Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer

Abstract

Background: A recently published randomized controlled trial compared single-dose psilocybin with single-dose niacin in conjunction with psychotherapy in participants with cancer-related psychiatric distress. Results suggested that psilocybin-assisted psychotherapy facilitated improvements in psychiatric and existential distress, quality of life, and spiritual well-being up to seven weeks prior to the crossover. At the 6.5-month follow-up, after the crossover, 60–80% of participants continued to meet criteria for clinically significant antidepressant or anxiolytic responses. Methods: The present study is a long-term within-subjects follow-up analysis of self-reported symptomatology involving a subset of participants that completed the parent trial. All 16 participants who were still alive were contacted, and 15 participants agreed to participate at an average of 3.2 and 4.5 years following psilocybin administration. Results: Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at the first and second follow-ups. Within-group effect sizes were large. At the second (4.5 year) follow-up approximately 60–80% of participants met criteria for clinically significant antidepressant or anxiolytic responses. Participants overwhelmingly (71–100%) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives. Conclusion: These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress. Limited conclusions, however, can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study. Nonetheless, the present study adds to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological, emotional, and spiritual well-being of patients with life-threatening cancer.

Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance

“…In recent years, several early-phase clinical trials have provided evidence that classic serotonergic psychedelics-in most cases psilocybin, but also lysergic acid diethylamide (LSD) and the dimethyltryptamine (DMT)-containing brew ayahuasca-may occasion substantial and often sustained symptom reductions in patients treated for depression (1)(2)(3), psychological distress related to life-threatening illness (4)(5)(6)(7)(8), obsessive-compulsive disorder (9), and substance use disorders (10,12). It has been proposed that psychedelic therapy works by reducing patterns of experiential avoidance and promoting more adaptive acceptance [ (13); see below for definitions of these terms].…”

Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin

“… 8 , 9 In contrast to currently available pharmacotherapies for the aforementioned conditions, a remarkable feature of psychedelic-mediated approaches is the apparent lasting effect produced by a single dose of a drug. 10 Though more than 100 different chemicals built upon phenethylamine, tryptamine, or lysergamide scaffolds have been shown to produce characteristic psychedelic effects in humans mediated in part by agonist activity at the 5-HT 2A receptor in the central nervous system, 11 − 14 the fungal natural product psilocybin was selected as the most suitable candidate to usher in the modern era of clinical research into psychedelics for several reasons. Psilocybin has been likely consumed by humans for thousands of years, 15 has been shown to be well tolerated across escalating doses (18–72 mg) with a clinically acceptable 4–6 h duration of action, 16 and is generally free from the manufactured stigma associated with other known psychedelic molecules, such as lysergic acid diethylamide (LSD).…”

Psychedelic‐assisted therapy for functional neurological disorders: A theoretical framework and review of prior reports

“…In the two larger studies, continued benefit was seen in 60%-80% of patients at 6 months [48][49][50] ; a recent follow-up to one of those studies found effects to be sustained at 4.5 years. 51 Promising preliminary results have also been observed with psilocybin-assisted psychotherapy in alcoholism, 52 smoking cessation, 53 obsessive compulsive disorder, 54 and treatment-refractory major depression. 55,56 There is interest in psychedelic-assisted therapy as a potential treatment for a number of other disorders including anorexia nervosa, 57 bipolar disorder, 58 chronic pain, 59 and cocaine addiction.…”