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Objective: Psilocybin-assisted therapy has shown promising efficacy on clinical depressive symptoms. However, diverse psychological support or psychotherapy was performed with psilocybin treatment. This study aimed to explore the association of psychological protocols with the efficacy of psilocybin-assisted therapy for depressive symptoms. Method: Five major databases were systemic searched for clinical trials addressing psilocybin-assisted therapy for patients with clinical depressive symptoms. A Bayesian random-effects meta-analysis and meta-regression were performed. The effect size was mean difference (with 95% credible interval) measured by 17-Item Hamilton Depression Rating Scale. Results: There were 10 eligible studies including 515 adult patients with clinically diagnosed depression. The psychological protocols could be categorized into four types: (i) manualized directive psychotherapy(k=1); (ii) manualized nondirective psychological support (k=3), (iii) non-manualized nondirective psychological support (k=5); and (iv) non-manualized supportive psychotherapy (k=1). The pooled standard mean difference of psilocybin-assisted therapy was 10.08 (5.03-14.70). Conclusion: Compared with manualized nondirective psychological support, the other three psychological approaches did not differ significantly. The improvement of depressive symptoms was not associated with the psychological protocols in adult patients receiving psilocybin-assisted therapy [ABSTRACT FROM AUTHOR]

Background: Chronic pain is a leading cause of disability worldwide. Fibromyalgia is a particularly debilitating form of widespread chronic pain. Fibromyalgia remains poorly understood, and treatment options are limited or moderately effective at best. Here, we present a protocol for a mechanistic study investigating the effects of psychedelic-assisted-therapy in a fibromyalgia population. The principal focus of this trial is the central mechanism(s) of psilocybin-therapy i.e., in the brain and on associated mental schemata, primarily captured by electroencephalography (EEG) recordings of the acute psychedelic state, plus pre and post Magnetic Resonance Imaging (MRI). Methods: Twenty participants with fibromyalgia will complete 8 study visits over 8 weeks. This will include two dosing sessions where participants will receive psilocybin at least once, with doses varying up to 25mg. Our primary outcomes are 1) Lempel-Ziv complexity (LZc) recorded acutely using EEG, and the 2) the (Brief Experiential Avoidance Questionnaire (BEAQ) measured at baseline and primary endpoint. Secondary outcomes will aim to capture broad aspects of the pain experience and related features through neuroimaging, self-report measures, behavioural paradigms, and qualitative interviews. Pain Symptomatology will be measured using the Brief Pain Inventory Interference Subscale (BPI-IS), physical and mental health-related function will be measured using the 36-Item Short Form Health Survey (SF-36). Further neurobiological investigations will include functional MRI (fMRI) and diffusion tensor imaging (changes from baseline to primary endpoint), and acute changes in pre- vs post-acute spontaneous brain activity – plus event-related potential functional plasticity markers, captured via EEG. Discussion: The results of this study will provide valuable insight into the brain mechanisms involved in the action of psilocybin-therapy for fibromyalgia with potential implications for the therapeutic action of psychedelic-therapy more broadly. It will also deliver essential data to inform the design of a potential subsequent RCT. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a major source of morbidity and mortality worldwide, particularly for racial and ethnic minorities who face higher rates of hypertension and worse health-related outcomes. Recent research has reported on protective associations between classic psychedelics and hypertension; however, there is a need to explore how race and ethnicity may moderate such associations. Methods: We used data from the National Survey on Drug Use and Health (2005-2014) to assess whether race and ethnicity moderate the associations between classic psychedelic use - specifically psilocybin - and past year hypertension. Results: Hispanic identity moderated the associations between psilocybin use and past year hypertension. Furthermore, individuals who used psilocybin and identified as Non-Hispanic White had reduced odds of hypertension (aOR: 0.83); however, these associations were not observed for any other racial or ethnic groups in our study for individuals who used psilocybin. Conclusion: Overall, our results demonstrate that the associations between psychedelics and hypertension may vary by race and ethnicity. Longitudinal studies and clinical trials can further advance this research and determine whether such differences exist in causal contexts. [ABSTRACT FROM AUTHOR]

Resistance to traditional treatment methods is still a major obstacle in modern psychiatry. As a result, several studies are currently being conducted to find effective alternatives to traditional therapies. One of these alternatives is psilocybin, a psychedelic substance that has been tested in clinical trials as an adjunct to psychotherapy. These studies focus on patients with major depressive disorder (MDD), obsessive-compulsive disorder (OCD) and substance use disorder (SUD), particularly alcohol and nicotine dependence. This article looks at the current understanding of psilocybin, including data from clinical trials conducted, psilocybin's mechanism of action, its safety and the level of risk associated with it. [ABSTRACT FROM AUTHOR]

Introduction and aim: It is important to understand how mental health practitioners view recent findings on psychedelic-assisted psychotherapy (PAP) as there is potential this treatment may be incorporated into clinical practice. The aim of our study was to explore how psychiatrists who are not involved in psychedelic research and who are located in the European region perceive psychedelics and PAP. Methods: We conducted online semi-structured interviews with 12 psychiatry specialists and psychiatry trainees from8 European countries. Data were analyzed using a general inductive approach informed by codebook thematic analysis. Results: Based on the interviews, we developed four main themes and 14 subthemes, including (1) Psychedelics hold potential, (2) Psychedelics are dangerous, (3) Future of psychedelics is uncertain, and (4) Psychiatry is ambivalent toward psychedelics. Discussion: Our respondents-psychiatrists acknowledged the potential of PAP but remained cautious and did not yet perceive its evidence base as robust enough. Education on psychedelics is lacking in medical and psychiatric training and should be improved to facilitate the involvement of mental health experts in decision-making on PAP. [ABSTRACT FROM AUTHOR]

Intense interest surrounds current research on psychedelics, particularly regarding their potential in treating mental health disorders. Various studies suggest a link between the subjective effects produced by psychedelics and their therapeutic efficacy. Neuroimaging evidence indicates an association of changes in brain functional connectivity with the subjective effects of psychedelics. We conducted a review focusing on psychedelics and brain functional connectivity. The review focused on four psychedelic drugs: ayahuasca, psilocybin and LSD, and the entactogen MDMA. We conducted searches in databases of MEDLINE, Embase, APA PsycInfo and Scopus from inception to Jun 2023 by keywords related to functional connectivity and psychedelics. Using the PRISMA framework, we selected 24 articles from an initial pool of 492 for analysis. This scoping review and analysis investigated the effects of psychedelics on subjective experiences and brain functional connectivity in healthy individuals. The studies quantified subjective effects through psychometric scales, revealing significant experiences of altered consciousness, mood elevation, and mystical experiences induced by psychedelics. Neuroimaging results indicated alterations in the functional connectivity of psychedelics, with consistent findings across substances of decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. Correlations between these neurophysiological changes and subjective experiences were noted, suggesting a brain network basis of the psychedelics' neuropsychological impact. While the result of the review provides a potential neural mechanism of the subjective effects of psychedelics, direct clinical evidence is needed to advance their clinical outcomes. Our research serves as a foundation for further exploration of the therapeutic potential of psychedelics. [ABSTRACT FROM AUTHOR]

Introduction: Patients with incurable illnesses often experience existential distress, profoundly impacting their well-being. Current medical approaches have limitations in addressing these burdens. Psilocybin, a promising psychedelic compound, may offer therapeutic benefits. This pilot survey study aimed to investigate the attitudes and openness toward psilocybin-assisted psychotherapy (PAT) among patients with incurable illnesses. The objective is to assess patients' attitudes toward PAT and identify potential barriers and concerns, including exploring the association between beliefs in psilocybin's therapeutic benefits and interest in receiving this treatment. Methods: The survey study was conducted at the Tampa General Hospital Palliative Care Outpatient office in the United States. Participants were 32 English-fluent patients, aged 18 or older, with incurable illnesses. The survey included demographic questions, a validated tool to measure existential distress, and questions about knowledge and concerns regarding psilocybin. Attitudes toward PAT and interest in its future use were assessed using Likert scale responses. Results: Among the 31 analyzed participants, 51.6% expressed interest in future psilocybin treatment, while 32.3% did not indicate interest. Belief in the psilocybin's therapeutic benefits for stress and anxiety significantly correlated with interest in use. Concerns included risk of psychosis, lack of trained providers, and potential for exploitation. No demographic factors were associated with interest or levels of distress. Conclusions: This pilot study provides insights into the attitudes and concerns toward PAT among patients with incurable illnesses. Over half of participants expressed interest. However, concerns regarding its use were identified, with patients' concern for the risk of exploitation associated with PAT as an especially novel concern documented in this patient population. This highlighted the need for further education of risks and benefits or PAT by trained clinicians and rigorous training of clinicians with the establishment of safeguards against exploitation. Further research is necessary to explore the potential benefits of PAT and related non-psilocybin psychedelic compounds in addressing existential distress among patients with incurable illnesses. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between psychiatry and spirituality. It highlights the rise in deaths from suicide, drug overdoses, and alcoholism, and the impact of loneliness and isolation on mental and physical health. The article argues that psychiatry often overlooks spirituality as a need and resource for patients, despite evidence that spirituality can have both negative and positive impacts on mental illness. It suggests that recognizing and addressing spiritual needs could improve well-being and treatment outcomes. The article also explores the role of psychedelic therapy in facilitating spiritual experiences and its potential therapeutic benefits. [Extracted from the article]

Psilocybin has reemerged as a promising treatment for difficult-to-treat depression (DTD). Although there is limited evidence regarding interactions between psilocybin and other psychotropic drugs, clinical trials require that patients discontinue their antidepressants before study entry to isolate the benefits of psilocybin and to minimize the risk of adverse events. We present the first case of an adult patient with DTD who received psilocybin-assisted psychotherapy (PAP) in combination with two serotoninergic antidepressants (duloxetine and vortioxetine). Since he displayed a partial response after the first PAP session, he agreed to discontinue duloxetine (but refused to stop vortioxetine) before the second PAP session to see if it could improve the therapeutic efficacy of psilocybin. However, his anxiety and depressive symptoms worsened. Psilocybin was well-tolerated in both PAP sessions; mild headaches were the main adverse effects experienced by the patient, and there were no cardiovascular safety concerns. This case report suggests that serotoninergic antidepressants combination with psilocybin appears to be safe and that antidepressant discontinuation prior to PAP may not be necessary. Since the continuation of antidepressants during PAP has the potential to improve treatment acceptability and accessibility, future research should assess whether psilocybin can be administered concurrently with antidepressants. [ABSTRACT FROM AUTHOR]

Introduction: Recent research suggests that psychedelics may have potential for the treatment of various substance use disorders. However, most studies to date have been limited by small sample sizes and neglecting to include non-North American and European populations. Methods: We conducted a global, cross-sectional online survey of adults (n = 5,268, 47.2%women) self-reporting past or current psychedelic use and investigated whether psychedelic use was associated with changes in use of other substances. Results: Nearly three-quarters (70.9%; n = 3,737/5,268) reported ceasing or decreasing use of one or more non-psychedelic substances after naturalistic psychedelic use. Among those with previous use, 60.6% (n = 2,634/4,344) decreased alcohol use, 55.7% (n = 1,223/2,197) decreased antidepressant use, and 54.2% (n = 767/1,415) decreased use of cocaine/crack. Over a quarter of the sample indicated that their decrease in substance use persisted for 26 weeks or more following use of a psychedelic. Factors associated with decreased use included a motivation to either decrease one's substance use or self-treat a medical condition. Importantly, 19.8% of respondents also reported increased or initiated use of one or more other substances after psychedelic use, with illicit opioids (14.7%; n = 86/584) and cannabis (13.3%; n = 540/4,064) having the highest proportions. Factors associated with increased substance use included having a higher income and residing in Canada or the US. Discussion: Although limited by cross-sectional study design, this large observational study will help inform future studies aiming to investigate the relationship between substance use patterns and psychedelic use. [ABSTRACT FROM AUTHOR]

Background: To date, few randomized controlled trials of psilocybin with nondirective support exist for obsessive-compulsive disorder (OCD). Results and participant feedback from an interim analysis of an ongoing single-dose trial (NCT03356483) converged on the possibility of administering a higher fixed dose and/or more doses of psilocybin in future trials for presumably greater benefits. Objectives: This trial aims to evaluate the safety, feasibility, tolerability, and clinical effects of two doses of psilocybin paired with non-directive support in the treatment of OCD. This trial also seeks to examine whether two doses of psilocybin lead to greater OCD symptom reduction than a single dose, and to elucidate psychological mechanisms underlying the effects of psilocybin on OCD. Design: A randomized (1:1), waitlist-controlled design with blinded ratings will be used to examine the effects of two doses of oral psilocybin paired with non-directive support vs. waitlist control on OCD symptoms. An adaptive dose selection strategy will be implemented (i.e., first dose: 25 mg; second dose: 25 or 30 mg). Methods and analysis: This single-site trial will enroll 30 adult participants with treatment-refractory OCD. Aside from safety, feasibility, and tolerability metrics, primary outcomes include OCD symptoms assessed on the Yale-Brown Obsessive-Compulsive Scale - Second Edition (Y-BOCS-II). A blinded independent rater will assess primary outcomes at baseline and the primary endpoint at the end of the second dosing week. Participants will be followed up to 12 months post-second dosing. Participants randomized to waitlist will be rescreened after 7 weeks post-randomization, and begin their delayed treatment phase thereafter if still eligible. Ethics: Written informed consent will be obtained from participants. The institutional review board has approved this trial (protocol v. 1.7; HIC #2000032623). Discussion: This study seeks to advance our ability to treat refractory OCD, and catalyze future research seeking to optimize the process of psilocybin treatment for OCD through understanding relevant psychological mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: Migration is often accompanied by interpersonal, material and abstract losses and can be associated with migratory grief. The correlates of migratory grief have not yet been sufficiently addressed in research. This review aims to systematically investigate the relationship between migratory grief and psychopathology, to map the current state of research on this highly relevant topic and to derive relevant implications for the target group. Method: A systematic literature search of electronic databases (PubMed/Medline, PsycINFO, Web of Science) was conducted up until January 2023. Primary empirical quantitative and qualitative studies with migrants were included that assessed the association between migratory grief and psychopathology, using a specific instrument for migratory grief (quantitative) or named migratory grief as relevant topic (qualitative). Studies that only captured aspects of migratory grief, were not written in English, or were descriptive/non-peer-reviewed publications, were excluded. A quality assessment of all studies included was performed using the Mixed Methods Appraisal Tool. The results were synthesized using a narrative synthesis approach. Results: All studies (quan. = 4; qual. = 1)were cross-sectional and used convenience samples. The studies had a mean number of 83 participants with a total of N = 487 participants included in the current review. All included studies reported a significant relationship between migratory grief and psychological distress. Discussion: Despite the quality of the included studies being limited, our results show that there is a link between migratory grief and depression among refugees and migrants. However, there are only few studies in this currently and certainly also in the future relevant field of research, which is why further studies on factors influencing migratory grief as well as associations with other disorders would be desirable. [ABSTRACT FROM AUTHOR]

Introduction: Psilocybin is a classic psychedelics, which has been shown to have antidepressant effects by many studies in recent years. In this study, we aim to evaluate the efficacy, acceptability and tolerability of psilocybin in the treatment of primary (major depressive disorder) or secondary (experiencing distress related to life-threatening diagnoses and terminal illness) depression. Methods: We searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov for clinical trials of psilocybin for depression (updated to 4 October, 2023). Effect size Hedges' g was used as an indicator of efficacy, and other outcomes included response rate, drop-out rate, and adverse events. Results: A total of 10 studies were finally included in systematic review. 8 studies were included in the meta-analysis, involving a total of 524 adult patients, and produced a large effect size in favor of psilocybin (Hedge's g =-0.89, 95% CI -1.25~-0.53, I² = 70.19%, P<0.01). The therapeutic effects of psilocybin increase with increasing doses. Adverse events caused by psilocybin are generally transient and reversible, but serious adverse events also may occur. Discussion: Our study shows that psilocybin has both short-term and long-term antidepressant effects and holds promise as a potential complementary or alternative therapy for depression, probably. Further research may reveal more about its therapeutic potential. [ABSTRACT FROM AUTHOR]

Introduction: The practice of taking small, sub-hallucinogenic doses of psychedelics, known as microdosing, has exploded in popularity over the last decade. Users claim benefits ranging from improved mood and enhanced creativity to an increased sense of meaning and connectedness in life. While research on microdosing is still lagging behind the shift in public opinion, several papers have been published in the last five years which attempted to assess the effects of microdosing. Methods: This review paper aimed to critically analyze the research practices used in the recent wave of microdosing research: We reviewed 15 papers published before the closing date of this review in March 2022. Results: Our review concludes that it is premature to draw any conclusions about the efficacy or safety of microdosing since the research quality cannot be considered confirmatory. Discussion: We propose some potential causes for the current state of the literature and some suggestions for how these causes may be ameliorated. [ABSTRACT FROM AUTHOR]

Introduction: The use of the psychedelic compound psilocybin in conjunction with psychotherapy has shown promising results in the treatment of psychiatric disorders, though the underlying mechanisms supporting these effects remain unclear. Psilocybin is a Schedule I substance that is dephosphorylated in vivo to form an active metabolite, psilocin. Psilacetin, also known as O-acetylpsilocin or 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), is an unscheduled compound that has long been suggested as an alternative psilocin prodrug, though direct in vivo support for this hypothesis has thus far been lacking. Methods: This study employed liquid chromatography--tandem mass spectrometry (LC--MS/MS) to assess the time-course and plasma concentrations of psilocin following the intraperitoneal (IP) administration of psilacetin fumarate or psilocybin to male and female C57Bl6/J mice. Results: Direct comparisons of the time courses for psilocin exposure arising from psilocybin and psilacetin found that psilocybin led to 10-25% higher psilocin concentrations than psilacetin at 15-min post-injection. The half-life of psilocin remained approximately 30 min, irrespective of whether it came from psilocybin or psilacetin. Overall, the relative amount of psilocin exposure from psilacetin fumarate was found to be approximately 70% of that from psilocybin. Discussion: These findings provide the first direct support for the longstanding assumption in the field that psilacetin functions as a prodrug for psilocin in vivo. In addition, these results indicate that psilacetin fumarate results in lower peripheral psilocin exposure than psilocybin when dosed on an equimolar basis. Thoughtful substitution of psilocybin with psilacetin fumarate appears to be a viable approach for conducting mechanistic psychedelic research in C57Bl6/J mice. [ABSTRACT FROM AUTHOR]

BackgroundHypertension is a major source of morbidity and mortality worldwide, particularly for racial and ethnic minorities who face higher rates of hypertension and worse health-related outcomes. Recent research has reported on protective associations between classic psychedelics and hypertension; however, there is a need to explore how race and ethnicity may moderate such associations.MethodsWe used data from the National Survey on Drug Use and Health (2005–2014) to assess whether race and ethnicity moderate the associations between classic psychedelic use – specifically psilocybin – and past year hypertension.ResultsHispanic identity moderated the associations between psilocybin use and past year hypertension. Furthermore, individuals who used psilocybin and identified as Non-Hispanic White had reduced odds of hypertension (aOR: 0.83); however, these associations were not observed for any other racial or ethnic groups in our study for individuals who used psilocybin.ConclusionOverall, our results demonstrate that the associations between psychedelics and hypertension may vary by race and ethnicity. Longitudinal studies and clinical trials can further advance this research and determine whether such differences exist in causal contexts.Project registrationhttps://osf.io/xsz2p/?view_only=0bf7b56749034c18abb2a3f8d3d4bc0b.

Resistance to traditional treatment methods is still a major obstacle in modern psychiatry. As a result, several studies are currently being conducted to find effective alternatives to traditional therapies. One of these alternatives is psilocybin, a psychedelic substance that has been tested in clinical trials as an adjunct to psychotherapy. These studies focus on patients with major depressive disorder (MDD), obsessive-compulsive disorder (OCD) and substance use disorder (SUD), particularly alcohol and nicotine dependence. This article looks at the current understanding of psilocybin, including data from clinical trials conducted, psilocybin’s mechanism of action, its safety and the level of risk associated with it.

BackgroundChronic pain is a leading cause of disability worldwide. Fibromyalgia is a particularly debilitating form of widespread chronic pain. Fibromyalgia remains poorly understood, and treatment options are limited or moderately effective at best. Here, we present a protocol for a mechanistic study investigating the effects of psychedelic-assisted-therapy in a fibromyalgia population. The principal focus of this trial is the central mechanism(s) of psilocybin-therapy i.e., in the brain and on associated mental schemata, primarily captured by electroencephalography (EEG) recordings of the acute psychedelic state, plus pre and post Magnetic Resonance Imaging (MRI).MethodsTwenty participants with fibromyalgia will complete 8 study visits over 8 weeks. This will include two dosing sessions where participants will receive psilocybin at least once, with doses varying up to 25mg. Our primary outcomes are 1) Lempel-Ziv complexity (LZc) recorded acutely using EEG, and the 2) the (Brief Experiential Avoidance Questionnaire (BEAQ) measured at baseline and primary endpoint. Secondary outcomes will aim to capture broad aspects of the pain experience and related features through neuroimaging, self-report measures, behavioural paradigms, and qualitative interviews. Pain Symptomatology will be measured using the Brief Pain Inventory Interference Subscale (BPI-IS), physical and mental health-related function will be measured using the 36-Item Short Form Health Survey (SF-36). Further neurobiological investigations will include functional MRI (fMRI) and diffusion tensor imaging (changes from baseline to primary endpoint), and acute changes in pre- vs post-acute spontaneous brain activity – plus event-related potential functional plasticity markers, captured via EEG.DiscussionThe results of this study will provide valuable insight into the brain mechanisms involved in the action of psilocybin-therapy for fibromyalgia with potential implications for the therapeutic action of psychedelic-therapy more broadly. It will also deliver essential data to inform the design of a potential subsequent RCT.

Introduction and aimIt is important to understand how mental health practitioners view recent findings on psychedelic-assisted psychotherapy (PAP) as there is potential this treatment may be incorporated into clinical practice. The aim of our study was to explore how psychiatrists who are not involved in psychedelic research and who are located in the European region perceive psychedelics and PAP.MethodsWe conducted online semi-structured interviews with 12 psychiatry specialists and psychiatry trainees from 8 European countries. Data were analyzed using a general inductive approach informed by codebook thematic analysis.ResultsBased on the interviews, we developed four main themes and 14 sub-themes, including (1) Psychedelics hold potential, (2) Psychedelics are dangerous, (3) Future of psychedelics is uncertain, and (4) Psychiatry is ambivalent toward psychedelics.DiscussionOur respondents-psychiatrists acknowledged the potential of PAP but remained cautious and did not yet perceive its evidence base as robust enough. Education on psychedelics is lacking in medical and psychiatric training and should be improved to facilitate the involvement of mental health experts in decision-making on PAP.

IntroductionPatients with incurable illnesses often experience existential distress, profoundly impacting their well-being. Current medical approaches have limitations in addressing these burdens. Psilocybin, a promising psychedelic compound, may offer therapeutic benefits. This pilot survey study aimed to investigate the attitudes and openness toward psilocybin-assisted psychotherapy (PAT) among patients with incurable illnesses. The objective is to assess patients’ attitudes toward PAT and identify potential barriers and concerns, including exploring the association between beliefs in psilocybin’s therapeutic benefits and interest in receiving this treatment.MethodsThe survey study was conducted at the Tampa General Hospital Palliative Care Outpatient office in the United States. Participants were 32 English-fluent patients, aged 18 or older, with incurable illnesses. The survey included demographic questions, a validated tool to measure existential distress, and questions about knowledge and concerns regarding psilocybin. Attitudes toward PAT and interest in its future use were assessed using Likert scale responses.ResultsAmong the 31 analyzed participants, 51.6% expressed interest in future psilocybin treatment, while 32.3% did not indicate interest. Belief in the psilocybin’s therapeutic benefits for stress and anxiety significantly correlated with interest in use. Concerns included risk of psychosis, lack of trained providers, and potential for exploitation. No demographic factors were associated with interest or levels of distress.ConclusionsThis pilot study provides insights into the attitudes and concerns toward PAT among patients with incurable illnesses. Over half of participants expressed interest. However, concerns regarding its use were identified, with patients’ concern for the risk of exploitation associated with PAT as an especially novel concern documented in this patient population. This highlighted the need for further education of risks and benefits or PAT by trained clinicians and rigorous training of clinicians with the establishment of safeguards against exploitation. Further research is necessary to explore the potential benefits of PAT and related non-psilocybin psychedelic compounds in addressing existential distress among patients with incurable illnesses.

Objective: To compare group and individual psychedelic-assisted therapy in terms of clinician time, costs and patient access. Methods: Using 2023 data from two group therapy trial sites, one using 3,4-Methylenedioxymethamphetamine (MDMA) to treat posttraumatic stress disorder (PTSD), and one using psilocybin to treat major depressive disorder (MDD), we compared overall variable costs, clinician costs and clinician time required by therapy protocols utilizing groups versus individual patient therapy. Using published literature, we estimated the prevalence of adults with PTSD and MDD eligible for treatment with psychedelic therapy and projected the savings in time and cost required to treat these prevalent cases. Results: Group therapy saved 50.9% of clinician costs for MDMA-PTSD and 34.7% for psilocybin-MDD, or $3,467 and $981 per patient, respectively. To treat all eligible PTSD and MDD patients in the U.S. in 10  years with group therapy, 6,711 fewer full-time equivalent (FTE) clinicians for MDMA-PTSD and 1,159 fewer for FTE clinicians for psilocybin-MDD would be needed, saving up to $10.3 billion and $2.0 billion respectively, discounted at 3% annually. Conclusion: Adopting group therapy protocols where feasible would significantly reduce the cost of psychedelic-assisted therapies. By enhancing the number of patients served per clinician, group therapy could also ameliorate the anticipated shortage of appropriately trained clinicians, thereby accelerating access to these promising new therapies. [ABSTRACT FROM AUTHOR]

In contrast to well established psychedelics such as lysergic acid diethylamide (LSD) and psilocybin, ergot alkaloids of the clavine subclass have not been thoroughly investigated, in spite of their broad occurrence in nature and their well-established potent physiological effects. This study presents the current knowledge on the biological properties of clavine alkaloids, draws comparisons to the pharmacology of ergolines and related psychedelics, and demonstrates opportunities to develop novel structure–activity relationship (SAR) profiles. The latter could usher in a new stage of medicinal chemistry studies that enable an expansion of the currently structurally limited portfolio of psychedelic therapeutics. [ABSTRACT FROM AUTHOR]

Objective: In recent years, there has been a renewed interest in investigating the use of classic psychedelics such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of mental disorders and substance use disorders. However, knowledge about the epidemiology of classic psychedelics in the Nordic countries is limited. Methods: We recruited adult, Norwegian participants who have had a memorable experience after taking a classic psychedelic substance. They filled in an anonymous internet survey with 119 items covering matters related to recreational use of psychedelics using a secure, web-based application. Data are presented by using descriptive statistics (frequencies, means, and standard deviations). Results: We recruited 841 participants, 770 (72% male; 88% 45 years or younger) of which were included in the data analysis. The intentions behind taking the psychedelic substance were mainly recreational (46.1%) or therapeutic (42.3%). Most participants reported that their most memorable experience was with psilocybin. As in modern era clinical trials, most participants were well-prepared before, did processing during, and did integration work after the experience, whereas only a minority were supported by a therapist. Self-perceived symptoms of various mental disorders and substance use disorders were prevalent in the sample. Most subjects reported improvements in their condition. Although adverse reactions were usually mild and short-lived, 4.2% lasted for 1 year or more. Persisting flashbacks were present for a year or more among 2.9% of the participants. Conclusion: In this cross-sectional sample of Norwegian, self-selecting adults, we shed light on what characterizes the most memorable experience with a classic psychedelic substance, including short- and long-term risks and benefits. For the most part, the psychedelic experience led to improvements in selfperceived symptoms of mental disorders and substance use disorders. However, a small subset experienced persisting adverse reactions. [ABSTRACT FROM AUTHOR]

There has been an increase in research on the topic of psychedelic substances and their effects as treatment options in neuropsychiatric conditions. Psilocybin is a psychedelic drug that has recently garnered increased interest as an effective treatment modality for treatment-resistant depression, depression associated with terminal conditions, certain substance use disorders, and obsessive--compulsive disorder. However, sparse data exist as to the effects that psilocybin might have on patients at risk for mania, in large part secondary to the exclusion of this patient population from studies due to the concern for inducing mania or worsening illness course. We describe a case of a 21-year-old male with a recent diagnosis of bipolar II disorder who developed a manic episode following the ingestion of psilocybin in the form of hallucinogenic mushrooms. Given the incidence of depression in those with bipolar disorder, impulsivity, and a tendency to abuse substances associated with the illness, further research is needed into the risks of psilocybin and other psychedelic use in those with bipolar disorder. [ABSTRACT FROM AUTHOR]

Introduction: Psychedelic-assisted therapy with psilocybin has shown promise in Phase 2 trials for alcohol use disorder (AUD). Set and setting, particularly factors facilitating a connection with nature, may positively influence the psychedelic experience and therapeutic outcomes. But to date, randomized controlled trials of interventions to enhance set and setting for psychedelic-assisted therapy are lacking. Methods: This was a pilot randomized, controlled trial of Visual Healing, a nature-themed video intervention to optimize set and setting, versus Standard set and setting procedures with two open-label psilocybin 25  mg dosing sessions among 20 participants with AUD. For the first session, participants randomized to Visual Healing viewed nature-themed videos during the preparation session and the “ascent” and “descent” phases of the psilocybin dosing session while participants randomized to the Standard condition completed a meditation during the preparatory session and wore eyeshades and listened to a music playlist throughout the dosing session. For the second session 4 weeks later, participants chose either Visual Healing or Standard procedures. Primary outcomes were feasibility, safety, and tolerability of Visual Healing. Secondary and exploratory outcomes were changes in alcohol use, psychedelic effects, anxiety and stress. Results: Nineteen of 20 (95%) randomized participants (mean age 49  ±  11  years, 60% female) completed the 14-week study. During the first psilocybin session, participants viewed an average of 37.9  min of the 42-min video and there were no video-related adverse events. Peak increase in post-psilocybin blood pressure was significantly less for participants randomly assigned to Visual Healing compared to Standard procedures. Alcohol use decreased significantly in both Visual Healing and Standard groups and psychedelic effects, stress, and anxiety were similar between groups. Discussion: In this open-label pilot study, viewing Visual Healing videos during preparation and psilocybin dosing sessions was feasible, safe, and well-tolerated among participants with AUD. Preliminary findings suggest that Visual Healing has potential to reduce the cardiovascular risks of psychedelic therapy, without interfering with the psychedelic experience or alcohol-related treatment outcomes. Studies to replicate our findings as well as studies of different set and setting interventions with other psychedelic medications and indications are warranted. [ABSTRACT FROM AUTHOR]

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]

IntroductionRecent research suggests that psychedelics may have potential for the treatment of various substance use disorders. However, most studies to date have been limited by small sample sizes and neglecting to include non-North American and European populations.MethodsWe conducted a global, cross-sectional online survey of adults (n = 5,268, 47.2% women) self-reporting past or current psychedelic use and investigated whether psychedelic use was associated with changes in use of other substances.ResultsNearly three-quarters (70.9%; n = 3,737/5,268) reported ceasing or decreasing use of one or more non-psychedelic substances after naturalistic psychedelic use. Among those with previous use, 60.6% (n = 2,634/4,344) decreased alcohol use, 55.7% (n = 1,223/2,197) decreased antidepressant use, and 54.2% (n = 767/1,415) decreased use of cocaine/crack. Over a quarter of the sample indicated that their decrease in substance use persisted for 26 weeks or more following use of a psychedelic. Factors associated with decreased use included a motivation to either decrease one’s substance use or self-treat a medical condition. Importantly, 19.8% of respondents also reported increased or initiated use of one or more other substances after psychedelic use, with illicit opioids (14.7%; n = 86/584) and cannabis (13.3%; n = 540/4,064) having the highest proportions. Factors associated with increased substance use included having a higher income and residing in Canada or the US.DiscussionAlthough limited by cross-sectional study design, this large observational study will help inform future studies aiming to investigate the relationship between substance use patterns and psychedelic use.

IntroductionThe practice of taking small, sub-hallucinogenic doses of psychedelics, known as microdosing, has exploded in popularity over the last decade. Users claim benefits ranging from improved mood and enhanced creativity to an increased sense of meaning and connectedness in life. While research on microdosing is still lagging behind the shift in public opinion, several papers have been published in the last five years which attempted to assess the effects of microdosing.MethodsThis review paper aimed to critically analyze the research practices used in the recent wave of microdosing research: We reviewed 15 papers published before the closing date of this review in March 2022.ResultsOur review concludes that it is premature to draw any conclusions about the efficacy or safety of microdosing since the research quality cannot be considered confirmatory.DiscussionWe propose some potential causes for the current state of the literature and some suggestions for how these causes may be ameliorated.

IntroductionThe use of the psychedelic compound psilocybin in conjunction with psychotherapy has shown promising results in the treatment of psychiatric disorders, though the underlying mechanisms supporting these effects remain unclear. Psilocybin is a Schedule I substance that is dephosphorylated in vivo to form an active metabolite, psilocin. Psilacetin, also known as O-acetylpsilocin or 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), is an unscheduled compound that has long been suggested as an alternative psilocin prodrug, though direct in vivo support for this hypothesis has thus far been lacking.MethodsThis study employed liquid chromatography–tandem mass spectrometry (LC–MS/MS) to assess the time-course and plasma concentrations of psilocin following the intraperitoneal (IP) administration of psilacetin fumarate or psilocybin to male and female C57Bl6/J mice.ResultsDirect comparisons of the time courses for psilocin exposure arising from psilocybin and psilacetin found that psilocybin led to 10–25% higher psilocin concentrations than psilacetin at 15-min post-injection. The half-life of psilocin remained approximately 30 min, irrespective of whether it came from psilocybin or psilacetin. Overall, the relative amount of psilocin exposure from psilacetin fumarate was found to be approximately 70% of that from psilocybin.DiscussionThese findings provide the first direct support for the long-standing assumption in the field that psilacetin functions as a prodrug for psilocin in vivo. In addition, these results indicate that psilacetin fumarate results in lower peripheral psilocin exposure than psilocybin when dosed on an equimolar basis. Thoughtful substitution of psilocybin with psilacetin fumarate appears to be a viable approach for conducting mechanistic psychedelic research in C57Bl6/J mice.

BackgroundTo date, few randomized controlled trials of psilocybin with non-directive support exist for obsessive-compulsive disorder (OCD). Results and participant feedback from an interim analysis of an ongoing single-dose trial (NCT03356483) converged on the possibility of administering a higher fixed dose and/or more doses of psilocybin in future trials for presumably greater benefits.ObjectivesThis trial aims to evaluate the safety, feasibility, tolerability, and clinical effects of two doses of psilocybin paired with non-directive support in the treatment of OCD. This trial also seeks to examine whether two doses of psilocybin lead to greater OCD symptom reduction than a single dose, and to elucidate psychological mechanisms underlying the effects of psilocybin on OCD.DesignA randomized (1:1), waitlist-controlled design with blinded ratings will be used to examine the effects of two doses of oral psilocybin paired with non-directive support vs. waitlist control on OCD symptoms. An adaptive dose selection strategy will be implemented (i.e., first dose: 25 mg; second dose: 25 or 30 mg).Methods and analysisThis single-site trial will enroll 30 adult participants with treatment-refractory OCD. Aside from safety, feasibility, and tolerability metrics, primary outcomes include OCD symptoms assessed on the Yale-Brown Obsessive-Compulsive Scale – Second Edition (Y-BOCS-II). A blinded independent rater will assess primary outcomes at baseline and the primary endpoint at the end of the second dosing week. Participants will be followed up to 12 months post-second dosing. Participants randomized to waitlist will be rescreened after 7 weeks post-randomization, and begin their delayed treatment phase thereafter if still eligible.EthicsWritten informed consent will be obtained from participants. The institutional review board has approved this trial (protocol v. 1.7; HIC #2000032623).DiscussionThis study seeks to advance our ability to treat refractory OCD, and catalyze future research seeking to optimize the process of psilocybin treatment for OCD through understanding relevant psychological mechanisms.Clinical trial registration: ClinicalTrials.gov, identifier NCT05370911.

ObjectiveTo compare group and individual psychedelic-assisted therapy in terms of clinician time, costs and patient access.MethodsUsing 2023 data from two group therapy trial sites, one using 3,4-Methylenedioxymethamphetamine (MDMA) to treat posttraumatic stress disorder (PTSD), and one using psilocybin to treat major depressive disorder (MDD), we compared overall variable costs, clinician costs and clinician time required by therapy protocols utilizing groups versus individual patient therapy. Using published literature, we estimated the prevalence of adults with PTSD and MDD eligible for treatment with psychedelic therapy and projected the savings in time and cost required to treat these prevalent cases.ResultsGroup therapy saved 50.9% of clinician costs for MDMA-PTSD and 34.7% for psilocybin-MDD, or $3,467 and $981 per patient, respectively. To treat all eligible PTSD and MDD patients in the U.S. in 10 years with group therapy, 6,711 fewer full-time equivalent (FTE) clinicians for MDMA-PTSD and 1,159 fewer for FTE clinicians for psilocybin-MDD would be needed, saving up to $10.3 billion and $2.0 billion respectively, discounted at 3% annually.ConclusionAdopting group therapy protocols where feasible would significantly reduce the cost of psychedelic-assisted therapies. By enhancing the number of patients served per clinician, group therapy could also ameliorate the anticipated shortage of appropriately trained clinicians, thereby accelerating access to these promising new therapies.

ObjectiveIn recent years, there has been a renewed interest in investigating the use of classic psychedelics such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of mental disorders and substance use disorders. However, knowledge about the epidemiology of classic psychedelics in the Nordic countries is limited.MethodsWe recruited adult, Norwegian participants who have had a memorable experience after taking a classic psychedelic substance. They filled in an anonymous internet survey with 119 items covering matters related to recreational use of psychedelics using a secure, web-based application. Data are presented by using descriptive statistics (frequencies, means, and standard deviations).ResultsWe recruited 841 participants, 770 (72% male; 88% 45 years or younger) of which were included in the data analysis. The intentions behind taking the psychedelic substance were mainly recreational (46.1%) or therapeutic (42.3%). Most participants reported that their most memorable experience was with psilocybin. As in modern era clinical trials, most participants were well-prepared before, did processing during, and did integration work after the experience, whereas only a minority were supported by a therapist. Self-perceived symptoms of various mental disorders and substance use disorders were prevalent in the sample. Most subjects reported improvements in their condition. Although adverse reactions were usually mild and short-lived, 4.2% lasted for 1 year or more. Persisting flashbacks were present for a year or more among 2.9% of the participants.ConclusionIn this cross-sectional sample of Norwegian, self-selecting adults, we shed light on what characterizes the most memorable experience with a classic psychedelic substance, including short- and long-term risks and benefits. For the most part, the psychedelic experience led to improvements in self-perceived symptoms of mental disorders and substance use disorders. However, a small subset experienced persisting adverse reactions.

Introduction: Psilocybin use has been linked to lowered odds of crime-related outcomes across a host of observational studies. No studies have investigated how these associations may differ among those of different races and ethnicities. Methods: Using a nationally-representative sample of 734,061 adults from the National Survey on Drug Use and Health (2002–2020), we investigated whether race and ethnicity moderate the associations between lifetime psilocybin use and four measures of crime arrests (property crime, assault, serious violence, and miscellaneous crimes). Results: First, we replicated prior findings and demonstrated that psilocybin confers lowered odds of crime arrests for all four outcomes in question. Second, we demonstrated that race and ethnicity moderate the associations between lifetime psilocybin use and crime arrests for three of our four outcomes. Third, we examined the associations between psilocybin and crime arrests across different races and ethnicities (White, Black, Indigenous, Asian, Multiracial, and Hispanic participants). Psilocybin conferred lowered odds of at least one crime arrest outcome for all racial and ethnic groups except for Black and Hispanic participants. Discussion: Future investigations should take an intersectional approach to studying the interrelationship of sociodemographic factors, psychedelic use, and crime, examine the structural factors (i.e., systemic racism) that may underlie these results, and investigate whether psychedelics can alleviate mental health disorders that contribute to cycles of recriminalization for communities of color. [ABSTRACT FROM AUTHOR]

Introduction: There is substantial public interest in psychedelics as potential treatments for psychiatric conditions. However, most psychedelics are criminalized under federal law in the USA, so it is unclear whether use occurs with clinical support. Our objective was to assess whether naturalistic psychedelic use occurs with clinical support, interactions between those using psychedelics and healthcare providers (psychiatrist, therapist, or primary physicians), and use characteristics. Methods: We conducted an online, anonymous, confidential, cross-sectional survey of adults reporting psychedelic use (N = 1221) through a psychedelics advocacy event and social media between 9/18/2022 and 11/5/2022. We assessed participant disclosure of psychedelic use with their psychiatric care provider (PsyCP) and/or primary care provider (PCP), desire for provider support, access to support, and rate of taking prescribed psychoactive medications alongside psychedelics. Results: Among participants with such care providers, 22% disclosed psychedelic use to their PCP vs. 58% to their PsyCP. Participants were less confident in PCP vs. PsyCP ability to integrate psychedelics into treatment. Common reasons for nondisclosure included stigma, inadequate provider knowledge, and legal concerns. 23% reported taking psychedelics on the same day as potentially interacting psychiatric medications (e.g., anxiolytics, antidepressants). Despite 81% of participants desiring therapist support during psychedelic experiences, only 15% had received such support. Discussion: Our results show that psychedelic use is generally disconnected from primary and psychiatric clinical care. This disconnection may result in safety issues, including inadequate screening for contraindicated conditions, lack of support during emergent adverse events, and drug interactions. Enhanced clinical education and orienting drug policy towards known harms and benefits of psychedelics is needed. [ABSTRACT FROM AUTHOR]

Introduction: Attention-deficit/hyperactivity disorder (ADHD) was originally treated as a neurodevelopmental disorder that occurs mainly in children and tends to diminish or disappear with age, but we now know that symptoms persist into adulthood in over 50% of ADHD patients. Undiagnosed individuals often turn to psychoactive substance to minimize the negative aspects of functioning and improve quality of life. Methods: The study was conducted online using random sampling through a Facebook group administered by physicians and targeted to patients diagnosed with ADHD. The study was naturalistic and exploratory, therefore no hypothesis was made. 438 correctly completed questionnaires were received. Analysis of the results showed that people with ADHD turn to psychoactive substances relatively frequently. Results: The most commonly used stimulants include alcohol, marijuana, 3,4- methylenedioxymethamphetamine (MDMA), amphetamine/methamphetamine, and psilocybin. In the study population, methylphenidate is the most commonly used drug among patients. After treatment with psychostimulants, the majority of respondents note a decrease in symptoms of hyperactivity disorder, especially in male patients. Conclusion: It is necessary to perform proper diagnostics and actively look for ADHD symptoms in patients who tend to use psychoactive substances. [ABSTRACT FROM AUTHOR]

The efficacy of psilocybin and other psychedelics as modes of treatment have been demonstrated through clinical trials and other studies in the management of a number of mental illnesses, including some treatment resistant cases. In Psychedelic Assisted Psychotherapy (PAP), psychedelics catalyze or enhance the experience fostered by psychotherapeutic methods. Psychohistoriographic Brief Psychotherapy, conceptualized by the late Professor Frederick Hickling in the 1970/s in Kingston, Jamaica, offers a pathway for exploration in the Jamaican context. Applied to individuals, Psychohistoriographic Brief Therapy (PBT) has already shown success in patients with personality disorders in Jamaica through a process which includes documenting life experiences in a psychohistoriogram. In the De La Haye psilocybin Treatment Protocol (DPTP), micro-doses of crushed, dried psilocybin mushrooms are taken throughout an 8-week outpatient process of documenting the components of the psychohistoriogram, making use of the increased openness and empathy associated with the use of psychedelic agents. These sessions are followed by supervised in-office therapeutic/mystical doses of crushed, dried psilocybin mushrooms in the 9th week. Given the legal status and availability of psilocybin containing products in a few countries like Jamaica, there is a potential role for a regulated psychedelic industry contributing to the body of useful and rigorous clinical research which is needed in this area. Clients could benefit as we venture into this new frontier in psychiatry. [ABSTRACT FROM AUTHOR]

Introduction: Although certain psychedelic agents may soon gain federal approval for use in treating specific psychiatric conditions, the utilization of such therapies in clinical practice will depend largely on the attitudes of healthcare providers. Therefore, this study assesses the current attitudes, knowledge, exposure, and acceptance of psychedelics and psychedelic-assisted therapies amongst medical students. Methods: In fall semester of 2022, surveys were emailed to 580 medical students attending medical institutions in the state of Nevada in the United States. Utilizing knowledge and attitude items from previously published studies, the survey collected demographic data and assessed student attitudes with five-point Likert-scale variables. Data was analyzed using summary statistics and Kruskal-Wallis tests for differences in mean survey scores (i.e., attitudes towards psychedelics) based on demographic factors. Results: 132 medical students participated in the survey (22.7% response rate). Medical students demonstrated overall positive attitudes towards psychedelics, lack of knowledge regarding psychedelics, and uncertainty towards neurocognitive risks of psychedelics. Overall, 78.6% of students agreed that psychedelics have therapeutic potential, while 95.2% agreed that psychedelics deserves further research in assessing this potential. Additionally, there was no statistically significant effect of demographic variables, including age, sex, and level of training, on attitudes. Discussion: Although students are overall curious and optimistic about psychedelics, they demonstrate a lack of knowledge regarding recent research efforts. As the field of psychiatry prepares to implement psychedelics and psychedelic-assisted therapies, education and awareness of such agents should be initiated early on in medical clinical training. [ABSTRACT FROM AUTHOR]

Introduction: Cannabis use disorder (CUD) is prevalent in 2-5% of adults in the United States and is anticipated to increase as restrictions to cannabis decrease and tetrahydrocannabinol (THC) content in cannabis products increase. No FDA-approved medications for CUD are currently available, despite trials of dozens of re-purposed and novel drugs. Psychedelics have garnered interest as a therapeutic class in other substance use disorders, and self-report surveys suggest they may result in positive outcomes for CUD. Herein, we review the existing literature pertaining to psychedelic use in persons with or at risk for CUD and consider the potential rationale underpinning psychedelics as a treatment for CUD. Methods: A systematic search was performed in several databases. Inclusion criteria were primary research reporting use of psychedelics or related substances and CUD for treatment in human subjects. Exclusion criteria were results including psychedelics or related substances without changes in cannabis use or risks associated with CUD. Results: Three hundred and five unique results were returned. One article was identified using the non-classical psychedelic ketamine in CUD; three articles were identified as topically relevant based on their secondary data or consideration of mechanism. Additional articles were reviewed for purposes of background, review of safety considerations, and formulating rationale. Conclusion: Limited data and reporting are available on the use of psychedelics in persons with CUD, and more research is needed given the anticipated increase in CUD incidence and increasing interest in psychedelic use. While psychedelics, broadly, have a high therapeutic index with infrequent serious adverse effects, particular adverse effects at risk in the CUD population, such as psychosis and cardiovascular events, should be considered. Possible mechanisms by which psychedelics have therapeutic potential in CUD are explored. [ABSTRACT FROM AUTHOR]

There has been an increase in research on the topic of psychedelic substances and their effects as treatment options in neuropsychiatric conditions. Psilocybin is a psychedelic drug that has recently garnered increased interest as an effective treatment modality for treatment-resistant depression, depression associated with terminal conditions, certain substance use disorders, and obsessive-compulsive disorder. However, sparse data exist as to the effects that psilocybin might have on patients at risk for mania, in large part secondary to the exclusion of this patient population from studies due to the concern for inducing mania or worsening illness course. We describe a case of a 21-year-old male with a recent diagnosis of bipolar II disorder who developed a manic episode following the ingestion of psilocybin in the form of hallucinogenic mushrooms. Given the incidence of depression in those with bipolar disorder, impulsivity, and a tendency to abuse substances associated with the illness, further research is needed into the risks of psilocybin and other psychedelic use in those with bipolar disorder.

IntroductionPsychedelic-assisted therapy with psilocybin has shown promise in Phase 2 trials for alcohol use disorder (AUD). Set and setting, particularly factors facilitating a connection with nature, may positively influence the psychedelic experience and therapeutic outcomes. But to date, randomized controlled trials of interventions to enhance set and setting for psychedelic-assisted therapy are lacking.MethodsThis was a pilot randomized, controlled trial of Visual Healing, a nature-themed video intervention to optimize set and setting, versus Standard set and setting procedures with two open-label psilocybin 25 mg dosing sessions among 20 participants with AUD. For the first session, participants randomized to Visual Healing viewed nature-themed videos during the preparation session and the “ascent” and “descent” phases of the psilocybin dosing session while participants randomized to the Standard condition completed a meditation during the preparatory session and wore eyeshades and listened to a music playlist throughout the dosing session. For the second session 4 weeks later, participants chose either Visual Healing or Standard procedures. Primary outcomes were feasibility, safety, and tolerability of Visual Healing. Secondary and exploratory outcomes were changes in alcohol use, psychedelic effects, anxiety and stress.ResultsNineteen of 20 (95%) randomized participants (mean age 49 ± 11 years, 60% female) completed the 14-week study. During the first psilocybin session, participants viewed an average of 37.9 min of the 42-min video and there were no video-related adverse events. Peak increase in post-psilocybin blood pressure was significantly less for participants randomly assigned to Visual Healing compared to Standard procedures. Alcohol use decreased significantly in both Visual Healing and Standard groups and psychedelic effects, stress, and anxiety were similar between groups.DiscussionIn this open-label pilot study, viewing Visual Healing videos during preparation and psilocybin dosing sessions was feasible, safe, and well-tolerated among participants with AUD. Preliminary findings suggest that Visual Healing has potential to reduce the cardiovascular risks of psychedelic therapy, without interfering with the psychedelic experience or alcohol-related treatment outcomes. Studies to replicate our findings as well as studies of different set and setting interventions with other psychedelic medications and indications are warranted.

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.

IntroductionPsilocybin use has been linked to lowered odds of crime-related outcomes across a host of observational studies. No studies have investigated how these associations may differ among those of different races and ethnicities.MethodsUsing a nationally-representative sample of 734,061 adults from the National Survey on Drug Use and Health (2002–2020), we investigated whether race and ethnicity moderate the associations between lifetime psilocybin use and four measures of crime arrests (property crime, assault, serious violence, and miscellaneous crimes).ResultsFirst, we replicated prior findings and demonstrated that psilocybin confers lowered odds of crime arrests for all four outcomes in question. Second, we demonstrated that race and ethnicity moderate the associations between lifetime psilocybin use and crime arrests for three of our four outcomes. Third, we examined the associations between psilocybin and crime arrests across different races and ethnicities (White, Black, Indigenous, Asian, Multiracial, and Hispanic participants). Psilocybin conferred lowered odds of at least one crime arrest outcome for all racial and ethnic groups except for Black and Hispanic participants.DiscussionFuture investigations should take an intersectional approach to studying the interrelationship of sociodemographic factors, psychedelic use, and crime, examine the structural factors (i.e., systemic racism) that may underlie these results, and investigate whether psychedelics can alleviate mental health disorders that contribute to cycles of recriminalization for communities of color.

IntroductionThere is substantial public interest in psychedelics as potential treatments for psychiatric conditions. However, most psychedelics are criminalized under federal law in the USA, so it is unclear whether use occurs with clinical support. Our objective was to assess whether naturalistic psychedelic use occurs with clinical support, interactions between those using psychedelics and healthcare providers (psychiatrist, therapist, or primary physicians), and use characteristics.MethodsWe conducted an online, anonymous, confidential, cross-sectional survey of adults reporting psychedelic use (N = 1221) through a psychedelics advocacy event and social media between 9/18/2022 and 11/5/2022. We assessed participant disclosure of psychedelic use with their psychiatric care provider (PsyCP) and/or primary care provider (PCP), desire for provider support, access to support, and rate of taking prescribed psychoactive medications alongside psychedelics.ResultsAmong participants with such care providers, 22% disclosed psychedelic use to their PCP vs. 58% to their PsyCP. Participants were less confident in PCP vs. PsyCP ability to integrate psychedelics into treatment. Common reasons for nondisclosure included stigma, inadequate provider knowledge, and legal concerns. 23% reported taking psychedelics on the same day as potentially interacting psychiatric medications (e.g., anxiolytics, antidepressants). Despite 81% of participants desiring therapist support during psychedelic experiences, only 15% had received such support.DiscussionOur results show that psychedelic use is generally disconnected from primary and psychiatric clinical care. This disconnection may result in safety issues, including inadequate screening for contraindicated conditions, lack of support during emergent adverse events, and drug interactions. Enhanced clinical education and orienting drug policy towards known harms and benefits of psychedelics is needed.

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]

Background: Psilocybin may help treat obsessive-compulsive disorder (OCD). To date, only one open-label study of psilocybin for OCD exists, necessitating further investigation with a randomized controlled design. The neural correlates of psilocybin's effects on OCD have also not been studied. Objectives: This first-of-its-kind trial aims to evaluate the feasibility, safety, and tolerability of psilocybin in the treatment of OCD, provide preliminary evidence on the effects of psilocybin on OCD symptoms, and elucidate neural mechanisms that may mediate psilocybin's effects on OCD. Design: We use a randomized (1:1), double-blind, placebo-controlled, noncrossover design to examine the clinical and neural effects of either a single dose of oral psilocybin (0.25 mg/kg) or active placebo-control agent (250 mg of niacin) on OCD symptoms. Methods and analysis: We are enrolling 30 adult participants at a single site in Connecticut, USA who have failed at least one trial of standard care treatment (medication/psychotherapy) for OCD. All participants will also receive unstructured, non-directive psychological support during visits. Aside from safety, primary outcomes include OCD symptoms over the past 24 h, assessed by the Acute Yale-Brown Obsessive-Compulsive Scale and Visual Analog Scale ratings. These are collected by blinded, independent raters at baseline and the primary endpoint of 48 h post-dosing. Total follow-up is 12 weeks post-dosing. Resting state neuroimaging data will be collected at baseline and primary endpoint. Participants randomized to placebo will be offered the chance to return for an open-label dose of 0.25 mg/kg. Ethics statement: All participants will be required to provide written informed consent. The trial (protocol v. 5.2) was approved by the institutional review board (HIC #2000020355) and registered with ClinicalTrials.gov (NCT03356483). Discussion: This study may represent an advance in our ability to treat refractory OCD, and pave the way for future studies of neurobiological mechanisms of OCD that may respond to psilocybin. [ABSTRACT FROM AUTHOR]

Methamphetamine use disorder is a chronic relapsing condition associated with substantial mental, physical, and social harms and increasing rates of mortality. Contingency management and psychotherapy interventions are the mainstays of treatment but are modestly effective with high relapse rates, while pharmacological treatments have shown little to no efficacy. Psilocybin-assisted psychotherapy is emerging as a promising treatment for a range of difficult-to-treat conditions, including substance use disorders; however, no studies have yet been published looking at psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder. Here we review the rationale for psilocybin-assisted psychotherapy as a potential treatment for this indication, and describe practical considerations based on our early experience designing and implementing four separate clinical trials of psilocybin-assisted psychotherapy for methamphetamine use disorder. [ABSTRACT FROM AUTHOR]