The U.S. Food and Drug Administration (FDA) has recently granted approval for Incannex Healthcare Inc. to proceed with a Phase 2 clinical trial that will investigate the use of psilocybin-assisted therapy for treating Generalized Anxiety Disorder (GAD). This milestone represents a promising step forward in the exploration of alternative treatments for anxiety disorders, particularly for those who have not found relief through conventional therapies.
Trial objectives and set-up
The primary aim of this Phase 2 trial, known as PsiGAD2, is to evaluate the efficiency and safety of Incannex’s psilocybin formulation, PSX-001, when combined with psychotherapy in treating GAD. The trial hopes to build on the encouraging results of a previous Phase 2 trial, PsiGAD1, conducted in collaboration with Monash University in Melbourne. PsiGAD1 demonstrated significant reductions in anxiety symptoms among participants, providing a strong foundation for further investigation.
The new trial will include 94 patients who meet the criteria for GAD, including those already receiving treatment with selective serotonin reuptake inhibitors (SSRIs). Participants will be randomly assigned to receive one of two doses of PSX-001 under double-blind conditions, ensuring neither the patients nor the researchers know which dose is being administered. Each participant will undergo two dosing sessions, accompanied by psychotherapy sessions. The primary endpoint will be the change in anxiety symptoms as measured by the Hamilton Anxiety Rating Scale (HAM-A) two weeks after the second dosing session.
How PsiGAD1 results supported FDA’s phase 2 approval
In PsiGAD1, participants who received psilocybin-assisted therapy experienced a notable 12.8-point reduction in Hamilton Anxiety Rating Scale (HAM-A) scores from baseline (meaning, on average, the participants’ anxiety scores decreased by 12.8 points from their initial score on the scale), compared to a much smaller decrease in the placebo group. Additionally, 44% of the psilocybin group achieved a reduction of over 50% in their anxiety scores, with 27% reaching full remission. These results highlighted the potential of psilocybin as a powerful tool in the treatment of anxiety, paving the way for the FDA’s approval of the current Phase 2 trial.
Psilocybin-assisted therapy benefits and risks
Psilocybin-assisted therapy offers several potential benefits over traditional anxiety treatments. One of the most significant advantages is its ability to bring profound, lasting changes in mood and perception after just one or two sessions, compared to the weeks or months it often takes for conventional therapies to show results. Psilocybin works by interacting with serotonin receptors in the brain, promoting neuroplasticity and enabling patients to break free from entrenched patterns of negative thinking that contribute to anxiety.
However, despite its promise, psilocybin therapy is not without risks. Adverse effects, though generally mild, can include distressing “bad trips,” temporary confusion, or increased anxiety during the experience. In rare cases, especially among those with a history of psychotic disorders, psilocybin can trigger episodes of psychosis. The controlled, clinical setting of the trial, with carefully monitored dosing and professional supervision, is designed to minimize these risks.
How PsiGAD2 could change the future of anxiety therapy
The PsiGAD2 trial will use a detailed methodology to ensure the reliability of its findings. The primary outcome measure will be the change in HAM-A scores, with secondary endpoints including assessments of quality of life, healthcare utilization, and electroencephalography (EEG) data. The trial will also monitor safety and tolerability, paying close attention to any adverse events that may arise during the treatment process.
The FDA’s approval of the Phase 2 PsiGAD2 trial marks a crucial step in the ongoing exploration of psilocybin-assisted therapy as a treatment for anxiety disorders. By building on the success of previous research, this trial has the potential to provide stronger evidence supporting the use of psilocybin in mental health care. If successful, PsiGAD2 could pave the way for new, more effective treatments for anxiety, offering hope to millions of people who struggle with this debilitating condition.
