Psilocybin + Acetaminophen, Dextromethorphan, Pseudoephedrine
Acetaminophen, Dextromethorphan, Pseudoephedrine brand names: Alka-Seltzer PLUS Flu Liquid Gels, Tylenol Flu Daytime Ex Strength, Non Aspirin Cold Caps, Tylenol Cold, Tylenol Flu Ex Strength.
Acetaminophen, Dextromethorphan, Pseudoephedrine falls into 2 drug categories that Psilocybin can interact with; the most serious is rated moderate. Theoretically, combining psilocybin with serotonergic drugs might cause additive serotonergic effects.
Read the full interaction reportPsilocybin and Acetaminophen, Dextromethorphan, Pseudoephedrine
These two interact in 2 distinct ways. Each one is explained separately below.
Why Are There 2 Interactions?
Psilocybin interacts with whole categories of medication. Acetaminophen, Dextromethorphan, Pseudoephedrine falls into 2 of those categories, so it can interact with Psilocybin in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
SEROTONERGIC DRUGS
1 of 2Why this applies to Acetaminophen, Dextromethorphan, Pseudoephedrine
Acetaminophen, Dextromethorphan, Pseudoephedrine falls under SEROTONERGIC DRUGS — the group Psilocybin interacts with.
Psilocybin has serotonin 2A (5-HT2A) receptor agonist activity. Theoretically, combining serotonergic drugs with psilocybin might increase the risk of serotonergic side effects, including serotonin syndrome. However, this interaction has not been reported in humans.
Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
This is a combination cold and flu product, and the piece that matters here is the dextromethorphan (the cough suppressant). Dextromethorphan nudges serotonin activity in the brain, and psilocybin works on serotonin receptors too. On paper, stacking them could add up and raise the chance of too much serotonin, which can show up as agitation, a racing heart, sweating, shivering, tremor, or confusion. Pseudoephedrine, a stimulant decongestant, could add to that jittery, fast-heartbeat feeling.
I want to be honest: this is a theoretical concern drawn from how these act, not something actually reported in people. Still, psilocybin is unpredictable and not approved for use. Please run any combination past your pharmacist or doctor before mixing them.
- Rosenbaum D, Weissman C, Anderson T, et al. Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities. J Psychopharmacol 2020;34(6):612-622. 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
- Winter JC, Rice KC, Amorosi DJ, Rabin RA. Psilocybin-induced stimulus control in the rat. Pharmacol Biochem Behav 2007;87(4):472-80. 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
STIMULANT DRUGS
2 of 2Acetaminophen, Dextromethorphan, Pseudoephedrine also falls under STIMULANT DRUGS.
Due to the central nervous system (CNS) stimulant effects of psilocybin, concomitant use with stimulant drugs may increase the risk of adverse effects.
Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..
Here's the part that matters in this combo product: the pseudoephedrine is a stimulant decongestant, and on its own it can speed up your heart, raise your blood pressure, and leave you feeling jittery or wired. The concern with psilocybin is that it also revs up the nervous system, so stacking the two could pile on those stimulant-type effects. The dextromethorphan adds another wrinkle, since it also touches serotonin pathways like psilocybin does.
To be honest, this is a theoretical caution based on how these compounds work, not on solid studies, so I don't want to overstate it. Still, faster heartbeat, anxiety, and spiking blood pressure are nothing to gamble with. Please run this by your pharmacist or doctor before mixing them.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Bravermanová A, Viktorinová M, Tyl š 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
- 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
- Fadiman J, Korb S. Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. J Psychoactive Drugs 2019;51(2):118-122. PubMed
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
- ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
- PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
- UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
- AHigh-quality meta-analysis (quantitative systematic review).
- BCase-control study.
- CConsensus.
- DAnecdotal evidence.
These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.
Psilocybin Also Interacts With Other Medications
Psilocybin has 292 moderate known drug interactions in our database — the Acetaminophen, Dextromethorphan, Pseudoephedrine one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Psilocybin
We haven’t checked that one against Psilocybin yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Psilocybin. Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Dextromethorphan, Pseudoephedrine
This page covers Psilocybin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Dextromethorphan, Pseudoephedrine page lists 262 supplements it has a documented interaction with, worst first, each one explained.
The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Ephedra (major) and Grapefruit (major).
By severity: 12 major · 207 moderate · 43 minor.
From our pharmacist’s overview on the Acetaminophen, Dextromethorphan, Pseudoephedrine page
“Ephedra is the ingredient to notice first here. Pseudoephedrine, the decongestant in Tylenol Flu, Alka-Seltzer PLUS Flu, and other acetaminophen, dextromethorphan, and pseudoephedrine combinations, is itself a stimulant, and 44 entries push the same direction, raising the odds of high blood pressure and a racing heart.”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Dextromethorphan, Pseudoephedrine interaction page
Where Psilocybin and Acetaminophen, Dextromethorphan, Pseudoephedrine 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.
#431 of 1,452 supplements looked up here in the last 7 days
#364 of 2,830 medications looked up here in the last 7 days
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.
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.
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.
No drugs match “”.
292 interactions
- Phentermine ›
- Methylphenidate ›
- Phenylpropanolamine ›
- Fentanyl ›
- Nicotine ›
- Carbamazepine ›
- Dextromethorphan ›
- Phenylephrine ›
- Pseudoephedrine ›
- Trimipramine ›
- Amphetamine ›
- Buprenorphine ›
- Diethylpropion ›
- Nortriptyline ›
- Selegiline ›
- Sumatriptan Succinate ›
- Aripiprazole ›
- Caffeine (otc Drug) ›
- Cyclobenzaprine ›
- Desipramine ›
- Doxepin ›
- Duloxetine ›
- Metoclopramide ›
- Modafinil ›
- Oxymetazoline Hydrochloride ›
- Paroxetine ›
- Prucalopride ›
- Tramadol ›
- Valproic Acid ›
- Vortioxetine ›
- Almotriptan ›
- Amphetamine Sulfate ›
- Aripiprazole Lauroxil ›
- Caffeine (prescription Drug) ›
- Chlorpheniramine ›
- Clozapine ›
- Cocaine Hydrochloride (prescription Drug) ›
- Desvenlafaxine ›
- Dexchlorpheniramine ›
- Dihydroergotamine ›
- Ephedrine Sulfate ›
- Fluoxetine ›
- Granisetron ›
- Imipramine ›
- Linezolid ›
- Lithium Carbonate (prescription Drug) ›
- Meperidine ›
- Methylene Blue ›
- Methylphenidate Hydrochloride ›
- Pemoline ›
- Pseudoephedrine Sulfate ›
- Quetiapine ›
- Risperidone ›
- Rizatriptan Benzoate ›
- Tapentadol ›
- Trazodone ›
- Venlafaxine ›
- Alosetron ›
- Ambenonium Chloride ›
- Amitriptyline ›
Showing 60 of 292 moderate interactions — see all 292 on the Psilocybin page.
No interaction 2,537 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.
- Apixaban ›
- Levothyroxine ›
- Amlodipine ›
- Warfarin ›
- Testosterone ›
- Losartan Potassium ›
- Metoprolol ›
- Ivermectin ›
- Aspirin ›
- Rivaroxaban ›
- Rosuvastatin ›
- Acetaminophen ›
- Tadalafil ›
- Clopidogrel ›
- Atorvastatin ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Abemaciclib ›
- Ibuprofen ›
- Semaglutide ›
- Tirzepatide ›
- Warfarin Sodium ›
- Prednisone ›
- Propranolol ›
- Bupropion ›
- Metformin ›
- Amoxicillin ›
- Acyclovir ›
- Lisinopril ›
- Bendamustine ›
- Doxycycline ›
- Methotrexate ›
- Lamotrigine ›
- Gabapentin ›
- Pregabalin ›
- Acetaminophen, Codeine ›
- Azithromycin ›
- Isotretinoin ›
- Clonazepam ›
- Omeprazole ›
- Amlodipine Besylate ›
- Letrozole ›
- Naproxen ›
- Ciprofloxacin ›
- Bisoprolol ›
- Levothyroxine, Liothyronine ›
- Acetaminophen, Oxycodone ›
- Dapsone ›
- Diazepam ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Cephalexin ›
- Mannitol ›
- Roxithromycin ›
- Atorvastatin Calcium ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Finasteride ›
Showing the 60 most looked-up of 2,537 medications checked with no known interaction — see the full Psilocybin list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.
Parts of this content are provided by the Therapeutic Research Center, LLC.
DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.
© 2021 Therapeutic Research Center, LLC
Acetaminophen, Dextromethorphan, Pseudoephedrine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Dextromethorphan, Pseudoephedrine 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 Acetaminophen, Dextromethorphan, Pseudoephedrine 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.
Taking Psilocybin and Acetaminophen, Dextromethorphan, Pseudoephedrine Together: Common Questions
Can you take Psilocybin with Acetaminophen, Dextromethorphan, Pseudoephedrine?
Why are there 2 interactions listed for Psilocybin and Acetaminophen, Dextromethorphan, Pseudoephedrine?
How serious is the Psilocybin and Acetaminophen, Dextromethorphan, Pseudoephedrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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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.