Drug & supplement interaction

Psilocybin + Lisdexamfetamine

Lisdexamfetamine brand name: Vyvanse.

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

Lisdexamfetamine 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 Lisdexamfetamine

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. Lisdexamfetamine 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 Lisdexamfetamine

Lisdexamfetamine 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: both of these affect serotonin in your brain. Vyvanse (lisdexamfetamine) is a stimulant that nudges up brain chemicals like dopamine and norepinephrine, but it bumps serotonin too. Psilocybin works mainly by switching on serotonin receptors. Stack them together and, in theory, you could push serotonin activity too high.

The worry is something called serotonin syndrome, which can show up as a racing heart, high blood pressure, sweating, shakiness, agitation, or in serious cases confusion and a dangerous fever. I'll be honest with you though: this concern comes from how the drugs work on paper, not from real cases in people. Even so, I wouldn't take the chance. Psilocybin is also illegal in most places and unpredictable. Please talk with your doctor or pharmacist before mixing anything with your Vyvanse.

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

Lisdexamfetamine 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 about mixing psilocybin with Vyvanse: both are stimulating to the brain and nervous system. Psilocybin (turned into psilocin in your body) revs up serotonin activity, while Vyvanse boosts dopamine and norepinephrine. Stack them together and those effects can pile on, so the worry is more of what Vyvanse already does, things like a racing or pounding heart, higher blood pressure, jitteriness, anxiety, trouble sleeping, and overheating.

I'll be honest with you: this concern is theoretical, based on how the two work rather than solid studies in people. Still, combining two stimulating substances isn't something to take lightly, and psilocybin is investigational and illegal in most places. Please talk with your doctor or pharmacist before changing anything on your own.

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 Lisdexamfetamine 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. Lisdexamfetamine)
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.

From our Q&A

Questions About Psilocybin or Lisdexamfetamine

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 Lisdexamfetamine, 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 Lisdexamfetamine

This page covers Psilocybin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Lisdexamfetamine page lists 126 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 6 major · 98 moderate · 22 minor.

Open the Lisdexamfetamine interaction page

How much people look this up

Where Psilocybin and Lisdexamfetamine 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

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

29 days ago today
Medication Lisdexamfetamine
Top 5%

#41 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 Lisdexamfetamine

What Is Lisdexamfetamine Used For?

Brand name: Vyvanse

Lisdexamfetamine treats Attention Deficit Hyperactivity Disorder (ADHD) in adults and children age 6 and older. It is also approved to treat moderate to severe binge eating disorder (BED) in adults.

It is not approved or recommended for weight loss, and its safety and effectiveness for treating obesity have not been established. It is not recommended in children under 6 years old.

See full Lisdexamfetamine 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
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 Lisdexamfetamine, 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 Lisdexamfetamine supplement interactions › Every supplement checked against Lisdexamfetamine, ranked by severity Lisdexamfetamine drug information › The full plain-English guide to this medication 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 Lisdexamfetamine Together: Common Questions

Can you take Psilocybin with Lisdexamfetamine?
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 Lisdexamfetamine?
Lisdexamfetamine 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 Lisdexamfetamine 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

Still Have a Question About Lisdexamfetamine and Psilocybin?

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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.