Guest perspective from Julien Chupin and Amandine Luquiens, CHU de Nîmes
Following the launch of France’s ERPPAD Phase 3 trial, Julien Chupin and Amandine Luquiens have contributed a guest article explaining the research behind the study. ERPPAD investigates whether psilocybin, added to usual care, can help prevent relapse in people with alcohol use disorder and persistent depressive symptoms after detoxification. It builds on the team’s earlier Psilocybin Alcohol Depression (PAD) pilot study.
Alcohol use disorder and depression frequently occur together, and depressive symptoms can complicate recovery after detoxification. The authors describe the need for better treatment approaches for this combined clinical picture. Their research asks whether psilocybin delivered with psychological support can improve outcomes alongside an intensive relapse prevention programme.
The PAD pilot recruited 30 participants at a single centre in less than nine months. According to the guest contribution, the study supported the feasibility and acceptability of the approach and produced encouraging preliminary findings. At 12 weeks, the authors report abstinence rates of 55% in the 25 mg group, compared with 11% in the 1 mg group, alongside differences favouring the higher-dose group in measures of drinking, craving and depression. Efficacy was not the pilot’s primary outcome. These results therefore provide a rationale for further investigation, rather than confirmation of treatment efficacy.
Funded by the French Ministry of Health, ERPPAD is a double-blind, multicentre randomised controlled trial. It compares two administrations of 25 mg psilocybin with two administrations of 3 mg, given three weeks apart. Treatment is provided alongside usual care for alcohol use disorder and persistent depressive symptoms. Participants will be followed for 12 months from baseline and can opt for a third, 25 mg dose at six months.
The clinical programme follows a preparation, dosing and integration cycle. Preparation includes psychoeducation and mindfulness, dosing takes place with psychological support, and an integration session provides an opportunity for debriefing. The protocol includes hospital stays around each psilocybin cycle. Between the first and second dosing sessions, usual care includes an intensive relapse prevention programme with at least two individual or group sessions each week.
The design also responds to difficulties encountered in the pilot. The comparison dose has increased from 1 mg to 3 mg, and an optional third dose has been introduced. The authors explain that these changes seek to address participants’ guesses about their treatment allocation, disappointment in the lower-dose group, and the risk of participants using psychedelics outside the trial during follow-up.
The larger study will examine whether the preliminary findings translate into more sustained relapse prevention. Its contribution will depend on the outcomes of the ongoing trial. For European research, ERPPAD extends the investigation of psychedelic therapies to a population with overlapping alcohol-related and depressive symptoms, while testing treatment within a structured hospital and continuing-care setting.
