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Psychiatry & Medicine

d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders.

August 31, 2018 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , , ,

Abstract

Depression and anxiety are psychiatric diagnoses commonly associated with low quality of life and low percentage of responsiveness by patients treated with currently available drugs. Thus, research into alternative compounds to treat these disorders is essential to guarantee a patient’s remission. The last decade has witnessed a revamped interest for the application of psychedelic medicine for the treatment of mental disorders due to anecdotal reports and clinical studies which show that low doses of d-lysergic acid diethylamide (LSD) and psilocybin may have antidepressant effects. LSD and psilocybin have demonstrated mood-modulating properties likely due to their capacity to modulate serotonergic (5-HT), dopaminergic (DA) and glutamatergic systems. LSD, belonging to the category of “classic halluginogens,” interacts with the 5-HT system through 5HT1A, and 5HT2A receptors, with the DA system through D2 receptors, and indirectly also the glutamatergic neurotransmission thought the recruitment of N-methyl-d-aspartate (NMDA) receptors. Randomized clinical studies have confirmed its antidepressant and anxiolytic effects in humans. Thus, in this chapter, we will review the pharmacology of psychedelic drugs, report the most striking clinical evidence which substantiate the therapeutic potentials of these fascinating compounds in mood disorders, and look into the horizon of where psychedelic medicine is heading.
De, D. G., Enns, J. P., Nuñez, N. A., Posa, L., & Gobbi, G. (2018). d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders. Progress in brain research, 242, 69-96., 10.1016/bs.pbr.2018.07.008
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Therapeutic Potential Ascribed to Ayahuasca by Users in the Czech Republic

August 30, 2018 / Ayahuasca, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / By / , ,

ABSTRACT

This article focuses on the therapeutic potential ascribed to ayahuasca by users in the Czech Republic. Following an online survey, the fieldwork among users of ayahuasca was carried out from November 2015 to December 2016. The research sample consisted of 46 persons (23 women and 23 men), who took part at least once in some type of ayahuasca ritual and/or were the facilitators of the ayahuasca sessions. We held semi-structured interviews with participants in order to discover the therapeutic potential of ayahuasca. Transcribed recordings were analyzed using the Grounded Theory Method. The results suggest that the intensity of effects produced by ayahuasca is not directly proportional to its therapeutic effect. According to the informants, ayahuasca is applicable in the treatment of drug addiction. They consider it to have a broad spectrum of therapeutic potential. This therapeutic potential could be based on memory recall.
Horák, M., Hasíková, L., & Verter, N. (2018). Therapeutic Potential Ascribed to Ayahuasca by Users in the Czech Republic. Journal of psychoactive drugs, 50(5), 430-436., 10.1080/02791072.2018.1511878
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Legitimate Medicine in the Age of Consumerism

August 21, 2018 / Anthropology & Sociology, Papers, Psychiatry & Medicine, Psychology, Publications / By /

Abstract

From the opioid epidemic and medical marijuana to abortion restrictions and physician-assisted suicide, disputes over the proper uses of medicine loom large in American life. Nowhere is this conflict more apparent than in federal drug control policy, which is premised on a clear distinction between legitimate “medical” uses and illicit “abuse.” Yet the Controlled Substances Act defines neither of these foundational concepts. While it is tempting to imagine medicine’s scope is limited to treating or preventing disease – rendering nontherapeutic drug use “abuse” – in fact medical practice has always included interventions that are not aimed at healing. This trend has only accelerated as medical practice has become increasingly consumer-oriented. From Adderall to Xanax, patients now routinely seek prescriptions not to treat diagnosable illnesses, but to relieve stress, improve productivity, and otherwise enhance quality of life.

As physicians increasingly prescribe psychoactive drugs to help healthy people obtain desirable mental states, distinguishing legitimate drug use from recreational abuse becomes ever more difficult. Having failed to acknowledge this challenge, the DEA, courts, and scholars have not offered a principled way to make this distinction, rendering drug control policy increasingly incoherent. As a result, doctors face criminal prosecution without clear standards governing prescribing, potentially valuable interventions are arbitrarily barred from the market, and millions seek the benefits of drugs without professional medical guidance to mitigate their risks.

Rather than being limited to therapeutic aims, medicine is better understood as the application of a loosely-defined set of knowledge and interventions that the law entrusts to specific professionals, with accompanying duties to use these tools to benefit patients. Medical practice includes treating and preventing illnesses, but can also include enhancing social and cognitive functioning and promoting the well-being of people whose challenges do not rise to the level of disorders. Discarding a narrow conception of medicine does not require abandoning the enforcement of drug laws or the policing of doctors. But acknowledging the expansiveness of medicine’s domain does argue for clarifying the scope of physicians’ criminal liability and pursuing new strategies for harnessing drugs’ benefits while mitigating their risks.

Lamkin, M. (2018). Legitimate Medicine in the Age of Consumerism., 10.2139/ssrn.3228692
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Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress

August 13, 2018 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Psychology, Publications / By /

Abstract

Cancer is highly prevalent and one of the leading causes of global morbidity and mortality. Psychological and existential suffering is common in cancer patients, associated with poor psychiatric and medical outcomes. Promising early-phase clinical research (1960s to early 1970s) suggested a therapeutic signal for serotoninergic psychedelics (e.g. psilocybin, LSD) in treating cancer-related psychiatric distress. After several decades of quiescence, research on psychedelic-assisted therapy to treat psychiatric disorders in cancer patients has resumed within the last 2 decades in the US and Europe. This review article is based on a systematic search of clinical trials from 1960–2018 researching the therapeutic use of psychedelic treatment in patients with serious or terminal illnesses and related psychiatric illness. The search found 10 eligible clinical trials, with a total of 445 participants, with the vast majority of the patients having advanced or terminal cancer diagnoses. Six open label trials, published between 1964 and 1980 (n = 341), suggested that psychedelic therapy (mostly with LSD) may improve cancer-related depression, anxiety, and fear of death. Four RCTs trials were published between 2011 and 2016 (n = 104), mostly with psilocybin treatment (n = 92), and demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.
Ross, S. (2018). Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress. International Review of Psychiatry, 30(4), 317-330., 10.1080/09540261.2018.1482261
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Psychedelics as anti-inflammatory agents

August 13, 2018 / Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Publications / By / ,

Abstract

Serotonin (5-hydroxytryptamine, 5-HT)2A receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the medical community and populace at large. One emerging therapeutic area that holds significant promise is their use as anti-inflammatory agents. Activation of 5-HT2A receptors produces potent anti-inflammatory effects in animal models of human inflammatory disorders at sub-behavioural levels. This review discusses the role of the 5-HT2A receptor in the inflammatory response, as well as highlight studies using the 5-HT2A agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] to treat inflammation in cellular and animal models. It also examines potential mechanisms by which 5-HT2A agonists produce their therapeutic effects. Overall, psychedelics regulate inflammatory pathways via novel mechanisms, and may represent a new and exciting treatment strategy for several inflammatory disorders.

Flanagan, T. W., & Nichols, C. D. (2018). Psychedelics as anti-inflammatory agents. International Review of Psychiatry, 30(4), 363-375., 10.1080/09540261.2018.1481827

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Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition

July 30, 2018 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , ,

Abstract

Objectives

Classic psychedelics (serotonin 2A receptor agonists) and dissociative hallucinogens (NMDA receptor antagonists), though differing in pharmacology, may share neuropsychological effects. These drugs, however, have undergone limited direct comparison. This report presents data from a double-blind, placebo-controlled within-subjects study comparing the neuropsychological effects of multiple doses of the classic psychedelic psilocybin with the effects of a single high dose of the dissociative hallucinogen dextromethorphan (DXM).

Methods

Twenty hallucinogen users (11 females) completed neurocognitive assessments during five blinded drug administration sessions (10, 20, and 30 mg/70 kg psilocybin; 400 mg/70 kg DXM; and placebo) in which participants and study staff were informed that a large range of possible drug conditions may have been administered.

Results

Global cognitive impairment, assessed using the Mini-Mental State Examination during peak drug effects, was not observed with psilocybin or DXM. Orderly and dose-dependent effects of psilocybin were observed on psychomotor performance, working memory, episodic memory, associative learning, and visual perception. Effects of DXM on psychomotor performance, visual perception, and associative learning were in the range of effects of a moderate to high dose (20 to 30 mg/70 kg) of psilocybin.

Conclusions

This was the first study of the dose effects of psilocybin on a large battery of neurocognitive assessments. Evidence of delirium or global cognitive impairment was not observed with either psilocybin or DXM. Psilocybin had greater effects than DXM on working memory. DXM had greater effects than all psilocybin doses on balance, episodic memory, response inhibition, and executive control.

Barrett, F. S., Carbonaro, T. M., Hurwitz, E., Johnson, M. W., & Griffiths, R. R. (2018). Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition. Psychopharmacology, 235(10), 2915-2927., 10.1007/s00213-018-4981-x
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Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review

July 24, 2018 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , ,

Abstract

Background: Despite advances in behavioral and pharmacotherapy interventions, substance use disorders (SUDs) are frequently refractory to treatment. Glutamatergic dysregulation has received increasing attention as one common neuropathology across multiple substances of abuse. Ketamine is a potent N-methyl-D-aspartate (NMDA) glutamatergic receptor antagonist which has been found to be effective in the treatment of severe depression. Here we review the literature on the efficacy of ketamine in the treatment of SUDs.

Methods: A systematic review of the PubMed, Scopus, and ClinicalTrials.gov databases was undertaken to identify completed and ongoing human studies of the effectiveness of ketamine in the treatment of SUDs between January 1997 and January 2018.

Results and conclusion: Seven completed studies were identified. Two studies focused on alcohol use disorder, two focused on cocaine use disorder, and three focused on opioid use disorder. Both cocaine studies found improvements in craving, motivation, and decreased cocaine use rates, although studies were limited by small sample sizes, a homogeneous population and short follow-up. Studies of alcohol and opioid use disorders found improvement in abstinence rates in the ketamine group, with significant between-group effects noted for up to two years following a single infusion, although these were not placebo-controlled trials. These results suggest that ketamine may facilitate abstinence across multiple substances of abuse and warrants broader investigation in addiction treatment. We conclude with an overview of the six ongoing studies of ketamine in the treatment of alcohol, cocaine, cannabis, and opioid use disorders and discuss future directions in this emerging area of research.

Jones, J. L., Mateus, C. F., Malcolm, R. J., Brady, K. T., & Back, S. E. (2018). Efficacy of ketamine in the treatment of substance use disorders: a systematic review. Frontiers in Psychiatry, 9., 10.3389/fpsyt.2018.00277
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Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine

July 12, 2018 / Humanities & Art, MDMA, Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Psychology, Publications / By / , ,

Abstract

Better known as “ecstasy”, 3,4-methylenedioxymethamphetamine (MDMA) is a small molecule that has played a prominent role in defining the ethos of today’s teenagers and young adults, much like lysergic acid diethylamide (LSD) did in the 1960s. Though MDMA possesses structural similarities to compounds like amphetamine and mescaline, it produces subjective effects that are unlike any of the classical psychostimulants or hallucinogens and is one of the few compounds capable of reliably producing prosocial behavioral states. As a result, MDMA has captured the attention of recreational users, the media, artists, psychiatrists, and neuropharmacologists alike. Here, we detail the synthesis of MDMA as well as its pharmacology, metabolism, adverse effects, and potential use in medicine. Finally, we discuss its history and why it is perhaps the most important compound for the future of psychedelic science-having the potential to either facilitate new psychedelic research initiatives, or to usher in a second Dark Age for the field.

Dunlap, L. E., Andrews, A. M., & Olson, D. E. (2018). Dark classics in chemical neuroscience: 3, 4-Methylenedioxymethamphetamine. ACS chemical neuroscience, 9(10), 2408-2427., 10.1021/acschemneuro.8b00155
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Ketamine normalizes brain activity during emotionally valenced attentional processing in depression

July 5, 2018 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , , ,

Abstract

BACKGROUND:

An urgent need exists for faster-acting pharmacological treatments in major depressive disorder (MDD). The glutamatergic modulator ketamine has been shown to have rapid antidepressant effects, but much remains unknown about its mechanism of action. Functional MRI (fMRI) can be used to investigate how ketamine impacts brain activity during cognitive and emotional processing.

METHODS:

This double-blind, placebo-controlled, crossover study of 33 unmedicated participants with MDD and 26 healthy controls (HCs) examined how ketamine affected fMRI activation during an attentional bias dot probe task with emotional face stimuli across multiple time points. A whole brain analysis was conducted to find regions with differential activation associated with group, drug session, or dot probe task-specific factors (emotional valence and congruency of stimuli).

RESULTS:

A drug session by group interaction was observed in several brain regions, such that ketamine had opposite effects on brain activation in MDD versus HC participants. Additionally, there was a similar finding related to emotional valence (a drug session by group by emotion interaction) in a large cluster in the anterior cingulate and medial frontal cortex.

CONCLUSIONS:

The findings show a pattern of brain activity in MDD participants following ketamine infusion that is similar to activity observed in HCs after placebo. This suggests that ketamine may act as an antidepressant by normalizing brain function during emotionally valenced attentional processing.

CLINICAL TRIAL:

NCT#00088699: https://www.clinicaltrials.gov/ct2/show/NCT00088699.

Reed, J. L., Nugent, A. C., Furey, M. L., Szczepanik, J. E., Evans, J. W., & Zarate Jr, C. A. (2018). Ketamine normalizes brain activity during emotionally valenced attentional processing in depression. NeuroImage: Clinical, 20, 92-101., 10.1016/j.nicl.2018.07.006
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Cardiac arrest after ibogaine intoxication

June 12, 2018 / Iboga / Ibogaine, Papers, Psychiatry & Medicine, Publications / By / ,

Abstract

Ibogaine is a psychoactive herbal medication with alleged antiaddiction properties. We report a case of ibogaine intoxication mimicking Long-QT syndrome resulting in ventricular flutter and nearby cardiac arrest. A 61-year-old man experienced massive QT prolongation and ventricular flutter at a rate of 270 beats per minute requiring defibrillation after ingestion of a large dose of Ibogaine. The ingested dose of 65-70 mg/kg represents the highest survived ibogaine dose reported to date. As a result of the long plasma half-life of ibogaine, it took 7 days for the patient’s QT interval to normalize.

Steinberg, C., & Deyell, M. W. (2018). Cardiac arrest after ibogaine intoxication. Journal of arrhythmia, 34(4), 455-457.,  10.1002/joa3.12061

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