in turn will induce the attenuation of drug-like craving behavior. Finally, pharmacological therapies have had limited success because these powerful agents have focused on maintenance or interference with drug euphoria rather than correcting or compensating for pre-morbid dopamine system deficits These concepts await further confirmation via required neuro-imaging studies. Copyright © 2011. Published by Elsevier Ltd.

Detecting leafy spurge in native grassland using hyperspectral image analysis

NASA Astrophysics Data System (ADS)

Kloppenburg, Catherine

Leafy spurge (Euphoria esula L.) is a perennial noxious weed that has been encroaches on the native grassland regions of North America resulting in biological and economic impacts. Leafy spurge growth is most prevalent along river banks and in pasture areas. Due to poor accessibility and the cost and labour associated with data collection, estimates of number and size of leafy spurge infestations is poor. Remote sensing has the ability to cover large areas, providing an alternate means to ground surveys and will allow for the capability to create an accurate baseline of infestations. Airborne hyperspectral data were collected over the two test sites selected on the Blood Reserve in Southern Alberta using a combined Airborne Imaging Spectrometer for different Applications (AISA) Eagle and Hawk sensor systems in July, 2010. This study used advanced analysis tools, including spectral mixture analysis, spectral angle mapper and mixture-tuned matched filter techniques to evaluate the ability to detect leafy spurge patches. The results show that patches of leafy spurge with flowering stem density >40 stems m-2 were identified with 85 % accuracy while identification of lower density stems were less accurate (10 - 40 %). The results are promising with respect to quantifying areas of significant leafy spurge infestation and targeting biological control and potential insect release sites.

Confidence in Airline Performance in Difficult Market Conditions: An Analysis of JetBlue's Financial Market Results

NASA Technical Reports Server (NTRS)

Flouris, Triant; Walker, Thomas

2005-01-01

This paper examines the stock market s reaction to JetBlue s Initial Public Offering (1PO) and subsequent price movements of the stock. In particular, w e examine whether the euphoria surrounding JetBlue s IPO carried over to other firms in the sector by testing whether the shares of JetBlue s competitors showed a significant price reaction to JetBlue s IPO. JetBlue's IPO took place just a few months following September 11, 2001. These events resulted in dramatic changes in the airline industry and had significant implications on the economic gains of airlines. We examine JetBlue s accounting and stock performance and compare it to the relative performance of Southwest Airlines (SWA), a representative of the loa-cost carrier group. In addition, we compare both JetBlue's and SWA's financial condition and the relative performance of their stock to two mainline U S. carriers, Continental and Northwest. representatives of the conventional-cost carrier group. We analyze whether there are any performance differences among the low-cost carriers and between low-cost carriers and conventional-cost carriers. In particular, we examine whether low-cost carriers were able to sustain the economic impacts of 9/11 better than the conventional-cost carriers.

Perception of emotional climate in a revolution: Test of a multistage theory of revolution in the Tunisian context.

PubMed

Rimé, Bernard; Yzerbyt, Vincent; Mahjoub, Abdelwahab

2017-12-01

Participation in social movements and collective action depends upon people's capacity to perceive their societal context. We examined this question in the context of Arab Spring revolutions. In a classic theory of revolution highlighting the role of collective emotions, Brinton (1938) claimed that revolutions, far from chaos, proceed in an orderly sequence involving four stages: euphoria, degradation, terror, and restoration. The emotional climate (EC) as perceived by ordinary Tunisian citizens (2,699 women and 3,816 men) was measured during the 4 years of the Tunisian revolution. A quadratic pattern of perceived EC measures over time provided strong support to Brinton's model. In addition, three different analyses suggested the presence of four distinct stages in the evolution of perceived EC. Third, the socio-political developments in Tunisia during the four stages proved entirely consistent with both Brinton's theoretical model and the perceived EC indicators. Finally, social identification proved closely related to the temporal evolution of positive EC scores. In sum, data from this study not only lend support to the views put forth in an heretofore untested classic theory of revolution but also demonstrate that psychosocial measurements can validly monitor a major process of socio-political transformation. © 2017 The British Psychological Society.

The toxicology of cannabis and cannabis prohibition.

PubMed

Grotenhermen, Franjo

2007-08-01

The acute side effects caused by cannabis use are mainly related to psyche and cognition, and to circulation. Euphoria, anxiety, changes in sensory perception, impairment of memory and psychomotor performance are common effects after a dose is taken that exceeds an individually variable threshold. Cannabis consumption may increase heart rate and change blood pressure, which may have serious consequences in people with heart disease. Effects of chronic use may be induction of psychosis and development of dependency to the drug. Effects on cognitive abilities seem to be reversible after abstinence, except possibly in very heavy users. Cannabis exposure in utero may have negative consequences on brain development with subtle impairment of cognitive abilities in later life. Consequences of cannabis smoking may be similar to those of tobacco smoking and should be avoided. Use by young people has more detrimental effects than use by adults. There appear to be promising therapeutic uses of cannabis for a range of indications. Use of moderate doses in a therapeutic context is usually not associated with severe side effects. Current prohibition on cannabis use may also have harmful side effects for the individual and the society, while having little influence on prevalence of use. Harm is greatest for seriously ill people who may benefit from a treatment with cannabis. This makes it difficult to justify criminal penalties against patients.

The medicalisation of revolt: a sociological analysis of medical cannabis users.

PubMed

Pedersen, Willy; Sandberg, Sveinung

2013-01-01

In a qualitative study, we investigated the medical motives of 100 Norwegian cannabis users, none of whom had legal access to medical cannabis. Cannabis was used therapeutically for conditions such as multiple sclerosis, attention deficit hyperactivity disorder and rheumatism, as well as for quality of life conditions such as quality of sleep, relaxation and wellbeing. The borders between medical and recreational cannabis use were blurred. This article identifies strategies of medical cannabis users to gain social acceptance. Several respondents downplayed effects such as intoxication and euphoria. Others used the language of medicine and knowledge of current research in psychopharmacology. Cannabis was contrasted with the potential for abuse of prescription medicines. The medical cannabis movement has had little success in Norway. Medical professionals are unable to accept that users may be more knowledgeable than experts and medical users cannot discard the values of traditional cannabis culture. Calls for medical cannabis use are thus perceived as a gambit in attempts to have cannabis legalised. We argue that, despite having had little effect on health authorities, the medical cannabis movement may be having the unintended effect of medicalising cannabis use and using it as a cure for everyday problems. © 2012 The Authors. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

A Prospective Observation Study of Medical Toxicology Consultation in a U.S. Combat Theater.

PubMed

Maddry, Joseph K; Ng, Patrick C; Sessions, Daniel; Bebarta, Vikhyat S

2016-11-01

Since 2001, U.S. military personnel and active duty, uniformed physicians providing medical support have been deployed to Afghanistan. Medical toxicologists are among the physicians deployed. There is a paucity of information present in the literature that has documented cases treated by toxicologists in theater. This prospective observational study describes 15 male patients treated in theater by a military medical toxicologist. We performed a prospective observational study in which a medical toxicologist consulted and reported on deployed toxicology cases occurring during a 5-month deployment to Bagram, Afghanistan. Fifteen toxicology cases were collected during the 5-month period. The patients included three Afghan civilians, three U.S. civilians, and nine U.S. military personnel. Eight cases were attempts at recreational euphoria, two were self-harm attempts, two were from performance-enhancing supplements, two were accidental occupational exposures and one was alcohol withdrawal. Methanol was the most common exposure followed by dextromethorphan, supplements, opiates, and chlorine gas. In our study, we found that toxic alcohols and nonprescription medications were the most common exposures. In addition, this is the first study to describe bedside toxicology consults for U.S. combat forces in theater and the use of an observation unit for critically ill patients. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Psychological and sociocultural adjustment of first-year international students: Trajectories and predictors.

PubMed

Hirai, Reiko; Frazier, Patricia; Syed, Moin

2015-07-01

Despite the increasing number of international students in U.S. universities, the temporal course of international students' adjustment has not been adequately tested, and only 1 study to date has examined multiple trajectories of adjustment. Therefore, the first goal of the current study was to explore multiple trajectories of adjustment among first-year international students using a broader range of adjustment measures (i.e., psychological distress, positive psychological adjustment, sociocultural adjustment). The second goal was to identify important predictors of trajectories. A wide range of individual and interpersonal predictor variables was examined, including academic stress and perceived control over academic stress, personality, social relationships, and language-related factors. Undergraduate and graduate international students in their first semester at a large midwestern university participated in this 5-wave longitudinal study (N = 248) that spanned 1 academic year. Multiple trajectories emerged, and the trajectories varied across the 3 adjustment measures. Average trajectories masked the trajectories of small groups of students who maintained or increased in terms of adjustment difficulties across outcomes. Contrary to popular theories, the U-shape adjustment trajectory (characterized by initial euphoria, distress, and then recovery) did not emerge. The most consistent predictors of adjustment trajectories were perceived present control over academic stress and Neuroticism. (c) 2015 APA, all rights reserved).

The comparative analysis of the forecasts of development of rocket propulsion in past and now

NASA Astrophysics Data System (ADS)

Nedaivoda, A.; Prisniakov, V.

2001-03-01

Consideration is being given to use the known long and short forecasts of development of rocket engines in past - at the beginning of development of a missile engineering (K. Tsiolkovsky etc. pioneers of rocket propulsion); on the eve of launching of the artificial satellite of Earth (A. Blagonravov); after manned flight of Yu. Gagarin (V. Gluchko); after manned flight on Moon (" The Forecasts on 2001 " on materials of readings R. Goddard in USA); in middle of 70-s' years (D. Sevruk, V. Prisniakov) and at the end of 20 centure. Last years under the initiative R. Beichel and M. Pouliquen IAA. Advanced Propulsion Working Group carries out large researches on definition of the tendencies of development of rocket propulsion for the next forty years, the outcomes which one will be used in the report. The comparison of development of rocket propulsion expected to the end of 20 century and real-life is given. The report analyses the errors of the forecasts of the past - the absence reliable prognostic procedure; the euphoria of the maiden successes of conquest of space; dominance of military and political- propaganda motives of implementation of the space programs before economical; to keep developments secret; competition of two super-powers USSR and USA etc.

Winning and losing: an evolutionary approach to mood disorders and their therapy.

PubMed

Sloman, Leon; Sturman, Edward D; Price, John S

2011-06-01

To advance a new evolutionary model that examines the effects of winning and losing on mood and physiological variables. Previous studies have focused on the involuntary defeat strategy in de-escalating conflict. Here, we propose that there also exists an involuntary winning strategy (IWS) that is triggered by success and characterized by euphoria and increased self-confidence. It motivates efforts to challenge, and promotes reconciliation. Previous studies are presented, including data on student athletes, demonstrating the impact of winning and losing on mood. Winning is consistently shown to be related to physiological changes such as increased testosterone and serotonin levels in primates. It reliably leads to mood changes that serve to motivate winners to continue their competitive efforts. When the IWS functions optimally, success leads to success in an adaptive cycle. Over time, the initial differences between the winners and losers of agonistic encounters become magnified in a process known as difference amplification. As a result of assortative mating, the children of people who have entered into an adaptive cycle will inherit traits from both parents that will, in turn, give them an increased competitive advantage. In this manner, difference amplification could have accelerated human evolution by natural selection. Vignettes of clinical interventions are also used to illustrate therapeutic strategies designed to disrupt maladaptive cycles and promote adaptive behaviour.

Symptoms of anxiety and depression in childhood and use of MDMA: prospective, population based study.

PubMed

Huizink, Anja C; Ferdinand, Robert F; van der Ende, Jan; Verhulst, Frank C

2006-04-08

To investigate whether using ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is preceded by symptoms of behavioural and emotional problems in childhood and early adolescence. Prospective, longitudinal, population based study The Dutch province of Zuid-Holland. A sample of 1580 individuals, followed up across a 14 year period, from childhood into adulthood. The first assessment took place in 1983 before MDMA appeared as a recreational drug in the Netherlands and included the child behaviour checklist to obtain standardised parents' reports of their children's behavioural and emotional problems. Use of the drug was assessed with the composite international diagnostic interview 14 years later. Eight syndrome scales of childhood behaviour were examined. Scores in the deviant range for the scales designated as anxious or depressed in childhood were significantly related to use of MDMA in adolescents and adults, resulting in an increased risk (hazard ratio 2.22, 95% confidence interval 1.20 to 4.11, P = 0.01). Individuals with childhood symptoms of anxiety and depression may have an increased tendency to use MDMA in adolescence or young adulthood. Its effects are supposed to include enhanced feelings of bonding with other people, euphoria, or relaxation. Especially individuals with symptoms of anxiety or depression may be susceptible to these positive effects.

Reward, motivation, and emotion systems associated with early-stage intense romantic love.

PubMed

Aron, Arthur; Fisher, Helen; Mashek, Debra J; Strong, Greg; Li, Haifang; Brown, Lucy L

2005-07-01

Early-stage romantic love can induce euphoria, is a cross-cultural phenomenon, and is possibly a developed form of a mammalian drive to pursue preferred mates. It has an important influence on social behaviors that have reproductive and genetic consequences. To determine which reward and motivation systems may be involved, we used functional magnetic resonance imaging and studied 10 women and 7 men who were intensely "in love" from 1 to 17 mo. Participants alternately viewed a photograph of their beloved and a photograph of a familiar individual, interspersed with a distraction-attention task. Group activation specific to the beloved under the two control conditions occurred in dopamine-rich areas associated with mammalian reward and motivation, namely the right ventral tegmental area and the right postero-dorsal body and medial caudate nucleus. Activation in the left ventral tegmental area was correlated with facial attractiveness scores. Activation in the right anteromedial caudate was correlated with questionnaire scores that quantified intensity of romantic passion. In the left insula-putamen-globus pallidus, activation correlated with trait affect intensity. The results suggest that romantic love uses subcortical reward and motivation systems to focus on a specific individual, that limbic cortical regions process individual emotion factors, and that there is localization heterogeneity for reward functions in the human brain.

[Liver transplantation with living donor : current aspects, perspectives and significance in Germany].

PubMed

Settmacher, U; Bauschke, A; Malessa, C; Scheuerlein, H; Zanow, J; Rauchfuß, F

2013-05-01

More than 20 years ago living donor liver transplantation was introduced into clinical practice. Specifics of this method were developed initially for children and later on for adults particularly in regions where a liver transplantation program using deceased donors was not readily available. The most sensitive aspect of living donation, namely the danger to a healthy relative in order to perform the transplantation is immanent in the system and, thus, it is definitively a secondary option as compared to deceased organ donation. Following worldwide initial euphoria the numbers have markedly decreased in the western world since the start of the new millennium. In Asian countries in particular, much work has been done to optimize the procedure so that the donor safety and the outcome quality for the recipient have been impressively demonstrated in large patient populations. There is still a severe donor organ shortage and the option to allocate an optimal (partial) organ on an individual basis by living donation has given new impact to the discussion about a further rise in the profile of living donations here as well. The new version of the German transplantation legislation implemented in summer 2012 requires a number of conditions with respect to insurance for living donors. The current state and perspectives are presented here.

Health Effects Associated With Exposure to Anesthetic Gas Nitrous Oxide-N2O in Clinical Hospital - Shtip Personel.

PubMed

Eftimova, Bilijana; Sholjakova, Marija; Mirakovski, Dejan; Hadzi-Nikolova, Marija

2017-10-15

To show certain health effects associated with acute and chronic exposure to nitrous oxide of staff of the Department of Anaesthesiology and Intensive Care at the Clinical Hospital in Shtip. A transversal study was conducted, that include 43 health workers (23 - exposed and 20 - unexposed). Personal exposure to nitrous oxide for this group members was assessed through continuous measurement over 8 hours shift within breathing zone of the subjects involved, using handheld electrochemical instrument with datalogging option direct. In order to determine presence of possible health effects associated with acute and chronic exposure to nitrous oxide in ORs and ICUs, a specially designed questionnaire was prepared and distributed to be anonymously filled out, by all the examinees from both examined groups. Data were statistically tested for normality and also quantitative and qualitative assessment was performed. From the results obtained, a significant difference in several health effects between exposed and unexposed groups can be noted, including headaches, dizziness, nausea and vomiting, euphoria and tachycardia. Regarding the excitement, the appearance of depression, the feeling of numbness and tingling of the hands and feet, the differences between the two examined groups were not significant. It can be concluded that chronic exposure to nitrous oxide is associated with the adverse health effects.

[Sigmund Freud and cocaine].

PubMed

Lebzeltern, G

1983-11-11

The basic tenet proposed by J. V. Scheidt states that the narcotic drug, cocaine played a role in the development of psychoanalysis which has been underestimated up to the present day. It is a fact that Freud himself took cocaine (in small doses) for about two years, and that he began his dream interpretation approximately ten years later. Scheidt believes that a long, unconscious conflict related to the cocaine-induced states of euphoria (ten years later) suddenly led to the beginnings of dream interpretation. The question to be answered now is: Why did this happen precisely in 1895? The foundations of psychoanalysis had already been laid, the application of the new method to the treatment of nervous disorders (heart complaints, train phobias, etc.) was certainly obvious. During this self-analysis it became necessary, first of all, to come to terms with the self-reproaches-which lay on the surface and were more accessible to consciousness-related to Freud's cocaine period (Fleischl-Marxow becomes addicted to cocaine, the most terrible night ever experienced, death of this friend, Freud's warning came too late). It was only when Freud has come to terms with this phase of his life that the road to the deepest part, the discovery of the Oedipus complex in the fall of 1897, was cleared.

Chemistry, Pharmacology, and Toxicology of Khat (Catha Edulis Forsk): A Review

PubMed Central

Wabe, Nasir Tajure

2011-01-01

Catha edulis (khat) is a plant grown commonly in the horn of Africa. The leaves of khat are chewed by the people for its stimulant action. Its young buds and tender leaves are chewed to attain a state of euphoria and stimulation. Khat is an evergreen shrub, which is cultivated as a bush or small tree. The leaves have an aromatic odor. The taste is astringent and slightly sweet. The plant is seedless and hardy, growing in a variety of climates and soils. Many different compounds are found in khat including alkaloids, terpenoids, flavonoids, sterols, glycosides, tannins, amino acids, vitamins and minerals. The phenylalkylamines and the cathedulins are the major alkaloids which are structurally related to amphetamine. The major effects of khat include those on the gastro-intestinal system and on the nervous system. Constipation, urine retention and acute cardiovascular effects may be regarded as autonomic (peripheral) nervous system effects; increased alertness, dependence, tolerance and psychiatric symptoms as effects on the central nervous system. The main toxic effects include increased blood pressure, tachycardia, insomnia, anorexia, constipation, general malaise, irritability, migraine and impaired sexual potency in men. Databases such as Pubmed, Medline, Hinary, Google search, Cochrane and Embase were systematically searched for literature on the different aspects of khat to summarize chemistry, pharmacology, toxicology of khat (Catha edulis Forsk). PMID:24494129

Caregiver burden associated with behavioral and psychological symptoms of dementia in elderly people in the local community.

PubMed

Matsumoto, Naomi; Ikeda, Manabu; Fukuhara, Ryuji; Shinagawa, Shunichiro; Ishikawa, Tomohisa; Mori, Takaaki; Toyota, Yasutaka; Matsumoto, Teruhisa; Adachi, Hiroyoshi; Hirono, Nobutsugu; Tanabe, Hirotaka

2007-01-01

Despite many studies about the association between caregiver burden and behavioral and psychological symptoms of dementia (BPSD), there have been no population-based studies to evaluate caregiver burden associated with each BPSD. To evaluate caregiver burden associated with the individual BPSD in elderly people living in the community. The subjects were 67 participants with dementia living with their caregivers (diagnosed in the third Nakayama study): 51 Alzheimer's disease, 5 vascular dementia and 11 other. The Neuropsychiatric Inventory (NPI) and NPI Caregiver Distress Scale (NPI-D) were used to assess subjects' BPSD and related caregiver distress, respectively. In the subjects exhibiting BPSD, aberrant motor behavior had the highest mean NPI score, and depression/dysphoria had the lowest. Agitation/aggression had the highest mean NPI-D score, and euphoria/elation had the lowest. Delusion, agitation/aggression, apathy/indifference, irritability/lability and aberrant motor behavior showed a correlation between the NPI and NPI-D scores. The burden associated with BPSD is different for each symptom and does not always depend on frequency and severity of BPSD. These findings suggest that some symptoms, such as agitation/aggression and irritability/lability, may affect the caregivers significantly, although their frequency and severity are low. Copyright (c) 2007 S. Karger AG, Basel.

Alcoholism: recent advances in epidemiology, biochemistry and genetics.

PubMed

Ginter, E; Simko, V

2009-01-01

Countries traditionally consuming beer and wine have high alcohol consumption as compared to East Asia, where the fact of low alcoholism prevalence can be attributed to a defect in metabolic degradation of ethanol. Dependence on alcohol is multifactorial and is related to a complex interplay of metabolic, genetic, social and environmental factors. Repetitive alcohol ingestion and its resulting dependence is associated with false euphoria triggered by an inhibition of glutamate receptors and other brain neurotransmitters, namely dopamine and serotonine. Genetic polymorphisms of genes encoding the alcohol metabolism enzymes and neurotransmitter signaling molecules in dopamine, gamma aminobutyric acid, opioid and serotonin systems, are involved in individual variations for susceptibility to alcohol dependence. Prominent progress has been achieved toward identification of genes related to alcoholism. Six genes were described on chromosomes 4, 7, 8, 11, 15 and 20, which are known to have influence on neuronal signal transfer and generation of dopamine receptors. It is suggested that such genes carry the risk for alcoholism. In the last years, the role of (GABA) receptors in the development of alcoholism is studied in detail. In future it may be possible to separate the genetic, enzymatic and environmental factors that are responsible for increased vulnerability of some individuals to alcohol abuse (Fig. 2, Tab. 1, Ref. 19). Full Text (Free, PDF) www.bmj.sk.

Effects of ecstasy on cooperative behaviour and perception of trustworthiness: a naturalistic study.

PubMed

Stewart, L H; Ferguson, B; Morgan, C J A; Swaboda, N; Jones, L; Fenton, R; Wall, M B; Curran, H V

2014-11-01

Acute recreational use of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') can promote pro-social effects which may alter interpersonal perceptions. To explore such effects, this study investigated whether acute recreational use of ecstasy was associated with changes in individual perception of trustworthiness of people's faces and co-operative behaviours. An independent group, repeated measures design was used in which 17 ecstasy users were tested on the night of drug use (day 0) and again three days later (day 3); 22 controls were tested on parallel days. On each day, participants rated the trustworthiness of 66 faces, carried out three co-operative behaviour tasks (public good; dictator; ultimatum game) and completed mood self-ratings. Acute ecstasy use was associated with increased face trustworthiness ratings and increased cooperative behaviour on the dictator and ultimatum games; on day 3 there were no group differences on any task. Self-ratings showed the standard acute ecstasy effects (euphoria, energy, jaw clenching) with negative effects (less empathy, compassion, more distrust, hostility) emerging on day 3. Our findings of increased perceived trustworthiness and co-operative behaviours following use of ecstasy suggest that a single dose of the drug enhances aspects of empathy. This may in turn contribute to its popularity as a recreational drug and potentially to its enhancement of the therapeutic alliance in psychotherapy. © The Author(s) 2014.

Neuropsychiatric effects of anabolic steroids in male normal volunteers.

PubMed

Su, T P; Pagliaro, M; Schmidt, P J; Pickar, D; Wolkowitz, O; Rubinow, D R

1993-06-02

To evaluate the acute effects of anabolic steroids on mood and behavior in male normal volunteers. A 2-week, double-blind (subject and rater), fixed-order, placebo-controlled crossover trial of methyltestosterone. An inpatient research unit at the National Institutes of Health. A volunteer sample of 20 men who were medication free, free of medical and psychiatric illness, not involved in athletic training, and had no prior history of anabolic steroid use. A sequential trial for 3 days each of the following four drug conditions: placebo baseline, low-dose methyltestosterone (40 mg/d), high-dose methyltestosterone (240 mg/d), and placebo withdrawal. Mood and behavioral ratings were completed during each drug condition and included both subjective and objective measures. Significant (P < .05) albeit subtle increases in symptom scores were observed during high-dose methyltestosterone administration compared with baseline in positive mood (euphoria, energy, and sexual arousal), negative mood (irritability, mood swings, violent feelings, and hostility), and cognitive impairment (distractibility, forgetfulness, and confusion). An acute manic episode was observed in one of the 20 subjects, representing a 5% incidence, even under these conservative conditions. An additional subject became hypomanic. Baseline characteristics including family psychiatric history or previous drug abuse did not predict symptom changes. This is the first placebo-controlled prospective study demonstrating the adverse and activating mood and behavioral effects of anabolic steroids.

Digital Revolution and Innovative Business Models in Healthcare: Global Trends and Russian Realities.

PubMed

Bereznoy, A V; Saygitov, R T

Digital revolution is one of the major global trends resulting in the unprecedented scale and depth of penetration of information and communication technologies into all sectors of national economy, including healthcare. The development of this trend brought about high expectations related to the improvement of quality of medical assistance, accessibility and economic efficiency of healthcare services. However, euphoria of the first steps of digital revolution is passing now, opening doors to more realistic analysis of opportunities and conditions of realization of the true potential hidden in the digital transformation of healthcare. More balanced perception of the peculiarities of innovation processes in the sector is coming together with understanding of the serious barriers, hampering implementation of the new ideas and practices due to complicated interweaving of social, economic, ethical and psychological factors. When taking into account the industry specifics it becomes evident that digital revolution cannot be a quick turnaround but rather would pass a number of phases and is likely to last more than one decade. In this context the article focuses on the prospects of the new business models, capable of making significant changes in today’s economic landscape of the sector (including uber-medicine, retail clinics, retainer medicine, network models of medical services). The authors also provide assessment of the current situation and perspectives of digital healthcare development in Russia.

Nabilone for the Management of Pain.

PubMed

Tsang, Corey C; Giudice, Mirella G

2016-03-01

Nabilone, a synthetic cannabinoid, is approved in many countries including, but not limited to, Canada, the United States, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy. Clinical evidence is emerging for its use in managing pain conditions with different etiologies. We review the efficacy and safety of nabilone for various types of pain as well as its abuse potential, precautions and contraindications, and drug interactions; summarize pertinent clinical practice guidelines; and provide recommendations for dosing, monitoring, and patient education. Citations involving nabilone were identified through systematic reviews evaluating cannabinoids for pain. A systematic search (updated July 23, 2015) of the Ovid MEDLINE, EMBASE, PubMed, and Cochrane Library databases was performed. Eight randomized controlled trials, two prospective cohort trials, and one retrospective chart review were retrieved. Cancer pain, chronic noncancer pain, neuropathic pain, fibromyalgia, and pain associated with spasticity were the pain conditions evaluated. Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain. The most common adverse drug reactions included euphoria, drowsiness, and dizziness. Nabilone was rarely associated with severe adverse drug reactions requiring drug discontinuation, and the likelihood of abuse was thought to be low. Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third-line agent. © 2016 Pharmacotherapy Publications, Inc.

Immunotherapy for the treatment of drug abuse.

PubMed

Kosten, Thomas; Owens, S Michael

2005-10-01

Antibody therapy (as either active or passive immunization) is designed primarily to prevent drugs of abuse from entering the central nervous system (CNS). Antidrug antibodies reduce rush, euphoria, and drug distribution to the brain at doses that exceed the apparent binding capacity of the antibody. This is accomplished through a pharmacokinetic antagonism, which reduces the amount of drug in the brain, the rate of clearance across the blood-brain barrier, and the volume of drug distribution. Because the antibodies remain primarily in the circulatory system, they have no apparent central nervous system side effects. Active immunization with drug-protein conjugate vaccines has been tested for cocaine, heroin, methamphetamine, and nicotine in animal, with 1 cocaine and 3 nicotine vaccines in Phase 2 human trials. Passive immunization with high affinity monoclonal antibodies has been tested for cocaine, methamphetamine, nicotine, and phencyclidine (PCP) in preclinical animal models. Antibodies have 2 immediate clinical applications in drug abuse treatment: to treat drug overdose and to reduce relapse to drug use in addicted patients. The specificity of the therapies, the lack of addiction liability, minimal side effects, and long-lasting protection against drug use offer major therapeutic benefit over conventional small molecule agonists and antagonists. Immunotherapies can also be combined with other antiaddiction medications and enhance behavioral therapies. Current immunotherapies already show efficacy, but improved antigen design and antibody engineering promise highly specific and rapidly developed treatments for both existing and future addictions.

Exercise reinforcement, stress, and β-endorphins: an initial examination of exercise in anabolic-androgenic steroid dependence.

PubMed

Hildebrandt, Tom; Shope, Sydney; Varangis, Eleanna; Klein, Diane; Pfaff, Donald W; Yehuda, Rachel

2014-06-01

Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity×frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image. Between group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence. The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The mediating effect of psychological distress on functional dependence in stroke patients.

PubMed

Huang, Hui-Chuan; Huang, Li-Kai; Hu, Chaur-Jong; Chang, Chien-Hung; Lee, Hsin-Chien; Chi, Nai-Fang; Shyu, Meei-Ling; Chang, Hsiu-Ju

2014-12-01

To explore varied forms of psychological distress and to determine the mediating influence of psychological distress on functional outcomes in stroke patients. Previous studies attest to the influence of depression on poststroke functional recovery. While there is evidence for neuropathological deficits that occur after stroke to be associated with psychological distress, few studies have explored the effect of various types of psychological distress on functional recovery. A cross-sectional study was used. Data were collected from 178 first-time stroke patients. Study variables included demographic and disease characteristics (stroke location and stroke syndrome classification), psychological distress (the Chinese language version of the Emotional and Social Dysfunction Questionnaire) and functional outcome (Barthel index). Regression and mediation models were used to evaluate the effect of psychological distress on functional outcome. Results revealed that stroke patients experience various forms of mild psychological distress, including anger, helplessness, emotional dyscontrol, indifference, inertia and euphoria, after stroke. Regression and mediation analyses further confirmed that various forms of psychological distress significantly mediated the effect of severe stroke syndromes on functional dependence. The various forms of psychological distress after stroke might play a mediating role in functional recovery and explain how stroke severity affects functional dependence. By understanding the nature of various forms of psychological distress, healthcare professionals should adopt appropriate assessment instruments and design effective interventions to help improve mental and physical function of stroke patients. © 2014 John Wiley & Sons Ltd.

[Operative differential therapy of rheumatic wrists].

PubMed

Dinges, H; Fürst, M; Rüther, H; Schill, S

2007-09-01

The wrists are affected in the long-term in 90% of people with rheumatism and are often (42%) the first manifestation of a destructive disease. The functionality of the wrist and the whole hand is of great importance because in many cases loss of function of the wrists leads to severe limitations. Local and operative treatment of the wrist in rheumatoid arthritis (RA) is one of the main duties in rheuma-orthopaedics. For operative treatment there is a finely tuned differential therapeutic spectrum available. The diagnostic indications take the local and total pattern of affection, the current systemic therapy as well as patient wishes and patient compliance into consideration. In the early stages according to LDE (Larsen, Dale, Eek), soft tissues operations such as articulo-tenosynovectomy (ATS) are most commonly carried out. In further advanced stages osseus stabilisation must often be performed. At this point a smooth transition from partial arthrodesis to complete fixation is possible. After initial euphoria, arthroplasty of the wrist is being increasingly less used for operative treatment due to the unconvincing long-term results and high complication rate. With reference to the good long-term results of all operative procedures, in particular early ATS with respect to pain, function and protection of tendons, after failure of medicinal treatment and persistence of inflammatory activity in the wrist, patients should be transferred to an experienced rheuma-orthopaedic surgeon.

Animal Models of Nicotine Exposure: Relevance to Second-Hand Smoking, Electronic Cigarette Use, and Compulsive Smoking

PubMed Central

Cohen, Ami; George, Olivier

2013-01-01

Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine and that a large proportion of smokers eventually become dependent on nicotine. In humans, nicotine acutely produces positive reinforcing effects, including mild euphoria, whereas a nicotine abstinence syndrome with both somatic and affective components is observed after chronic nicotine exposure. Animal models of nicotine self-administration and chronic exposure to nicotine have been critical in unveiling the neurobiological substrates that mediate the acute reinforcing effects of nicotine and emergence of a withdrawal syndrome during abstinence. However, important aspects of the transition from nicotine abuse to nicotine dependence, such as the emergence of increased motivation and compulsive nicotine intake following repeated exposure to the drug, have only recently begun to be modeled in animals. Thus, the neurobiological mechanisms that are involved in these important aspects of nicotine addiction remain largely unknown. In this review, we describe the different animal models available to date and discuss recent advances in animal models of nicotine exposure and nicotine dependence. This review demonstrates that novel animal models of nicotine vapor exposure and escalation of nicotine intake provide a unique opportunity to investigate the neurobiological effects of second-hand nicotine exposure, electronic cigarette use, and the mechanisms that underlie the transition from nicotine use to compulsive nicotine intake. PMID:23761766

Current Developments and Perspectives on the Diagnosis and Treatment of Urinary Incontinence and Genital Prolapse in Women

PubMed Central

Naumann, G.; Kölbl, H.

2012-01-01

As a key area of gynaecology, urogynaecology has undergone impressive changes in the past few years. Together with the high prevalence of functional pelvic floor disorders, modern anaesthesia procedures and the introduction of new, innovative minimally invasive operation techniques have led to a dramatic increase in the number of operations for incontinence and prolapses. The increasingly subtle diagnostic options, such as, e. g., 2D and 3D sonography of the pelvic floor provide unambiguous findings and facilitate decision making. Tension-free vaginal slings in retro-pubic, trans-obturator or single-incision techniques show a high success rate with few complications and have almost completely replaced the more invasive abdominal surgical techniques for the operative management of stress incontinence. Especially for recurrent prolapse the use of alloplastic nets leads to a markedly improved anatomic and functional outcome. In spite of the euphoria about modern operation techniques and novel net materials, in-depth knowledge of pelvic floor anatomy, sufficient surgical experience and unequivocal guideline-conform indications are mandatory for satisfactory treatment outcomes. The afflicted women must be informed in detail about alternative procedures and more emphasis should be placed on conservative therapy. Novel surgical techniques should be monitored by registers or clinical trials. The professional society is called upon to improve the training curricula for pelvic floor surgery. PMID:25308980

Illnesses and deaths among persons attending an electronic dance-music festival - New York City, 2013.

PubMed

Ridpath, Alison; Driver, Cynthia R; Nolan, Michelle L; Karpati, Adam; Kass, Daniel; Paone, Denise; Jakubowski, Andrea; Hoffman, Robert S; Nelson, Lewis S; Kunins, Hillary V

2014-12-19

Outdoor electronic dance-music festivals (EDMFs) are typically summer events where attendees can dance for hours in hot temperatures. EDMFs have received increased media attention because of their growing popularity and reports of illness among attendees associated with recreational drug use. MDMA (3,4-methylenedioxymethamphetamine) is one of the drugs often used at EDMFs. MDMA causes euphoria and mental stimulation but also can cause serious adverse effects, including hyperthermia, seizures, hyponatremia, rhabdomyolysis, and multiorgan failure. In this report, MDMA and other synthetic drugs commonly used at dance festivals are referred to as "synthetic club drugs." On September 1, 2013, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) received reports of two deaths of attendees at an EDMF (festival A) held August 31-September 1 in NYC. DOHMH conducted an investigation to identify and characterize adverse events resulting in emergency department (ED) visits among festival A attendees and to determine what drugs were associated with these adverse events. The investigation identified 22 cases of adverse events; nine cases were severe, including two deaths. Twenty-one (95%) of the 22 patients had used drugs or alcohol. Of 17 patients with toxicology testing, MDMA and other compounds were identified, most frequently methylone, in 11 patients. Public health messages and strategies regarding adverse health events might reduce illnesses and deaths at EDMFs.

Internalizing and externalizing personality and subjective effects in a sample of adolescent cannabis users.

PubMed

García-Sánchez, Sara; Matalí, Josep Lluís; Martín-Fernández, María; Pardo, Marta; Lleras, Maria; Castellano-Tejedor, Carmina; Haro, Josep Maria

2016-10-06

Cannabis is the illicit substance most widely used by adolescents. Certain personality traits such as impulsivity and sensation seeking, and the subjective effects experienced after substance use (e.g. euphoria or relaxation) have been identified as some of the main etiological factors of consumption. This study aims to categorize a sample of adolescent cannabis users based on their most dominant personality traits (internalizing and externalizing profile). Then, to make a comparison of both profiles considering a set of variables related to consumption, clinical severity and subjective effects experienced. From a cross-sectional design, 173 adolescents (104 men and 69 women) aged 13 to 18 asking for treatment for cannabis use disorder in an Addictive Behavior Unit (UCAD) from the hospital were recruited. For the assessment, an ad hoc protocol was employed to register consumption, the Millon Adolescent Clinical Inventory (MACI) and the Addiction Research Center Inventory (ARCI) 49-item short form were also administered. Factor analysis suggested a two-profile solution: Introverted, Inhibited, Doleful, Dramatizing (-), Egotistic (-), Self-demeaning and Borderline tendency scales composed the internalizing profile, and Submissive (-), Unruly, Forceful, Conforming (-) and Oppositional scales composed the externalizing profile. The comparative analysis showed that the internalizing profile has higher levels of clinical severity and more subjective effects reported than the externalizing profile. These results suggest the need to design specific intervention strategies for each profile.

Test-retest reliability of the underlying latent factor structure of alcohol subjective response.

PubMed

Lutz, Joseph A; Childs, Emma

2017-04-01

Alcohol subjective experiences are multi-dimensional and demonstrate wide inter-individual variability. Recent efforts have sought to establish a clearer understanding of subjective alcohol responses by identifying core constructs derived from multiple measurement instruments. The aim of this study was to evaluate the temporal stability of this approach to conceptualizing alcohol subjective experiences across successive alcohol administrations in the same individuals. Healthy moderate alcohol drinkers (n = 104) completed six experimental sessions each, three with alcohol (0.8 g/kg), and three with a non-alcoholic control beverage. Participants reported subjective mood and drug effects using standardized questionnaires before and at repeated times after beverage consumption. We explored the underlying latent structure of subjective responses for all alcohol administrations using exploratory factor analysis and then tested measurement invariance over the three successive administrations using multi-group confirmatory factor analyses. Exploratory factor analyses on responses to alcohol across all administrations yielded four factors representing "Positive mood," "Sedation," "Stimulation/Euphoria," and "Drug effects and Urges." A confirmatory factor analysis on the separate administrations indicated acceptable configural and metric invariance and moderate scalar invariance. In this study, we demonstrate temporal stability of the underlying constructs of subjective alcohol responses derived from factor analysis. These findings strengthen the utility of this approach to conceptualizing subjective alcohol responses especially for use in prospective and longitudinal alcohol challenge studies relating subjective response to alcohol use disorder risk.

The challenge of complex drug use: Associated use of codeine-containing medicines and new psychoactive substances in a European cross-sectional online population.

PubMed

Kimergård, Andreas; Foley, Michelle; Davey, Zoe; Wadsworth, Elle; Drummond, Colin; Deluca, Paolo

2017-05-01

Misuse of codeine-containing medicines in combination with new psychoactive substances (NPS) is inadequately described. This study characterises codeine consumption amongst NPS users and non-NPS users to provide warning of health issues. Online survey conducted between July 2015 and March 2016. Out of 340 respondents, residing in a country in Europe and using codeine recently, 63.8% were female. Mean age: 34.9 years (SD = 12.4). Substance use included NPS (18.5%) and illicit controlled drugs (55.9%). Factors relating to codeine use found to significantly predict NPS use were consuming codeine extracted from combination tablets (OR = 16.79, 95% CI [8.67, 32.51]), obtaining codeine from friends, family, and acquaintances (OR = 3.98, 95% CI [1.82, 8.7]), use of illicit controlled drugs (OR = 34.99, 95% CI [8.39, 145.94]) and use of codeine to experience euphoria (OR = 6.41, 95% CI [3.42, 12.04]). Amongst NPS users, codeine is less likely to be used daily but more likely to be used for recreational purposes. Smaller populations engaging in high-risk use exist who take multiple drugs in high doses. Combinations of misused codeine and NPS highlight the need for policy to respond to a more complex drug situation. Copyright © 2017 John Wiley & Sons, Ltd.

Grouping and trajectories of the neuropsychiatric symptoms in patients with Alzheimer's disease, part I: symptom clusters.

PubMed

Garre-Olmo, Josep; López-Pousa, Secundino; Vilalta-Franch, Joan; de Gracia Blanco, Manuel; Vilarrasa, Antoni Bulbena

2010-01-01

Behavioral and psychological symptoms of dementia (BPSD) are frequently observed in Alzheimer's disease (AD) and affect more than 80% of patients over the course of AD. The goal of this study was to establish a model for grouping the symptoms of BPSD into clinical syndromes. Over a 24-month period, an observational study was conducted using a population of ambulatory patients with AD of mild to moderate severity. The Neuropsychiatric Inventory (NPI) was administered to the patients' caregivers every 6 months. BPSD were grouped using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of the NPI scores of each assessment. The sample population consisted of 491 patients (70.9% women) with an average age of 75.2 years (SD=6.6). The five EFA suggested that there was a stable three-factor structure. According to the results of the EFA, three models of symptom grouping were adjusted using CFA methodology. The CFA model that satisfactorily grouped the NPI scores into three factors included a psychotic syndrome (hallucinations, delusions), an affective syndrome (depression, anxiety, irritability, agitation) and a behavior syndrome (euphoria, disinhibition, apathy, aberrant motor behavior). Based on our findings, we propose a model for grouping the BDSD in which there are core nuclear syndromes (psychotic and affective) as well as an unspecified behavior syndrome comprising satellite symptoms that may be related to the presence of the nuclear syndromes.

Marijuana: A Realistic Approach

PubMed Central

Chun, George

1971-01-01

Much of the current confusion concerning marijuana has been caused by a lack of definition of terms. Variations in drug effect that are related to the type and potency of cannabis preparation and route of administration need clarification. When domestic strength marijuana is smoked recreationally, the subjective effects include relaxation, mild euphoria and increased sensory awareness. The objective effects include tachycardia, reddening of the conjunctivae and a distorted sense of time. Undesirable effects such as panic reactions, amotivational behavior, and acute toxic psychosis occur infrequently and are reversible with proper therapy. Other effects which have been attributed to marijuana are unsubstantiated. The recent upsurge in use of marijuana involves persons of a different type than those who used it heretofore and has greatly increased the number of people familiar with the drug. The disparity between what many people know empirically and the information disseminated through official media has lessened the credibility of physicians with many of our younger citizens. When young people recognize misinformation about marijuana, they are no longer listening when the facts are presented about more dangerous drugs, and the abuse of these drugs must be our main concern. To be considered is the potential hazard to adolescent users who may concomitantly be exposed to a subculture of experimentation with stronger drugs at a time when the opinion of a peer group is a strong factor in their behavior. PMID:5551311

The development and maintenance of drug addiction.

PubMed

Wise, Roy A; Koob, George F

2014-01-01

What is the defining property of addiction? We dust off a several-decades-long debate about the relative importance of two forms of reinforcement—positive reinforcement, subjectively linked to drug-induced euphoria, and negative reinforcement, subjectively linked to the alleviation of pain—both of which figure importantly in addiction theory; each of these forms has dominated addiction theory in its time. We agree that addiction begins with the formation of habits through positive reinforcement and that drug-opposite physiological responses often establish the conditions for negative reinforcement to come into play at a time when tolerance, in the form of increasing reward thresholds, appears to develop into positive reinforcement. Wise’s work has tended to focus on positive-reinforcement mechanisms that are important for establishing drug-seeking habits and reinstating them quickly after periods of abstinence, whereas Koob’s work has tended to focus on the negative-reinforcement mechanisms that become most obvious in the late stages of sustained addiction. While we tend to agree with each other about the early and late stages of addiction, we hold different views as to (i) the point between early and late at which the diagnosis of ‘addiction’ should be invoked, (ii) the relative importance of positive and negative reinforcement leading up to this transition, and (iii) the degree to which the specifics of negative reinforcement can be generalized across the range of addictive agents.

The new weight-loss drugs, lorcaserin and phentermine-topiramate: slim pickings?

PubMed

Woloshin, Steven; Schwartz, Lisa M

2014-04-01

In 2012, the US Food and Drug Administration approved 2 drugs for long-term weight loss: lorcaserin hydrochloride (Belviq; Eisai Inc) and phentermine-topiramate (Qysmia; Vivus Inc). The approvals were based on 1-year trials showing that on top of recommendations to follow a calorie-restricted diet and to increase exercise, patients randomized to either drug lost more weight than patients randomized to placebo (3% [95% CI, 3%-4%] more weight lost with lorcaserin; 7% [95% CI, 3%-4%] more with phentermine /topiramate). The drugs have been associated with serious harms: Both drugs' labels include warnings about memory, attention, or language problems and depression; for lorcaserin, the label also warns of valvular heart disease and euphoria; and for phentermine-topiramate, the label warns of metabolic acidosis, increased heart rate, anxiety, insomnia, and elevated creatinine levels. Neither medication is marketed in Europe because of safety concerns. The manufacturer withdrew its application for lorcaserin in Europe after the European Medicines Agency (EMA) said approval was unlikely, and the EMA rejected phentermine-topiramate. In the United States, the required postmarketing safety trials are behind schedule. Until there is more convincing evidence about the cardiovascular safety of these drugs, physicians and patients should approach them cautiously. Patients who do not lose at least 5% of their body weight within 12 weeks of starting to take either drug should stop taking it, as stated in the prescribing information.

Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone.

PubMed

Bosch, Oliver G; Eisenegger, Christoph; Gertsch, Jürg; von Rotz, Robin; Dornbierer, Dario; Gachet, M Salomé; Heinrichs, Markus; Wetter, Thomas C; Seifritz, Erich; Quednow, Boris B

2015-12-01

Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analogue-scales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic-hormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected. GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABAB-receptors and progesterone in mood and prosocial behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

Challenges of Tobacco Control Program in Iran.

PubMed

Poorolajal, Jalal; Mohammadi, Younes; Mahmoodi, Azam

2017-04-01

This study assessed the status of cigarette marketing in Iran as well as the attitude of smokers toward smoking and the policies and tobacco control programs in the country. This cross-sectional study was conducted on 3480 volunteer smokers in six provinces, using a stratified cluster random sampling method. The study population consisted of smokers who used at least one cigarette per day. The data collection tool was an anonymous self-administered questionnaire including basic information and 20 five-choice questions related to participants' attitude toward smoking habits (Cronbach's alpha; 79.73%.). The majority (66.9%) of participants started smoking at the age of 10 to 19 years and 61.1% used foreign cigarettes. Of 160 marketed brands, 38 (23.8%) were domestic and 122 (76.2%) were foreign, including 63 (39.3%) imported and 59 (36.9%) smuggled brands. Being tempted (25.0%), getting nervous (24.1%), and seeking euphoria (24.1%) were the most common reasons for restarting cigarette smoking after cessation. The majority of participants believed that smoking in public places was a violation of the rights of others and smoking should be avoided in such places. Smoking prevention programs should focus on adolescents as the most vulnerable age group. Raising the retail price of tobacco products through increasing taxes can reduce consumption, particularly among first starters and youth. However, increasing taxes and prices of tobacco products may be effective when simultaneous effective measures are implemented to eliminate all kinds of illicit trade in all forms of tobacco products.

Effects of Betel chewing on the central and autonomic nervous systems.

PubMed

Chu, N S

2001-01-01

Betel chewing has been claimed to produce a sense of well-being, euphoria, heightened alertness, sweating, salivation, a hot sensation in the body and increased capacity to work. Betel chewing also leads to habituation, addiction and withdrawal. However, the mechanisms underlying these effects remain poorly understood. Arecoline, the major alkaloid of Areca nut, has been extensively studied, and several effects of betel chewing are thought to be related to the actions of this parasympathomimetic constituent. However, betel chewing may produce complex reactions and interactions. In the presence of lime, arecoline and guvacoline in Areca nut are hydrolyzed into arecaidine and guvacine, respectively, which are strong inhibitors of GABA uptake. Piper betle flower or leaf contains aromatic phenolic compounds which have been found to stimulate the release of catecholamines in vitro. Thus, betel chewing may affect parasympathetic, GABAnergic and sympathetic functions. Betel chewing produces an increase in heart rate, blood pressure, sweating and body temperature. In addition, EEG shows widespread cortical desynchronization indicating a state of arousal. In autonomic function tests, both the sympathetic skin response and RR interval variation are affected. Betel chewing also increases plasma concentrations of norepinephrine and epinephrine. These results suggest that betel chewing mainly affects the central and autonomic nervous systems. Future studies should investigate both the acute and chronic effects of betel chewing. Such studies may further elucidate the psychoactive mechanisms responsible for the undiminished popularity of betel chewing since antiquity. Copyright 2001 National Science Council, ROC and S. Karger AG, Basel.

Heritability of lifetime ecstasy use.

PubMed

Verweij, Karin J H; Treur, Jorien L; Vreeker, Annabel; Brunt, Tibor M; Willemsen, Gonneke; Boomsma, Dorret I; Vink, Jacqueline M

2017-09-01

Ecstasy is a widely used psychoactive drug that users often take because they experience positive effects such as increased euphoria, sociability, elevated mood, and heightened sensations. Ecstasy use is not harmless and several immediate and long term side effects have been identified. Lifetime ecstasy use is likely to be partly influenced by genetic factors, but no twin study has determined the heritability. Here, we apply a classical twin design to a large sample of twins and siblings to estimate the heritability of lifetime ecstasy use. The sample comprised 8500 twins and siblings aged between 18 and 45 years from 5402 families registered at the Netherlands Twin Registry. In 2013-2014 participants filled out a questionnaire including a question whether they had ever used ecstasy. We used the classical twin design to partition the individual differences in liability to ecstasy use into that due to genetic, shared environmental, and residual components. Overall, 10.4% of the sample had used ecstasy during their lifetime, with a somewhat higher prevalence in males than females. Twin modelling indicated that individual differences in liability to lifetime ecstasy use are for 74% due to genetic differences between individuals, whereas shared environmental and residual factors explain a small proportion of its liability (5% and 21%, respectively). Although heritability estimates appeared to be higher for females than males, this difference was not significant. Lifetime ecstasy use is a highly heritable trait, which indicates that some people are genetically more vulnerable to start using ecstasy than others. Copyright © 2017. Published by Elsevier B.V.

Review of Androgenic Anabolic Steroid Use

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

T. Borges; G. Eisele; C. Byrd

An area that has been overlooked within personnel security evaluations is employee use of androgenic-anabolic steroids (AAS). Current drug testing within the federal government does not include testing for anabolic steroids, and the difficulties to implement such testing protocols-not to mention the cost involved-make AAS testing highly improbable. The basis of this report is to bring to the forefront the damage that anabolic steroids can cause from both a physical and a psychological standpoint. Most individuals who use AASs do so to increase their muscle mass because they wish to gain some type of competitive edge during athletic competition ormore » they wish to enhance their physical features for self-satisfaction and self-esteem (i.e., body building). Security officers are one group of men who often take high doses of anabolic steroids, according to the Second Report of the Senate Standing Committee (1990). The negative psychological characteristics for AAS use is extensive and includes prominent hostility, aggressiveness, irritability, euphoria, grandiose beliefs, hyperactivity, reckless behavior, increased sexual appetite, unpredictability, poor impulse control, mood fluctuations, and insomnia. The drug may invoke a sense of power and invincibility (Leckman and Scahill, 1990). Depressive symptoms, such as anhedonia, fatigue, impaired concentration, decreased libido, and even suicidality (Pope and Katz, 1992) have been noted with steroid withdrawal. It appears that long-term users of AAS experience similar characteristics as other substance abusers (i.e., craving, dependence, and withdrawal symptoms).« less

Human Pharmacology of Mephedrone in Comparison with MDMA.

PubMed

Papaseit, Esther; Pérez-Mañá, Clara; Mateus, Julián-Andrés; Pujadas, Mitona; Fonseca, Francina; Torrens, Marta; Olesti, Eulàlia; de la Torre, Rafael; Farré, Magí

2016-10-01

Mephedrone (4-methylmethcathinone) is a novel psychoactive substance popular among drug users because it displays similar effects to MDMA (3,4-methylenedioxymethamphetamine, ecstasy). Mephedrone consumption has been associated with undesirable effects and fatal intoxications. At present, there is no research available on its pharmacological effects in humans under controlled and experimental administration. This study aims to evaluate the clinical pharmacology of mephedrone and its relative abuse liability compared with MDMA. Twelve male volunteers participated in a randomized, double-blind, crossover, and placebo-controlled trial. The single oral dose conditions were: mephedrone 200 mg, MDMA 100 mg, and placebo. Outcome variables included physiological, subjective, and psychomotor effects, and pharmacokinetic parameters. The protocol was registered in ClinicalTrials.gov (NCT02232789). Mephedrone produced a significant increase in systolic and diastolic blood pressure, heart rate, and pupillary diameter. It elicited stimulant-like effects, euphoria, and well-being, and induced mild changes in perceptions with similar ratings to those observed after MDMA administration although effects peaked earlier and were shorter in duration. Maximal plasma concentration values for mephedrone and MDMA peaked at 1.25 h and 2.00 h, respectively. The elimination half-life for mephedrone was 2.15 h and 7.89 h for MDMA. In a similar manner to MDMA, mephedrone exhibits high abuse liability. Its earlier onset and shorter duration of effects, probably related to its short elimination half-life, could explain a more compulsive pattern of use as described by the users.

The right cerebral hemisphere: emotion, music, visual-spatial skills, body-image, dreams, and awareness.

PubMed

Joseph, R

1988-09-01

Based on a review of numerous studies conducted on normal, neurosurgical and brain-injured individuals, the right cerebral hemisphere appears to be dominant in the perception and identification of environmental and nonverbal sounds; the analysis of geometric and visual space (e.g., depth perception, visual closure); somesthesis, stereognosis, the maintenance of the body image; the production of dreams during REM sleep; the perception of most aspects of musical stimuli; and the comprehension and expression of prosodic, melodic, visual, facial, and verbal emotion. When the right hemisphere is damaged a variety of cognitive abnormalities may result, including hemi-inattention and neglect, prosopagnosia, constructional apraxia, visual-perceptual disturbances, and agnosia for environmental, musical, and emotional sounds. Similarly, a myriad of affective abnormalities may occur, including indifference, depression, hysteria, gross social-emotional disinhibition, florid manic excitement, childishness, euphoria, impulsivity, and abnormal sexual behavior. Patients may become delusional, engage in the production of bizzare confabulations and experience a host of somatic disturbances such as pain and body-perceptual distortions. Based on studies of normal and "split-brain" functioning, it also appears that the right hemisphere maintains a highly developed social-emotional mental system and can independently perceive, recall and act on certain memories and experiences without the aid or active reflective participation of the left. This leads to situations in which the right and left halves of the brain sometime act in an uncooperative fashion, which gives rise to inter-manual and intra-psychic conflicts.

Testing the self-medication hypothesis of depression and aggression in cannabis-dependent subjects.

PubMed

Arendt, Mikkel; Rosenberg, Raben; Fjordback, Lone; Brandholdt, Jack; Foldager, Leslie; Sher, Leo; Munk-Jørgensen, Povl

2007-07-01

A self-medication hypothesis has been proposed to explain the association between cannabis use and psychiatric and behavioral problems. However, little is known about the reasons for use and reactions while intoxicated in cannabis users who suffer from depression or problems controlling violent behavior. We assessed 119 cannabis-dependent subjects using the Schedules of Clinical Assessment in Neuropsychiatry (SCAN), parts of the Addiction Severity Index (ASI), and questionnaires on reasons for cannabis use and reactions to cannabis use while intoxicated. Participants with lifetime depression and problems controlling violent behavior were compared to subjects without such problems. Validity of the groupings was corroborated by use of a psychiatric treatment register, previous use of psychotropic medication and convictions for violence. Subjects with lifetime depression used cannabis for the same reasons as others. While under the influence of cannabis, they more often experienced depression, sadness, anxiety and paranoia, and they were less likely to report happiness or euphoria. Participants reporting problems controlling violent behavior more often used cannabis to decrease aggression, decrease suspiciousness, and for relaxation; while intoxicated they more often reacted with aggression. Subjects with prior depression do not use cannabis as a mean of self-medication. They are more likely to experience specific increases of adverse symptoms while under the influence of cannabis, and are less likely to experience specific symptom relief. There is some evidence that cannabis is used as a means of self-medication for problems controlling aggression.

Neurotrophin 3 genotype and emotional adverse effects of osmotic-release oral system methylphenidate (OROS-MPH) in children with attention-deficit/hyperactivity disorder.

PubMed

Park, Subin; Kim, Bung-Nyun; Kim, Jae-Won; Shin, Min-Sup; Cho, Soo-Churl; Kim, Ji-Hoon; Son, Jung-Woo; Shin, Yun-Mi; Chung, Un-Sun; Han, Doug-Hyun

2014-03-01

Neurotrophin 3 (NTF3) has been studied in relation to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and mood disorders as well as psychostimulant action. We hypothesized that the risk of an emotional side effect to methylphenidate (MPH) treatment may be associated with NTF3 genotypes. Ninety-six medication-naïve children with ADHD (mean age 8.70, standard deviation 1.41 years, 79 males) were genotyped and treated with MPH. At baseline, which was prior to MPH treatment, and after two weeks of medication, investigators asked children and their parents or caregivers about adverse events using a symptom rating scale. ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest 'Emotionality' and 'Over-focus/euphoria' factor scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.042 and p=0.045, respectively). ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest 'Proneness to crying' and 'Nail biting' item scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.047 and p=0.017, respectively). These data provide preliminary evidence that genetic variation in the NTF3 gene is related to susceptibility to emotional side effects in response to MPH treatment in Korean children with ADHD.

Methamphetamine induces the release of endothelin.

PubMed

Seo, Jeong-Woo; Jones, Susan M; Hostetter, Trisha A; Iliff, Jeffrey J; West, G Alexander

2016-02-01

Methamphetamine is a potent psychostimulant drug of abuse that increases release and blocks reuptake of dopamine, producing intense euphoria, factors that may contribute to its widespread abuse. It also produces severe neurotoxicity resulting from oxidative stress, DNA damage, blood-brain barrier disruption, microgliosis, and mitochondrial dysfunction. Intracerebral hemorrhagic and ischemic stroke have been reported after intravenous and oral abuse of methamphetamine. Several studies have shown that methamphetamine causes vasoconstriction of vessels. This study investigates the effect of methamphetamine on endothelin-1 (ET-1) release in mouse brain endothelial cells by ELISA. ET-1 transcription as well as endothelial nitric oxide synthase (eNOS) activation and transcription were measured following methamphetamine treatment. We also examine the effect of methamphetamine on isolated cerebral arteriolar vessels from C57BL/6 mice. Penetrating middle cerebral arterioles were cannulated at both ends with a micropipette system. Methamphetamine was applied extraluminally, and the vascular response was investigated. Methamphetamine treatment of mouse brain endothelial cells resulted in ET-1 release and a transient increase in ET-1 message. The activity and transcription of eNOS were only slightly enhanced after 24 hr of treatment with methamphetamine. In addition, methamphetamine caused significant vasoconstriction of isolated mouse intracerebral arterioles. The vasoconstrictive effect of methamphetamine was attenuated by coapplication of the endothelin receptor antagonist PD145065. These findings suggest that vasoconstriction induced by methamphetamine is mediated through the endothelin receptor and may involve an endothelin-dependent pathway. © 2015 Wiley Periodicals, Inc.

Functional Chemical Groups that May Likely Become a Source for the Synthesis of Novel Central Nervous System (CNS) Acting Drugs.

PubMed

Saganuwan, Saganuwan A

2017-01-01

Central Nervous System (CNS) disorders are on increase perhaps due to genetic, enviromental, social and dietetic factors. Unfortunately, a large number of CNS drugs have adverse effects such as addiction, tolerance, psychological and physical dependence. In view of this, literature search was carried out with a view to identify functional chemical groups that may serve as lead molecules for synthesis of compounds that may have CNS activity. The search revealed that heterocycles that have heteroatoms such as nitrogen (N), sulphur (S) and oxygen (O) form the largest class of organic compounds. They replace carbon in a benzene ring to form pyridine. Compounds with furan, thiophene, pyrrole, pyridine, azole, imidazole, indole, purine, pyrimidine, esters, carboxylic acid, aldehyde, pyrylium, pyrone, pyrodine, barbituric acid, barbiturate, quinoline, quinolone, isoquinolone, coumarin, alkylpyridine, picoline, piperidine, diazine, carboxamide, flavonoid glycoside, oxindole, aminophenol, benzimidazole, benzoxazole, benzothiazole, and chromone chemical groups among others may have CNS effects ranging from depression passing through euphoria to convulsion. Examples of the compounds with the functional groups include but not limited to coal tar, pyridostigmine, pralidoxime, quinine, mefloquine, pyrilamine, pyronaridine, ciprofloxacin and piroxicam. A number of them can undergo keto-enol tautomerism. Chiral amines may be used for derivation of chiral carboxylic acids which are components of tautomers. Some tautomers may cause parkinsonism and Stevens Johnson syndrome. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cocaine affects foraging behaviour and biogenic amine modulated behavioural reflexes in honey bees.

PubMed

Søvik, Eirik; Even, Naïla; Radford, Catherine W; Barron, Andrew B

2014-01-01

In humans and other mammals, drugs of abuse alter the function of biogenic amine pathways in the brain leading to the subjective experience of reward and euphoria. Biogenic amine pathways are involved in reward processing across diverse animal phyla, however whether cocaine acts on these neurochemical pathways to cause similar rewarding behavioural effects in animal phyla other than mammals is unclear. Previously, it has been shown that bees are more likely to dance (a signal of perceived reward) when returning from a sucrose feeder after cocaine treatment. Here we examined more broadly whether cocaine altered reward-related behaviour, and biogenic amine modulated behavioural responses in bees. Bees developed a preference for locations at which they received cocaine, and when foraging at low quality sucrose feeders increase their foraging rate in response to cocaine treatment. Cocaine also increased reflexive proboscis extension to sucrose, and sting extension to electric shock. Both of these simple reflexes are modulated by biogenic amines. This shows that systemic cocaine treatment alters behavioural responses that are modulated by biogenic amines in insects. Since insect reward responses involve both octopamine and dopamine signalling, we conclude that cocaine treatment altered diverse reward-related aspects of behaviour in bees. We discuss the implications of these results for understanding the ecology of cocaine as a plant defence compound. Our findings further validate the honey bee as a model system for understanding the behavioural impacts of cocaine, and potentially other drugs of abuse.

Psychostimulants and Cognition: A Continuum of Behavioral and Cognitive Activation

PubMed Central

Wood, Suzanne; Sage, Jennifer R.; Shuman, Tristan

2014-01-01

Psychostimulants such as cocaine have been used as performance enhancers throughout recorded history. Although psychostimulants are commonly prescribed to improve attention and cognition, a great deal of literature has described their ability to induce cognitive deficits, as well as addiction. How can a single drug class be known to produce both cognitive enhancement and impairment? Properties of the particular stimulant drug itself and individual differences between users have both been suggested to dictate the outcome of stimulant use. A more parsimonious alternative, which we endorse, is that dose is the critical determining factor in cognitive effects of stimulant drugs. Herein, we review several popular stimulants (cocaine, amphetamine, methylphenidate, modafinil, and caffeine), outlining their history of use, mechanism of action, and use and abuse today. One common graphic depiction of the cognitive effects of psychostimulants is an inverted U–shaped dose-effect curve. Moderate arousal is beneficial to cognition, whereas too much activation leads to cognitive impairment. In parallel to this schematic, we propose a continuum of psychostimulant activation that covers the transition from one drug effect to another as stimulant intake is increased. Low doses of stimulants effect increased arousal, attention, and cognitive enhancement; moderate doses can lead to feelings of euphoria and power, as well as addiction and cognitive impairment; and very high doses lead to psychosis and circulatory collapse. This continuum helps account for the seemingly disparate effects of stimulant drugs, with the same drug being associated with cognitive enhancement and impairment. PMID:24344115

Pediatric Mania: The Controversy between Euphoria and Irritability

PubMed Central

Serra, Giulia; Uchida, Mai; Battaglia, Claudia; Casini, Maria Pia; De Chiara, Lavinia; Biederman, Joseph; Vicari, Stefano; Wozniak, Janet

2017-01-01

Abstract: Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and associated with high levels of morbidity and disability and with a great risk of suicide. While there is a general consensus on the symptomatology of depression in childhood, the phenomenology of pediatric mania is still highly debated and the course and long-term outcome of pediatric BD still need to be clarified. We reviewed the available studies on the phenomenology of pediatric mania with the aim of summarizing the prevalence, demographics, clinical correlates and course of these two types of pediatric mania. Eighteen studies reported the number of subjects presenting with either irritable or elated mood during mania. Irritability has been reported to be the most frequent clinical feature of pediatric mania reaching a sensitivity of 95–100% in several samples. Only half the studies reviewed reported on number of episodes or cycling patterns and the described course was mostly chronic and ultra-rapid whereas the classical episodic presentation was less common. Few long-term outcome studies have reported a diagnostic stability of mania from childhood to young adult age. Future research should focus on the heterogeneity of irritability aiming at differentiating distinct subtypes of pediatric psychiatric disorders with distinct phenomenology, course, outcome and biomarkers. Longitudinal studies of samples attending to mood presentation, irritable versus elated, and course, chronic versus episodic, may help clarify whether these are meaningful distinctions in the course, treatment and outcome of pediatric onset bipolar disorder. PMID:28503110

Grouping and trajectories of neuropsychiatric symptoms in patients with Alzheimer's disease. Part II: two-year patient trajectories.

PubMed

Garre-Olmo, Josep; López-Pousa, Secundino; Vilalta-Franch, Joan; de Gracia Blanco, Manuel; Vilarrasa, Antoni Bulbena

2010-01-01

Behavioral and psychological symptoms of dementia (BPSD) are characterized by fluctuations in their frequency and severity as well as by differences in the concurrent presentation of different symptoms. The goal of the current study was to identify groups of patients with Alzheimer's disease (AD) that had similar trajectories in the expression of BPSD. Over a 24-month period, an observational study was conducted using a population of ambulatory patients with AD of mild or moderate severity. The Neuropsychiatric Inventory (NPI) was administered every 6 months to the patient's caregiver. To classify patients according to changes in the frequency and severity of BPSD, growth mixture models were fitted to the applied to the grouping of NPI subscales in the following three categories: psychotic syndrome (hallucinations and delusions), affective syndrome (depression, anxiety, irritability, and agitation), and behavioral syndrome (disinhibition, euphoria, apathy, and aberrant motor behavior). The sample population consisted of 491 patients (70.9% women) that had an average age of 75.2 years (SD=6.6). Different trajectory patterns were identified based on differences in changes over the time in the frequency (stable, increasing, decreasing, or fluctuating in course) and severity (low, moderate, or elevated severity) for psychotic syndrome, emotional syndrome, and behavior syndrome. Patients with AD display a high degree of variability in the evolutionary course of BPSD. It is possible to identify groups of patients with similar evolutionary trajectories in terms of changes in the frequency and severity of BPSD.

[Cocaine base paste: experience from the Montevideo Poison Control Center].

PubMed

Pascale, Antonio; Negrin, Alba; Laborde, Amalia

2010-01-01

In Uruguay, cocaine base paste (CBP, pasta base) is a widely used form of cocaine. The aim of our study is to determine the main clinical characteristics of CBP abusers. Retrospective, single-center study of consultations at the Montevideo Poison Control Center between January 1, 2004 and December 31, 2005. One hundred and thirteen consultations were included, with an average age of 22 years (+ - 0.5 years) and a female-male sex ratio of 1:4.3. The consultations were related to drug overdose (77%), suicide attempt (16.8%), and wanting to give up CBP use (6.2%). In 48.1% the time elapsed since inhalation of CBP was less than 6 hours. Doses varied between 0.5 gr. and 25 gr. Use of other drugs at the same time, such as alcohol, marijuana or benzodiazepines, was common (51 cases). The symptoms most frequently observed were neuropsychiatric and cardiovascular, followed by respiratory symptoms. In 16.8% of patients, reason for the consultation was intentional acute ingestion of drugs, considered as a suicide attempt, occurring within a few hours of drug consumption. CBP users are mostly young males. Although clinical findings are compatible with those for cocaine abuse, euphoria is a major clinical feature in CBP abusers. The presence of respiratory symptoms reflects the complications associated with the ingestion route. Suicide attempts occurring within a few hours of CBP confirm the high prevalence of suicidal ideation reported by other authors. cocaine base paste, clinical features, suicide attempts.

Classification of Neuropsychiatric Symptoms Requiring Antipsychotic Treatment in Patients with Alzheimer's Disease: Analysis of the CATIE-AD Study.

PubMed

Nagata, Tomoyuki; Shinagawa, Shunichiro; Nakajima, Shinichiro; Plitman, Eric; Mihashi, Yukiko; Hayashi, Shogo; Mimura, Masaru; Nakayama, Kazuhiko

2016-01-01

The Neuropsychiatric Inventory (NPI) comprises 12 items, which were conventionally determined by psychopathological symptoms of patients with dementia. The clinical rating scales with structured questionnaires have been useful to evaluate neuropsychiatric symptoms (NPSs) of patients with dementia over the past twenty year. The aim of this study was to classify the conventional NPSs in patients with Alzheimer's disease (AD) requiring antipsychotic treatment for their NPSs into distinct clusters to simplify assessment of these numerous symptoms. Twelve items scores (product of severity and frequency of each symptom) in the NPI taken from the baseline visit were classified into subgroups by principle component analysis using data from 421 outpatients with AD enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Phase 1. Chi square tests were conducted to examine the co-occurrence of the subgroups. We found four distinct clusters: aggressiveness (agitation and irritabilities), apathy and eating problems (apathy and appetite/eating disturbance), psychosis (delusions and hallucinations), and emotion and disinhibition (depression, euphoria, and disinhibition). Anxiety, aberrant motor behavior, and sleep disturbance were not included by these clusters. Apathy and eating problems, and emotion and disinhibition co-occurred (p = 0.002), whereas aggressiveness and psychosis occurred independent of the other clusters. Four distinct category clusters were identified from NPSs in patients with AD requiring antipsychotic treatment. Future studies should investigate psychosocial backgrounds or risk factors of each distinct cluster, in addition to their longitudinal course over treatment intervention.

The Effect of the Association between Donepezil and Choline Alphoscerate on Behavioral Disturbances in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial.

PubMed

Carotenuto, Anna; Rea, Raffaele; Traini, Enea; Fasanaro, Angiola Maria; Ricci, Giovanna; Manzo, Valentino; Amenta, Francesco

2017-01-01

Behavioral and psychological symptoms of dementia (BPSD) are a group of psychological reactions, psychiatric symptoms, and behaviors commonly found in Alzheimer's disease (AD). Four clusters of BPSD have been described: mood disorders (depression, anxiety, and apathy), psychotic symptoms (delusions and hallucinations), aberrant motor behaviors (pacing, wandering, and other purposeless behaviors), and inappropriate behaviors (agitation, disinhibition, and euphoria). Most of them are attributed to acetylcholine deficiency. To evaluate if a higher amount of acetylcholine obtained by associating donepezil and choline alphoscerate might have a favorable effect on BPSD. BPSD were measured at baseline and after 24 months in 113 mild/moderate AD patients, included in the double-blind randomized trial ASCOMALVA, by the Neuropsychiatric Inventory (NPI). Two matched groups were compared: group A treated with donepezil (10 mg/day) plus choline alphoscerate (1200 mg/day), and group B treated with donepezil (10 mg/day) plus placebo. Data of NPI revealed a significant decrease of BPSD severity and distress of the caregiver in patients of group A compared with group B. Mood disorders (depression, anxiety and apathy) were significantly decreased in subjects treated with donepezil and choline alphoscerate, while their severity and frequency was increased in the other group. Patients treated with donepezil plus choline alphoscerate showed a lower level of behavioral disturbances than subjects treated with donepezil only, suggesting that the association can have beneficial effects.

Pediatric Mania: The Controversy between Euphoria and Irritability.

PubMed

Serra, Giulia; Uchida, Mai; Battaglia, Claudia; Casini, Maria Pia; De Chiara, Lavinia; Biederman, Joseph; Vicari, Stefano; Wozniak, Janet

2017-04-01

Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and associated with high levels of morbidity and disability and with a great risk of suicide. While there is a general consensus on the symptomatology of depression in childhood, the phenomenology of pediatric mania is still highly debated and the course and long-term outcome of pediatric BD still need to be clarified. We reviewed the available studies on the phenomenology of pediatric mania with the aim of summarizing the prevalence, demographics, clinical correlates and course of these two types of pediatric mania. Eighteen studies reported the number of subjects presenting with either irritable or elated mood during mania. Irritability has been reported to be the most frequent clinical feature of pediatric mania reaching a sensitivity of 95-100% in several samples. Only half the studies reviewed reported on number of episodes or cycling patterns and the described course was mostly chronic and ultra-rapid whereas the classical episodic presentation was less common. Few long-term outcome studies have reported a diagnostic stability of mania from childhood to young adult age. Future research should focus on the heterogeneity of irritability aiming at differentiating distinct subtypes of pediatric psychiatric disorders with distinct phenomenology, course, outcome and biomarkers. Longitudinal studies of samples attending to mood presentation, irritable versus elated, and course, chronic versus episodic, may help clarify whether these are meaningful distinctions in the course, treatment and outcome of pediatric onset bipolar disorder.

Prescription Opioid Use, Misuse, and Diversion among Street Drug Users in New York City

PubMed Central

Rees Davis, W.; Johnson, Bruce D.

2008-01-01

Objective The use of heroin, cocaine, and other drugs is well researched in New York City, but prescription opioids (POs) have been overlooked. This study documents patterns of PO use, misuse, and diversion among street drug users, and begins to indicate how drug culture practices interact with the legitimate therapeutic goals of PO prescriptions (e.g. pain management). Methods Staff completed interviews inquiring about the reasons for use of POs and illicit drugs with 586 street drug users. Ethnographers wrote extensive field notes about subjects’ complex patterns of PO use. Results Methadone was used (71.9%) and sold (64.7%) at a higher level than OxyContin, Vicodin, and Percocet, used by between 34% and 38% of the users and sold by between 28% and 41% of the sellers. Recent PO use is associated with the recency of using heroin and cocaine (p<.001). Half of the heroin/cocaine sellers sold POs, and one quarter of the PO sellers only sold POs. Subjects were classified into four groups by whether they diverted POs or used POs to relieve pain or withdrawal rather than for euphoria. This classification was associated with frequency of PO use, whether POs were obtained from doctors/pharmacies or from drug dealers and family members, and those mostly likely to use POs for pain and withdrawal. Conclusions POs are an important component of street drug users’ drug-taking regimes, especially those who are Physically III Chemical Abusers (PICA). Future research is needed to model PO use, misuse, and diversion among this population. PMID:17913395

Prescription opioid use, misuse, and diversion among street drug users in New York City.

PubMed

Davis, W Rees; Johnson, Bruce D

2008-01-01

The use of heroin, cocaine, and other drugs is well researched in New York City, but prescription opioids (POs) have been overlooked. This study documents patterns of PO use, misuse, and diversion among street drug users, and begins to indicate how drug culture practices interact with the legitimate therapeutic goals of PO prescriptions (e.g. pain management). Staff completed interviews inquiring about the reasons for use of POs and illicit drugs with 586 street drug users. Ethnographers wrote extensive field notes about subjects' complex patterns of PO use. Methadone was used (71.9%) and sold (64.7%) at a higher level than OxyContin, Vicodin, and Percocet, used by between 34% and 38% of the users and sold by between 28% and 41% of the sellers. Recent PO use is associated with the recency of using heroin and cocaine (p<.001). Half of the heroin/cocaine sellers sold POs, and one quarter of the PO sellers only sold POs. Subjects were classified into four groups by whether they diverted POs or used POs to relieve pain or withdrawal rather than for euphoria. This classification was associated with frequency of PO use, whether POs were obtained from doctors/pharmacies or from drug dealers and family members, and those mostly likely to use POs for pain and withdrawal. POs are an important component of street drug users' drug-taking regimes, especially those who are Physically Ill Chemical Abusers (PICA). Future research is needed to model PO use, misuse, and diversion among this population.

Jezebel: Reconstructing a Critical Experiment from 60 Years Ago

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

Favorite, Jeffrey A.

The Jezebel experiment of 1954-1955 was a very small, nearly-spherical, nearly-bare (unreflected), nearly-homogeneous assembly of plutonium alloyed with gallium. This experiment was used to determine the critical mass of spherical, bare, homogeneous Pu-alloy. In 1956, the critical mass of Pu-alloy was determined to be 16.45 ± 0.05 kg. The experiment was reevaluated in 1969 using logbooks from the 1950s and updated nuclear cross sections. The critical mass of Pu-alloy was determined to be 16.57 ± 0.10 kg. In 2013, the 239Pu Jezebel experiment was again reevaluated, this time using detailed geometry and materials models and modern nuclear cross sections inmore » high-fidelity Monte Carlo neutron transport calculations. Documentation from the 1950s was often inconsistent or missing altogether, and assumptions had to be made. The critical mass of Pu-alloy was determined to be 16.624 ± 0.075 kg. Historic documents were subsequently found that validated some of the 2013 assumptions and invalidated others. In 2016, the newly found information was used to once again reevaluate the 239Pu Jezebel experiment. The critical mass of Pu-alloy was determined to be 16.624 ± 0.065 kg. This talk will discuss each of these evaluations, focusing on the calculation of the uncertainty as well as the critical mass. We call attention to the ambiguity, consternation, despair, and euphoria involved in reconstructing the historic Jezebel experiment. This talk is quite accessible for undergraduate students as well as non-majors.« less

Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

PubMed

Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

2012-06-01

Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

Protective effect of Lycium Barbarum polysaccharides on dextromethorphan-induced mood impairment and neurogenesis suppression.

PubMed

Po, Kevin Kai-Ting; Leung, Joseph Wai-Hin; Chan, Jackie Ngai-Man; Fung, Timothy Kai-Hang; Sánchez-Vidaña, Dalinda Isabel; Sin, Emily Lok-Lam; So, Kwok-Fai; Lau, Benson Wui-Man; Siu, Andrew Man-Hong

2017-09-01

Dextromethorphan (DXM) is one of the common drugs abused by adolescents. It is the active ingredient found in cough medicine which is used for suppressing cough. High dosage of DXM can induce euphoria, dissociative effects and even hallucinations. Chronic use of DXM may also lead to depressive-related symptoms. Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of ageing-related neurodegenerative diseases. A recent study has shown the potential beneficial effect of Lycium barbarum to reduce depression-like behavior. In the present study, we investigated the role of Lycium barbarum polysaccharide (LBP) to alleviate DXM-induced emotional distress. Sprague Dawley rats were divided into 4 groups (n=6 per group), including the normal control (vehicles only), DXM-treated group (40 mg/kg DXM), LBP-treated group (1 mg/kg LBP) and DXM+ LBP-treated group (40 mg/kg DXM and 1 mg/kg LBP). After two-week treatment, the DXM-treated group showed increased depression-like and social anxiety-like behaviors in the forced swim test and social interaction test respectively. On the other hand, the adverse behavioral effects induced by DXM were reduced by LBP treatment. Histological results showed that LBP treatment alone did not promote hippocampal neurogenesis when compared to the normal control, but LBP could lessen the suppression of hippocampal neurogenesis induced by DXM. The findings provide insights for the potential use of wolfberry as an adjunct treatment option for alleviating mood disturbances during rehabilitation of cough syrup abusers. Copyright © 2017 Elsevier Inc. All rights reserved.

The hidden sister of motor fluctuations in Parkinson's disease: A review on nonmotor fluctuations.

PubMed

Martínez-Fernández, Raul; Schmitt, Emmanuelle; Martinez-Martin, Pablo; Krack, Paul

2016-08-01

Only a few years after the introduction of levodopa, the first descriptions of motor fluctuations and dyskinesia related to dopaminergic therapy appeared. In PD, attention turned to their management, that had dampened the euphoria of the "levodopa miracle." It soon became clear that neuropsychiatric, autonomic, and sensory features also tend to develop fluctuations after chronic exposure to l-dopa. The diversity of fluctuating nonmotor symptoms, their largely subjective nature, coupled with a frequent lack of insight led to difficulties in identification and quantification. This may explain why, despite the high impact of nonmotor symptoms on patient autonomy and quality of life, evaluation of nonmotor fluctuations is not part of clinical routine. In view of the lack of specific validated assessment tools, detailed anamnesis should ideally be coupled with an evaluation in both ON and OFF drug conditions. The mechanisms of nonmotor fluctuations are not well understood. It is thought that they share dopaminergic presynaptic pharmacokinetic and postsynaptic pharmacodynamic mechanisms with the classical motor complications, but involve different neural pathways. Although symptoms fluctuate with dopaminergic treatment, serotonine and norepinephrine denervation, as well as interactions between neurotransmitter systems, probably contribute to their diversity. The lack of validated tools for assessment of these phenomena explains the almost complete absence of treatment studies. Management, largely resulting from expert opinion, includes psychiatric follow-up, nondopaminergic drugs, and advanced dopaminergic treatment, including drug delivery pumps and DBS. This review aims to provide a starting point for the understanding, diagnosis, and management of nonmotor fluctuations. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Post heroin dose tissue distribution of 6-monoacetylmorphine (6-MAM) with MALDI imaging.

PubMed

Teklezgi, Belin G; Pamreddy, Annapurna; Baijnath, Sooraj; Gopal, Nirmala D; Naicker, Tricia; Kruger, Hendrik G; Govender, Thavendran

2017-08-01

Heroin is an illicit opioid drug which is commonly abused and leads to dependence and addiction. Heroin is considered a pro-drug and is rapidly converted to its major active metabolite 6-monoacetylmorphine (6-MAM) which mediates euphoria and reward through the stimulation of opioid receptors in the brain. The aim of this study was to investigate the distribution and localization of 6-MAM in the healthy Sprague Dawley rat brain following intraperitoneal (i.p) administration of heroin (10 mg/kg), using matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI), in combination with quantification via liquid chromatography mass spectrometry (LC-MS/MS). These findings revealed that 6-MAM is present both in plasma and brain tissue with a T max of 5 min (2.8 µg/mL) and 15 min (1.1 µg/mL), respectively. MSI analysis of the brain showed high intensities of 6-MAM in the thalamus-hypothalamus and mesocorticolimbic system including areas of the cortex, caudate putamen, and ventral pallidum regions. This finding correlates with the distribution of opioid receptors in the brain, according to literature. In addition, we report a time-dependent distribution in the levels of 6-MAM, from 1 min with the highest intensity of the drug observed at 15 min, with sparse distribution at 45 min before decreasing at 60 min. This is the first study to use MSI as a brain imaging technique to detect a morphine's distribution over time in the brain.

Who goes, who stays?

PubMed

Light, D A

2001-01-01

The merger announcement between DeWaal Pharmaceuticals and BioHealth Labs was front-page news. Pictures of CEO Steve Lindell and chairman Kaspar van de Velde had appeared in newspapers around the world. Two months later, the press had moved on to a new story, and the hard labor of integration loomed. Steve had worked tirelessly to clear regulatory hurdles, and all signs pointed toward approval in the near future. Now Steve was feeling pressure to attack the real challenge of the merger: bringing together two very different cultures as quickly and efficiently as possible. DeWaal was an established drug-maker based in the Netherlands, and BioHealth, headquartered just north of New York City, had in recent years become competitive at the highest tier of the market. The first step in integrating the two companies was to select the top layers of management for the new company. At the moment, there were some 120 people on two continents for about 65 senior-level jobs. Steve's urgency was not without cause: talented people from both sides were jumping ship, and BioHealth's stock price had dipped 20% after the initial euphoria over the deal had worn off. Complicating matters was confusion over who was really in charge: Steve wanted to take leadership and move ahead rapidly, but he was often disarmed by Kaspar's charming persuasiveness. As the two men attempt to work through the important personnel issues during a lunch meeting, they quickly hit a roadblock. How can they come to agreement about who goes and who stays? Four commentators offer advice in response to this fictional case.

User Identified Positive Outcome Expectancies of Electronic Cigarette Use: a Concept Mapping Study

PubMed Central

Soule, Eric K.; Maloney, Sarah F.; Guy, Mignonne C.; Eissenberg, Thomas; Fagan, Pebbles

2017-01-01

Electronic cigarette (ECIG) use is growing in popularity, however, little is known about the perceived positive outcomes of ECIG use. This study used concept mapping (CM) to examine positive ECIG outcome expectancies. Sixty-three past 30-day ECIG users (38.1% female) between the ages of 18 and 64 (M = 37.8, SD = 13.3) completed a CM module. In an online program, participants provided statements that completed a prompt: “A specific positive, enjoyable, or exciting effect (i.e., physical or psychological) that I have experienced WHILE USING or IMMEDIATELY AFTER USING an electronic cigarette/electronic vaping device is…”. Participants (n = 35) sorted 123 statements into “piles” of similar content and rated (n = 43) each statement on a 7-point scale (1-Definitely NOT a positive effect to 7-Definitely a positive effect). A cluster map was created using data from the sorting task and analysis indicated a seven cluster model of positive ECIG use outcome expectancies: Therapeutic/Affect Regulation, High/Euphoria, Sensation Enjoyment, Perceived Health Effects, Benefits of Decreased Cigarette Use, Convenience, and Social Impacts. The Perceived Health Effects cluster was rated highest, though all mean ratings were greater than 4.69. Mean cluster ratings were compared and females, younger adults, past 30-day cigarette smokers, users of more “advanced” ECIG devices, and non-lifetime (less than 100 lifetime cigarettes) participants rated certain clusters higher than comparison groups (ps < 0.05). ECIG users associate positive outcomes with ECIG use. ECIG outcome expectancies may affect product appeal and tobacco use behaviors and should be examined further to inform regulatory policies. PMID:28277706

Poppers Maculopathy: Complete Restitution of Macular Changes in OCT after Drug Abstinence.

PubMed

Pahlitzsch, Milena; Mai, Christian; Joussen, Antonia M; Bergholz, Richard

2016-01-01

"Poppers" is a slang term for a group of alkyl nitrites that are used as recreational drugs. Their inhalative intoxication leads to muscle relaxation, analgesia, and euphoria. Maculopathy is a rare but serious side-effect. Clinical, imaging, and electrophysiological findings of seven patients with maculopathy after consumption of poppers were presented. All seven patients were male with a median age of 35 years (range 28-45 years), the median duration of periodical poppers use until the onset of symptoms was 9.8 years (one day to 25 years). Five of seven patients were HIV-positive, one patient was negative, and the HIV-status of one patient was unknown. Median average of visual acuity at presentation was 20/30 in each eye. In all patients, optical coherence tomography (OCT) showed pathognomonic alterations of the outer foveal retina. One patient showed an almost complete restitution of the maculopathy six months after cessation of drug use and following the oral intake of Lutein. Imaging alterations returned to normal and visual acuity recovered from 20/50 and 20/30 (right and left eye, respectively) to 20/20 on both eyes. Follow up of two other cases showed no relevant functional decline or improvement. Toxic maculopathy due to the consumption of poppers is an important differential diagnosis in acute visual loss without clinico-morphological correlate. Optical coherence tomography is the only reliable diagnostic tool in these cases. Complete recovery of visual function and macular morphology is rare, even after cessation of drug abuse. Oral lutein therapy may have a beneficial effect.

Psychoactive “bath salts”: not so soothing

PubMed Central

Baumann, Michael H.; Partilla, John S.; Lehner, Kurt R.

2012-01-01

Recently there has been a dramatic rise in the abuse of so-called “bath salts” products that are purchased as legal alternatives to illicit drugs like cocaine and 3,4-methylenedioxymethamphetamine (MDMA). Baths salts contain one or more synthetic derivatives of the naturally-occurring stimulant cathinone. Low doses of bath salts produce euphoria and increase alertness, but high doses or chronic use can cause serious adverse effects such as hallucinations, delirium, hyperthermia and tachycardia. Owing to the risks posed by bath salts, the governments of many countries have made certain cathinones illegal, namely: 4-methylmethcathinone (mephedrone), 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV). Similar to other psychomotor stimulants, synthetic cathinones target plasma membrane transporters for dopamine (i.e., DAT), norepinephrine (i.e., NET) and serotonin (i.e, SERT). Mephedrone and methylone act as non-selective transporter substrates, thereby stimulating non-exocytotic release of dopamine, norepinephrine and serotonin. By contrast, MDPV acts as a potent blocker at DAT and NET, with little effect at SERT. Administration of mephedrone or methylone to rats increases extracellular concentrations of dopamine and serotonin in the brain, analogous to the effects of MDMA. Not surprisingly, synthetic cathinones elicit locomotor activation in rodents. Stimulation of dopamine transmission by synthetic cathinones predicts a high potential for addiction and may underlie clinical adverse effects. As popular synthetic cathinones are rendered illegal, new replacement cathinones are appearing in the marketplace. More research on the pharmacology and toxicology of abused cathinones is needed to inform public health policy and develop strategies for treating medical consequence of bath salts abuse. PMID:23178799

Psychological distress and psychiatric disorders in primary health care patients in East and West Germany 1 year after the fall of the Berlin Wall.

PubMed

Achberger, M; Linden, M; Benkert, O

1999-04-01

The reunification of Germany confronted citizens in East and West Germany with many changes in their lives. These changes may be considered as critical life events. Especially for those in East Germany, life circumstances drastically changed, and individuals were increasingly required to adopt and develop coping capabilities. In addition to new opportunities and freedom, there was threatening uncertainty about the future. Theories of life events and stress postulate that threat events have an impact on human well-being. It was expected that there would be an increased rate of psychiatric morbidity after unification, especially in the eastern part of Germany. An international study by the WHO on psychiatric disorders in general health care was carried out in 1990, 1 year after the opening of the Berlin Wall, in both parts of Berlin and in Mainz, West Germany. This allowed for a comparison of the prevalence rates of psychiatric disorders among general health care patients in the East and West, after the euphoria immediately following unification had subsided. The prevalence rates of current ICD-10 diagnoses and of subthreshold disorders in East Berlin were similar to the rates in West Berlin and Mainz. The recognition rate of psychiatric disorders by physicians did not differ in East Berlin as compared to West Berlin and Mainz. Contrary to the prediction expected from the literature on individual negative life events, major changes in life circumstances and stressful life events on a societal level within 1 year did not have a major impact on psychological function.

Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease.

PubMed

Spalletta, Gianfranco; Musicco, Massimo; Padovani, Alesandro; Rozzini, Luca; Perri, Roberta; Fadda, Lucia; Canonico, Vincenzo; Trequattrini, Alberto; Pettenati, Carla; Caltagirone, Carlo; Palmer, Katie

2010-11-01

Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. Cross-sectional, multicenter, clinical study. A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N = 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N = 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. The authors' study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms.

Marihuana use. Biologic and behavioral aspects.

PubMed

Mendelson, J H

1976-11-01

More than 70 male chronic marihuana users were studied under research ward conditions for a 31-day period consisting of 5 days of baseline assessment, 21 days of marihuana availability, and 5 days of postsmoking assessment. Biological findings were for the most part within normal limits. Blood chemistry studies showed no abnormalities. Plasma testosterone levels for all subjects at all times during the study were well within normal limits, suggesting that previous reports of testosterone suppression by marihuana may have statistical but not biologic singificance. A significant reduction in baseline vital capacity was observed in six subjects, a compromise in pulmonary function similar to that characteristically produced by chronic inhalation of substances, such as tobacco smoke, which are irritants to the lung. Increased caloric intake and weight gain occurred in virtually all subjects and were causally related to marihuana smoking. The weight gain may be attributable to water retention as well as increased caloric intake. Behavioral findings indicated that no uniform alteration in mood is produced by marihuana smoking--all subjects reported becoming "high", but experienced no consistent degree of euphoria. Mood changes which occurred were relatively mild and were largely dependent on group determinants rather than individual experience. No relationship could be established between marihuana use and motivation to work or engage in socially desirable activities. Evidence that pulmonary function may be compromised as a function of marihuana smoking suggests the need for alerting individuals to this potential health hazard. As was true of cigarette smoking, the eventual public health consequences of marihuana use may become apparent only after large numbers of individuals have smoked marihuana for two or three decades.

A systematic review of the relationship between behavioral and psychological symptoms (BPSD) and caregiver well-being.

PubMed

Feast, Alexandra; Moniz-Cook, Esme; Stoner, Charlotte; Charlesworth, Georgina; Orrell, Martin

2016-11-01

Behavioral and psychological symptoms in dementia (BPSD) are important predictors of institutionalization as well as caregiver burden and depression. Previous reviews have tended to group BPSD as one category with little focus on the role of the individual symptoms. This review investigates the role of the individual symptoms of BPSD in relation to the impact on different measures of family caregiver well-being. Systematic review and meta-analysis of papers published in English between 1980 and December 2015 reporting which BPSD affect caregiver well-being. Paper quality was appraised using the Downs and Black Checklist (1998). Forty medium and high quality quantitative papers met the inclusion criteria, 16 were suitable to be included in a meta-analysis of mean distress scores. Depressive behaviors were the most distressing for caregivers followed by agitation/aggression and apathy. Euphoria was the least distressing. Correlation coefficients between mean total behavior scores and mean distress scores were pooled for four studies. Irritability, aberrant motor behavior and delusions were the most strongly correlated to distress, disinhibition was the least correlated. The evidence is not conclusive as to whether some BPSD impact caregiver well-being more than others. Studies which validly examined BPSD individually were limited, and the included studies used numerous measures of BPSD and numerous measures of caregiver well-being. Future research may benefit from a consistent measure of BPSD, examining BPSD individually, and by examining the causal mechanisms by which BPSD impact well-being by including caregiver variables so that interventions can be designed to target BPSD more effectively.

Effects of low to moderate acute doses of pramipexole on impulsivity and cognition in healthy volunteers.

PubMed

Hamidovic, Ajna; Kang, Un Jung; de Wit, Harriet

2008-02-01

The neurotransmitter dopamine is integrally involved in the rewarding effects of drugs, and it has also been thought to mediate impulsive behaviors in animal models. Most of the studies of drug effects on impulsive behaviors in humans have involved drugs with complex actions on different transmitter systems and different receptor subtypes. The present study was designed to characterize the effect of single doses of pramipexole, a D2/D3 agonist, on measures of cognitive and impulsive behavior, as well as on mood in healthy volunteers. Healthy men and women (N = 10) received placebo and 2 doses of pramipexole, 0.25 and 0.50 mg, in a within-subject, double-blinded study. Outcome measures included changes in cognitive performance, assessed by the Automated Neuropsychological Assessment Metrics, several behavioral measures related to impulsive behavior, including the Balloon Analogue Risk Task, Delay Discounting Task, Go/No-Go Task, Card Perseveration Task, and subjective ratings of mood assessed by Addiction Research Center Inventory, Profile of Mood States, and Drug Effects Questionnaire. Pramipexole decreased positive ratings of mood (euphoria, intellectual efficiency, and energy) and increased both subjectively reported sedation and behavioral sedation indicated by impaired cognitive performance on several measures of the Automated Neuropsychological Assessment Metrics. Single low to medium doses of this drug did not produce a decrease in impulsive responding on behavioral measures included in this study. The sedative-like effects observed in this study may reflect presynaptic actions of the drug. Higher doses with postsynaptic actions may be needed to produce either behavioral or subjective stimulant-like effects.

Lorcaserin. In obesity: unacceptable risks.

PubMed

2014-05-01

Treatment of obesity and overweight is based primarily on dietary measures and physical exercise.There are still no drugs with a favourable harm-benefit balance in this setting. Lorcaserin, a "selective" 5HT2C serotonin receptor agonist, has been refused marketing authorisation in the European Union despite approval in the United States. Clinical evaluation of lorcaserin is based on three placebo-controlled trials, each lasting one year, in a total of about 6000 patients. Two trials involved obese patients, and one obese patients with type 2 diabetes. The results of these trials are undermined by the large proportion (40% to 50%) of patients who were lost to follow-up before the end of the trial. None of the trials examined the impact of lorcaserin on the clinical complications of obesity. From an average initial weight of about 100 kg, patients taking lorcaserin lost only about 3 kg more than those in the placebo groups.The patients put on weight again after lorcaserin was discontinued. Adverse effects observed in clinical trials were mainly gastrointestinal (dry mouth, nausea) and neuropsychiatric (dizziness, fatigue, headache, euphoria). The incidence of cardiac valve disorders was higher with lorcaserin than with placebo. These trials were too short in duration to exclude a risk of cancer (breast cancer and astrocytoma) that was reported in experimental animals. This serotonin agonist is metabolised by the liver, creating a risk of multiple drug interactions. In practice, lorcaserin has not been shown to prevent complications of obesity or even lead to substantial weight loss.There is therefore no justification for exposing patients to the risk of adverse effects.

Analysis of the medical use of marijuana and its societal implications.

PubMed

Taylor, H G

1998-01-01

To review the pharmacology, therapeutics, adverse effects, and societal implications of the medical use of marijuana. MEDLINE and manual searches of English-language marijuana literature, supplemented with interviews of scientists currently conducting cannabinoid research. Search terms included pain OR palliative care AND cannabis or ALL marijuana; cachexia OR appetite OR appetite stimulants; muscle spasticity OR spasm; immune system and cannabis; nausea and vomiting and cancer and cannabis. MEDLINE search terms: cannabis OR marijuana smoking OR marijuana abuse; all glaucoma; multiple sclerosis AND cannabis OR marijuana smoking OR marijuana abuse. Studies on pharmacology, risks, and medical potential of marijuana. Not applicable. The most prominent effects of marijuana are mediated by receptors in the brain. Acute intoxication is characterized by euphoria, loss of short-term memory, stimulation of the senses, and impaired linear thinking. Depersonalization and panic attacks are adverse effects. Increased heart rate and reddened conjunctivae are common physical effects. Chronic, high doses may cause subtle impairment of cognitive abilities that are appear to be long-term, but of unknown duration. Marijuana may be a risk factor for individuals with underlying mental illness. It causes dependence, but compared with cocaine, alcohol, heroin, and nicotine, marijuana has little addictive power and produces only mild withdrawal symptoms. Marijuana shows clinical promise for glaucoma, nausea and vomiting, analgesia, spasticity, multiple sclerosis, and AIDS wasting syndrome. As a recreational drug, marijuana poses dangers, particularly to social and emotional development during adolescence and young adulthood. As a medical drug, marijuana should be available for patients who do not adequately respond to currently available therapies.

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity

PubMed Central

Carhart-Harris, Robin L.; Murphy, Kevin; Leech, Robert; Erritzoe, David; Wall, Matthew B.; Ferguson, Bart; Williams, Luke T.J.; Roseman, Leor; Brugger, Stefan; De Meer, Ineke; Tanner, Mark; Tyacke, Robin; Wolff, Kim; Sethi, Ajun; Bloomfield, Michael A.P.; Williams, Tim M.; Bolstridge, Mark; Stewart, Lorna; Morgan, Celia; Newbould, Rexford D.; Feilding, Amanda; Curran, H. Val; Nutt, David J.

2015-01-01

Background The compound 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals. Methods In a double-blind, placebo-controlled, balanced-order study, MDMA was orally administered to 25 physically and mentally healthy individuals. Arterial spin labeling and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA administration. Participants underwent two arterial spin labeling and two blood oxygen level–dependent scans in a 90-minute scan session; MDMA and placebo study days were separated by 1 week. Results Marked increases in positive mood were produced by MDMA. Decreased CBF only was observed after MDMA, and this was localized to the right medial temporal lobe (MTL), thalamus, inferior visual cortex, and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of global subjective effects of MDMA. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex, and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects. Conclusions The MTLs appear to be specifically implicated in the mechanism of action of MDMA, but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity. PMID:24495461

Receptor Heteromerization Expands the Repertoire of Cannabinoid Signaling in Rodent Neurons

PubMed Central

Rozenfeld, Raphael; Bushlin, Ittai; Gomes, Ivone; Tzavaras, Nikos; Gupta, Achla; Neves, Susana; Battini, Lorenzo; Gusella, G. Luca; Lachmann, Alexander; Ma'ayan, Avi; Blitzer, Robert D.; Devi, Lakshmi A.

2012-01-01

A fundamental question in G protein coupled receptor biology is how a single ligand acting at a specific receptor is able to induce a range of signaling that results in a variety of physiological responses. We focused on Type 1 cannabinoid receptor (CB1R) as a model GPCR involved in a variety of processes spanning from analgesia and euphoria to neuronal development, survival and differentiation. We examined receptor dimerization as a possible mechanism underlying expanded signaling responses by a single ligand and focused on interactions between CB1R and delta opioid receptor (DOR). Using co-immunoprecipitation assays as well as analysis of changes in receptor subcellular localization upon co-expression, we show that CB1R and DOR form receptor heteromers. We find that heteromerization affects receptor signaling since the potency of the CB1R ligand to stimulate G-protein activity is increased in the absence of DOR, suggesting that the decrease in CB1R activity in the presence of DOR could, at least in part, be due to heteromerization. We also find that the decrease in activity is associated with enhanced PLC-dependent recruitment of arrestin3 to the CB1R-DOR complex, suggesting that interaction with DOR enhances arrestin-mediated CB1R desensitization. Additionally, presence of DOR facilitates signaling via a new CB1R-mediated anti-apoptotic pathway leading to enhanced neuronal survival. Taken together, these results support a role for CB1R-DOR heteromerization in diversification of endocannabinoid signaling and highlight the importance of heteromer-directed signal trafficking in enhancing the repertoire of GPCR signaling. PMID:22235275

Viewing pictures of a romantic partner reduces experimental pain: involvement of neural reward systems.

PubMed

Younger, Jarred; Aron, Arthur; Parke, Sara; Chatterjee, Neil; Mackey, Sean

2010-10-13

The early stages of a new romantic relationship are characterized by intense feelings of euphoria, well-being, and preoccupation with the romantic partner. Neuroimaging research has linked those feelings to activation of reward systems in the human brain. The results of those studies may be relevant to pain management in humans, as basic animal research has shown that pharmacologic activation of reward systems can substantially reduce pain. Indeed, viewing pictures of a romantic partner was recently demonstrated to reduce experimental thermal pain. We hypothesized that pain relief evoked by viewing pictures of a romantic partner would be associated with neural activations in reward-processing centers. In this functional magnetic resonance imaging (fMRI) study, we examined fifteen individuals in the first nine months of a new, romantic relationship. Participants completed three tasks under periods of moderate and high thermal pain: 1) viewing pictures of their romantic partner, 2) viewing pictures of an equally attractive and familiar acquaintance, and 3) a word-association distraction task previously demonstrated to reduce pain. The partner and distraction tasks both significantly reduced self-reported pain, although only the partner task was associated with activation of reward systems. Greater analgesia while viewing pictures of a romantic partner was associated with increased activity in several reward-processing regions, including the caudate head, nucleus accumbens, lateral orbitofrontal cortex, amygdala, and dorsolateral prefrontal cortex--regions not associated with distraction-induced analgesia. The results suggest that the activation of neural reward systems via non-pharmacologic means can reduce the experience of pain.

Subjective and physiological effects of oromucosal sprays containing cannabinoids (nabiximols): potentials and limitations for psychosis research.

PubMed

Schoedel, Kerri A; Harrison, Sarah Jane

2012-01-01

Cannabis use is associated with a spectrum of effects including euphoria, relaxation, anxiety, perceptual alterations, paranoia, and impairments in attention and memory. Cannabis is made up of approximately 80 different cannabinoid compounds, which have synergistic or antagonistic effects on the principle active ingredient in cannabis, delta-9-tetrahydrocannabinol (THC). The net overall effect of cannabis is thought to be related to the ratio of its composite constituents; in particular, the ratio of THC to cannabidiol (CBD). Since cannabinoids induce subjective and cognitive changes that share qualitative similarities with schizophrenia, cannabinoids have been used to model psychosis. Some limitations of cannabinoid models of psychosis include the relatively high variability in experiences between different individuals, the potential for inducing unwanted effects, such as toxic psychosis in study subjects, and the lack of data showing that effective anti-psychotic treatments can reverse the behavioural and cognitive/motor effects of cannabinoids. Nabiximols (Sativex®) is an oromucosal spray containing THC and CBD in an approximate 1:1 ratio. While not extensively studied, most studies confirm that nabiximols, despite the different route of administration and presence of CBD, have similar or slightly reduced subjective/cognitive effects compared to similar doses of oral THC. While the presence of CBD may have utility in some models, it is likely that the concentrations are not high enough to meaningfully affect those aspects important for psychosis research. This review suggests that while it may present an alternative to the use of oral THC, oromucosal nabiximols may not present substantial advantages for use in psychosis research.

Dose-related Behavioral, Subjective, Endocrine and Psychophysiological Effects Of the Kappa Opioid Agonist Salvinorin A in Humans

PubMed Central

Ranganathan, Mohini; Schnakenberg, Ashley; Skosnik, Patrick D.; Cohen, Bruce; Pittman, Brian; Sewell, R. Andrew; D’Souza, Deepak Cyril

2012-01-01

Background Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA), a highly selective agonist at the kappa opiate receptor (KOR), is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans. Methods In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological and endocrine effects of 0 mg, 8 mg and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia. Results SA produced psychotomimetic effects and perceptual alterations including dissociative and somaesthetic effects, increased plasma cortisol and prolactin and reduced resting EEG spectral power. SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits or changes in vital signs. The effects were transient and not dose-related. SA administration was very well tolerated without acute or delayed adverse effects. Conclusions SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with KOR agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, to elucidate the underlying mechanisms involved and to explore the basis for individual variability in its effects. PMID:22817868

Magic and the aesthetic illusion.

PubMed

Balter, Leon

2002-01-01

The aesthetic illusion is the subjective experience that the content of a work of art is reality. It has an intrinsic relation to magic, an intrapsychic maneuver oriented toward modification and control of the extraspyschic world, principally through ego functioning. Magic is ontogenetically and culturally archaic, expresses the omnipotence inherent in primary narcissism, and operates according to the logic of the primary process. Magic is a constituent of all ego functioning, usually latent in later development. It may persist as an archaic feature or may be evoked regressively in global or circumscribed ways. It causes a general disinhibition of instincts and impulses attended by a sense of confidence, exhiliration, and exuberance. The aesthetic illusion is a combination of illusions: (1) that the daydream embodied by the work of art is the beholder's own, the artist being ignored, and (2) that the artistically described protagonist is a real person with a real "world." The first illusion arises through the beholder's emotional-instinctual gratification from his or her own fantasy-memory constellations; the second comes about because the beholder, by taking the protagonist as proxy, mobilizes the subjective experience of the imaginary protagonist's "reality." The first illusion is necessary for the second to take place; the second establishes the aesthetic illusion proper. Both illusions are instances of magic. Accordingly, the aesthetic illusion is accompanied by a heady experience of excitement and euphoria. The relation among the aesthetic illusion, magic, and enthusiasm is illustrated by an analytic case, J. D. Salinger's "The Laughing Man," Woody Allen's Play It Again, Sam, Don Quixote, and the medieval Cult of the Saints.

Concomitant consumption of marijuana, alcohol and tobacco in oral squamous cell carcinoma development and progression: recent advances and challenges.

PubMed

Lopes, Caio Fabio Baeta; de Angelis, Bruno Brandão; Prudente, Henrique Maciel; de Souza, Bernardo Vieira Goulart; Cardoso, Sérgio Vitorino; de Azambuja Ribeiro, Rosy Iara Maciel

2012-08-01

Oral squamous cell carcinoma (OSCC) corresponds to 95% of all malignant tumours of the mouth. The association between alcohol and tobacco is the major risk factor for this disease, increasing the chances for the development of OSCC by 35-fold. The plant, Cannabis sativa is smoked as cigarettes or blunts and is commonly used in association with tobacco and alcohol. Any type of smoking habit exposes individuals to a wide range of carcinogens or pro-carcinogens, such as polycyclic aromatic hydrocarbons, as well as some ethanol derived substances such as acetaldehyde (AA), and all are genotoxic in the same way. In addition, ethanol acts in the oral mucosa as a solvent and therefore increases the cellular membrane permeability to carcinogens. Carcinogens found in tobacco are also concentrated in marijuana, but the latter also contains high levels of cannabinoids, bioactive compounds responsible for several effects such as euphoria and analgesia. However, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the major psychotropic cannabinoid found in plants, causes a reduction of cellular metabolism and induction of apoptosis, both of which are anti-neoplastic properties. Apart from limited epidemiologic and experimental data, the effects of concomitant chronic exposure to marijuana (or Δ(9)-THC), tobacco and alcohol in OSCC development and progression is poorly known. This paper reviews the most recent findings on the effects of marijuana over cellular proliferation, as well as in the risk for OSCC, with emphasis on its interaction with tobacco and ethanol consumption. Copyright © 2012 Elsevier Ltd. All rights reserved.

Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers

PubMed Central

Mick, Inge; Myers, Jim; Ramos, Anna C; Stokes, Paul R A; Erritzoe, David; Colasanti, Alessandro; Gunn, Roger N; Rabiner, Eugenii A; Searle, Graham E; Waldman, Adam D; Parkin, Mark C; Brailsford, Alan D; Galduróz, José C F; Bowden-Jones, Henrietta; Clark, Luke; Nutt, David J; Lingford-Hughes, Anne R

2016-01-01

Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [11C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [11C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [11C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [11C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions. PMID:26552847

Use and acute toxicity associated with the novel psychoactive substances diphenylprolinol (D2PM) and desoxypipradrol (2-DPMP).

PubMed

Wood, David M; Dargan, Paul I

2012-09-01

Over the last decade there has been greater use of novel psychoactive substances ('legal highs') across Europe and the United States, including increasing reports of use of diphenylprolinol (D2PM) and desoxypipradrol (2-DPMP). This review will discuss the pharmacology and mechanisms of action of these two compounds, available data on their sources and prevalence of use and reports of acute toxicity and fatalities associated with their use. PubMed was searched using the search terms 'D2PM', '2-DPMP', 'diphenyl-2-pyrrolidinyl-methanol', 'diphenylprolinol', '2-diphenylmethylpiperidine' and 'desoxypipradrol'. These searches identified 70 articles, only five of which were relevant. PHARMACOLOGY AND MECHANISMS OF ACTION: D2PM is a pyrrolidine analogue and 2-DPMP is a desoxy analogue of pipradrol. Animal studies have shown that 2-DPMP increases the release of dopamine and decreases dopamine re-uptake comparable to the effects of cocaine. The binding and activity of D2PM at the dopamine re-uptake transporter, based on currently published data, is also similar to cocaine, although it appears that D2PM has less biological activity. SOURCES AND PREVALENCE OF USE: D2PM and 2-DPMP is available from internet-based suppliers and street level drug dealers; there is currently no systematic data to be able to determine the relative importance of these routes of supply. There is no population level, and limited subpopulation level, data on the prevalence of use of D2PM/2-DPMP. In one 2011 study, 1.6% of 315 individuals in 'gay friendly' nightclubs in South London reported that they had used a pipradrol: 1.0% had used within the last year and 0.6% had used or were planning to use a pipradrol on the night of the survey. ACUTE TOXICITY: Reports on internet discussion fora describe prolonged euphoria and stimulant effects including euphoria, sweating and bruxism with use of D2PM and 2-DPMP. The first report of analytically confirmed acute D2PM toxicity described chest pain and sympathomimetic features (hypertension and tachycardia). Five individuals with analytically confirmed acute D2PM toxicity developed agitation/anxiety and/or insomnia lasting 24-96 h in addition to sympathomimetic features (palpitations, anxiety and agitation). Reports of 49 enquiries relating to a 'legal high' product called 'Whack' (which on analysis was found to contain 2-DPMP and fluorotropacocaine) commonly described unwanted cardiovascular (hypertension in 10/49 and tachycardia in 12/49) and neuropsychiatric (agitation in 14/49 and psychosis in 13/49) effects; the neuropsychiatric effects were prolonged, and persisted for up to 5 days. No analysis of biological samples was undertaken so it is not possible to determine which of these agents if any was responsible for the clinical features. In a series of 26 cases related to the use of 'Ivory Wave' (analysis of a similar 'Ivory Wave' product showed that it contained 2-DPMP), 96% had neuropsychiatric features. Cases presented up to 1 week after use with tachycardia, dystonia, rhabdomyolysis, agitation, hallucinations and paranoia. Confirmatory biological sample analysis was either not available (85.3% of cases) or negative (2.9% of cases) for 2-DPMP; it was positive for 2-DPMP in four (11.8%) of the cases (80% of those where biological analysis was undertaken). D2PM AND 2-DPMP RELATED FATALITIES: Although 2-DPMP has been detected in three fatalities, its role in these deaths has not yet been established. There have been no reports of deaths directly attributed to either D2PM or 2-DPMP. There is emerging evidence of the use of D2PM and 2-DPMP in Europe. D2PM and 2-DPMP have sympathomimetic properties similar to cocaine and, in addition, prolonged and clinically significant neuropsychiatric symptoms have been reported.

Damage to Left Frontal Regulatory Circuits Produces Greater Positive Emotional Reactivity in Frontotemporal Dementia

PubMed Central

Sturm, Virginia E.; Yokoyama, Jennifer S.; Eckart, Janet A.; Zakrzewski, Jessica; Rosen, Howard J.; Miller, Bruce L.; Seeley, William W.; Levenson, Robert W.

2015-01-01

Positive emotions foster social relationships and motivate thought and action. Dysregulation of positive emotion may give rise to debilitating clinical symptomatology such as mania, risk-taking, and disinhibition. Neuroanatomically, there is extensive evidence that the left hemisphere of the brain, and the left frontal lobe in particular, plays an important role in positive emotion generation. Although prior studies have found that left frontal injury decreases positive emotion, it is not clear whether selective damage to left frontal emotion regulatory systems can actually increase positive emotion. We measured happiness reactivity in 96 patients with frontotemporal dementia, a neurodegenerative disease that targets emotion-relevant neural systems and causes alterations in positive emotion (i.e., euphoria and jocularity), and in 34 healthy controls. Participants watched a film clip designed to elicit happiness and a comparison film clip designed to elicit sadness while their facial behavior, physiological reactivity, and self-reported emotional experience were monitored. Whole-brain voxel-based morphometry analyses revealed that atrophy in predominantly left hemisphere fronto-striatal emotion regulation systems including left ventrolateral prefrontal cortex, orbitofrontal cortex, anterior insula, and striatum (pFWE < .05) was associated with greater happiness facial behavior during the film. Atrophy in left anterior insula and bilateral frontopolar cortex was also associated with higher cardiovascular reactivity (i.e., heart rate and blood pressure) but not self-reported positive emotional experience during the happy film (p< .005, uncorrected). No regions emerged as being associated with greater sadness reactivity, which suggests that left-lateralized fronto-striatal atrophy is selectively associated with happiness dysregulation. Whereas previous models have proposed that left frontal injury decreases positive emotional responding, we argue that selective disruption of left hemisphere emotion regulating systems can impair the ability to suppress positive emotions such as happiness. PMID:25461707

Epidemiology and management of neuropsychiatric disorders in Behçet's syndrome.

PubMed

Talarico, Rosaria; Palagini, Laura; d'Ascanio, Anna; Elefante, Elena; Ferrari, Claudia; Stagnaro, Chiara; Tani, Chiara; Gemignani, Angelo; Mauri, Mauro; Bombardieri, Stefano; Mosca, Marta

2015-03-01

Behçet's syndrome (BS) is a systemic, chronic, relapsing vasculitis, typically characterized by recurrent orogenital ulcers, ocular inflammation and skin manifestations; articular, vascular, gastroenteric and neurological involvement may also occur. Besides the other clinical features of BS, it seems relatively frequent that patients with BS develop a neurobehavioural syndrome, characterized by euphoria, bipolar disorders and paranoid attitudes, loss of insight/disinhibition, and indifference to their disease, defined as 'neuro-psycho-BS'. To date, the pathogenetic mechanism underlying neuro-psycho-BS has not been determined. It may be secondary to organic neurological involvement, or it may be related to poor quality of life and the relapsing course of the disease. Another engaging theory suggests that it could be related to the frequent observation of psychiatric symptoms during relapses or, in some cases, in the phases preceding reactivation of the disease; these elements suggest that psychiatric disorders in BS could represent a crucial element, whether a psychiatric subset or a distinct clinical feature of the disease. Moreover, it has been reported that cognitive impairment in BS can be seen with or without central nervous system involvement. Globally, psychiatric symptoms have been described as being multifaceted, ranging from anxiety disorders to depressive-bipolar disorders or to psychotic ones. In addition, some psychological characteristics of BS patients seem to predispose them to maladaptive stress management, which may lead to stress-related disorders, including anxiety and depression. Therefore, the aims of this review are to explore the epidemiology of neuro-psycho-BS by evaluating the relationship between the stress system and the multifaceted psychiatric manifestations in BS, and to summarize the therapeutic strategy used.

[Progress of the laparoscopic colorectal surgery with special consideration regarding cancer treatment].

PubMed

Buchmann, P; Dinçler, S

2006-04-26

The development of laparoscopic surgery began with the diagnostic coelioscopy in 1901 and the first appendectomy in 1983. Its worldwide spread started in 1987 with the cholecystectomy. Four years later the right hemicolectomy and sigmoid resection were also described. The initial euphoria however evaporated when the first reports of port-site-metastasis appeared. The controversy whether one should be allowed or not to operate carcinomas laparoscopically, provoked a boom in research with as result that in 2000 it had been confirmed that the incidence of port-site-metastasis was about the same as drain-site-metastasis after open procedures (0.9%). Randomized studies comparing laparoscopic interventions and open surgery showed no difference in the long-term results of colon-carcinoma. For experienced surgeons this is also the case for rectum-carcinoma. Hereby the learning curve is of great importance and has been put at 30 to 70 procedures, taken into account the duration of the operation or other criteria such as conversion to open surgery and complications. With growing experience the amount of material used during an operation goes down, which results in a lower overall cost of the minimal-invasive technique compared with open surgery. In cost calculations one should also take into account the fact that the recovery time and the return to every-day life is generally quicker for patients after laparoscopic surgery while overall they also have a significant better quality of life score (SF-36) in the longer term. Currently, i.e. in 2006 the laparoscopic colorectal surgery has become an established procedure. It is thought that laparoscopic interventions give additional advantages because the immune system is less affected but this must still be confirmed through research.

Rising to the Forensic Analytical Challenges Associated with the Global Increase in Seizures of Cathinone-derived "Legal Highs"

NASA Astrophysics Data System (ADS)

Sutcliffe, O.; Daeid, N. Nic; Kemp, H. F.; Meier-Augenstein, W.

2012-04-01

Substances touted as "legal highs" and known by names such as "ivory wave" or "NRG-1" mimic the effects of illegal drugs such as amphetamine, cocaine and ecstasy. Sold as "bath salts", plant food or incense these so-called "designer drugs" can be dangerous but despite this health danger many have not yet been made illegal and are difficult to detect with current drug tests. These "bath salts" can cause euphoria, paranoia, anxiety and hallucinations. They often contain mephedrone, a synthetic compound structurally related to methcathinone, which is found in Khat - a plant that, like mephedrone itself, is illegal to possess in many countries. "Bath salts" are usually labelled as being "not for human consumption" and the name "bath salts" is used by those who sell these substances as a way of circumventing legislation when supplying them. Mephedrone (a synthetic cathinone) was legal (or at least not illegal) in the UK until April 2010 when it was classified as a Class B, Schedule 1 substance (UK Misuse of Drugs Act 1971). The current challenges to law enforcement agencies are: (1) Identification and quantification of new and emerging illicit substances. (2) Tracing or linking product to precursor (i.e. source identification). Here, we present as a potential way of tracing the source of the raw materials, and consequently providing information as to who is making the "bath salts", which is based on identification of products and/or adulterants/excipients by GCMS in combination with isotopic profiling of both precursor and product to determine characteristic shifts or linkages in isotopic composition between starting material used, synthetic processes employed and resultant drug produced.

Selective κ receptor partial agonist HS666 produces potent antinociception without inducing aversion after i.c.v. administration in mice.

PubMed

Spetea, Mariana; Eans, Shainnel O; Ganno, Michelle L; Lantero, Aquilino; Mairegger, Michael; Toll, Lawrence; Schmidhammer, Helmut; McLaughlin, Jay P

2017-08-01

The κ receptor has a central role in modulating neurotransmission in central and peripheral neuronal circuits that subserve pain and other behavioural responses. Although κ receptor agonists do not produce euphoria or lead to respiratory suppression, they induce dysphoria and sedation. We hypothesized that brain-penetrant κ receptor ligands possessing biased agonism towards G protein signalling over β-arrestin2 recruitment would produce robust antinociception with fewer associated liabilities. Two new diphenethylamines with high κ receptor selectivity, HS665 and HS666, were assessed following i.c.v. administration in mouse assays of antinociception with the 55°C warm-water tail withdrawal test, locomotor activity in the rotorod and conditioned place preference. The [ 35 S]-GTPγS binding and β-arrestin2 recruitment in vitro assays were used to characterize biased agonism. HS665 (κ receptor agonist) and HS666 (κ receptor partial agonist) demonstrated dose-dependent antinociception after i.c.v. administration mediated by the κ receptor. These highly selective κ receptor ligands displayed varying biased signalling towards G protein coupling in vitro, consistent with a reduced liability profile, reflected by reduced sedation and absence of conditioned place aversion for HS666. HS665 and HS666 activate central κ receptors to produce potent antinociception, with HS666 displaying pharmacological characteristics of a κ receptor analgesic with reduced liability for aversive effects correlating with its low efficacy in the β-arrestin2 signalling pathway. Our data provide further understanding of the contribution of central κ receptors in pain suppression, and the prospect of dissociating the antinociceptive effects of HS665 and HS666 from κ receptor-mediated adverse effects. © 2017 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

[Cocaine - Characteristics and addiction].

PubMed

Girczys-Połedniok, Katarzyna; Pudlo, Robert; Jarząb, Magdalena; Szymlak, Agnieszka

Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4):537-544. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Imaging opiate receptors with positron emission tomography

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

Frost, J.J.; Dannals, R.F.; Ravert, H.T.

Opiate receptors exist in the mammalian brain and are thought to meditate the diverse pharmacological actions of the opiates, such as analgesia, euphoria, and sedation. The 4-carbomethoxyl derivatives of fentanyl, such as lofentanil and R31833 (4-carbomethoxyfentanyl) bind to the opiate receptor with high affinity. C-11 R31833 was synthesized by reacting C-11 methyl iodide with the appropriate carboxylate. Male ICR mice were injected intravenously with C-11 R31833 (5..mu..g/kg), killed 30 minutes later, and the brains rapidly dissected. The thalami, striata, and cerebral cortex are rich in opiate receptors, but the cerebellum contains a very low concentration of opiate receptors. The thalamus/cerebellummore » and striatum/cerebellum activity ratios, calculated per mg of wet tissue, were 4.1 and 5.2 respectively. Coinjection of 5mg/kg naloxone reduced the ratios to 1.1, which indicates that the preferential localization of C-11 R31833 in the thalami and striata is due to binding to opiate is due to binding to opiate receptors. A 22 kg anesthetized male baboon was imaged using the NeuroECAT after injection of 18.9 mCi of C-11 R13833 (0.50 ..mu..g/kg, specific activity 616 Ci/mmole at time of injection). From 15-70 minutes after injection preferential accumulation of activity could be seen in the thalami, caudate nuclei, and cerebral cortex and, conversely, low activity was demonstrated in the cerebellum. At one hour postinjection the maximum measured caudate/cerebellum activity ratio per pixel was 2.9. For the NeuroECAT the recovery coefficient for the baboon caudate is ca. 0.2-0.3, and therefore the actual caudate/cerebellum ratio is ca. 10-15.« less

Prevalence of neuropsychiatric symptoms in Alzheimer's disease: a cross-sectional descriptive study in Thailand.

PubMed

Charernboon, Thammanard; Phanasathit, Muthita

2014-05-01

To estimate the prevalence of neuropsychiatric symptoms in Thai patients with Alzheimer's disease. The present study is a cross-sectional descriptive design. The participants comprised 62 patients from the Memory Clinic at Thammasat University Hospital, Thailand. Subjects were diagnosed as having Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria and received global Clinical Dementia Rating scale (CDR) score of at least stage 1. All participants were assessed using the Neuropsychiatric Inventory Questionnaire (NPI) and the Thai Mental State Examination (TMSE). The subjects were female 62.9% and male 37.1%, the mean age was 76 +/- 6.7 years. The majority of them (62.9%) were in the mild stage (CDR = 1). The result showed that the prevalence of neuropsychiatric symptoms (> or = 1 symptom) reported was 100%. The most common symptoms were apathy (71%), aberrant motor behavior (61.3%), sleep problems (56.5%), eating problems (51.6%) and agitation/aggression (45.2%), whereas the least was euphoria (6.5%). The number of neuropsychiatric symptoms increased with severity of the disease. The result also showed that 61.3% of the participants presented with the chief complaint of neuropsychiatric symptoms, whereas memory complaints were only 38.7%. Neuropsychiatric symptoms are very common in Thai Alzheimer's disease patients. Therefore, management of Alzheimer's patients should include an assessment of neuropsychiatric symptoms and also concentrate on reducing these symptoms. The number of neuropsychiatric symptoms increases with disease progression. Moreover, neuropsychiatric symptoms were the most common presenting problem rather than memory problem in Thai patients with Alzheimer's disease.

Safety of atomoxetine in combination with intravenous cocaine in cocaine-experienced participants.

PubMed

Cantilena, Louis; Kahn, Roberta; Duncan, Connie C; Li, Shou-Hua; Anderson, Ann; Elkashef, Ahmed

2012-12-01

Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine and also whether cognitive function was affected by atomoxetine during short-term administration. In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 and 40 mg) was infused intravenously in sequential daily sessions. Preinfusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Preinfusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80- and 100-mg atomoxetine doses. All electrocardiogram parameters were unchanged. Visual Analog Scale (VAS) scores for "bad effect" in the atomoxetine group were significantly higher at baseline, then declined, and for "likely to use" declined with atomoxetine treatment. On the Addiction Research Center Inventory, the atomoxetine group scored significantly lower on amphetamine, euphoria, and energy subscales (P < 0.0001). Other VAS descriptors, Brief Substance Craving Scale, Profile of Moods State, and Brief Psychiatric Rating Scale showed no differences. Atomoxetine did not affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine. Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine.

User identified positive outcome expectancies of electronic cigarette use: A concept mapping study.

PubMed

Soule, Eric K; Maloney, Sarah F; Guy, Mignonne C; Eissenberg, Thomas; Fagan, Pebbles

2017-05-01

Electronic cigarette (ECIG) use is growing in popularity, but little is known about the perceived positive outcomes of ECIG use. This study used concept mapping (CM) to examine positive ECIG outcome expectancies. Sixty-three past 30-day ECIG users (38.1% female) between the ages of 18 and 64 (M = 37.8, SD = 13.3) completed a CM module. In an online program, participants provided statements that completed a prompt: "A specific positive, enjoyable, or exciting effect (i.e., physical or psychological) that I have experienced WHILE USING or IMMEDIATELY AFTER USING an electronic cigarette/electronic vaping device is. . . ." Participants (n = 35) sorted 123 statements into "piles" of similar content and rated (n = 43) each statement on a 7-point scale (1 = Definitely NOT a positive effect to 7 = Definitely a positive effect). A cluster map was created using data from the sorting task, and analysis indicated a 7 cluster model of positive ECIG use outcome expectancies: Therapeutic/Affect Regulation, High/Euphoria, Sensation Enjoyment, Perceived Health Effects, Benefits of Decreased Cigarette Use, Convenience, and Social Impacts. The Perceived Health Effects cluster was rated highest, although all mean ratings were greater than 4.69. Mean cluster ratings were compared, and females, younger adults, past 30-day cigarette smokers, users of more "advanced" ECIG devices, and nonlifetime (less than 100 lifetime cigarettes) participants rated certain clusters higher than comparison groups (ps < 0.05). ECIG users associate positive outcomes with ECIG use. ECIG outcome expectancies may affect product appeal and tobacco use behaviors and should be examined further to inform regulatory policies. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Isolation and characterization of ellagitannins as the major polyphenolic components of Longan (Dimocarpus longan Lour) seeds.

PubMed

Sudjaroen, Yuttana; Hull, William E; Erben, Gerhard; Würtele, Gerd; Changbumrung, Supranee; Ulrich, Cornelia M; Owen, Robert W

2012-05-01

Longan (Dimocarpus longan Lour, syn. Euphoria longan Lam.) represents an important fruit in Northern Thailand and has significant economic impact. The fruit is either consumed fresh or as commercially prepared dried and canned products. The canning industry in Thailand produces considerable quantities of waste products, in particular Longan seeds. Because these seeds may be an exploitable source of natural phenolic antioxidants, it was of interest to identify, purify and quantitate the major potential antioxidant phenolics contained therein. The polyphenolic fraction from ground Longan seeds was obtained by extraction with methanol after delipidation with hexane. The hexane extract contained predominantly long-chain fatty acids with major contributions from palmitic (35%) and oleic (28%) acids. The polyphenolic fraction (80.90 g/kg dry weight) was dominated by ellagic acid (25.84 g/kg) and the known ellagitannins corilagin (13.31 g/kg), chebulagic acid (13.06 g/kg), ellagic acid 4-O-α-l-arabinofuranoside (9.93 g/kg), isomallotinic acid (8.56 g/kg) and geraniin (5.79 g/kg). Structure elucidation was performed with mass spectrometry and complete assignment of (1)H and (13)C NMR signals. The methanol extracts exhibited strong antioxidant capacities with an IC(50) of 154 μg/ml for reactive oxygen species attack on salicylic acid and 78 μg/ml for inhibition of xanthine oxidase in the hypoxanthine/xanthine oxidase assay. The extracts were less effective in the 2-deoxyguanosine assay (IC(50)=2.46 mg/ml), indicating that gallates along with ellagic acid and its congeners exert their potential antioxidant effects predominantly by precipitation of proteins such as xanthine oxidase. This was confirmed for the pure compounds gallic acid, methyl gallate, ellagic acid and corilagin. Copyright © 2012 Elsevier Ltd. All rights reserved.

Is love passion an addictive disorder?

PubMed

Reynaud, Michel; Karila, Laurent; Blecha, Lisa; Benyamina, Amine

2010-09-01

Inquiry regarding the relationship between passionate love and addiction has long been a topic of intense debate. Recent advances in neurobiology now allow for an examination between these two states. After describing the clinical distinctions between "love passion," "love addiction," and "sex addiction," we compare clinical, neuropsychological, neurobiological, and neuroimaging data on love, passion, pathological gambling (PG) and substance dependence. There are no recognized definitions or diagnostic criteria for "love addiction," but its phenomenology has some similarities to substance dependence: euphoria and unrestrained desire in the presence of the love object or associated stimuli (drug intoxication); negative mood, anhedonia, and sleep disturbance when separated from the love object (drug withdrawal); focussed attention on and intrusive thoughts about the love object; and maladaptive or problematic patterns of behavior (love relation) leading to clinically significant impairment or distress, with pursuit despite knowledge of adverse consequences. Limited animal and human studies suggest that brain regions (e.g., insula, anterior cingulated [ACC], orbitofrontal [OFC]) and neurotransmitters (dopamine) that mediate substance dependence may also be involved with love addiction (as for PG). Ocytocin (OT), which is implicated in social attachment and mating behavior, may also be involved in substance dependence. There are no data on the epidemiology, genetics, co-morbidity, or treatment of love addiction. There are currently insufficient data to place some cases of "love passion" within a clinical disorder, such as "love addiction," in an official diagnostic nomenclature or to firmly classify it as a behavioral addiction or disorder of impulse control. Further clinical and scientific studies are needed to improve our understanding and treatment of this condition. For these studies, we propose new criteria for evaluating addiction to love.

Involvement of dopamine D1/D2 receptors on harmane-induced amnesia in the step-down passive avoidance test.

PubMed

Nasehi, Mohammad; Piri, Morteza; Nouri, Maryam; Farzin, Davood; Nayer-Nouri, Touraj; Zarrindast, Mohammad Reza

2010-05-25

Ingestion of harmane and other alkaloids derived from plant Peganum harmala has been shown to elicit profound behavioural and toxic effects in humans, including hallucinations, excitation, feelings of elation, and euphoria. These alkaloids in the high doses can cause a toxic syndrome characterized by tremors and convulsions. Harmane has also been shown to act on a variety of receptor systems in the mammalian brain, including those for serotonin, dopamine and benzodiazepines. In animals, it has been reported to affect short and long term memory. In the present study, effects of dopamine D1 and D2 receptor antagonists on the harmane (HA)-induced amnesia and exploratory behaviors were examined in mice. One-trial step-down and hole-board paradigms were used for the assessment of memory retention and exploratory behaviors in adult male NMRI mice respectively. Intraperitoneal (i.p.) administration of HA (5 and 10 mg/kg) immediately after training decreased memory consolidation, while had no effect on anxiety-like behavior. Memory retrieval was not altered by 15- or 30 min pre-testing administration of the D1 (SCH23390, 0.025, 0.05 and 0.1 mg/kg) or D2 (sulpiride 12.5, 25 and 50 mg/kg) receptor antagonists, respectively. In contrast, SCH23390 (0.05 and 0.1 mg/kg) or sulpiride (25 and 50 mg/kg) pre-test administration fully reversed HA-induced impairment of memory consolidation. Finally, neither D1 nor D2 receptor blockade affected exploratory behaviors in the hole-board paradigm. Altogether, these findings strongly suggest an involvement of D1 and D2 receptors modulation in the HA-induced impairment of memory consolidation. Copyright 2010 Elsevier B.V. All rights reserved.

Optimizing the detection of bipolar II disorder in outpatient private practice: toward a systematization of clinical diagnostic wisdom.

PubMed

Akiskal, Hagop S; Benazzi, Franco

2005-07-01

We review a clinical diagnostic approach to validate a redefinition of bipolar II disorder (BPII), which bypasses several conservative steps in the DSM-IV Mood Module of the Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV) to make detection of BPII more "clinician-friendly." 563 consecutive private outpatients presenting with a DSM-IV-diagnosed major depressive episode (MDE) were included in the analyses. We used a modified SCID-CV in a semistructured way, used a duration of hypomania > or =2 days (rather than the 4-day floor cutoff recommended), did not follow the SCID-CV's stem (mood) skip-out instruction, focused more on past history of overactive behavior rather than mood change, and assessed hypomanic features both outside and during index MDE. Validation of BPII so-defined against major depressive disorder (MDD) was undertaken in the Washington University tradition. The study was conducted from June 1999 to December 2003. BPII occurred in 56.8% of patients. Compared with MDD, BPII had a significantly earlier index age and age at onset of first MDE and higher rates of atypical features, depressive recurrences, hypomanic symptoms during MDE, trait mood lability, and bipolar family history (p = .0000 for all variables). Our experience suggests that when probing history for past hypomanic episodes, behavioral activation should be inquired first, thereby facilitating the patient's subsequent recall of euphoria and/or irritability during such activated periods. Information from significant others or past records is also crucial. In light of these clinical procedures, BPII emerged as more prevalent than MDD. We submit that clinicians have the distinct advantage of intimate knowledge of their patients, which, coupled with the procedures outlined herein, can maximize the yield of BPII diagnoses.

Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials.

PubMed

Savaskan, Egemen; Mueller, Heiko; Hoerr, Robert; von Gunten, Armin; Gauthier, Serge

2018-03-01

ABSTRACTBackground:In randomized controlled trials, Ginkgo biloba extract EGb 761® has been found to be effective in the treatment of behavioral and psychological symptoms of dementia (BPSD). To assess the effects of EGb 761® on specific BPSD, we analyzed data from all randomized, placebo-controlled, at least 20-week, trials of EGb 761® enrolling patients with dementia (probable Alzheimer's disease (AD), probable vascular dementia or probable AD with cerebrovascular disease) who had clinically significant BPSD (Neuropsychiatric Inventory (NPI) total score at least 6). Data were pooled and joint analyses of NPI single item composite and caregiver distress scores were performed by meta-analysis with a fixed effects model. Four trials involving 1628 patients (EGb 761®, 814; placebo, 814) were identified; treatment duration was 22 or 24 weeks; the daily dose of EGb 761® was 240 mg in all trials. Pooled analyses including data from the full analysis sets of all trials (EGb 761®, 796 patients; placebo, 802 patients) revealed significant superiority of EGb 761® over placebo in total scores and 10 single symptom scores. Regarding caregiver distress scores, EGb 761®-treated patients improved significantly more than those receiving placebo in all symptoms except delusions, hallucinations, and elation/euphoria. The benefit of EGb 761® mainly consists of improvement in symptoms present at baseline, but the incidence of some symptoms was also decreased. Twenty two- to twenty four-week treatment with Ginkgo biloba extract EGb 761® improved BPSD (except psychotic-like features) and caregiver distress caused by such symptoms.

Personalizing Stem Cell Research and Therapy: The Arduous Road Ahead or Missed Opportunity?

PubMed Central

Patel, S.A.; King, C.C.; Lim, P.K.; Habiba, U.; Dave, M.; Porecha, R.; Rameshwar, P.

2010-01-01

The euphoria of stem cell therapy has diminished, allowing scientists, clinicians and the general public to seriously re-examine how and what types of stem cells would effectively repair damaged tissue, prevent further tissue damage and/or replace lost cells. Importantly, there is a growing recognition that there are substantial person-to-person differences in the outcome of stem cell therapy. Even though the small molecule pharmaceuticals have long remained a primary focus of the personalized medicine research, individualized or targeted use of stem cells to suit a particular individual could help forecast potential failures of the therapy or identify, early on, the individuals who might benefit from stem cell interventions. This would however demand collaboration among several specialties such as pharmacology, immunology, genomics and transplantation medicine. Such transdisciplinary work could also inform how best to achieve efficient and predictable stem cell migration to sites of tissue damage, thereby facilitating tissue repair. This paper discusses the possibility of polarizing immune responses to rationalize and individualize therapy with stem cell interventions, since generalized “one-size-fits-all” therapy is difficult to achieve in the face of the diverse complexities posed by stem cell biology. We also present the challenges to stem cell delivery in the context of the host related factors. Although we focus on the mesenchymal stem cells in this paper, the overarching rationale can be extrapolated to other types of stem cells as well. Hence, the broader purpose of this paper is to initiate a dialogue within the personalized medicine community by expanding the scope of inquiry in the field from pharmaceuticals to stem cells and related cell-based health interventions. PMID:20563265

Safety of Atomoxetine in Combination with Intravenous Cocaine in Cocaine- Experienced Participants

PubMed Central

Cantilena, Louis; Kahn, Roberta; Duncan, Connie C.; Li, Shou-Hua; Anderson, Ann; Elkashef, Ahmed

2012-01-01

Objectives Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine, and also whether cognitive function was affected by atomoxetine during short-term administration. Methods In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 mg and 40 mg) was infused intravenously in sequential daily sessions. Results Pre-infusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Pre-infusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80 mg and 100 mg atomoxetine doses. All ECG parameters were unchanged. VAS scores for “bad effect” in the atomoxetine group were significantly higher at baseline, then declined, and for “likely to use” declined with atomoxetine treatment. On the ARCI the atomoxetine group scored significantly lower on amphetamine, euphoria and energy subscales (p<0.0001). Other VAS descriptors, BSCS, POMS, and BPRS showed no differences. Atomoxetine did not affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine. Conclusions Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine. PMID:22987022

Discriminating the effects of Cannabis sativa and Cannabis indica: a web survey of medical cannabis users.

PubMed

Pearce, Daniel D; Mitsouras, Katherine; Irizarry, Kristopher J

2014-10-01

To evaluate the opinions of medical cannabis (MC) users on the effects of Cannabis indica vs. those of Cannabis sativa on conditions and symptoms through an online survey. Survey of 95 non-randomly assigned MC users. A two-sided chi-square test followed by Bonferroni post hoc multiple comparison and Fisher exact test were used to determine correlations. The Cronbach α was used to determine internal consistency. Announcements on 13 MC websites with links to SurveyMonkey.com. Self-identified MC users. Web survey. Species effects were compared regarding health symptoms, conditions, purpose, route, and trust in product label. Trust in the purity, the route of administration, or the purpose (recreational vs. medicinal) did not differ between the two species. A preference for C. indica was statistically significant for pain management (p=0.001), helping with sedation (p=0.015), and sleep (p<0.001). C. sativa was preferred for euphoria (p<0.001) and enhancing energy (p=0.022). The conditions reaching statistical significance for C. indica preference were: nonmigraine headaches (p=0.042), glaucoma (p=0.036), neuropathy (p=0.024), spasticity (p=0.048), seizures (p=0.031), insomnia (p<0.001), and joint pain (p=0.048). For C. sativa, no conditions reached significance. The MC websites' descriptions of effects that agreed with the survey results are listed. Some conditions had very few respondents. The internal consistency/reliability (Cronbach α) was adequate for the condition scale but not for the symptom survey. In this anonymous Web survey, which had limitations, the two species had different effect associations on symptoms and conditions, possibly because of ingredient differences. Future surveys and subsequent prospective definitive trials are needed to confirm the findings.

Ethylphenidate: availability, patterns of use, and acute effects of this novel psychoactive substance.

PubMed

Ho, James H; Bailey, George P; Archer, John R H; Dargan, Paul I; Wood, David M

2015-10-01

Ethylphenidate is a novel psychoactive substance that is an analogue of methylphenidate. This paper describes its availability, patterns of use, and acute effects. Searches of the scientific and grey literature (publicly accessible Internet resources) were undertaken, using the keywords "Ethylphenidate", "Ethyl phenidate", "Ethyl phenyl(piperidin-2-yl)acetate", and "Nopaine", to identify information on the prevalence and patterns of use, desired effects, and toxicity of ethylphenidate. An Internet snapshot survey was performed on 10 February 2015 to provide information on availability and cost of ethylphenidate. The literature search identified 1 case series of acute recreational ethylphenidate toxicity, 1 case report of ethylphenidate dependence, 1 qualitative analysis of user reports on Internet drug forums, 2 conference abstracts for surveillance studies, 1 report of two cases of ethylphenidate detected in post-mortem analyses, and 198 user reports on Internet discussion forums and social media sites. The Internet snapshot survey found 83 websites selling ethylphenidate, with purchase prices ranging from £28.20 ± 0.63 (€37.71 ± 0.85) per gram for a 500-mg amount to £2.64 ± 0.57 (€3.53 ± 0.77) per gram for 1 kg. The published cases and Internet user reports suggest the acute effects of ethylphenidate are similar to other stimulant drugs; the most common route of use was by nasal insufflation. The most common desired effects were euphoria, stimulation, and increased concentration, sociability, and energy levels; the most common unwanted effects included anxiety, palpitations, insomnia, and paranoia. This review of the scientific and grey literature has demonstrated that the acute harms associated with its use are stimulant in nature and that ethylphenidate is widely available to users over the Internet, with significant discounts for bulk purchases.

A pilot study of inhaled methoxyflurane for procedural analgesia in children.

PubMed

Babl, Franz; Barnett, Peter; Palmer, Greta; Oakley, Ed; Davidson, Andrew

2007-02-01

Methoxyflurane (MF), a potent volatile anesthetic, can be used as an analgesic in subanesthetic concentrations. In Australia, MF is extensively used in children and adults as an analgesic in the prehospital setting via a hand-held inhaler device. We conducted a pilot study to explore its use as a patient controlled analgesic for painful procedures in children in the emergency department (ED). This is a prospective observational case series of children aged 5 years and older requiring procedural analgesia for brief painful procedures. Pain scores, depth of sedation, adverse events and patient, parent and staff satisfaction were assessed as well as consumption of MF measured. Fourteen patients (aged 6-13 years) received MF mainly for extremity injuries. Amount of MF consumed ranged from 0.36 to 3.06 g per patient inhaled over 4-25 min. There were no serious adverse events. No patient was deeply sedated. Five patients had mild brief self-resolving adverse events including agitation, euphoria, blurry vision, dizziness and cough. Four patients with fractures with initial high pain scores (> or =6) received MF for bridging analgesia with large drops in pain scores. Four patients who required fracture reductions with initial low scores did not achieve adequate analgesia. The remaining six patients had painful procedures undertaken with satisfactory analgesia. On the basis of this small pilot study of MF use in children in the ED, this agent appears to be a powerful analgesic. MF seems most useful as a self-titrated bridging analgesic agent in patients after extremity trauma. It appears less useful as a procedural agent when patients are unable to anticipate and achieve a sufficient level of analgesia before painful stimulus infliction. Pre- and intraprocedure coaching is an important aspect of its use especially if initial pain scores are low.

Early signal of diverted use of tropicamide eye drops in France.

PubMed

Ponté, Camille; Pi, Christian; Palmaro, Aurore; Jouanjus, Emilie; Lapeyre-Mestre, Maryse

2017-08-01

Tropicamide is a mydriatic drug used as eye-drops for diagnostic or therapeutic purposes. From 2013, a diverted use by intravenous route has been suspected in Eastern Europe in opioids users. To date, no signal of misuse has been identified in France. The aims of this study were to investigate any early signals of a diverted use of tropicamide eye drops and to collect information regarding motives for the misuse and tropicamide-induced effects. Information was obtained at three levels: (1) at regional level (Midi-Pyrénées area), from reimbursement data and pharmacists' reports on suspicious requests; (2) at national level: from reimbursement data and prescriptions suggesting possible abuse from the OSIAP (Ordonnances Suspectes, Indicateur d'Abus Possible) survey; and (3) at international level: from VigiBase ® reports and Web sources. Beta-blocker eye-drops were used as comparators. In France, in 2014-2015, 17 (0.91%, 95% CI [0.53-1.46%]) falsified prescriptions involving tropicamide were identified in the OSIAP survey (compared with 0%, 95% CI [0-0.19%] for beta-blockers). Moreover, 37 other suspicious prescriptions were presented in 2015 (notified in 2016). In Midi-Pyrénées, seven patients aged 35-49 were reimbursed for 19-45 vials of 10 ml, in a year. Since September 2014, the regional Addictovigilance Centre has received 91 notifications of suspicious requests to obtain tropicamide. In VigiBase ® , two cases were identified but none in France. An increased interest in tropicamide-related Internet searches was observed from Russia and Ukraine. These results represent the first early warnings of a tropicamide diverted use in France. Tropicamide abusers would seek euphoria or hallucinations. The high doses involved in intravenous administration could lead to serious complications. © 2017 The British Pharmacological Society.

The Phosphodiesterase 5-Inhibitors (PDE-5i) for ERECTILE DYSFUNCTION (ED): A Therapeutic Challenge For Psychiatrists.

PubMed

Koon, Chong Siew; Sidi, Hatta; Kumar, Jaya; Das, Srijit; Xi, Ong Wan; Hatta, Muhammad Hizri; Alfonso, Cesar

2017-02-15

Erectile function (EF) is a prerequisite for satisfactory sexual intercourse (SI) and central to male sexual functioning. Satisfactory SI eventually leads to orgasm - a biopsychophysiological state of euphoria - leading to a sense of bliss, enjoyment and positive mental well being. For a psychiatrist, treating ED is self-propelled to harmonize these pleasurable experiences alongside with encouragement of physical wellness and sensuality. Hence, the role of PDE-5i is pivotal in the context of treating ED constitutes a therapeutic challenge. PDE-5i work via the dopaminergic-oxytocin-nitric oxide pathway by increasing the availability of endothelial's guanosine monophosphate (GMP), immediately causing relaxation of the penile smooth muscle and an erection. The PDE-5i, like sildenafil, vardenafil and tadalafil, are effective in the treatment of ED with some benefits and disadvantages compared to other treatment modalities. Prescribed PDE-5i exclusively improve EF, fostering male's self-confidence and self-esteem. Treatment failures are associated with factors such as absent (or insufficient) sexual stimulation, psychosexual conflicts and the co-existence of medical disorders. Managing ED requires dealing with underlying medical diseases, addressing other co-morbid sexual dysfunctions like premature ejaculation (PE), and educating the patient on healthy life-styles beside being cautious with the potential side-effects and drug-drug interactions. Furthermore, by dealing with interpersonal dynamics within the couple and embracing adequate lifestyles (managing stress and revising one's sexual scripts), PDE-5i treatment benefits may be enhanced. In this review, we propose a holistic conceptual framework approach for psychiatric management of patients with ED. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Alcoholism between Fiction and Reality.

PubMed

Carota, Antonio; Calabrese, Pasquale

2013-01-01

Alcoholism has always been emphasized in literature, narratives, and theater as its prevalence and related disability are very high, is found throughout the world, and affects women and men of all ages and social classes. There is a tragic or romantic fascination in the deep sense of personal failure that drinking is able to relieve and in the uncontrollable inability to stop drinking. These aspects have been portrayed well by fictional alcoholics in movies and novels. It has become evident that biological traits together with a complex series of psychosocial factors (e.g. negative life events, depression, anxiety, and other psychiatric or personality disorders), which are also well represented in novels and movies, can lead to alcohol addiction. Behavioral (euphoria, disinhibiting behaviors, aggressiveness) and neurological changes (confusion, bradypsychism, slurred speech, ataxia, blackouts) related to alcohol intoxication are also well portrayed by fictional characters. Delirium tremens, epilepsy, alcohol dementia, and Wernicke-Korsakoff disease, however, find less representation in literature and on the stage and screen. The treatment of alcoholic dependence is very difficult (as often reported by fictional and real stories), but should never be considered hopeless. It should be initiated at any stage of the disease. The support offered by Alcoholics Anonymous has always had great appeal for the public. Fictional works can portray alcohol addiction superbly and show some dark sides of human nature (negative emotions and autodestructive thoughts and behaviors), and, at the same time, the severity and pervasiveness of mental illnesses. The psychiatric and psychosocial aspects of alcohol addiction in movies and novels could be an inspiring source for new psychological studies and rehabilitation programs. Copyright © 2013 S. Karger AG, Basel.

Changes in cue reactivity and attentional bias following experimental cue exposure and response prevention: a laboratory study of the effects of D-cycloserine in heavy drinkers.

PubMed

Kamboj, Sunjeev K; Massey-Chase, Rachel; Rodney, Lydia; Das, Ravi; Almahdi, Basil; Curran, H Valerie; Morgan, Celia J A

2011-09-01

The effects of D-cycloserine (DCS) in animal models of anxiety disorders and addiction indicate a role for N-methyl D-aspartate (NMDA) receptors in extinction learning. Exposure/response prevention treatments for anxiety disorders in humans are enhanced by DCS, suggesting a promising co-therapy regime, mediated by NMDA receptors. Exposure/response prevention may also be effective in problematic drinkers, and DCS might enhance habituation to cues in these individuals. Since heavy drinkers show ostensible conditioned responses to alcohol cues, habituation following exposure/response prevention should be evident in these drinkers, with DCS enhancing this effect. The objective of this study is to investigate the effect of DCS on exposure/response prevention in heavy drinkers. In a randomised, double-blind, placebo-controlled study, heavy social drinkers recruited from the community received either DCS (125 mg; n = 19) or placebo (n = 17) 1 h prior to each of two sessions of exposure/response prevention. Cue reactivity and attentional bias were assessed during these two sessions and at a third follow-up session. Between-session drinking behaviour was recorded. Robust cue reactivity and attentional bias to alcohol cues was evident, as expected of heavy drinkers. Within- and between-session habituation of cue reactivity, as well as a reduction in attentional bias to alcohol cues over time was found. However, there was no evidence of greater habituation in the DCS group. Subtle stimulant effects (increased subjective contentedness and euphoria) which were unrelated to exposure/response prevention were found following DCS. DCS does not appear to enhance habituation of alcohol cue reactivity in heavy non-dependent drinkers. Its utility in enhancing treatments based on exposure/response prevention in dependent drinkers or drug users remains open.

A review of the acute subjective effects of MDMA/ecstasy.

PubMed

Baylen, Chelsea A; Rosenberg, Harold

2006-07-01

Although several relatively recent reviews have summarized the neuropsychiatric effects associated with chronic ecstasy use, there is no published comprehensive review of studies on the acute subjective effects (ASEs) of MDMA/ecstasy. The present study reviewed the prevalence, intensity and duration of ASEs collected from 24 studies that provided frequency data on the prevalence of self-reported ecstasy effects and/or provided data on the intensity of ecstasy effects. Although hundreds of ASEs have been reported following MDMA consumption, we identified a subset of effects reported repeatedly by meaningful proportions and large numbers of participants across multiple investigations, most of which were either emotional (e.g. anxiety, depression, closeness, fear, euphoria, calmness) or somatic (e.g. nausea/vomiting, bruxism, muscle aches/headache, sweating, numbness, body temperature changes, fatigue, dizziness, dry mouth, increased energy). Only one sexual ASE (sexual arousal/increased sensual awareness), one cognitive ASE (confused thought), one sensory-perceptual ASE (visual effects/changes in visual perception), one sleep-related ASE (sleeplessness) and one appetite-related ASE (decreased appetite) were reported across five or more investigations. Three factors-number of hours between ingestion and assessment, dose level, and gender-have been associated with the acute subjective experience of MDMA/ecstasy. This review provides useful information for clinicians and researchers who want to understand the desirable and undesirable ASEs that may motivate and restrain ecstasy use, for public health advocates who seek to reduce biomedical harms (e.g. fainting, dehydration, shortness of breath, bruxism) associated with recreational use of MDMA/ecstasy, and for educators who wish to design credible prevention messages that neither underestimate nor exaggerate users' experiences of this drug.

Staff Distress Improves by Treating Pain in Nursing Home Patients With Dementia: Results From a Cluster-Randomized Controlled Trial.

PubMed

Aasmul, Irene; Husebo, Bettina Sandgathe; Flo, Elisabeth

2016-12-01

Most people with dementia develop neuropsychiatric symptoms (NPSs), which are distressing for their carers. Untreated pain may increase the prevalence and severity of NPSs and thereby staff burden. We investigated the association between NPSs and the impact of individual pain treatment on distress in nursing home staff. Nursing home (NH) units were cluster-randomized to an intervention group (33 NH units; n = 175) or control group (27 NH units; n = 177). Patients in the intervention group received individual pain treatment for eight weeks, followed by a four-week washout period; control groups received care as usual. Staff informants (n = 138) used the Neuropsychiatric Inventory-NH version (including caregiver distress) as primary outcome to assess their own distress. Other outcomes were pain (Mobilization-Observation-Behavior-Intensity-Dementia-2 Pain Scale) and cognitive functioning (Mini-Mental State Examination). Using hierarchical regression analysis, all NPS items at baseline were associated with staff distress (P < 0.01) apart from euphoria; agitation had the largest contribution (β = 0.24). Using mixed models, we found significantly lower staff distress in the intervention group compared to the control group. Moreover, we also found significantly reduced distress in the control group, and there were still effects in both groups throughout the washout period. Individual pain treatment reduced staff distress in the intervention group compared to control group especially in regard to agitation-related symptoms and apathy. Furthermore, our results indicated a multifactorial model of staff distress, in which enhanced knowledge and understanding of NPSs and pain in people with advanced dementia may play an important role. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Use of granulocyte-colony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations.

PubMed

Myles, Nicholas; Myles, Hannah; Clark, Scott R; Bird, Robert; Siskind, Dan

2017-10-01

Clozapine is the most effective medication for treatment-refractory schizophrenia; however, its use is contraindicated in people who have had previous clozapine-induced neutropenia. Co-prescription of granulocyte-colony stimulating factor may prevent recurrent neutropenia and allow continuation or rechallenge of clozapine. Systematic review of literature reporting the use of granulocyte-colony stimulating factor to allow rechallenge or continuation of clozapine in people with previous episodes of clozapine-induced neutropenia. The efficacy of granulocyte-colony stimulating factor and predictors of successful rechallenge will be determined to elucidate whether evidence-based recommendations can be made regarding the use of granulocyte-colony stimulating factor in this context. A total of 17 articles were identified that reported on clozapine rechallenge with granulocyte-colony stimulating factor support. In all, 76% of cases were able to continue clozapine at median follow-up of 12 months. There were no clear clinical or laboratory predictors of successful rechallenge; however, initial neutropenia was more severe in successful cases compared to unsuccessful cases. Cases co-prescribed lithium had lower success rates of rechallenge (60%) compared to those who were not prescribed lithium (81%). The most commonly reported rechallenge strategy was use of filgrastim 150-480 µg between daily to three times a week. There were no medication-specific side effects of granulocyte-colony stimulating factor reported apart from euphoria in one case. Three cases who failed granulocyte-colony stimulating factor had bacterial infection at time of recurrent neutropenia. No deaths were reported. Preliminary data suggest granulocyte-colony stimulating factor is safe and effective in facilitating rechallenge with clozapine. Clinical recommendations for use are discussed.

Behavioral and Psychological Symptoms Impact Clinical Competence in Alzheimer’s Disease

PubMed Central

Bertrand, Elodie; van Duinkerken, Eelco; Landeira-Fernandez, J.; Dourado, Marcia C. N.; Santos, Raquel L.; Laks, Jerson; Mograbi, Daniel C.

2017-01-01

Decision-making is considered a fundamental aspect of personal autonomy and can be affected in psychiatric and neurologic diseases. It has been shown that cognitive deficits in dementia impact negatively on decision-making. Moreover, studies highlighted impaired clinical competence in neuropsychiatric disorders, such as schizophrenia and bipolar disorder. In this context, the current study explored the relationship between behavioral and psychological symptoms of dementia (BPSD) and clinical competence, especially the capacity to consent to treatment, in Alzheimer’s disease (AD). Seventy-one patients with mild to moderate AD participated, completing assessments for capacity to consent to treatment, general cognition and neuropsychiatric disturbances. For each neuropsychiatric symptom, patients with and without the particular disturbance were compared on the different subscales of the MacArthur Competence Tool for Treatment (MacCAT-T; Understanding, Appreciation, Reasoning and Expression). The results showed that patients presenting delusions, as well as apathetic patients, had a lower ability to express a clear treatment choice compared to patients without these symptoms. By contrast, patients with dysphoria/depression had higher scores on this variable. Additionally, AD patients with euphoria had more difficulties discussing consequences of treatment alternatives compared to patients without this disturbance. None of the differences were confounded by global cognition. There were no between-group differences in clinical decision-making for patients with hallucinations, agitation/aggression, anxiety, irritability, disinhibition and aberrant motor behavior. These findings highlight the importance of taking BPSD into account when assessing decision-making capacity, especially clinical competence, in AD. Furthermore, reducing BPSD may lead to better clinical competence in patients with AD, as well as to improvements in patients and caregivers’ quality of life. PMID:28670272

Dopamine and the Biology of Creativity: Lessons from Parkinson’s Disease

PubMed Central

Lhommée, Eugénie; Batir, Alina; Quesada, Jean-Louis; Ardouin, Claire; Fraix, Valérie; Seigneuret, Eric; Chabardès, Stéphan; Benabid, Alim-Louis; Pollak, Pierre; Krack, Paul

2014-01-01

Background: Parkinson’s disease (PD) is characterized by reduced flexibility, conceptualization, and visuo-spatial abilities. Although these are essential to creativity, case studies show emergence of creativity during PD. Knowledge about the role of dopamine in creativity so far only stems from a few case reports. We aim at demonstrating that creativity can be induced by dopaminergic treatments in PD, and tends to disappear after withdrawal of dopamine agonists. Methods: Eleven consecutive creative PD patients were selected from candidates for subthalamic nucleus deep brain stimulation (STN DBS) surgery, and compared to 22 non-creative control PD patients. Motor disability (UPDRS III), cognition (Frontal score, Mattis scale), and behavior (Ardouin scale) were assessed before surgery and 1 year after. Results: Before surgery, whereas cognitive and motor assessments were similar between groups, dopamine agonist (but not levodopa) dosages were higher in creative patients (p = 0.01). The Ardouin scale revealed also a specific psycho-behavioral profile of creative patients which had higher scores for mania (p < 0.001), hobbyism (p = 0.001), nocturnal hyperactivity (p = 0.041), appetitive functioning (p = 0.003), and ON euphoria (p = 0.007) and lower scores for apathy and OFF dysphoria (p = 0.04 for each). Post-operative motor, cognitive, and behavioral scores as dopaminergic treatment dosages were equivalent between groups. Motor improvement allowed for a 68.6% decrease in dopaminergic treatment. Only 1 of the 11 patients remained creative after surgery. Reduction of dopamine agonist was significantly correlated to the decrease in creativity in the whole population of study (Spearman correlation coefficient ρ = 0.47 with confidence index of 95% = 0.16; 0.70, p = 0.0053). Conclusion: Creativity in PD is linked to dopamine agonist therapy, and tends to disappear after STN DBS in parallel to reduction of dopamine agonists, which are relatively selective for the mesolimbic D3 dopamine receptors. PMID:24795692

Arecoline augments cellular proliferation in the prostate gland of male Wistar rats

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

Saha, Indraneel; Chatterjee, Aniruddha; Mondal, Anushree

Areca nut chewing is the fourth most popular habit in the world due to its effects as a mild stimulant, causing a feeling of euphoria and slightly heightened alertness. Areca nuts contain several alkaloids and tannins, of which arecoline is the most abundant and known to have several adverse effects in humans, specially an increased risk of oral cancer. On evaluating the effects of arecoline on the male endocrine physiology in Wistar rats, it was found that arecoline treatment led to an overall enlargement and increase in the wet weight of the prostate gland, and a two-fold increase in serummore » gonadotropin and testosterone levels. Since the prostate is a major target for testosterone, the consequences of arecoline consumption were studied specifically in the prostate gland. Arecoline treatment led to an increase in the number of rough endoplasmic reticulum and reduction of secretory vesicles, signifying a hyperactive state of the prostate. Increased expression of androgen receptors in response to arecoline allowed for enhanced effect of testosterone in the prostate of treated animals, which augmented cell proliferation, subsequently confirmed by an increase in the expression of Ki-67 protein. Cellular proliferation was also the outcome of concomitant over expression of the G{sub 1}-to-S cell cycle regulatory proteins, cyclin D1 and CDK4, both at the transcriptional and translational levels. Taken together, the findings provide the first evidence that regular use of arecoline may lead to prostatic hyperplasia and hypertrophy, and eventually to disorders associated with prostate enlargement. - Highlights: > Effect of arecoline was investigated on the endocrine physiology of male Wistar rats. > Increase observed in prostate size, wet weight, serum testosterone and gonadotropins. > Arecoline increased RER, expression of androgen receptor and cellular proliferation. > Upregulation of cyclin D1 and CDK4 seen at transcriptional and translational levels. > It may cause disorders associated with prostatic hyperplasia and hyperactivity.« less

Laboratory measures of methylphenidate effects in cocaine-dependent patients receiving treatment.

PubMed

Roache, J D; Grabowski, J; Schmitz, J M; Creson, D L; Rhoades, H M

2000-02-01

Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness to medication. Patients were randomly assigned to receive either placebo or methylphenidate treatment and received their first dose in the human laboratory environment before continuing in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release dose (twice daily) plus an additional 5-mg immediate-release dose combined with the morning dose. Methylphenidate increased heart rate and subjective ratings; however, the subjective effects were primarily of a "dysphoric" nature, and significant effects were limited to increases in anxiety, depression, and anger on the Profile of Mood States; shaky/jittery ratings on a visual analog scale; and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction Research Center Inventory. Methylphenidate did not increase cocaine craving nor ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or drug-liking scores, etc.). None of the drug effects observed in the human laboratory was of clinical concern, and no subject was precluded from continuing in the outpatient study. After outpatient treatment completion, 12 patients were brought back into a second double-blind human laboratory study in which three doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered in an ascending series preceded and followed by placebo. Methylphenidate produced dose-related increases in heart rate, subjective ratings of shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving or stimulant euphoria ratings. These results suggest that stimulant substitution-type approaches to the treatment of cocaine dependence are not necessarily contraindicated because of cardiovascular toxicity or medication abuse potential. However, they also suggest that the subjective effects of methylphenidate may not be positive enough for an adequate replacement approach.

Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Δ-9-tetrahydrocannabinol in humans

PubMed Central

Braley, Gabriel; Blaise, Rebecca; Vendetti, Michael; Oliver, Stephen; Pittman, Brian; Ranganathan, Mohini; Bhakta, Savita; Zimolo, Zoran; Cooper, Thomas; Perry, Edward

2010-01-01

Introduction Cannabinoids produce a spectrum of effects in humans including euphoria, cognitive impairments, psychotomimetic effects, and perceptual alterations. The extent to which dopaminergic systems contribute to the effects of Δ-9-tetrahydrocannabinol (Δ-9-THC) remains unclear. This study evaluated whether pretreatment with a dopamine receptor antagonist altered the effects of Δ-9-THC in humans. Materials and methods In a 2-test-day double-blind study, 28 subjects including healthy subjects (n=17) and frequent users of cannabis (n=11) were administered active (0.057 mg/kg) or placebo oral haloperidol in random order followed 90 and 215 min later by fixed order intravenous administration of placebo (vehicle) and active (0.0286 mg/kg) Δ-9-THC, respectively. Results Consistent with previous reports, intravenous Δ-9-THC produced psychotomimetic effects, perceptual alterations, and subjective effects including “high.” Δ-9-THC also impaired verbal recall and attention. Haloperidol pretreatment did not reduce any of the behavioral effects of Δ-9-THC. Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Δ-9-THC. Haloperidol and Δ-9-THC worsened distractibility and vigilance. Neither drug impaired performance on a motor screening task, the Stockings of Cambridge task, or the delayed match to sample task. Frequent users had lower baseline plasma prolactin levels and blunted Δ-9-THC induced memory impairments. Conclusions The deleterious effects of haloperidol pretreatment on the cognitive effects of Δ-9-THC are consistent with the preclinical literature in suggesting crosstalk between DAergic and CBergic systems. However, it is unlikely that DA D2 receptor mechanisms play a major role in mediating the psychotomimetic and perceptual altering effects of Δ-9-THC. Further investigation is warranted to understand the basis of the psychotomimetic effects of Δ-9-THC and to better understand the crosstalk between DAergic and CBergic systems. PMID:18228005

[Recreational usage of dextromethorphan--analysis based on internet users experiences].

PubMed

Zajac, Maciej; Andrzejczyk, Agata; Kuich, Aleksandra; Tyrańska-Fobke, Anna; Waldman, Wojciech; Sein Anand, Jacek

2013-01-01

In the last decade we have observed a considerable increase in nonmedical usage of dextromethorphan (DXM) among young age groups, especially school children between 13 and 16 yrs. We analysed the "trip reports" after use of DXM, available on a website: www.hyperreal.info in the years 1999-2013. The data collected by authors were analysed according to: age, sex, symptoms, dose of DXM, a reason and a place of using the drug. A review of 124 "trip reports" showed that the majority of their writers are male (M 90.3%, F 9.7%). Young people, aged 16-20 (80.4%), dominated among the study population. The most common place of using DXM was a flat of a drug user (70.2%), and the reason of using a willingness to experiment with new psychoactive substances (41.9%) as well as the desire of "get high" (25.8%). The majority of users used DXM at least once again in their lives (56.5%). A single dose of the ingested drug ranged from 120 mg to 1575 mg (mean 539.25 mg). Most often received doses were 450 mg (30.4%), 300 mg (12%), 900 mg (11.2%). DXM was positively assessed by the internauts as a recreational psychoactive substance (84.7%). The most common clinical symptoms described by internauts were: difficulties with walking (74.2%), visual illusions (73.4%), altered sense of time (41.9%), feeling of exteriorisation (35.5%), euphoria (33.1%), nausea and vomiting (32.3%), auditory illusions (30.6%) and pruritus (29.8%). 1. DXM is the popular psychoactive substance which has gained a positive opinion among the Internet users. 2. Easy accessibility of DXM may pose a serious threat to health of young people who experiment with psychoactive substances. 3. The improvement of DXM sales control should be considered.

Pharmacovigilance in hospice/palliative care: the net immediate and short-term effects of dexamethasone for anorexia.

PubMed

Hatano, Yutaka; Moroni, Matteo; Wilcock, Andrew; Quinn, Stephen; Csikós, Ágnes; Allan, Simon G; Agar, Meera; Clark, Katherine; Clayton, Josephine M; Currow, David C

2016-09-01

Loss of appetite is prevalent in palliative care and distressing for patients and families. Therapies include corticosteroids or progestogens. This study explores the net effect of dexamethasone on anorexia. Prospective data were collected when dexamethasone was started for anorexia as part of routine care. The National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCICTCAE) Likert scales assessed severity of anorexia and immediate and short-term harms at 2 time points: baseline and 7 days. This study (41 sites, 8 countries) collected data (July 2013 to July 2014) from 114 patients (mean age 71 (SD 11), 96% with cancer). Median Australian-modified Karnofsky Performance Scale was 50% (range 20-70). Mean baseline NCICTCAE anorexia score was 2.7 (SD 0.6; median 3). 6 patients died by day 7. Of 108 evaluable patients, 74 (68.5%; 95% CI 59.0% to 76.7%) reported ≥1 reduction anorexia scores by day 7, of whom 30 were 0. Mean dexamethasone dose on day 7 was 4.1 mg/day (SD 3.4; median 4; range 0-46 mg). 24 patients reported ≥1 harms (32.4% CI 22.6% to 44.1%; insomnia n=10, depression n=7, euphoria n=7 and hyperglycaemia n=7). Of 24 patients with no benefit, 10 reported ≥1 harms. This study shows positive and negative effects of 7 days of dexamethasone as an appetite stimulant in patients with advanced life-limiting illnesses. Identifying clinicodemographic characteristics of people most at risk of harms with no benefit is a crucial next step. Longer term follow-up will help to understand longer term and cumulative harms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.

PubMed

Solowij, Nadia; Broyd, Samantha J; Beale, Camilla; Prick, Julie-Anne; Greenwood, Lisa-Marie; van Hell, Hendrika; Suo, Chao; Galettis, Peter; Pai, Nagesh; Fu, Shanlin; Croft, Rodney J; Martin, Jennifer H; Yücel, Murat

2018-01-01

Introduction: Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ 9 -tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition. Materials and Methods: Twenty frequent cannabis users (16 male, median age 25 years) underwent a 10-week open-label trial of 200 mg of daily oral CBD treatment, while continuing to use cannabis as usual. The majority of participants were daily cannabis users who had used cannabis for several years (median 5.5 years of regular use). Participants underwent psychological and cognitive assessments at baseline (BL) and post-treatment (PT) and were monitored weekly throughout the trial. Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users. Conclusions: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence.

Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial

PubMed Central

Solowij, Nadia; Broyd, Samantha J.; Beale, Camilla; Prick, Julie-Anne; Greenwood, Lisa-marie; van Hell, Hendrika; Suo, Chao; Galettis, Peter; Pai, Nagesh; Fu, Shanlin; Croft, Rodney J.; Martin, Jennifer H.; Yücel, Murat

2018-01-01

Abstract Introduction: Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ9-tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition. Materials and Methods: Twenty frequent cannabis users (16 male, median age 25 years) underwent a 10-week open-label trial of 200 mg of daily oral CBD treatment, while continuing to use cannabis as usual. The majority of participants were daily cannabis users who had used cannabis for several years (median 5.5 years of regular use). Participants underwent psychological and cognitive assessments at baseline (BL) and post-treatment (PT) and were monitored weekly throughout the trial. Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users. Conclusions: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence. PMID:29607408

Mixed features in patients with a major depressive episode: the BRIDGE-II-MIX study.

PubMed

Perugi, Giulio; Angst, Jules; Azorin, Jean-Michel; Bowden, Charles L; Mosolov, Sergey; Reis, Joao; Vieta, Eduard; Young, Allan H

2015-03-01

To estimate the frequency of mixed states in patients diagnosed with major depressive episode (MDE) according to conceptually different definitions and to compare their clinical validity. This multicenter, multinational cross-sectional Bipolar Disorders: Improving Diagnosis, Guidance and Education (BRIDGE)-II-MIX study enrolled 2,811 adult patients experiencing an MDE. Data were collected per protocol on sociodemographic variables, current and past psychiatric symptoms, and clinical variables that are risk factors for bipolar disorder. The frequency of mixed features was determined by applying both DSM-5 criteria and a priori described Research-Based Diagnostic Criteria (RBDC). Clinical variables associated with mixed features were assessed using logistic regression. Overall, 212 patients (7.5%) fulfilled DSM-5 criteria for MDE with mixed features (DSM-5-MXS), and 818 patients (29.1%) fulfilled diagnostic criteria for a predefined RBDC depressive mixed state (RBDC-MXS). The most frequent manic/hypomanic symptoms were irritable mood (32.6%), emotional/mood lability (29.8%), distractibility (24.4%), psychomotor agitation (16.1%), impulsivity (14.5%), aggression (14.2%), racing thoughts (11.8%), and pressure to keep talking (11.4%). Euphoria (4.6%), grandiosity (3.7%), and hypersexuality (2.6%) were less represented. In multivariate logistic regression analysis, RBDC-MXS was associated with the largest number of variables including diagnosis of bipolar disorder, family history of mania, lifetime suicide attempts, duration of the current episode > 1 month, atypical features, early onset, history of antidepressant-induced mania/hypomania, and lifetime comorbidity with anxiety, alcohol and substance use disorders, attention-deficit/hyperactivity disorder, and borderline personality disorder. Depressive mixed state, defined as the presence of 3 or more manic/hypomanic features, was present in around one-third of patients experiencing an MDE. The valid symptom, illness course and family history RBDC criteria we assessed identified 4 times more MDE patients as having mixed features and yielded statistically more robust associations with several illness characteristics of bipolar disorder than did DSM-5 criteria. © Copyright 2015 Physicians Postgraduate Press, Inc.

Inhibition of mirtazapine metabolism by Ecstasy (MDMA) in isolated perfused rat liver model.

PubMed

Jamshidfar, Sanaz; Ardakani, Yalda H; Lavasani, Hoda; Rouini, Mohammadreza

2017-06-28

Nowadays MDMA (3,4-methylendioxymethamphetamine), known as ecstasy, is widely abused among the youth because of euphoria induction in acute exposure. However, abusers are predisposed to depression in chronic consumption of this illicit compound. Mirtazapine (MRZ), an antidepressant agent, may be prescribed in MDMA-induced depression. MRZ is extensively metabolized in liver by CYP450 isoenzymes. 8-hydroxymirtazapine (8-OH) is mainly produced by CYP2D6. N-desmethylmirtazapine (NDES) is generated by CYP3A4. MDMA is also metabolized by the mentioned isoenzymes and demonstrates mechanism-based inhibition (MBI) in association with CYP2D6. Several studies revealed that MDMA showed inhibitory effects on CYP3A4. In the present study, our aim was to evaluate the impact of MDMA on the metabolism of MRZ in liver. Therefore, isolated perfused rat liver model was applied as our model of choice in this assessment. The subjects of the study were categorized into two experimental groups. Rats in the control group received MRZ-containing Krebs-Henselit buffer (1 μg/ml). Rats in the treatment group received aqueous solution of 1 mg/ml MDMA (3 mg/kg) intraperitoneally 1 hour before receiving MRZ. Perfusate samples were analyzed by HPLC. Analyses of perfusate samples showed 80% increase in the parent drug concentrations and 50% decrease in the concentrations of both metabolites in our treatment group compared to the control group. In the treatment group compared to the control group, AUC (0-120) of the parent drug demonstrated 50% increase and AUC (0-120) of 8-OH and NDES showed 70% and 60% decrease, respectively. Observed decrease in metabolic ratios were 83% and 79% for 8-OH and NDES in treatment group compared to control group, respectively. Hepatic clearance (CL h ) and intrinsic clearance (Cl int ) showed 20% and 60% decrease in treatment group compared to control group. All findings prove the inhibitory effects of ecstasy on both CYP2D6 and CYP3A4 hepatic isoenzymes. In conclusion, this study is the first investigation of MRZ metabolism in presence of MDMA in isolated perfused rat liver model.

Reusable launch vehicle facts and fantasies

NASA Astrophysics Data System (ADS)

Kaplan, Marshall H.

2002-01-01

Many people refuse to address many of the realities of reusable launch vehicle systems, technologies, operations and economics. Basic principles of physics, space flight operations, and business limitations are applied to the creation of a practical vision of future expectations. While reusable launcher concepts have been proposed for several decades, serious review of potential designs began in the mid-1990s, when NASA decided that a Space Shuttle replacement had to be pursued. A great deal of excitement and interest was quickly generated by the prospect of ``orders-of-magnitude'' reduction in launch costs. The potential for a vastly expanded space program motivated the entire space community. By the late-1990s, and after over one billion dollars were spent on the technology development and privately-funded concepts, it had become clear that there would be no new, near-term operational reusable vehicle. Many factors contributed to a very expensive and disappointing effort to create a new generation of launch vehicles. It began with overly optimistic projections of technology advancements and the belief that a greatly increased demand for satellite launches would be realized early in the 21st century. Contractors contributed to the perception of quickly reachable technology and business goals, thus, accelerating the enthusiasm and helping to create a ``gold rush'' euphoria. Cost, schedule and performance margins were all highly optimistic. Several entrepreneurs launched start up companies to take advantage of the excitement and the availability of investor capital. Millions were raised from private investors and venture capitalists, based on little more than flashy presentations and animations. Well over $500 million were raised by little-known start up groups to create reusable systems, which might complete for the coming market in launch services. By 1999, it was clear that market projections, made just two years earlier, were not going to be realized. Investors stopped funding the many private projects, and NASA grew weary of the lack of progress in its funded programs. The elements leading to the demise of NASA's X-33 and other programs are addressed, and lessons for the future offered. .

The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative.

PubMed

Timpone, J G; Wright, D J; Li, N; Egorin, M J; Enama, M E; Mayers, J; Galetto, G

1997-03-01

This randomized, open-labeled, multicenter study was designed to assess safety and pharmacokinetics of dronabinol (Marinol) tablets and megestrol acetate (Megace) micronized tablets, alone and in combination, for treatment of HIV wasting syndrome. Weight and quality of life data were also collected. Fifty-two patients (mean CD4+ count, 59 cells/microliter) were randomized to one of four treatment arms: dronabinol 2.5 mg twice/day (D); megestrol acetate 750 mg/day (M750); megestrol acetate 750 mg/day+dronabinol 2.5 mg twice/day (M750+D); or megestrol acetate 250 mg/day+dronabinol 2.5 mg twice/day (M250+D). After therapy initiation, 47 patients returned for at least one visit, and 39 completed the planned 12 weeks of study visits. Occurrence of adverse events, drug discontinuation, new AIDS-defining conditions, or CD4+ T lymphocyte changes were not statistically significantly different among arms. Serious adverse events assessed as related to dronabinol included CNS events (e.g., confusion, anxiety, emotional lability, euphoria, hallucinations) and those assessed as related to megestrol acetate included dyspnea, liver enzyme changes, and hyperglycemia. The mean weight change +/- SE over 12 weeks was as follows: D, -2.0 +/- 1.3 kg; M750, +6.5 +/- 1.1 kg; M750+D, +6.0 +/- 1.0 kg; and M250+D, -0.3 +/- 1.0 kg (difference among treatment arms, p = 0.0001). Pharmacokinetic parameters measured after 2 weeks of therapy for M750 were Cmax = 985 ng/ml and AUC = 22,487 ng x hr/ml, and for dronabinol and its active metabolite (HO-THC), respectively, were Cmax = 2.01; 4.61 ng/ml and AUC = 5.3; 23.7 ng x hr/ml. For megestrol acetate, but not dronabinol, there was a positive correlation at week 2 between both Cmax and AUC with each of the following: (1) weight change, (2) breakfast visual analog scale for hunger (VASH) score, and (3) dinner VASH score.

Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.

PubMed

Whiting, Penny F; Wolff, Robert F; Deshpande, Sohan; Di Nisio, Marcello; Duffy, Steven; Hernandez, Adrian V; Keurentjes, J Christiaan; Lang, Shona; Misso, Kate; Ryder, Steve; Schmidlkofer, Simone; Westwood, Marie; Kleijnen, Jos

Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. Twenty-eight databases from inception to April 2015. Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs. A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.

Animal emotions, behaviour and the promotion of positive welfare states.

PubMed

Mellor, D J

2012-01-01

This paper presents a rationale that may significantly boost the drive to promote positive welfare states in animals. The rationale is based largely, but not exclusively, on an experimentally supported neuropsychological understanding of relationships between emotions and behaviour, an understanding that has not yet been incorporated into animal welfare science thinking. Reference is made to major elements of the neural/cognitive foundations of motivational drives that energise and direct particular behaviours and their related subjective or emotional experiences. These experiences are generated in part by sensory inputs that reflect the animal's internal functional state and by neural processing linked to the animal's perception of its external circumstances. The integrated subjective or emotional outcome of these inputs corresponds to the animal's welfare status. The internally generated subjective experiences represent motivational urges or drives that are predominantly negative and include breathlessness, thirst, hunger and pain. They are generated by, and elicit specific behaviours designed to correct, imbalances in the animal's internal functional state. Externally generated subjective experiences are said to be integral to the operation of interacting 'action-orientated systems' that give rise to particular behaviours and their negative or positive emotional contents. These action-orientated systems, described in neuropsychological terms, give rise to negative emotions that include fear, anger and panic, and positive emotions that include comfort, vitality, euphoria and playfulness. It is argued that early thinking about animal welfare management focused mainly on minimising disturbances to the internal functional states that generate associated unpleasant motivational urges or drives. This strategy produced animal welfare benefits, but at best it could only lift a poor net welfare status to a neutral one. In contrast, strategies designed to manipulate the emotional action-orientated systems have the potential to replace the negative emotions generated within those systems with positive ones, and thereby may lift a poor net state of welfare beyond the neutral point to a net positive state. It is hoped that the analysis presented here will enhance the drive to promote positive welfare states by providing cogent and convincing neuropsychological support for the formulation of additional, more directed welfare code recommendations and standards that focus on the animal's behaviour.

The dark side of emotion: the addiction perspective.

PubMed

Koob, George F

2015-04-15

Emotions are "feeling" states and classic physiological emotive responses that are interpreted based on the history of the organism and the context. Motivation is a persistent state that leads to organized activity. Both are intervening variables and intimately related and have neural representations in the brain. The present thesis is that drugs of abuse elicit powerful emotions that can be interwoven conceptually into this framework. Such emotions range from pronounced euphoria to a devastating negative emotional state that in the extreme can create a break with homeostasis and thus an allostatic hedonic state that has been considered key to the etiology and maintenance of the pathophysiology of addiction. Drug addiction can be defined as a three-stage cycle-binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation-that involves allostatic changes in the brain reward and stress systems. Two primary sources of reinforcement, positive and negative reinforcement, have been hypothesized to play a role in this allostatic process. The negative emotional state that drives negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain incentive salience and stress systems. Specific neurochemical elements in these structures include not only decreases in incentive salience system function in the ventral striatum (within-system opponent processes) but also recruitment of the brain stress systems mediated by corticotropin-releasing factor (CRF), dynorphin-κ opioid systems, and norepinephrine, vasopressin, hypocretin, and substance P in the extended amygdala (between-system opponent processes). Neuropeptide Y, a powerful anti-stress neurotransmitter, has a profile of action on compulsive-like responding for drugs similar to a CRF1 receptor antagonist. Other stress buffers include nociceptin and endocannabinoids, which may also work through interactions with the extended amygdala. The thesis argued here is that the brain has specific neurochemical neurocircuitry coded by the hedonic extremes of pleasant and unpleasant emotions that have been identified through the study of opponent processes in the domain of addiction. These neurochemical systems need to be considered in the context of the framework that emotions involve the specific brain regions now identified to differentially interpreting emotive physiological expression. Published by Elsevier B.V.

GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

PubMed Central

Busardò, Francesco P.; Jones, Alan W.

2015-01-01

The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant withdrawal symptoms. There is no evidence-based protocol available to deal with GHB withdrawal, apart from administering benzodiazepines. PMID:26074743

In vitro model to study cocaine and its contaminants.

PubMed

Steinmetz, Aline; Steffens, Luiza; Morás, Ana Moira; Prezzi, Flávia; Braganhol, Elizandra; Saffi, Jenifer; Ortiz, Rafael Scorsatto; Barros, Helena M T; Moura, Dinara Jaqueline

2018-04-01

Cocaine is one of the most popular illicit drug worldwide. Due its great addictive potential, which leads to euphoria and hyperactivity, it is considered a public health concern. At the central nervous system, the drug acts inhibiting catecholamine re-uptake. It is now known that in addition to the toxicity of the drug itself, the contaminants present in the street drug have raised concern about the harmful effects on health. Toxicological in vivo and in vitro studies have demonstrated the toxic effects of cocaine correlated with the generation of reactive oxygen species (ROS), which in turn lead to oxidative damage to the cells. Therefore the aim of this work was to propose an in vitro model that reunites the main parameters of toxicity of the cocaine already observed in the literature so far, and we tested this model using cocaine and seizure cocaine sample (SCS), kindly provided by Federal Police of Brazil. For that, we used a C6 glioblastoma cells and evaluated cell death, oxygen reactive species induction, oxidation of macromolecules as membrane lipids and DNA and loss of mitochondrial membrane potential after cocaine exposure. The results showed that cocaine can decrease cellular viability in a dose-dependent way in the C6 cell immortalized and astrocytes primary culture. Cocaine also induced cellular death by apoptosis. However, in the seizure cocaine sample (SCS), the predominant cell death was due to necrosis. Using dichlorofluorescein (DCF) assay, we confirmed ROS production after cocaine exposition. In agreement with these findings, occurred an increasing in MDA production, as well as increased superoxide dismutase (SOD) and catalase (CAT) activity. The induction of DNA damage was observed after cocaine. Our results demonstrate the occurrence of mitochondrial dysfunction by depolarization of mitochondrial membrane as a consequence of cocaine treatment. In summary, these results demonstrated that cocaine can induce reactive oxygen species formation, leading to oxidative stress. As a consequence of this unbalance, DNA damage, lipidic peroxidation and loss of mitochondrial membrane occurred, which could be an answer to cell death observed. Copyright © 2018 Elsevier B.V. All rights reserved.

The dark side of emotion: the addiction perspective

PubMed Central

Koob, George F.

2015-01-01

Emotions are “feeling” states and classic physiological emotive responses that are interpreted based on the history of the organism and the context. Motivation is a persistent state that leads to organized activity. Both are intervening variables and intimately related and have neural representations in the brain. The present thesis is that drugs of abuse elicit powerful emotions that can be interwoven conceptually into this framework. Such emotions range from pronounced euphoria to a devastating negative emotional state that in the extreme can create a break with homeostasis and thus an allostatic hedonic state that has been considered key to the etiology and maintenance of the pathophysiology of addiction. Drug addiction can be defined as a three-stage cycle—binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation—that involves allostatic changes in the brain reward and stress systems. Two primary sources of reinforcement, positive and negative reinforcement, have been hypothesized to play a role in this allostatic process. The negative emotional state that drives negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain incentive salience and stress systems. Specific neurochemical elements in these structures include not only decreases in incentive salience system function in the ventral striatum (within-system opponent processes) but also recruitment of the brain stress systems mediated by corticotropin-releasing factor (CRF), dynorphin-κ opioid systems, and norepinephrine, vasopressin, hypocretin, and substance P in the extended amygdala (between-system opponent processes). Neuropeptide Y, a powerful anti-stress neurotransmitter, has a profile of action on compulsive-like responding for drugs similar to a CRF1 antagonist. Other stress buffers include nociceptin and endocannabinoids, which may also work through interactions with the extended amygdala. The thesis argued here is that the brain has specific neurochemical neurocircuitry coded by the hedonic extremes of pleasant and unpleasant emotions that have been identified through the study of opponent processes in the domain of addiction. These neurochemical systems need to be considered in the context of the framework that emotions involve the specific brain regions now identified as differentially interpreting emotive physiological expression. PMID:25583178

Neurogentics of Dopaminergic Receptor Super-sensitivity in Activation of Brain Reward Circuitry and Relapse: Proposing “Deprivation-Amplification Relapse Therapy” (DART)

PubMed Central

Downs, B. William; Bowirrat, Abdalla; Waite, Roger L.; Braverman, Eric R.; Madigan, Margaret; Oscar-Berman, Marlene; DiNubile, Nicholas; Gold, Mark

2013-01-01

Background and Hypothesis It is well known that after prolonged abstinence, individuals who imbibe or use their drug of choice experience a powerful euphoria that precipitates serious relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed “super sensitivity” might be tied to genetic dopaminergic polymorphisms. Another therapeutic conundrum relates to the paradoxical finding that the dopaminergic agonist bromocriptine induces stronger activation of brain reward circuitry in individuals who carry the DRD2 A1 allele compared to DRD2 A2 allele carriers. Based upon the fact that carriers of the A1 allele relative to the A2 allele of the DRD2 gene have significantly lower D2 receptor density, a reduced sensitivity to dopamine agonist activity would be expected in the former. Thus, it is perplexing that with low D2 density there is an increase in reward sensitivity with the dopamine agonist bromocriptine. Moreover, under chronic or long-term therapy, the potential proliferation of D2 receptors with bromocriptine has been shown in vitro. This seems to lead to a positive outcome and significantly better treatment compliance only in A1 carriers. Proposal and Conclusion We propose that low D2 receptor density and polymorphisms of the D2 gene are associated with risk for relapse of substance abuse including alcohol dependence, heroin craving, cocaine dependence, methamphetamine abuse, nicotine sensitization, and glucose craving. With this in mind, we suggest a putative physiological mechanism that may help to explain the enhanced sensitivity following intense acute dopaminergic D2 receptor activation: “denervation supersensitivity.” Thus, the administration of dopamine D2 agonists would target D2 sensitization and attenuate relapse, especially in D2 receptor A1 allele carriers. This hypothesized mechanism is supported by clinical trials utilizing the amino-acid neurotransmitter precursors, enkephalinase and catechol-O-methyl-transferase (COMT) enzyme inhibition, which have resulted in attenuated relapse rates in Reward Deficiency Syndrome (RDS) probands. Future warranted translational research with positive outcome showing prevented or lower relapse in RDS will ultimately support the proposed concept, which we term “Deprivation-Amplification Relapse Therapy (DART).” PMID:19940429

Chronic Obstructive Pulmonary Disease: Safety and Tolerability of Hyperpolarized 129Xe MR Imaging in Healthy Volunteers and Patients

PubMed Central

Martinez-Jimenez, Santiago; Cleveland, Zackary I.; Metz, Gregory M.; Beaver, Denise M.; Nouls, John C.; Kaushik, S. Sivaram; Firszt, Rafael; Willis, Christine; Kelly, Kevin T.; Wolber, Jan; Kraft, Monica; McAdams, H. Page

2012-01-01

Purpose: To evaluate the safety and tolerability of inhaling multiple 1-L volumes of undiluted hyperpolarized xenon 129 (129Xe) followed by up to a 16-second breath hold and magnetic resonance (MR) imaging. Materials and Methods: This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained. Forty-four subjects (19 men, 25 women; mean age, 46.1 years ± 18.8 [standard deviation]) were enrolled, consisting of 24 healthy volunteers, 10 patients with chronic obstructive pulmonary disease (COPD), and 10 age-matched control subjects. All subjects received three or four 1-L volumes of undiluted hyperpolarized 129Xe, followed by breath-hold MR imaging. Oxygen saturation, heart rate and rhythm, and blood pressure were continuously monitored. These parameters, along with respiratory rate and subjective symptoms, were assessed after each dose. Subjects’ serum biochemistry and hematology were recorded at screening and at 24-hour follow-up. A 12-lead electrocardiogram (ECG) was obtained at these times and also within 2 hours prior to and 1 hour after 129Xe MR imaging. Xenon-related symptoms were evaluated for relationship to subject group by using a χ2 test and to subject age by using logistic regression. Changes in vital signs were tested for significance across subject group and time by using a repeated-measures multivariate analysis of variance test. Results: The 44 subjects tolerated all xenon inhalations, no subjects withdrew, and no serious adverse events occurred. No significant changes in vital signs (P > .27) were observed, and no subjects exhibited changes in laboratory test or ECG results at follow-up that were deemed clinically important or required intervention. Most subjects (91%) did experience transient xenon-related symptoms, most commonly dizziness (59%), paresthesia (34%), euphoria (30%), and hypoesthesia (30%). All symptoms resolved without clinical intervention in 1.6 minutes ± 0.9. Conclusion: Inhalation of hyperpolarized 129Xe is well tolerated in healthy subjects and in those with mild or moderate COPD. Subjects do experience mild, transient, xenon-related symptoms, consistent with its known anesthetic properties. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11102172/-/DC1 PMID:22056683

Intense, Passionate, Romantic Love: A Natural Addiction? How the Fields That Investigate Romance and Substance Abuse Can Inform Each Other

PubMed Central

Fisher, Helen E.; Xu, Xiaomeng; Aron, Arthur; Brown, Lucy L.

2016-01-01

Individuals in the early stage of intense romantic love show many symptoms of substance and non-substance or behavioral addictions, including euphoria, craving, tolerance, emotional and physical dependence, withdrawal and relapse. We have proposed that romantic love is a natural (and often positive) addiction that evolved from mammalian antecedents by 4 million years ago as a survival mechanism to encourage hominin pair-bonding and reproduction, seen cross-culturally today in Homo sapiens. Brain scanning studies using functional magnetic resonance imaging support this view: feelings of intense romantic love engage regions of the brain’s “reward system,” specifically dopamine-rich regions, including the ventral tegmental area, also activated during drug and/or behavioral addiction. Thus, because the experience of romantic love shares reward pathways with a range of substance and behavioral addictions, it may influence the drug and/or behavioral addiction response. Indeed, a study of overnight abstinent smokers has shown that feelings of intense romantic love attenuate brain activity associated with cigarette cue-reactivity. Could socially rewarding experiences be therapeutic for drug and/or behavioral addictions? We suggest that “self expanding” experiences like romance and expanding one’s knowledge, experience and self-perception, may also affect drug and/or behavioral addiction behaviors. Further, because feelings of romantic love can progress into feelings of calm attachment, and because attachment engages more plastic forebrain regions, there is a rationale for therapies that may help substance and/or behavioral addiction by promoting activation of these forebrain systems through long-term, calm, positive attachments to others, including group therapies. Addiction is considered a negative (harmful) disorder that appears in a population subset; while romantic love is often a positive (as well as negative) state experienced by almost all humans. Thus, researchers have not categorized romantic love as a chemical or behavioral addiction. But by embracing data on romantic love, it’s classification as an evolved, natural, often positive but also powerfully negative addiction, and its neural similarity to many substance and non-substance addictive states, clinicians may develop more effective therapeutic approaches to alleviate a range of the addictions, including heartbreak–an almost universal human experience that can trigger stalking, clinical depression, suicide, homicide, and other crimes of passion. PMID:27242601

Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale.

PubMed

Strassman, R J; Qualls, C R; Uhlenhuth, E H; Kellner, R

1994-02-01

Validation of animal models of hallucinogenic drugs' subjective effects requires human data. Previous human studies used varied groups of subjects and assessment methods. Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs' dysphoric properties. We describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abuse, in a group of experienced hallucinogen users. We also present preliminary data from a new rating scale for these effects. Twelve highly motivated volunteers received two doses (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate "nonblind," before entering a double-blind, saline placebo-controlled, randomized study using four doses of IV DMT. Subjects were carefully interviewed after resolution of drug effects, providing thorough and systematic descriptions of DMT's effects. They also were administered a new instrument, the Hallucinogen Rating Scale (HRS). The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users, and modified during early stages of the study. Psychological effects of IV DMT began almost immediately after administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes. This time course paralleled DMT blood levels previously described. Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completely replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and somaesthetic, while 0.1 mg/kg elicited the least desirable effects. Clustering of HRS items, using either a clinical, mental status method or principal components factor analysis provided better resolution of dose effects than did the biological variables described previously. These clinical and preliminary quantitative data provide bases for further psychopharmacologic characterization of DMT's properties in humans. They also may be used to compare the effects of other agents affecting relevant brain receptors in volunteer and psychiatric populations.

Medical psychology in exercise and sport.

PubMed

Dishman, R K

1985-01-01

Several psychological outcomes that accompany acute and chronic exercise have medical significance. Transient reductions in somatic tension and subjective anxiety appear most reliable. Symptom abatement in moderate depression can occur with chronic exercise in a manner comparable to psychotherapy and may offer a better prognosis in some instances. Other cognitive, behavioral, and perceptual events associated with exercise may assist in managing mental health, and exercise has been successfully used as a therapeutic adjunct in a variety of psychiatric disorders. Regular exercise may also complement treatments designed to manage aspects of coronary-prone behavior and psychoendocrine responsivity to mental stress. The lack of strict experimental control or effective placebo contrasts in most exercise studies precludes a convincing argument that exercise causes the psychological outcomes observed. Rather, expectancy of benefits, generalized treatment or attention effects, social reinforcement, and past history or selection bias represent likely alternatives. These competing explanations do not discount, however, that many individuals benefit in a clinically significant way. Exercise offers a low-cost alternative or adjunct with side effects that appear largely health-related. Although the effective psychological dosage or modality has not been quantified, current physiologic guidelines of the American College of Sports Medicine (large muscle rhythmic activity, for 20 to 60 minutes, 3 to 5 days per week at 60 to 80 per cent age-adjusted maximal heart rate), or a weekly caloric cost of 2000 kcal, should be effective with little medical risk. However, no evidence confirms that an increase in metabolic or psychoendocrine tolerance to exercise is necessary or sufficient for psychological outcomes to occur. Although biologic adaptations are known to follow exercise training and subside with diminished activity, there is currently no objective evidence that habitual exercise leads to dependence. If exercise has use in managing subjective or somatic symptoms, these may return during periods of exercise abstinence. Moreover, despite popular hypotheses concerning endorphins and biogenic amines, no direct relationships have yet been shown between exercise-induced mood swings and peripheral biochemical events. A proportion of habitual runners have reported acute episodes of euphoria-like states during or following exercise, but this remains a subjective and unpredictable event that may be related to psychophysiologic relaxation or acute changes in self-esteem.(ABSTRACT TRUNCATED AT 400 WORDS)

The university-promoted patent at the crossroads of the research results and immediate industrial use.

PubMed

Doddoli, R

2007-02-01

The departments, indeed the laboratories of the public research institutions, no longer are satisfied with displaying a certain number of annual scientific publications meant to highlight their expertise and know-how. In effect, for some years now, a new trend has been in vogue: stimulated by all the national and international public bodies, they are calling increasingly on the "patent pending" solution to make optimum use of the results of specific researches on the one hand and, on the other hand, to assert their excellence vis-à-vis the Ministry of Research of their country which is supposed to finance them. However, caught up in the euphoria of the research results, and lost in their formulae and practices, these researchers lose sight of the basis for a patent and its real reason for being (patent charter). A patent necessarily must be of service to the community, that is to say that essentially it must contribute to the improvement of the quality of life of the population. To achieve this goal, going through certain stages is a must, namely that to start with a patent must be absolutely profitable to industry in order that, subsequently, it be consistent with its being of service to the community. In this context, its validity is set at 10 years renewable for another 10 years based on specific parameters as stipulated by the national and international patent institutions, indeed by the EPO (European Patent Office) the headquarters of which is in Munich. Its use by industry ensures proceeds for 10, even 20 years and must represent the material fruit of the applicant's effort. Beyond this period, the patent becomes public and therefore available to everyone. But the crucial problem is this: when can a patent really be used and how to do so as best as possible to guarantee profits for both parties involved and thus justify its reason for being? The purpose of this work thus is to incite university researchers to think about the real usefulness of a patent on the one hand and, on the other hand, to ponder over the best way of using, in close cooperation with industry, the fruit of the research and the registering of the patent, both financed by public funds. For the latter, owing to their nature, demand that there be no wastage and cautious management thereof.

History of Antibiotics Research.

PubMed

Mohr, Kathrin I

2016-01-01

For thousands of years people were delivered helplessly to various kinds of infections, which often reached epidemic proportions and have cost the lives of millions of people. This is precisely the age since mankind has been thinking of infectious diseases and the question of their causes. However, due to a lack of knowledge, the search for strategies to fight, heal, and prevent the spread of communicable diseases was unsuccessful for a long time. It was not until the discovery of the healing effects of (antibiotic producing) molds, the first microscopic observations of microorganisms in the seventeenth century, the refutation of the abiogenesis theory, and the dissolution of the question "What is the nature of infectious diseases?" that the first milestones within the history of antibiotics research were set. Then new discoveries accelerated rapidly: Bacteria could be isolated and cultured and were identified as possible agents of diseases as well as producers of bioactive metabolites. At the same time the first synthetic antibiotics were developed and shortly thereafter, thousands of synthetic substances as well as millions of soil borne bacteria and fungi were screened for bioactivity within numerous microbial laboratories of pharmaceutical companies. New antibiotic classes with different targets were discovered as on assembly line production. With the beginning of the twentieth century, many of the diseases which reached epidemic proportions at the time-e.g., cholera, syphilis, plague, tuberculosis, or typhoid fever, just to name a few, could be combatted with new discovered antibiotics. It should be considered that hundred years ago the market launch of new antibiotics was significantly faster and less complicated than today (where it takes 10-12 years in average between the discovery of a new antibiotic until the launch). After the first euphoria it was quickly realized that bacteria are able to develop, acquire, and spread numerous resistance mechanisms. Whenever a new antibiotic reached the market it did not take long until scientists observed the first resistant germs. Since the marketing of the first antibiotic there is a neck-on-neck race between scientists who discover natural or develop semisynthetic and synthetic bioactive molecules and bacteria, which have developed resistance mechanisms. The emphasis of this chapter is to give an overview of the history of antibiotics research. The situation within the pre-antibiotic era as well as in the early antibiotic era will be described until the Golden Age of Antibiotics will conclude this time travel. The most important antibiotic classes, information about their discovery, activity spectrum, mode of action, resistance mechanisms, and current application will be presented.

Opioid-Induced "Likeability" and "Feeling Good" Are Not Associated With Return Visits to an ED Among Migraine Patients Administered IV Hydromorphone.

PubMed

Friedman, Benjamin W; Latev, Alexander; Campbell, Caron; White, Deborah

2018-05-01

Parenteral opioids are used in more than 50% of emergency department (ED) visits for migraine. Use of opioids for migraine has been associated with subsequent ED visits, perhaps because of opioid-induced euphoria. In this study, we quantify the extent to which nontherapeutic effects of opioids influence migraine outcomes. We hypothesized that "feeling good" and medication likeability would in fact be associated with receipt of opioids (rather than relief of migraine pain) and that receipt of opioids (rather than relief of migraine pain) would be associated with return visits to the ED. During an ED-based clinical trial, migraine patients were randomized to receive hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg IV. Thirty minutes after medication administration, we asked, (1) How much did you like the medication you received? and (2) How good did the medication make you feel? Participants were asked to provide answers on a 0-10 scale. We also determined 0-10 pain scores at baseline and 1 hour and number of return visits for headache during the subsequent month. Sixty-three patients received prochlorperazine and 64 hydromorphone. Prochlorperazine pain scores improved by 6.8 (SD: 2.6), hydromorphone by 4.7 (SD: 3.3) (95%CI for difference of 2.1: 1.0, 3.2). On the 0-10 likeability scale, prochlorperazine patients reported a mean of 7.2 (SD: 2.8), hydromorphone 6.9 (SD: 2.9) (95% CI for difference of 0.3: -0.7, 1.3). On the 0-10 feeling good scale, prochlorperazine patients reported a mean of 7.5 (SD: 2.3), hydromorphone 6.8 (SD: 2.8) (95%CI: for difference of 0.7: -0.2, 1.6). In the hydromorphone group, 8/57 (14%, 95%CI: 7, 26%) returned to the ED vs 5/63 (8%, 95%CI: 3,18%) in the prochlorperazine group. In regression modeling, feeling good was independently associated with pain relief (P < .01) but not with medication received (P = .67) or return visits (P = .12). Similarly, medication likeability was independently associated with pain relief (P < .01) but not medication received (P = .12) or return visits (P = .16). We did not detect an association between hydromorphone and medication likeability, feeling good, or return visits to the ED. Headache relief was associated with medication likeability and feeling good. © 2018 American Headache Society.

Baclofen for alcohol withdrawal.

PubMed

Liu, Jia; Wang, Lu-Ning

2017-08-20

Baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review published in 2015, Issue 4. To assess the efficacy and safety of baclofen for people with AWS. We updated our searches of the following databases to March 2017: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. We used standard methodological procedures expected by Cochrane. We included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no significant difference in CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low quality evidence), adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence). No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low quality evidence.

Genomic misconception: a fresh look at the biosafety of transgenic and conventional crops. A plea for a process agnostic regulation.

PubMed

Ammann, Klaus

2014-01-25

The regulation of genetically engineered crops, in Europe and within the legislation of the Cartagena biosafety protocol is built on false premises: The claim was (and unfortunately still is) that there is a basic difference between conventional and transgenic crops, this despite the fact that this has been rejected on scientifically solid grounds since many years. This contribution collects some major arguments for a fresh look at regulation of transgenic crops, they are in their molecular processes of creation not basically different from conventional crops, which are based in their breeding methods on natural, sometimes enhanced mutation. But the fascination and euphoria of the discoveries in molecular biology and the new perspectives in plant breeding in the sixties and seventies led to the wrong focus on transgenic plants alone. In a collective framing process the initial biosafety debates focused on the novelty of the process of transgenesis. When early debates on the risk assessment merged into legislative decisions, this wrong focus on transgenesis alone seemed uncontested. The process-focused view was also fostered by a conglomerate of concerned scientists and biotechnology companies, both with a vested interest to at least tolerate the rise of the safety threshold to secure research money and to discourage competitors of all kinds. Policy minded people and opponent activists without deeper insight in the molecular science agreed to those efforts without much resistance. It is interesting to realize, that the focus on processes was uncontested by a majority of regulators, this despite of serious early warnings from important authorities in science, mainly of US origin. It is time to change the regulation of genetically modified (GM) crops toward a more science based process-agnostic legislation. Although this article concentrates on the critique of the process-oriented regulation, including some details about the history behind, there should be no misunderstanding that there are other important factors responsible for the failure of this kind of process-oriented regulation, most importantly: the predominance of politics in the decision making processes combined with the lack of serious scientific debates on regulatory matters within the European Union and also in the Cartagena system, the obscure and much too complex decision making structures within the EU, and the active, professional, negative and intimidating role of fundamental opposition against GM crops on all levels dealing with flawed science, often declared as better parallel science published by 'independent' scientists. Copyright © 2013 Elsevier B.V. All rights reserved.

[Manic episode in a patient with Beçhet's disease].

PubMed

Bozikas, V; Ramnalis, A; Dittopoulos, J; Iakovou, J; Garyfallos, G; Fokas, K

2015-01-01

Beçhet's disease (BD) is a chronic, heterogeneous, multisystem disease that affects young males and females around the Mediterranean region, as well as from Far and Middle East. Its etiology is vague with vasculitis being its main pathological feature. International diagnostic criteria have been established and they require the presence of recurrent oral ulcerations plus two of the following: Recurrent genital ulceration, eye lesions, skin lesions and positive pathergy test. A significant number of patients with Beçhet's disease suffers from symptoms from the central nervous system (CNS), while the most common clinical symptoms are pyramidal signs, mental-behavioral changes, hemiparesis and brain stem syndrome. The existence of mental-behavioral changes seems to be one of the most common findings in patients with Neuro-Beçhet (N-BD). These changes seem to be related with memory and attention deficits, and the process of deterioration continues even in attack-free periods, suggesting a continuously active disease process in the CNS. The prevalence of anxiety, depression and general psychiatric symptoms is higher among patients with BD compared to healthy individuals. However, the association between psychiatric symptoms and BD is not clearly understood. On the other hand, syndromes like psychosis or bipolar disorder appear to be less frequent, especially in attack-free periods. We describe the case of a 52-year old woman with Beçhet's disease who developed a single manic episode 13 years after the onset of Beçhet's disease. A 52-year old woman, suffering from Beçhet's disease since the age of 39, developed manic symptoms, namely elevated mood, pressured speech, flight of ideas, distractibility and decreased need for sleep. The above symptoms developed during a period that no other symptoms of Beçhet's disease were present. Moreover there was no other manifestation from the nervous system. A brain MRI was unremarkable, while a brain SPECT study revealed severe hypoperfusion of the left prefrontal cortex. Neuropsychological examination revealed severe disturbance in attention, working memory and learning ability, while her visuaspatial ability and executive functions were well spared. Her symptoms were well controlled after treated with quetiapine 800 mg. The manic episode developed in the absence of any neurological manifestation (Neuro-Beçhet), or other symptom of Beçhet's disease, and was clearly distinguishable from euphoria, disinhibition or irritability that are common in patients with Beçhet's disease. It looks probable that CNS damage caused by the disease constitutes a biological substrate for the development of manic episodes in patients suffering from Beçhet's disease.

[The concept of temperament and its contribution to the understanding of the bipolar spectrum].

PubMed

Koufaki, I; Polizoidou, V; Fountoulakis, K N

2017-01-01

The present article attempts first to provide a historical overview of the concept of temperament,The present article attempts first to provide a historical overview of the concept of temperament,since its foundation by Polybos (4th century B.C.) and the school of Cos, its predominant role in theshaping of the anthropological and humanitarian sciences, until the modern theoretical formulations,such as those proposed by Robert Cloninger and Hagop Akiskal. Secondly, recent literature ispresented, which suggests a strong link of different temperament structures to mental health andpsychopathology. Hans Eysenck (1916-1997) was the first psychologist to establish approaches topersonality differences and to distinguish three dimensions of personality: Neuroticism, Extraversionand Psychotisism. Eysenck was followed by McCrae and Costa who proposed that there are five basicdimensions of personality ("Big Five"). In the mid-1980s, Robert Cloninger developed a distinctivedimensional model of temperament and character traits. Hagop Akiskal emphasized on the affectivecomponents of temperament and their possible connections to mood disorders and creativity.Specifically, temperament assessment seems to help in differentiating between the relationship ofvarious temperaments and the clinical manifestations of bipolar illness. Within the area of mood disorders,specific affective temperaments might constitute vulnerability factors, as well as clinical pictureand illness course modifiers. Viewing mood disorders under this prism gives birth to the concept ofthe bipolar spectrum with major implications for all aspects of mental health research and providingof care. The hyperthymic and the depressive temperaments are related to the more 'classic' bipolarpicture (that is euphoria, grandiose and paranoid thinking, antisocial behavior, psychomotor accelerationand reduced sleep and depressive episodes respectively). On the contrary cyclothymic, anxiousand irritable temperaments are related to more complex pictures and might predict poor responseto treatment, violent or suicidal behavior and high comorbidity. Unipolar disorder diagnosis is oftenchanged due to the fact that a manic or mixed episode can occur after several years of treatment failure.In these cases the evaluation of temperament can prove to be effective in distinguishing betweenunipolar and bipolar depression and thus favoring treatment planning. In addition, temperament assessmentchanges the definition of bipolarity by supporting the concept of "bipolar spectrum". This isa factor that can lead to a rise in prevalence of bipolar cases. Furthermore, the evaluation of temperamenthas shifted our understanding of bipolarity towards the concept of the 'bipolar spectrum'. It hasalso led to an increase in the prevalence of bipolar disorder cases, notably bipolar II, and a decrease in unipolar cases. Finally, incorporating the concept of temperament in our understanding of bipolardisorder constitutes a challenging issue, which can lead to better treatment and outcome of patients.

[Time profile of serum THC levels in occasional and chronic marihuana smokers after acute drog use - implication for drivind motor vehicles].

PubMed

Balíková, Marie; Hložek, Tomáš; Páleníček, Tomáš; Tylš, Filip; Viktorinová, Michaela; Melicher, Tomáš; Androvičová, Renáta; Tomíček, Pavel; Roman, Michal; Horáček, Jiří

2014-01-01

Cannabis consumption has individual influence to cognitive and psychomotor functions of drivers and it has been generally accepted that driving under influence is risky in the perspective of traffic safety. However, rules how to assess fitness to drive are not quite clear. The psychoactive compound delta-9-tetrahydrocannabinol (THC) impairs cognition, psychomotor behaviour and driving performance in a dose-related manner approximately. After a single drug dose, THC blood concentration peaks within minutes, before the end of smoking, with a subsequent rapid decrease to the analytical limit of detection. Peak euphoria is delayed compared to THC peak blood concentration and physiological and behavioural effects return to baseline within 3-5 hours. In chronic users, the lipophilic THC accumulates in fat tissues, where its slow redistribution into blood is the rate limiting process in its terminal elimination. In our experimental study we have attempted to contribute to this discussion with results obtained from human volunteers - cannabis consumers in Czech Republic. Aim of our study was to document the time profile of serum THC level in occasional and chronic cannabis users. The observational interval covered the time immediately after the drug consumption (an own cigarette/joint) till 24 hours after. Our preliminary results have shown that in occasional users, THC serum levels cannot be detected already 4 hours after usual cannabis dose, whereas in chronic users measurable THC concentrations in serum persist longer. Moreover, some chronic consumers were practically with permanent THC detection during our observation period and also the chronic users consumed higher THC doses significantly related to doses in occasional ones. Presented results of the experimental study with human volunteers confirm a great individual variability of the kinetic profile of THC in blood due to complicated redistribution. The practical forensic question is how long the psychotropic effects of THC can persist after the last drug dose. In chronic users there are well documented indications of long term adverse effects to neurocognitive functions. THC blood level itself can not directly document the intensity of impairment of a driver. Moreover, the concentration of THC in blood at the time of driving is probably substantially higher than at the time of blood sampling. Therefore due to the prevention of traffic risk, some countries adopted per se traffic legislation based on analytical principle with minimum tolerance to illegal drugs in blood of drivers at driving. Low blood concentrations of THC close to the limit of detection of a specific toxicological method (GC-MS or LC-MS) are justified in an effective traffic legislation.

Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom.

PubMed

Fluyau, Dimy; Revadigar, Neelambika

2017-01-01

Kratom ( Mitragyna speciosa ) is a tropical tree with a long history of traditional use in parts of Africa and Southeast Asia. Kratom is also known as Thom, Thang, and Biak. Its leaves and the teas brewed from them have long been used by people in that region to manage pain and opioid withdrawal and to stave off fatigue. Kratom is actually consumed throughout the world for its stimulant effects and as an opioid substitute (in form of tea, chewed, smoked, or ingested in capsules). Some case reports have associated kratom exposure with psychosis, seizures, intrahepatic cholestasis, other medical conditions, and deaths. The clinical manifestations of kratom effects are not well defined and the clinical studies are limited. Data research suggest that both stimulant and sedative dose-dependent effects do exist, in addition to antinociceptive, antidepressant activity, anxiolytic-like effects, and anorectic effects, but a growing concern for the drug's effects and safety of use has resulted in national and international attention primarily due to an increase in hospital visits and deaths in several countries that are believed to have been caused by extracts of the plant. There is a dearth of double blind controlled studies. In this study, we aim to use existing literature to clarify both benefits and risks of kratom as well as its diagnosis evaluation as kratom misuse is an emerging trend in the Western world. Literature review using databases such as Embase, Medline, PubMed, Cochrane Library, and Mendeley from 2007 to 2017 were evaluated by all authors to analyze current state on benefits, risks, and diagnosis evaluation of kratom ( M. speciosa ). Data analysis suggested that kratom possesses some benefits such as stimulant and sedative effects as wells as antinociceptive effects. It seems to inhibit pro-inflammatory mediator release and vascular permeability and can enhance immunity. In addition, it may be an antidepressant and anorectic. However, kratom can cause intrahepatic cholestasis, seizure, arrhythmia, impair memory function, coma, and death. Psychological manifestations described are euphoria and feeling relaxed to severe symptoms such as aggression, hostility, and psychosis. Medical manifestations described are polyuria, dry mouth, vomiting, and jerky movements. Currently, liquid chromatography/mass spectrometry and ion mobility spectrometry (IMS) are suggested as the most promising to rapidly screen kratom products providing a positive success rate. Our data analysis has not determined if biochemical benefits of kratom may prove to outweigh its toxicity and risks. On the contrary, it seems that its potential side effects outweigh the benefits, and severe and real health hazards can, insidiously, lead to death. Kratom clinical, psychological, and medical manifestations can be disturbing. Kratom ( M. speciosa ) use, among multiple compounds of the leaf, appear to be increasing in the Western world. Promising methods to accurately identify kratom compounds are still ongoing.

Planning like an Olympian. How London Ambulance Service successfully handled their 'summer of sport'.

PubMed

Killens, Jason

2013-03-01

LOCOG Medical managed thousands of patient contacts across all the Games venues without our intervention. A polyclinic in the athlete's village had extensive diagnostic options, including X-ray and magnetic resonance imaging for athletes and the Olympic family. These helped limit the number of patients who needed transport to the ED. Although the delivery was seamless, there were "behind the scenes" moments in the final stages of planning that made us think. We received additional requests for ambulance cover at training venues that hadn't been planned for on short notice. In addition, the torch relay attracted bigger crowds than initially planned for. Some of the planning assumptions and agreements changed on short notice for various reasons. This meant we had to adjust our plans while also solving human resource issues that you would expect to see among a workforce of around 500 across a six-week period. As part of the National Health Service (NHS) ambulance service Games cohort, more than 500 staff were deployed across 18 venues and 30 days of sport in London. In doing so, they delivered in excess of 165,000 hours of standby and care, responded to nearly 1,500 Games-related incidents and conveyed 800 patients to emergency departments across the capital. After such an influx, it wasn't easy to return to business as usual. Officials with previous host cities had advised us that there would be a feeling of "what next" once the Games concluded. When I first heard this, I thought the opposite would be the case. I expected feeling relieved of overwhelming emotion as well as from the exhaustion of the long days. I do have to say that although this was the case, it's also true that there is a "post Games" come down. We had just been part of a fantastic summer of sport with a brilliant medal tally from Team Great Britain and Paralympics Great Britain that, of course, helped the euphoria. But we did feel real sense of uncertainty about what to do next. We had spent five years planning for it, lived it for the past six months and been part of it for the past 30 days. And now it was over. Overwhelmingly the experience was truly great. There was an immense sense of pride in achievement and participation on the part of every EMT, paramedic EMD, officer and ambulance service employee who helped deliver prehospital care at the Games. The Games and cultural events were a truly once-in-a-lifetime experience. We were privileged to be part of that experience, to provide prehospital care during the Games and to be able to say we were part of something that inspired a generation.

Anatomical relationship between traditional acupuncture point ST 36 and Omura's ST 36 (True ST 36) with their therapeutic effects: 1) inhibition of cancer cell division by markedly lowering cancer cell telomere while increasing normal cell telomere, 2) improving circulatory disturbances, with reduction of abnormal increase in high triglyceride, L-homocystein, CRP, or cardiac troponin I & T in blood by the stimulation of Omura's ST 36--Part 1.

PubMed

Omura, Yoshiaki; Chen, Yemeng; Lu, Dominic P; Shimotsura, Yasuhiro; Ohki, Motomu; Duvvi, Harsha

2007-01-01

Using Bi-Digital O-Ring Test Resonance Phenomena between 2 identical substances, Omura, Y. succeeded in making the image of the outline of internal organs without use of standard imaging devices since 1982. When he imaged the outline of the stomach on the abdominal wall, a number of the lines came out from upper and lower parts of stomach wall. When the lines were followed, they were very close to the well-known stomach meridians. Subsequently, he found a method of localizing meridians and their corresponding acupuncture points as well as shapes and diameters accurately. At the anatomical location of ST 36 described in traditional textbooks, Omura, Y. found there is no acupuncture point. However, in the close vicinity, there is an acupuncture point which he named as true ST 36 in the mid 1980s, but it is generally known as Omura's ST 36. When the effects of the acupuncture on these 2 locations were compared, Omura's ST 36 (true ST 36) produced very significant well-known acupuncture beneficial effects including improved circulation and blood chemistry, while in the traditional ST 36, the effects were small. In this article, the anatomical relationship between these two acupuncture points, with a short distance of 0.6 approximately 1.5 cm between the centers of these locations, was described. In early 2000, Omura, Y. found Press Needle Stimulation of Omura's ST 36, using "Press-Release" procedure repeated 200 times, 4 times a day to cancer patients reduced high cancer cell telomere of 600-1500ng and high Oncogen C-fos Ab2 and Integrin alpha5beta1 of 100-700ng BDORT units to close to lyg (= 10(-24) g) BDORT units. In addition there was a significant reduction of Asbestos and Hg from cancer cells, while markedly reduced normal cell telomere of lyg was increased to optimally high amounts of 500-530ng BDORTunits. Thus, cancer cells can no longer divide and cancer activity is inhibited. The authors have successfully applied this method for a variety of cancers as well as for cardio-vascular diseases with hypertriglyceridemia, hyperglycemia, high L-homocystein, and CRP, high cardiac Troponim I & T, and some hypertension. These beneficial effects were accompanied by euphoria, & relaxation with increased alpha waves in EEG. Thus Omura's ST 36 stimulation is a safe, effective and highly desirable supplemental treatment. In addition to manual stimulation, similar beneficial effects can be induced by finger tip stmulation (without any needle) or with electroacupuncture stimulation, (+) Qi Gong energy stored paper and (+) solar energy stored paper which often resulted in significant clinical improvement.

[Cathinones use in Paris].

PubMed

Batisse, A; Grégoire, M; Marillier, M; Fortias, M; Djezzar, S

2016-08-01

The pattern of recreational drug use has changed over the last decade and now includes a multitude of substances sold as "research chemicals" or new psychoactive substances, "NPS". In France, synthetic cathinones emerged in 2008 (while first mentioned by the French police force in 2007 first alerts among users appeared in 2008) and have grown to be popular drugs of abuse. Under the Official Journal dated 11th June 2010, only mephedrone has been listed as narcotics but "designer drugs" have synthesized new substitute cathinones in order to avoid anti-drug laws. However, since July 2012, in France, all synthetic drugs from the cathinones family have been banned and listed as narcotics following the example of United Kingdom. Despite their recent classification and inclusion on narcotic list, they are readily available on Internet and used widely. Paris Addictovigilance Centre observed a signal of derivate cathinones abuse (21 cases over a two-year period). Paris Addictovigilance Centre and Marmottan Hospital wanted to describe the use of cathinones in the Paris area and alert the health care community about the abuse identification and risk assessment problems of these compounds. After a review of derivated cathinone's chemical structure, pharmacology and toxicology, this article seeks to provide patricians with a clinical description and treatment's modality. Most users of synthetic cathinones will experience euphoria, increased energy, talkativeness, openness and increased sexual arousal. Signs and symptoms of toxicity are consistent with a sympathomimetic toxidrome. The main reasons for care access are psychiatric (hallucinations, psychotic symptoms, agitation) and addiction disorders. Somatic complications were described with various patterns of symptoms such as headache, tachycardia, confusional states, rhabdomyolysis with renal failure or serotonin syndrome. The most important fact is the apparition of the "slam" phenomenon among men who have sex with men (MSM). The "slam" is a compound of three characteristic elements: injection, sexual party and psychostimulant drug. According to users, "slam" is convenient for group sex and is used it to put them into a good mood and a disinhibition state. These compounds cause fast dependence syndrome with strong craving and prolonged psychiatric symptoms and increase infectious risk (HIV, VHC, VHB…). The cathinones family is not detected in conventional urine drug screenings. We point out the lack of confirmatory analytic testing data which remains the only way to determine the actual etiology of the clinical effects observed since drug users do not always know exactly what they took. These substances can be identified by special analyses using gas chromatography or liquid chromatography and mass spectroscopy technology. This injection drug is used in order to increase sexual desire, delay orgasm and decrease sexual inhibition and is prevalent in many studies on MSM samples. Cathinones would popularize the "slam". Harm reduction policy requires specific MSM interventions on both sexual and drug addiction networks. Copyright © 2015 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

[Mixed depression and DSM-5: A critical review].

PubMed

Weibel, S; Bertschy, G

2016-02-01

Mixed depression is a depressive syndrome characterized by the presence, along with the typical depressive symptoms of depression, of those of over activation and excitation. If sometimes this activation is expressed by classical hypomanic symptoms, it is often observed by means of more subtle expression: inner tension, crowded thoughts, dramatic expression suffering, and unproductive agitation. It is important to identify mixed depression because such patients are particularly at risk of suicidal behaviors, substance abuse and therapeutic resistance. Even if therapeutic strategies continue to be discussed, treatments should rely on mood stabilizers and antipsychotics instead of antidepressants as in pure depression. Even though the concept of mixed depression has been described for more than twenty years, first by Koukopoulos and then by other authors, it had been little studied, especially because it did not appear in international psychiatric classifications. The DSM-IV supported a very narrow conception of the mixed states because the criteria required simultaneous full manic and full depressive syndromes, corresponding only to some dysphoric manias. The recently published DSM-5 proposes modifications in mood and bipolar disorder classifications, and especially introduces the possibility to specify depressive and manic episodes with "mixed features". To diagnose depression with mixed features, a full depressive syndrome has to be present together most of time with three hypomanic symptoms, except symptoms that are considered as overlapping (that can be observed either in mania or in depression), i.e. agitation, irritability and distractibility. Critical analysis of DSM criteria and review of literature. We first analyzed the clinical relevance of the definition of depression with mixed features which could correspond to mixed depression. The problem is that the hypomanic symptoms allowed by the manual lead to symptom associations that are rather illogical (as euphoria with depression) or improbable (as increased or excessive involvement in activities that have a high potential for painful consequences). Also, some more specific symptoms that can be observed in mixed depression are not mentioned (such as hypersensitivity to light or noise, absence of motor retardation, dramatic expressivity of suffering). The DSM-5, as did DSM-IV, refers to an understanding of mixed depression as a simple addition of depressive and manic symptoms. The classification does not take into account that the symptoms could be rather different from hypomania, as the expression of an overactive thought in a depressed mind. Secondly, we reviewed cohort studies using the DSM-5 criteria (or similar criteria with the exclusion of overlapping symptoms), and as a consequence of the poorly defined symptoms, we found that the diagnosis of mixed depression according to DSM-5 is almost impossible, either in unipolar or in bipolar depression. We think, with others, that the definition of the mixed depression by the DSM-5 is not clinically relevant and misses important information about the concept. Clinicians can be attentive to the identification of mixed character in depression, even if DSM-5 criteria are not fully met. Unfortunately, the DSM-5 definition could undermine research efforts for a better understanding of epidemiology, phenomenology and therapeutics of mixed depression. We propose and discuss alternative solutions for defining mixed depression, such as the absence of exclusion of "overlapping" symptoms, a more insighted phenomenology, or a dimensional approach. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

[Risk-taking in adolescence: A neuroeconomics approach].

PubMed

Barbalat, G; Domenech, P; Vernet, M; Fourneret, P

2010-04-01

Risk-taking behaviors represent the main cause of morbi-mortality in adolescence. Here, we analyze their neural correlates, based on a neuroeconomics approach. This approach postulates that risk-taking behaviors result from multiple decision-making biases that impair the selection of the most appropriate action among alternatives based on their subjective evaluation. Specifically, we investigate three important domains in value-based decision-making: risk aversion, loss aversion and intertemporal choice. First, when people have to make a decision between two rewarding options, they will usually prefer the more certain, even possibly lower, option - a phenomenon called "risk aversion". Yet adolescent people have been found to be less averse to risk than adults. This observation was linked to hypoactivation in (1) the anterior insula, involved in negative emotion such as fear and disgust and (2) the anterior cingular and the posterior ventromedial prefrontal cortices, involved in the monitoring of conflict and error detection. Second, people are generally described as being more sensitive to the possibility of losing objects than to that of gaining the same objects - "loss aversion". Here, we suggest that adolescents may be less averse to losses than adults when estimating the prospects of gaining and losing objects. Indeed, adolescent people have been found to be more affected by reward (e.g. euphoria or social integration consecutive to drug absorption) and less affected by punishment (e.g. malaise after drug consumption) than adults. Whereas the former process is subserved by hyperactivations in regions involved in reward evaluation such as the nucleus accumbens, the latter has been proposed to be subserved by hypoactivations in regions involved in negative emotions such as the amygdala or the insular cortex. This lower sensitivity to losses compared to gains in adolescents could be another important mechanism underlying risk-taking behaviors. A third dimension of adolescents' decision-making biases is temporality. It has been shown that adolescents favor immediate over delayed prospects, reflecting how future consequences of their decisions are heavily discounted. For example, adolescents can fail in projecting the future benefits of having safe sex - and thereby avoiding the risk of sexually transmitted disease or pregnancy - being more interested in the immediate reward of having romantic uninterrupted sexual intercourse. This impairment in inhibiting the choice of the early alternative could be related to the hypofunctionality of the lateral prefrontal cortex. Importantly, these three biases in the evaluation of decisions by adolescents may be related to the maturation of two neuronal systems. On the one hand, the early reorganization of dopaminergic neurons in the motivational system, due to the brutal secretion of sex hormones (mostly estrogens, testosterone and oxytocin) at the beginning of puberty, impels adolescents toward thrill seeking. On the other hand, the slow maturation of the cognitive control system, mostly exerted by the prefrontal cortex, implies that these impulses cannot be appropriately regulated. Two important neurodevelopmental mechanisms are thought to play a key role in the genesis of risk-taking behaviors in adolescence: the brutal secretion of sex hormones at the beginning of puberty and the delayed maturation of cognitive control. As such, these behaviors can be considered as inevitable, even if other factors, like sex, heredity and precariousness, can enhance their frequency. The implications of these conclusions for the prevention of risk-taking behaviors in adolescence are discussed. 2009 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

[On the risk of dependence on gabapentinoids].

PubMed

Bonnet, Udo; Scherbaum, Norbert

2018-02-01

In the last ten years, the prescriptions of the gabapentinoids gabapentin and pregabalin increased largely also in Germany. Since several national and international pharmacovigilance-databases have warned for abuse liabilities and overdose fatalities in association with both gabapentinoids, which moreover, became to be sold on internet and black-markets, their addictive power has been subject to an ongoing clinical debate. As pre- and post-approval clinical trials did not reveal significant signs of dependence on gabapentin or pregabalin, we systematically searched in PubMed and Scopus for clinical studies and case reports being associated with abuse of and dependence on these drugs. We found 14 clinical-epidemiologic studies and 38 case reports/series. These were evaluated for i) fulfilled dependence criteria according to ICD-10, ii) non-medical self-administration and their duration, iii) relapses, iv) social sequels, and v) cases seeking treatment for misusing gabapentin or pregabalin. Mostly, the cases of abuse of and dependence on gabapentinoids appeared to be associated with other substance dependencies, primarily opiate dependence and polyvalent drug use. Drug users preferred pregabalin citing a faster and stronger euphoria ("liking") than achievable with oral gabapentin. Both gabapentinoids were anxiolytic in therapeutic doses, stimulating in lower and sedating along with increasing doses. Fatalities have been described mainly in the population of opiate dependents and polyvalent drug users, predominantly together with excessive pregabalin overdosing. It is debated whether the gabapentinoids were indeed the main cause of death in these cases or whether gabapentin and pregabalin had been only bystanders. Tolerance and withdrawal symptoms (physical dependence) of gabapentinoids appeared to be common in medical and non-medical use of gabapentinoids. There were only 4 persons who had fulfilled behavioral dependence criteria of gabapentinoids (all had used pregabalin) and had no association with other substance use disorders (apart from nicotine). Regarding the transitions from prescription to non-medical self-administration, the frequency and duration of self-administrations as well as the number of reported relapses, pregabalin appeared also to be more addictive than gabapentin. However, all these events were reported rather infrequently compared with traditional substances of abuse. We did not find a case with social sequalea due to the use of gabapentinoids or a person who sought treatment for his gabapentin or pregabalin use. Therefore, the gabapentinoids were assumed to possess a lower "wanting" in consideration of Berridge's and Robinsons's incentive-sensitization theory of addiction. Also, anti-adverse selection of gabapentinoids is discussed to be present in the population of opioid and multi-drug users. Based upon all these results and assumptions, we have estimated the relative risk of dependence on gabapentinoids by using an algorithm which was previously developed by Griffith and Johnson for evaluation of the abuse liabilities of sedatives. Overall, the risk of harm and dependence on gabapentinoids appeared to be lower than that of other sedatives (and stimulants). In addition, pregabalin appeared to be somewhat riskier than gabapentin. We think that in patients with current or past substance use disorders, the treatment with gabapentinoids should be avoided or if indispensable, these drugs should be administered exclusively over a limited time span with caution by using a therapeutic and prescription monitoring. Georg Thieme Verlag KG Stuttgart · New York.

[Acting out and psychoactive substances: alcohol, drugs, illicit substances].

PubMed

Gillet, C; Polard, E; Mauduit, N; Allain, H

2001-01-01

In humans, some psychotropic agents (alcohol, drugs, illicit substances) have been suggested to play a role in the occurrence of major behavioural disorders, mainly due to the suppression of psychomotor inhibition. Behavioural disinhibition is a physiological mechanism which allows humans to behave appropriately according to a given environmental situation. The behavioural disinhibition induced by either therapeutic dosage or misuse involves the loss of restraint over certain types of social behaviour and may increase the risk of auto or hetero-aggression and acting out. The increased use of psychotropic agents in recent years and the occurrence of unwanted effects are worrying and must be detected and evaluated. The objective of the present study was to establish a causal relationship between psychoactive substance use and occurrence of major behavioural disorders, such as paradoxical rage reactions and suicidal behaviour, based on a literature analysis. It consisted of reviewing reports of drug-induced violent reactions in healthy volunteers and demonstrating, where possible, a cause-effect relationship. Patients with schizophrenia and psychopathic personalities were not included in our study since psychiatric comorbidity could influence behavioural responses. Psychotropic agents included drugs, licit and illicit substances already associated with violence in the past. Many reports used the "Go/No Go test" to evaluate the disinhibiting effect of psychotropic substances; this allows the "cognitive mapping" of drugs. The results suggest that only alcohol, antidepressants, benzodiazepines and cocaïne are related to aggressive behaviour. The best known precipitant of behavioural disinhibition is alcohol, which induces aggressive behaviour. However, there are large differences between individuals, and attentional mechanisms are now recognised as being important in mediating the effects of alcohol. Suicidal tendency as an adverse antidepressant reaction is rare, especially with atypical antidepressants. However, the risk of acting out exists and the responsibility of antidepressant agents in the genesis of suicidal tendencies is now established. The disinhibiting effects of benzodiazepines are well-known and proven by clinical trials. It's a "model" of acting out, and the causal relationship is undeniable. That cocaïne is related to violent behaviour is demonstrated by its pharmacological actions on CNS. The chronic use of cocaïne induces "a limbic dyscontrol syndrome" based on the altered activity of limbic structures. On the contrary, we could not demonstrate a causal relationship between aggression and either cannabis, ecstasy or phencyclidine. Cannabis abusers look particularly for euphoria and relaxing effects. Aggression as an adverse cannabis reaction is very rare and occurs in most cases in association with other drugs and in predisposed individuals. Ecstasy use may lead to long-term alterations of neuronal function in the human CNS and cause psychiatric disorders. However, there is insufficient information about long-term use of ecstasy to estimate its role in the occurrence of behavioural disorders. Clinical and forensic assumptions about phencyclidine and violence were not warranted. However, the substance-effect relationships can be criticized in the case of alcohol, antidepressants, benzodiazepines and cocaïne. In fact, individual, social and psychiatric factors exert an influence on behaviour that is superior to the pharmacological effect of psychotropic agents. The most important parameter in drug-induced behavioural disinhibition is dosage, but mode of administration is also important. In addition, polysubstance abuse is very common. Substances may be taken simultaneously and alcohol is frequently combined with drugs. The combinations of substances result in multiple interactions, and very little is known about the effects of these interactions on violence in humans. Co-occurrence of substance abuse and other mental disorders is also very frequent. Multiple substance abuse should be avoided, because potential interactions between two or more drugs are more likely to cause violent behaviour. In the future, a specific treatment of these deleterious phenomena will have to be considered in order to reduce drug-induced iatrogenic behavioural disorders.

Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy.

PubMed

Smith, Lesley A; Azariah, Fredric; Lavender, Verna T C; Stoner, Nicola S; Bettiol, Silvana

2015-11-12

Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use. To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer. We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication. We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy. At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI). We included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I(2) = 0% in both analyses).People had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I(2) = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I(2) = 0%).People reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence). Comparison with other anti-emetics There was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I(2) = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I(2) = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I(2) = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross-over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I(2) = 0%).People had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I(2) = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.People had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I(2) = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I(2) = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I(2) = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I(2) = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I(2) = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.People reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I(2) = 51%; low quality evidence).In comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.Two trials with 141 participants compared an anti-emetic drug alone with a cannabinoid added to the anti-emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events. Quality of the evidence The trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti-emetic treatment regimens. Furthermore, the quality of evidence arising from meta-analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results. Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.

Beware the Medical-Industrial Complex.

PubMed

Stevens; Glatstein

1996-01-01

". we must guard against the acquisition of unwarranted influence, whether sought or unsought, by the military industrial complex." Dwight D. Eisenhower, 34th President of the United States (1953-1961). Farewell Address, January 17, 1961. If Ike were with us today, he might well expand his views on power and influence to include modern American medicine. The corporatization of health care in the United States has moved rapidly in recent years. Physicians are now in a position that requires us to adapt to an increasingly Darwinian existence. Years of training to be "rugged individualists" pushing the frontiers of medical knowledge have not equipped us to fight corporate battles, nor to justify our treatment decisions to bean counters. When the most important consideration becomes the bottom line, then innovation, creativity, and research diminish in importance. They will, in fact, be selected against because they cost money. Up to now, these have been the hallmarks of American medicine, and we must strive to maintain our position of American leadership in biotechnology. New developments in cancer treatment include expensive technological "bells and whistles" which physicians must ultimately evaluate objectively, despite lush advertisements from companies with obvious vested interests, and authoritative testimonials from biased investigators who presumably believe in their own work to the point of straining credulity and denying common sense. The 3-D image that was created by a computer may look beautiful (and cost accordingly), but it is hard to believe that it can fundamentally change the outcome of patients when it does not add any new data that bear on basic issues. For example, where is the exact edge of the tumor? If one pays through the nose for increasing precision where there is no new accuracy, the purchase appears less attractive, perhaps, than the hype of the salesman or the enthusiasm of a neurosurgeon or a "stereotactic" radiation oncologist (showing biased data, if any at all). For radiation therapy, the 20th century has largely represented progress by creating larger, higher energy machines for treatment. Now, with the 21st century on the horizon, x-ray treatment parameters have probably been optimized over the past 10 years or so. We see no obvious advantage in an x-ray beam beyond about 18 MeV, and none for electrons beyond 20-25 MeV. Exotic particles such as protons, neutrons, and negative pions, though expensive and difficult to deliver, have not yielded yet significant gains in either local control or survival. A variety of new afterloading machines, such as pulsed high dose rate machines, have also been developed with no clear biologic advantage over more standard remote afterloaders. Thus, new equipment will be exploiting issues of convenience, efficiency, and increased throughput (translate: economic improvement, not biological superiority). Today's technology is vastly ahead of our biologic understanding of malignant cells. Our true challenge for the 21st century is to understand the biology of malignant cells and to bring our technology to bear on the biological aspects of cancer. To improve results, cellular manipulations of some sort will probably be necessary. Perhaps these will be mediated through gene therapy, although the manipulation of some genes, to the exclusion of all others, in only tumor cells and in all tumor cells may be a biological challenge beyond our limitations. One is reminded of another time, a decade or two ago, when some tumor immunologists were predicting monoclonal antibodies would soon replace other modalities. Eventually, over time, the immunologists began to appreciate the enormous adaptability that cancer cells possess; the cells are much more than passive receptacles of antigens simply waiting to be destroyed by antibodies. Drugs which affect the function of specific oncogenes, such as the farnesyl transferase inhibitor effect on ras genes, are also quite promising. Clearly, however, there are not "magic bullets" for most cancers. The effects of gene manipulation on patient outcome, if any, are likely to be found only in the setting of combined modality therapy. The most promising clinical research from the last decade or so reinforces the utility of a combined approach in treating cancers. Unfortunately, combined treatments and the development of new combined treatments are expensive. In today's world of corporate medicine and managed care, academic centers are under considerable pressures. They are perceived as being too expensive, and thus they are in danger of being shut out of contractual arrangements with third-party representatives. If these centers are to survive, they must reform themselves: One, they must establish meaningful relationships with community hospitals and community physicians. Two, the academic programs must learn to minimize charges and deliver a true multidisciplinary service to patients in an efficient way. Three, the centers must learn to invest wisely in new technologies that community hospitals cannot and will not be expected to support. This "wisdom" refers to selection of technology that truly may have impact on the outcome of patients' lives by early detection or by treatment. The euphoria associated with projected gains of some investigational treatments can be misleading: randomized prospective trials have shown in the past that postoperative radiation following a complete resection of lung cancer, breast cancer, or rectal cancer adds a major improvement to local control, but with relatively little improvement in survival. How many times will it be necessary for companies and self-impressed investigators to rediscover this particular wheel? We must remember that every new therapy costs money, so we must focus our research time and money in promising areas. If cost is allowed to be the most important mitigator of health care, research as we know it will end. The relative lack of new therapies means that some people will die prematurely because of our lack of foresight. As scientists, we must be seen as providers of a value-added product. Improvement in cancer cure rates has been frustratingly slow. We work against a clever, tenacious adversary - both in the clinic and in the corporate board room. It is our responsibility to tout our accomplishments, admit our failures, and provide progressively better basic and clinical research with an eye toward future improvements in outcome. We must not be seen as yet another special interest come to drink at the well of public spending, but as advocates for the public good. If we fail to become important to those who control medical spending, we will be unable to make any important long-term contribution to those who matter most - our patients.