Drug & supplement interaction

Psilocybin + Phenobarbital

Phenobarbital brand names: Phenobarbital, Solfoton, Luminal.

No Known Interaction

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS · Updated July 2026 · Pair last verified Sep 20, 2026

The bottom line No known interaction

We found no known interaction between Psilocybin and Phenobarbital in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Psilocybin and Phenobarbital

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Phenobarbital and Psilocybin in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Psilocybin safety at a glance

Psilocybin overall Avoid Psilocybin is a controlled substance with powerful mind-altering effects and is not a safe or legal dietary supplement.

Pregnancy Avoid There is no safety data; avoid during pregnancy.

Breastfeeding Avoid There is no safety data; avoid while breastfeeding.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Phenobarbital and Psilocybin? Ask Dr. Brian Staiger, PharmD, BCPS directly ›

How we checked

Why No Interaction Is Listed for Phenobarbital

Interactions in our licensed database are recorded against drug classes, not just single drug names. Phenobarbital is filed under 11 classifications — including cytochrome p450 2b6 (cyp2b6) substrates, cytochrome p450 2c9 (cyp2c9) inducers, barbiturates. Psilocybin has documented interactions with 2 drug classes — the most serious being serotonergic drugs (moderate) and stimulant drugs (moderate) — and none of Phenobarbital’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Psilocybin Does Interact With Other Medications

Psilocybin has 293 moderate known drug interactions in our database — Phenobarbital isn’t one of them. If you take anything else, check it against the full list below.

Moderate 293 No known interaction 2,537 (incl. Phenobarbital)

Taking anything else?

Check Another of Your Medications Against Psilocybin

Covers the 2,830 medications we’ve checked against Psilocybin. Pick one to open its full report.

What to actually watch for

No Interaction Found — But Data Suggests Psilocybin and Phenobarbital May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. 4 of them are worth acting on rather than waiting out — marked below.

Dependence or withdrawal symptoms Worth acting on Additional detail
Psilocybin
“Psilocybin has psychedelic or hallucinogenic effects, with side effects including visual, auditory, tactile, and other illusions, as well as changes in time and space perception, and "mystical experiences". The severity of some of these responses may be dose-dependent.”

Psilocybin · Natural Medicines adverse-effect record, reported in anxiety.
6 sources cited

106129. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol 2016;30(12):1181-1197. PubMed

106137. Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol 2015;29(3):289-99. PubMed

106138. Grob CS, Danforth AL, Chopra GS, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry 2011;68(1):71-8. PubMed

106146. Brown RT, Nicholas CR, Cozzi NV, et al. Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Clin Pharmacokinet 2017;56(12):1543-1554. PubMed

106150. Griffiths RR, Johnson MW, Richards WA, et al. Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial at

106154. Carbonaro TM, Bradstreet MP, Barrett FS, et al. Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. J Psychopharmacol 2016;30(12):1268-1278. PubMed
Phenobarbital

Listed in the ADVERSE REACTIONS section of the FDA label for Phenobarbital. Read the label on DailyMed ›
A slow heartbeat Worth acting on Additional detail
Psilocybin
“Orally, psilocybin in single doses of 0.2-0.6 mg/kg have been shown to dose-dependently increase the resting heart rate by up to 11 beats per minute. However, decreased heart rate has also been reported in clinical research. In clinical trials, single doses of psilocybin as low as 0.2 mg/kg have been shown to have a moderate or large effect on blood pressure.”

Psilocybin · Natural Medicines adverse-effect record, reported in cardiac arrest.
6 sources cited

106132. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol 2016;30(12):1165-1180. PubMed

106138. Grob CS, Danforth AL, Chopra GS, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry 2011;68(1):71-8. PubMed

106139. Vargas AS, Luís Â, Barroso M, Gallardo E, Pereira L. Psilocybin as a new approach to treat depression and anxiety in the context of life-threatening diseases-A systematic review and meta-analysis of clinical trials. Biomedicines 2020;8(9):331. PubMed

106142. Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol 2014;28(11):983-92.

106165. Dahmane E, Hutson PR, Gobburu JVS. Exposure-Response Analysis to Assess the Concentration-QTc Relationship of Psilocybin/Psilocin. Clin Pharmacol Drug Dev 2021;10(1):78-85. PubMed

106167. Carbonaro TM, Johnson MW, Hurwitz E, Griffiths RR. Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences. Psychopharmacology (Berl) 2018;235(2):521-534. PubMed
Phenobarbital

Listed in the ADVERSE REACTIONS section of the FDA label for Phenobarbital. Read the label on DailyMed ›
Seizures Worth acting on Additional detail
Psilocybin
“Orally, single doses of psilocybin have resulted in mild to moderate headache in numerous case studies and experimental studies. Headaches have been reported in up to 50% of individuals, starting a mean of 7 hours after intake and lasting for 1-2 days. Severity and duration seem to be dose-dependent.”

Psilocybin · Natural Medicines adverse-effect record, reported in anxiety.
6 sources cited

106129. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol 2016;30(12):1181-1197. PubMed

106131. Carhart-Harris RL, Bolstridge M, Day CMJ, et al. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl) 2018;235(2):399-408. PubMed

106132. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol 2016;30(12):1165-1180. PubMed

106134. Carhart-Harris RL, Bolstridge M, Rucker J, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry 2016;3(7):619-27. PubMed

106135. Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder: A randomized clinical trial. JAMA Psychiatry 2021;78(5):481-489. PubMed

106137. Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol 2015;29(3):289-99. PubMed
“Severe rhabdomyolysis, followed by acute kidney failure and posterior encephalopathy resulting in short-term vision loss, disorientation, agitation, and seizures has been reported in a 25-year-old male following use of an unknown quantity of Psilocybe cubensis mushrooms.”

Psilocybin · Natural Medicines adverse-effect record, reported in epilepsy.
2 sources cited

106181. Bickel M, Ditting T, Watz H, et al. Severe rhabdomyolysis, acute renal failure and posterior encephalopathy after 'magic mushroom' abuse. Eur J Emerg Med 2005;12(6):306-8. PubMed

110795. Suleiman M, Basu A, Belal S, Jacob T. From mushrooms to myolysis: A case of rhabdo in psilocybin-induced mood and psychotic disorder. J Nerv Ment Dis 2022;210(8):638-639. PubMed
Phenobarbital

Listed in the ADVERSE REACTIONS section of the FDA label for Phenobarbital. Read the label on DailyMed ›
Kidney problems Worth acting on Additional detail

Psilocybin

“Orally, psilocybin seems to be generally well tolerated when single doses are used with appropriate medical supervision. However, the United States Drug Enforcement Administration (DEA) lists psilocybin as a Schedule I controlled substance and a thorough evaluation of safety outcomes related to its use without medical supervision, including in micro dosing amounts, has not been conducted.

Most Common Adverse Effects:…”

Psilocybin · Natural Medicines adverse-effect record, reported in anxiety.

Phenobarbital

Listed in the ADVERSE REACTIONS section of the FDA label for Phenobarbital. Read the label on DailyMed ›
Drowsiness Additional detail

Psilocybin

Recorded for Psilocybin in the same Natural Medicines adverse-effect record shown under Seizures above.

Phenobarbital

Listed in the ADVERSE REACTIONS section of the FDA label for Phenobarbital. Read the label on DailyMed ›

Reported for Psilocybin but not commonly for Phenobarbital: a heart attack, mood changes or irritability, thoughts of self-harm and a change in sex drive.

Effects for Phenobarbital come from the ADVERSE REACTIONS section of its FDA label; effects for Psilocybin come from the Natural Medicines adverse-effect record, quoted above. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Overlapping uses

What Phenobarbital Is Prescribed For, and What Psilocybin Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Phenobarbital is a prescription medicine with approved uses on its FDA label. Psilocybin is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Phenobarbital is prescribed for: Phenobarbital tablets and oral solutions are used to treat generalized and partial seizures and as a sedative. Phenobarbital Sodium injection is used as a long-term anticonvulsant for generalized tonic-clonic and focal seizures, for emergency control of acute convulsive episodes (including status epilepticus), for sedation, short-term treatment of insomnia, and as a preanesthetic. It is also used in pediatric patients as an anticonvulsant and sedative, including before and after surgery. Sezaby (phenobarbital injection, intravenous) is specifically indicated for the treatment of neonatal seizures in term and preterm infants.

Read the rest of what Phenobarbital is prescribed for

It is not approved for use in adolescents or adults.

Psilocybin has been studied for:

Anxiety studied, not established Psilocybin has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

Psilocybin for anxiety

It is unclear if oral psilocybin is beneficial for reducing anxiety.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Phenobarbital on your own; if you are taking Psilocybin for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Psilocybin or Phenobarbital

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Psilocybin or Phenobarbital, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Phenobarbital

This page covers Psilocybin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenobarbital page lists 174 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Henbane (major).

By severity: 10 major · 143 moderate · 21 minor.

Open the Phenobarbital interaction page

How much people look this up

Where Psilocybin and Phenobarbital Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Psilocybin

Top half

#463 of 1,452 supplements looked up here in the last 7 days

29 days ago today

Medication Phenobarbital

Steady interest

#2,259 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?

Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Psilocybin reference on this page ↓
Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Psilocybin and Phenobarbital records this page draws on were last updated July 10, 2026.
What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.

Data structure & sourcing designed and verified by Dr. Brian Staiger, PharmD, BCPS.

Supplement

About Psilocybin

What is Psilocybin?

Depression
Anxiety (including in serious illness)
Substance use disorders
Post-traumatic stress
Spiritual or psychological exploration

Psilocybin is a powerful psychedelic compound found in certain mushrooms and is being studied for hard-to-treat depression, anxiety, and addiction, but it is still investigational and not an approved supplement. It is illegal in most places, can cause intense and unpredictable mental effects, and should never be used outside of a supervised clinical setting.

Psilocybin is a compound found in certain mushrooms (often called 'magic mushrooms') · Dried mushrooms, capsules, isolated/synthetic psilocybin (used in clinical trials)

An interaction check asks whether these two react with each other — it does not ask whether Psilocybin is a good idea for someone in your situation. Here is what our Psilocybin record says about it on its own.

Psilocybin: dosing

There is no established, safe over-the-counter dose of psilocybin. In research studies, doses are carefully measured, purified, and given under medical supervision with psychological support before, during, and after.Mushroom strength varies widely, so there is no reliable way to know how much you are taking from wild or non-medical sources. Because psilocybin is illegal in most places and can cause strong reactions, we cannot recommend any home dose.

From our Psilocybin monograph — the full record covers uses, side effects and every documented interaction.

Read the full Psilocybin monograph & all interactions

Medication

About Phenobarbital

What Is Phenobarbital Used For?

Brand names: Phenobarbital, Solfoton, Luminal

Phenobarbital tablets and oral solutions are used to treat generalized and partial seizures and as a sedative. Phenobarbital Sodium injection is used as a long-term anticonvulsant for generalized tonic-clonic and focal seizures, for emergency control of acute convulsive episodes (including status epilepticus), for sedation, short-term treatment of insomnia, and as a preanesthetic. It is also used in pediatric patients as an anticonvulsant and sedative, including before and after surgery.

Sezaby (phenobarbital injection, intravenous) is specifically indicated for the treatment of neonatal seizures in term and preterm infants. It is not approved for use in adolescents or adults.

Most-Reported Side Effects for Phenobarbital

From FAERS, the FDA’s public side-effect reporting system (15,690 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Seizure 1,669 reports

Toxicity to various agents 647 reports

Status epilepticus 532 reports

Somnolence 492 reports

Multiple-drug resistance 475 reports

See full Phenobarbital drug information

Keep checking

Other Drugs & Psilocybin

Browse every other medication we’ve checked against Psilocybin — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major

293Moderate

0Minor

2,536No known interaction

293 Moderate 2,536 No interaction

Moderate

293 interactions

Showing 60 of 293 moderate interactions — see all 293 on the Psilocybin page.

No interaction 2,536 drugs checked — show the list

We also checked Psilocybin against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,536 medications checked with no known interaction — see the full Psilocybin list.

See the full Psilocybin interactions page

See every supplement checked against Phenobarbital, ranked by severity

Evidence & sources

Psilocybin References

The 65 references that drive our Psilocybin monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol 2016;30(12):1181-1197. PubMed
Carhart-Harris RL, Bolstridge M, Day CMJ, et al. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl) 2018;235(2):399-408. PubMed
Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol 2016;30(12):1165-1180. PubMed
Carhart-Harris RL, Bolstridge M, Rucker J, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry 2016;3(7):619-27. PubMed
Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder: A randomized clinical trial. JAMA Psychiatry 2021;78(5):481-489. PubMed
Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol 2015;29(3):289-99. PubMed
Grob CS, Danforth AL, Chopra GS, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry 2011;68(1):71-8. PubMed
Vargas AS, Luís Â, Barroso M, Gallardo E, Pereira L. Psilocybin as a new approach to treat depression and anxiety in the context of life-threatening diseases-A systematic review and meta-analysis of clinical trials. Biomedicines 2020;8(9):331. PubMed
Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol 2014;28(11):983-92.
Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology 2018;142:143-166. PubMed
Brown RT, Nicholas CR, Cozzi NV, et al. Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Clin Pharmacokinet 2017;56(12):1543-1554. PubMed
Moreno FA, Wiegand CB, Taitano EK, Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry 2006;67(11):1735-40. PubMed
Griffiths RR, Johnson MW, Richards WA, et al. Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial at
Schindler EAD, Sewell RA, Gottschalk CH, et al. Exploratory controlled study of the migraine-suppressing effects of psilocybin. Neurotherapeutics 2021;18(1):534-543. PubMed
Carbonaro TM, Bradstreet MP, Barrett FS, et al. Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. J Psychopharmacol 2016;30(12):1268-1278. PubMed
Barrett FS, Carbonaro TM, Hurwitz E, Johnson MW, Griffiths RR. Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition. Psychopharmacology (Berl) 2018;235(10):2915-2927. PubMed
Studerus E, Kometer M, Hasler F, Vollenweider FX. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J Psychopharmacol 2011;25(11):1434-52. PubMed
Hasler F, Grimberg U, Benz MA, Huber T, Vollenweider FX. Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose-effect study. Psychopharmacology (Berl) 2004;172(2):145-56. PubMed
Bienemann B, Ruschel NS, Campos ML, Negreiros MA, Mograbi DC. Self-reported negative outcomes of psilocybin users: A quantitative textual analysis. PLoS One 2020;15(2):e0229067. PubMed
Rosenbaum D, Weissman C, Anderson T, et al. Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities. J Psychopharmacol 2020;34(6):612-622. PubMed
Carbonaro TM, Johnson MW, Griffiths RR. Subjective features of the psilocybin experience that may account for its self-administration by humans: a double-blind comparison of psilocybin and dextromethorphan. Psychopharmacology (Berl) 2020;237(8):2293-2304. PubMed
Anderson BT, Danforth A, Daroff PR, et al. Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study. EClinicalMedicine 2020;27:100538. PubMed
Dahmane E, Hutson PR, Gobburu JVS. Exposure-Response Analysis to Assess the Concentration-QTc Relationship of Psilocybin/Psilocin. Clin Pharmacol Drug Dev 2021;10(1):78-85. PubMed
Carhart-Harris R, Giribaldi B, Watts R, et al. Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med 2021;384(15):1402-1411. PubMed
Carbonaro TM, Johnson MW, Hurwitz E, Griffiths RR. Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences. Psychopharmacology (Berl) 2018;235(2):521-534. PubMed
Higgins GA, Carroll NK, Brown M, et al. Low Doses of Psilocybin and Ketamine Enhance Motivation and Attention in Poor Performing Rats: Evidence for an Antidepressant Property. Front Pharmacol 2021;12:640241. PubMed
Hesselgrave N, Troppoli TA, Wulff AB, Cole AB, Thompson SM. Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. Proc Natl Acad Sci U S A 2021;118(17):e2022489118. PubMed
Bravermanová A, Viktorinová M, Tyl &scaron; F, et al. Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing-study on P300 and mismatch negativity in healthy volunteers. Psychopharmacology (Berl) 201 PubMed
Winter JC, Rice KC, Amorosi DJ, Rabin RA. Psilocybin-induced stimulus control in the rat. Pharmacol Biochem Behav 2007;87(4):472-80. PubMed
Johnson MW, Sewell RA, Griffiths RR. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers. Drug Alcohol Depend 2012;123(1-3):132-40. PubMed
Nicholas CR, Henriquez KM, Gassman MC, et al. High dose psilocybin is associated with positive subjective effects in healthy volunteers. J Psychopharmacol 2018;32(7):770-778. PubMed
Kometer M, Schmidt A, Bachmann R, Studerus E, Seifritz E, Vollenweider FX. Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors. Biol Psychia PubMed
Hasler F, Bourquin D, Brenneisen R, Vollenweider FX. Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man. J Pharm Biomed Anal 2002;30(2):331-9. PubMed
Wackermann J, Wittmann M, Hasler F, Vollenweider FX. Effects of varied doses of psilocybin on time interval reproduction in human subjects. Neurosci Lett 2008;435(1):51-5. PubMed
Bickel M, Ditting T, Watz H, et al. Severe rhabdomyolysis, acute renal failure and posterior encephalopathy after 'magic mushroom' abuse. Eur J Emerg Med 2005;12(6):306-8. PubMed
van Poorten JF, Stienstra R, Dworacek B, Moleman P, Rupreht J. Physostigmine reversal of psilocybin intoxication. Anesthesiology 1982;56(4):313. PubMed
Borowiak KS, Ciechanowski K, Waloszczyk P. Psilocybin mushroom (Psilocybe semilanceata) intoxication with myocardial infarction. J Toxicol Clin Toxicol 1998;36(1-2):47-9.
Hendin HM, Penn AD. An episode of mania following self-reported ingestion of psilocybin mushrooms in a woman previously not diagnosed with bipolar disorder: A case report. Bipolar Disord 2021. PubMed
Anderson T, Petranker R, Christopher A, et al. Psychedelic microdosing benefits and challenges: an empirical codebook. Harm Reduct J 2019;16(1):43. PubMed
Fadiman J, Korb S. Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. J Psychoactive Drugs 2019;51(2):118-122. PubMed
Becker AM, Holze F, Grandinetti T, et al. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Clin Pharmacol Ther 2022;111(4):886-895. PubMed
Kotts WJ, Gamble DT, Dawson DK, Connor D. Psilocybin-induced takotsubo cardiomyopathy. BMJ Case Rep 2022;15(5):e245863. PubMed
Müller F, Kraus E, Holze F, et al. Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants. Psychopharmacology (Berl) 2022. PubMed
Rucker JJ, Marwood L, Ajantaival RJ, et al. The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparati
Holze F, Ley L, Müller F, et al. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology 2022;47(6):1180-1187. PubMed
Bogenschutz MP, Ross S, Bhatt S, et al. Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: a randomized clinical trial [published online ahead of print, 20 PubMed
Cavanna F, Muller S, de la Fuente LA, et al. Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study. Transl Psychiatry. 2022;12(1):307. PubMed
Goodwin GM, Aaronson ST, Alvarez O, et al. Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med 2022;387(18):1637-1648.
Breeksema JJ, Kuin BW, Kamphuis J, van den Brink W, Vermetten E, Schoevers RA. Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review. J Psychopharmacol 2022;36(10):1100-1117. PubMed
von Rotz R, Schindowski EM, Jungwirth J, et al. Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial [published correction appears in EClinicalMedicine. 2023 Jan 30;56:101841.
Ledwos N, Rosenblat JD, Blumberger DM, et al. A critical appraisal of evidence on the efficacy and safety of serotonergic psychedelic drugs as emerging antidepressants: Mind the evidence gap. J Clin Psychopharmacol 2022;42(6):581-588. PubMed
Suleiman M, Basu A, Belal S, Jacob T. From mushrooms to myolysis: A case of rhabdo in psilocybin-induced mood and psychotic disorder. J Nerv Ment Dis 2022;210(8):638-639. PubMed
Schindler EAD, Sewell RA, Gottschalk CH, et al. Exploratory investigation of a patient-informed low-dose psilocybin pulse regimen in the suppression of cluster headache: Results from a randomized, double-blind, placebo-controlled trial. Headache 2022;62(1 PubMed
Barber G, Nemeroff CB, Siegel S. A case of prolonged mania, psychosis, and severe depression after psilocybin use: Implications of increased psychedelic drug availability. Am J Psychiatry 2022;179(12):892-896. PubMed
Schneier FR, Feusner J, Wheaton MG, et al. Pilot study of single-dose psilocybin for serotonin reuptake inhibitor-resistant body dysmorphic disorder. J Psychiatr Res. 2023;161:364-370. PubMed
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Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Related: nutrient depletion

Phenobarbital Is Linked to Lower Levels of 11 Nutrients

Natural Medicines records Phenobarbital as a medicine that can lower these. This is not an interaction with Psilocybin — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:

Read the full Phenobarbital nutrient depletion report ›

Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.

Pharmacist Counseling Corner

Taking Psilocybin and Phenobarbital Together: Common Questions

Is it safe to take Psilocybin with Phenobarbital?

We do not list a known interaction between Psilocybin and Phenobarbital. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.

Do Psilocybin and Phenobarbital have any of the same side effects?

Yes — our sources link each of them separately to 5 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.

Are Psilocybin and Phenobarbital used for the same thing?

They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Psilocybin in each. That is a conversation for your prescriber, especially if Phenobarbital is being adjusted to a target.

How was the Psilocybin and Phenobarbital combination checked?

Interactions in our licensed database are recorded against drug classes. Phenobarbital is filed under 11 classifications, and Psilocybin has documented interactions with 2 drug classes — none of Phenobarbital's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.

Does Psilocybin interact with any other medications?

Yes. Psilocybin has 293 documented drug interactions in our database — Phenobarbital is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.

Does Phenobarbital interact with any supplements?

Yes. Phenobarbital has documented interactions with 174 supplements in our database — Psilocybin is not one of them. The Phenobarbital interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Psilocybin monograph Uses, safety profile, and every drug interaction in one place Phenobarbital drug information The full plain-English guide to this medication Phenobarbital supplement interactions Every supplement checked against Phenobarbital, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 65 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.