Psychedelic PSX-001 for Generalized Anxiety Disorder: A Conversation With Lou Barbato, MD

CLINICAL CONVERSATIONS

Earlier this year, Incannex Healthcare shared positive data from a phase 2 clinical trial of PSX-001 (formerly known as Psi-GAD), a psilocybin-assisted psychotherapy treatment for generalized anxiety disorder (GAD). Investigators found statistically significant and clinically meaningful improvements across every key endpoint assessed in the study, reinforcing PSX-001’s potential as a potential therapy for patients with moderate to severe GAD.¹ Psychiatric Times sat down with Lou Barbato, MD, the chief medical officer of Incannex, to discuss this news and the overall potential of psychedelics in treating mental health disorders.

Psychiatric Times: Incannex recently shared some information on PSX-001, a psilocybin-assisted psychotherapy treatment for GAD. How could PSX-001 alter the treatment paradigm and improve outcomes for patients with anxiety?

Lou Barbato, MD:GAD remains one of the most common and burdensome psychiatric conditions, yet many patients continue to struggle despite currently available medications and therapy. PSX-001 represents a fundamentally different approach. Rather than simply suppressing symptoms, the combination of psilocybin and guided psychotherapy helps patients process thoughts and emotions in a new way. The psilocybin experience appears to make patients more open to the therapeutic process, it can “loosen” rigid patterns of thought and behavior, increasing the impact of psychotherapy itself.

In a phase 2 study conducted by Incannex, PSX-001 demonstrated clinically meaningful and statistically significant improvements across all validated measures, including reductions in anxiety, improved mood, enhanced quality of life, and better day-to-day functioning. To emphasize, nearly half of participants achieved a 50% or greater reduction in their Hamilton Anxiety Rating Scale score compared with baseline, alongside significant improvements in quality-of-life measures. These results position Incannex as a global leader in anxiety innovation and suggest that PSX-001 could meaningfully change how clinicians treat anxiety disorders—moving beyond symptom management toward real, lasting improvements in well-being.

PT: There has been some hesitation associated with psychedelic-assisted psychotherapies, such as MDMA-assisted psychotherapy. Can you share your thoughts this hesitation? Do you believe psychedelic-assisted psychotherapies posed to change the psychiatric landscape? Why?

Barbato: The hesitation is understandable. These are powerful compounds, and psychiatry is a field that rightfully values safety, structure, and evidence. However, what has changed over the past few years is the quality of the data and the rigor of the science. Studies are now being conducted under controlled, double-blind conditions with defined psychotherapeutic protocols and regulatory oversight.

As a result, clinicians and regulators alike are beginning to view psychedelic-assisted therapies not as “alternative,” but as potentially complementary tools within the psychiatric toolkit. When administered in a clinical setting and paired with psychotherapy, psilocybin can catalyze meaningful psychological change in a short number of sessions. That is a paradigm shift worth paying attention to.

PT: PSX-001 also improved patient quality of life, as per measurement via the Personal Wellbeing Index. Can you talk to us about challenges patients with GAD face? Why are new, innovative treatments so important?

Barbato: GAD can profoundly affect a person’s ability to function day-to-day. Patients often live with constant, uncontrollable worry, sleep disturbance, fatigue, and difficulty concentrating. Traditional treatments, like selective serotonin reuptake inhibitors, are effective for some, but they primarily work by suppressing anxiety rather than addressing its root causes. Even with these medications, symptoms often persist or return.

Innovative treatments like PSX-001 are important because they target both the neurobiological and psychological aspects of anxiety. By combining the neuroplastic effects of psilocybin with structured psychotherapy, PSX-001 offers not only symptom relief but a shift from mere suppression toward hopefulness and meaningful change. Patients experience improvements in overall functioning and well-being, helping them live fuller, more engaged lives.

PT: Psychedelic treatments are occasionally associated with increased suicidality, psychosis, or prolonged psychological distress. Can you share some details about the safety profile of PSX-001? How does it differ from other psychedelic treatments?

Barbato: Safety is at the core of our program. In our phase 2 trial, PSX-001 was well tolerated, with no serious adverse events reported among the 73 participants. Each treatment was conducted in a controlled, supportive environment under the supervision of trained clinicians. The therapy component is essential as it provides a structured framework for patients to process their experiences safely. Our formulation, dose, and protocol have been carefully designed to maximize therapeutic benefit while minimizing risk. Our results indicate that PSX-001 can be administered safely when proper preparation, dosing, and integration support are in place. These findings highlight its favorable risk-benefit balance and support its continued advancement into late-stage development.

It is important to note that this was a relatively small study. While no safety issues related to suicidality, psychosis, or prolonged psychological distress were observed, Incannex plans to conduct larger clinical trials. As the number of participants increases, we will gather additional safety data to further evaluate PSX-001’s risk-benefit profile.

PT: Do you have any recommendations or best practices on treating GAD to offer your peers?

Barbato: I think it is important for clinicians to take a holistic view, recognizing that GAD is not only a neurochemical disorder but also one of mindset and coping patterns. While medications and psychotherapy remain the mainstays, emerging therapies like PSX-001 highlight the potential of integrating biological and experiential modalities.

For now, I would encourage clinicians to stay informed about these developments, consider participating in clinical research, and approach the evolving field of psychedelic medicine with both curiosity and scientific rigor.

PT: Anything else you would like clinicians to know?

Barbato: The psychiatric field is entering an exciting phase of innovation. At Incannex, our goal is not simply to create new drugs, it is to reshape how we think about mental health treatment by addressing the underlying biology and psychology together.

PSX-001 is one example of how thoughtful, evidence-based integration of psychedelics and psychotherapy could redefine care for patients who have not found relief through conventional means. We are excited to continue that journey with our centers of excellence, global research partners, and the clinical community. Equally important, we believe collaboration with patient advocacy and support groups is essential. Many of these organizations play a critical role in empowering patients, and we want to ensure their voices help shape how new treatments are developed and delivered.

PT: Thank you!

Dr Barbato is the chief medical officer of Incannex Healthcare.

Reference

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 December 4, 2025. https://ir.incannex.com/news-releases/news-release-details/incannex-reports-positive-results-phase-2-clinical-trial-psx-001