Drug & supplement interaction

Cannabis + Pitolisant Hydrochloride

Pitolisant Hydrochloride brand name: Wakix.

Moderate Interaction
The bottom line Moderate

Pitolisant Hydrochloride falls into 2 drug categories that Cannabis can interact with; the most serious is rated moderate. Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of cannabis.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabis and Pitolisant Hydrochloride

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Cannabis interacts with whole categories of medication. Pitolisant Hydrochloride falls into 2 of those categories, so it can interact with Cannabis in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

1 of 2

Why this applies to Pitolisant Hydrochloride

Pitolisant Hydrochloride falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Cannabis interacts with.

Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of cannabis.
Delta-9-tetrahydrocannabinol (THC), an active constituent of cannabis, is a substrate of CYP3A4 enzymes.
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 spotlight is actually on the cannabis side, not your Wakix. One of cannabis's main ingredients, THC, gets broken down by a liver enzyme called CYP3A4. Pitolisant can act as a mild blocker of that same enzyme, so in theory it could slow how fast THC clears from your body. The practical worry is that THC effects might hang around longer or feel stronger, meaning more drowsiness, dizziness, a foggy head, or a faster heartbeat.

Keep in mind this is a theoretical concern based on how these substances are processed, not something proven in real patients. Still, because cannabis can cause sleepiness, it works against what pitolisant is trying to do for your narcolepsy. Please check with your pharmacist or doctor before combining them.

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

2 of 2

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

Theoretically, cannabis may increase the levels and adverse effects of CYP3A4 substrates.
In vitro research shows that cannabis can inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates. In vitro research also shows that cannabis extracts modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids CBD and cannabigerol (CBG) had stronger inhibitory effects than extracts containing THC and CBD.
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 situation with Wakix (pitolisant) and cannabis. Pitolisant is an active drug (not a prodrug), and your body relies partly on a liver enzyme called CYP3A4 to clear it out. Lab studies suggest cannabis can gently slow this enzyme down. In theory, that could let pitolisant build up a bit more than usual, which might mean stronger effects or more side effects like headache, trouble sleeping at night, nausea, anxiety, or a faster heartbeat.

I want to be honest about the strength of this, though. This concern comes only from test-tube research, not real-world human studies, so we don't truly know how much it matters day to day. Still, since both can affect your nervous system, it's worth a quick chat with your doctor or pharmacist before combining them.

References
  1. Pellinen, P., Honkakoski, P., Stenback, F., Niemitz, M., Alhava, E., Pelkonen, O., Lang, M. A., and Pasanen, M. Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors. Eur.J Pharmacol 1-3-1994;2 PubMed
  2. 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

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

Cannabis Also Interacts With Other Medications

Cannabis has 2 major, 1,108 moderate, 25 minor 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.

Taking anything else?

Check Another of Your Medications Against Cannabis

Covers the 2,830 medications we’ve checked against Cannabis. Pick one to open its full report.

From our Q&A

Questions About Cannabis or Pitolisant Hydrochloride

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Cannabis or Pitolisant Hydrochloride, 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 Pitolisant Hydrochloride

This page covers Cannabis 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

One more smart check

Taking Cannabis as Part of a Dietary Supplement Product? Check It for Interactions

We hold 21 real supplement products containing Cannabis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cannabis. Your product may carry other ingredients that interact with Pitolisant Hydrochloride too, on top of Cannabis — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Cannabis 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 Cannabis
Top 25%

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

29 days ago today
Medication Pitolisant Hydrochloride
Top half

#1,029 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 Cannabis

What is Cannabis?

Cannabis
  • Chronic pain
  • Nausea and vomiting from chemotherapy
  • Muscle spasticity (e.g., multiple sclerosis)
  • Anxiety and stress
  • Sleep problems
  • Appetite stimulation

Cannabis contains many active compounds, mainly THC (which causes a 'high') and CBD (which does not). Some uses, such as chemotherapy-related nausea, certain seizure disorders, and muscle spasticity, have meaningful evidence, while many other popular uses are not well proven. It can cause real side effects and impairment, so talk to your doctor or pharmacist and follow your local laws before using it.

Read the full Cannabis 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 & Cannabis

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

2Major
1,108Moderate
25Minor
1,694No known interaction
Major

2 interactions

Moderate

1,108 interactions

Showing 60 of 1,108 moderate interactions — see all 1,108 on the Cannabis page.

Minor

25 interactions

No interaction 1,694 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 Cannabis and Pitolisant Hydrochloride Together: Common Questions

Can you take Cannabis 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 2 interactions listed for Cannabis and Pitolisant Hydrochloride?
Pitolisant Hydrochloride belongs to more than one drug category, and Cannabis 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 Cannabis 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 Cannabis?

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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.