Positive Phase 2 Results: Psilocybin-Assisted Psychotherapy Treatment, PSX-001, for Generalized Anxiety Disorder

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Incannex Healthcare shared positive data from its phase 2 clinical trial of PSX-001 (formerly known as Psi-GAD), a psilocybin-assisted psychotherapy treatment for generalized anxiety disorder (GAD). Participants treated with PSX-001 achieved statistically significant and clinically meaningful improvements across every key endpoint assessed in the study, reinforcing its potential as a treatment for patients with moderate to severe GAD.

“These are outstanding results for Incannex and a major milestone for our clinical pipeline,” said Joel Latham, president and chief executive officer of Incannex. “The success of PSX-001 significantly de-risks another of our lead assets and further validates our strategy of developing innovative combination and psychedelic-based therapies. To deliver back-to-back positive phase 2 results for both PSX-001 and IHL-42X is an exceptional achievement, and one that gives us tremendous confidence as we progress towards late-stage development.”

In the randomized, double-blind, placebo-controlled phase 2 study, investigators enrolled 73 adult participants diagnosed with moderate to severe GAD. Participants were randomly assigned to complete 2 dosing sessions with either a 25 mg dose of synthetic psilocybin or placebo, which was administered in a controlled clinical setting as part of a proprietary psychotherapeutic protocol. All participants received equal hours of psychological support and preparation, ensuring that any treatment effect could be attributed to psilocybin itself and not therapeutic bias. Efficacy was assessed using a suite of validated clinical measures at multiple timepoints post-treatment, with the primary endpoint focused on change in Hamilton Anxiety Rating Scale (HAM-A) scores.

Results demonstrated a robust and consistent pattern of efficacy, showing that PSX-001 delivered statistically significant and clinically meaningful improvements across all primary and secondary endpoints. Participants treated with PSX-001 achieved an average statistically significant 12.8-point reduction in HAM-A scores from baseline, compared with a 3.6-point reduction in the placebo group (P<0.0001). This effect was sustained across the 11-week follow-up period and 44.1% of participants had a reduction in HAM-A score from baseline of ≥50%, a response rate more than 4 times higher than the placebo group. Additionally, 27% of participants receiving PSX-001 achieved full disease remission (HAM-A ≤7), a rate 5 times higher than placebo. Treatment with PSX-001 also resulted in an average 7.4-point reduction in Generalized Anxiety Disorder 7-item scale (GAD-7 scores), compared with a 3.5-point reduction for placebo (P<0.0004).

PSX-001 also demonstrated improvements on several other scales.

Participants treated with PSX-001 experienced a 6.0-point reduction in Sheehan Disability Scale scores vs 1.3 points in the placebo group (P<0.007), a 3.9-point reduction in Patient Health Questionnaire-9 scores vs 0.3 points in the placebo group (P<0.005), and 10.6 point improvement in quality of life as measured by the Personal Wellbeing Index vs 2.7 points for placebo (P<0.002).

As to safety profile, treatment with PSX-001 was well tolerated across the study population. No serious adverse events were reported, and only 1 of the 73 subjects withdrew from the trial during the 7-week treatment program. Most treatment-emergent adverse events were transient, mild to moderate in nature, and consistent with the expected pharmacological effects of psilocybin. Investigators noted that there were no signs of increased suicidality, psychosis, or prolonged psychological distress, which have been points of concern with other novel psychedelic treatments.^2,3

“These results speak for themselves—statistically significant, clinically meaningful, and consistent across every validated measure. Psi-GAD demonstrated a reduction in anxiety, improved mood, enhanced quality of life, and better day-to-day functioning. Importantly, the treatment effect was durable and observed across 11 weeks,” said Lou Barbato, MD, chief medical officer of Incannex. “These outcomes reinforce the power of our proprietary psychotherapeutic model and position Psi-GAD as a global leader in anxiety treatment innovation. We are also very pleased with the safety profile of Psi-GAD, particularly when considered alongside comparator programs in the market, which strengthens our confidence in both the clinical utility and scalability of this treatment.”

References

1. Incannex reports positive results from phase 2 clinical trial of PSX-001 (Psi-GAD) for generalised anxiety disorder. News release. August 26, 2025. Accessed August 26, 2025. https://ir.incannex.com/news-releases/news-release-details/incannex-reports-positive-results-phase-2-clinical-trial-psx-001

2. Zeifman RJ, Singhal N, Breslow L, Weissman CR. On the relationship between classic psychedelics and suicidality: a systematic review. ACS Pharmacol Transl Sci. 2021;4(2):436-451.

3. Barber G, Nemeroff CB, Siegel S. A case of prolonged mania, psychosis, and severe depression after psilocybin use: implications of increased psychedelic drug availability. Am J Psychiatry. 2022;179(12):892-896.