Psilocybin-assisted therapy and HIV-related shame

While antiretroviral therapy has transformed HIV into a manageable chronic condition, people with HIV (PWH) in the United States continue to experience high rates of psychological distress and substance use disorders. The paper frames shame—an intensely painful inward-focused emotion involving negative self-evaluation—as a key mediator linking stigma-related environmental stressors to adverse mental and physical health outcomes among PWH, including depression, PTSD, substance use, poor ART adherence and worse physical health via stress-related biological pathways. Shame is described as more deeply ingrained than guilt and therefore difficult to address with conventional psychotherapies, which can be time-consuming and require sustained engagement that shame itself can impede. This study aimed to explore whether psilocybin-assisted psychotherapy could reduce HIV-related and sexual abuse-related shame. The intervention combined group-based preparatory and integration therapy with a single open-label, individually dosed psilocybin session. The authors focused on a specific population—gay-identified, older, long-term AIDS survivor men—and conducted exploratory analyses of changes in shame from baseline to three months after dosing, noting that no prior studies had formally evaluated psychedelic therapies for shame and that this trial is the only interventional study to date explicitly examining psychedelics in sexual and gender minority (SGM) patients with HIV.

The analysis used data from an open-label pilot trial of psilocybin-assisted group therapy for demoralisation in older long-term AIDS survivor men conducted in San Francisco between July 2017 and January 2019 (clinicaltrials.gov NCT02950467). The parent trial enrolled three group cohorts (total N = 18), and the present analysis reports outcomes for the last two cohorts (n = 12) who completed the HIV and Abuse Related Shame Inventory (HARSI). The trial was approved by an institutional review board; participants provided written informed consent and all procedures followed Good Clinical Practices. The therapeutic protocol comprised four preparatory group therapy sessions, a single mid-treatment individual psilocybin dosing session administered orally at 0.30–0.36 mg/kg in an open-label fashion, and four-to-six integrative group therapy sessions delivered over a 6-week period. Group therapy was modelled on a brief Supportive Expressive Group Therapy adaptation for PWH. The HARSI was used to measure shame: a 13-item HIV-related shame subscale (possible score 0–52) for all participants and a 9-item sexual abuse-related shame subscale (possible score 0–36) for those reporting lifetime sexual abuse. Responses used a 0–4 Likert scale reflecting the past week. Statistical analyses evaluated internal consistency and changes over time. Cronbach's α was calculated for the two HARSI subscales. A Friedman test (α = 0.05) assessed differences across five time points (baseline, 1-week pre-psilocybin, 1-week post-, 3-weeks post-, and 3-months post-dosing). Where the Friedman test was significant, post-hoc pairwise comparisons used the Wilcoxon matched-pairs signed-rank test to compare baseline versus each subsequent time point. The investigators plotted subscale trajectories to aid interpretation of potential group-therapy and psilocybin effects. Given the small sample and exploratory aims, the analysis did not account for nesting by cohort, and no corrections were applied for multiple comparisons. Analyses were performed in Excel and Stata version 18.0.

HARSI data were available for all n = 12 participants in the two analysed cohorts. Internal reliability was excellent: Cronbach's α was 0.96 for the HIV-related shame subscale and 0.94 for the sexual abuse-related shame subscale. The Friedman test indicated significant differences across time points for both subscales: HIV-related shame χ2(2) = 45.25, p < 0.001; sexual abuse-related shame χ2(2) = 16.66, p = 0.005. Pairwise Wilcoxon comparisons showed no significant change in HIV-related shame from baseline to 1-week pre-psilocybin (Z = -1.9, p = 0.056, r = -0.60), but significant reductions after dosing: 1-week post-psilocybin Z = -2.9, p = 0.004, r = -0.87; 3-weeks post Z = -2.5, p = 0.012, r = -0.79; and 3-months post Z = -2.6, p = 0.009, r = -0.75. Median (IQR) change in HIV-related shame from baseline to 3-months follow-up was -5.5 (-6.5, -3.5) points. The authors note that reductions appeared greatest among participants with baseline HARSI scores ≥ 20, and that the sample's median baseline score of 7.5 (IQR 5, 22.5) was lower than means reported in larger population-based studies. Among the subset reporting lifetime sexual abuse (n = 6), there was no significant overall change in sexual abuse-related shame from baseline to pre- or post-psilocybin time points. Two participants experienced increases in sexual abuse-related shame following the intervention; one of these had a subscore of 0 at baseline that rose to 13 at end-of-treatment and later decreased to 7 by 3-months follow-up. The extracted text does not report additional adverse events or safety measures beyond these observations.

Mehtani and colleagues interpret the findings as preliminary evidence that psilocybin-assisted group psychotherapy may reduce HIV-related shame among older long-term AIDS survivor men, with reductions persisting at three months and a large effect size reported for the primary comparison (r = -0.75). The investigators acknowledge that group therapy alone likely contributed to decreases in shame—evidenced by a sizable pre-psilocybin decrease from baseline to 1-week pre-dosing (r = -0.60, p = 0.056)—and therefore the effects of group therapy and psilocybin cannot be disentangled in this open-label design. They characterise the overall pattern as suggestive of synergistic effects between group psychotherapy and the psilocybin session. The authors situate their results within emerging literature on psychedelic therapies for mental health conditions and note that this is the first empirical evaluation of a psychedelic intervention specifically targeting shame. They invoke the Self-entropic Broadening framework, which proposes that psychedelics reduce maladaptive self-focus and broaden cognitive flexibility, as a possible mechanism by which psilocybin might alleviate chronic shame and enable adoption of more adaptive coping strategies. At the same time, the unexpected exacerbation of sexual abuse-related shame in two participants prompts caution; the investigators highlight the limited evidence for psilocybin in PTSD and suggest that trauma histories may occasion transient worsening of some symptoms. They recommend trauma-informed consent, possible extended integration therapy, or additional dosing opportunities in future trials to address complex trauma more safely. Key limitations acknowledged include the small sample size, absence of a control group, and a deliberately homogenous participant set (gay-identified, cis-gender, older adult men) that limits generalisability. The sample was drawn from a single urban area and was disproportionately White (75%), which the authors note is a shortcoming given the demographics of the HIV epidemic. Self-reported measures introduce potential recall and social desirability bias, although the HARSI has shown good reliability and uses a 1-week recall window. The investigators call for larger, more diverse, and controlled trials that incorporate measures of shame, longer follow-up, complementary measures of self-efficacy and resilience, and qualitative work to clarify mechanisms and the dynamics of shame following psychedelic-assisted therapy.

The authors conclude that psilocybin-assisted therapy shows promise as an approach to address shame among people with HIV, a contributor to disparities in mental and physical health outcomes. They emphasise that further research is required and suggest that these preliminary results offer hope for developing innovative and accessible psychedelic therapy interventions tailored to reduce the burden of shame in this population.