Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study

Abstract

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).

Keywords: Demoralization; HIV/AIDS; Long-term survivors; Psilocybin; Trauma.

Fig. 1

Trial profile.

Fig. 2

Timeline includes baseline assessment (“Week -3”), two weeks of group therapy with assessment after the fourth group therapy visit (“Week -1”), 1-2 weeks of individual psilocybin administration sessions (“medication visits”; “Week 0”), and then 2-3 weeks of group therapy. Medication visits for Cohort 1 occurred over a 2-week period; for Cohorts 2 and 3, all six medication visits occurred over a 1-week period, two per day in separate rooms. Post-drug participant-reported outcomes were collected on the same day for all participants in each cohort, hence there was a variable 3-day to 2-week period between drug administration and the next self-report assessment of symptoms, which occurred immediately after the fifth group therapy visit (“Week 1-2”). The primary endpoint was assessed immediately after the final group therapy visit (“end-of-treatment” a.k.a., “Week 3”). Final follow-up occurred 3 months after end-of-treatment.

Fig. 3

Blood Pressure During Medication Visit. Error bars are 1 SD.

Fig. 4

Primary clinical outcome (DS-II). Error bars are 1 SD. Mean change from Baseline (Week-3) to primary endpoint (Week 3) to 3-month follow-up has standardized effect size η_p² = 0·47, 90% CI 0·21-0·60.

Fig. 5

Selected secondary clinical outcomes. Error bars are 1 SD. A: PCL-5, B: ICG-R.