In a pilot clinical trial (N = 12), psilocybin-assisted group therapy produced a large, statistically significant reduction in HIV-related shame from baseline to three-month follow-up. However, two participants experienced a paradoxical worsening of sexual abuse–related shame, highlighting potential risks for trauma-exposed patients.
Papers cited by this study that are also in Blossom
Andersen, K. A. A., Carhart-Harris, R. L., Nutt, D. J. et al. · Acta Psychiatrica Scandinavica (2020)
As a proposed mediator between stigma-related stressors and negative mental health outcomes, HIV-related shame has been predictive of increased rates of substance use and difficulties adhering to antiretroviral treatment among people with HIV. These downstream manifestations have ultimately impeded progress toward national goals to End the HIV Epidemic, in part due to limited success of conventional psychotherapies in addressing HIV-related shame. In a pilot clinical trial (N = 12), receipt of psilocybin-assisted group therapy was associated with a large pre-post decrease in HIV-related shame as measured by the HIV and Abuse Related Shame Inventory, with a median (IQR) change of − 5.5 (− 6.5, − 3.5) points from baseline to 3-months follow-up (Z = − 2.6, p = 0.009, r = − 0.75). A paradoxical exacerbation of sexual abuse-related shame experienced by two participants following receipt of psilocybin raises critical questions regarding the use of psilocybin therapy among patients with trauma. These preliminary findings carry potential significance for the future of HIV care.
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.
Complete pre and post data were collected for all n = 12 study participants administered the HIV and Abuse Related Shame Inventory (HARSI)(Table). Cronbach's α for the HIV-and sexual-abuse related shame subscales in this sample were 0.96 and 0.94, respectively, indicating excellent internal reliability. A Friedman test indicated significant differences on scores of both HARSI sub-scales across five time points from baseline to 3-months following psilocybin dosing (χ 2 (2) = 45.25, p < 0.001 for HIV-related shame; χ 2 (2) = 16.66, p = 0.005 for sexual abuse-related shame). Pairwise comparisons evaluated using the Wilcoxon matched-pairs signed-rank test indicated significant reductions in HIV-related shame from baseline to all time points following but not prior to psilocybin dosing (1-week pre-psilocybin: Z = -1.9, p = 0.056, r = -0.60; 1-week post-psilocybin: Z = -2.9, p = 0.004, r =-0.87; 3-weeks post-psilocybin: Z = -2.5, p = 0.012, r = -0.79; 3-months post-psilocybin: Z = -2.6, p = 0.009, r = -0.75). There was an overall median (IQR) change of -5.5 (-6.5, -3.5) points in HIV-related shame from baseline to 3-months follow up (Fig.). Pairwise comparisons indicated no overall change in sexual abuse-related shame from baseline to any of the pre-or post-psilocybin time points among the subset of participants reporting a history of sexual abuse (n = 6), and two participants experienced increases in sexual abuse-related shame following psilocybin-assisted group therapy (Fig.). Table. Baseline characteristics of psilocybin group therapy study participants (N = 12) administered the HIV and Abuse Related Shame Inventory (2017-19). *Participants reported a median (IQR) of 8 (3,21) prior experiences using a classic psychedelic (i.e., psilocybin, lysergic acid diethylamide, N,N-dimethyltryptamine or mescaline), with a median (IQR) of 6 (1,28) years since their last use.
Findings from this study provide insights into the potential of psilocybin-assisted psychotherapy as an innovative approach for addressing shame among PWH. Despite a small sample size, results revealed a statistically significant reduction in HIV-related shame among older, long-term AIDS survivor men following completion of a 6-week psilocybin-assisted group therapy intervention that remained durable at 3 months follow-up with a large effect size (r = -0.75). While pre-post changes in sexual abuse-related shame sub-scores were not significant, it is noteworthy that half of the 12 study participants reported a history of sexual abuse and that two experienced an exacerbation of sexual abuse-related shame following receipt of psilocybin (Fig.). These preliminary findings support the pursuit of further research into the use of psychedelic therapies to address shame and associated mental health sequelae among PWH. The observed overall reduction in HIV-related shame following psilocybin-assisted group therapy is a promising signal of potential benefit. Of note, the median (IQR) baseline score among participants in this study of 7.5 (5, 22.5) was lower than the mean (SD) scores reported in larger population-based studies, which have ranged from 17.1 (13.4) to 17.8 (13.1) out of 52. In our sample, reductions in HIV-related shame appeared greatest among participants with baseline scores ≥ 20 (Fig.). While previous research has demonstrated the efficacy of psychedelic therapies in addressing various forms of psychological distress, including depression, anxiety, and SUDs, this is the first study to empirically evaluate the impact of a psychedelic therapy on shame. These findings also draw from the only interventional trial to-date focused explicitly on evaluating the effects of psilocybin therapy among SGM patients and PWH, who face unique challenges in accessing and maintaining care engagement. While all participants in this trial were virologically suppressed and taking ART, for many PWH, the impacts of shame-mediated mental health conditions contribute toward challenges with ART adherence. Therefore, by offering a promising approach toward addressing HIV-related shame, psilocybin therapy may indirectly support improved adherence to HIV pharmacotherapies, subsequent improvement in clinical outcomes, and reductions in HIV transmission. Importantly, the trial's behavioral intervention involved a form of group therapy, which was modeled on brief Supportive Expressive Group Therapy 14 and its prior adaptations for PWH. Compared with individual therapy, group therapy itself may foster decreased shame among PWH. While not statistically significant, our analyses revealed a large decrease in HIV-related shame from baseline to 1-week pre-psilocybin dosing (r = -0.60, Fig.), suggesting that the group therapy alone likely contributed to decreased HIV-related shame among participants. However, further decreases were experienced following psilocybin dosing. Therefore, while the contributory effects of group therapy and psilocybin in this study cannot be disentangled, overall findings suggest synergistic effects of these modalities on reducing HIV-related shame. These data also provide preliminary empiric support for a recently proposed theory suggesting a unique therapeutic potential of psychedelics in alleviating chronic shame among SGM. This theory aligns with the Selfentropic Broadening framework, which posits that psychedelics induce long-term mental health improvements by reducing self-focus and promoting hyper-associative thinking, facilitating a broadening of attentional scope and an expansion of thought-action repertoire. In the context of this study, chronic shame related to HIV could be considered a form of negative self-focused attention, and psilocybin may mitigate the physiological responses associated with this shame. Such a reduction in shame may encourage PWH and SGM to adopt a wider range of adaptive coping strategies to regulate negative affect. This might involve engaging in mental health care or other health-promoting activities instead of seeking escape through substance use or risky sexual behaviors, thus allowing for a potential break from activities that could perpetuate a 'spiral' of shame. The unexpected increase in sexual abuse-related shame observed in two participants raises critical questions regarding the use of psilocybin therapy in populations known to have histories of trauma. While two phase III clinical trials have demonstrated efficacy of MDMA-assisted therapy in treating PTSDand studies of psilocybin therapy for PTSD are currently underway, existing literature on the use of psilocybin in PTSD is limited. In the current analysis, one participant reported no sexual abuse-related shame at baseline, yet his sub-score increased to 13 by the end-of-treatment (Fig.). Based on clinical observation, he demonstrated increased comfort with self-disclosure in group settings during the first two weeks following psilocybin but subsequently experienced an exacerbation of social anxiety and self-critical thinking in the therapy group. While future research is needed to interrogate these temporal relations, given that his sub-score decreased from 13 to seven by 3-months follow-up, his experience may ultimately reflect habituation to distressing cognitions previously avoided. Nevertheless, these findings underscore the importance of addressing ethical considerations, safety, and potential adverse effects of psychedelics among diverse populations as this field of research evolves. For example, specific counseling regarding psilocybin-related risks may be warranted for people with significant histories of trauma, as some symptoms might be expected to temporarily worsen before improving. Future trials should also consider potential needs for extended integration therapy sessions or inclusion of multiple psychedelic dosing sessions, which may provide participants with multiple opportunities to address complex trauma. This study has important limitations. The absence of a control group and small sample size restrict the interpretability of results, as the original trial was not designed or powered to evaluate efficacy outcomes. Additionally, the trial intentionally selected for a relatively homogenous group of gay-identified, cis-gender, older-adult male participants to enhance a sense of trust and safety within group therapy cohorts over a brief period. These inclusion criteria notably narrow the generalizability of study findings. Moreover, PWH from a single urban area who volunteered to participate in a trial of psilocybin group therapy may not be representative of the broader population of PWH. In particular, the over-representation of white men in this sample (75%) is a notable shortcoming given the extent to which sexual and minority of men of color have been disproportionately affected by the HIV epidemic. Finally, the use of self-reported survey data is susceptible to recall and social desirability bias. Nevertheless, the HARSI has exhibited excellent internal consistency and test-retest reliability in other populations, and its use of a 1-week recall period should help minimize such biases. In future clinical trials of psychedelic therapies, it will be critical to incorporate measures of shame and recruit larger, more diverse populations, including PWH across various age groups, lengths of time since HIV diagnosis, sexual and gender identities, substance use patterns/diagnoses, and sociodemographic and racial/ethnic backgrounds, with interventions tailored to the specific needs of these communities. Long-term follow-up studies may provide insights into the dynamics of HIV-and sexual abuse-related shame following psilocybin therapy and their impact on mental and physical health outcomes. Moreover, the incorporation of complementary measures of self-efficacy and resilience and the expansion of qualitative research may further elucidate the psychological mechanisms underlying the observed changes.
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