Drug & supplement interaction

Psilocybin + Dextromethorphan HBr, Phenylephrine HCl

Dextromethorphan HBr, Phenylephrine HCl brand name: Vicks Formula 44D Cough & Head Congestion Relief.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Dextromethorphan HBr, Phenylephrine HCl 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 report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Psilocybin and Dextromethorphan HBr, Phenylephrine HCl

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. Dextromethorphan HBr, Phenylephrine HCl 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).

Moderate

SEROTONERGIC DRUGS

1 of 2

Why this applies to Dextromethorphan HBr, Phenylephrine HCl

Dextromethorphan HBr, Phenylephrine HCl falls under SEROTONERGIC DRUGS — the group Psilocybin interacts with.

Theoretically, combining psilocybin with serotonergic drugs might cause additive serotonergic effects.
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.
Severity Moderate Likelihood Possible Evidence D

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to know about this combo. The dextromethorphan in Vicks Formula 44D nudges serotonin activity in your brain, and psilocybin (really its active form, psilocin) revs up serotonin receptors too. Stack them together and you could, in theory, get too much serotonin signaling at once. We call the worst version of that serotonin syndrome, which can show up as agitation, a racing heart, sweating, shivering, muscle twitching, or confusion.

I want to be honest about the strength of this concern. It's theoretical, based on how these substances work, and hasn't actually been reported in people. The phenylephrine (a decongestant) isn't really the worry here; it's the dextromethorphan side. Psilocybin also isn't a legal, approved supplement. If you're considering anything like this, please talk it through with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Rosenbaum D, Weissman C, Anderson T, et al. Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities. J Psychopharmacol 2020;34(6):612-622. PubMed
  2. 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
  3. 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
  4. Winter JC, Rice KC, Amorosi DJ, Rabin RA. Psilocybin-induced stimulus control in the rat. Pharmacol Biochem Behav 2007;87(4):472-80. PubMed
  5. 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
Moderate

STIMULANT DRUGS

2 of 2

Dextromethorphan HBr, Phenylephrine HCl also falls under STIMULANT DRUGS.

Theoretically, concomitant use of psilocybin with stimulant drugs might increase stimulant adverse effects.
Due to the central nervous system (CNS) stimulant effects of psilocybin, concomitant use with stimulant drugs may increase the risk of adverse effects.
Severity Moderate Likelihood Probable Evidence D

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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to know about this combo. Your Vicks Formula 44D has two active pieces: dextromethorphan (a cough suppressant) and phenylephrine (a decongestant). Phenylephrine is a stimulant-type ingredient, and dextromethorphan also nudges serotonin pathways. Psilocybin works on serotonin too and has its own stimulating effects on the brain and body.

So on paper, pairing them could stack up effects like a racing or pounding heart, higher blood pressure, jitteriness, anxiety, or feeling overheated. I want to be honest though: this concern is theoretical, based on how these compounds behave rather than real-world case reports. Neither drug here is a prodrug that flips the direction. Since psilocybin isn't legal or approved for home use, please run any real-world questions by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • 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.
Evidence the quality of the studies behind the rating (graded A–D)
  • 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.

Keep it in perspective

Psilocybin Also Interacts With Other Medications

Psilocybin has 292 moderate known drug interactions in our database — the Dextromethorphan HBr, Phenylephrine HCl one above is among them. If you take anything else, check it against the full list below.

Moderate 292 No known interaction 2,538 (incl. Dextromethorphan HBr, Phenylephrine HCl)
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.

Everything else you take

See Every Supplement That Interacts With Dextromethorphan HBr, Phenylephrine HCl

This page covers Psilocybin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Dextromethorphan HBr, Phenylephrine HCl page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Grapefruit (major), Lithium (major) and Peyote (major).

By severity: 8 major · 148 moderate · 41 minor.

From our pharmacist’s overview on the Dextromethorphan HBr, Phenylephrine HCl page

“The supplement interactions with Dextromethorphan HBr and Phenylephrine HCl (Vicks Formula 44D) deserve real respect, and the small cluster of major-rated ones should be understood before you reach for the bottle. Phenylephrine is a stimulant-type decongestant, so anything with caffeine (coffee, tea, cola nut) or ephedrine-like herbs s…”

Reviewed by 2 · Jul 18, 2026

Open the Dextromethorphan HBr, Phenylephrine HCl interaction page

How much people look this up

Where Psilocybin and Dextromethorphan HBr, Phenylephrine HCl 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

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

29 days ago today
Medication Dextromethorphan HBr, Phenylephrine HCl
Steady interest

#2,095 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.

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.

Read the full Psilocybin monograph & all interactions
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
292Moderate
0Minor
2,537No known interaction
292 Moderate 2,537 No interaction
Moderate

292 interactions

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.

Showing the 60 most looked-up of 2,537 medications checked with no known interaction — see the full Psilocybin list.

See the full Psilocybin interactions page
See every supplement checked against Dextromethorphan HBr, Phenylephrine HCl, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

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

Keep exploring
Psilocybin monograph › Uses, safety, and every drug interaction in one place Dextromethorphan HBr, Phenylephrine HCl supplement interactions › Every supplement checked against Dextromethorphan HBr, Phenylephrine HCl, 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 Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Psilocybin and Dextromethorphan HBr, Phenylephrine HCl Together: Common Questions

Can you take Psilocybin with Dextromethorphan HBr, Phenylephrine HCl?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Psilocybin and Dextromethorphan HBr, Phenylephrine HCl?
Dextromethorphan HBr, Phenylephrine HCl belongs to more than one drug category, and Psilocybin interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Psilocybin and Dextromethorphan HBr, Phenylephrine HCl interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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.