The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder.

We examined if the therapeutic alliance between study participants and intervention facilitators in a psilocybin-assisted therapy (PAT) trial changed over time and whether there were relationships between alliance, acute psilocybin experiences, and depression outcomes. In a randomized, waiting list-controlled clinical trial for major depressive disorder in adults (N = 24), participants were randomized to an immediate (N = 13) or delayed (N = 11) condition with two oral doses of psilocybin (20mg/70kg and 30mg/70kg). Ratings of therapeutic alliance significantly increased from the final preparation session to one-week post-intervention (p = .03, d = .43). A stronger total alliance at the final preparation session predicted depression scores at 4 weeks (r = -.65, p = .002), 6 months (r = -.47, p = .036), and 12 months (r = -.54, p = .014) post-intervention. A stronger total alliance in the final preparation session was correlated with higher peak ratings of mystical experiences (r = .49, p = .027) and psychological insight (r = .52, p = .040), and peak ratings of mystical experience and psychological insight were correlated with depression scores at 4 weeks (r = -.45, p = .030 for mystical; r = -.75, p < .001 for insight). Stronger total alliance one week after the final psilocybin session predicted depression scores at 4 weeks (r = -.85, p < .001), 3 months (r = -.52, p = .010), 6 months (r = -.77, p < .001), and 12 months (r = -.61, p = .001) post-intervention. These findings highlight the importance of the therapeutic relationship in PAT. Future research should explore therapist and participant characteristics which maximize the therapeutic alliance and evaluate its relationship to treatment outcomes. Trial registration: Registration: Clinicaltrials.gov NCT03181529. https://classic.clinicaltrials.gov/ct2/show/NCT03181529.

Effects of Ayahuasca on Gratitude and Relationships with Nature: A Prospective, Naturalistic Study.

Qualitative studies and anecdotal reports suggest that experiences with ayahuasca, a psychedelic brew found in Central and South America, may be followed by individuals enduringly feeling more grateful and connected to nature. Yet, to date, these changes have been understudied. Here, participants (N = 54) completed validated surveys related to gratitude, nature relatedness, and nature appreciation one-week before, one-week after, and one-month after attending an ayahuasca retreat center. Compared to baseline, there was a significant increase in gratitude, nature relatedness, and nature appreciation at the one-week and one-month follow-ups. Ratings of mystical-type experiences and awe, but not ego dissolution, during participants' ayahuasca sessions were weakly-to-moderately correlated with these increases. The number of ayahuasca ceremonies attended at the retreat was not related to change in outcomes, underscoring the importance of the quality rather than the quantity of the experiences in post-acute change. Lastly, participant age was negatively related to the occurrence of mystical-type experiences and awe, supporting literature indicating blunted psychedelic effects with increased age. In the context of study limitations, the results suggest that mystical-type experiences and awe occasioned by ayahuasca may be linked to prosocial changes in gratitude and relationships with nature that may be beneficial to mental health.

Prospective associations of psychedelic treatment for co-occurring alcohol misuse and posttraumatic stress symptoms among United States Special Operations Forces Veterans.

This study evaluated prospective associations of ibogaine and 5-MeO-DMT treatment for risky alcohol use and post-traumatic stress disorder (PTSD) symptoms among United States (US) Special Operations Forces Veterans (SOFV). Data were collected during standard clinical operations at pre-treatment and 1-month (1 m), 3-months (3 m), and 6-months (6 m) post-treatment in an ibogaine and 5-MeO-DMT treatment program in Mexico. Of the 86 SOFV that completed treatment, 45 met criteria for risky alcohol use at pre-treatment (mean age = 44; male = 100%; White = 91%). There was a significant reduction in alcohol use from pre-treatment (M = 7.2, SD = 2.3) to 1 m (M = 3.6; SD = 3.5) post-treatment, which remained reduced through 6 m (M = 4.0; SD = 2.9; p < .001, partial eta squared = .617). At 1 m, 24% were abstinent, 33% were non-risky drinking, and 42% were risky drinkers. At 6 m, 16% were abstinent, 31% were non-risky drinking, and 53% were risky drinkers. There were no differences between responders (abstinent/non-risky drinkers) and non-responders (risky drinkers) in demographics/clinical characteristics. However, there were significant and very large differences between responders and non-responders in PTSD symptom (p < .01, d = -3.26) and cognitive functioning change (p < .01, d = -0.99). Given these findings, future clinical trials should determine whether psychedelic-assisted therapy holds promise for individuals with complex trauma and alcohol misuse who have not been successfully treated with traditional interventions.

Exploring the intersectionality of stigma and substance use help-seeking behaviours among lesbian, gay, bisexual, transgender, queer, questioning or otherwise gender or sexuality minority (LGBTQ+) individuals in the United States: A scoping review.

Problematic substance use (SU) is a significant issue among LGBTQ+ individuals, but rates of treatment/help-seeking in this population remain low. This review aimed to investigate literature about intersectional stigma of SU and LGBTQ+ identity and its impact on SU help-seeking behaviours in the U.S. Eligible studies from eight-database were included if peer-reviewed, in English, from the U.S., published between 2000 and 2022, focused on SU, stigma, SU help-seeking behaviours, among LGBTQ+ adults. Of 458 search results, 50 underwent full-text review, 12 were included in the final sample. Minority Stress Theory emerged as a relevant theoretical framework. Findings revealed that increased SU as a coping strategy was associated with minority stress. Intersectional stigma negatively impacted SU treatment experience among LGBTQ+ individuals, leading to avoidance of help-seeking or poor treatment outcomes. Patterns of SU and impact of stigma among LGBTQ+ individuals differ, wherein bisexual and transgender individuals reported significantly more treatment barriers and unique stressors. LGBTQ+ individuals reported earlier age of SU onset and were more likely to encounter opportunities for SU. This review highlights the impact of intersectional stigma on SU help-seeking behaviour among LGBTQ+ individuals in the U.S. Recommendations are provided for future clinical practice, research, and policy to better support LGBTQ+ individuals.

Incremental Predictive Validity of the Dualistic Model of Passion for Cannabis Use Among College Undergraduate Students With and Without a Cannabis Use Disorder.

Introduction: We examined whether the Dualistic Model of Passion (DMP; i.e., obsessive passion [OP] and harmonious passion [HP]) for cannabis use was prospectively associated with cannabis use and use-related outcomes, and with academic performance, relationship attachment style, and social connectedness among college students. We also explored whether the DMP was associated with outcomes when included in a model using established constructs (e.g., coping motives, refusal self-efficacy, cannabis use disorder [CUD] symptoms) as predictors of cannabis use and outcomes. Methods: Using a longitudinal cohort design (baseline, 5-month, 10-month [timepoints chosen to better correspond to 9-month academic year]), 513 undergraduate students from two universities who reported using cannabis at least four times in the past month completed a baseline survey (308 meeting criteria for CUD). We used Generalized Estimating Equations to assess longitudinal associations between OP/HP and cannabis use and academic/social outcomes at 5-month and 10-month. Results: At baseline, participants were young adults (Mean age = 20.57, SD = 2.51), 78.8% non-Hispanic, 83.8% White, 55.0% female, and 72.3% heterosexual. Greater HP was not associated with greater past month cannabis use or cannabis-related problems. Greater OP was associated with greater past month cannabis use and more cannabis-related problems. There were no significant passion by time interactions. Greater HP was associated with more anxious attachment. OP was associated with less social connection. Conclusion: This research suggests that the DMP provides novel information about factors associated with cannabis use and use-related consequences, which can aid in our understanding of cannabis use, misuse, and CUD among college students.

Implementing traumatic brain injury screening in behavioral health treatment settings: results of an explanatory sequential mixed-methods investigation.

BACKGROUND: Traumatic brain injury (TBI) is a complex condition common among individuals treated in behavioral healthcare, but TBI screening has not been adopted in these settings which can affect optimal clinical decision-making. Integrating evidence-based practices that address complex health comorbidities into behavioral healthcare settings remains understudied in implementation science, limited by few studies using theory-driven hypotheses to disentangle relationships between proximal and medial indicators on distal implementation outcomes. Grounded in the Theory of Planned Behavior, we examined providers' attitudes, perceived behavioral control (PBC), subjective norms, and intentions to adopt The Ohio State University TBI Identification Method (OSU TBI-ID) in behavioral healthcare settings. METHODS: We used an explanatory sequential mixed-methods design. In Phase I, 215 providers from 25 organizations in the USA completed training introducing the OSU TBI-ID, followed by a survey assessing attitudes, PBC, norms, and intentions to screen for TBI. After 1 month, providers completed another survey assessing the number of TBI screens conducted. Data were analyzed using structural equation modeling (SEM) with logistic regressions. In Phase II, 20 providers were purposively selected for semi-structured interviews to expand on SEM results. Qualitative data were analyzed using thematic analysis, integrated with quantitative results, and combined into joint displays. RESULTS: Only 25% (55/215) of providers adopted TBI screening, which was driven by motivations to trial the intervention. Providers who reported more favorable attitudes (OR: 0.67, p < .001) and greater subjective norms (OR: 0.12, p < .001) toward TBI screening demonstrated increased odds of intention to screen, which resulted in greater TBI screening adoption (OR: 0.30; p < .01). PBC did not affect intentions or adoption. Providers explained that although TBI screening can improve diagnostic and clinical decision-making, they discussed that additional training, leadership engagement, and state-level mandates are needed to increase the widespread, systematic uptake of TBI screening. CONCLUSIONS: This study advances implementation science by using theory-driven hypothesis testing to disentangle proximal and medial indicators at the provider level on TBI screening adoption. Our mixed-methods approach added in-depth contextualization and illuminated additional multilevel determinants affecting intervention adoption, which guides a more precise selection of implementation strategies.

Translation and Initial Psychometric Evaluation of Spanish Versions of Three Psychedelic Acute Effects Measures: Mystical, Challenging, and Insight Experiences.

This study translated and tested the psychometric properties of acute psychedelic effects measures among Spanish-speaking people. The Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ) were translated before being incorporated into a web-based survey. We recruited native Spanish-speakers (N = 442; Mage = 30.8, SD = 10.9; Latino/Latina = 62%; Hispanic = 91.4%; male = 71.5%) to assess their previous experience with one of two psychedelics (LSD = 58.4%; Psilocybin = 41.6%) and their acute and enduring effects. Confirmatory factor analysis (confirming factor structure based on the English version) revealed a good fit for the MEQ, PIQ and the CEQ. Repeating our analysis in each drug subsample revealed consistency in factor structure for each assessment tool. Construct validity was supported by significant positive associations between the PIQ and MEQ, and between the PIQ and MEQ and changes in cognitive fusion and negative associations between changes in prosocial behaviors. As a signal of predictive validity, persisting effects (PEQ) were strongly related to scores on the MEQ and PIQ. Findings demonstrate that the Spanish versions of these measures can be reliably employed in studies of psychedelic use or administration in Spanish-speaking populations.

Assessing the risk of symptom worsening in psilocybin-assisted therapy for depression: A systematic review and individual participant data meta-analysis.

We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N = 102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants in the waitlist condition (63.6%). Using data from the two trials with control arms, the psilocybin arm showed a lower likelihood of symptom worsening versus waitlist, and no difference in the likelihood of symptom worsening versus escitalopram. The limitation of a relatively small sample size should be addressed in future studies.

Study protocol of an open-label proof-of-concept trial examining the safety and clinical efficacy of psilocybin-assisted therapy for veterans with PTSD.

INTRODUCTION: Psilocybin-assisted therapy has shown significant promise in treating the cluster of mood and anxiety symptoms that comprise post-traumatic stress disorder (PTSD) but has yet to be tested specifically in this condition. Furthermore, current pharmacological and psychotherapeutic treatments for PTSD are difficult to tolerate and limited in efficacy, especially in the US Military Veteran (USMV) population. This open-label pilot study will examine the safety and efficacy of two psilocybin administration sessions (15 mg and 25 mg), combined with psychotherapy, among USMVs with severe, treatment resistant PTSD. METHODS AND ANALYSIS: We will recruit 15 USMVs with severe, treatment resistant PTSD. Participants will receive one low dose (15 mg) and one moderate/high dose (25 mg) of psilocybin in conjunction with preparatory and post-psilocybin therapy sessions. The primary safety outcome will be the type, severity and frequency of adverse events and suicidal ideation/behaviour, as measured by the Columbia Suicide Severity Rating Scale. The primary outcome measure for PTSD will be the Clinician Administered PTSD Scale-5. The primary endpoint will be 1 month following the second psilocybin administration session, and the total follow-up time will be 6 months. ETHICS AND DISSEMINATION: All participants will be required to provide written informed consent. The trial has been authorised by the Ohio State University Institutional Review Board (study number: 2022H0280). Dissemination of results will occur via a peer-reviewed publication and other relevant media. TRIAL REGISTRATION NUMBER: NCT05554094.

Investigating the associations of acute psychedelic experiences and changes in racial trauma symptoms, psychological flexibility, and substance use among People with Racial and Ethnic Minoritized Identities in the United States and Canada.

INTRODUCTION: Evidence suggests that psychedelics may serve as a therapeutic approach to reduce substance use; however, people with racial and ethnic minoritized (REM) identities are often excluded from this research. We investigated whether psychedelic use affects other substance use among REM people and whether perceived changes in psychological flexibility and racial trauma mediates this association. METHODS: REM people in the United States and Canada (N = 211; 32 % Black, 29 % Asian, 18 % American Indian/Indigenous Canadian, 21 % Native Hawaiian/Pacific Islander; 57 % female; mean age = 33.1, SD = 11.2) completed an online survey retrospectively reporting their substance use, psychological flexibility, and racial trauma symptoms 30 days before and after their most memorable psychedelic experience. RESULTS: Analyses showed a significant perceived reduction in alcohol (p < .0001, d = 0.54) and drug use (p = .0001, d = 0.23) from before to after the psychedelic experience. Preliminary associations found perceived reductions in racial trauma symptoms were associated with perceived reductions in alcohol use and this association varied by race, dose, ethnic identity, and change in depressive symptoms. Specifically, Indigenous participants experienced greater perceived reductions in alcohol use relative to participants who identified as Asian, Black, or other. Those who took a high dose of psychedelics experienced greater perceived reductions in alcohol use relative to those who took a low dose. Participants with a stronger ethnic identity and those with a perceived reduction in depressive symptoms experienced a perceived reduction in alcohol use. Serial mediation indicated a perceived increase in psychological flexibility and reduction in racial trauma symptoms mediated the association between acute psychedelic effects and perceived reductions in alcohol and drug use. CONCLUSION: These findings suggest that psychedelic experiences may contribute to an increase in psychological flexibility and reduction in racial trauma symptoms and alcohol and drug use among REM people. REM people have been largely excluded from psychedelic treatment research even though psychedelic use is considered a traditional healing practice in many communities of color. Longitudinal studies of REM people should replicate our findings.

Knowledge, Perceptions, and Use of Psychedelics among Individuals with Fibromyalgia.

Fibromyalgia (FM) is a difficult to treat chronic pain condition for which there is strong interest in alternative treatments. There is growing interest in the potential of psychedelic substances (e.g., psilocybin) in conjunction with psychotherapy to treat chronic pain. Via a cross-sectional, anonymous, online survey, we aimed to characterize knowledge, perceptions, and past use of serotonergic ("classic") and non-serotonergic psychedelics among a population of individuals with FM, and to investigate interest in psychedelic-based FM treatments. Among a North American population of 354 participants with FM, 29.9% reported past use of a psychedelic, with lysergic acid diethylamide (LSD) and psilocybin mushrooms being most commonly used. Perceptions of benefit from psychedelic use were generally neutral (59.4%) or positive (36.8%), with <3% reporting negative impacts on overall health or pain symptoms. Among 12 participants who used psychedelics with intentions of treating chronic pain, 11 reported improved symptoms. Regardless of past use, the majority of participants believed that psychedelics have potential for chronic pain treatments and would be willing to participate in a psychedelic-based clinical trial for their pain. These findings support the need for additional studies to understand the potential and effectiveness of psychedelic substances in managing FM symptoms.

Effects of Psychedelic Use on Racial Trauma Symptoms and Ethnic Identity among Asians in North America.

There is a need to understand ways in which Asians in North America attempt to heal from racial trauma, given their well-documented high risk of exposure and associated adverse mental health outcomes. We conducted a secondary analysis of Asians from a survey of people of color in North America who have consumed psychedelics in response to racial discrimination. Ninety-two Asian participants (Mage = 30.25, SD = 6.83) completed online questions assessing demographics, racial discrimination frequency, characteristics and acute effects of their most meaningful psychedelic experience, change in racial trauma symptoms 30 days before and after their psychedelic experience, and current ethnic identity. Participants reported improvements in racial trauma symptoms (d = 0.52). Bootstrapped mediation analyses controlling for racial discrimination frequency and psychedelic dose and duration indicated complete mediation of the link between higher intensity of insightful experiences and stronger ethnic identity, via improvements in racial trauma symptoms (indirect effect = .08, 95% CI = [.004, .19]). There was partial mediation for the independent variable of lower intensity of challenging experiences (indirect effect = -.08, 95% CI = [-.18, -.005]). This study highlights the central role of higher-intensity insightful experiences and both higher- and lower-intensity challenging experiences in alleviating racial trauma symptoms and promoting ethnic identity among Asians in North America who have experienced racial discrimination. Future research should attune to culturally relevant outcomes of psychedelic use in response to racial discrimination among Asians.

What undergraduates want in campus sexual assault prevention programming: Findings from a formative research study.

OBJECTIVE: Campus sexual assault (SA) prevention programs are widely implemented, despite few having strong empirical support. To inform the development and refinement of prevention programs, we collected pilot qualitative data to capture undergraduates' perspectives regarding desirable program characteristics. PARTICIPANTS: Undergraduates completed an audio-taped interview (n = 19) or a focus group (n = 16) in June - November 2016. METHODS: We double-coded transcripts for a priori and emerging themes using NVivo 11. A third coder resolved disagreements; we assessed intercoder reliability using Cohen's Kappa. RESULTS: Participants preferred SA prevention programming to be delivered in-person to small, coed groups of unfamiliar students. Students preferred programming with peer-facilitated, candid conversation about SA outcomes and prevention strategies. Participants also preferred for the tone of these training sessions to match the serious subject matter. CONCLUSIONS: Students' perceptions of desirable program characteristics differ somewhat from current evidence-based programs in several ways, highlighting important future directions for SA prevention research.

Subtypes of the psychedelic experience have reproducible and predictable effects on depression and anxiety symptoms.

BACKGROUND: Subjective experiences seem to play an important role in the enduring effects of psychedelic experiences. Although the importance of the subjective experience on the impact of psychedelics is frequently discussed, a more detailed understanding of the subtypes of psychedelic experiences and their associated impacts on mental health has not been well documented. METHODS: In the current study, machine learning cluster analysis was used to derive three subtypes of psychedelic experience in a large (n = 985) cross sectional sample. RESULTS: These subtypes are not only associated with reductions in anxiety and depression symptoms and other markers of psychological wellbeing, but the structure of these subtypes and their subsequent impact on mental health are highly reproducible across multiple psychedelic substances. LIMITATIONS: Data were obtained via retrospective self-report, which does not allow for definitive conclusions about the direction of causation between baseline characteristics of respondents, qualities of subjective experience, and outcomes. CONCLUSIONS: The present analysis suggests that psychedelic experiences, in particular those that are associated with enduring improvements in mental health, may be characterized by reproducible and predictable subtypes of the subjective psychedelic effects. These subtypes appear to be significantly different with respect to the baseline demographic characteristics, baseline measures of mental health, and drug type and dose. These findings also suggest that efforts to increase psychedelic associated personal and mystical insight experiences may be key to maximizing beneficial impact of clinical approaches using this treatment in their patients.

Reactivations after 5-methoxy-N,N-dimethyltryptamine use in naturalistic settings: An initial exploratory analysis of the phenomenon's predictors and its emotional valence.

Background: The psychedelic 5-MeO-DMT has shown clinical potential due to its short duration and ability to induce mystical experiences. However, a phenomenon known as "reactivations" (similar to "flashbacks") is a poorly understood and frequently reported phenomenon which appears associated with 5-MeO-DMT use and warranted further investigation. Aims: This study examined whether differences in age, gender, education, lifetime use, use location, and preparation strategies predict reactivations (primary outcome). Additionally, we explored how reactivations were perceived by survey respondents and whether demographic data predicted emotional valence (secondary outcome) of reported reactivations. Materials and methods: This study used secondary quantitative data from a survey assessing epidemiological and behavioral associations of 5-MeO-DMT use in non-clinical settings (N = 513). Descriptive statistics, chi-square tests, t-tests, and logistic regressions were utilized to explore aims. Results: Being female, older at the time of first 5-MeO-DMT dose, having higher educational attainment, and dosing in a structured group setting were associated with increased odds of reporting a reactivation event. Higher mystical experience scores, greater personal wellbeing and having had a non-dual awareness experience that was not substance-induced were associated with higher likelihood of reporting a neutral or positive emotional valence of a reactivation event. Conclusion: These findings suggest that reactivation phenomena, in this particular sample may most often represent a neutral or positive byproduct of the acute 5-MeO-DMT experience. More information is needed to best identify individuals most likely to experience a reactivation as a negative event to prevent such potential challenging outcomes.

Inconsistencies between national drug policy and professional beliefs about psychoactive drugs among psychiatrists in the United States.

BACKGROUND: Evidence points to an incongruence between international drug policy and expert opinion about safety, abuse potential, and therapeutic potential of specific drugs. However, no prior studies have directly explored psychiatrists' attitudes about the current drug schedule. Therefore, we examined whether American psychiatrists' perceptions of four psychoactive drugs differed from those indicated by their schedules. METHODS: A quasi-experimental online survey of a convenience sample of psychiatrists in the United States (N=181; Mean age=48.7; Female=35%). Participants were randomized to receive 1-of-4 vignettes, each depicting a depressed patient reporting relief from symptoms after non-prescribed psychoactive drug use (i.e., psilocybin [Schedule I], methamphetamine [SchedII], ketamine [SchedIII], or alprazolam [SchedIV]). Participants responded to questions related to this clinical scenario and then rated the safety, therapeutic, and abuse potentials of these four drugs and alcohol. RESULTS: There were significant differences by vignette condition in mean likelihood ratings of: warning against engaging in drug use again (p<.01), being concerned about developing a new psychiatric problem (p<.001), being concerned about increased suicide risk (p<.01) and being supportive of further use of this drug as part of the treatment plan (p<.001). Overall, non-prescribed use of methamphetamine and alprazolam was rated more concerning and less acceptable than non-prescribed use of psilocybin and ketamine. Compared to psilocybin and ketamine, participants rated methamphetamine and alprazolam as less safe (p<.001), having less therapeutic potential (p<.001), and having more abuse potential (p<.001). Mean ratings of safety and abuse/therapeutic potential of alprazolam and methamphetamine were equivalent to that of alcohol, and all three were rated more harmful than psilocybin and ketamine. CONCLUSION: American psychiatrists' perceptions about safety and abuse/therapeutic potentials associated with certain psychoactive drugs were inconsistent with those indicated by their placement in drug schedules. These findings add to a growing consensus amongst experts that the current drug policy is not scientifically coherent.

A randomized controlled trial of social media interventions for risky drinking among adolescents and emerging adults.

PURPOSE: Alcohol use among adolescents and emerging adults is an important public health issue requiring prevention approaches. Herein, we describe outcomes from a randomized controlled trial testing the efficacy of group-based social media interventions targeting risky drinking among youth. PROCEDURES: Using social media advertisements to screen potential participants, we recruited 955 youth (ages 16-24) reporting recent risky drinking. After completing a baseline assessment, participants were randomized to 8-week secret Facebook group conditions: Social Media Intervention + Incentives for engagement, Social Media Intervention only, and attention-placebo control. Electronic coaches trained in motivational interviewing facilitated interaction in intervention groups. Primary outcomes include past 3-month alcohol use and consequences over 3-, 6-, and 12-month follow-ups. Secondary outcomes include other drug use, consequences, and impaired driving. We also measured intervention engagement and acceptability. RESULTS: The interventions were well-received, with significantly greater acceptability ratings and engagement in the SMI+I condition relative to other groups. In adjusted analyses, there were no significant differences between interventions and control on alcohol-related outcomes, with all groups showing reductions. Regarding secondary outcomes (70.4% used other drugs), compared to control, the incentivized group reduced other drug use, consequences, and cannabis-impaired driving; the non-incentivized group did not significantly differ from the control condition. CONCLUSIONS: Among this predominantly poly-substance using sample, findings were mixed, with significant effects of the incentivized social media intervention on drug (but not alcohol) outcomes. Future studies are needed to further refine social media-delivered interventions to reduce alcohol and other drug use. TRIAL REGISTRATION: ClinicalTrials.gov NCT02809586; University of Michigan HUM#00102242.

The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT).

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring tryptamine that primarily acts as an agonist at the 5-HT1A and 5-HT2A receptors, whereby affinity for the 5-HT1A subtype is highest. Subjective effects following 5-MeO-DMT administration include distortions in auditory and time perception, amplification of emotional states, and feelings of ego dissolution that usually are short-lasting, depending on the route of administration. Individual dose escalation of 5-MeO-DMT reliably induces a "peak" experience, a state thought to be a core predictor of the therapeutic efficacy of psychedelics. Observational studies and surveys have suggested that single exposure to 5-MeO-DMT can cause rapid and sustained reductions in symptoms of depression, anxiety, and stress. 5-MeO-DMT also stimulates neuroendocrine function, immunoregulation, and anti-inflammatory processes, which may contribute to changes in mental health outcomes. To date, only one clinical trial has been published on 5-MeO-DMT, demonstrating the safety of vaporized dosing up to 18 mg. Importantly, the rapid onset and short duration of the 5-MeO-DMT experience may render it more suitable for individual dose-finding strategies compared with longer-acting psychedelics. A range of biotech companies has shown an interest in the development of 5-MeO-DMT formulations for a range of medical indications, most notably depression. Commercial development will therefore be the most important resource for bringing 5-MeO-DMT to the clinic. However, fundamental research will also be needed to increase understanding of the neurophysiological and neural mechanisms that contribute to the potential clinical effects of 5-MeO-DMT and its sustainability and dissemination over time. Such studies are less likely to be conducted as part of drug development programs and are more likely to rely on independent, academic initiatives.

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up.

BACKGROUND: Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes. AIMS: This study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe MDD who received psilocybin. METHODS: This randomized, waiting-list controlled study enrolled 27 patients aged 21-75 with moderate to severe unipolar depression (GRID-Hamilton Depression Rating Scale (GRID-HAMD) ⩾ 17). Participants were randomized to an immediate or delayed (8 weeks) treatment condition in which they received two doses of psilocybin with supportive psychotherapy. Twenty-four participants completed both psilocybin sessions and were followed through 12 months following their second dose. RESULTS: All 24 participants attended all follow-up visits through the 12-month timepoint. Large decreases from baseline in GRID-HAMD scores were observed at 1-, 3-, 6-, and 12-month follow-up (Cohen d = 2.3, 2.0, 2.6, and 2.4, respectively). Treatment response (⩾50% reduction in GRID-HAMD score from baseline) and remission were 75% and 58%, respectively, at 12 months. There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported psilocybin use outside of the context of the study. Participant ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months, but did not predict improvement in depression. CONCLUSIONS: These findings demonstrate that the substantial antidepressant effects of psilocybin-assisted therapy may be durable at least through 12 months following acute intervention in some patients.