Drug & supplement interaction

Delta-9-tetrahydrocannabinol (thc) + Midazolam

Midazolam brand names: Versed, Seizalam, Nayzilam.

Moderate Interaction
The bottom line Moderate

Midazolam 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 Midazolam

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. Midazolam 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 Midazolam

Midazolam 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

Here's the short version: both THC and midazolam can slow down the brain, just in different ways. Midazolam (Versed) is a benzodiazepine that calms brain activity to make you drowsy and relaxed, and THC has its own sedating, mind-altering effects. Stack them together and those effects can pile on top of each other. That could mean more grogginess, deeper sedation, slowed breathing, confusion, or feeling unsteady.

I'll be straight with you, this concern is theoretical, based on how each one works rather than strong studies. Still, since midazolam is usually given right before a procedure or surgery, it really matters that your care team knows about any cannabis or THC use beforehand. Please don't change anything on your own. Just tell your doctor, anesthesiologist, or pharmacist so they can plan safely.

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

ANESTHESIA

2 of 3

Midazolam also falls under ANESTHESIA.

THC use might alter the safety and clinical effects of various forms of anesthesia.
Cannabis contains THC. A small clinical study shows that higher doses of propofol may be needed to achieve relaxation and loss of consciousness in chronic cannabis users compared with nonusers. Another small clinical study shows that use of cannabis within 72 hours prior to undergoing surgery requiring atropine anesthesia may increase the risk of sustained postoperative tachycardia. The exact mechanisms of these interactions are unclear. Obtain a patient's history of cannabis use preoperatively and advise patients to discontinue use for at least 2 weeks prior to undergoing surgery.
Severity Moderate Likelihood Possible Evidence B

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 practical takeaway if you use cannabis and you're scheduled for a procedure where they give midazolam (Versed). The concern isn't that THC chemically reacts with midazolam in your bloodstream. It's that regular cannabis users sometimes need different amounts of sedation drugs to get the same effect. We've seen this most clearly with propofol, where chronic users needed higher doses to fully relax and drift off.

For midazolam specifically, your anesthesia team simply needs to know about your cannabis use ahead of time so they can dose you safely and watch your sedation, breathing, and heart rate. The evidence here is limited and based on small studies, so don't panic. Just be honest with your providers, and ask your pharmacist or surgical team how far in advance they'd like you to pause cannabis.

References
  1. Huson HB, Granados TM, Rasko Y. Surgical considerations of marijuana use in elective procedures. Heliyon. 2018;4(9):e00779. PubMed
  2. Goyal H, Awad HH, Ghali JK. Role of cannabis in cardiovascular disorders. J Thorac Dis. 2017;9(7):2079-2092. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Midazolam 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: your body uses an enzyme called CYP3A4 to break down midazolam (Versed). Lab studies hint that THC might slow that enzyme down a little, which in theory could let midazolam linger longer and feel a bit stronger. With a sedative like this, that could mean more drowsiness, deeper relaxation, or feeling groggy and foggy for longer than expected.

That said, I don't want to overstate it. This concern comes only from test-tube research, and an actual human study found that oral THC did not meaningfully block CYP3A4. So a real-world interaction is considered unlikely and minor. Still, because midazolam already makes you sleepy and THC does too, the bigger practical worry is added sedation. Let your anesthesia team or pharmacist know you use cannabis so they can plan safely.

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 Midazolam 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 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 Midazolam

This page covers Delta-9-tetrahydrocannabinol (thc) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Midazolam page lists 202 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), Beer (major), Bitter Orange (major) and Fever Bark (major).

By severity: 11 major · 153 moderate · 38 minor.

From our pharmacist’s overview on the Midazolam page

“Sedation stacked on sedation is the headline risk with midazolam (Versed, Seizalam, Nayzilam). Midazolam is a benzodiazepine used for sedation and seizure emergencies, and 78 of the 202 interacting ingredients here, beer and wine included, add their own drowsiness, which can slide into dangerously slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Midazolam interaction page

How much people look this up

Where Delta-9-tetrahydrocannabinol (thc) and Midazolam 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

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

29 days ago today
Medication Midazolam
Steady interest

#1,773 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 Midazolam

What Is Midazolam Used For?

Brand names: Versed, Seizalam, Nayzilam

Midazolam is used in several different forms depending on the setting. Injectable midazolam (given by IV or IM shot) is used before and during surgery or procedures — such as endoscopy, cardiac catheterization, or bronchoscopy — to cause sedation, reduce anxiety, and prevent memory of the event. It can also be used to start general anesthesia or to keep heavily sedated, ventilated patients comfortable in a critical care unit. Midazolam HCl oral syrup is used specifically in children for sedation and anxiety relief before procedures or anesthesia induction, in a monitored medical setting only.

Nayzilam nasal spray is indicated for a different purpose: the acute treatment of seizure clusters (also called acute repetitive seizures) in people aged 12 and older who have epilepsy. It is used intermittently — not as a daily seizure medicine — when a cluster of seizures breaks through the person's usual pattern.

See full Midazolam 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
761Moderate
336Minor
1,732No known 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
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
Pharmacist Counseling Corner

Taking Delta-9-tetrahydrocannabinol (thc) and Midazolam Together: Common Questions

Can you take Delta-9-tetrahydrocannabinol (thc) with Midazolam?
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 Midazolam?
Midazolam 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 Midazolam 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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