Psilocybin and tramadol
DangerousOpioid analgesic, serotonergic · also: ultram, zydol, tramal, tramacet
Psilocybin and tramadol: avoid, because tramadol carries its own seizure and serotonin-syndrome warnings, although this exact combination has never been studied.
Raised seizure risk. Seizures are a recognised adverse effect of tramadol: common in overdose, and also reported in prescribed use, usually alongside other risk factors.
Claims re-checked against the cited sources:
Why it happens
Tramadol is an opioid that also inhibits serotonin and noradrenaline reuptake. Its label warns that seizures can occur within the recommended dose range, that other drugs can raise that risk, and that serotonin syndrome can occur, particularly with other serotonergic drugs. The concern with psilocybin rests on these properties rather than on any reported case.
What is known
Tramadol's independent seizure risk is well documented in the clinical literature. The specific combination with psilocybin has not been studied; the concern is based on the mechanism and is treated as serious because the base rate for tramadol alone is already non-trivial.
- 2026
- The tramadol label states seizures have been reported within the recommended dose range, risk rises above it, and concomitant drugs and seizure history increase risk; it also warns of serotonin syndrome, particularly with other serotonergic drugs. Tramadol hydrochloride tablets US prescribing information (Amneal), DailyMed (label version Sep 2026)
- 2000
- In 9,218 tramadol users in a US managed-care population, fewer than 1% (80) had a presumed incident seizure claim; risk was 2 to 6 times higher than non-users after adjustment, and the 8 cases confirmed from records all had other seizure risk factors. Gardner et al., 'Tramadol and seizures: a surveillance study in a managed care population', Pharmacotherapy
- 2009
- Among 132 tramadol poisoning admissions in Tehran without co-ingestions or seizure history, 61 (46.2%) had a seizure within 24 hours, and seizure occurrence did not track the dose taken. Talaie et al., 'Dose-independent occurrence of seizure with tramadol', J Med Toxicol
- 2024
- A 2024 systematic review of drug interactions with classic psychedelics identified no human study of psilocybin with tramadol. Halman et al., 'Drug-drug interactions involving classic psychedelics: a systematic review', J Psychopharmacol
Safety guidance
- Avoid combining psilocybin with tramadol.
- Do not skip or stop tramadol doses on your own; it can cause withdrawal. Ask your prescriber about the interaction or alternatives.
- The risk is higher with a seizure history, alcohol misuse, head injury, or other serotonergic drugs such as SSRIs.
- Never take extra tramadol during or after a trip; tramadol seizures were common in overdose.
When to seek help
Call emergency services for any seizure, or for high fever, muscle rigidity or twitching, severe agitation or confusion, which can signal serotonin syndrome. Also call if breathing becomes slow or shallow. Emergency red flags.
Common questions
Has anyone had a seizure from psilocybin plus tramadol?
No published case was found. The warning comes from tramadol's own seizure and serotonin-syndrome risks, which are well documented.
Is a normal prescribed dose of tramadol safe with mushrooms?
Not clearly. The label says seizures have occurred at recommended doses, so a normal dose does not remove the concern.
Can I skip my tramadol for a day?
Talk to your prescriber first. Stopping suddenly can cause withdrawal, and pain control matters.
Sources
- [1]Gardner et al., 'Tramadol and seizures: a surveillance study in a managed care population' (2000)
- [2]Talaie et al., 'Dose-independent occurrence of seizure with tramadol' (2009)
- [3]Sansone & Sansone, 'Tramadol: seizures, serotonin syndrome, and coadministered antidepressants' (2009)
- [4]Savage, 'Serious reactions with tramadol: seizures and serotonin syndrome', Medsafe Prescriber Update (2007)
How we research this: sources, evidence grading, review and updates.