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.

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.

Rapid effects of tryptamine psychedelics on perceptual distortions and early visual cortical population receptive fields.

N, N-dimethyltryptamine (DMT) is a psychedelic tryptamine acting on 5-HT2A serotonin receptors, which is associated with intense visual hallucinatory phenomena and perceptual changes such as distortions in visual space. The neural underpinnings of these effects remain unknown. We hypothesised that changes in population receptive field (pRF) properties in the primary visual cortex (V1) might underlie visual perceptual experience. We tested this hypothesis using magnetic resonance imaging (MRI) in a within-subject design. We used a technique called pRF mapping, which measures neural population visual response properties and retinotopic maps in early visual areas. We show that in the presence of visual effects, as documented by the Hallucinogen Rating Scale (HRS), the mean pRF sizes in V1 significantly increase in the peripheral visual field for active condition (inhaled DMT) compared to the control. Eye and head movement differences were absent across conditions. This evidence for short-term effects of DMT in pRF may explain perceptual distortions induced by psychedelics such as field blurring, tunnel vision (peripheral vision becoming blurred while central vision remains sharp) and the enlargement of nearby visual space, particularly at the visual locations surrounding the fovea. Our findings are also consistent with a mechanistic framework whereby gain control of ongoing and evoked activity in the visual cortex is controlled by activation of 5-HT2A receptors.

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.

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.

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.

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.

Attitudes of European psychiatrists on psychedelics: a qualitative study.

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 from 8 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 sub-themes, 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.

Crafting effective regulatory policies for psychedelics: What can be learned from the case of cannabis?

The turn of the century brought a resurgence of interest in psychedelics as a treatment for addiction and other psychiatric conditions, accompanied by extensive positive media attention and private equity investment. Government regulatory bodies in Australia, Israel, Canada and the United States now permit use of psychedelics for medical purposes. In the United States, citizen action and corporate financing have led to petitions and ballot initiatives to legalize psilocybin and other psychedelics for medical and recreational use. Given this momentum, policymakers must grapple with important questions that define whether and how psychedelics are made available to the public, as well as how companies produce and promote them. The current push to broaden the production, sale, and use of psychedelics bears many parallels to the movement to legalize cannabis in the United States and other nations-most notably, the use of poorly-evidenced therapeutic claims to create a de facto recreational market via the health care system. Experience with cannabis highlights the value of debating the question of legalization for nonmedical use as such rather than misrepresenting it as a medical issue. The lessons of cannabis policy also suggest a need to challenge hyping of psychedelic research findings; to promote rigorous clinical research on dosing and potency; to minimize the influence of for-profit industry in shaping policies to their economic advantage; and to coordinate federal, state, and local governments to regulate the manufacture, sale and distribution of psychedelic drugs (regardless of whether they are legalized for medical and/or recreational use).

Attitudes toward psychedelics and psychedelic-assisted therapy among potential mental health service users and the general population in Australia.

OBJECTIVE: Despite rapid advances in psychedelic sciences and the increasing number of countries legalizing psychedelics for the treatment of mental illnesses, the attitudes, knowledge and readiness of both mental health consumers and the general population remain largely unknown. METHODS: A cross-sectional survey was conducted among Australians, targeting individuals with mental illness as potential mental health service users. A sub-sample of individuals free of mental illness was also surveyed to assess attitudes in the general population. Participants completed the Attitudes on Psychedelics Questionnaire, the Basic Knowledge of Psychedelics Test and a questionnaire by Corrigan et al. to capture attitudes toward psychedelic therapy by mental health service users. RESULTS: Of the 502 respondents, 64.5% self-identified as having a mental illness. A significant proportion favored legalizing psychedelics for medical use (43%) and were open to their use (52.4%), yet fewer viewed their effects positively (24%) or considered them safe (33%). Most participants reported to be psychedelic naive (61%). Participants with mental illness had significantly more experience with psychedelics than participant free of mental illness (44.1% vs 29.7%). Experience, perceived knowledge and actual knowledge significantly predicted attitudes toward legalization, effects, risks and openness to psychedelics. CONCLUSIONS: While a large proportion of Australians are in favor of legalizing psychedelics for medical purposes, concerns about safety remain. People with self-identified mental illness, those with previous recreational psychedelic experience and those with greater knowledge of psychedelics were more likely to have positive attitudes toward psychedelics and psychedelic-assisted therapy.

Psilocybin and 4-Bromo-2,5-Dimethoxyphenethylamine (2C-B) at Encoding Distort Episodic Familiarity.

BACKGROUND: As research on psychedelics (hallucinogenic 5-HT2A agonists) progresses, it is important to delineate the reliability of supposedly unique effects across this drug class. One such effect is how psychedelics impair the formation (i.e., encoding) of hippocampal-dependent recollections (retrieval of specific details) while potentially enhancing the encoding of cortical-dependent familiarity (a feeling of knowing that a stimulus has been previously experienced). METHODS: In a double-blind, placebo-controlled, within-subjects study (N = 20), we tested the acute effects of two distinct psychedelics, psilocybin and 4-bromo-2,5-dimethoxyphenethylamine (2C-B), on the encoding of emotional episodic memories. During acute drug effects, participants viewed negative, neutral, and positive pictures. The following day (while sober), participants completed two separate memory tests for these pictures. RESULTS: Using computational models of memory confidence, we found trends for psilocybin and 2C-B at encoding to impair estimates of recollection that were supported by other measures/analyses. Surprisingly, psilocybin and 2C-B at encoding impaired estimates of familiarity, but these impairments were likely due to a misattribution of heightened familiarity, as both drugs at encoding selectively increased familiarity-based false alarms, especially for negative and positive stimuli. Psilocybin and 2C-B at encoding also tended to impair estimates of metamemory (understanding one's own memory) for negative and neutral memories but enhance estimates of metamemory for positive memories, though these effects were less reliable in additional analyses. CONCLUSIONS: Despite differences in their chemistry, pharmacology, and subjective effects, both psilocybin and 2C-B distort episodic familiarity, alluding to a common neurocognitive mechanism across psychedelics that may drive other phenomena.

The Global Psychedelic Survey: Consumer characteristics, patterns of use, and access in primarily anglophone regions around the world.

OBJECTIVES: Despite advancements in policies governing psychedelic substances globally, our understanding of real-world psychedelic use and its variations across international jurisdictions remains limited. We implemented the Global Psychedelic Survey (GPS) to capture information about psychedelic consumer characteristics, access, and usage patterns around the world. METHODS: The GPS was administered online in Spring 2023 to English-speaking adults (≥21 years) who use(d) psychedelics. We categorized survey responses into major catchment regions (Canada/US, Europe/UK, Australia/NZ, All Other). We used descriptive and bivariable statistics to characterize consumers' socio-demographic characteristics, psychedelic access sources, and usage patterns. We examined regional differences in psychedelic use patterns using multinomial logistic regression. RESULTS: We analyzed 6379 responses from 85 countries including Canada/US (n = 4434), Europe/UK (n = 771), Australia/NZ (n = 864), and Other (n = 310). Psilocybin, LSD, and MDMA were the most used psychedelics and personal growth was the most common use motive across all catchments. There were significant regional differences in psychedelic use patterns, including types of psychedelics used (e.g., less ibogaine use in Europe/UK and Australia/NZ relative to Canada/US), frequency of use (e.g., lower frequency use in Australia/NZ relative to Canada/US), motivations for use (e.g., less therapeutic use in Europe/UK and Other relative to Canada/US), and types of dosing regimens (e.g., more "micro"-dosing in Canada/US). DISCUSSION: In this large sample of adult psychedelic consumers from regions around the world, infrequent psychedelic use centered around life enhancement was common. Respondents indicated preference for legal access via quality-controlled sources. Jurisdictional differences in access and usage patterns likely reflect region-specific regulations and traditional practices. Further research should explore opportunities to increase representation of non-White respondents in psychedelic research via translation of studies into several languages and incorporation of culturally reflective, community-based study development.

Unlocking the healing power of psilocybin: an overview of the role of psilocybin therapy in major depressive disorder, obsessive-compulsive disorder and substance use disorder.

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.

Do classic psychedelics increase the risk of seizures? A scoping review.

Seizures are a concerning adverse event frequently associated with the use of psychedelics, and hence, studies involving these substances tend to exclude patients with past history of epilepsy. This is especially relevant because epileptic seizures are markedly increased in the population suffering from mental disorders, and psychedelic assisted therapy is being researched as a promising treatment for several of them. To determine the extent of the current literature on the relationship between classic psychedelics and seizures, a scoping review was performed using the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). The search was conducted in PubMed, Web of Science, Google scholar, LILACS and Scielo, and both animal and human models were included. A total of 16 publications on humans, and 11 on animals, were found. The results are heterogeneous, but globally suggest that psychedelics may not increase the risk of seizures in healthy individuals or animals in the absence of other drugs. However, concomitant use of other substances or drugs, such as kambo or lithium, could increase the risk of seizures. Additionally, these conclusions are drawn from data lacking sufficient external validity, so they should be interpreted with caution. Future paths for research and a summary on possible neurobiological underpinnings that might clarify the relationship between classical psychedelics and seizures are also provided.

Coming back together: a qualitative survey study of coping and support strategies used by people to cope with extended difficulties after the use of psychedelic drugs.

Introduction: A growing body of literature is investigating the difficulties that some individuals encounter after psychedelic experiences. Existing research has explored the nature and predictors of these difficulties; however, a research gap exists in understanding how individuals endeavour to cope with such difficulties. Methods: The current study collected data from an international cohort of 608 participants who reported experiencing difficulties that persisted for at least one day after a psychedelic experience. They provided written data on how they used coping strategies to alleviate these difficulties. The qualitative analysis of the written data on coping was conducted using Structured Tabular Thematic Analysis. Results: A wide range of individual and social coping strategies were employed that were found helpful. The most common individual strategies were meditation and prayer, followed by self-educational activities such as reading and journaling. The most prevalent forms of social coping involved seeking support from friends or family members, followed by obtaining assistance from a therapist or coach. Features of social coping that were reported to be helpful included feeling heard/accepted, a non-judgemental attitude and sharing similar experiences. Discussion: Our findings hold potential for informing the design of therapeutic interventions and educational resources aimed at enhancing positive outcomes for those experiencing extended difficulties after psychedelic use.

Development of the Japanese version of the Challenging Experience Questionnaire.

INTRODUCTION: The therapeutic potential of psychedelics for various mental disorders has gained significant interest. Previous studies have highlighted that psychedelics induce psychoactive effects, including challenging aspects of experiences. These experiences are assessed using the Challenging Experience Questionnaire (CEQ), yet its Japanese version has been unavailable. This study aimed to create a Japanese version of the CEQ. METHODS: We followed the "Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes (PRO) Measures: Report of the ISPOR Task Force for Translation and Cultural Adaptation." Initially, two Japanese psychiatrists independently conducted the forward translations. These were then reconciled into a single version, which was back-translated into English. The original authors reviewed this back-translation for accuracy, leading to revisions through continuous dialogue until the original authors approved the final version. RESULTS: The final, approved back-translated version of the CEQ is presented in the figure. CONCLUSIONS: This study developed a Japanese version of the CEQ, enabling the assessment of challenging experiences during psychedelic-assisted therapy for Japanese speakers. Further studies are needed to assess the reliability and validity of this newly translated version.

Psychedelics and disorders of consciousness: the current landscape and the path forward.

Modern medicine has been shaken by the surge of psychedelic science that proposes a new approach to mitigate mental disorders, such as depression and post-traumatic stress disorder. Clinical trials to investigate whether psychedelic substances can treat psychiatric conditions are now underway, yet less discussion gravitates around their use in neurological disorders due to brain injury. One suggested implementation of brain-complexity enhancing psychedelics is to treat people with post-comatose disorders of consciousness (DoC). In this article, we discuss the rationale of this endeavour, examining possible outcomes of such experiments by postulating the existence of an optimal level of complexity. We consider the possible counterintuitive effects of both psychedelics and DoC on the functional connectivity of the default mode network and its possible impact on selfhood. We also elaborate on the role of computational modelling in providing complementary information to experimental studies, both contributing to our understanding of the treatment mechanisms and providing a path towards personalized medicine. Finally, we update the discourse surrounding the ethical considerations, encompassing clinical and scientific values.

Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics.

Mounting evidence points towards a crucial role of the kynurenine pathway (KP) in the altered gut-brain axis (GBA) balance in severe mental illness (SMI, namely depression, bipolar disorder, and schizophrenia) and cardiometabolic comorbidities. Preliminary evidence shows that serotonergic psychedelics and their analogues may hold therapeutic potential in addressing the altered KP in the dysregulated GBA in SMI and comorbidities. In fact, aside from their effects on mood, psychedelics elicit therapeutic improvement in preclinical models of obesity, metabolic syndrome, and vascular inflammation, which are highly comorbid with SMI. Here, we review the literature on the therapeutic modulation of the KP in the dysregulated GBA in SMI and comorbidities, and the potential application of psychedelics to address the altered KP in the brain and systemic dysfunction underlying SMI and comorbidities. Psychedelics might therapeutically modulate the KP in the altered GBA in SMI and comorbidities either directly, via altering the metabolic pathway by influencing the rate-limiting enzymes of the KP and affecting the levels of available tryptophan, or indirectly, by affecting the gut microbiome, gut metabolome, metabolism, and the immune system. Despite promising preliminary evidence, the mechanisms and outcomes of the KP modulation with psychedelics in SMI and systemic comorbidities remain largely unknown and require further investigation. Several concerns are discussed surrounding the potential side effects of this approach in specific cohorts of individuals with SMI and systemic comorbidities.

Stutterers' experiences on classic psychedelics: A preliminary self-report study.

Stuttering poses challenges to social, occupational, and educational aspects of life. Traditional behavioral therapies can be helpful but effects are often limited. Pharmaceutical treatments have been explored but there are no FDA-approved treatments for stuttering. Interest has grown in the potential use of classic psychedelics, including psilocybin and LSD, which have shown effectiveness in treating disorders with similar symptoms (e.g., anxiety, depression, PTSD). The potential effects of psychedelics on stuttering have not been explored. We conducted a preliminary investigation of self-identified stutterers who report their experiences taking classic psychedelics on the online messaging forum, Reddit. We qualitatively analyzed 114 publicly available posts, extracting meaningful units and assigning descriptor codes inductively. We then deductively organized responses into an established framework of psychedelics which includes behavioral, emotional, cognitive, belief-based, and social effects. These effects were subsequently grouped under organizing themes (positive, negative, neutral). Descriptive statistics revealed that the majority of users (74.0%) reported positive overall short-term effects particularly related to behavioral and emotional change (e.g., reduced stuttering and anxiety), but negative (9.6%), mixed (positive and negative; 4.8%), and neutral overall experiences (11.6%) were also reported. The results support the possibility that psychedelics may impact stuttering, but caution must be applied in their interpretation given the entirely uncontrolled research setting and potential adverse health effects of psychedelics as reported elsewhere. While these results do not encourage the use of psychedelics by stutterers, they suggest that future work could examine the impact of psychedelics on stuttering under supervised and in clinically controlled settings.