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Mushrooms / Psilocybin

Return of the psychedelics: Psilocybin for treatment resistant depression

Abstract

Psilocybin, the clinically most researched classic psychedelic has recently been tested for its safety and efficacy in a clinical population of treatment resistant depression. The efficacy of psilocybin in clinical depression previously demonstrated in the elecrophysiologic and neuroimaging findings as also in neuropsychological assessments is further validated by the findings of this rigorously conducted randomized trial. Mechanism of action of psilocybin and efficacy in treatment resistant depression are discussed in this paper. Ethical issues of conducting clinical trials with psychedelics are also discussed with particular emphasis on their relative safety and absence of addiction potential. Implications of these issues for conduct of larger trials for establishing risk benefit ratio in treatment resistant depression are further suggested.

Patra, S. (2016). Return of the psychedelics: Psilocybin for treatment resistant depression. Asian Journal of Psychiatry, 24, 51-52. http://dx.doi.org/10.1016/j.ajp.2016.08.010
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Psilocybin for treating substance use disorders?

Abstract

INTRODUCTION: Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human) studies on the putative therapeutic effects of psilocybin, and discusses the receptor systems, brain regions and cognitive and emotional processes mediating psilocybin’s effects. Psilocybin’s chemical structure is similar to that of serotonin. Dysregulations in the serotonin system are associated with alterations in stress hormones, such as cortisol, and mood disorders. After psilocybin administration cortisol levels spike and activate the executive control network, with subsequent increased control over emotional processes, and relief of negative thinking and persistent negative emotions. Preliminary data of ongoing alcohol and smoking addiction studies in humans shows promising effects of psilocybin administration on substance use. Importantly, psilocybin has a low risk of toxicity and dependence and can be used safely under controlled clinical conditions.

AREAS COVERED: This paper is a narrative review based on the search terms: psilocybin, substance use disorder, addiction, depression, serotonin. Literature on potential efficacy and mechanisms of action of psilocybin in SUD is discussed. Expert commentary: Recent positive findings with psilocybin need confirmation in well-designed placebo controlled randomized trials employing a large sample size.

de Veen, B. T., Schellekens, A. F., Verheij, M. M., & Homberg, J. R. (2016). Psilocybin for treating substance use disorders?. Expert Review of Neurotherapeutics, 1-10. 10.1080/14737175.2016.1220834
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The Associations of Naturalistic Classic Psychedelic Use, Mystical Experience, and Creative Problem Solving

Abstract

Developing methods for improving creativity is of broad interest. Classic psychedelics may enhance creativity; however, the underlying mechanisms of action are unknown. This study was designed to assess whether a relationship exists between naturalistic classic psychedelic use and heightened creative problem-solving ability and if so, whether this is mediated by lifetime mystical experience. Participants (N = 68) completed a survey battery assessing lifetime mystical experience and circumstances surrounding the most memorable experience. They were then administered a functional fixedness task in which faster completion times indicate greater creative problem-solving ability. Participants reporting classic psychedelic use concurrent with mystical experience (n = 11) exhibited significantly faster times on the functional fixedness task (Cohen’s d = –.87; large effect) and significantly greater lifetime mystical experience (Cohen’s d = .93; large effect) than participants not reporting classic psychedelic use concurrent with mystical experience. However, lifetime mystical experience was unrelated to completion times on the functional fixedness task (standardized β = –.06), and was therefore not a significant mediator. Classic psychedelic use may increase creativity independent of its effects on mystical experience. Maximizing the likelihood of mystical experience may need not be a goal of psychedelic interventions designed to boost creativity.

Sweat, N. W., Bates, L. W., & Hendricks, P. S. (2016). The Associations of Naturalistic Classic Psychedelic Use, Mystical Experience, and Creative Problem Solving. Journal of Psychoactive Drugs, 1-7. 10.1080/02791072.2016.1234090
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Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics

Abstract

Despite reports of apparent benefits, social and political pressure beginning in the late 1960s effectively banned scientific inquiry into psychedelic substances. Covert examination of psychedelics persisted through the 1990s; the turn of the century and especially the past 10 years, however, has seen a resurgent interest in psychedelic substances (eg, LSD, ayahuasca, psilocybin). This chapter outlines relevant EEG and brain imaging studies evaluating the effects of psychedelics on the brain. This chapter also reviews evidence of the use of psychedelics as adjunct therapy for a number of psychiatric and addictive disorders. In particular, psychedelics appear to have efficacy in treating depression and alcohol-use disorders.

Tófoli, L. F., & de Araujo, D. B. (2016). Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics. International Review of Neurobiology. 10.1016/bs.irn.2016.06.005
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Long-term follow up of psilocybin-assisted smoking cessation

Abstract

Background: A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. Objectives: To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration.
Methods: The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin.
Results: All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16–57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives.
Conclusion: These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

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Clinical Applications of Hallucinogens: A Review

Abstract

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

Garcia-Romeu, A., Kersgaard, B., & Addy, P. H. (2016). Clinical applications of hallucinogens: A review. Experimental and clinical psychopharmacology, 24(4), 229. 10.1037/pha0000084
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Magic mushroom compound is a potential treatment for patients with major depression

Abstract

A hallucinogenic compound derived from magic mushrooms could provide a new route for antidepressant research.

Carhart-Harris, R. L. Magic mushroom compound is a potential treatment for patients with major depression. http://dx.doi.org/10.7748/ns.30.41.15.s18
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Psilocybine-ondersteunde therapie toont veelbelovende resultaten voor behandelingsresistente depressie

psilocybin depression 2Het onderzoeksteam van het Imperial College in London heeft het potentieel van psilocybine-ondersteunde therapie om behandelingsresistente depressie te verlichten in een nieuw onderzoek getest. Uit statistieken blijkt dat 20% van mensen met zware depressieklachten niet reageren op conventionele behandelwijzen zoals SSRI-medicatie of cognitieve gedragstherapie (Carhart-Harris et al., 2016).

Twaalf deelnemers (zes mannen en zes vrouwen), allen gediagnosticeerd met zware depressie, deden mee aan de studie. Ze kregen twee orale doses psilocybine – 10 mg en 25 mg – waarbij de eerste de veiligheidsdosis was en de tweede, die zeven dagen later werd toegediend, de behandeldosis. De deelnemers werden geselecteerd uit 70 kandidaten; een van de belangrijkste selectiecriteria was de afwezigheid van psychotische voorvallen bij de kandidaten zelf, en bij hun naaste familieleden.

Alle participanten, in de leeftijd 30 tot 60, hadden een lange geschiedenis van depressie, en behandelpogingen hadden steeds slechts minimale effecten. Sommigen van hen leden al ongeveer 30 jaar aan middelzware tot zware depressie. Voorgaande behandelpogingen bestonden zowel uit chemische als psychologische middelen: medicatie zoals serotonine of dopamine heropname-inhibitoren (SSRI, NDRI, SNRI, etc.) en therapieën als cognitieve gedrags-, groeps-, en gesprekstherapie.

De farmacologie van psilocybine verschilt van die van selectieve serotonine heropname-inhibitoren (SSRI’s), de meest gebruikte medicatie voor dit type depressie. SSRI’s voorkomen dat de reeds afgegeven serotonine – een van de neurotransmitters die betrokken zijn in emotieregulatie – weer wordt opgenomen door dezelfde neuronen die het produceerden, zodat het kan worden opgenomen door serotoninereceptoren. Anders dan SSRI’s lijkt psilocybine structureel gezien op serotonine, waardoor het hetzelfde effect heeft als een algehele stijging van het serotonineniveau.

Gedurende het onderzoek werd psychologische steun gegeven voor, tijdens en na de psilocybinesessies. Tijdens de sessies was er minimale bemoeienis met de ervaringen van de patiënten. Hen werden enkel vragen gesteld die noodzakelijk waren om de effecten van de psilocybine op hun fysieke en mentale welzijn te kunnen evalueren. De meest voorkomende bijwerkingen waren misselijkheid, hoofdpijn, angst en verwarring, en deze waren alle van voorbijgaande aard. Slechts één patiënt had last van tijdelijke paranoia, die na een uur wegtrok.

Het onderzoek liet zien dat de depressiesymptomen bij alle 12 de deelnemers enigszins waren afgenomen. De scores op het Quick Inventory of Depressive Symptoms (QIDS) gaven aan dat het depressieniveau was gedaald van 16-20 (zware depressie) naar 6-10 (milde depressie). Vijf vervolgbeoordelingen vonden plaats tussen een week en drie maanden na de behandeling. De maximale positieve resultaten werden twee weken na de behandeling gehaald. Acht deelnemers ervoeren een week na de behandeling een complete remissie van hun depressie en bij zeven van hen bleef een significante afname van depressie na drie maanden aanhouden. Één patiënt beleefde een toename in depressieve klachten gedurende de drie maanden na de behandeling.

Dit onderzoek was het eerste dat de werkzaamheid van psilocybine bij de behandeling van zware depressie verkende, en toonde het potentieel van psilocybine aan voor het doen afnemen van zware, behandelingsresistente depressie en de veiligheid van de stof bij toediening onder de juiste omstandigheden. Voorgaand onderzoek met psilocybine-ondersteunde therapie had reeds aangetoond dat het angst bij terminale kanker kan verlichten (Grob C.S. et al., 2011).

Nader onderzoek onder striktere condities (placebo-gecontroleerd en op grotere schaal) is nodig om het potentieel van psilocybine voor de behandeling van zware depressie te bevestigen. Als deze belofte kan worden waargemaakt, dan zou dat voor miljoenen mensen die worstelen met zware depressie een nieuwe kans kunnen betekenen.

Verwijzingen:

Carhart-Harris R.L., Bolstridge M., Rucker J., Day C.M.J., Erritzoe D., Kaelen M., Bloomfield M., Rickard J.A., Forbes B., Fielding A., Taylor D., Pilling S., Curran V.H., Nutt D.J. (2016) Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. http://dx.doi.org/10.1016/S2215-0366(16)30065-7

Grob C.S., Danforth A.L., Chopra G.S., Hagerty M., McKay C.R., Halberstadt A.L. and Greer G.R. (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry, 68, pp. 71–78 http://dx.doi.org/10.1001/archgenpsychiatry.2010.116

Psilocybin-assisted therapy shows promising results for treatment-resistant depression

psilocybin depression 2In a new study, the research team at the Imperial College London has tested the potential of psilocybin-assisted therapy to alleviate treatment-resistant depression. Statistics show that 20% of people suffering from major depression are unresponsive to conventional treatments like SSRI medication or cognitive behavioural therapy (Carhart-Harris et al., 2016).

Twelve subjects (six men and six women), all diagnosed with major depression, participated in the study. They received two oral doses of psilocybin – 10 mg and 25 mg – the former being the safety dose and the latter, administered seven days later, the treatment dose. The participants had been selected among 70 candidates; one of the main selection criteria was the absence of psychotic episodes in subjects themselves and in their immediate family members.

All participants, aged between 30 and 60, had a long history of major depression, with treatment attempts having had only minimal effects. Some of them had been suffering moderate to severe depression for about three decades. Previous treatment attempts included both chemical and psychological means: medication like serotonin or dopamine reuptake inhibitors (SSRI, NDRI, SNRI, etc.) and therapies like cognitive behavioural, group and counselling therapy.

The pharmacology of psilocybin is different from that of selective serotonin reuptake inhibitors (SSRIs), the most common medication for this kind of depression. SSRIs prevent the already released serotonin – one of the neurotransmitters involved in the regulation of emotion – from being taken back up by the same neurons that produced it, so that it can be taken up by serotonin receptors. Unlike SSRIs, psilocybin (converted in the body to psilocin) is structurally similar to serotonin, and causes the same effect as an overall increase in serotonin levels.

Over the course of the study, psychological support was provided before, during and after the psilocybin sessions. During the sessions, there was minimal intrusion into the patients´ experience. The patients were only asked the necessary questions to evaluate the effects of psilocybin on their physical and mental well-being. The most common adverse reactions reported included nausea, headaches, anxiety and confusion, all of which were transient. Only one patient reported transient paranoia that subsided after one hour.

The study demonstrated that the symptoms of depression were somewhat reduced in all of the twelve participants. The scores on the Quick Inventory of Depressive Symptoms (QIDS) showed that the depression level was reduced from 16-20 (severe depression) to 6-10 (mild depression). Five follow-up assessments took place between one week and three months after the treatment. The maximum positive effects were reached two weeks after the treatment. Eight subjects experienced complete remission in their depression one week after the treatment and in seven of them significant reduction in depression persisted after three months. One patient experienced an increase in depressive symptoms during the three months following the treatment.

This study was the first to explore the efficacy of psilocybin in treating major depression, and demonstrated the potential of psilocybin for reducing the symptoms of major treatment-resistant depression and the safety of the substance when administered under proper conditions. Previous research with psilocybin-assisted therapy has already showed that it can alleviate anxiety related to end-stage cancer (Grob C.S. et al., 2011).

Further research in more rigorous conditions (placebo-controlled and on a larger scale) is needed to confirm the potential of psilocybin in treating major depression. If this promise can be fulfilled, it could mean a new chance for millions of people struggling with severe depression.

References:

Carhart-Harris R.L., Bolstridge M., Rucker J., Day C.M.J., Erritzoe D., Kaelen M., Bloomfield M., Rickard J.A., Forbes B., Fielding A., Taylor D., Pilling S., Curran V.H., Nutt D.J. (2016) Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. http://dx.doi.org/10.1016/S2215-0366(16)30065-7

Grob C.S., Danforth A.L., Chopra G.S., Hagerty M., McKay C.R., Halberstadt A.L. and Greer G.R. (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry, 68, pp. 71–78 http://dx.doi.org/10.1001/archgenpsychiatry.2010.116

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