May 2026
Psilocybin
What May 2026's 25 new studies found, synthesized from the papers below. All Psilocybin research →
The synthesis
Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below
Found by searching the library for Psilocybin, magic mushrooms, psilocin, psychedelic mushrooms, then ranked by relevance.
In May 2026, research on psilocybin showed large within-group effects on anxiety (g=0.96) and small between-group effects (g=0.48), with long-term antidepressant benefits persisting up to 12 months in treatment-resistant depression. However, blinding integrity was insufficient, with psilocybin showing the highest rates of functional unblinding, and evidence for cocaine use disorder and other conditions remains mixed or preliminary. The main caveat is that many studies are open-label, small, or have high heterogeneity, limiting the strength of conclusions.
Confidence in the evidence
Low-Moderate- One meta-analysis of 25 studies found large within-group but small between-group effects for anxiety, with high heterogeneity.
- A phase 2b trial with 126 participants showed long-term antidepressant effects up to 12 months, but was a naturalistic follow-up without a control group.
- A double-blind RCT on blinding integrity with 120 participants found insufficient blinding for psilocybin, raising methodological concerns.
- Several studies are open-label, small (e.g., n=20 for suicidal ideation, n=11 for cluster headache), or are protocols/corrigenda without results.
- Evidence for cocaine use disorder is mixed: one RCT found no significant effect on abstinence, while another study (non-peer-reviewed) claims efficacy.
How we rate confidence
Confidence reflects the strength of the underlying evidence, not whether the result is favorable. It weighs the number and size of studies, their design (randomized trials count for more than observational or single-case work), how consistently they point the same way, and their risk of bias.
Tiers run from Insufficient to High. High is rare in this field: small, early, or open-label studies land lower even when their direction is encouraging.
Evidence by study
Direction is each study's finding relative to your question: Supports, Opposes, No effect, Mixed, or Unclear.
| Study | Design | Sample size | Direction | Finding |
|---|---|---|---|---|
| Effect of psilocybin-assisted psychotherapy on anxiety symptoms: A systematic review and meta-analysis 2026 | systematic review and meta-analysis | 25 | Supports | Psilocybin-assisted psychotherapy showed a large within-group effect (g=0.96) and a small between-group effect (g=0.48) on anxiety, with high heterogeneity. |
| E8‑Based Neurochemical Simulation Accelerates Psilocybin Therapy for Cocaine Addiction — E8 Intelligence Research 2026 | theoretical/modeling | — | Unclear | An E8-based neurochemical simulation framework was used to model psilocybin therapy for cocaine addiction, but no empirical data are presented. |
| Effects of psilocybin on sleep quality and brain microstructure in chronic cluster headache. 2026 | observational | 11 | Supports | Psilocybin improved subjective sleep quality (PSQI change -2.50, p=0.015) but did not significantly change brain microstructure or water diffusivity. |
| A spatiotemporal gating hypothesis for psilocybin plasticity: reconciling the 5-HT₂A-TrkB mechanistic paradox. 2026 | theoretical | — | Unclear | A spatiotemporal gating hypothesis was proposed to reconcile the 5-HT2A-TrkB mechanistic paradox in psilocybin plasticity. |
| Psilocybin-induced neurocardiogenic syncope: a case report. 2026 | case report | 1 | Opposes | A case of neurocardiogenic syncope occurred 60 minutes after 25 mg psilocybin, highlighting a rare hypotensive adverse event. |
| Blinding integrity in psychedelic research: Evidence from a comparative randomized controlled trial of psilocybin, MDMA, and methylphenidate in healthy volunteers. 2026 | RCT | 120 | Opposes | Blinding was insufficient, with psilocybin showing the highest rates of functional unblinding compared to MDMA and methylphenidate. |
| Rapid and Sensitive Detection of Psilocybin and Psilocin in Urine by Surface‐Enhanced Raman Spectroscopy 2026 | methodological | — | Unclear | A SERS method was developed for rapid detection of psilocybin and psilocin in urine with high sensitivity. |
| Long-Term Efficacy of Psilocybin with Adjunct Psychotherapy in Treatment-Resistant Major Depression (EPIsoDE): 6- and 12-Month Naturalistic Follow-Up of a Phase 2b Trial. 2026 | phase 2b trial (naturalistic follow-up) | 126 | Supports | Psilocybin with adjunct psychotherapy showed significant antidepressant effects at 6 months (-7.93 HAMD17) and 12 months (-7.74 HAMD17) in a naturalistic follow-up. |
| Epigenome-wide association study of psilocybin-induced methylome changes in alcohol use disorder. 2026 | observational (EWAS) | 37 | Mixed | Psilocybin was associated with methylation changes in TLE4 and RASGRP4, but primary endpoints (abstinence, alcohol use) were not reached. |
| Psilocybin modulates social behaviour in male and female mice in a time-dependent manner. 2026 | preclinical | — | Mixed | Psilocybin modulated social behavior in a sex- and time-dependent manner, with acute effects in females and delayed effects in males. |
| PsiConnect: Multimodal Neuroimaging of Context-Dependent Brain and Behaviour Dynamics under Psilocybin. 2026 | observational (neuroimaging protocol) | 62 | Unclear | PsiConnect is a large-scale multimodal neuroimaging study designed to investigate context-dependent effects of psilocybin; no results reported. |
| Implementing psilocybin-assisted therapy in palliative care settings: A survey of stakeholders 2026 | cross-sectional survey | 121 | Supports | 95% of physicians had favorable attitudes toward psilocybin-assisted therapy, but lack of trained providers was a key barrier. |
| Ancient Wisdom, Modern Questions: Western and Orthodox Christianity Engage Psychedelic Spirituality 2026 | theoretical/review | — | Unclear | Orthodox Christian theology offers resources for evaluating psychedelic spirituality, including psilocybin-induced mystical experiences. |
| Corrigendum to: "Psilocybin in the real world: Regulatory, ethical, and operational challenges in Australia's clinical landscape". 2026 | corrigendum | — | Unclear | This is a corrigendum to a previous article on regulatory challenges in Australia; no new findings. |
| Appetite for change: How psilocybin reshapes food reward learning through striatal dopamine function 2026 | preclinical | — | Supports | Psilocybin enhanced reversal learning and amplified nucleus accumbens dopamine transients, with effects moderated by calorie restriction. |
| Short-Term and Late-Term Effects of Psilocybin on Symptoms in Major Depression 2026 | RCT | 35 | Supports | A single 25 mg psilocybin dose with psychotherapy met its primary endpoint, showing significant antidepressant effects at day 8 (MADRS) compared to niacin placebo. |
| Low doses of psilocybin as adjunct pharmacological treatment to virtual reality exposure therapy for social anxiety disorder: A study protocol for a double-blind randomized controlled trial. 2026 | study protocol | — | Unclear | This is a protocol for a double-blind RCT testing low-dose psilocybin as adjunct to VR exposure therapy for social anxiety disorder; no results. |
| Psilocybin-Assisted Therapy for Adolescent Anorexia Nervosa: Clinical Considerations and Emerging Models of Care. 2026 | theoretical/review | — | Unclear | Psilocybin-assisted therapy for adolescent anorexia nervosa is discussed theoretically, with proposed adaptations to adult models. |
| Inaugural year of regulated psilocybin services in Oregon: safety, motivations, and utilization 2026 | observational (descriptive analysis) | 5935 | Supports | In the inaugural year of regulated psilocybin services in Oregon, adverse events were rare (2.42-2.79 per 1000 sessions), with 5,935 clients served. |
| Microdosing psilocybin for major depressive disorder: study protocol for a phase II double-blind placebo-controlled randomised partial crossover trial - CORRIGENDUM. 2026 | corrigendum | — | Unclear | This is a corrigendum to a study protocol for microdosing psilocybin for MDD; no results. |
| Ethical Complexities and Best Practices in Informed Consent Processes for Psilocybin Services: A Qualitative Study 2026 | qualitative | 36 | Unclear | Experts recommended informed consent as an ongoing process, with detailed discussions of risks, benefits, and boundaries in psilocybin services. |
| Efficacy and Safety of a Single Dose of Psilocybin for Chronic Suicidal Ideation: An Open-Label Trial. 2026 | open-label trial | 20 | Supports | A single 25 mg psilocybin dose with psychological support significantly reduced suicidal ideation (MSSI) at week 3 (d=1.73), with effects lasting to week 12. |
| Safety and Efficacy of Psilocybin in the Management of Treatment-Resistant Depression: A Systematic Review 2026 | systematic review | 6 | Supports | Psilocybin showed promising results in lowering depressive scores in TRD, with common adverse events including anxiety, nausea, and headache, but no serious safety concerns. |
| Psilocybin in Older Adults: Therapeutic Opportunities in Inflammation-Driven Disorders of Aging-From Depression to Neurodegeneration. 2026 | review | — | Supports | Psilocybin is proposed as a multimodal therapeutic for inflammation-driven disorders of aging, with rapid onset, short half-life, and immunomodulatory effects. |
| Psilocybin in the Treatment of Cocaine Use Disorder 2026 | RCT | — | No effect | Psilocybin compared to placebo did not yield a higher percentage of cocaine abstinent days, greater likelihood of complete abstinence, or greater latency to first lapse. |
Psilocybin-assisted psychotherapy showed a large within-group effect (g=0.96) and a small between-group effect (g=0.48) on anxiety, with high heterogeneity.
systematic review and meta-analysis · Sample size: 25
An E8-based neurochemical simulation framework was used to model psilocybin therapy for cocaine addiction, but no empirical data are presented.
theoretical/modeling
Psilocybin improved subjective sleep quality (PSQI change -2.50, p=0.015) but did not significantly change brain microstructure or water diffusivity.
observational · Sample size: 11
A spatiotemporal gating hypothesis was proposed to reconcile the 5-HT2A-TrkB mechanistic paradox in psilocybin plasticity.
theoretical
A case of neurocardiogenic syncope occurred 60 minutes after 25 mg psilocybin, highlighting a rare hypotensive adverse event.
case report · Sample size: 1
Blinding was insufficient, with psilocybin showing the highest rates of functional unblinding compared to MDMA and methylphenidate.
RCT · Sample size: 120
A SERS method was developed for rapid detection of psilocybin and psilocin in urine with high sensitivity.
methodological
Psilocybin with adjunct psychotherapy showed significant antidepressant effects at 6 months (-7.93 HAMD17) and 12 months (-7.74 HAMD17) in a naturalistic follow-up.
phase 2b trial (naturalistic follow-up) · Sample size: 126
Psilocybin was associated with methylation changes in TLE4 and RASGRP4, but primary endpoints (abstinence, alcohol use) were not reached.
observational (EWAS) · Sample size: 37
Psilocybin modulated social behavior in a sex- and time-dependent manner, with acute effects in females and delayed effects in males.
preclinical
PsiConnect is a large-scale multimodal neuroimaging study designed to investigate context-dependent effects of psilocybin; no results reported.
observational (neuroimaging protocol) · Sample size: 62
95% of physicians had favorable attitudes toward psilocybin-assisted therapy, but lack of trained providers was a key barrier.
cross-sectional survey · Sample size: 121
Orthodox Christian theology offers resources for evaluating psychedelic spirituality, including psilocybin-induced mystical experiences.
theoretical/review
This is a corrigendum to a previous article on regulatory challenges in Australia; no new findings.
corrigendum
Psilocybin enhanced reversal learning and amplified nucleus accumbens dopamine transients, with effects moderated by calorie restriction.
preclinical
A single 25 mg psilocybin dose with psychotherapy met its primary endpoint, showing significant antidepressant effects at day 8 (MADRS) compared to niacin placebo.
RCT · Sample size: 35
This is a protocol for a double-blind RCT testing low-dose psilocybin as adjunct to VR exposure therapy for social anxiety disorder; no results.
study protocol
Psilocybin-assisted therapy for adolescent anorexia nervosa is discussed theoretically, with proposed adaptations to adult models.
theoretical/review
In the inaugural year of regulated psilocybin services in Oregon, adverse events were rare (2.42-2.79 per 1000 sessions), with 5,935 clients served.
observational (descriptive analysis) · Sample size: 5935
This is a corrigendum to a study protocol for microdosing psilocybin for MDD; no results.
corrigendum
Experts recommended informed consent as an ongoing process, with detailed discussions of risks, benefits, and boundaries in psilocybin services.
qualitative · Sample size: 36
A single 25 mg psilocybin dose with psychological support significantly reduced suicidal ideation (MSSI) at week 3 (d=1.73), with effects lasting to week 12.
open-label trial · Sample size: 20
Psilocybin showed promising results in lowering depressive scores in TRD, with common adverse events including anxiety, nausea, and headache, but no serious safety concerns.
systematic review · Sample size: 6
Psilocybin is proposed as a multimodal therapeutic for inflammation-driven disorders of aging, with rapid onset, short half-life, and immunomodulatory effects.
review
Psilocybin compared to placebo did not yield a higher percentage of cocaine abstinent days, greater likelihood of complete abstinence, or greater latency to first lapse.
RCT
Points of agreement
- Psilocybin shows rapid and sustained antidepressant effects in major depressive disorder and treatment-resistant depression.
- Psilocybin-assisted therapy is generally well-tolerated, with rare serious adverse events in controlled settings.
- Blinding is a significant methodological challenge in psilocybin research, with high rates of functional unblinding.
- Psilocybin modulates neuroplasticity and dopamine signaling, which may underlie its therapeutic effects.
Conflicts
- One RCT found psilocybin ineffective for cocaine use disorder (null result), while another non-peer-reviewed study claims efficacy.
- The meta-analysis on anxiety found high heterogeneity, indicating inconsistent effects across studies.
- Preclinical studies show sex- and time-dependent effects on social behavior, but human studies rarely examine sex differences.
Gaps
- Long-term durability of effects beyond 12 months is not well studied.
- Blinding integrity remains a major issue, with few studies using active placebos that effectively blind for psilocybin.
- Research on psilocybin for adolescent populations is limited to theoretical discussions.
- Dose-response relationships and optimal psychotherapy integration are not fully characterized.
- Racial and socioeconomic disparities in access to psilocybin services are documented but not addressed.