Psilocybin and bupropion
CautionAntidepressant, NDRI · also: wellbutrin, zyban, elontril, aplenzin
Psilocybin and bupropion: caution, because bupropion raises seizure risk in a dose-related way, although the combination itself has not been studied.
Raised seizure risk, particularly at higher bupropion doses, in the immediate-release formulation, or where there is any additional risk factor such as an eating disorder history or alcohol withdrawal.
Claims re-checked against the cited sources:
Why it happens
Bupropion is a weak noradrenaline and dopamine reuptake inhibitor that does not inhibit serotonin reuptake or MAO, so serotonin toxicity is not the concern. Its label states it can cause seizures, with dose-related risk that also depends on patient factors and other medications.
What is known
Bupropion's independent seizure risk is well established and is the reason for its dose ceiling. The combination itself is unstudied.
- 2026
- The Wellbutrin XL label: seizure risk is dose-related; about 0.1% with sustained-release up to 300 mg/day, about 0.4% with immediate-release 300 to 450 mg/day, and almost tenfold higher between 450 and 600 mg/day. It is contraindicated with seizure disorder, current or past bulimia or anorexia, and abrupt withdrawal from alcohol or benzodiazepines. WELLBUTRIN XL (bupropion) US prescribing information, DailyMed (label version Feb 2026)
- 1998
- In 3,094 depressed patients without seizure risk factors on bupropion SR up to 300 mg/day, 3 had seizures (0.10%). Dunner et al., 'A prospective safety surveillance study for bupropion sustained-release in the treatment of depression', J Clin Psychiatry
- 1989
- With immediate-release bupropion at 450 mg/day or less, seizure incidence was 0.35% to 0.44%, risk rose above the maximum dose, and predisposing factors were present in over half of 37 cases. Davidson, 'Seizures and bupropion: a review', J Clin Psychiatry
- 2026
- The label says bupropion does not inhibit MAO or serotonin reuptake. WELLBUTRIN XL (bupropion) US prescribing information, DailyMed (label version Feb 2026)
- 2024
- A 2024 systematic review found no human study of psilocybin with bupropion. Halman et al., 'Drug-drug interactions involving classic psychedelics: a systematic review', J Psychopharmacol
Safety guidance
- Take real care, especially at higher bupropion doses or with any added seizure risk factor.
- Avoid stacking other seizure-threshold-lowering drugs (for example tramadol) or heavy drinking.
- Do not change or stop bupropion on your own; talk to your prescriber.
- Do not assume a full dose is safe because the experience feels unblunted.
When to seek help
Call emergency services for any seizure, jerking or loss of consciousness, and tell responders about the bupropion. Emergency red flags.
Common questions
Does bupropion cause serotonin syndrome with mushrooms?
That is not the main concern. Bupropion does not inhibit serotonin reuptake; the concern is its seizure risk.
Does the dose matter?
Yes. Seizure risk with bupropion is dose-related, about 0.1% at up to 300 mg/day SR in the label, rising at higher doses.
I have an eating disorder history. Does that matter?
Yes. Bulimia or anorexia raise bupropion seizure risk enough that the label contraindicates it; talk to your prescriber.
Sources
How we research this: sources, evidence grading, review and updates.