Drug & supplement interaction

Cannabidiol (cbd) + Pitolisant Hydrochloride

Pitolisant Hydrochloride brand name: Wakix.

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

Pitolisant Hydrochloride falls into 3 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2D6.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabidiol (cbd) and Pitolisant Hydrochloride

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Pitolisant Hydrochloride falls into 3 of those categories, so it can interact with Cannabidiol (cbd) in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 3

Why this applies to Pitolisant Hydrochloride

Pitolisant Hydrochloride falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Cannabidiol (cbd) interacts with.

Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2D6.
In vitro research shows that cannabidiol inhibits CYP2D6. Theoretically, concomitant use of cannabidiol with CYP2D6 substrates might increase the risk for adverse effects from these substrates. However, a clinical crossover trial in healthy adults shows that cannabidiol does not inhibit dextromethorphan, a substrate of CYP2D6.
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

Your body uses an enzyme called CYP2D6 to help clear pitolisant (Wakix) from your system. CBD may slow that enzyme down a bit, at least in lab studies. The concern here is that if pitolisant gets cleared more slowly, levels could creep up and you might notice more of its side effects, like headache, trouble sleeping at night, nausea, anxiety, or a faster heartbeat.

I want to be honest about how shaky this one is. It's theoretical, based mostly on test-tube data. In fact, a human study found CBD did not slow down another CYP2D6 drug as expected. So this may turn out to be a non-issue, but since pitolisant already carries a heart-rhythm caution, it's worth a quick chat with your pharmacist or doctor before combining the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yamaori S, Okamoto Y, Yamamoto I, Watanabe K. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos 2011;39(11):2049-56. PubMed
  2. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
  3. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

2 of 3

Pitolisant Hydrochloride also falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS.

Theoretically, CYP3A4 inhibitors might increase cannabidiol levels.
Cannabidiol is a substrate of CYP3A4 enzymes. Theoretically, drugs that inhibit CYP3A4 enzymes might increase levels of cannabidiol, increasing its effects and adverse effects.
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 the roles are flipped from what you might expect. In this pairing, pitolisant (Wakix) acts as the mild CYP3A4 inhibitor, and CBD is the one being affected. Pitolisant can theoretically slow down how your liver breaks down CBD, which means CBD could build up a bit higher than usual.

If that happens, you might notice more of CBD's own effects, like drowsiness, tiredness, an upset stomach, or changes in appetite. The good news is this is only a theoretical concern based on how the enzymes work, not something proven in real patients, so I wouldn't lose sleep over it. Still, since CBD product quality varies and doses differ a lot, it's worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Product information for Marinol. AbbVie. North Chicago, IL 60064. August 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Pitolisant Hydrochloride also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Cannabidiol may increase levels of drugs that are metabolized by CYP3A4.
In vitro and animal research shows that cannabidiol inhibits CYP3A4. In human studies and case reports, cannabidiol has been associated with an increase in plasma levels of the CYP3A4 substrates zonisamide, tacrolimus, everolimus, citalopram, midazolam, and methadone.
Severity Moderate Likelihood Probable Evidence A

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 gist: your body uses a liver enzyme called CYP3A4 to help clear pitolisant (Wakix). CBD can slow that enzyme down, which may let pitolisant build up higher than usual in your bloodstream. Pitolisant is an active drug (not a prodrug that needs activating), so more of it means a stronger effect and a bigger chance of side effects.

For pitolisant, that could look like trouble sleeping at night, headache, nausea, anxiety, or a faster or irregular heartbeat. The concern here is reasonable since CBD is a known CYP3A4 blocker, though the exact bump for this particular drug isn't well studied. Please don't change anything on your own. Just loop in your pharmacist or doctor so they can watch your dose and how you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yamaori S, Ebisawa J, Okushima Y, et al. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci 2011;88(15-16):730-6. PubMed
  2. Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
  3. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
  4. Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Sep;58(9):1586-92. PubMed
  5. Leino AD, Emoto C, Fukuda T, Privitera M, Vinks AA, Alloway RR. Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus. Am J Transplant. 2019;19(10):2944-2948. PubMed
  6. Wiemer-Kruel A, Stiller B, Bast T. Cannabidiol Interacts Significantly with Everolimus-Report of a Patient with Tuberous Sclerosis Complex. Neuropediatrics. 2019. PubMed
  7. Madden K, Tanco K, Bruera E. Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol. Pediatrics. 2020;e20193256. PubMed
  8. Anderson LL, Doohan PT, Oldfield L, et al. Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People. J Clin Psychopharmacol. 2021. PubMed
  9. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
  10. Treyer A, Reinhardt JK, Eigenmann DE, Oufir M, Hamburger M. Phytochemical comparison of medicinal cannabis extracts and study of their CYP-mediated interactions with coumarinic oral anticoagulants. Med Cannabis Cannabinoids. 2023;6(1):21-31. PubMed
  11. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.

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

Cannabidiol (cbd) Also Interacts With Other Medications

Cannabidiol (cbd) has 1,050 moderate known drug interactions in our database — the Pitolisant Hydrochloride one above is among them. If you take anything else, check it against the full list below.

Moderate 1,050 No known interaction 1,780 (incl. Pitolisant Hydrochloride)
Taking anything else?

Check Another of Your Medications Against Cannabidiol (cbd)

Covers the 2,830 medications we’ve checked against Cannabidiol (cbd). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Pitolisant Hydrochloride

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Pitolisant Hydrochloride page lists 158 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), 1,3-dmaa (moderate) and Acacia Rigidula (moderate).

By severity: 3 major · 114 moderate · 41 minor.

From our pharmacist’s overview on the Pitolisant Hydrochloride page

“Pitolisant (Wakix) keeps people with narcolepsy awake through the day, and it only works when a steady amount reaches the bloodstream. Most of the 158 supplement ingredients on this page can disturb exactly that, so this is a list worth slowing down for.”

Reviewed by 2 · Jul 18, 2026

Open the Pitolisant Hydrochloride interaction page

How much people look this up

Where Cannabidiol (cbd) and Pitolisant 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 Cannabidiol (cbd)
Top half

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

29 days ago today
Medication Pitolisant Hydrochloride
Steady interest

#2,522 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 Cannabidiol (cbd)

What is Cannabidiol (cbd)?

  • Anxiety and stress
  • Sleep problems
  • Chronic pain
  • Certain seizure disorders
  • Inflammation

CBD is a compound from the cannabis (hemp) plant that does not cause a 'high.' It has strong evidence only for certain rare seizure disorders (as a prescription drug), while most other popular uses are still backed by limited or early research. Product quality varies a lot, so talk with your pharmacist or doctor before using it, especially if you take other medicines.

Read the full Cannabidiol (cbd) monograph & all interactions
Medication

About Pitolisant

What Is Pitolisant Used For?

Brand name: Wakix

Wakix (pitolisant) is used to treat two hallmark problems of narcolepsy: excessive daytime sleepiness (feeling overwhelmingly tired and unable to stay awake during the day) and cataplexy (sudden episodes of muscle weakness or loss of muscle control, often triggered by emotion). It is approved for adults and children 6 years of age and older.

Both uses are specific to Wakix tablets taken by mouth. The drug is not approved for sleepiness or cataplexy caused by conditions other than narcolepsy.

See full Pitolisant drug information
Keep checking

Other Drugs & Cannabidiol (cbd)

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

0Major
1,050Moderate
0Minor
1,779No known interaction
1,050 Moderate 1,779 No interaction
Moderate

1,050 interactions

Showing 60 of 1,050 moderate interactions — see all 1,050 on the Cannabidiol (cbd) page.

No interaction 1,779 drugs checked — show the list

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

Showing the 60 most looked-up of 1,779 medications checked with no known interaction — see the full Cannabidiol (cbd) list.

See the full Cannabidiol (cbd) interactions page
See every supplement checked against Pitolisant Hydrochloride, 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
Cannabidiol (cbd) monograph › Uses, safety, and every drug interaction in one place Pitolisant Hydrochloride supplement interactions › Every supplement checked against Pitolisant Hydrochloride, ranked by severity Pitolisant 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 Cannabidiol (cbd) and Pitolisant Hydrochloride Together: Common Questions

Can you take Cannabidiol (cbd) with Pitolisant 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 3 interactions listed for Cannabidiol (cbd) and Pitolisant Hydrochloride?
Pitolisant Hydrochloride belongs to more than one drug category, and Cannabidiol (cbd) 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 Cannabidiol (cbd) and Pitolisant 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

Still Have a Question About Pitolisant Hydrochloride and Cannabidiol (cbd)?

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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.