Intravenously administered psilocin for binge eating disorder: Preliminary safety and psychedelic intensity from a Phase 1 open-label trial

Introduction

Binge eating disorder (BED) is the most prevalent eating disorder globally, characterised by recurrent episodes of compulsive overconsumption, loss of control over eating, and significant psychological distress. Pharmacotherapeutic options remain limited, underscoring the need for novel approaches. Psilocybin has demonstrated promise in treatment-resistant psychiatric conditions through its capacity to reduce cognitive rigidity, enhance neuroplasticity, and modulate the default mode network via serotonin 2A (5-HT₂A) receptor agonism. However, oral psilocybin-assisted psychotherapy is constrained by variable bioavailability, unpredictable onset and duration, and limited capacity to manage adverse events in real time. Psilocin, the active metabolite directly responsible for psilocybin’s psychoactive effects, offers a compelling alternative when administered intravenously (IV), conferring 100% bioavailability, rapid and predictable onset, precise dose titration, and the capacity to attenuate or terminate effects rapidly if required.

Aims

To report on the safety and psychedelic intensity of ten doses of intravenously administered psilocin in a cohort of adults with binge eating disorder.

Methods

Five adults meeting DSM-5 criteria for binge eating disorder were enrolled in an open-label, single-arm trial. Each participant received two fixed intravenous dose of 10mg of psilocin via controlled infusion (5mg/20minutes loading dose, 5mg/120minute maintenance dose) separated by two weeks administered in combination with supportive preparation and integration psychotherapy. Safety was assessed continuously during infusion and at follow-up timepoints up to seven days post-dose, including blood pressure, electrocardiography (ECG), and vital signs monitoring. Adverse events were recorded and graded using the Common Terminology Criteria for Adverse Events (CTCAE). Psychedelic intensity was assessed in four participants across eight dosing sessions using the Psychedelic Intensity Rating (PIR), a single-item self-report scale (0–10) administered at 10, 20, and 40 minutes after infusion commencement, then every 40 minutes until discharge.

Results

Across ten dosing sessions, 63 adverse events were recorded. The majority were mild in severity; seven events were graded moderate and one severe. No serious adverse events occurred. The most frequently reported events were acute post-dose headache, fatigue, and nausea. PIR scores demonstrated rapid onset, with a median time to peak intensity of 20 minutes post-infusion commencement. Six of eight sessions reached peak intensity at the 20-minute timepoint. Seven of eight sessions achieved a maximum PIR score of 10/10, with one session peaking at 9/10 (mean peak: 9.9/10). From approximately 160 minutes, PIR scores demonstrated a consistent and progressive decline across all sessions, attenuating to 0–3/10 by 240 minutes.

Conclusions

IV psilocin demonstrated an acceptable safety profile in this preliminary BED cohort, with adverse events consistent in nature with those reported in oral psilocybin-assisted therapy. Psychedelic intensity was robust and consistent, with the majority of sessions achieving maximum PIR scores and peak effects emerging rapidly following infusion commencement. The progressive and predictable resolution of psychedelic effects within the session window further supports the controllability of this approach.

References

No References.