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This article provides an overview of the psychological and neural mechanisms of psychedelic compounds and their potential use in treating mental health and medical conditions. It discusses the therapeutic effects of psychedelics on various mental health conditions, including depression, anxiety disorders, autism, PTSD, and substance use disorders. The article explores the cellular, molecular, network, and circuit-level mechanisms through which psychedelics work, as well as the psychological and behavioral effects they produce. It also highlights the role of mystical experiences, reactivations, ayahuasca-induced personal death experiences, and environmental factors in psychedelic therapy. The article concludes by emphasizing the importance of interdisciplinary research and responsible use of psychedelics in psychiatry and mental health. The document includes references to studies and clinical trials that investigate the use of psychedelics in the treatment of mental health conditions, such as depression, anxiety, and alcohol dependence. These studies suggest that substances like ayahuasca, psilocybin, and MDMA may have positive effects on symptoms and outcomes for individuals with these conditions. However, further research is needed to fully understand the efficacy and safety of these treatments. [Extracted from the article]

Introduction: The classic psychedelic psilocybin, found in some mushroom species, has received renewed interest in clinical research, showing potential mental health benefits in preliminary trials. Naturalistic use of psilocybin outside of research settings has increased in recent years, though data on the public health impact of such use remain limited. Methods: This prospective, longitudinal study comprised six sequential automated web-based surveys that collected data from adults planning to take psilocybin outside clinical research: at time of consent, 2  weeks before, the day before, 1–3  days after, 2–4  weeks after, and 2–3  months after psilocybin use. Results: A sample of 2,833 respondents completed all baseline assessments approximately 2  weeks before psilocybin use, 1,182 completed the 2–4  week post-use survey, and 657 completed the final follow-up survey 2–3  months after psilocybin use. Participants were primarily college-educated White men residing in the United States with a prior history of psychedelic use; mean age  =  40  years. Participants primarily used dried psilocybin mushrooms (mean dose  =  3.1 grams) for “self-exploration” purposes. Prospective longitudinal data collected before and after a planned psilocybin experience on average showed persisting reductions in anxiety, depression, and alcohol misuse, increased cognitive flexibility, emotion regulation, spiritual wellbeing, and extraversion, and reduced neuroticism and burnout after psilocybin use. However, a minority of participants (11% at 2–4  weeks and 7% at 2–3  months) reported persisting negative effects after psilocybin use (e.g., mood fluctuations, depressive symptoms). Discussion: Results from this study, the largest prospective survey of naturalistic psilocybin use to date, support the potential for psilocybin to produce lasting improvements in mental health symptoms and general wellbeing. [ABSTRACT FROM AUTHOR]

Contemporary research on serotonergic psychedelic compounds has been rife with references to so-called 'mystical' subjective effects. Several psychometric assessments have been used to assess such effects, and clinical studies have found quantitative associations between 'mystical experiences' and positive mental health outcomes. The nascent study of psychedelic-induced mystical experiences, however, has only minimally intersected with relevant contemporary scholarship from disciplines within the social sciences and humanities, such as religious studies and anthropology. Viewed from the perspective of these disciplines--which feature rich historical and cultural literatures on mysticism, religion, and related topics--'mysticism' as used in psychedelic research is fraught with limitations and intrinsic biases that are seldom acknowledged. Most notably, existing operationalizations of mystical experiences in psychedelic science fail to historicize the concept and therefore fail to acknowledge its perennialist and specifically Christian bias. Here, we trace the historical genesis of the mystical in psychedelic research in order to illuminate such biases, and also offer suggestions toward more nuanced and culturally-sensitive operationalizations of this phenomenon. In addition, we argue for the value of, and outline, complementary 'non-mystical' approaches to understanding putative mystical-type phenomena that may help facilitate empirical investigation and create linkages to existing neuro-psychological constructs. It is our hope that the present paper helps build interdisciplinary bridges that motivate fruitful paths toward stronger theoretical and empirical approaches in the study of psychedelic-induced mystical experiences. [ABSTRACT FROM AUTHOR]

IntroductionThe classic psychedelic psilocybin, found in some mushroom species, has received renewed interest in clinical research, showing potential mental health benefits in preliminary trials. Naturalistic use of psilocybin outside of research settings has increased in recent years, though data on the public health impact of such use remain limited.MethodsThis prospective, longitudinal study comprised six sequential automated web-based surveys that collected data from adults planning to take psilocybin outside clinical research: at time of consent, 2 weeks before, the day before, 1–3 days after, 2–4 weeks after, and 2–3 months after psilocybin use.ResultsA sample of 2,833 respondents completed all baseline assessments approximately 2 weeks before psilocybin use, 1,182 completed the 2–4 week post-use survey, and 657 completed the final follow-up survey 2–3 months after psilocybin use. Participants were primarily college-educated White men residing in the United States with a prior history of psychedelic use; mean age = 40 years. Participants primarily used dried psilocybin mushrooms (mean dose = 3.1 grams) for “self-exploration” purposes. Prospective longitudinal data collected before and after a planned psilocybin experience on average showed persisting reductions in anxiety, depression, and alcohol misuse, increased cognitive flexibility, emotion regulation, spiritual wellbeing, and extraversion, and reduced neuroticism and burnout after psilocybin use. However, a minority of participants (11% at 2–4 weeks and 7% at 2–3 months) reported persisting negative effects after psilocybin use (e.g., mood fluctuations, depressive symptoms).DiscussionResults from this study, the largest prospective survey of naturalistic psilocybin use to date, support the potential for psilocybin to produce lasting improvements in mental health symptoms and general wellbeing.

Contemporary research on serotonergic psychedelic compounds has been rife with references to so-called ‘mystical’ subjective effects. Several psychometric assessments have been used to assess such effects, and clinical studies have found quantitative associations between ‘mystical experiences’ and positive mental health outcomes. The nascent study of psychedelic-induced mystical experiences, however, has only minimally intersected with relevant contemporary scholarship from disciplines within the social sciences and humanities, such as religious studies and anthropology. Viewed from the perspective of these disciplines—which feature rich historical and cultural literatures on mysticism, religion, and related topics—‘mysticism’ as used in psychedelic research is fraught with limitations and intrinsic biases that are seldom acknowledged. Most notably, existing operationalizations of mystical experiences in psychedelic science fail to historicize the concept and therefore fail to acknowledge its perennialist and specifically Christian bias. Here, we trace the historical genesis of the mystical in psychedelic research in order to illuminate such biases, and also offer suggestions toward more nuanced and culturally-sensitive operationalizations of this phenomenon. In addition, we argue for the value of, and outline, complementary ‘non-mystical’ approaches to understanding putative mystical-type phenomena that may help facilitate empirical investigation and create linkages to existing neuro-psychological constructs. It is our hope that the present paper helps build interdisciplinary bridges that motivate fruitful paths toward stronger theoretical and empirical approaches in the study of psychedelic-induced mystical experiences.

Lysergic acid diethylamide (LSD) and similar psychoactive drugs have been used in psychotherapy since 1949, when the first clinical study with lowerdose LSD showed therapeutically relevant effects. This caused an intense interest among psychotherapists and researchers, alike, on an international scale. In 1960, the use of serial lower-dose LSD/psilocybin sessions in a psychoanalytical framework, which was dominant at the time, was named "psycholytic therapy". Psycholytic therapy was usually conducted in clinical environments, on both an inpatient and outpatient basis. Psycholytic therapy was developed and established over a 15-year period on the European continent, where it was used at 30 clinical treatment centers and by more than 100 outpatient psychotherapists. Psycholytic approaches were employed minimally in North America, where the psychedelic approach (use of one or two high-dose sessions for "personality-transforming mystical experiences") became the dominant method in use. The leading figure in psycholytic therapy was Professor Hanscarl Leuner in Germany, who laid the ground with his uniquely fine grained analysis of the LSD reaction in a 1962 monograph. He was central in establishing and distributing psycholytic therapy in Europe and abroad. The article provides comprehensive background information and outlines the essential features of psycholytic therapy. Evidence for the efficacy of psycholytic therapy is reviewed and a case for the inclusion of the psycholytic approach in the field of substance-assisted psychotherapy is made. [ABSTRACT FROM AUTHOR]

Lysergic acid diethylamide (LSD) and similar psychoactive drugs have been used in psychotherapy since 1949, when the first clinical study with lower-dose LSD showed therapeutically relevant effects. This caused an intense interest among psychotherapists and researchers, alike, on an international scale. In 1960, the use of serial lower-dose LSD/psilocybin sessions in a psychoanalytical framework, which was dominant at the time, was named “psycholytic therapy”. Psycholytic therapy was usually conducted in clinical environments, on both an inpatient and outpatient basis. Psycholytic therapy was developed and established over a 15-year period on the European continent, where it was used at 30 clinical treatment centers and by more than 100 outpatient psychotherapists. Psycholytic approaches were employed minimally in North America, where the psychedelic approach (use of one or two high-dose sessions for “personality-transforming mystical experiences”) became the dominant method in use. The leading figure in psycholytic therapy was Professor Hanscarl Leuner in Germany, who laid the ground with his uniquely fine grained analysis of the LSD reaction in a 1962 monograph. He was central in establishing and distributing psycholytic therapy in Europe and abroad. The article provides comprehensive background information and outlines the essential features of psycholytic therapy. Evidence for the efficacy of psycholytic therapy is reviewed and a case for the inclusion of the psycholytic approach in the field of substance-assisted psychotherapy is made.

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. [ABSTRACT FROM AUTHOR]

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.