Supervised clinical trial: worsened suicidality and prolonged nausea after 25 mg synthetic psilocybin for treatment-resistant depression

Source note

Anonymised summary of a peer-reviewed case report from a supervised Phase 2b trial (Wahba et al., 2024, BJPsych Open). Names, locations, and other identifiers from the original report are omitted here.

Participant profile (non-identifying)

• Sex: female
• Clinical picture: recurrent major depression (current episode ~2.5 years), comorbid social anxiety; baseline MADRS 33 (moderate) and Hamilton depression score 25 (severe range in the report)
• Prior treatment: inadequate response to citalopram and sertraline at adequate dose/duration
• Other history (as published): chronic fatigue syndrome in 2017 (resolved clinically for trial purposes); lifelong/episodic suicidal ideation without intent at screening; possible ADHD signal on screening scale

Intervention

• Randomised to 25 mg synthetic psilocybin under double-blind dose conditions
• Two preparation sessions and therapist-supported dosing day, followed by integration sessions

Course

After an initially tolerable onset, the latter half of the dosing day became highly distressing. Post-session, the participant described existence as pointless and death by suicide as inevitable (without immediate intent to act), with family support arranged overnight.

The next morning she reported feeling “hung over,” persistent nausea preventing breakfast, and intensified, harder-to-control suicidal thoughts. MADRS rose to 43 (severe). Over subsequent days she experienced panic attacks, sleep disruption, inability to eat due to nausea, and fluctuating suicidal ideation with some intent — managed with crisis-team involvement and additional integration support.

Longer-term sequelae

Severe nausea and marked dietary restriction persisted for many months (reported inability to take in more than ~300 kcal/day at the worst point), with physical consequences including hair thinning, rapid weight loss, and at least one fainting episode. Weight figures are omitted per the participant’s preference in the source paper. Functional life changes (including later employment) were described as subjectively helpful even while depression scale response remained limited until later conventional antidepressant adjustment.

Why this anecdote is included

PSILORIS includes adverse trajectories alongside positive reports. Supervised settings reduce — but do not eliminate — risk of serious psychological and somatic sequelae after high-dose psilocybin.