Drug & supplement interaction

Delta-9-tetrahydrocannabinol (thc) + Amitriptyline, Chlordiazepoxide

Amitriptyline, Chlordiazepoxide brand name: Limbitrol DS.

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

Amitriptyline, Chlordiazepoxide falls into 3 drug categories that Delta-9-tetrahydrocannabinol (thc) can interact with; the most serious is rated moderate. Theoretically, THC might have additive effects if used with other CNS depressants.

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

Delta-9-tetrahydrocannabinol (thc) and Amitriptyline, Chlordiazepoxide

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

Why Are There 3 Interactions?

Delta-9-tetrahydrocannabinol (thc) interacts with whole categories of medication. Amitriptyline, Chlordiazepoxide falls into 3 of those categories, so it can interact with Delta-9-tetrahydrocannabinol (thc) in 3 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 3

Why this applies to Amitriptyline, Chlordiazepoxide

Amitriptyline, Chlordiazepoxide falls under CNS DEPRESSANTS — the group Delta-9-tetrahydrocannabinol (thc) interacts with.

Theoretically, THC might have additive effects if used with other CNS depressants.
Cannabis containing THC can have CNS depressant effects. Combining THC with other CNS depressants might result in additive or synergistic 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

Limbitrol DS is a combo pill: amitriptyline (a sedating older antidepressant) plus chlordiazepoxide (a benzodiazepine, in the same family as Valium). Both of these already calm the brain down. THC also has its own calming, mind-altering effects. So the concern here isn't about one changing how the other is broken down. It's simpler than that, the sedation just stacks up.

Put them together and you could feel extra drowsy, foggy, dizzy, or slow to react. Driving and operating machinery get riskier, and falls are a real worry for older folks. This is a theoretical warning based on how these things work, not hard proof, but it's a sensible caution. Please loop in your pharmacist or doctor before mixing them.

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.
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

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

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 thing to keep in mind with Limbitrol DS (which combines amitriptyline and chlordiazepoxide) alongside THC. On paper, THC might slow down one of the liver enzymes (CYP2C9) that helps clear these medications, which could let them build up a bit. If that happened, you'd mostly notice stronger sedation, more drowsiness, dry mouth, dizziness, constipation, or trouble concentrating.

That said, the evidence here is weak. This concern comes only from lab and test-tube studies, and one human study actually showed oral THC did not block this enzyme. The bigger, more real-world worry is simply added drowsiness and fuzzy thinking, since THC, amitriptyline, and chlordiazepoxide all sedate you on their own. Please check with your pharmacist or doctor before combining them.

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

3 of 3

Amitriptyline, Chlordiazepoxide 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 honest picture with Limbitrol DS (the amitriptyline plus chlordiazepoxide combo) and THC. On paper, THC might slightly slow the CYP3A4 enzyme that helps clear these medicines, which could let them build up a bit. If that happened, you might feel more of their usual effects: extra drowsiness, dizziness, dry mouth, constipation, or feeling foggy and unsteady.

That said, this concern comes only from lab-dish studies, and a human study actually found oral THC did not block CYP3A4. So the metabolism worry is weak. The bigger, more realistic issue is simple overlap: both amitriptyline and chlordiazepoxide already cause sedation, and so does THC. Stacking them can make you very sleepy and impair driving. Please check 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 761 moderate, 336 minor known drug interactions in our database — the Amitriptyline, Chlordiazepoxide one above is among them. If you take anything else, check it against the full list below.

Moderate 761 Minor 336 No known interaction 1,733 (incl. Amitriptyline, Chlordiazepoxide)
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.

Everything else you take

See Every Supplement That Interacts With Amitriptyline, Chlordiazepoxide

This page covers Delta-9-tetrahydrocannabinol (thc) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline, Chlordiazepoxide page lists 298 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: 17 major · 231 moderate · 50 minor.

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

“Alcohol is the first thing to know about here. Beer and wine both carry major, well-documented interactions with Amitriptyline and Chlordiazepoxide (Limbitrol DS), because both drugs already slow the central nervous system, and anything sedating layered on top can deepen ordinary drowsiness into something dangerous.”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline, Chlordiazepoxide interaction page

How much people look this up

Where Delta-9-tetrahydrocannabinol (thc) and Amitriptyline, Chlordiazepoxide 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

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

29 days ago today
Medication Amitriptyline, Chlordiazepoxide
Steady interest

#1,796 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
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
761Moderate
336Minor
1,732No known interaction
761 Moderate 336 Minor 1,732 No interaction
Moderate

761 interactions

Showing 60 of 761 moderate interactions — see all 761 on the Delta-9-tetrahydrocannabinol (thc) page.

Minor

336 interactions

Showing 60 of 336 minor interactions — see all 336 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 Amitriptyline, Chlordiazepoxide, 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 Amitriptyline, Chlordiazepoxide supplement interactions › Every supplement checked against Amitriptyline, Chlordiazepoxide, 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 Delta-9-tetrahydrocannabinol (thc) and Amitriptyline, Chlordiazepoxide Together: Common Questions

Can you take Delta-9-tetrahydrocannabinol (thc) with Amitriptyline, Chlordiazepoxide?
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 Delta-9-tetrahydrocannabinol (thc) and Amitriptyline, Chlordiazepoxide?
Amitriptyline, Chlordiazepoxide 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 Amitriptyline, Chlordiazepoxide 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

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