Can CBD be used with antipsychotics and lithium?

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?

Lithium is not broken down in the liver; it is removed almost entirely by the kidneys. So CBD's effect on liver enzymes is not expected to affect lithium directly. Lithium's product information, however, states that medicines that affect kidney function, fluid loss and changes in salt balance increase the risk of lithium toxicity. (Lithium prescribing information (Warnings and Precautions), PMID 32851114, PMID 39719830)

As a possible explanation, the doctors who wrote up the case pointed to a 25% rise in creatinine (a blood value that shows kidney function) after CBD was started, even though it stayed within normal limits, and to the patient drinking little fluid as the toxicity set in; they also noted that this rise in creatinine alone would hardly explain such a large increase. According to the product information for approved CBD, CBD can raise creatinine by about 10% within two weeks of starting; the cause is not known. (PMID 32851114, EMA Epidyolex prescribing information 4.8)

Antipsychotics are broken down by different enzymes: clozapine mainly by CYP1A2, as well as CYP3A4 and CYP2D6; olanzapine by CYP1A2 and glucuronidation (binding by UGT enzymes); quetiapine by CYP3A4; aripiprazole by CYP3A4 and CYP2D6; and risperidone mostly by CYP2D6. CBD's effect on these enzymes also differs: approved CBD raised the total amount in the blood of caffeine, which is broken down by CYP1A2, about 2-fold (weak inhibition), but did not change midazolam, which is broken down by CYP3A4; a CBD-dominant extract also did not change CYP2D6 activity in healthy volunteers. Clozapine's product information asks for the patient to be monitored closely when it is used with substances that weakly or moderately slow CYP1A2, such as caffeine. Whether CBD changes clozapine or olanzapine levels, however, has not been measured. (Clozapine prescribing information §2.7 and §7.1 and §12.3, Olanzapine prescribing information §12.3, Quetiapine prescribing information §12.3, Aripiprazole prescribing information §12.3, Risperidone prescribing information §12.3, PMID 33951339, FDA Epidiolex label §7.2 and §12.3 (05/2026), PMID 37313955)

Regardless of blood levels, CBD and many antipsychotics can cause sleepiness; the product information states that sleepiness may increase when such medicines are used together. In one schizophrenia study, sleepiness was more common with CBD added to an antipsychotic than with placebo. (FDA Epidiolex label §5.2 and §7.4 (05/2026), Clozapine prescribing information §5.16, PMID 29619533)

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. Case report

   Lithium: toxicity in a 13-year-old patient (2020)

   A 13-year-old boy with autism and Lennox–Gastaut syndrome had been taking the same dose of lithium for more than a year, and his lithium level was stable at 1–1.3 mmol/L. CBD was started for his seizures (5 mg/kg a day, 10 mg/kg after two weeks). Shortly after the dose was increased, he developed drowsiness, weakness, unsteadiness and refusal to eat; his lithium level was found to be 2.4 mmol/L. When lithium was stopped and fluids were given into a vein, he recovered within three days; CBD was continued. The patient was also taking clobazam, felbamate, quetiapine, perphenazine, trazodone and clonidine. A review assessing interaction reports in children rated the interaction as possible, but no plausible mechanism could be shown.

   Source: PMID 32851114, PMID 39719830

2. Controlled study

   Schizophrenia: CBD added to an antipsychotic was generally well tolerated (2018)

   In two placebo-controlled studies, CBD was added for 6 weeks to the antipsychotic taken by people with schizophrenia. In the study of 88 patients (1000 mg CBD a day), side-effect rates were similar to placebo. In the study of 36 patients (600 mg CBD a day), side effects were also similar; the only difference was that sleepiness was more common in those taking CBD. The effect on symptoms was inconsistent: the first study saw a small improvement, the second did not. No published study measuring antipsychotic blood levels with CBD could be found.

   Source: PMID 29241357, PMID 29619533

3. Drug-level study

   Clozapine: no direct study; the CYP1A2 pathway

   There is no study looking at clozapine together with CBD. Clozapine's product information asks for the clozapine dose to be clearly reduced with medicines that strongly slow CYP1A2, and for the patient to be monitored closely with those that weakly or moderately slow it, such as caffeine and the birth control pill; with clozapine, the risk of seizures rises with dose. Approved CBD (750 mg twice a day) raised the total amount in the blood of caffeine, which is broken down by the same pathway, by 95%; the US product information describes CBD as a weak inhibitor of CYP1A2.

   Source: Clozapine prescribing information §2.7 and §5.4 and §7.1, PMID 33951339, FDA Epidiolex label §7.2 and §12.3 (05/2026)

4. Drug-level study

   Olanzapine, quetiapine, aripiprazole and risperidone: no human data

   No study with published results measuring the blood levels of these medicines with CBD could be found; the assessment rests on indirect data. Olanzapine is partly broken down by CYP1A2, and its level rises with fluvoxamine, which strongly slows this enzyme; CBD, by contrast, weakly slows this enzyme. Approved CBD did not affect CYP3A4, which breaks down quetiapine and aripiprazole; the activity of CYP2D6, which breaks down aripiprazole and risperidone, also did not change with a CBD-dominant extract in healthy volunteers. A 74-person study in healthy volunteers in Germany (ClinicalTrials.gov NCT02051387) looking at a new CBD tablet and its interaction with amisulpride, olanzapine, quetiapine and risperidone (including the blood levels of these medicines) was completed in August 2017; as of October 2026, drug-level results are neither in the study's registry entry nor in any publication we could find.

   Source: Olanzapin prescribing information §7.1, FDA Epidiolex label §7.2 and §12.3 (05/2026), EMA Epidyolex prescribing information 5.2, PMID 37313955, ClinicalTrials.gov NCT02051387

5. 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 antipsychotic or benzodiazepine 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

6. Case report

   Severe side effects reported with cannabis containing THC (2024)

   In side-effect records of patients using medical cannabis with a high THC content (18–22%), inflammation of the heart muscle, kidney failure and a very slow heartbeat were reported with quetiapine, and QT prolongation on the ECG (a finding that indicates a tendency to heart rhythm problems) and serious rhythm disorders with aripiprazole and haloperidol. These findings relate to cannabis containing THC, not to CBD.

   Source: PMID 39502532

7. Official drug information

   Product information for approved CBD

   Antipsychotics and lithium are not named in the US (Epidiolex, 05/2026) or European (Epidyolex) product information. The US product information recommends considering a dose reduction for medicines broken down by CYP1A2 in which small changes in level can lead to serious side effects. The product information also states that CBD can increase sleepiness together with other medicines that cause sleepiness and can raise creatinine by about 10%.

   Source: FDA Epidiolex label §7.2 and §7.4 (05/2026), EMA Epidyolex prescribing information 4.4 and 4.5 and 4.8

What is monitored?

• Signs of lithium toxicity: diarrhea, vomiting, drowsiness, muscle weakness and poor coordination can be early signs; at higher levels, dizziness, trouble walking, blurred vision, ringing in the ears and passing large amounts of urine may occur. If you notice any such sign, tell your doctor right away. (Lithium prescribing information (Yan etkiler))
• Lithium level and kidney tests: the doctors who wrote up the case recommend close monitoring of patients who start CBD and take several medicines. Your doctor decides when your lithium level and kidney tests are measured. (PMID 32851114, Lithium prescribing information (Boxed Warning and Warnings))
• Fluid and salt intake: while taking lithium, it is important to drink enough fluid and take in a normal amount of salt. Diarrhea and reduced appetite are among CBD's common side effects; if you are eating and drinking little for these reasons, tell your doctor. (Lithium prescribing information (Precautions), EMA Epidyolex prescribing information 4.8)
• If you take clozapine: tell your doctor about changes after starting CBD, such as increased sleepiness, dizziness on standing up or seizures; clozapine's product information states that substances that raise its level can cause side effects. (Clozapine prescribing information §5.2 and §5.4 and §5.16 and §7.1)
• Sleepiness and driving: do not drive or operate machinery until you know how CBD affects you together with your antipsychotic. (FDA Epidiolex label §5.2 and §7.4 (05/2026), EMA Epidyolex prescribing information 4.7, Clozapine prescribing information §5.16) CBD and driving

Frequently asked questions

References

Last reviewed: October 30, 2026. On this date, each source was opened and checked against the related sentence.