Psilocybin

Our assessments of evidence for each medical benefit fall into one of these categories:

• Strong evidence: consistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analysesa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results
• Good evidence: significant effects in one large or several mid-sized and well-designed clinical studies ( randomized controlled trialsa study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects with an appropriate placebo or other strong comparison control or observational studies that control for confounds)
• Modest evidence: significant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies), or several small studies aggregated into a meta-analysis
• Preliminary evidence: significant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect
• Weak evidence: one or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects
• Insufficient evidence: preclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example)

Learn more about how we research and rate therapies and practices in How We Rate Therapies ›

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of less anxiety among people with cancer with either end-of-life anxiety or psychiatric distress treated with psilocybin

• Less state anxietya temporary emotional state or condition characterized by feelings of nervousness, tension, and apprehension; physical symptoms may also be present both 1 day after treatment and 2 weeks, and a weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward less anxiety at 6 months, but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. at 3 months among people with end-of-life anxiety, mostly with cancer, treated with a single dose of psilocybin compared to controls in separate meta-analysesstatistical analyses that combine the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 3 of 5 total RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹Yu CL, Yang FC et al. Psilocybin for end-of-life anxiety symptoms: a systematic review and meta-analysis. Psychiatry Investigation. 2021 Oct;18(10):958-967.
• Less trait anxietya stable, enduring tendency to experience anxiety across a wide range of situations, reflecting a personality characteristic after 1 day, 2 weeks, and 6 months among people with end-of-life anxiety, mostly with cancer, treated with psilocybin compared to controls in separate meta-analyses of 3 of 5 total RCTs²Yu CL, Yang FC et al. Psilocybin for end-of-life anxiety symptoms: a systematic review and meta-analysis. Psychiatry Investigation. 2021 Oct;18(10):958-967.

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of fewer symptoms of depression among people with cancer and depression and/or anxiety treated with psilocybin

• Less loss of meaning enduring up to 4.5 years and weak trendsan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward less suicide ideation, hopelessness, and demoralization among people with advanced cancer and cancer-related anxiety and depression treated with a single, moderate-to-high dose of oral psilocybin (0.3 mg/kg) compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a within-group analysis in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects³Ross S, Agin-Liebes G et al. Acute and sustained reductions in loss of meaning and suicidal ideation following psilocybin-assisted psychotherapy for psychiatric and existential distress in life-threatening cancer. ACS Pharmacology & Translational Science. 2021 Mar 18;4(2):553-562.
• Less suicide ideation among people with advanced cancer with elevated suicide ideation at baseline when treated with psilocybin compared to baseline in a within-group analysis in a small RCT⁴Ross S, Agin-Liebes G et al. Acute and sustained reductions in loss of meaning and suicidal ideation following psilocybin-assisted psychotherapy for psychiatric and existential distress in life-threatening cancer. ACS Pharmacology & Translational Science. 2021 Mar 18;4(2):553-562.
• Lower depression scores after 2 and 26 weeks among people with cancer dealing with depressive symptoms treated with 3 group preparatory sessions, 1 high-dose (25 mg) group psilocybin session, and 3 group integration sessions with cohorts of four participants compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design⁵Lewis BR, Garland EL et al. HOPE: a pilot study of psilocybin enhanced group psychotherapy in patients with cancer. Journal of Pain and Symptom Management. 2023 Sep;66(3):258-269.
• Sustained reductions in depression, hopelessness, and demoralization at 3.2 and 4.5 years among people with cancer-related psychiatric distress treated with a single dose of psilocybin compared to placebo in a small RCT⁶Agin-Liebes GI, Malone T et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Journal of Psychopharmacology. 2020 Feb;34(2):155-166.
• Lower depression scores for at least 6 months among people with life-threatening cancer diagnoses and symptoms of depression and/or anxiety treated with 22 or 30 mg psilocybin per 70 kg compared to a placebo-like dose of 1 or 3 mg/70 kg in a small RCT⁷Griffiths RR, Johnson MW et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. Journal of Psychopharmacology. 2016 Dec;30(12):1181-1197.
• Immediate, substantial, and sustained improvements in depression and decreases in cancer-related demoralization and hopelessness, and improved spiritual well-being among people with cancer-related anxiety and depression treated with a single-dose psilocybin (0.3 mg/kg) compared to placebo in a small RCT⁸Ross S, Bossis A et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology. 2016 Dec;30(12):1165-1180.
• A weak trend toward lower depression scores at 2 weeks, becoming significant at 6 months, and a weak trend toward lower adverse mood tone scores after 2 weeks but not 6 months among people with advanced-stage cancer and reactive anxiety treated with 0.2 mg psilocybin per kilogram compared to placebo in a small RCT⁹Grob CS, Danforth AL et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry. 2011 Jan;68(1):71-8.
• Lower depression scores among people with cancer and major depression disorder treated with 25 mg COMP360 after 1 group preparation and 2 group integration sessions, supplemented by individual therapy, compared to baseline in a small uncontrolled trial¹⁰Agrawal M, Emanuel E et al. Assessment of psilocybin therapy for patients with cancer and major depression disorder. JAMA Oncology. 2023 Jun 1;9(6):864-866; Errors in Table. JAMA Oncology. 2024 Jul 11:e243130. Erratum for: JAMA Oncology. 2023 Jun 1;9(6):864-866.

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of better quality of life among people with cancer-related anxiety and/or depression treated with psilocybin

• Immediate, substantial, and sustained improvements in distress and quality of life in a woman with advanced lung cancer and substantial existential and psychological distress self-treated initially with about 1.5 g dried  mushrooms and then about 2 to 3 weeks later with a supervised 5 g of dried psilocybin mushrooms as a tea compared to baseline in a case studya descriptive and exploratory analysis of a person, group, or event regarding changes observed over time; because changes due to treatment are not compared to similar changes over time without treatment, a case study is considered a weak study design¹¹Patchett-Marble R, O’Sullivan S, Tadwalkar S, Hapke E. Psilocybin mushrooms for psychological and existential distress: treatment for a patient with palliative lung cancer. Canadian Family Physician. 2022 Nov;68(11):823-827.
• Increased quality of life among people with cancer-related anxiety and depression treated with a single dose of psilocybin (0.3 mg/kg) compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹²Ross S, Bossis A et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology. 2016 Dec;30(12):1165-1180.

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of less depression among people with depression treated with psilocybin

• Greater reductions in depression scores among people with major depressive disorder treated with a single dose of synthetic psilocybin and psychological support compared to placeboa pill, medicine, or procedure—thought to be both harmless and ineffective—prescribed for the psychological benefit to the patient or as a sham treatment in a study to allow a comparison to a therapy of interest and psychological support in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹³Raison CL, Sanacora G et al. Single-dose psilocybin treatment for major depressive disorder: a randomized clinical trial. JAMA. 2023 Sep 5;330(9):843-853.
• Fewer depression symptoms among people (not specific to cancer) treated with 1 or 2 doses of psilocybin compared to placebo or baseline in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 6 clinical trials¹⁴Yu CL, Liang CS et al. Trajectory of antidepressant effects after single- or two-dose administration of psilocybin: a systematic review and multivariate meta-analysis. Journal of Clinical Medicine. 2022 Feb 11;11(4):938.
• Comparable improvements in depression scores during psychological support among people with long-standing, moderate-to-severe major depressive disorder treated with either 2 separate 25 mg doses of psilocybin 3 weeks apart or 6 weeks of daily oral escitalopram in a small RCT¹⁵Carhart-Harris R, Giribaldi B et al. Trial of psilocybin versus escitalopram for depression. New England Journal of Medicine. 2021 Apr 15;384(15):1402-1411.
• Lower risk psychological distress during the past month and lower risk of suicidal thinking, suicidal planning, or suicide attempt in the past year among people ever using psilocybin in a very large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹⁶Hendricks PS, Thorne CB, Clark CB, Coombs DW, Johnson MW. Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. Journal of Psychopharmacology. 2015 Mar;29(3):280-8; Hendricks PS, Johnson MW, Griffiths RR. Psilocybin, psychological distress, and suicidality. Journal of Psychopharmacology. 2015 Sep;29(9):1041-3.

Psilocybin combined with psychotherapy

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of less depression among people with cancer and major depressive disorder treated with group therapeutic support sessions (some also receiving individual sessions) and a single dose of psilocybin

• Substantially lower depression severity scores, sustained at 8 weeks, among people with cancer and major depressive disorder treated with a single 25-mg dose of psilocybin with individual and group therapeutic support compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design¹⁷Agrawal M, Richards W et al. Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder. Cancer. 2024 Apr 1;130(7):1137-1146.
• Higher psycho-social-spiritual well-being scores for at least 8 weeks among people with cancer and major depressive disorder treated with group preparation sessions, a single dose of 25 mg of psilocybin, and group integration sessions, along with individual care compared to baseline in a small uncontrolled trial¹⁸Shnayder S, Ameli R, Sinaii N, Berger A, Agrawal M. Psilocybin-assisted therapy improves psycho-social-spiritual well-being in cancer patients. Journal of Affective Disorders. 2023 Feb 15;323:592-597.

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of less depression severity among people with major depressive disorder treated with 2 sessions of psilocybin in the context of supportive psychotherapy

• Less depression severity for at least 4 weeks among people with major depressive disorder treated with 2 sessions of psilocybin (20 mg/70 kg and then 30 mg/70 kg) in the context of supportive psychotherapy in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁹Davis AK, Barrett FS et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2021 May 1;78(5):481-489.

Psilocybin with meditation/spiritual practices: preliminary evidence of positive changes in interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, and religious faith and coping among healthy people treated with psilocybin in 2 sessions at 1 and 2 months after initiating spiritual practice

• Large, significant, positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings among healthy people treated with psilocybin in 2 sessions of 20 and 30 mg per 70 kg at 1 and 2 months after initiating spiritual practice compared to very low doses (1 mg/70 kg) in a small RCT²⁰Griffiths RR, Johnson MW et al. Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors. Journal of Psychopharmacology. 2018 Jan;32(1):49-69.