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      Adverse effects of psychedelics: From anecdotes and misinformation to systematic science

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          Abstract

          Background:

          Despite an increasing body of research highlighting their efficacy to treat a broad range of medical conditions, psychedelic drugs remain a controversial issue among the public and politicians, tainted by previous stigmatisation and perceptions of risk and danger.

          Objective:

          This narrative review examines the evidence for potential harms of the classic psychedelics by separating anecdotes and misinformation from systematic research.

          Methods:

          Taking a high-level perspective, we address both psychological and psychiatric risks, such as abuse liability and potential for dependence, as well as medical harms, including toxicity and overdose. We explore the evidence base for these adverse effects to elucidate which of these harms are based largely on anecdotes versus those that stand up to current scientific scrutiny.

          Results:

          Our review shows that medical risks are often minimal, and that many – albeit not all – of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a regulated and/or medical context.

          Conclusions:

          This highlights the importance for clinicians and therapists to keep to the highest safety and ethical standards. It is imperative not to be overzealous and to ensure balanced media reporting to avoid future controversies, so that much needed research can continue.

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          Most cited references162

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          Diagnostic and Statistical Manual of Mental Disorders

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            Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.

            Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions. The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer's attitudes and behavior. Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.
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              Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.

              Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.
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                Author and article information

                Journal
                J Psychopharmacol
                J Psychopharmacol
                JOP
                spjop
                Journal of Psychopharmacology (Oxford, England)
                SAGE Publications (Sage UK: London, England )
                0269-8811
                1461-7285
                2 February 2022
                March 2022
                : 36
                : 3
                : 258-272
                Affiliations
                [1 ]Drug Science, London, UK
                [2 ]Department of Brain Sciences, Imperial College London, London, UK
                [3 ]Department of Geography, King’s College London, London, UK
                [4 ]Department of Psychology, Central Michigan University, Mount Pleasant, MI, USA
                [5 ]Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA, USA
                [6 ]Division of Pharmacy and Optometry, School of Health Sciences, The University of Manchester, Manchester, UK
                Author notes
                [*]David J Nutt, Department of Brain Sciences, Imperial College London, Burlington Danes Building, The Hammersmith Hospital, London W12 0NN, UK. Email: D.Nutt@ 123456imperial.ac.uk
                Author information
                https://orcid.org/0000-0003-2074-1917
                https://orcid.org/0000-0003-0578-8530
                https://orcid.org/0000-0002-2717-9739
                Article
                10.1177_02698811211069100
                10.1177/02698811211069100
                8905125
                35107059
                13ddfc57-1251-4b8a-927d-fa1a03aee2d5
                © The Author(s) 2022

                This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

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                Pharmacology & Pharmaceutical medicine
                psilocybin,dimethyltryptamine,ayahuasca,mescaline,d-lysergic acid diethylamide,abuse liability/dependence,hallucinogen persistent perception disorder,toxicity,hypertension

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