Drug & supplement interaction

Cannabis + Amitriptyline, Perphenazine

Amitriptyline, Perphenazine brand names: Triavil, Etrafon, Etrafon-A, Etrafon-Forte.

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

Amitriptyline, Perphenazine falls into 5 drug categories that Cannabis can interact with; the most serious is rated moderate. Theoretically, cannabis might have additive effects if used with other CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions5
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabis and Amitriptyline, Perphenazine

These two interact in 5 distinct ways. Each one is explained separately below.

Why Are There 5 Interactions?

Cannabis interacts with whole categories of medication. Amitriptyline, Perphenazine falls into 5 of those categories, so it can interact with Cannabis in 5 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 5

Why this applies to Amitriptyline, Perphenazine

Amitriptyline, Perphenazine falls under CNS DEPRESSANTS — the group Cannabis interacts with.

Theoretically, cannabis might have additive effects if used with other CNS depressants.
Cannabis can have CNS depressant effects. Combining cannabis with other CNS depressants might result in additive or synergistic effects. A small clinical trial in healthy adults shows that inhaling a high-grade cannabis (Bedrocan International B.V., Veendam, The Netherlands) 100 mg, containing delta-9-tetrahydrocannabinol 21.8% and cannabinol 0.1%, modestly increases subjective feelings of sedation when compared with cannabis alone.
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

This combo pill pairs amitriptyline (a tricyclic antidepressant) with perphenazine (an antipsychotic). Both already tend to make people drowsy and a bit foggy. Cannabis works through a different pathway, but it also calms down the central nervous system, so stacking them can pile on the sedation. The concern here is mostly about overlapping effects, not one drug changing how the other is broken down.

In real life, that might mean feeling extra sleepy, dizzy, slowed down, or unsteady on your feet, plus a dry mouth or low blood pressure when you stand up. The evidence for this is theoretical, based on how these substances behave, so it is not a hard rule. Still, please check with your pharmacist or doctor before mixing them, and never adjust your medication on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Marinol Prescribing Information. Solvay Pharmaceuticals, Rev March 2008. Available at: http://www.solvaypharmaceuticals-us.com/static/wma/pdf/1/3/2/5/0/004InsertText500012RevMar2008.pdf (Accessed 2 July 2009).
  2. Hollister, L. E. Interactions of cannabis with other drugs in man. NIDA Res.Monogr 1986;68:110-116. DOI
  3. van Dam CJ, van der Schrier R, van Velzen M, et al. Inhaled Delta(9)-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers. Br J Anaesth 2023;130(4):485-493.
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 5

Amitriptyline, Perphenazine also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, cannabis might increase the levels and adverse effects of CYP2C9 substrates.
In vitro research shows that the cannabis constituents delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol moderately inhibit the CYP2C9-mediated 7-hydroxylation of S-warfarin in a concentration-dependent manner. In vitro research also shows that cannabis extracts modestly inhibit the CYP2C9 metabolism of tolbutamide; 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

This combo pill pairs amitriptyline (a tricyclic antidepressant) with perphenazine (an antipsychotic). The concern on file is that cannabis can mildly slow down a liver enzyme called CYP2C9, which helps break these medicines down. If that clearing slows, more drug could linger in your body and push its effects up a notch.

In real life that might mean stronger drowsiness, dry mouth, blurry vision, constipation, dizziness on standing, or a faster heartbeat. Honestly though, this is based only on lab dish studies, not people, so it's more theoretical than proven. Cannabis on its own also adds sedation. I wouldn't panic, but please check with your doctor or pharmacist before combining them so they can watch how you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Damkier P, Lassen D, Christensen MMH, Madsen KG, Hellfritzsch M, Pottegård A. Interaction between warfarin and cannabis. Basic Clin Pharmacol Toxicol. 2019;124(1):28-31. 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
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 5

Amitriptyline, Perphenazine 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

This combination pill pairs amitriptyline (a tricyclic antidepressant) with perphenazine (an antipsychotic), and both are partly broken down by a liver enzyme called CYP3A4. Lab studies hint that cannabis may slow this enzyme down, which in theory could let these medicines build up a little higher in your body. If that happened, you might notice stronger versions of their usual effects, like heavy drowsiness, dizziness, dry mouth, constipation, blurred vision, or feeling foggy. Neither drug is a prodrug, so the direction here is more effect, not less.

Keep in mind this is based only on test-tube research, so it's a theoretical concern, not a proven one. Still, cannabis on its own can add to the sleepiness and dizziness. Please run this by your doctor or pharmacist before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
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
Moderate

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

4 of 5

Amitriptyline, Perphenazine also falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES.

Cannabis may increase levels of drugs metabolized by CYP2C19.
Research shows that cannabidiol (CBD), a constituent of cannabis, inhibits CYP2C19. In clinical studies and case reports, cannabidiol use resulted in significant increases in the serum levels of topiramate, methadone, citalopram, omeprazole, and N-desmethylclobazam, the primary active metabolite of clobazam. These chemicals are metabolized by CYP2C19. Concomitant use of cannabis with CYP2C19 substrates may increase the risk for adverse effects from these substrates.
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

This combination pill pairs amitriptyline (a tricyclic antidepressant) with perphenazine (an antipsychotic). The CBD in cannabis can block an enzyme called CYP2C19, which helps clear amitriptyline. When that pathway slows down, amitriptyline can build up in your body. That may mean stronger side effects like drowsiness, dry mouth, constipation, blurry vision, dizziness on standing, and a faster heartbeat.

Keep in mind this concern is mostly theoretical, based on how the drugs are processed rather than strong human studies. Concentrated CBD products are more likely to matter than an occasional small amount. Both cannabis and this medicine can also make you sleepy, so the combined drowsiness is worth watching. Please check with your pharmacist or doctor before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
  2. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
  3. 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
  4. Devinsky O, Marsh E, Friedman D, et la. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016 Mar;15(3):270-8.
  5. Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015 Aug;56(8):1246-51. PubMed
  6. Madden K, Tanco K, Bruera E. Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol. Pediatrics. 2020;e20193256. PubMed
  7. 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
  8. 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
  9. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
Minor

ANTIPSYCHOTIC DRUGS

5 of 5

Amitriptyline, Perphenazine also falls under ANTIPSYCHOTIC DRUGS.

Cannabis does not seem to affect blood levels or effects of some antipsychotic drugs.
Human research shows that cannabis use does not affect blood levels or clinical effects of amisulpride, aripiprazole, or olanzapine in patients with schizophrenia and related disorders.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Here's the reassuring part: the research we have suggests cannabis doesn't seem to change the blood levels or the actual effects of antipsychotic medicines, which is the perphenazine half of this combo pill. So from a drug-level standpoint, this interaction is considered minor and unlikely to cause a problem.

That said, I'd still be thoughtful. Both this medication (especially the amitriptyline portion) and cannabis can cause drowsiness, dizziness, dry mouth, and a foggy, slowed-down feeling. Stacking them can add up, so you might feel more sleepy or off-balance than usual. The evidence here isn't airtight, so please loop in your pharmacist or doctor before combining them, and go easy until you know how you react.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Alisauskiene R, Johnsen E, Gjestad R, et al. Does drug use affect the efficacy of amisulpride, aripiprazole and olanzapine in patients with schizophrenia spectrum disorders? Results from a pragmatic, randomised study. Gen Hosp Psychiatry 2023;83:185-193. 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 Amitriptyline, Perphenazine one above is among them. If you take anything else, check it against the full list below.

Major 2 Moderate 1,108 Minor 25 No known interaction 1,695 (incl. Amitriptyline, Perphenazine)
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 Amitriptyline, Perphenazine

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 Amitriptyline, Perphenazine, 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 Amitriptyline, Perphenazine

This page covers Cannabis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline, Perphenazine page lists 311 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 19 major · 235 moderate · 57 minor.

From our pharmacist’s overview on the Amitriptyline, Perphenazine page

“Alcohol is the risk I'd flag first for anyone taking amitriptyline with perphenazine (Triavil, Etrafon). Beer and wine both carry major ratings here, and 78 of the 311 ingredients on file deepen the drowsiness this antidepressant and antipsychotic combination already causes, sometimes to the point of slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine 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%

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

29 days ago today
Medication Amitriptyline, Perphenazine
Top half

#1,098 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
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
2 Major 1,108 Moderate 25 Minor 1,694 No 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

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

Showing the 60 most looked-up of 1,694 medications checked with no known interaction — see the full Cannabis list.

See the full Cannabis interactions page
See every supplement checked against Amitriptyline, Perphenazine, 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
Cannabis monograph › Uses, safety, and every drug interaction in one place Amitriptyline, Perphenazine supplement interactions › Every supplement checked against Amitriptyline, Perphenazine, 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 Cannabis and Amitriptyline, Perphenazine Together: Common Questions

Can you take Cannabis with Amitriptyline, Perphenazine?
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 5 interactions listed for Cannabis and Amitriptyline, Perphenazine?
Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine 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 Amitriptyline, Perphenazine 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.