Documenting and defining emergent phenomenology: theoretical foundations for an extensive research strategy.

Meditation, psychedelics, and other similar practices or induction methods that can modulate conscious experience, are becoming increasingly popular in clinical and non-clinical settings. The phenomenology associated with such practices or modalities is vast. Many similar effects and experiences are also reported to occur spontaneously. We argue that this experiential range is still not fully described or understood in the contemporary literature, and that there is an ethical mandate to research it more extensively, starting with comprehensive documentation and definition. We review 50 recent clinical or scientific publications to assess the range of phenomena, experiences, effects, after-effects, and impacts associated with a broad variety of psychoactive compounds, meditative practices, and other modalities or events. This results in a large inventory synthesizing the reports of over 30,000 individual subjects. We then critically discuss various terms and concepts that have been used in recent literature to designate all or parts of the range this inventory covers. We make the case that specialized terminologies are needed to ground the nascent research field that is forming around this experiential domain. As a step in this direction, we propose the notion of "emergence" and some of its derivatives, such as "emergent phenomenology," as possibly foundational candidates.

Ketanserin exhibits dose- and concentration-proportional serotonin 2A receptor occupancy in healthy individuals: Relevance for psychedelic research.

The serotonin 2A (5-HT2A) receptor is an important target for drug development and the main receptor through which classical psychedelics elucidate their hallucinogenic effects. The 5-HT2A receptor antagonist ketanserin has frequently been used as a tool to block the receptor. Here, we establish the dose-occupancy relation of ketanserin and the cerebral 5-HT2A receptor in healthy participants by conducting a positron emission tomography (PET) study. 120-min PET scans using the 5-HT2A receptor agonist radiotracer [11C]Cimbi-36 were conducted at baseline and after oral doses of either 10, 20, or 40 mg of ketanserin; each participant underwent one or two scans after ketanserin administration. Occupancy was defined as the percent change in neocortex binding potential (BPND), estimated using the simplified reference tissue model (SRTM) with the cerebellum as reference region. Peroral ketanserin intake resulted in a plasma concentration-related increase in cerebral 5-HT2A receptor occupancy with the highest plasma ketanserin concentrations measured after ∼2 h. The relation between mean plasma ketanserin concentrations and 5-HT2A receptor occupancy conformed to a single-site binding model with an estimated EC50 (95 % CI) of 2.52 (0.75; 8.1) ng/mL, which corresponds to a peroral dose of ketanserin of approximately 10 mg. These data elucidate for the first time in humans the cerebral pharmacodynamics of ketanserin, both benefitting its use as a pharmacological tool for probing brain function and adding to its potential for therapeutic use in rescuing a bad psychedelic experience.

The Influence of Stakeholder Interests on Safety Outcome Reporting in Psychedelic Research and Implications for Science Communication.

Psychedelics are a group of psychoactive substances which produce complex and subjective changes to consciousness and carry unique safety considerations. There is a growing body of work investigating the use of psychedelics for mental health treatment alongside increasing socio-cultural and political acceptance. This rapid evolution has prompted corporations to fund psychedelic clinical trials, leading to a potential rise in conflicts of interest in relevant studies and publications. However, the body of evidence for the safety and efficacy of psychedelic-assisted psychotherapy for psychiatric illnesses is early. There is concern regarding the introduction of bias in psychedelic clinical trials and the selective reporting of results amidst and beyond corporate involvement. At a crucial time in psychedelic drug reform, this paper explores the safety concerns associated with psychedelics, the potential influences of financial stakeholders on safety outcome reporting and the importance of balanced science communication in maintaining public health and safety.

Can mind-altering prescription medicines be safe? Lessons from ketamine and esketamine.

INTRODUCTION: Recent decades have witnessed an extraordinary global crisis of drug misuse. Although opioid analgesics receive the most attention, numerous other drugs have increased rates of misuse. KETAMINE AND ESKETAMINE: Ketamine and esketamine offer a unique natural experiment to explore two medications that are similar pharmacologically but differ in their availability to users and in their regulation by government agencies. MISUSE AND ABUSE OF KETAMINE AND ESKETAMINE: Multisystem "mosaic" surveillance of many drugs using real-world data has emerged in recent years. Ketamine and esketamine have been monitored concurrently. Ketamine is much more widely available than esketamine and shows clear signs of increasing misuse and abuse. In contrast, esketamine is difficult to detect in postmarket surveillance even though availability is increasing. DISCUSSION: Ketamine and esketamine offer insights regarding the safety of prescription medications with the potential for misuse. Since the pharmacology of ketamine and esketamine are similar, the regulatory apparatus may be the primary difference that limits misuse. Ketamine has few restrictions and can be prescribed or administered by many healthcare providers, and is available as an illicit drug. In contrast, the product labeling for esketamine has rigorous restrictions on its use. Many important issues remain to be addressed. We need a more rigorous evaluation of the natural experiment of ketamine and esketamine. How does this experience relate to the introduction of new psychedelics? CONCLUSIONS: Ketamine misuse use and misuse are increasing while esketamine use in increasing, but misuse is not increasing. It is reasonable to reevaluate the regulatory controls on ketamine to reduce its misuse and abuse.

Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis.

Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain axis, may also have a role in mediating the positive effects of psychedelics on behaviour. In this review, we present existing evidence that the composition of the gut microbiota may be responsive to psychedelic drugs, and in turn, that the effect of psychedelics could be modulated by microbial metabolism. We discuss various alternative mechanistic models and emphasize the importance of incorporating hypotheses that address the contributions of the microbiome in future research. Awareness of the microbial contribution to psychedelic action has the potential to significantly shape clinical practice, for example, by allowing personalised psychedelic therapies based on the heterogeneity of the gut microbiota.

Psilocybin-assisted therapy and HIV-related shame.

As a proposed mediator between stigma-related stressors and negative mental health outcomes, HIV-related shame has been predictive of increased rates of substance use and difficulties adhering to antiretroviral treatment among people with HIV. These downstream manifestations have ultimately impeded progress toward national goals to End the HIV Epidemic, in part due to limited success of conventional psychotherapies in addressing HIV-related shame. In a pilot clinical trial (N = 12), receipt of psilocybin-assisted group therapy was associated with a large pre-post decrease in HIV-related shame as measured by the HIV and Abuse Related Shame Inventory, with a median (IQR) change of - 5.5 (- 6.5, - 3.5) points from baseline to 3-months follow-up (Z = - 2.6, p = 0.009, r = - 0.75). A paradoxical exacerbation of sexual abuse-related shame experienced by two participants following receipt of psilocybin raises critical questions regarding the use of psilocybin therapy among patients with trauma. These preliminary findings carry potential significance for the future of HIV care.

Magic of the Mushrooms: Effects of Psilocybin Decriminalization.

In the past few years, psilocybin, a psychedelic compound found in "magic mushrooms" (psilocybin mushrooms), has undergone decriminalization in numerous cities across the US and has been legalized in Oregon and Colorado. Proponents of psilocybin decriminalization have emphasized its therapeutic potential in treating mental health disorders. Furthermore, psilocybin mushrooms are considered the safest psychedelic option, with lower potency and a reduced risk of overdoses and emergency hospitalizations compared to other prevalent psychedelics, such as LSD (lysergic acid diethylamide) and MDMA (3,4-methylenedioxymethamphetamine). We analyzed the impact of psilocybin reforms on public interest in psilocybin, as well as their cross-commodity effects on LSD and MDMA, utilizing extensive web-based search data. We observe a significant increase in psilocybin search volume and a notable reduction in search volume associated with LSD and MDMA. Our results are consistent nationwide across states, irrespective of their stance on psilocybin reforms. The shift in public interest toward psilocybin, which is considered the safest psychedelic, away from LSD and MDMA, carries positive implications for public health.

Simultaneous cannabis and psychedelic use among festival and concert attendees in Colorado: characterizing enhancement and adverse reactions using mixed methods.

BACKGROUND: Most studies examining the simultaneous use of cannabis with other drugs have focused on cannabis and alcohol, with fewer studies examining simultaneous use of cannabis with other drugs. The United States is currently experiencing an upward trend in psychedelic use and there is an increasing need to characterize cannabis and psychedelic drug interactions to best inform public health recommendations. MATERIALS AND METHODS: A mixed methods field study design was used to survey participants (N = 128) on their lifetime co-use of cannabis with other drugs. Participants who reported lifetime co-use of cannabis and psychedelics (N = 63) were then asked open-ended questions about their most recent simultaneous co-use experience (i.e., how cannabis enhanced their psychedelic experience and whether they experienced any adverse reactions). We conducted a thematic analysis of responses describing how cannabis enhanced the psychedelic experience (N = 54). However, due to low response rate for participants reporting an adverse reaction (N = 7, 11.1%), responses to this question were not analyzed thematically and are instead presented individually. RESULTS: Themes included tension reduction and balancing of drug effects (N = 27, 50%), enhancement to psychological processes (N = 11, 20.4%), intensified psychedelic drug effects (N = 12, 22.2%), enhanced psychedelic come-down experience (N = 8, 14.8%), and overall ambiguous enhancement (N = 7, 13%). Among participants reporting an adverse reaction, individual responses included increased anxiety and intensity of the experience, decreased sociability, increased negative affect, sleepiness, disassociation, and confusion. CONCLUSION: Additional research is warranted to better characterize cannabis and psychedelic drug interactions to best inform public health recommendations.

Analytical and behavioral characterization of 1-hexanoyl-LSD (1H-LSD).

The development of lysergic acid diethylamide (LSD) derivatives and analogs continues to inform the design of novel receptor probes and potentially new medicines. On the other hand, a number of newly developed LSD derivatives have also emerged as recreational drugs, leading to reports of their detection in some countries. One position in the ergoline scaffold of LSD that is frequently targeted is the N1-position; numerous N1-alkylcarbonyl LSD derivatives have been reported where the acyl chain is attached to the indole nitrogen, for example, in the form of linear n-alkane substituents, which represent higher homologs of the prototypical 1-acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52). In this study, 1-hexanoyl-LSD (1H-LSD, SYN-L-027), a novel N1-acyl LSD derivative, was characterized analytically using standard techniques, followed by evaluation of its in vivo behavioral effects using the mouse head-twitch response (HTR) assay in C57BL/6J mice. 1H-LSD induced the HTR, with a median effective dose (ED50) of 192.4 µg/kg (equivalent to 387 nmol/kg), making it roughly equipotent to ALD-52 when tested previously under similar conditions. Similar to other N1-acylated analogs, 1H-LSD is anticipated to by hydrolyzed to LSD in vivo and acts as a prodrug. It is currently unknown whether 1H-LSD has appeared as on the research chemical market or is being used recreationally.

Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin's acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression. METHODS: Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures. DISCUSSION: This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin's antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

Potential Differences in Psychedelic Actions Based on Biological Sex.

The resurgence of interest in psychedelics as treatments for psychiatric disorders necessitates a better understanding of potential sex differences in response to these substances. Sex as a biological variable (SABV) has been historically neglected in medical research, posing limits to our understanding of treatment efficacy. Human studies have provided insights into the efficacy of psychedelics across various diagnoses and aspects of cognition, yet sex-specific effects remain unclear, making it difficult to draw strong conclusions about sex-dependent differences in response to psychedelic treatments. Compounding this further, animal studies used to understand biological mechanisms of psychedelics predominantly use one sex and present mixed neurobiological and behavioral outcomes. Studies that do include both sexes often do not investigate sex differences further, which may hinder the translation of findings to the clinic. In reviewing sex differences in responses to psychedelics, we will highlight the direct interaction between estrogen (the most extensively studied steroid hormone) and the serotonin system (central to the mechanism of action of psychedelics), and the potential that estrogen-serotonin interactions may influence the efficacy of psychedelics in female participants. Estrogen influences serotonin neurotransmission by affecting its synthesis and release, as well as modulating the sensitivity and responsiveness of serotonin receptor subtypes in the brain. This could potentially influence the efficacy of psychedelics in females by modifying their therapeutic efficacy across menstrual cycles and developmental stages. Investigating this interaction in the context of psychedelic research could aid in the advancement of therapeutic outcomes, especially for conditions with sex-specific prevalence.

Lysergic acid diethylamide induces behavioral changes in Caenorhabditis elegans.

Lysergic acid diethylamide (LSD) is a synthetic psychedelic compound with potential therapeutic value for psychiatric disorders. This study aims to establish Caenorhabditis elegans as an in vivo model for examining LSD's effects on locomotor behavior. Our results demonstrate that LSD is absorbed by C. elegans and that the acute treatment reduces animal speed, similar to the role of endogenous serotonin. This response is mediated in part by the serotonergic receptors SER-1 and SER-4. Our findings highlight the potential of this nematode as a new experimental model in psychedelic research.

The rising use of cognitive enhancement drugs and predictors of use during COVID-19: findings from a cross-sectional survey of students and university staff in the UK.

Background: The use of psychoactive substances to increase cognitive performance while studying has been termed 'pharmacological cognitive enhancement' (PCE). In previous years, several large-scale national surveys have focused on their use by students at university, including drug types, prevalence rates, and predictive factors. The recent coronavirus pandemic brought about widespread structural changes for UK universities, as students were forced to adapt to home-based learning and in many cases reduced academic support. No study has yet focused primarily on the impact of pandemic social restrictions on PCE in students and academic staff, and whether personality and demographic factors reveal user profiles that predict use during the pandemic period. Method: A convenience sample of 736 UK students and staff aged 18-54 (M = 22.2, SD = 5.2) completed a cross-sectional survey assessing PCE prevalence rates, polydrug use, perceived effects, academic self-efficacy and personality during the first year of social restrictions (March 2020 - February 2021) compared with the previous year (March 2019 - February 2020). Results: There was a significant self-reported rise in the use of all drug types (all ps < 0.001) during social restrictions, particularly with Modafinil (+42%), nutraceuticals (+30.2%) and microdose LSD (+22.2%). Respondents also indicated stronger PCE effects for all substances, except alcohol, in comparison to the previous year. Polydrug use with modafinil and other prescription stimulants increased the most during social restrictions. Personality factors and gender identity reliably predicted PCE use and lower agreeableness was often the strongest predictor, followed by identifying as male and lower conscientiousness. Academic self-efficacy and student/academic staff status were not consistent predictors. Conclusion: This is the first survey of UK students to investigate PCE during coronavirus social restrictions and to assess predictive factors. Findings reveal a rise in PCE use and polydrug use which we suggest is because of increased pressures on students created by the lockdown and reduced access to university resources.

AA, Bill Wilson, Carl Jung and LSD.

Alcoholics Anonymous (AA) is an established resource for people suffering from alcohol use disorder (AUD). However, Bill Wilson, the co-founder of AA, in his second letter to Jung referred to its low success rate. One evidence-based alternative, dating back to the 1950s, is the clinical use of lysergic acid diethylamide (LSD) for treating AUD. Bill Wilson was a strong advocate of using LSD as a preparation for alcoholics who had difficulty grasping the spiritual aspect of the 12-step programme. Bill Wilson wrote a "secret" four-page letter to Carl Jung detailing his own use of LSD and the success two psychiatrists in Canada had in treating alcoholics and asked for his advice on using LSD to help alcoholics. Aniela Jaffé, a Jungian analyst and co-worker of Jung, replied to Wilson on May 29, 1961, "… as soon as Dr. Jung feels better and has enough strength to begin again his mail, I will show it to him." Jung died a week later. This article quotes Jung's previous hostile opinions on psychedelics and asks: Just as Jung overcame his negative views on groups when giving "complete instructions" on extending the 12-step programme of AA to "general neurotics", might he similarly have changed his mind when he saw the documented success of using LSD with recalcitrant alcoholics?

Alcooliques Anonymes (A.A.) est une ressource reconnue pour les personnes souffrant du Trouble de l'Usage de l'Alcool (TUA). Bill Wilson, co­fondateur des AA, dans sa deuxième lettre à Jung, a fait référence à son faible taux de réussite. Une alternative fondée sur des preuves, et qui remonte aux années 1950, est l'utilisation médicale de l'acide lysergique diéthylamide (LSD) pour le traitement du TUA. Bill Wilson a fortement préconisé l'utilisation du LSD pour la préparation des alcooliques qui avaient des difficultés à saisir l'aspect spirituel du programme en douze étapes. Bill Wilson écrivit à Carl Jung une lettre de quatre pages, « secrète ¼, exposant en détails sa propre utilisation du LSD et le succès de deux psychiatres canadiens dans le traitement de personnes alcooliques avec le LSD. Il demandait conseil à Jung sur l'utilisation du LSD pour aider les alcooliques. Aniela Jaffé, une analyste jungienne et collaboratrice de Jung répondit à Wilson le 29 mai 1961 : « … dès que le Dr Jung se sentira mieux et aura suffisamment de force pour recommencer à s'occuper de son courrier, je lui montrerai. ¼ Jung est mort une semaine plus tard. Cet article cite les opinions antérieures négatives de Jung concernant les drogues psychédéliques et pose la question suivante: tout comme Jung avait dépassé ses perspectives négatives sur les groupes en donnant des « instructions complète ¼ sur l'extension du programme en douze étapes pour les « névrosés de base ¼, aurait­il de la même manière changé d'avis s'il avait vu les résultats probants de l'utilisation du LSD avec les alcooliques récalcitrants?

Alcohólicos Anónimos (A.A.) es un recurso establecido para las personas que padecen Trastorno por Consumo de Alcohol (AUD). Sin embargo, Bill Wilson, cofundador de AA, en su segunda carta a Jung se refirió a su baja tasa de éxito. Una alternativa basada en la evidencia, que se remonta a la década de 1950, es el uso clínico de la dietilamida del ácido lisérgico (LSD) para tratar el AUD. Bill Wilson era un firme defensor del uso del LSD como preparación para los alcohólicos que tenían dificultades para captar el aspecto espiritual del programa de 12 pasos. Bill Wilson escribió una carta "secreta" de cuatro páginas a Carl Jung en la que detallaba su propio uso del LSD y el éxito que habían tenido dos psiquiatras en Canadá en el tratamiento de alcohólicos con LSD y le pedía consejo a Jung sobre el uso del LSD para ayudar a los alcohólicos. Aniela Jaffé, analista Junguiana y compañera de trabajo de Jung, respondió a Wilson el 29 de mayo de 1961: "…tan pronto como el Dr. Jung se sienta mejor y tenga fuerzas suficientes para mirar de nuevo su correo, se lo mostraré". Jung murió una semana después. Este artículo cita las anteriores opiniones hostiles de Jung sobre los psicodélicos y pregunta: Del mismo modo que Jung superó sus opiniones negativas sobre los grupos al dar "instrucciones completas" sobre la extensión del programa de 12 pasos de A.A. a los "neuróticos en general", ¿podría haber cambiado de opinión de forma similar cuando vio el éxito documentado del uso del LSD con alcohólicos recalcitrantes?

From chaos to kaleidoscope: Exploring factors in psychedelic self-treatment for mental health conditions.

INTRODUCTION: This study explores how individuals self-treat psychiatric conditions with psychedelics outside medical guidance bridging the gap in understanding unregulated therapeutic use. AIMS: The primary objective was to extract specific factors underlying the effects of psychedelics, exploring their relationship with the need for medication, particularly for mental health conditions like depression and anxiety. Additionally, we aimed to understand how the likelihood of being prescribed pharmacological medication varies based on mental health diagnoses and demographic factors. METHODS: This research utilised the Global Drug Survey 2020, an annual online survey focused on substance use patterns and demographics, incorporating modules addressing mental health and psychedelic use. The study employed Exploratory Factor Analysis to discern latent factors underlying the self-reported effects of psychedelics. Bivariable and multivariable logistic regressions were conducted to investigate the association between identified factors and the likelihood of current prescribed medication usage. RESULTS: In all, 2552 respondents reported using psychedelics for self-treatment of mental health conditions. Three significant factors were identified: Improved Mental Health, Improved Self-Awareness and Neuro-Sensory Changes. The majority of the sample reported a history of depression (80%) or anxiety (65.6%), with a significant association observed between reported factors of psychedelics' effects and current medication usage for mental health, especially notable in cases of depression or comorbid depression and anxiety. CONCLUSIONS: Perceived symptom improvement following psychedelic self-treatment may reduce the need for medically supervised pharmacological interventions. These findings highlight the potential of psychedelics to positively influence mental health and self-awareness, paving the way for further research into their therapeutic application.

Ethnoracial inclusion in clinical trials of psychedelics: a systematic review.

Background: Prior data indicate limited ethnoracial diversity in studies testing psychedelic-assisted treatments. Regulatory approval for psychedelic treatments may be imminent given growing evidence for safety and efficacy in a variety of psychiatric conditions. Data on racial and ethnic inclusion rates in clinical psychedelic studies since 2018 have not been systematically reported to date. With the publication of multiple new studies in the field, an update to existing ethnoracial inclusion data is needed to inform the state of the science and future directions for research. Methods: Systematic review of Pubmed/MEDLINE, EMBASE, and Web of Science for studies of any design testing a psychedelic treatment for a psychiatric or substance use disorder published between January 1, 1994 and May 24, 2024. Search terms related to serotonergic psychedelics and MDMA, psychedelic therapies, psychiatric disorders, and substance use disorders were used. References of reviewed studies were screened for inclusion. Studies were rated for quality on a five-point scale ranging from 1 (most rigorous, i.e., properly powered randomized clinical trial) to 5 (least rigorous, e.g., case reports). Separate analyses were performed for two groups of studies, one involving all included studies meeting search criteria, and the other involving only studies from the USA. Rates of inclusion of different ethnoracial groups were calculated between studies published before and after December 31, 2017. Additionally, the proportion of White vs. non-White participants was compared between studies published before and after December 31, 2017. Finally, a nonparametric Mann-Whitney U test was used to compare the relative quality ratings of studies published before and after December 31, 2017. Findings: 787 studies were screened, and 39 studies were included. This included 16 studies (n = 282) from a prior review published in 2018 with an additional 23 studies (n = 1111) that were published after 2017, consisting of 14 randomized controlled studies, 8 open-label studies, and 1 placebo-controlled, within-subject, fixed-order study. In all included studies published after 2017, 85.6% of participants identified as non-Hispanic White, 3.1% as Black, 6.8% as Latinx/Hispanic, 3.6% as Asian, 1.2% as Indigenous, 3.5% as mixed race, 1.4% as other, Pooled data from all included studies (n = 1393) found 85.0% of participants identified as non-Hispanic White, 2.9% as Black, 5.9% as Latinx/Hispanic, 3.2% as Asian, 1.9% as Indigenous, 3.7% as mixed race, 1.4% as other. In studies conducted in the USA (n = 1074), 908 (84.5%) of participants identified as White, 36 (3.4%) as Black, 80 (7.4%) as Latinx/Hispanic, 43 (4.0%) as Asian, 15 (1.4%) as Indigenous, 40 (3.7%) as Mixed, and 9 (0.8%) as Other. Differences in inclusion rates were found when comparing studies published before and after December 31, 2017 for all included studies and all studies conducted in the USA. The proportion of White to non-White participants was found to have decreased in studies conducted in the USA over the same period, but not for all included studies. Interpretation: Underrepresentation of ethnoracial minoritized populations persists in studies examining psychedelic therapies, despite growing calls for diversity. Non-Hispanic White participants remain an over-represented majority by a large margin, though, there were greater proportions of ethnic minoritized populations included in studies since 2018, particularly in studies conducted in the USA. This indicates progress towards equity in psychedelic research, though much work is needed to inform the safety and efficacy of psychedelic treatments in the general population. Funding: There was no funding source for this study.

Pharmacological Properties of Psychedelics with a Special Focus on Potential Harms.

Psychedelics are a group of substances within the heterogeneous class of hallucinogenic drugs. Via binding to the serotonin (5-HT) 2A receptor, psychedelics exert profound alterations in various mental domains, including sensation, cognition, emotions, and self-perception. Psychedelics comprise phenethylamines (e.g., mescaline), tryptamines (e.g., psilocybin), and ergolines (e.g., LSD). These drugs have been used recreationally for decades but have also regained attention as potential treatments for various psychiatric as well as neurological illnesses. While psychedelics are generally considered to be relatively safe from a physiological standpoint, especially when compared to other recreational drugs, they are not without risks. The main safety concerns are lasting psychological adverse reactions such as persisting anxiety, dissociation, or flashbacks.This chapter provides a comprehensive overview of the pharmacology of classic psychedelics, including their origins, psychological and autonomic effects, interactions, and potential risks and side effects. Furthermore, the origin, dosing, and consumption methods are discussed. It differentiates psychedelics from other psychoactive drugs, such as MDMA and ketamine, and elaborates on their distinct receptor profiles. Overall, this chapter provides an overview of the pharmacological underpinnings necessary for understanding the harms caused by psychedelic drugs.

Set and Setting for Psychedelic Harm Reduction.

Set and setting is a fundamental concept in the field of psychedelic studies, denoting the crucial importance of context to determining the character and quality of experiences with psychedelics. This paper suggests a framework for thinking of set and setting and its relevance for psychedelic harm reduction. It discusses how "set," the diverse factors related to an individual's mindset, and "setting," the diverse environmental dimensions, influence the psychedelic experience and its outcomes, and the relevance to the field of harm reduction. It additionally provides an overview of four basic modalities of set and setting, the therapeutic, the clinical trial, the ritualistic, and the recreational, examining the differences in set and setting between each and the other according to several key parameters, the implications of such differences, and the ways in which harm reduction strategies informed by the principles of set and setting can be integrated to increase safety and benefits in each case. The integration of set and setting principles into public health policies, alongside education on their significance, could further the efficacy of harm reduction programs in the field of psychedelics.

Neurobiological Correlates of Psychedelic Experiences and Psychedelic-Associated Adverse Effects.

This chapter offers a comprehensive overview of our current understanding of the neural mechanisms underlying the effects of psychedelic drugs, with a primary focus on human neuroimaging studies. Whenever possible, we explore the neurobiological mechanisms that may underly acute and subacute adverse effects and describe hypotheses on how these results may inform on the pathophysiology of psychiatric illnesses. We delve into the general effects of psychedelics on EEG, fMRI, and PET measurements, drawing insights from experiments that have assessed their acute biological mechanisms. Additionally, we review the relatively limited literature exploring pre- to postdrug changes. Throughout this chapter, we explore the prevailing models of psychedelic drug actions, including the Cortico-Striato-Thalamo-Cortical (CSTC) feedback loop model, the entropic brain hypothesis, the REBUS principle (an extension of predictive brain theories), and the claustrum hypothesis. Finally, we delve into the neural correlates of distinct features of the psychedelic experience, encompassing visual effects, social and emotional impacts, and the phenomenon of ego dissolution. We offer speculations on how our current understanding of acute drug effects might relate to the rarely occurring long-term adverse effects. It is important to note that due to the scarcity of data, these speculations remain tentative.

Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy.

Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving compassionate access since 2020, there has been little examination of these 'real-world' patients. We conducted a prospective longitudinal survey which focused on Canadians who were granted Section 56 exemptions for legal psilocybin-assisted psychotherapy. Surveys assessing various symptom dimensions were conducted at baseline, two weeks following the session (endpoint), and optionally one day post-session. Participant characteristics were examined using descriptive statistics, and paired sample t-tests were used to quantify changes from baseline to the two-week post-treatment endpoint. Eight participants with Section 56 exemptions (four females, Mage = 52.3 years), all with cancer diagnoses, fully completed baseline and endpoint surveys. Significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being were observed. Attitudes towards death, medical assistance in dying, and desire for hastened death remained unchanged. While most participants found the psilocybin sessions highly meaningful, if challenging, one reported a substantial decrease in well-being due to the experience. These preliminary data are amongst the first to suggest that psilocybin-assisted psychotherapy can produce psychiatric benefits in real-world patients akin to those observed in clinical trials. Limited enrollment and individual reports of negative experiences indicate the need for formal real-world evaluation programs to surveil the ongoing expansion of legal access to psychedelics.