Background Psilocybin therapy has shown promise as a rapid-acting treatment for depression, anxiety, and demoralization in patients with serious medical illness (e.g., cancer) when paired with individual psychotherapy. This study assessed the safety and feasibility of psilocybin-assisted group therapy for demoralization in older long-term AIDS survivor (OLTAS) men, a population with a high degree of demoralization and traumatic loss. Methods Self-identified gay men OLTAS with moderate-to-severe demoralization (Demoralization Scale-II ≥8) were recruited from the community of a major US city for a single-site open-label study of psilocybin-assisted group therapy comprising 8–10 group therapy visits and one psilocybin administration visit (0·3–0·36 mg/kg po). Primary outcomes were rate and severity of adverse events, and participant recruitment and retention. The primary clinical outcome was change in mean demoralization from baseline to end-of-treatment and to 3-month follow-up assessed with a two-way repeated measures ANOVA. Trial registration: Clinicaltrials.gov (NCT02950467) Findings From 17 July 2017 to 16 January 2019, 18 participants (mean age 59·2 years (SD 4·4)) were enrolled, administered group therapy and psilocybin, and included in intent-to-treat analyses. We detected zero serious adverse reactions and two unexpected adverse reactions to psilocybin; seven participants experienced self-limited, severe expected adverse reactions. We detected a clinically meaningful change in demoralization from baseline to 3-month follow-up (mean difference -5·78 [SD 6·01], η p 2 = 0·47, 90% CI 0·21–0·60). Interpretation We demonstrated the feasibility, relative safety, and potential efficacy of psilocybin-assisted group therapy for demoralization in OLTAS. Groups may be an effective and efficient means of delivering psychotherapy pre- and post-psilocybin to patients with complex medical and psychiatric needs. Funding Carey Turnbull, Heffter Research Institute, NIMH R25 MH060482, NIH UL1 TR001872, River Styx Foundation, Saisei Foundation, Sarlo Foundation, Stupski Foundation, Usona Institute, US Department of Veterans Affairs (Advanced Neurosciences Fellowship and IK2CX001495).

30-60% of patients receiving methadone for opioid use disorder (OUD) actively use cocaine. Cocaine use disorder (CUD) has no FDA-approved pharmacological treatment; existing psychosocial treatments are inadequate. Oxytocin, a social neuropeptide, has preclinical promise as an adjunctive treatment for both OUD and CUD. Twenty-two individuals receiving methadone for OUD with co-occurring CUD were randomized to receive oxytocin or placebo intranasally 40 IU twice daily for two weeks. A priori aims were feasibility and safety. Exploratory effectiveness aims included laboratory-based measures of drug craving, drug-related implicit cognition, and drug use. High retention rates (93.5%), the absence of study-related adverse events, and the fact that oxytocin was well tolerated in this population support the feasibility of larger trials. Two weeks of oxytocin (but not placebo) significantly reduced cocaine craving at day 15 compared to baseline (mean change±SD: OT=−0.23±0.19, p=0.004; PL=−0.16±0.29, p=0.114). For heroin craving, the placebo group reported a trend-level increase over time while the oxytocin group remained unchanged - with medium to large effect sizes between the groups (Cohen's d=0.71-0.90). Oxytocin led to a significant switch from implicit self-association with drugs to implicitly associating drugs with others (mean change±SD: 0.25±0.35, p=0.037) and a trend-level reduction in self-reported cocaine use over time (Z=−1.78, p=0.075). Furthermore, oxytocin significantly increased the accuracy of self-reported cocaine use when correlated with quantitative urine levels of cocaine metabolite. This proof-of-concept study provides promising early evidence that oxytocin may be an effective adjunct to the treatment of co-occurring CUD and OUD. Further investigation with larger trials is warranted.

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Contemporary research with classic psychedelic drugs (e.g. lysergic acid diethylamide (LSD) and psilocybin) is indebted to the 20th century researchers and clinicians who generated valuable clinical knowledge of these substances through experimentation. Several recent reviews that highlight the contributions of this early literature have focused on psychedelic-assisted individual psychotherapy modalities. None have attempted to systematically identify and compile experimental studies of psychedelic-assisted group therapy. In therapeutic settings, psychedelics were often used to enhance group therapy for a variety of populations and clinical indications. We report on the results of a systematic review of the published literature in English and Spanish on psychedelic-assisted group therapies. Publications are characterized by their clinical approach, experimental method, and clinical outcomes. Given the renewed interest in the clinical use of psychedelic medicines, this review aims to stimulate hypotheses to be tested in future research on psychedelic-assisted psychotherapy, group process, and interpersonal functioning.

Attachment insecurity is determined early in life, is a risk factor for psychopathology, and can be measured on two separate continuous dimensions: attachment anxiety and attachment avoidance. Therapeutic changes toward more secure attachment correlate with reduction in psychiatric symptoms. Psilocybin-assisted psychotherapy has demonstrated promise in the treatment of psychopathology, such as treatment-resistant depression and substance use disorders. We hypothesized that psilocybin-assisted psychotherapy would reduce attachment anxiety and attachment avoidance, thus increasing attachment security. We also hypothesized that baseline measures of attachment insecurity, which can reflect a diminished capacity for trust and exploration, would inform the quality of the psilocybin session. Participants were male long-term AIDS survivors with moderate-severe demoralization (n = 18). Using the Experiences in Close Relationships scale, we measured attachment insecurity at baseline as well as immediately, and 3 months, after completion of a brief group therapy course, which included a single midtreatment open-label psilocybin session conducted individually. Clinically important aspects of the psilocybin session were assessed using the revised Mystical Experience Questionnaire and the Challenging Experience Questionnaire the day following psilocybin administration. Self-reported ratings of attachment anxiety decreased significantly from baseline to 3-months post-intervention, t(16) = −2.2; p = 0.045; d rm = 0.45; 95% CI 0.01, 0.87. Attachment avoidance did not change significantly. Baseline attachment anxiety was strongly correlated with psilocybin-occasioned mystical-type experiences, r(15) = 0.53, p = 0.029, and baseline attachment avoidance was strongly correlated with psilocybin-related challenging experiences, r(16) = 0.62, p = 0.006. These findings have important implications for the general treatment of psychopathology as well as optimizing psilocybin-assisted psychotherapy as a broadly applicable treatment modality.

Introduction Social isolation and alcohol and substance use disorders (ASUD) have been identified as global health risks. Social support is protective against developing ASUD and is associated with beneficial addiction treatment outcomes. Socially stigmatized populations are at higher risk of both social isolation and ASUD, and the link between social support and substance use in these populations has been less researched than in general substance-using populations. We hypothesized that perceived social support, as measured by the Social Provisions Scale (SPS), would have an inverse relationship with frequency of substance use, from subsections of the Addiction Severity Index (ASI) that estimate use over the past 30 days and over an individual's lifetime. Methods Using a cross-sectional design, we conducted secondary correlational analyses with pre-existing data to test our hypothesis in two separate samples made up of socially marginalized populations entering ASUD treatment programs. Sample 1: substance-using male prison inmates ( n = 72, average age = 30.79) and Sample 2: primary methamphetamine-using men who have sex with men ( n = 86, average age = 43.41). Results Significant negative correlations were found between SPS and lifetime use of alcohol, tobacco, and cannabis ( r s − 0.27, −0.39, −0.26; p -values 0.04, 0.001, 0.04, respectively) in Sample 1 and 30-day use of methamphetamine ( r s − 0.28; p -value 0.008) in Sample 2. Discussion Differences in results between the samples (lifetime vs 30-day use) may reflect psychosocial and contextual differences impacting perceived social support. Our findings provide support for an important link between perceived social support and frequency of substance use in socially stigmatized populations.

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Methadone Oxytocin Option. ClinicalTrials.gov identifier: NCT01728909.