Psilocybin and apomorphine in coma: an early-trial protocol

Psiconáutica Editorial Team · September 25, 2026

A team at Copenhagen University Hospital, Rigshospitalet, in Denmark, has published the protocol for a clinical trial that will test a combination of psilocybin and apomorphine in coma patients admitted to intensive care. The goal is to see if the psychedelic drug, administered alongside this dopaminergic agonist already used in neurology, can help stimulate arousal following severe brain injury.

Two distinct pieces of consciousness

The authors base their work on a specific premise: consciousness has two components that can be addressed separately with drugs. One is arousal, which depends on brainstem networks and is stimulated by apomorphine. The other is awareness of the environment, linked to activity in the cerebral cortex, which psilocybin is hypothesized to influence. The team maintains that therapeutic trials designed to directly stimulate the recovery of consciousness in the ICU are, in their own words, literally nonexistent; research on comas has almost always focused on calculating prognosis rather than intervening.

Psilocybin is a prodrug of psilocin, which acts as an agonist at the 5-HT2A serotonin receptor, highly prevalent in cortical areas involved in cognition. As the authors explain, previous studies show that a dose of psilocybin increases the complexity of brain electrical activity recorded by electroencephalogram and strengthens connectivity between the cortex and the thalamus—two measures related to the level of consciousness. Hence the hypothesis that, when added to a drug that activates arousal, it may awaken brain reserves still active in unresponsive patients.

How the trial is designed

This is a prospective, open-label, two-center, phase 1b dose-escalation study, already authorized by Danish medical research ethics committees and the Danish Medicines Agency through the European clinical trials system. It will recruit 80 ICU patients with disorders of consciousness, divided into three cohorts: the first (26 people) will receive 1 mg of psilocybin, the second (27) 10 mg, and the third (27) 25 mg. One hour after the psilocybin, all participants will receive 2 mg of apomorphine subcutaneously. An independent safety committee will review the data before authorizing each dose escalation.

The primary objective is the time to awakening within the following 30 days; secondary objectives include recording serious adverse events, both physical and neuropsychiatric. Exploratorily, the team will also measure clinical consciousness scales, automated pupillometry, electroencephalograms, and the functional status of patients at 90 days.

What it implies

This is, above all, a safety trial: as it is open-label and lacks a control group, the authors themselves acknowledge that it can evaluate tolerability and exploratory efficacy signals, but cannot firmly attribute recovery to treatment. Previous psilocybin experience in other settings does not establish general safety or safety in these patients, and note that its psychedelic effects peak at 2 to 3 hours and are practically nonexistent by 6 hours. If the results show that the combination is safe, the team plans to proceed to a larger, randomized, multicenter trial to measure whether it truly helps with awakening. For now, it is a very early-stage hypothesis in a field—patients who remain unresponsive after brain injury—where almost no treatments have been tested with this intent.

Source

• Eigenbrodt AK, Laigaard PP, Hassani M, et al. Apomorphine and psilocybin to improve recovery from coma in the intensive care unit: protocol for a prospective, open-label, dose-escalation study. BMJ Open, 2026.

Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.