Can CBD be used with benzodiazepines and sleeping pills?

Medicines and the importance of their interactions

From peer-reviewed publications and drug labels: the warnings, most important first. The same warnings also appear in the interaction checker. A medicine that is not listed can still interact with CBD.

How does the interaction happen?

There are two separate pathways. The first is an added effect: CBD, benzodiazepines, sleeping pills, hydroxyzine, gabapentin and pregabalin can all cause sleepiness or drowsiness; the product information states that the effects of such medicines can add up when they are used together. This added effect can occur even if the blood levels of the medicines do not change. (FDA Epidiolex label §5.2 and §7.4 (05/2026), EMA Epidyolex prescribing information 4.4, Alprazolam prescribing information §5.4, Zolpidem prescribing information §5.2, Hydroxyzine prescribing information (Precautions), Gabapentin prescribing information §5.4, Pregabalin prescribing information §5.6)

The second is blood levels. Alprazolam and buspirone are broken down by CYP3A4; zolpidem levels also rose by 70% with ketoconazole, which strongly slows this enzyme. For CYP3A4, the CBD data conflict: approved CBD (750 mg twice a day) did not change the level of midazolam, which is broken down by the same pathway, while a CBD-dominant cannabis extract raised midazolam by 56% after a single dose. (Alprazolam prescribing information §5.5, Buspirone prescribing information (Drug Interactions), Zolpidem prescribing information §12.3, FDA Epidiolex label §12.3 (05/2026), PMID 37313955)

Diazepam is converted by CYP3A4 and CYP2C19 into the active breakdown product N-desmethyldiazepam, and by CYP3A4 into temazepam; these are converted into oxazepam, and temazepam and oxazepam are largely removed by glucuronidation (binding by UGT enzymes). CBD moderately slows CYP2C19: it raised the clobazam breakdown product, which is broken down by the same pathway, about 3-fold. In the laboratory, CBD also slowed the removal of oxazepam by glucuronidation; model calculations predicted a meaningful rise, but this has not been measured in humans. (Diazepam prescribing information (Clinical pharmacology), FDA Epidiolex label §7.2 and §12.3 (05/2026), PMID 38399297)

Clonazepam is broken down by another pathway (reduction of its nitro group); CYP3A may also play a role. Gabapentin and pregabalin, by contrast, are removed by the kidneys with almost no breakdown in the liver; the product information states that these medicines are not expected to interact with other medicines through breakdown pathways. For these two, the main issue is added sleepiness and dizziness. (Clonazepam prescribing information (Clinical pharmacology), Gabapentin prescribing information §12.3, Pregabalin prescribing information §5.6 and §7)

What do studies and official drug information say?

Each finding shows the type of evidence it rests on. A case report describes a single patient; it does not prove cause and effect.

1. Controlled study

   Sleepiness: controlled studies of approved CBD

   In controlled studies in patients with Lennox–Gastaut and Dravet syndromes, sleepiness and drowsiness were seen in 32% of those taking approved CBD; in those on placebo, the rate was 11%, and the effect increased with dose. In patients also taking clobazam, from the benzodiazepine group, the rate was 46%, and in those not taking it, 16%. These effects were seen most at the start of treatment and could lessen over time.

   Source: FDA Epidiolex label §5.2 (05/2026), EMA Epidyolex prescribing information 4.8

2. Observational study

   Clonazepam: level did not change in 45 patients (2023)

   In an open-label access program using approved CBD (a study in which patient and doctor know the medicine and there is no comparison group), no significant change in clonazepam blood levels was seen in 45 patients taking clonazepam as the CBD dose increased. In the same study, no link was found with the levels of lorazepam (8 patients), gabapentin (7 patients) and pregabalin (3 patients) either; these numbers are very small. The study looked at blood levels; it did not measure added sleepiness separately.

   Source: PMID 37593907

3. Drug-level study

   Diazepam: blood level not measured; same enzyme pathway

   There is no study measuring diazepam blood levels with CBD. CBD slows CYP2C19, one of the enzymes that break down diazepam: approved CBD raised the level of the clobazam breakdown product, which is broken down by this enzyme, about 3-fold; a CBD-dominant extract also raised the total amount in the blood of omeprazole, which is broken down by the same enzyme, about 3-fold (a 207% increase). This is why it is thought that diazepam levels may also rise, but this has not been shown.

   Source: Diazepam prescribing information (Clinical pharmacology), FDA Epidiolex label §12.3 (05/2026), PMID 37313955

4. Observational study

   Diazepam nasal spray for seizures: safety and effect did not change (2023)

   Data from 163 patients using diazepam nasal spray as needed for seizure clusters were analyzed afterward: 23 were using approved CBD and 21 another CBD product. The overall side-effect rate was higher in those using any CBD (91% and 79%); however, side effects attributed to diazepam were lowest in the approved CBD group (13%), and the need for a second dose was also lowest (8%; 12% in those not using CBD). The authors concluded that CBD did not change the safety and effect of diazepam in this use; this applies to the spray used occasionally, not to diazepam taken every day.

   Source: PMID 37210793

5. Drug-level study

   Alprazolam, zolpidem and buspirone: no direct studies

   No study looking at these medicines together with CBD could be found. The blood levels of all three are affected by medicines that slow or speed up CYP3A4. Approved CBD (750 mg twice a day) did not change the level of midazolam, which is broken down by this pathway; the European product information also states that CBD does not slow CYP3A4. On the other hand, a single dose of a CBD-dominant extract (640 mg CBD and 20 mg THC) raised the total amount of midazolam in the blood by 56%. Added sleepiness, however, can occur regardless of blood levels.

   Source: Alprazolam prescribing information §5.5, Zolpidem prescribing information §7.2 and §12.3, Buspirone prescribing information (Drug Interactions), FDA Epidiolex label §7.4 and §12.3 (05/2026), EMA Epidyolex prescribing information 5.2, PMID 37313955

6. Laboratory study

   Lorazepam and oxazepam: laboratory data (2024)

   Oxazepam is removed in the liver by binding to UGT enzymes (glucuronidation). In experiments with samples from human liver, CBD slowed this pathway; model calculations predicted a rise of between 1.25-fold and 3.45-fold in the total amount of oxazepam in the blood with CBD or THC taken by mouth. This calculation has not been confirmed in humans. The European patient information for approved CBD lists lorazepam among the medicines whose dose may need adjusting; in 8 patients taking it, however, no link was found between lorazepam levels and the CBD dose.

   Source: PMID 38399297, EMA Epidyolex prescribing information (patient information section 2), PMID 37593907

7. Observational study

   Gabapentin and pregabalin: dizziness reported more often (2023)

   In an observational study following 275 patients who started a medical cannabis product (CBD alone or CBD with THC) for chronic pain, those taking gabapentin or pregabalin reported dizziness 2.4 times more often than those not taking these medicines. This comparison does not prove an interaction; dizziness is also among these medicines' own side effects. Side effects were less common with products containing CBD alone than with those also containing THC.

   Source: PMID 36445409, Gabapentin prescribing information §5.4, Pregabalin prescribing information §5.6

8. Controlled study

   Side effects did not increase in people with advanced cancer (2026)

   In a later analysis of a controlled study comparing CBD oil with placebo in people with advanced cancer, the amount of CBD patients chose themselves did not differ by benzodiazepine or antipsychotic use; in those taking these medicines, CBD did not increase the likelihood of new or worsening side effects. The measurements were indirect (medicine levels were not measured), and the authors state that the result applies to short-term use.

   Source: PMID 39539239

9. Official drug information

   Product information: added sleepiness with sedatives

   The US (05/2026) and European product information for approved CBD state that sleepiness and drowsiness may increase together with sedative medicines, including alcohol; among benzodiazepines, only clobazam is covered in detail, while the European patient information also lists lorazepam among medicines whose dose may be adjusted. The product information for alprazolam, clonazepam, zolpidem and hydroxyzine also asks for caution when used with other sedatives and alcohol; hydroxyzine's product information recommends that patients not use other sedative medicines at the same time.

   Source: FDA Epidiolex label §7.2 and §7.4 (05/2026), EMA Epidyolex prescribing information 4.4 and 4.5 and patient information section 2, Alprazolam prescribing information §5.4, Clonazepam prescribing information (Warnings), Zolpidem prescribing information §5.2, Hydroxyzine prescribing information (Precautions)

10. Controlled study

    Alcohol: in four small studies, CBD did not clearly change the effect of alcohol (1979, 2023, 2026)

    In two newer small placebo-controlled studies in healthy adults who drink alcohol, CBD taken by mouth shortly before alcohol did not clearly change breath alcohol levels or how alcohol's effects felt. In the 2023 study, 36 heavy drinkers were given 30 or 200 mg of CBD; breath alcohol fell slightly more slowly with CBD, but the researchers found this difference very small and unimportant. In the 2026 study, in 19 moderate drinkers, 50 or 100 mg of CBD isolate did not change the effect of alcohol or attention and balance tests 4 hours later; then, while 100 mg of CBD was taken daily for 4 weeks, the amount of drinking and the urge to drink did not change (there was no placebo group in this period), and only two side effects (drowsiness and headache) were reported, both gone by the next day. The second study was stopped before it reached the planned number of participants; a CBD company funded it, supplied the CBD and had a role in the study design. Two older small studies from 1979 had similar results: in 10 healthy volunteers, when 200 mg of CBD was taken with alcohol, breath alcohol levels were lower than with alcohol alone, but alcohol's impairing effect on movement and attention tests and how its effects felt were not very different between the two conditions; in 15 volunteers, 0.32 mg of CBD per kilogram of body weight did not change blood alcohol levels or test results. None of these four studies looked at using CBD and alcohol together with sedative medicines.

    Source: PMID 36939855, PMID 42288934, PMID 120541, PMID 115049, ClinicalTrials.gov NCT05317507

What is monitored?

• Sleepiness and drowsiness: when starting CBD and when increasing the amount, watch for daytime drowsiness, grogginess, slowing down or difficulty concentrating. With approved CBD, these effects are seen most at the start of treatment. If you notice a clear change, tell your doctor. (FDA Epidiolex label §5.2 and §7.4 (05/2026), EMA Epidyolex prescribing information 4.4)
• Driving and operating machinery: do not drive or operate machinery until you know how CBD affects you together with these medicines. Zolpidem's product information states that when taken with other sedatives, attention and driving ability may be impaired the next morning, too. (EMA Epidyolex prescribing information 4.7, FDA Epidiolex label §5.2 and §17 (05/2026), Zolpidem prescribing information §5.2) CBD and driving
• Alcohol: alcohol can increase the sleep-inducing effect of both CBD and these medicines; when taken with CBD, it also raises the amount of CBD in the blood (by 63% in one study). In small studies in healthy adults who drink alcohol, CBD did not clearly change the effect of alcohol; but these studies did not look at using CBD and alcohol together with the medicines on this page. (FDA Epidiolex label §7.4 and §12.3 (05/2026), EMA Epidyolex prescribing information 5.2, PMID 36939855, PMID 42288934, Alprazolam prescribing information §5.4)

Frequently asked questions

References

Last reviewed: November 1, 2026. On this date, each source was opened and checked against the related sentence.