Drug & supplement interaction

Psilocybin + Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride

Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride brand name: Azstarys.

Moderate Interaction
The bottom line Moderate

Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride 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 Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride

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. Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride 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 Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride

Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride 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 gist for Azstarys (which delivers dexmethylphenidate, a stimulant). Both psilocybin and this medication nudge your brain's serotonin system. Psilocybin acts directly on certain serotonin receptors, while stimulants like dexmethylphenidate can raise serotonin and other signaling chemicals. Put them together and, in theory, those effects could stack up.

If serotonin climbs too high, you might see what's called serotonin syndrome: a racing heart, high blood pressure, sweating, shakiness, agitation, or confusion. Some of those overlap with the stimulant's own side effects, so they could feel amplified. I'll be honest, this combo is theoretical and hasn't actually been reported in people. Still, psilocybin is investigational and risky on its own. Please loop in your doctor or pharmacist before mixing anything like this.

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

Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride 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

Azstarys is a stimulant for ADHD. The serdexmethylphenidate part is a prodrug, meaning your gut slowly converts it into active dexmethylphenidate, which revs up focus-related brain chemicals. Psilocybin is a psychedelic that also stirs up the brain and body. The concern here is that stacking two stimulating substances may pile on side effects rather than change how either one is broken down.

In real terms, that could mean a faster or pounding heartbeat, higher blood pressure, jitteriness, anxiety, trouble sleeping, or feeling overstimulated. Keep in mind this warning is theoretical, based on how these substances act, not on strong human studies. Still, combining them isn't something to take lightly. Psilocybin is also investigational and illegal in most places. Please talk with your doctor or pharmacist before changing anything.

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 Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride one above is among them. If you take anything else, check it against the full list below.

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 Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride

This page covers Psilocybin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride page lists 92 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Cesium (major) and Ephedra (major).

By severity: 10 major · 68 moderate · 14 minor.

From our pharmacist’s overview on the Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride page

“Ephedra tops my concerns for anyone taking Azstarys (serdexmethylphenidate and dexmethylphenidate), a stimulant medication for ADHD. It stacks a second stimulant onto the drug and carries a major rating for disturbing heart rhythm.”

Reviewed by 2 · Jul 18, 2026

Open the Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride interaction page

How much people look this up

Where Psilocybin and Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride 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

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

29 days ago today
Medication Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride
Steady interest

#1,963 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
Medication

About Serdexmethylphenidate and Dexmethylphenidate

What Is Serdexmethylphenidate and Dexmethylphenidate Used For?

Brand name: Azstarys

Azstarys (serdexmethylphenidate/dexmethylphenidate) is approved to treat Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older. It is not recommended for children younger than 6 because they experience higher drug levels in the blood and more side effects at the same doses used in older patients.

See full Serdexmethylphenidate and Dexmethylphenidate 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
292Moderate
0Minor
2,537No known 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
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

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Pharmacist Counseling Corner

Taking Psilocybin and Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride Together: Common Questions

Can you take Psilocybin with Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride?
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 Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride?
Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride 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 Serdexmethylphenidate Chloride, Dexmethylphenidate Hydrochloride 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.