Breakthrough Clinical Results

Compass Pathways announced the publication of positive Phase 2 results for their investigational drug COMP360, a synthetic psilocybin, in treating post-traumatic stress disorder (PTSD). The open-label study of 22 patients showed COMP360 to be well-tolerated with no serious adverse events. A single 25mg dose resulted in rapid and durable improvements in PTSD symptoms, as measured by CAPS-5 and SDS scores, lasting up to 12 weeks. High response and remission rates were observed. Compass Pathways is now finalizing designs for late-stage clinical trials based on these encouraging findings.

Incidence and Prevalence

Global Prevalence and Incidence of Post-Traumatic Stress Disorder

General Population Estimates

Lifetime PTSD prevalence rates in the U.S. population range from 7% to 8%. While 50-85% of Americans will experience a traumatic event in their lifetime, only 2-50% will develop PTSD. On a global scale, PTSD affects approximately 8% of the world's population during their lifetime, despite 80-90% of trauma-exposed individuals not developing PTSD.

Recent Regional and Population-Specific Findings

A 2024 systematic review and meta-analysis of PTSD in the Iranian population found an overall prevalence of 31.87% (95% confidence interval=17.87-45.87), with higher rates in men (36.64%) than women (35.52%).

In Ukraine, one year after the onset of the Russo-Ukrainian war (2023 data), 14.4% of adults had probable PTSD, and another 8.9% had complex PTSD (CPTSD).

Among college students during COVID-19, a 2023 meta-analysis found a pooled prevalence of PTSD at 25% (95% CI: 21-28%), with higher rates in Africa and Europe. Medical college students and those in lower-middle-income countries had higher PTSD prevalence than the overall average.

Specific Populations

Emergency department professionals show PTSD rates ranging from 0% to 23.6% with a mean of 10.47%, which is elevated compared to the general population.

Among treatment-seeking military veterans in the UK, rates of PTSD were high (68.7%), with most experiencing complex PTSD (62.5%) compared with PTSD (6.2%).

In older adults aged 60 years and older in the US, DSM-5 PTSD prevalence was 9.5% while ICD-11 prevalence was 8.7%.

A study of Ugandan nurses during the second wave of COVID-19 found an estimated prevalence of 65.7%.

Among psychology doctoral students, approximately 14.7% had probable PTSD.

In Chinese Shidu parents (who have lost their only child), the prevalence of PTSD was 14.45%, with 87.30% with PTSD having comorbid depression and anxiety symptoms.

A study of World Trade Center responders found that 16.5% had PTSD.

Risk Factors and Temporal Patterns

Risk factors include pre-existing individual-based factors, features of the traumatic event, and posttrauma social support. Women; Black, Indigenous, and people of color; and LGBQ+ individuals face heightened risks of PTSD.

A meta-analysis found that over a quarter of individuals presented with PTSD at 1 month post-trauma, with this proportion reducing by a third between 1 and 3 months. Recovery from PTSD following acute trauma exposure primarily occurs in the first 3 months post-trauma.

Intentional trauma, younger age, and female sex were associated with higher PTSD prevalence at 1 month post-trauma, while higher proportions of females, intentional trauma exposure, and higher baseline PTSD prevalence were each associated with larger reductions in prevalence over time.

Recent Studies

Recent PTSD Intervention Studies

Condensed Internet-Delivered Prolonged Exposure (CIPE) Study

This single-site randomised controlled trial evaluated CIPE in self-referred adults (N=102) exposed to trauma within 2 months. Participants received either 3 weeks of CIPE or were placed on a waiting list for 7 weeks. The study demonstrated statistically significant reductions in post-traumatic stress symptoms in the CIPE group with moderate effect sizes at week 3 (bootstrapped d=0.70) and large effect sizes at week 7 (bootstrapped d=0.83). Results were maintained at 6-month follow-up. Regarding safety, no severe adverse events were reported. CIPE was concluded to be a scalable intervention that may provide early benefits for trauma survivors.

Physical Activity (PA) Intervention Meta-Analysis

This was the first systematic review and meta-analysis examining the effect of physical activity on PTSD. Four unique RCTs (n=200) were included. The methodological quality was deemed satisfactory. For safety, no major adverse events were reported. Regarding efficacy, PA was significantly more effective than control conditions at decreasing both PTSD and depressive symptoms, suggesting PA may be a useful adjunct to usual care.

Trauma-Focused vs. Non-Trauma Focused Treatments Meta-Analysis

This meta-analysis included 22 studies with 24 head-to-head comparisons in RCTs involving 1694 patients. Results showed a small relative advantage for trauma-focused treatments at post-treatment (Hedges' g=0.14) and follow-ups. Prolonged exposure and exposure therapies (g=0.19) were slightly more efficacious than other therapies, with prolonged exposure showing higher recovery rates (RR=1.26).

Creative Arts Therapy Meta-Analysis (2025)

This meta-analysis assessed creative arts therapy for PTSD, analyzing seven controlled comparative studies. Results showed a significant decrease in PTSD symptoms (SMD=-1.98, 95% CI: -3.8 to -0.16, p<0.03). Drama therapy was notably effective, while music, art, and dance/movement therapies showed less pronounced effects.

Prazosin for PTSD Meta-Analysis (2017)

This systematic review and meta-analysis evaluated prazosin for PTSD treatment, including six randomized controlled trials. Patients receiving prazosin showed significant improvement in nightmares (SMD=1.01), overall PTSD symptoms (SMD=0.77), and clinical global improvement (SMD=0.94).

Couple Treatment for Alcohol Use Disorder and PTSD (CTAP) Trial (2016)

This uncontrolled trial studied CTAP in 13 U.S. male military veterans and their female partners. CTAP is a 15-session, manualized therapy integrating behavioral couples therapy for alcohol use disorder with cognitive-behavioral conjoint therapy for PTSD. Nine couples completed the study with significant group-level reductions in PTSD symptoms (d=0.94 to 1.71).

Drug used in other indications

COMP360 Psilocybin Clinical Trials Beyond PTSD

Indications Being Investigated

COMP360, a proprietary, synthetic formulation of psilocybin, is currently being trialled for several mental health conditions beyond Post-traumatic stress disorder:

1. Treatment-resistant depression (TRD) - This is the primary indication being investigated, with a phase 2 double-blind trial involving 233 participants already conducted.

2. Depression in healthcare workers - A recent trial (2024) specifically targeted depression in healthcare workers who developed symptoms from frontline work during the COVID-19 pandemic.

3. Antidepressant-free, treatment-resistant depression - COMPASS Pathways is conducting a phase 2b double-blind trial to determine safety, efficacy, and optimal dose.

4. Treatment-resistant depression in conjunction with SSRIs - An additional study with a centre in Dublin is addressing the efficacy and safety of psilocybin therapy alongside standard antidepressants.

Other potential indications mentioned in research include: - Addiction - Obsessive compulsive disorder - Cluster headache - Distress related to life-threatening diagnoses and terminal illness

Intervention Models

The intervention models for these trials typically follow a structured approach:

• Single dose administration of psilocybin (doses studied include 25 mg, 10 mg, or 1 mg)
• Psychological support from trained therapists

In the COVID-19 clinician study specifically, the intervention consisted of: - 2 preparation visits - 1 medication session - 3 integration visits

The general therapeutic framework appears to be consistent across indications, focusing on psilocybin administration with psychological support. This approach aims to leverage both the pharmacological effects of psilocybin and the therapeutic context to achieve clinical benefits.

Research indicates that psilocybin has shown promise as a transdiagnostic treatment strategy for disorders characterized by restricted and maladaptive habitual patterns of cognition and behaviour. The treatment typically involves 1-3 doses with both immediate and prolonged effects.

Most trials report common adverse events including headache, nausea, and dizziness, occurring in approximately 77% of participants in the TRD trials.

Researchers conclude that larger and longer trials, including comparison with existing treatments, are required to fully determine the efficacy and safety of psilocybin across these various indications.