Drug & supplement interaction

Delta-9-tetrahydrocannabinol (thc) + Imipramine

Imipramine brand names: Tofranil, Tofranil PM.

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

Imipramine falls into 2 drug categories that Delta-9-tetrahydrocannabinol (thc) can interact with; the most serious is rated minor. Theoretically, THC might increase the levels and adverse effects of CYP2C9 substrates.

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

Delta-9-tetrahydrocannabinol (thc) and Imipramine

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

Why Are There 2 Interactions?

Delta-9-tetrahydrocannabinol (thc) interacts with whole categories of medication. Imipramine falls into 2 of those categories, so it can interact with Delta-9-tetrahydrocannabinol (thc) in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

1 of 2

Why this applies to Imipramine

Imipramine falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Delta-9-tetrahydrocannabinol (thc) interacts with.

Theoretically, THC might increase the levels and adverse effects of CYP2C9 substrates.
In vitro research shows that THC moderately inhibits the CYP2C9-mediated 7-hydroxylation of S-warfarin in a concentration-dependent manner. In vitro research also shows that cannabis extracts containing THC modestly inhibit the CYP2C9 metabolism of tolbutamide; extracts providing the specific cannabinoids cannabidiol (CBD) or cannabigerol (CBG) alone had stronger inhibitory effects than extracts containing both THC and CBD. Theoretically, THC may inhibit the metabolism of other CYP2C9 substrates. Conversely, a crossover clinical study in healthy adults shows that oral THC does not inhibit CYP2C9.
Severity Minor Likelihood Unlikely Evidence D

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 gist for imipramine (Tofranil): on paper, THC might slow down one liver enzyme (CYP2C9) that helps clear this medicine. If that happened, imipramine could build up a bit, which in theory might nudge up its usual side effects like drowsiness, dry mouth, constipation, blurry vision, dizziness when standing, or a faster heartbeat.

But honestly, this is a very weak, mostly theoretical concern. It comes only from lab and test-tube studies, and a study in healthy people taking oral THC found it did not block this enzyme. CYP2C9 is also only a minor route for imipramine. I wouldn't lose sleep over it, but since this drug affects your heart and mood, it's worth a quick chat with your doctor or pharmacist before combining the two.

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
  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.
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

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

Theoretically, THC may increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that cannabis containing THC might modestly inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates. It is unclear if this effect is due to THC, other constituents, or the combination. In vitro research also shows that cannabis extracts containing THC modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids cannabidiol (CBD) or cannabigerol (CBG) alone had stronger inhibitory effects than extracts containing both THC and CBD. Conversely, a crossover clinical study in healthy adults shows that oral THC does not inhibit CYP3A4.
Severity Minor Likelihood Unlikely Evidence D

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 gist with imipramine and THC. Your liver uses an enzyme called CYP3A4 to help clear imipramine. Lab (test tube) studies suggest THC might slightly slow that enzyme down. If that happened in real life, imipramine could build up a bit, which in theory could nudge up its usual side effects, things like drowsiness, dry mouth, constipation, dizziness, or a faster heartbeat.

That said, I wouldn't lose sleep over this one. The evidence is weak and only theoretical, and a small human study actually found oral THC did not block CYP3A4. The interaction is rated minor and unlikely. Still, since both can make you sleepy and foggy, 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. 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
  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.

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

Delta-9-tetrahydrocannabinol (thc) Also Interacts With Other Medications

Delta-9-tetrahydrocannabinol (thc) has 762 moderate, 335 minor known drug interactions in our database — the Imipramine one above is among them. If you take anything else, check it against the full list below.

Moderate 762 Minor 335 No known interaction 1,733 (incl. Imipramine)
Taking anything else?

Check Another of Your Medications Against Delta-9-tetrahydrocannabinol (thc)

Covers the 2,830 medications we’ve checked against Delta-9-tetrahydrocannabinol (thc). Pick one to open its full report.

From our Q&A

Questions About Delta-9-tetrahydrocannabinol (thc) or Imipramine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Delta-9-tetrahydrocannabinol (thc) or Imipramine, 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 Imipramine

This page covers Delta-9-tetrahydrocannabinol (thc) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Imipramine page lists 254 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: 11 major · 190 moderate · 53 minor.

From our pharmacist’s overview on the Imipramine page

“Imipramine (Tofranil) is an older tricyclic antidepressant, and the supplements on this page deserve real scrutiny before you add one. Most of the list acts on the liver enzymes that process the drug, so an ingredient can quietly raise or lower imipramine levels: grapefruit pushes them up, while St.”

Reviewed by 2 · Jul 18, 2026

Open the Imipramine interaction page

How much people look this up

Where Delta-9-tetrahydrocannabinol (thc) and Imipramine 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 Delta-9-tetrahydrocannabinol (thc)
Top half

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

29 days ago today
Medication Imipramine
Steady interest

#2,002 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 Delta-9-tetrahydrocannabinol (thc)

What is Delta-9-tetrahydrocannabinol (thc)?

Delta-9-tetrahydrocannabinol (thc)
  • Chronic or nerve pain
  • Nausea and vomiting from chemotherapy
  • Appetite loss and weight loss
  • Muscle spasticity
  • Sleep problems
  • Anxiety and stress

THC is the main mind-altering compound in cannabis and is best known for causing a 'high.' A prescription form (dronabinol) is approved for chemotherapy-related nausea and appetite loss, but for most other uses the evidence is mixed or limited, and THC can impair thinking and driving. It should be avoided in pregnancy and breastfeeding and used only with medical guidance.

Read the full Delta-9-tetrahydrocannabinol (thc) monograph & all interactions
Medication

About Imipramine

What Is Imipramine Used For?

Brand names: Tofranil, Tofranil PM

Imipramine is used to relieve symptoms of depression. Both Imipramine Hydrochloride tablets and Imipramine Pamoate capsules are approved for this use. Endogenous depression — the kind that seems to arise from within rather than a clear outside cause — tends to respond especially well. It may take one to three weeks before you notice the full benefit.

Imipramine Hydrochloride tablets are also approved as a short-term, add-on treatment to help reduce nighttime bedwetting (nocturnal enuresis) in children aged 6 and older, after a doctor has ruled out physical causes.

See full Imipramine drug information
Keep checking

Other Drugs & Delta-9-tetrahydrocannabinol (thc)

Browse every other medication we’ve checked against Delta-9-tetrahydrocannabinol (thc) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
762Moderate
335Minor
1,732No known interaction
762 Moderate 335 Minor 1,732 No interaction
Moderate

762 interactions

Showing 60 of 762 moderate interactions — see all 762 on the Delta-9-tetrahydrocannabinol (thc) page.

Minor

335 interactions

Showing 60 of 335 minor interactions — see all 335 on the Delta-9-tetrahydrocannabinol (thc) page.

No interaction 1,732 drugs checked — show the list

We also checked Delta-9-tetrahydrocannabinol (thc) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,732 medications checked with no known interaction — see the full Delta-9-tetrahydrocannabinol (thc) list.

See the full Delta-9-tetrahydrocannabinol (thc) interactions page
See every supplement checked against Imipramine, 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
Delta-9-tetrahydrocannabinol (thc) monograph › Uses, safety, and every drug interaction in one place Imipramine supplement interactions › Every supplement checked against Imipramine, ranked by severity Imipramine 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 Delta-9-tetrahydrocannabinol (thc) and Imipramine Together: Common Questions

Can you take Delta-9-tetrahydrocannabinol (thc) with Imipramine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Delta-9-tetrahydrocannabinol (thc) and Imipramine?
Imipramine belongs to more than one drug category, and Delta-9-tetrahydrocannabinol (thc) 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 Delta-9-tetrahydrocannabinol (thc) and Imipramine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Imipramine and Delta-9-tetrahydrocannabinol (thc)?

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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.