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Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences

Abstract

Acute and enduring adverse effects of psilocybin have been reported anecdotally, but have not been well characterized. For this study, 1993 individuals (mean age 30 yrs; 78% male) completed an online survey about their single most psychologically difficult or challenging experience (worst “bad trip”) after consuming psilocybin mushrooms. Thirty-nine percent rated it among the top five most challenging experiences of his/her lifetime. Eleven percent put self or others at risk of physical harm; factors increasing the likelihood of risk included estimated dose, duration and difficulty of the experience, and absence of physical comfort and social support. Of the respondents, 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring psychological symptoms. Three cases appeared associated with onset of enduring psychotic symptoms and three cases with attempted suicide. Multiple regression analysis showed degree of difficulty was positively associated, and duration was negatively associated, with enduring increases in well-being. Difficulty of experience was positively associated with dose. Despite difficulties, 84% endorsed benefiting from the experience. The incidence of risky behavior or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants.

Carbonaro, T. M., Bradstreet, M. P., Barrett, F. S., MacLean, K. A., Jesse, R., Johnson, M. W., & Griffiths, R. R. (2016). Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Journal of Psychopharmacology, 0269881116662634.
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The effects of ecstasy on neurotransmitter systems: a review on the findings of molecular imaging studies

Abstract

Rationale: Ecstasy is a commonly used psychoactive drug with 3,4-methylenedioxymethamphetamine (MDMA) as the main content. Importantly, it has been suggested that use of MDMA may be neurotoxic particularly for serotonergic (5-hydroxytryptamine (5-HT)) neurons. In the past decades, several molecular imaging studies examined directly in vivo the effects of ecstasy/MDMA on neurotransmitter systems.

Objectives: The objective of the present study is to review the effects of ecstasy/MDMA on neurotransmitter systems as assessed by molecular imaging studies in small animals, non-human primates and humans.

Methods: A search in PubMed was performed. Eighty-eight articles were found on which inclusion and exclusion criteria were applied.

Results: Thirty-three studies met the inclusion criteria; all were focused on the 5-HT or dopamine (DA) system. Importantly, 9 out of 11 of the animal studies that examined the effects of MDMA on 5-HT transporter (SERT) availability showed a significant loss of binding potential. In human studies, this was the case for 14 out of 16 studies, particularly in heavy users. In abstinent users, significant recovery of SERT binding was found over time. Most imaging studies in humans that focused on the DA system did not find any significant effect of ecstasy/MDMA use.

Conclusions: Preclinical and clinical molecular imaging studies on the effects of ecstasy/MDMA use/administration on neurotransmitter systems show quite consistent alterations of the 5-HT system. Particularly, in human studies, loss of SERT binding was observed in heavy ecstasy users, which might reflect 5-HT neurotoxicity, although alternative explanations (e.g. down-regulation of the SERT) cannot be excluded.

Vegting, Y., Reneman, L., & Booij, J. (2016). The effects of ecstasy on neurotransmitter systems: a review on the findings of molecular imaging studies. Psychopharmacology, 1-29. 10.1007/s00213-016-4396-5

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Cytotoxic Effects of Salvinorin A, A Major Constituent of Salvia divinorum

Abstract

S. divinorum is a psychoactive plant that has been consumed as a recreational drug of abuse in the last years. Salvinorin A is its main constituent, and is responsible for the observed psychoactive effects. Both S. divinorum and salvinorin A have become controlled drugs in several countries, but they are not listed in the Schedules of the United Nations Drug Conventions. Regarding the effects of S. divinorum consumption, almost all studies are based on in vivo or on surveys, and there are no studies in vitro on its toxicity. Furthermore, all studies are focused on the acute toxicological effects of the plant. So, it is of utmost importance to further investigate the effects of S. divinorum and salvinorin A, particularly using in vitro models, after prolonged exposures. In this context, the present work evaluated the in vitro toxicity induced by S. divinorum or salvinorin A in six cell lines, through MTT assays and LC50 determination. Overall, results showed that both S. divinorum and salvinorin A are cytotoxic, dose- and time-dependent. Also, Hep G2 and Caco 2 (to a lesser extent) cells showed lower sensitivity to S. divinorum and salvinorin A when compared to the other studied cell lines. To our knowledge, this is the first work focused on the in vitro toxicity of S. divinorum and salvinorin A using a variety of cell lines, which are extensively described in literature and have been widely used in several in vitro studies.
Martinho, A., M Silva, S., & Gallardo, E. (2016). Cytotoxic Effects of Salvinorin A, A Major Constituent of Salvia divinorum. Medicinal Chemistry12(5), 432-440. 10.2174/1573406411666151005105617
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Ketamine abuse potential and use disorder

Abstract

Ketamine is a noncompetitive antagonist of N-methyl-d-asparate (NMDA) receptor and has been long used as an anesthetic agent in humans and veterinary medicine. The present article reviews the epidemiology, pharmacology, neurochemistry, and treatment of ketamine abuse. Ketamine has a unique mood controlling property and a number of studies have demonstrated a significant and rapid antidepressant effect of ketamine. However, the therapeutic value of ketamine to treat psychiatric disorders faces a major challenge that ketamine also owns significant reinforcing and toxic effects. Its abuse has posted severe harms on individuals and society. Disrupted learning and memory processing has long been related with ketamine use. It is hypothesized that ketamine blocks NMDA receptors on gamma-aminobutyric acid (GABA) neurons inside the thalamic reticular nucleus, which leads to disinhibition of dopaminergic neurons and increased release of dopamine. Currently, there is no specific treatment for treating every ketamine patient presenting peripheral toxicity. Interestingly, ketamine psychotherapy has been suggested to be a promising approach to treat addiction of other drugs. Future research can continue to develop creative ways to investigate potential mechanism and treatments related to ketamine abuse that have posted severe individual and social harms.

Liu, Y., Lin, D., Wu, B., & Zhou, W. (2016). Ketamine abuse potential and use disorder. Brain research bulletin. http://dx.doi.org/0.1016/j.brainresbull.2016.05.016
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The potential use of ayahuasca in psychiatry

Abstract

Ayahuasca is a decoctum made of admixture plants containing dimethyltryptamine and harmine. For millennia it has been used as a central element of spiritual, religious, initiation, and other – foremost healing – rituals, originally by the indigenous groups of the Amazon basin and later by the mestizo populations of the region. During the last two decades the brew has raised increased scientific and lay interest about its healing potentials within the framework of Western therapeutic settings. The typical ayahuasca effects consist of strong somatic reactions, vivid visions, relived personal memories, cathartic emotions, and insightful, introspective experiences when the emerging mental contents take different context and get deeper perspectives. The ayahuasca-experience can be exhausting necessitating the presence of an experienced leader for helping participants to pass difficult phases and for maximizing therapeutic benefits. No health damaging adverse effect has been confirmed thus far as result of its well-structured, institutionalized use. The scientific investigation of ayahuasca is hindered by legal issues, methodical problems, and sociocultural preconceptions. The present review outlines the therapeutic potentials of ayahuasca use in psychiatry with its psychobiological and spiritual background.

Frecska, E., Bokor, P., Andrassy, G., & Kovacs, A. (2016). The potential use of ayahuasca in psychiatry. Neuropsychopharmacologia Hungarica: a Magyar Pszichofarmakologiai Egyesulet lapja= official journal of the Hungarian Association of Psychopharmacology, 18(2), 79.
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Using the Theory of Planned Behavior to predict implementation of harm reduction strategies among MDMA/ecstasy users

Abstract

This prospective study was designed to test whether the variables proposed by the Theory of Planned Behavior (TPB) were associated with baseline intention to implement and subsequent use of 2 MDMA/ecstasy-specific harm reduction interventions: preloading/postloading and pill testing/pill checking. Using targeted Facebook advertisements, an international sample of 391 recreational ecstasy users were recruited to complete questionnaires assessing their ecstasy consumption history, and their attitudes, subjective norms, perceived behavioral control, habit strength (past strategy use), and intention to use these two strategies. Attitudes, subjective norms, and perceived behavioral control were significantly associated with baseline intention to preload/postload and pill test/pill check. Out of the 391 baseline participants, 100 completed the two-month follow-up assessment. Baseline habit strength and frequency of ecstasy consumption during the three months prior to baseline were the only significant predictors of how often participants used the preloading/postloading strategy during the follow-up. Baseline intention to pill test/pill check was the only significant predictor of how often participants used this strategy during the follow-up. These findings provide partial support for TPB variables as both correlates of baseline intention to implement and predictors of subsequent use of these two strategies. Future investigations could assess whether factors related to ecstasy consumption (e.g., subjective level of intoxication, craving, negative consequences following consumption), and environmental factors (e.g., accessibility and availability of harm reduction resources) improve the prediction of how often ecstasy users employ these and other harm reduction strategies.

Davis, A. K., & Rosenberg, H. (2016). Using the Theory of Planned Behavior to predict implementation of harm reduction strategies among MDMA/ecstasy users. Psychology of Addictive Behaviors, 30(4), 500.  http://dx.doi.org/10.1037/adb0000167
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Ibogaine and addiction in the animal model, a systematic review and meta-analysis

Abstract

Ibogaine is a naturally occurring substance which has been increasingly used in the lay-scene to reduce craving and relapse in patients with substance use disorders (SUDs). Although human clinical trials on the safety and efficacy of ibogaine are lacking, animal studies do support the efficacy of ibogaine. In this systematic review and meta-analysis (MA), we summarise these animal findings, addressing three questions: (1) does ibogaine reduce addictive behaviour in animal models of SUDs?; (2) what are the toxic effects of ibogaine on motor functioning, cerebellum and heart rhythm?; (3) what are neuropharmacological working mechanisms of ibogaine treatment in animal models of SUDs? MA of 27 studies showed that ibogaine reduced drug self-administration, particularly during the first 24 h after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 h after supplementation, and cerebral cell loss even weeks after administration. Data on ibogaines effect on cardiac rhythm, as well as on its neuropharmacological working mechanisms are limited. Our results warrant further studies into the clinical efficacy of ibogaine in SUD patients in reducing craving and substance use, but close monitoring of the patients is recommended because of the possible toxic effects. In addition, more work is needed to unravel the neuropharmacological working mechanisms of ibogaine and to investigate its effects on heart rhythm.

Belgers, M., Leenaars, M., Homberg, J. R., Ritskes-Hoitinga, M., Schellekens, A. F. A., & Hooijmans, C. R. (2016). Ibogaine and addiction in the animal model, a systematic review and meta-analysis. Translational psychiatry, 6(5), e826. http://dx.doi.org/10.1038/tp.2016.71
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