Long-term benefits of single-dose psilocybin in depressed patients with cancer

Agrawal and colleagues report outcomes from a Phase II, single-centre, fixed-dose, open-label trial of psilocybin combined with psychological support in adults with cancer and a concurrent major depressive disorder (MDD). The extracted text states that 30 participants with either curable or noncurable cancer were enrolled; patients were not taking antidepressant or antipsychotic medications or medical cannabis at screening and were screened to exclude suicide risk. The study received institutional review board approval and all participants provided written consent. Participants were organised into cohorts of three to four for preparatory work, with a 1:1 therapist-to-patient ratio for individual sessions. The treatment protocol comprised two baseline preparatory sessions (one group, one individual), a single oral dose of 25 mg psilocybin administered in one 6–7 hour session, and two group plus two individual integration sessions. In total each participant completed eight visits over approximately 8 weeks. Mental health outcomes were assessed at 2, 18, and 24 months post-treatment using the Montgomery–Åsberg Depression Rating Scale (MADRS) for depression and the Hamilton Anxiety Rating Scale (HAM-A) for anxiety. The investigators defined ‘‘significant reduction’’ as a ≥50% decrease in MADRS or HAM-A score, ‘‘sustained reduction’’ as having at least some improvement (the extracted text reports ≥0% reduction) at both the week 8 visit and the 24-month follow-up, and ‘‘remission’’ at 24 months as MADRS ≤10 or HAM-A ≤7. The text notes that design details and statistical analyses were described previously; the extracted material does not provide a complete description of the specific statistical models used beyond reporting group-level mean changes and p-values.

Two participants died during the follow-up interval, leaving 28 of the original 30 patients available for the 24-month effectiveness analysis. The median age at enrolment was 57.5 years and the majority of participants were female and White (further demographic detail is referenced but not fully reported in the extracted text). Over the 24-month observation period no participants were hospitalised for depression. Regarding subsequent treatments and substance use, 60.7% (17/28) did not receive additional psychiatric medications and 60.7% (17/28) did not use additional psychedelics; alcohol use decreased in 21.4% (6/28) of participants after the psilocybin session. Depression outcomes (MADRS): at 2 months post-treatment, 89.3% (25/28) of participants met the study definition of significant depression reduction, with an average change of −20.0 points from baseline (p < .001). At 24 months, 53.6% (15/28) retained significant depression reduction, with an average change of −15.0 points from baseline (p < .001). Half of the analysed sample, 50% (14/28), met the study’s criteria for both sustained reduction and remission at 24 months. The investigators report that 25% (7/28) of participants experienced sustained depression reduction at 24 months attributable to the single psilocybin dose without receiving any additional psychedelic or antidepressant treatments; the remainder included 25% (7/28) who had initiated antidepressant treatment after the psilocybin session, and three of those had received a second psychedelic treatment. Anxiety outcomes (HAM-A): at 2 months, 78.6% (22/28) met criteria for significant anxiety reduction, with an average change of −17.0 points from baseline (p < .001). At 24 months, 46.4% (13/28) continued to show significant anxiety reduction (average −13.9 points from baseline, p < .001). The extracted text indicates that 17.9% (5/28) achieved significant anxiety reduction at 24 months from a single psilocybin dose without additional psychedelic or antidepressant treatment, and 42.9% (12/28) experienced sustained anxiety reduction at 24 months. The paper presents these point estimates and associated p-values but the extracted text does not include confidence intervals or detailed model outputs.

Agrawal and colleagues interpret their findings as evidence that a single 25-mg dose of psilocybin administered with psychotherapy can produce durable reductions in depression and anxiety among patients with cancer who have MDD. They highlight that 50% of participants showed continued remission from depression at 24 months and note that for 25% of participants this sustained benefit occurred without subsequent antidepressant or psychedelic treatments. Similarly, the authors emphasise that clinically meaningful reductions in anxiety persisted for roughly 43% of participants at 24 months. The investigators position these results against prior literature on antidepressant use in cancer populations, citing a meta-analysis that showed only a small potential benefit for selective serotonin reuptake inhibitors at 6–12 weeks and no long-term follow-up beyond 12 weeks; they suggest their findings indicate a potentially longer-lasting therapeutic effect for psilocybin. The discussion flags outstanding questions to be addressed in future research, including which psychotherapeutic approaches best complement psilocybin, whether additional doses benefit non-responders, and the safety and efficacy of concurrent selective serotonin reuptake inhibitor use. The authors note an ongoing randomised, double-blind trial of a single 25-mg psilocybin dose versus placebo in patients with advanced cancer that they expect will provide more rigorous evidence. Key limitations and uncertainties are acknowledged implicitly by the authors’ call for further clinical research; the extracted text also indicates that aspects of the study design and analyses were described elsewhere and that some participants received additional psychiatric treatments during follow-up, which complicates attribution of long-term outcomes solely to the index psilocybin session. The authors conclude that psilocybin plus psychotherapy offers promising, potentially long-lasting relief of depression and anxiety for a substantial subset of cancer patients and argue for continued evaluation in clinical trials.