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Decision-making in chronic ecstasy users: a systematic review

/ MDMA, Papers, Psychology, Publications / / , ,

Abstract

Different cognitive impairments have been reported as a result of long-term MDMA/ecstasy use. Increased impulsivity and altered decision-making have been shown to be associated with the development and maintenance of addictive disorders pointing towards the necessity to understand a potential impairment of decision-making due to MDMA use. Thus, assessing the long-term effects of MDMA is crucial in order to evaluate its controversially discussed therapeutic use. The aim of this systematic review is to summarize the scientific literature on potential effects of chronic MDMA use on higher order decision-making processes in humans. Therefore, a systematic search for controlled trials relevant to the topic has been performed. Only studies using specific tasks on decision-making were included that involved subjects in the drug-free interval with drug-naïve, and/or polydrug control groups. A total of twelve studies could be identified that met the inclusion criteria, all of which were cross-sectional studies. The findings on decision-making disturbances in MDMA users were heterogeneous. Seven studies reported increased risky decisions, whereas five studies did not find MDMA-specific influences on decision-making. Increased impulsivity was observed both in MDMA groups and in (poly)drug control groups in almost all studies. Thus, the current state of research does not allow for the conclusion that long-term use of MDMA affects decision-making behavior in general. More detailed specifications as well as further investigations of the relevant processes are needed. Significant tendencies towards risky decision-making among long-term MDMA use have been observed, but need to be confirmed by studies using a longitudinal design.

Betzler, F., Viohl, L., & Romanczuk‐Seiferth, N. (2016). Decision‐making in chronic ecstasy users: a systematic review. European Journal of Neuroscience. 10.1111/ejn.13480
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The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens

/ LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / / ,

Abstract

Classic hallucinogens share pharmacology as serotonin 5-HT2A, 5-HT2B, and 5-HT2Creceptor agonists. Unique among most other Schedule 1 drugs, they are generally non-addictive and can be effective tools in the treatment of addiction. Mechanisms underlying these attributes are largely unknown. However, many preclinical studies show that 5-HT2C agonists counteract the addictive effects of drugs from several classes, suggesting this pharmacological property of classic hallucinogens may be significant. Drawing from a comprehensive analysis of preclinical behavior, neuroanatomy, and neurochemistry studies, this review builds rationale for this hypothesis, and also proposes a testable, neurobiological framework. 5-HT2C agonists work, in part, by modulating dopamine neuron activity in the ventral tegmental area—nucleus accumbens (NAc) reward pathway. We argue that activation of 5-HT2Creceptors on NAc shell, GABAergic, medium spiny neurons inhibits potassium Kv1.x channels, thereby enhancing inhibitory activity via intrinsic mechanisms. Together with experiments that show that addictive drugs, such as cocaine, potentiate Kv1.x channels, thereby suppressing NAc shell GABAergic activity, this hypothesis provides a mechanism by which classic hallucinogen-mediated stimulation of 5-HT2C receptors could thwart addiction. It also provides a potential reason for the non-addictive nature of classic hallucinogens.

Canal, C. E., & Murnane, K. S. (2016). The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens. Journal of Psychopharmacology, 0269881116677104.
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Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use

/ Ayahuasca, Depressive Disorders, Iboga / Ibogaine, Ketamine, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / / , , , ,

Abstract

Psychedelic drugs have been used as treatments in indigenous cultures for thousands of years. Yet, due to their legal status, there has been limited scientific research into the therapeutic potential of these compounds for psychiatric disorders. In the absence of other effective treatments however, researchers have begun again to systematically investigate such compounds and there is now evidence pointing to the use of psychedelic drugs in the treatment of addiction. In this review we focus on human evidence for the effectiveness of preparations used by indigenous cultures in the Amazon (ayahausca) and Africa (ibogaine) and worldwide (psilocybin), and more recently synthetised drugs such as the serotonergic hallucinogen LSD and the dissociative anaesthetic ketamine. Potential mechanisms explored are anti-depressant effects, changes in neuroplasticity and existential psychological effects of these drugs.

Morgan, C., McAndrew, A., Stevens, T., Nutt, D., & Lawn, W. (2017). Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use. Current Opinion in Behavioral Sciences, 13, 71-76. 10.1016/j.cobeha.2016.10.009
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Cognitive and behavioural effects induced by social stress plus MDMA administration in mice

/ Depressive Disorders, MDMA, Papers, Psychology, Publications / / , , , ,

Abstract

Adverse life experiences such as social stress may make an individual more vulnerable to drug addiction and mental disorders associated with drug consumption. The present work aimed to evaluate the effects of stress induced by acute social defeat combined with the administration of 3,4-methylenedioxymethamphetamine (MDMA) on depression-like behaviour, memory function and motor response to drug in late adolescent male mice. Two groups of mice were exposed to social defeat (SD) during four encounters with an aggressive co-specific, which took place on alternate days. Immediately after defeat, animals were treated with saline or MDMA 10mg/kg (SD+SAL and SD+MDMA). In control groups, mice were placed in a neutral cage without an opponent (Control+SAL, Control+MDMA). Corticosterone levels and temperature were measured on the last day of this phase. During the following days, the behaviour of the animals was evaluated in the tail suspension test (an animal model of depression), memory tasks (passive avoidance and object recognition) and, after administration of 5mg/kg of MDMA, in the open-field test. Exposure of adult mice to acute social defeat plus MDMA increased immobility in the tail suspension test (depression-like behaviour), produced cognitive impairment, and reduced the motor response to MDMA. An increase in corticosterone levels and a decrease of temperature were also observed. As hypothesised, a combination of social stress and consumption of MDMA increases the risk of developing mental and cognitive disorders. Our results support the idea that stress is a common contributing factor to the high rate of comorbidity between substance abuse and mental disease.

García-Pardo, M. P., Roger-Sánchez, C., Rodríguez-Arias, M., Miñarro, J., & Aguilar, M. A. (2017). Cognitive and behavioural effects induced by social stress plus MDMA administration in mice. Behavioural Brain Research, 319, 63-72. 10.1016/j.bbr.2016.11.012
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Potential Psychiatric Uses for MDMA

/ Anxiety Disorders / PTSD, Depressive Disorders, MDMA, Papers, Psychology, Publications / / ,

Abstract

Phase 2 trials of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy have demonstrated initial safety and efficacy for treatment of PTSD, with potential for expansion to depression and anxiety disorders. In these trials, single doses of MDMA are administered in a model of medication-assisted psychotherapy, differing from trials involving daily drug administration without psychotherapy. This model presents an opportunity to utilize accelerated regulatory pathways, such as FDA Breakthrough Therapy Designation, to most effectively and expeditiously test such novel approaches.

Klosinski, B. B., & Mithoefer, M. C. (2016). Potential Psychiatric Uses for MDMA. Clinical Pharmacology & Therapeutics. 10.1002/cpt.565
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Psychedelics as Medicines: An emerging new paradigm

/ Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / / , ,

Abstract

Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5-HT2Areceptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms, with potential advantages over existing anti-inflammatory agents. We propose that psychedelics exert therapeutic effects for psychiatric disorders by acutely destabilizing local brain network hubs and global network connectivity via amplification of neuronal avalanches, providing the occasion for brain network “resetting” after acute effects have resolved. Anti-inflammatory effects may hold promise for efficacy in treatment of inflammation-related non-psychiatric as well as potentially for psychiatric disorders. Serotonergic psychedelics operate through unique mechanisms that show promising effects for a variety of intractable, debilitating, and lethal disorders, and should be rigorously researched.

Nichols, D. E., Johnson, M. W., & Nichols, C. D. (2016). Psychedelics as Medicines: An emerging new paradigm. Clinical Pharmacology & Therapeutics. 10.1002/cpt.557
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Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / / , , , , , ,

Abstract

Background: An increasing number of studies are reporting that ketamine could be treated as a novel antidepressant for major depressive disorder (MDD). Therefore, we performed this meta-analysis to comprehensively and systematically assess the efficacy of ketamine for treating patients with MDD.

Method: Randomized, double-blind, placebo-controlled studies on ketamine versus placebo for treating MDD were searched up to April 2016 in medical databases (PubMed, CCTR, Web of Science, Embase, CBM-disc, and CNKI). Three treatment time points (24 and 72 h, and day 7) were chosen. Response and remission rates were the main outcomes. The random effects model was used. An intention-to-treat analysis was conducted.

Results: Nine high-quality studies that included 368 patients were selected to compare the efficacy of ketamine to placebo. The therapeutic effects of ketamine at 24 and 72 h, and day 7 were found to be significantly better than placebo. Response and remission rates in the ketamine group at 24 and 72 h, and day 7 were 52.2% and 20.6%; 47.9% and 23.8%; and 39.8% and 26.2%, respectively. No significant heterogeneity existed, and the Egger’s test showed no publication bias.

Conclusion: These results indicated that ketamine could yield a good efficacy in the rapid treatment of MDD. Future large-scale clinical studies are needed to confirm our results and investigate the mid- and long-term efficacy of ketamine in treating MDD.

Han, Y., Chen, J., Zou, D., Zheng, P., Li, Q., Wang, H., … & Xie, P. (2016). Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies. Neuropsychiatric Disease and Treatment, 12, 2859. 10.2147%2FNDT.S117146

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Rehabilitating LSD history in postwar America: Dilworth Wayne Woolley and the serotonin hypothesis of mental illness

/ LSD, Papers, Psychology, Publications / /

Abstract

Revisiting the history of postwar LSD (lysergic acid diethylamide) research illuminates how the work of a chemist at the Rockefeller Institute contributed to the development of a biochemical paradigm for mental functioning. Dilworth Wayne Woolley proposed one of the first theories of the biochemistry of mental illness based on empirical evidence. His research with LSD and serotonin had wide-ranging repercussions for pharmacology and fit neatly into the emerging medicalization of mental illness. Reevaluating Woolley’s ideas and the fruits of psychopharmacology leads to possible new approaches toward mental health and illness when considered alongside lessons learned from past research with psychedelic substances, and exemplifies a broader paradigm shift in cultural studies toward a biopsychosocial model that acknowledges the intersections between biology and culture.

Hewitt, K. (2016). Rehabilitating LSD history in postwar America: Dilworth Wayne Woolley and the serotonin hypothesis of mental illness. History of Science, 0073275316674724.
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Ketamine: NMDA Receptors and Beyond

/ Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Psychotic Disorders / / , ,

Abstract

Human studies examining the effects of the dissociative anesthetic ketamine as a model for psychosis and as a rapidly acting antidepressant have spurred great interest in understanding ketamine’s actions at molecular, cellular, and network levels. Although ketamine has unequivocal uncompetitive inhibitory effects on N-methyl-d-aspartate receptors (NMDARs) and may preferentially alter the function of NMDARs on interneurons, recent work has questioned whether block of NMDARs is critical for its mood enhancing actions. In this viewpoint, we examine the evolving literature on ketamine supporting NMDARs as important triggers for certain psychiatric effects and the possibility that the antidepressant trigger is unrelated to NMDARs. The rapidly evolving story of ketamine offers great hope for untangling and treating the biology of both depressive and psychotic illnesses.
Zorumski, C. F., Izumi, Y., & Mennerick, S. (2016). Ketamine: NMDA receptors and beyond. Journal of Neuroscience, 36(44), 11158-11164. 10.1523/JNEUROSCI.1547-16.2016
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New Studies on Hallucinogenic Mushrooms: History, Diversity, and Applications in Psychiatry

/ Humanities & Art, Mushrooms / Psilocybin, Papers, Publications / /

Abstract

This paper is a review of the new studies or new explanations of the hallucinogenic mushrooms, regarding their diversity, history, traditions, and problems in their recreational use, new taxonomic studies, and their modern applications in medicine, all of them since the 1970s to the present.

Guzmán, G. (2015). New Studies on Hallucinogenic Mushrooms: History, Diversity, and Applications in Psychiatry. International journal of medicinal mushrooms, 17(11). 10.1615/IntJMedMushrooms.v17.i11.10
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Journal Club #22: Applying the EU Regulatory Framework to Determine the Benefit–Risk Profile of Psychedelics - March 3

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