Psilocybin Associated With Potential Personality Changes in Patients With Cancer

Research suggests psilocybin-assisted psychotherapy may offer relief from psychiatric symptoms for people living with cancer.

A study published in Nature Mental Health reported that psilocybin-assisted psychotherapy (PAP) may offer therapeutic benefits for psychiatric symptoms in patients with cancer, with the potential for broader application as a comprehensive mental health intervention.¹

Investigators conducted the pooled analysis study based on previously unpublished data from a pair of phase 2 placebo-controlled crossover trials (NCT00957359, NCT00465595).^2,3 In the primary analyses, robust and sustained decreases in anxiety and depression were observed in patients with cancer-related psychiatric distress following a single PAP session. Investigators of the pooled analysis sought to investigate PAP’s effects on psychiatric symptoms beyond anxiety and depression.

Results from the analysis study found that PAP was associated with improved anxiety (P = .0049), depression (P = .0007), interpersonal sensitivity (P = .0005), obsession-compulsion (P = .0002), hostility (P = .009), and somatization (P < .0001). Improvements in these 6 dimensions subsequently remained when correcting for comparisons. Furthermore, after crossover, between-group differences lost significance at 6-month follow-up across all dimensions.

"Our findings suggest that the mental health benefits of psilocybin therapy for [patients with] cancer may reach far beyond what we have previously understood," Petros Petridis, MD, lead study author and clinical assistant professor in the Department of Psychiatry at NYU Grossman School of Medicine, said in a news release on the findings.⁴

Across both trials, 87 patients were randomly assigned 1:1 to receive either psilocybin first (n = 45) or control therapy first (n = 42), followed by crossover. A total of 79 patients completed at least post-dose 1 assessments. The final analysis data were collected through the first 6 months of follow-up from 68 patients (n = 34, 34).

Both trials randomly assigned patients to receive either 21 mg per 70 kg or 22 to 30 mg per 70 kg of psilocybin followed by control therapy with 250 mg of niacin or low-dose (1 to 3 mg per 70 kg) psilocybin; or the same control treatment first followed by high-dose psilocybin. Psychotherapy was conducted before and after each dosing session.

Of patients who completed at least post-dose 1 assessments, 42 were female vs 37 who were male, and the mean age was 55.6 years. The majority of patients were White (92.4%), with 2 patients identifying as Black (2.5%), 1 as East Asian (1.3%), and 3 as other races (3.8%). Most patients had at least a graduate or professional degree (50.6%) and were classified as married, partnered, or living together (64.6%).

Notably, 50 (63.5%) patients had advanced (stage III or IV), metastatic, or recurrent disease, including 57.5% of the psilocybin-first group. Prior hallucinogen use was observed in 48.1% of patients.

For the 6 dimensions improved by PAP, significant within-group improvements were observed in the psilocybin-first group for each assessment time point vs baseline. By the post-dose 2 period—when control-first patients would have taken psilocybin—significant within-group improvements were observed in the control-first group relative to baseline for the same 6 dimensions, which persisted through 6 months of follow-up for all but somatization.

PAP-related changes and placebo responses were consistent across clinical sites.

Of the 45 patients who began with psilocybin, 43 completed the first dose, 40 completed the post-dose 1 assessment, 38 completed dose 2 of control therapy, 37 completed post dose-2 assessments, and 34 finished follow-up. Of the 42 who were assigned to the initial control therapy dose, 42 completed dose 1, 39 completed the post-dose 1 assessment, 39 completed dose 2 with psilocybin, 35 completed post-dose 2 assessments, and 34 finished follow-up.

References

1. Petridis PD, Grinband J, Agin-Liebes G, et al. Psilocybin-assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer. Nat Mental Health. 2024;2:1408-1414. doi:10.1038/s44220-024-00331-0
2. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J. Psychopharmacol. 2016;30(12):1165-1180. doi:10.1177/0269881116675512
3. Griffiths RR, Johnson MW, Klinedinst MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J. Psychopharmacol. 2016;30(12):1181-1197. doi:10.1177/0269881116675513
4. Psychedelic drug therapy may address mental health concerns in people with cancer and addiction. News release. NYU Grossman School of Medicine and NYU Langone Health. January 2, 2025. Accessed January 2, 2025. https://tinyurl.com/54x4ze64