Our aim is to understand how those who use peyote in a naturalistic setting discuss it changed their lives and to what they attribute this change. To do this, we draw on data from a photo-ethnography of people who attended peyote ceremonies in rural Northcentral Alabama. Broadly, we found that participants discussed four core areas of change: reduced drug and alcohol misuse, new perspectives on life, improved mental health, and improved physical health. The duration of the experienced change varied for each type of change. Participants attributed change to improved ability to endure challenges, rewiring of the brain, and connecting with spiritual selves. Findings give insights into how people experience and make sense of change from peyote. In addition, the findings suggest specific areas of research for those interested in clinical and therapeutic settings relating to peyote in particular, and psychedelics in general.

INTRODUCTION:Methamphetamine use disorder (MeUD) is a debilitating condition with no FDA-approved pharmacotherapies that has been associated with poor neurological, psychiatric and cardiovascular outcomes, particularly among low-income populations. The use of methamphetamine also increases risks for sexually transmitted infections (STIs) by reducing behavioural inhibitions while enhancing sexual libido, disproportionately affecting sexual and gender minorities. The overlap of MeUD with HIV risks and psychological trauma underscores the need for innovative, accessible and culturally responsive therapies. Ketamine-assisted psychotherapy (KAP), which has shown promise for treatment-resistant depression and other substance use disorders, has yet to be explored for MeUD. The Ketamine-Assisted Recovery (KARE) trial seeks to address this gap. METHODS AND ANALYSIS:KARE is an open-label pilot study enrolling N=12-24 Medicaid-insured or Medicare-insured adults with moderate-to-severe MeUD and HIV risk factors. Participants will undergo three office-based intramuscular ketamine (0.50-0.75 mg/kg) sessions in combination with seven sessions of motivational enhancement therapy over 5 weeks. Recruitment efforts target community-based organisations, outpatient clinics offering HIV and STI testing/treatment, and substance use disorder treatment programmes. Feasibility, acceptability and tolerability will be assessed via recruitment and a priori retention benchmarks, surveys and semistructured interviews exploring participants' perceptions of KAP and ketamine's misuse potential. Safety will be evaluated through systematic monitoring for adverse events and serial measurement of vital signs during dosing., craving, withdrawal, HIV risk behaviours and psychological distress, as well as psychological and cognitive flexibility as potential mechanisms of ketamine's effects, laying the groundwork for future randomised controlled trials. ETHICS AND DISSEMINATION:Ethics approval has been obtained from the University of California, San Francisco Institutional Review Board (24-41588) and the Research Advisory Panel of California (202422S). Results will be disseminated through national conferences, peer-reviewed publications and presentations to community-based stakeholders. TRIAL REGISTRATION NUMBER:NCT06538285.

Background Findings from contemporary clinical trials suggest that psychedelics are generally safe and may be effective in the treatment of various psychiatric disorders. However, less is known about the risks associated with psychedelic use outside of medically supervised contexts, particularly in populations that are typically excluded from participation in clinical trials. Methods Using a preregistered longitudinal observational research design with a purposive sample of US residents between 18 and 50 years old ( N =21,990), we investigated associations between self-reported naturalistic psychedelic use and psychotic and manic symptoms, with emphasis on those with psychiatric histories of schizophrenia or bipolar I disorder. Results The follow-up survey was completed by 12,345 participants (56% retention), with 505 participants reporting psychedelic use during the 2-month study period. In covariate-adjusted regression models, psychedelic use during the study period was associated with increases in the severity of psychotic and manic symptoms. However, such increases were only observed for those who reported psychedelic use in an illegal context. While increases in the severity of psychotic symptoms appeared to depend on the frequency of use and the intensity of challenging psychedelic experiences, increases in the severity of manic symptoms appeared to be moderated by a personal history of schizophrenia or bipolar I disorder and the subjective experience of insight during a psychedelic experience. Conclusions The findings suggest that naturalistic psychedelic use specifically in illegal contexts may lead to increases in the severity of psychotic and manic symptoms. Such increases may depend on the frequency of use, the acute subjective psychedelic experience, and psychiatric history.

Previous research has investigated associations between psychedelic experiences and meditation practice, but knowledge gaps remain. Using a longitudinal research design with a sample of US residents between 18 and 50 years old (N = 13,012), we investigated associations between psychedelic-related and meditation-related variables. The follow-up survey was completed by 7484 respondents, of whom 336 reported psychedelic use during the two-month study. In covariate-adjusted regression models, psychedelic use was associated with greater increases in the number of days of mindfulness and loving-kindness or compassion meditation practice in the past week, especially among those with no prior experience of psychedelics or meditation. Among those who reported psychedelic use, trait mindfulness and trait self-compassion at baseline were associated with less severe challenging psychedelic experiences, as well as lower odds of psychedelic-occasioned thoughts or attempts of self- or other-harm. However, among those who practiced meditation at baseline, psychedelic use was associated with greater increases in past-week frequency of loving-kindness or compassion meditation-related difficulties and impairments. Future research is warranted.

The concept of cultural appropriation has drawn increasing attention from academic disciplines and nonacademic circles. Yet, there is no consensus on what constitutes cultural appropriation nor whether it is harmful. The contested nature of the concept suggests that it is important to understand how people respond to such accusations. Indeed, understanding how people resist accusations of cultural appropriation (i.e., how they account for their actions) can provide insights into defining cultural appropriation and understanding its impact. Accordingly, we rely on data from an ethnography of people who attended peyote ceremonies (a sacred Native American practice) in a Southern U.S. state to understand how they account for accusations of cultural appropriation when they are presented. Findings suggest that participants delegitimized accusations in one of two ways: saying that cultural appropriation does not exist (e.g., peyote is for everyone) or that appropriation exists but they are not appropriators (e.g., they were respectful of the ceremonies). Regardless of which approach they used, participants drew on broader narratives that allowed them to maintain a positive identity while minimizing the potential stigma of being appropriators.

Objective This article outlines recommendations from 30 psychedelic researchers on how to create a better psychedelic safety net. Methods A survey of 30 psychedelic researchers asked them to identify key critical research gaps around psychedelic harm and safety. Results The critical research gaps identified by the authors included defining the main types of psychedelic harm, the predictors of those harms, and the most effective way to treat those harms. They also call for better support for those experiencing post‐psychedelic difficulties, including better online information, peer support groups, affordable therapy, and psychiatric consultation and medication. Finally, the authors call for better funding to create a psychedelic safety net, and suggest psychedelic philanthropists, investors and companies could commit 1% of their investment in psychedelics into supporting safety measures such as research and support services. Conclusions The authors identify several practical steps to create a better psychedelic safety net and call for more funding to psychedelic safety measures such as research and support services. Relevance to clinical practice The authors outline important gaps in our knowledge around the safety and risk profile of psychedelic medicines and identify practical steps forward for researchers and clinical practitioners to make this promising field safer.

Background: Psilocybin has been granted breakthrough therapy status in the United States, speeding its advancement from research to clinical care. Due to the controversial nature of psilocybin, psychiatrists may not be fully prepared to incorporate it into clinical practice. The current study aimed to evaluate the opinions toward psilocybin among practicing psychiatrists in Louisiana. Louisiana serves as a representative state, modeling other areas with limited exposure to psychedelic research.Methods: A 30-question survey was distributed via mail and digital newsletter to all registered Louisiana psychiatrists. The survey consisted of demographic questions and questions pertaining to how strongly respondents agreed or disagreed with statements about psilocybin and psychedelics on a five-point Likert scale. The statements aimed to assess knowledge and exposure to psilocybin including opinions on research and legalization, safety and addiction potential, medical use, and potential benefits and usages.Results: Forty-nine responses were recorded. Eighty-two percent of participants reported having "some knowledge" of psilocybin. Eighty-six percent believed psilocybin should be researched for medicinal value, and 71% would prescribe psilocybin if it were proven beneficial for their patient's illness. Fifty-seven percent believed it should be considered a first-line treatment for certain conditions, while 73% believed it should be used only after exhausting all other treatment modalities. The study had an overall 10.5% response rate, potentially limiting the generalizability of the findings.Conclusion: Louisiana psychiatrists in our sample appear open to integrating psilocybin into their practice if there is strong regulatory support. Psilocybin research is rapidly expanding and will soon reach Louisiana and other states with a limited history of psychedelic clinical research. These findings warrant the development of an educational program on psychedelics to arm psychiatrists and patients with the knowledge to make the most informed decisions.

Background:Prior research examining the associations between psychedelic use and general psychotic symptoms has yielded mixed findings. However, no studies have investigated the relationships between psychedelic use and specific psychotic symptoms, and whether these relationships might differ among those with liability to psychosis, namely those with a history of psychotic or bipolar disorders. Methods:Using cross-sectional survey data from a purposive sample (n = 548), we first regressed estimated lifetime psychedelic use occasions and personal and family history of psychotic or bipolar disorders on the Magical Ideation Scale, Referential Thinking Scale, Self-Evaluation of Negative Symptoms, and Continuum of Auditory Hallucinations-State Assessment, unadjusted and adjusted for a range of covariates. We then tested the interactions of estimated lifetime psychedelic use occasions with personal and family history of psychotic or bipolar disorders on these same measures, unadjusted and adjusted for the same set of covariates. Results:In unadjusted models, the estimated number of lifetime psychedelic use occasions was robustly associated with less referential thinking, whereas personal and family histories of psychotic and bipolar disorders were each associated with moderately or slightly greater scores on all measures. Covariate-adjusted regression models revealed that the estimated number of lifetime psychedelic use occasions was not associated with any of the measured psychotic symptoms. A personal history of psychotic disorders was associated with moderately greater magical ideation, referential thinking, and auditory hallucinations, whereas a family history of psychotic disorders was associated with slightly greater negative symptoms. Neither personal nor family history of bipolar disorder was associated with any psychotic symptoms. Finally, estimated lifetime psychedelic use occasions interacted only with a personal history of psychotic disorders on one measure, such that auditory hallucinations were less severe as psychedelic use occasions increased among those with a personal history of psychotic disorder; there was no relationship between psychedelic use and auditory hallucinations among those without a personal history of psychotic disorder. Conclusion:Naturalistic psychedelic use may not be associated with psychotic symptoms, even among those with a personal or family history of psychotic or bipolar disorders. Further work probing the risk-benefit profile for people typically excluded from clinical trials involving psychedelics is needed.

U.S. rural counties have been shown to demonstrate higher rates of tobacco use, however, there is limited understanding concerning protective factors that may decrease the likelihood of tobacco use in these settings. The increased presence of the sense that one's life is meaningful has been found to be associated with engagement in health behaviors, including refraining from tobacco use. However, comprehensive population-based assessments are required to examine the association between meaning in life and tobacco abstinence. This is especially pertinent among sub-populations that are underrepresented in research, including Black and White rural residents. The purpose of this study was to examine if increased meaning in life would be associated with current tobacco abstinence among residents of rural Alabama. A population-based in-person survey was administered to 268 adults representing all census tracts within a rural Alabama county. Participants were provided a comprehensive list of tobacco products with product photos and queried about use, including use within the previous 30 days. Meaning in life was measured using the 10-item Meaning in Life Questionnaire. Increased meaning in life was associated with a greater likelihood of current abstinence from tobacco products while controlling for multiple demographic variables including sex, age, race, and educational attainment. This study identified meaning in life as a potential protective factor against current tobacco use that may generalize beyond rural settings. This finding has relevant research and public health implications within rural settings, providing preliminary evidence that this understudied construct may play an important role in protecting rural residents from engagement in an addictive behavior. Further research is needed to elucidate mechanisms that may underlie the protective capacity of meaning in life to inform interventions to boost this construct.

While growing evidence suggests that psychedelic-assisted therapy may have antidepressant effects in certain populations, little is known about the effects of psychedelic use on depressive symptoms in non-clinical, naturalistic settings. This observational cohort study included a large sample of US residents (18-50 years old) and longitudinally evaluated the relationships between naturalistic psychedelic use and changes in depressive symptoms. 21,990 participants completed the T1 survey and 12,345 completed the T2 survey (56.1 % retention). In total, 505 participants (i.e., 4.1 % of T2 survey completers) reported psychedelic use during the study period. The covariate-adjusted models showed a modest association between psychedelic use during the study period and increases in depressive symptoms (β = 0.12, p = .019). When disaggregated by context of use, psychedelic use in a 'risk context' (e.g., negative mindset prior to psychedelic experience, no psychological support present during psychedelic experience) was associated with moderate increases in depressive symptoms relative to no psychedelic use (β = 0.30, p < .001) and psychedelic use not in a 'risk context' (β = 0.27, p = .004). Notably, psychedelic use in a 'risk context' was strongly associated with having a more challenging psychedelic experience (β = 0.59, p < .001), which in turn was associated with modest increases in depressive symptoms (β = 0.16, p = .007) and accounted for the association between psychedelic use in a 'risk context' and increases in depressive symptoms. In conclusion, the findings suggest that naturalistic psychedelic use may not be generally therapeutic and may result in worsening depressive symptoms under certain circumstances. Future epidemiological research should further investigate factors associated with worsening depressive symptoms following naturalistic psychedelic use.

BACKGROUND:Recent legislative initiatives in the United States have focused on the medical and legal status of psychedelics, prompting interest in understanding public perceptions of their risks. This study investigates rural-urban differences in the perception of LSD and cannabis risks using national survey data. METHODS:Data from the National Survey of Drug Use and Health (NSDUH) between 2015 and 2021 were analyzed. Logistic regression models were used to compare risk perceptions of LSD and cannabis between rural and urban respondents, adjusting for relevant factors. RESULTS:Rural residents were 1.2 to 1.4 times more likely to perceive using LSD once or twice as of great risk compared to urban residents during the survey period. However, the perception of monthly cannabis use as having great risk was slightly higher among rural residents only until 2019, with no significant differences observed in 2020 and 2021. CONCLUSION:The study highlights a significant rural-urban divide in the perception of LSD risk, which could impact policymaking on psychedelic therapies. Understanding these differences is crucial for developing effective and equitable policies regarding psychedelic substances and treatments.

Objective Methamphetamine use disorder, associated with significant morbidity and mortality, has limited effective treatments. Psychedelic-assisted psychotherapy shows promise, but data on its safety and efficacy in this population are limited. This exploratory study describes the demographic, substance use, and mental health characteristics of people who used methamphetamine and psychedelics and the context and outcomes of their psychedelic experiences. Methods A retrospective survey collected data on demographics, substance use patterns, mental health, and psychedelic use. Binomial logistic regression explored associations of post-psychedelic positive mood and social functioning ('increased'/'not increased') and substance use ('reduced'/'not reduced') with demographics, psychosocial factors, mental health, substance use patterns, and psychedelic use context. Results Among 268 participants, 48.5 % had a diagnosed mental illness, 45.1 % were at risk of suicide, 61.2 % reported psychotic symptoms, 45.1 % had high-risk methamphetamine use, and 82.1 % had taken substances other than methamphetamine and psychedelics. Most psychedelic experiences were unplanned (52.6 %), recreationally motivated (73 %), and combined with other drugs (52.6 %). Post-experience, participants reported improved mood (59.3 %) and social functioning (49.6 %), and reduced use of methamphetamine (34.0 %) and other substances (35.1 %). Forward planning and less challenging experiences were linked to improved mood (aOR 1.84, p = 0.048; aOR 2.21, p = 0.012) and reduced substance use (aOR 2.27, p = 0.008; aOR 3.58, p < 0.001). Discussion Psychedelic use among people who use methamphetamine may improve mood and social function, and reduce substance use. The complex findings highlight the potential importance of psychosocial and environmental factors (“set and setting”) in determining outcomes, underscoring the need for controlled clinical trials and tailored harm reduction strategies.

Introduction: Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for personal and family history of potential contraindications, and psychoeducational preparation with psychological support. Research settings typically provide psychoeducation to participants verbally and in writing (e.g., informed consent), and such documents and conversations can provide safety-related information-but may also introduce a wide range of expectancies. Such expectancies might involve the specific character of the acute subjective effects of psychedelics, possible side effects, and anticipated outcomes.Methods: To better understand the content of this psychoeducation, we gathered study materials from many psilocybin studies conducted in the past two decades in healthy and therapeutic populations. We conducted a reflexive thematic analysis to better understand these documents.Results: While these documents varied substantially between studies, we identified themes intended to lower levels of risk and optimize therapeutic effects from psychedelic treatments. The most frequently coded themes related to (1) biological and physical safety, (2) psychological safety and well-being, (3) aspects of setting, and (4) potential for expectancies. Prioritizing biological and psychological safety was evident in the materials from all sites. Furthermore, we identify potential contributors to expectancy unrelated to safety and suggest that these extrapharmacological elements be studied systematically in future research.Conclusions: Ideally, future research should strive to maximize safety while attempting to minimize extraneous expectancies.

Background: Whereas findings from case reports and cross-sectional studies suggest that naturalistic psychedelic use may be associated with unusual visual experiences that occur after the acute pharmacological effects have subsided, such findings need to be replicated in longitudinal studies to better understand potential cause-and-effect relationships. Aims: To investigate longitudinal associations between naturalistic psychedelic use and unusual visual experiences. Methods: Using a longitudinal observational research design with samples representative of the US and UK adult populations with regard to sex, age, and ethnicity (N = 9732), we investigated the relationship between psychedelic use during the 2-month study period and changes in past-week unusual visual experiences. Results: The follow-up survey was completed by 79% of respondents (n = 7667), with 100 respondents reporting psychedelic use during the 2-month study period (1.3% of those who responded at follow-up). In covariate-adjusted regression models, the results showed that, as hypothesized, psychedelic use during the 2-month study period was associated with greater increases in unusual visual experiences. Notably, there was an interaction between lifetime psychedelic use and psychedelic use during the study period on unusual visual experiences such that those who used psychedelics for the first time reported greater increases in unusual visual experiences. Conclusions: Psychedelic use may elicit unusual visual experiences that occur after the acute pharmacological effects have subsided, especially among those who have not used psychedelics previously. Future longitudinal studies are warranted to further elucidate these relationships.

This Viewpoint discusses the need to better understand potential risks associated with psychedelic and 3,4-methylenedioxymethamphetamine (MDMA) use to ensure safe and ethical practice and identifies 4 key research goals.

OBJECTIVES:Smoking prevalence remains high among low-income smokers. Understanding processes (eg, withdrawal, craving, motivation) in early smoking cessation is crucially important for designing effective interventions for this population. METHODS:This is a secondary analysis of a novel, in-session sampling intervention (ie, In Vivo) as compared with standard care behavioral smoking cessation counseling (SC) among community-dwelling low-income smokers (n = 83). This analysis examined the effect of 5 in-session sampling interventions on cessation-related processes and perceived advantages or disadvantages of nicotine replacement therapy (NRT) products over time using daily diaries. RESULTS:The In Vivo treatment had an early positive impact in terms of decreasing withdrawal symptoms and cravings, and increasing perceived advantages to NRT, with moderate to large effect sizes. Results also showed that the treatment effectively reduced withdrawal symptoms and cravings in-session, with small-to-medium and medium-to-large effect sizes, respectively. In-session reduction of withdrawal symptoms and cravings did not occur for the SC group, with the exception of decreased withdrawal symptoms occurring during week 4. The In Vivo treatment did not impact quit goal, desire to quit, abstinence self-efficacy, perceived difficulty in quitting, motivational engagement, or perceived disadvantages to NRT. The In Vivo group reported less daily cigarette use relative to the SC group, in addition to reporting less cigarette use on days they reported greater combination NRT use. CONCLUSIONS:There is preliminary support for this In Vivo treatment over SC in reducing withdrawal, craving, and the number of cigarettes smoked per day, as well as promoting perceived advantages of NRT among low-income smokers.

There is increasing interest in establishing psychedelic research programs at academic medical centers. However, psychedelics are intensely psychoactive, carry considerable sociopolitical baggage, and most are Schedule I drugs, creating significant potential impediments to implementation. There is little formal guidance for investigators on navigating the complex on-the-ground obstacles associated with establishing psychedelic research programs. This article provides recommendations that may be helpful to investigators seeking to work with psychedelics, with a focus on academic medical centers in the United States. The academic literature on relevant matters is reviewed, and the authors provide observations from their experiences either working for relevant regulatory agencies or conducting basic science studies, investigator-initiated trials, or industry sponsored trials with psychedelics. Investigators planning to conduct psychedelic research should cultivate broad institutional support early. Challenges related to securing funding, obtaining approval for an Investigational New Drug application from the Food and Drug Administration, clinical grade drug sourcing, obtaining a Schedule I researcher registration from the Drug Enforcement Administration and an equivalent state license (if required), preparing spaces for treatment and study drug storage, managing controlled substance inventory, engaging the local community, and other issues should be anticipated. Investigators should anticipate several implementation challenges when planning to work with psychedelics. However, these are likely surmountable with planning, persistence, and assistance from colleagues and other experts.