Drug & supplement interaction

Delta-9-tetrahydrocannabinol (thc) + Sertraline

Sertraline brand name: Zoloft.

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

Sertraline falls into 3 drug categories that Delta-9-tetrahydrocannabinol (thc) can interact with; the most serious is rated moderate. Theoretically, CYP3A4 inhibitors might increase the levels and clinical effects of THC.

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 Sertraline

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. Sertraline 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

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

1 of 3

Why this applies to Sertraline

Sertraline falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Delta-9-tetrahydrocannabinol (thc) interacts with.

Theoretically, CYP3A4 inhibitors might increase the levels and clinical effects of THC.
THC 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's the gist: your body uses an enzyme called CYP3A4 to help break down THC. Sertraline (Zoloft) can mildly slow that enzyme down. So in theory, if you use THC while taking sertraline, the THC could hang around a little longer and feel a bit stronger than usual. That might mean more drowsiness, dizziness, a foggier head, or feeling more 'high' than you expected.

I want to be honest, though: this is a theoretical concern based on how the drugs work on paper, not on solid real-world studies. Sertraline is also only a weak CYP3A4 blocker, so for many people the effect is small. Still, if you notice you feel more out of it than normal, go slow and check in with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
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 2C9 (CYP2C9) INHIBITORS

2 of 3

Sertraline also falls under CYTOCHROME P450 2C9 (CYP2C9) INHIBITORS.

Theoretically, drugs that are CYP2C9 inhibitors might increase the levels and adverse effects of THC.
THC is a substrate of CYP2C9 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 really on the THC, not your Zoloft. Your body uses an enzyme called CYP2C9 to help break down THC. Sertraline can mildly slow that enzyme down, so in theory THC may clear a bit more slowly and build up. That could mean a stronger or longer 'high' and more of THC's usual effects, like dizziness, drowsiness, a racing heart, or feeling foggy and uncoordinated.

I want to be honest about how soft this is: it's a theoretical concern based on how these compounds behave on paper, not something proven in real patients. Both can cause drowsiness on their own too. If you use cannabis and take sertraline, just give your pharmacist or doctor a heads-up so they can keep an eye on you.

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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Sertraline 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 a liver enzyme called CYP3A4 to help clear sertraline, and lab (test tube) studies hint that THC might slow that enzyme down a little. In theory, that could let sertraline build up slightly, which might mean more of its usual side effects, things like nausea, drowsiness, jitteriness, headache, or trouble sleeping.

That said, I wouldn't lose sleep over this one. The evidence is weak and only from lab work, and one actual human study found that oral THC did not meaningfully block CYP3A4. Sertraline also leans on other enzymes too, so 3A4 isn't its only path out. Both can also cause drowsiness, so the bigger real-world concern is feeling extra foggy. Before combining them, check with your pharmacist or doctor.

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 Sertraline 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. Sertraline)
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 Sertraline

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 Sertraline, 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 Sertraline

This page covers Delta-9-tetrahydrocannabinol (thc) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Sertraline page lists 188 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: 9 major · 139 moderate · 40 minor.

From our pharmacist’s overview on the Sertraline page

“If you take sertraline (Zoloft) for depression, anxiety, or panic, treat this page with real care. Nine of the 188 supplements here carry a major rating, and the biggest issue is how your body clears the drug.”

Reviewed by 2 · Jul 18, 2026

Open the Sertraline interaction page

How much people look this up

Where Delta-9-tetrahydrocannabinol (thc) and Sertraline 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

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

29 days ago today
Medication Sertraline
Top 10

#5 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 Sertraline

What Is Sertraline Used For?

Brand name: Zoloft

Sertraline treats a range of mental health conditions. All formulations are approved for major depressive disorder (MDD) in adults and obsessive-compulsive disorder (OCD). The oral solution (including Zoloft oral solution) and several tablet formulations are also approved for panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD).

For OCD specifically, the capsule formulations and some tablet products are approved for use in adults and children aged 6 and older. Sertraline hydrochloride tablets (plain, not film-coated) are approved for OCD in pediatric patients as well. However, sertraline is not approved for major depressive disorder in children — only in adults.

See full Sertraline 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
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 Sertraline, 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 Sertraline supplement interactions › Every supplement checked against Sertraline, ranked by severity Sertraline 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 Sertraline Together: Common Questions

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