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The mystical experience is a potential psychological mechanism to influence outcome in psychedelic therapy. It includes features such as oceanic boundlessness, ego dissolution, and universal interconnectedness, which have been closely linked to both symptom reduction and improved quality of life. In this review, 12 studies of psychedelic therapy utilizing psilocybin, ayahuasca, or ketamine were analyzed for association between mystical experience and symptom reduction, in areas as diverse as cancer-related distress, substance use disorder, and depressive disorders to include treatment-resistant. Ten of the twelve established a significant association of correlation, mediation, and/or prediction. A majority of the studies are limited, however, by their small sample size and lack of diversity (gender, ethnic, racial, educational, and socioeconomic), common in this newly re-emerging field. Further, 6 out of 12 studies were open-label in design and therefore susceptible to bias. Future studies of this nature should consider a larger sample size with greater diversity and thus representation by use of randomized design. More in-depth exploration into the nature of mystical experience is needed, including predictors of intensity, in order to maximize its positive effects on treatment outcome benefits and minimize concomitant anxiety.Systematic Review Registration: PROSPERO, identifier CRD42021261752.

Introduction: In this paper, we systematically review literature from 1940 to 2000 relating to the combined use of psychological therapies and psychedelic drugs in the treatment of ICD-10 anxiety disorders. Methods: The databases Ovid MEDLINE(R), PsycINFO, and Multidisciplinary Association for Psychedelic Studies (MAPS) were searched for case reports and trials involving humans in the treatment of ICD-10 anxiety and related disorders. Twentyfour studies are described; four describe anxiety symptoms in diverse patient groups, 14 studies describe historic diagnoses that usefully correspond with ICD-10 anxiety disorders, six studies pooled results or failed to detail results specific to contemporary ICD-10 anxiety disorders. Two of the 24 studies reported are individual case reports while two of them were inadequate in terms of the reporting of outcome measures. Thus 20 studies were ultimately included in the summary analysis. Results: Three of the 20 studies reviewed described improvements in anxiety by standardized measures (p < .05) and two studies found that this effect was dose related. Of the 20 studies included in the final analysis, 94 of 145 (65%) cases of "psychoneurotic anxiety reaction" as defined by Diagnostic and Statistical Manual of Mental Disorders-I showed improvement that ranged from moderate improvement to full recovery. Despite methodological inadequacies, the results from previous studies are encouraging and should be used to guide and inform further investigation. Conclusion: The majority of studies indicate that a combination of psychedelic drug administration and psychological therapy was most beneficial. We found no study suggesting that the pharmacological action of psychedelic drugs in isolation is sufficient.

IntroductionPsilocybin-assisted therapy may be a new treatment for major depressive disorder (MDD), with encouraging data from pilot trials. In this trial (short name: PsiDeR) we aimed to test the feasibility of a parallel-group, randomised, placebo-controlled design. The primary outcomes in this trial are measures of feasibility: recruitment rates, dropout rates and the variance of the primary outcome measure of depression.Methods and analysisWe are recruiting up to 60 participants at a single centre in London, UK who are unresponsive to, or intolerant of, at least two evidence-based treatments for MDD. Participants are randomised to receive a single dosing session of 25 mg psilocybin or a placebo. All participants receive a package of psychological therapy. The primary outcome measure for depression is the Montgomery Asberg Depression Rating Scale collected by blinded, independent raters. The primary endpoint is at 3 weeks, and the total follow-up is 6 weeks. With further informed consent, this study collects neuroimaging and omics data for mechanism and biomarker analyses and offers participants an open label extension consisting of a further, open label dose of 25 mg of psilocybin.Ethics and disseminationAll participants will be required to provide written informed consent. The trial has been authorised by the National Research Ethics Committee (20-LO/0206), Health Research Authority (252750) and Medicine’s and Healthcare Products Regulatory Agency (CTA 14523/0284/001-0001) in the UK. Dissemination of results will occur via a peer-reviewed publication and other relevant media.Trial registration numbersEUDRACT2018-003573-97; NCT04959253.