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      Ethical and Practical Considerations for the Use of Psychedelics in Psychiatry

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      Psychiatric Services
      American Psychiatric Association Publishing

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          Abstract

          In recent years, psychedelic-assisted psychotherapies have reentered the realm of rigorous scientific inquiry, garnering much attention from both the psychiatric community and the broader public. Headlines on major media platforms frequently tout the psychedelic future of psychiatry, and patients increasingly ask about the prospect of using psychedelics during their sessions. Despite this enthusiasm, psychedelics remain in an investigational stage, and more research and regulatory work are required before psychedelics can be deemed appropriate for general clinical use. In this climate, psychiatrists are increasingly curious about the prospects of psychedelic treatments. This review's goal was to help psychiatrists better understand the complexities of the burgeoning field of psychedelic-assisted psychotherapy. The discussion encompasses issues surrounding psychedelics in their current investigational stage and issues for psychiatrists to consider should psychedelics become available for broad clinical use. This review discusses research equipoise in the context of the current enthusiasm for psychedelics, informed consent, patient vulnerability, equity and access, differences between clinical and nonclinical psychedelic uses, and psychedelic self-enhancement. As psychedelics move closer toward regulatory approval beyond research settings, it is vital that these promising treatments be used ethically. The unique features of psychedelic therapies, including the altered states of consciousness they produce and the vulnerability that such states entail for patients, require careful consideration to minimize potential ethical pitfalls. This review seeks to ensure that psychiatrists are equipped to use psychedelic psychotherapy both ethically and effectively.

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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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            Trial of Psilocybin versus Escitalopram for Depression

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              Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder : A Randomized Clinical Trial

              This randomized clinical trial examines the efficacy of psilocybin as an adjunct to psychotherapy and other treatments for major depressive disorder. Question Is psilocybin-assisted therapy efficacious among patients with major depressive disorder? Findings In this randomized clinical trial of 24 participants with major depressive disorder, participants who received immediate psilocybin-assisted therapy compared with delayed treatment showed improvement in blinded clinician rater–assessed depression severity and in self-reported secondary outcomes through the 1-month follow-up. Meaning This randomized clinical trial found that psilocybin-assisted therapy was efficacious in producing large, rapid, and sustained antidepressant effects in patients with major depressive disorder. Importance Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression. Objective To investigate the effect of psilocybin therapy in patients with MDD. Design, Setting, and Participants This randomized, waiting list–controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population). Interventions Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay. Main Outcomes and Measures The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR). Results Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d  = 2.5; 95% CI, 1.4-3.5; P  < .001) and week 8 (Cohen d  = 2.6; 95% CI, 1.5-3.7; P  < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d  = 2.6; 95% CI, 1.8-3.5; P  < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d  = 2.3; 95% CI, 1.5-3.0; P  < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score). Conclusions and Relevance Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression. Trial Registration ClinicalTrials.gov Identifier: NCT03181529
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                Author and article information

                Journal
                Psychiatric Services
                PS
                American Psychiatric Association Publishing
                1075-2730
                1557-9700
                August 01 2023
                August 01 2023
                : 74
                : 8
                : 838-846
                Affiliations
                [1 ]Private practice, Bethesda (Barber); Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut (Dike).
                Article
                10.1176/appi.ps.20220525
                36987705
                19a041dc-4dd2-4828-9996-fcff914676b0
                © 2023
                History

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