Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial - PubMed (original) (raw)
Clinical Trial
. 2016 Dec;30(12):1165-1180.
doi: 10.1177/0269881116675512.
Stephen Ross 1 2 3 4 5 6, Anthony Bossis 7 2 4, Jeffrey Guss 7 2 4, Tara Malone 7, Barry Cohen 9, Sarah E Mennenga 7, Alexander Belser 10, Krystallia Kalliontzi 2, James Babb 11, Zhe Su 3, Patricia Corby 2, Brian L Schmidt 2
Affiliations
- PMID: 27909164
- PMCID: PMC5367551
- DOI: 10.1177/0269881116675512
Clinical Trial
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial
Stephen Ross et al. J Psychopharmacol. 2016 Dec.
Abstract
Background: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression.
Methods: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks.
Results: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression.
Conclusions: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress.
Trial registration: ClinicalTrials.gov Identifier: NCT00957359.
Keywords: Psilocybin; anxiety; cancer; depression; mystical experience; psychedelic.
© The Author(s) 2016.
Conflict of interest statement
Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Figures
Figure 1.
CONSORT diagram.
Figure 2.
Interventions and assessments schedule. Temporal relationships between drug administration, psychosocial interventions, and assessments. Prep PT: preparatory psychotherapy; 1-day pre-D1: 1 day prior to dose 1; Dose 1: dosing session 1; 1-day post-D1: 1 day after dose 1; Post-integrative PT: post-integrative psychotherapy; 2-wks post-D1: 2 weeks after dose 1; 6-wks post-D1: 6 weeks after dose 1; Safety prep for D2: safety preparation for dosing dose 2; 1-day pre-D2: 1 day prior to dose 2; Dose 2: dosing session 2; 1-day post-D2: 1 day after dose 2; 6-wks post-D2: 6 weeks after dose 2; 26-wks post-D2: 2 weeks after dose 2.
Figure 3.
Primary outcome variables: cancer-related anxiety and depression (pre-crossover). Means (±SE) for primary outcome measures are shown in the two treatment groups at the following time points: baseline (psilocybin first _n_=14, niacin first _n_=15), 1 day pre-dose 1 (psilocybin first _n_=14, niacin first _n_=15), 1 day post-dose 1 (psilocybin first _n_=14, niacin first _n_=15), 2 weeks post-dose 1 (psilocybin first _n_=14, niacin first _n_=14), 6 weeks post-dose 1 (psilocybin first _n_=14, niacin first _n_=14), 7 weeks post-dose 1 (psilocybin first _n_=12, niacin first _n_=14). Asterisks indicate significance level of between-group _t_-tests. Effect sizes, represented as Cohen’s d, are shown above time points at which the treatment groups differ. Closed points represent significant within-group differences relative to scores at baseline.
Figure 4.
Primary outcome variables: cancer-related anxiety and depression (post-crossover). Means (±SE) for primary outcome measures are shown in the two treatment groups at the following time points: baseline (psilocybin first _n_=14, niacin first _n_=15), 1-day pre dose-1 (psilocybin first _n_=14, niacin first _n_=15), 1 day post-dose 1 (psilocybin first _n_=14, niacin first _n_=15), 6 weeks post-dose 1 (psilocybin first _n_=14, niacin first _n_=14), 7 weeks post-dose 1 (1 day pre-dose 2) (psilocybin first _n_=12, niacin first _n_=14), 1 day post-dose 2, 6 weeks post-dose 2 (psilocybin first _n_=12, niacin first _n_=11), 26 weeks post-dose 2 (psilocybin first _n_=11, niacin first _n_=12). Asterisks indicate significance level of between-group _t_-tests. Closed points represent significant within-group differences relative to scores at baseline.
Figure 5.
Percentage of participants with anti-depressant or anxiolytic response rates and anti-depressant symptom remission. Percentages of participants in each treatment group who met criteria for anti-depressant or anxiolytic response or anti-depressant symptom remission (BDI, HAD D) at 1 day post-dose 1 (psilocybin first _n_=14, niacin first _n_=15), 7 weeks post-dose 1 (psilocybin first _n_=12, niacin first _n_=14) and at 26 weeks post-dose 2 (psilocybin first _n_=11, niacin first _n_=12). Asterisks indicate significance level of between-group comparisons at each time point.
Figure 6.
Secondary outcome measures: existential distress, quality of life, spirituality, persisting effects attributed to psilocybin administration. (Top) Percentage of participants that reported ‘among the top 5’ or ‘the single most’ personally meaningful and spiritually significant experiences, ‘moderate’, ‘strong’ or ‘extreme’ positive behavioral change, and ‘increased moderately’ or ‘increased very much’ wellbeing or life satisfaction on the Persisting Effects Questionnaire (PEQ). Asterisks indicate significance level of comparison to the niacin first group at 2 weeks post-dose 1. There were no significant differences between the psilocybin first group at 2 weeks post-dose 1 versus the psilocybin first group at 26 weeks post-dose 2. (Bottom) Secondary measures of cancer-related existential distress (DEM, HAI, DAS, DTS), quality of life (WHO-Bref) and spirituality (FACIT). Measures are shown at 2 weeks post-dose 1 (psilocybin first _n_=14, niacin first _n_=14) and at 26 weeks post-dose 2 (psilocybin first _n_=11, niacin first _n_=12); asterisks indicate significance level of comparison to the niacin first group at 2 weeks post-dose 1. There were no significant differences between the psilocybin first group at 2 weeks post-dose 1 versus the psilocybin first group at 26 weeks post-dose 2.
Figure 7.
Subjective effects of psilocybin and relationship of mystical experience to clinical outcomes. (Top) Subjective effects as measured by the Mystical Experience Questionnaire (MEQ 30) in each treatment group at 7 hours post-session 1 (psilocybin first _n_=14, niacin first _n_=15), 7 hours post-session 2 (psilocybin first _n_=12, niacin first _n_=14), and 26 weeks post-dose 2 (psilocybin first _n_=11, niacin first _n_=12). Asterisks indicate significance level of between-group differences. (Bottom) Mediation model in which total scores on the MEQ transmit a portion of the effects of psilocybin versus niacin treatment on change in anxiety and depression is shown.
Comment in
- Back to the future: Research renewed on the clinical utility of psychedelic drugs.
Lieberman JA, Shalev D. Lieberman JA, et al. J Psychopharmacol. 2016 Dec;30(12):1198-1200. doi: 10.1177/0269881116675755. J Psychopharmacol. 2016. PMID: 27909166 No abstract available. - Psilocybin: Psychotherapy or drug?
Goodwin GM. Goodwin GM. J Psychopharmacol. 2016 Dec;30(12):1201-1202. doi: 10.1177/0269881116675757. J Psychopharmacol. 2016. PMID: 27909167 No abstract available. - Psilocybin in end of life care: Implications for further research.
Summergrad P. Summergrad P. J Psychopharmacol. 2016 Dec;30(12):1203-1204. doi: 10.1177/0269881116675758. J Psychopharmacol. 2016. PMID: 27909168 No abstract available. - Psycho-existential distress in cancer patients: A return to "entheogens".
Blinderman CD. Blinderman CD. J Psychopharmacol. 2016 Dec;30(12):1205-1206. doi: 10.1177/0269881116675761. J Psychopharmacol. 2016. PMID: 27909169 No abstract available. - Psilocybin and palliative end-of-life care.
Shelton RC, Hendricks PS. Shelton RC, et al. J Psychopharmacol. 2016 Dec;30(12):1207-1208. doi: 10.1177/0269881116675764. J Psychopharmacol. 2016. PMID: 27909170 No abstract available. - Psilocybin for depression and anxiety associated with life-threatening illnesses.
McCorvy JD, Olsen RH, Roth BL. McCorvy JD, et al. J Psychopharmacol. 2016 Dec;30(12):1209-1210. doi: 10.1177/0269881116675771. J Psychopharmacol. 2016. PMID: 27909171 No abstract available. - The successful return of psychedelics to psychiatry.
Kleber HD. Kleber HD. J Psychopharmacol. 2016 Dec;30(12):1211. doi: 10.1177/0269881116675779. J Psychopharmacol. 2016. PMID: 27909172 No abstract available. - The role of psychedelics in palliative care reconsidered: A case for psilocybin.
Kelmendi B, Corlett P, Ranganathan M, D'Souza C, Krystal JH. Kelmendi B, et al. J Psychopharmacol. 2016 Dec;30(12):1212-1214. doi: 10.1177/0269881116675781. J Psychopharmacol. 2016. PMID: 27909173 No abstract available. - Psilocybin-assisted psychotherapy for dying cancer patients - aiding the final trip.
Spiegel D. Spiegel D. J Psychopharmacol. 2016 Dec;30(12):1215-1217. doi: 10.1177/0269881116675783. J Psychopharmacol. 2016. PMID: 27909174 No abstract available. - Psilocybin: promising results in double-blind trials require confirmation by real-world evidence.
Breckenridge A, Grobbee DE. Breckenridge A, et al. J Psychopharmacol. 2016 Dec;30(12):1218-1219. doi: 10.1177/0269881116675784. J Psychopharmacol. 2016. PMID: 27909175 No abstract available.
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