Psilocybin & PTSD
0 serious adverse events
In the only published psilocybin PTSD trial, a single 25mg dose produced 117 treatment-emergent events and zero serious ones. 91.4% resolved by the following day.
McGowan et al., Journal of Psychopharmacology, 2025
22
PTSD patients in the first dedicated psilocybin PTSD safety trial, across 3 clinical sites (McGowan 2025)
91.4%
of adverse events on dosing day resolved by the following morning (McGowan 2025)
59
TRD patients in Carhart-Harris 2021 NEJM RCT; also zero serious adverse events in the psilocybin arm
McGowan et al., Journal of Psychopharmacology, 2025
View as image ↗The most common side effect in the only published clinical trial testing psilocybin specifically in PTSD patients was a headache. Half of participants experienced one. Nausea affected about one in three. Crying was reported by more than a quarter of participants. Fatigue appeared at the same rate.
Those are the concrete numbers from McGowan and colleagues' 2025 open-label safety trial, published in the Journal of Psychopharmacology.[1] Most online content about psilocybin PTSD safety either uses generic warnings without trial data or conflates MDMA evidence with psilocybin evidence. This article works from the published numbers.
Psilocybin remains a Schedule I controlled substance in the United States. Research described here is from supervised clinical trial settings only.
For the broader clinical picture, see Psilocybin for PTSD: What the Clinical Trials Show.
Key Takeaways
- The only published psilocybin PTSD trial (McGowan et al. 2025, n=22, 25mg COMP360) reported zero serious adverse events, zero trial withdrawals due to side effects, and 91.4% of dosing-day events resolved by the following day
- Most common adverse events in the PTSD trial: headache (50%), nausea (36.4%), crying (27.3%), fatigue (27.3%)
- In the Carhart-Harris 2021 NEJM randomized trial (n=59 treatment-resistant depression), psilocybin produced no serious adverse events across two 25mg doses over three weeks
- A 2025 meta-analysis covering four psychedelic therapies found adverse events in psilocybin arms were generally mild, transient, and similar to comparator conditions (Bahji et al., 2025)
- A 2025 systematic review found psilocybin produces transient blood pressure and heart rate increases during dosing sessions but no lasting cardiovascular changes in healthy adults; cardiac screening is flagged as especially relevant for veteran populations
- Qualitative data from 21 PTSD patients in a psilocybin trial found most did NOT directly revisit traumatic memories during sessions; they processed affect and body sensations around the trauma rather than through it (Modlin et al., 2025)
The Adverse Event Numbers Competitors Don't Show: McGowan 2025
McGowan and colleagues (2025) published the only study to date specifically recruiting PTSD patients for a psilocybin trial and reporting their safety data as a primary outcome.[1]
The trial enrolled 22 participants with PTSD at three clinical sites: King's College London, Mount Sinai, and Sunstone Therapies. Each received a single 25mg dose of COMP360 (synthetic psilocybin) in a structured session with two therapists, plus three preparatory sessions and three integration sessions surrounding the dosing day.
The adverse event profile:
| Adverse Event | Frequency (n=22) |
|---|---|
| Headache | 50% |
| Nausea | 36.4% |
| Crying | 27.3% |
| Fatigue | 27.3% |
| Serious adverse events | 0 |
| Withdrawals due to adverse events | 0 |
Source: McGowan et al., Journal of Psychopharmacology, 2025
117 treatment-emergent adverse events were recorded in total across all 22 participants and the entire study period. Of those, 59.8% occurred on the dosing day. Among events occurring on the dosing day, 91.4% had resolved by the following morning.
Adverse Event Profile · McGowan 2025 (n = 22)
What Happened to the 22 PTSD Patients Who Received Psilocybin
The bars show how often each side effect was reported in the only published trial of psilocybin in PTSD patients. The most common event was a headache, in half of participants. Across the whole study, 117 adverse events were recorded — and none were serious.
Headache
50.0% · 11 / 22Nausea
36.4% · 8 / 22Crying
27.3% · 6 / 22Fatigue
27.3% · 6 / 220
Serious adverse events
0
Withdrawals due to adverse events
91.4%
Dosing-day events resolved by the next day
How to read it: percentages are the share of the 22 participants who reported each event at least once, so they do not sum to 100%. This was an open-label trial with no placebo arm — without a comparison group, the baseline rate of events like headache or fatigue in a supervised clinical setting is not known.
Source: McGowan et al. 2025, Journal of Psychopharmacology [1]. Figures are the reported treatment-emergent adverse event frequencies among 22 enrolled participants; bar length is the actual reported percentage.
At 12-week follow-up, participants showed rapid and durable PTSD symptom improvement. The trial was not randomized or placebo-controlled, which limits what can be concluded about efficacy. For safety characterization, however, an open-label trial with systematic adverse event reporting provides meaningful data.
One note on crying appearing alongside headache and nausea in the adverse event table: in the context of PTSD and psilocybin therapy, crying during a session is a common element of emotional processing. Capturing it as an adverse event reflects rigorous reporting standards rather than indicating participant distress. The trial report contextualizes each event by severity and resolution.
How PTSD Safety Compares to Larger Depression Trials
McGowan 2025 enrolled only 22 participants, which limits statistical precision. Larger psilocybin depression trials provide useful context for interpreting the PTSD data.
The Carhart-Harris 2021 trial in the New England Journal of Medicine enrolled 59 patients with treatment-resistant depression and randomized them to psilocybin (n=30) or six weeks of escitalopram (n=29).[6] Participants in the psilocybin arm received two 25mg doses administered three weeks apart. No serious adverse events were recorded in the psilocybin arm across both sessions. The psilocybin group also showed greater emotional reconnection and well-being scores than the escitalopram group at the primary endpoint.
A 2025 meta-analysis by Bahji and colleagues covered psilocybin, MDMA, ketamine, and ayahuasca across depression, anxiety, and PTSD outcomes.[4] Adverse events across all four agents were generally mild, transient, and comparable to comparator conditions. Psilocybin showed durable symptom-reduction effects across all three outcome domains.
Yao and colleagues published a 2024 systematic review and meta-analysis of psychedelics across mental disorders, finding significant effect sizes for psilocybin on depression and anxiety, with adverse events described as manageable across studies.[5]
One consistent finding across these sources: the PTSD population in early trial data does not appear to generate a meaningfully different safety profile than the depression population. The adverse event types and rates in McGowan 2025 are broadly consistent with what larger depression trials have reported.
Veterans: Psilocybin in a Higher-Acuity Subgroup
Military veterans with PTSD often present with additional clinical complexity, including higher rates of comorbid traumatic brain injury, substance use history, cardiovascular disease, and broader medication burden. The first psilocybin study specifically in U.S. military veterans was published by Ellis and colleagues in 2025.[3]
That open-label pilot enrolled veterans with severe treatment-resistant depression, many with comorbid PTSD. The key finding: the treatment was well-tolerated in this high-acuity population. Ellis and colleagues noted that veteran-specific cultural factors, particularly stigma around mental health treatment and unit identity, required adapted therapeutic framing. Pharmacological tolerability was comparable to what other trials have reported.
Veterans represent one of the populations with the most urgent clinical need for effective PTSD treatment, and the question of whether psilocybin is safe in this higher-complexity group is clinically important. The Ellis 2025 data, while small, provides early reassurance.
Cardiovascular: Transient During Sessions, Nothing Lasting
A 2025 systematic review specifically examined cardiovascular safety data across psilocybin, LSD, and DMT trials.[7]
The finding: psilocybin produces transient increases in blood pressure and heart rate during the dosing session. These increases are time-limited and parallel the peak subjective effects. In healthy adults without pre-existing cardiovascular conditions, no lasting cardiovascular changes were documented after sessions ended.
The cardiovascular review flagged cardiac screening as important for populations with high cardiovascular comorbidity. This is directly relevant to veterans with PTSD, who show elevated rates of hypertension, atherosclerosis, and other cardiovascular conditions. The review's authors noted that active cardiac disease and certain cardiac medications are likely contraindication considerations for clinical practice.
The specific thresholds for cardiovascular exclusion are not standardized across trial protocols. Published trials have included medical screening procedures, but exact cardiac exclusion criteria vary by study.
Does Psilocybin Risk Re-Traumatizing Patients? What the Qualitative Data Found
The concern most often raised about psilocybin for PTSD is whether it could force participants to relive traumatic memories without adequate support, causing psychological harm rather than healing.
Modlin and colleagues published a 2025 qualitative study in eClinicalMedicine (a Lancet journal) nested within a psilocybin PTSD clinical trial, interviewing 21 participants about their experience.[2]
The finding was both specific and surprising: most participants did NOT directly revisit traumatic memories during their psilocybin sessions. Instead, they described engaging with affect, body sensations, and self-transcendent states that were related to their trauma emotionally but did not take the form of memory replay. Participants described this as processing around the trauma rather than through it, a fundamentally different experience from exposure-based therapies like prolonged exposure, which explicitly involve memory confrontation.
Participants in the Modlin 2025 study described four consistent themes across their experiences: the importance of non-pharmacological safety factors (setting, therapist relationship, preparation quality), the experiential rather than cognitive nature of the treatment, engagement with trauma-related material in indirect and somatic ways, and favorable comparison with prior treatment attempts.
This does not eliminate the possibility of psychological distress during psilocybin sessions. Difficult experiences do occur, including anxiety, confusion, and emotionally charged content. The trial adverse event data captures this. The qualitative picture from Modlin 2025 suggests that the feared scenario of forced trauma re-exposure is not the typical experience reported by PTSD patients in psilocybin sessions.
For context on how these experiential differences relate to psilocybin's mechanistic effects on trauma processing, see How Psilocybin Therapy Approaches Trauma Differently. And for the latest COMP360 PTSD results, see COMP360 for PTSD: Compass Pathways Trial Results.
Who Was Not in These Trials: Exclusion Criteria and Risk Profile
Understanding who was excluded from published psilocybin PTSD trials is part of interpreting the safety data. The favorable adverse event profile in McGowan 2025 describes a pre-screened population.
Miller and Zoladz (2025), in their systematic review of psilocybin's potential for PTSD, specifically addressed populations with elevated risk.[8] Standard exclusion considerations across published trials include: personal or family history of psychotic disorders; active suicidality; severe dissociative symptoms; and current substance use disorders. These exclusions reflect two primary concerns: risk of psychosis precipitation in vulnerable individuals, and difficulty managing session experiences safely in participants with severe dissociative or suicidal presentations.
The antidepressant interaction is also relevant for a PTSD population, since many PTSD patients are prescribed SSRIs as first-line treatment. SSRIs act on serotonin systems, and combining them with serotonergic compounds carries a theoretical risk of serotonin toxicity. Published trials have managed this by requiring participants to taper off SSRIs before psilocybin administration. Washout protocols vary by study and have not been standardized.
All of this means the safety data described here reflects supervised clinical research conditions with pre-screened populations. For ongoing trial information, see Psilocybin for PTSD: Current Clinical Trials and Preliminary Data.
Why Reading Psychedelic Safety Data Requires a Caveat
One methodological limitation applies across all psychedelic trials: functional unblinding. Participants generally know when they have received an active psychedelic versus a placebo, because the subjective effects are detectable. This means blinding does not work the way it does in SSRI trials.
Yao and colleagues' 2024 systematic review identified functional unblinding as a consistent methodological limitation that warrants cautious interpretation of effect size magnitude in psychedelic trials.[5]
This affects how to read both efficacy and safety data. On the safety side: adverse event reporting in open-label trials may be influenced by participants' knowledge that they received an active drug. Events like headache or fatigue are common in any supervised clinical setting, and without a placebo arm it is not possible to determine what baseline rate would look like without psilocybin.
The McGowan 2025 trial was open-label with no comparator arm. The adverse event rates reported are what they are: documented events in 22 participants who all received active psilocybin. The absence of serious adverse events and the rapid resolution rates are meaningful findings. The evidence base, however, is early, small, and predominantly from open-label designs. Phase 3 randomized data will provide more definitive safety characterization.
The Bottom Line
Published safety data for psilocybin in PTSD populations is encouraging but limited in scale. The McGowan 2025 trial, the only study specifically designed to assess psilocybin safety in PTSD patients, found the most common adverse events were headache (50%), nausea (36.4%), crying (27.3%), and fatigue (27.3%), with zero serious adverse events and 91.4% of dosing-day events resolving by the next morning. This profile is consistent with larger psilocybin depression trial data from Carhart-Harris 2021 and the Bahji 2025 meta-analysis. Qualitative data from Modlin 2025 suggests most participants did not relive traumatic memories during sessions. Cardiovascular monitoring is warranted given transient BP and HR elevations, with particular relevance for veteran populations. Phase 3 randomized data will be necessary for a definitive safety characterization.
Frequently Asked Questions
Sources & References
- 1RTHM-00941·McGowan, Niall M et al. (2025). “Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial..” Journal of psychopharmacology (Oxford.Study breakdown →PubMed →↩
- 2RTHM-02152·Modlin, Nadav Liam et al. (2025). “Investigational psilocybin treatment for post-traumatic stress disorder: a qualitative study of participant experience, trauma engagement, and differences from standard treatment..” EClinicalMedicine.Study breakdown →PubMed →↩
- 3RTHM-00923·Ellis, Sara et al. (2025). “Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - A first-in-kind open-label pilot study..” Journal of affective disorders.Study breakdown →PubMed →↩
- 4RTHM-02055·Bahji, Anees et al. (2025). “Efficacy and Safety of Four Psychedelic-Assisted Therapies for Adults with Symptoms of Depression, Anxiety, and Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis..” Journal of psychoactive drugs.Study breakdown →PubMed →↩
- 5RTHM-02028·Yao, Yuan et al. (2024). “Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis..” Psychiatry research.Study breakdown →PubMed →↩
- 6RTHM-00675·Carhart-Harris, Robin et al. (2021). “Trial of Psilocybin versus Escitalopram for Depression..” The New England journal of medicine.Study breakdown →PubMed →↩
- 7RTHM-02156·Nahlawi, Acile et al. (2025). “Cardiovascular effects and safety of classic psychedelics..” Nature cardiovascular research.Study breakdown →PubMed →↩
- 8RTHM-02149·Miller, Claire E et al. (2025). “Evaluating the potential for psilocybin as a treatment for post-traumatic stress disorder..” The Journal of pharmacology and experimental therapeutics.Study breakdown →PubMed →↩