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

This open-label feasibility study (n=17) showed that psilocybin-assisted group therapy (21-25mg/70kg) was safe and effective for the treatment of demoralization in older long-term AIDS survivors.

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.

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], ηp2 = 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.”

Authors: Brian T. Anderson, Alicia Danforth, Robert Daroff, Christopher Stauffer, Eve Ekman, Gabrielle Agin-Liebes, Alexander Trope, Matthew Tyler Boden, James Dilley, Jennifer Mitchell & Joshua D. Woolley

Notes

This paper is included in our ‘Top 10 Articles on Psychedelics in the Year 2020‘

You can find the study protocol here.

This study was supported by: 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).

A (positive) commentary can also be found in ‘Psilocybin-assisted group therapy: A new hope for demoralization‘.

This study has a follow-up by Stauffer and colleagues (2020) which finds that attachment anxiety was decreased up to three months later.

And a follow-up by Agin-Liebes and colleagues (2021) conducted interviews with nine of the participants.

Summary

Psilocybin therapy is promising as a treatment for depression, anxiety and demoralization in older long-term AIDS survivor men.

1. Introduction

We performed a pilot study to assess the safety, feasibility, and potential efficacy of psilocybin-assisted group therapy for demoralization in a population of OLTAS men.

Evidence before this study

We searched MEDLINE, Google Scholar, Erowid.org and the MAPS online bibliography for literature on group therapy for people living with HIV, existential psychotherapies for patients with serious medical illness, and psychedelic-assisted group therapy. We found promising, but non-systematic clinical evidence suggesting that psychedelic-assisted group therapy may be worth assessing. There are no data on psychotherapies for long-term AIDS survivors, nor on the use of psychedelics to treat distress in PLWH, however meaning-centered group psychotherapy provides the best evidence for efficacy.

Added value of this study

This pilot study aimed to demonstrate the feasibility, relative safety, and potential efficacy of psychedelic-assisted group therapy for distress in long-term AIDS survivors.

Implications of all the available evidence

Psilocybin therapy may be useful for demoralized patients with serious medical illness, including PLWH, but larger, randomized, controlled and well-blinded trials are needed.

The study comprised three sequential group therapy cohorts, with six post-drug group therapy visits in each cohort. The protocol was adapted in real-time in conjunction with feedback from the Data Safety Monitor and participant focus groups.

2.3.1. Psychotherapy

Participants met individually with two co-therapists for 90 minutes prior to the first group session, and again the day following the medication visit. They discussed their psilocybin experience with the clinicians.

Group therapy sessions were modeled on Brief Supportive Expressive Group Therapy (SEGT) and its prior adaptations for PLWH. They occurred twice per week and included 90 minutes of breathing exercises and guided meditations focused on self-compassion and mindfulness.

2.3.2. Medication visits

Crystalline psilocybin was synthesized by Dr. David Nichols and formulated by the UCSF Investigational Drug Service. Participants took 03 mg/kg po for Cohort 1 and 036 mg/kg po for Cohorts 2 and 3.

2.4. Outcomes

Safety was evaluated with multiple measures, including adverse events assessment interviews, the Columbia Suicidality Severity Rating Scale (C-SSRS) interval interview, blood pressure and heart rate monitoring, and assessments of benefits and harms at end-of-treatment and 3 month follow-up.

2.5. Data analysis

We performed descriptive statistics, intent-to-treat analyses, and nested repeated measures ANOVAs to assess change in clinical outcomes from baseline to end-of-treatment and to 3-month follow-up. We also calculated a bias-corrected standardized effect size for pre-post repeated measures (drm) with 95% confidence intervals.

2.6. Role of the funding source

This is an investigator-initiated study, and the Department of Veterans Affairs has no role in the design, data collection, analysis or interpretation, or the writing of the report.

3. Results

Adverse events occurring during the medication visit included moderate and severe anxiety reactions, paranoia, transient thought disorder, self-limited, asymptomatic, severe hypertension, and self-limited, moderate hypertension. Two participants met SCID-5-PD criteria for borderline personality disorder.

Fourteen participants experienced moderate to severe adverse reactions to psilocybin, seven experienced severe, but self-limited adverse reactions, and two unexpected psilocybin reactions occurred: one participant experienced a moderate post-traumatic stress flashback, and another participant with SCID-5 diagnosed generalized anxiety disorder and panic disorder experienced severe anxiety.

No change in suicidal ideation or behavior was detected over time with the C-SSRS, and no meaningful change was observed in SAHD or MoCA from baseline to 3-month follow-up.

4. Discussion

In a pilot study, demoralized, gay-identified, OLTAS men received psilocybin-assisted group therapy. The primary clinical outcome, self-reported demoralization, demonstrated robust change from baseline to end-of-treatment and to 3-month follow-up. Our findings resemble those of recent psilocybin therapy trials and those of two systematic reviews of individual psychedelic therapy for distress in patients with life-threatening illness, and compare favorably to a large trial of a brief (8-week), non-psychedelic, meaning-centered group psychotherapy for advanced cancer patients.

Modern trials of psilocybin have only administered the drug to carefully-screened clinical populations with adjunctive psychotherapy, and always in an individual format. Our study demonstrated the feasibility of administering psilocybin with adjuvant group psychotherapy, and that group therapy may help address social isolation, shame and stigma.

While some participants were slow to build rapport with the study clinicians, many participants reported that they were able to connect quickly with the other group members.

In many countries, psilocybin is regulated as a Schedule I drug. However, our data suggest that psilocybin can be safely administered under appropriate medical supervision.

Participants with significant trauma exposure and clinically active BPD symptoms reported higher rates of moderate-to-severe hypertension during the psilocybin session than have been reported in other studies with clinical populations and a comparable dose. However, severe hypertension seemed to co-occur with intense anxiety and self-resolved when the clinicians could calm the participant with verbal reassurance. Prior reports suggest that persons with borderline personality traits may have a harder time tolerating psilocybin, but that challenging psilocybin experiences may nevertheless be beneficial.

OLTAS may be a unique model of a distressed population that has faced serious adversity, traumatic loss, and both acute and chronic life-limiting illness.

This study highlights the need for controlled and well-blinded trials of psilocybin therapy for demoralization, complicated grief, and other forms of distress experienced by patients with serious medical illness and traumatic stress.

Contributors

BA, JW, JM, MB and JD designed the study, BA collected the data, and BA wrote the report. AD was the lead study clinician and supervised the psilocybin administration sessions.

Declaration of interests

The authors declare no financial conflicts of interest related to for-profit entities, and BA and JW received philanthropic gifts from individuals and non-profit organizations to support this trial.

Acknowledgements

The following grants supported the work on this trial: NIMH R25 MH060482, NIH UL1 TR001872, US Department of Veterans Affairs (Advanced Neurosciences Fellowship and IK2CX001495). BA and JW received philanthropic gifts from several individuals and non-profit organizations to conduct this trial.