Can CBD be used with methylphenidate and atomoxetine?

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?

In the body, methylphenidate is broken down mostly not by CYP enzymes but by an enzyme called carboxylesterase 1 (CES1) into an inactive breakdown product (ritalinic acid). In lab experiments, both CBD and THC slowed this enzyme. (Methylphenidate prescribing information §12.3, PMID 35512806)

A simple calculation using these lab data predicted an increase of up to 94% in the total amount of methylphenidate in the blood with approved CBD. A more detailed model, however, did not expect a clear interaction with a single dose of CBD; it predicted an increase of up to 55% when CBD is taken repeatedly at 10 mg/kg twice a day. A mild (34%) increase was also calculated for THC taken by smoking marijuana. The increase measured in healthy volunteers, however, was smaller than these estimates. (PMID 35512806, PMID 36467779)

Atomoxetine, on the other hand, is broken down mainly by CYP2D6; its prescribing information states that atomoxetine levels rise with medicines that strongly slow this enzyme. In the lab, CBD strongly slowed CYP2D6; but in a study in healthy volunteers with a CBD-dominant cannabis extract (640 mg CBD and 20 mg THC), CYP2D6 activity did not change. The prescribing information for approved CBD also does not list CYP2D6 among the enzymes CBD affects. (Atomoxetine prescribing information §7, PMID 21821735, PMID 37313955, FDA Epidiolex label §7.2 (05/2026), EMA Epidyolex prescribing information 4.5)

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. Drug-level study

   Methylphenidate: level rose by about 9% (2022)

   In a placebo-controlled crossover study, 12 healthy volunteers took 750 mg of approved CBD twice a day or a placebo for 3 days; then a single 10 mg dose of methylphenidate was given. With CBD, the total amount of methylphenidate in the blood (AUC) was on average 9% higher and its peak level 8% higher. Results varied from person to person; the researchers considered the average difference not clinically important. One of the volunteers taking CBD left the study because of nausea.

   Source: PMID 36467779

2. Laboratory study

   Methylphenidate: lab and modeling study (2022)

   In experiments with samples obtained from human liver, CBD and THC slowed CES1, the enzyme that breaks down methylphenidate. Model calculations did not expect a clear interaction with a single dose of CBD; with repeated high CBD doses (10 mg/kg twice a day), they predicted that the total amount of methylphenidate in the blood could rise by up to 55% and its peak level by up to 45%. The authors state that these estimates need to be confirmed by a clinical study.

   Source: PMID 35512806

3. Laboratory study

   Atomoxetine: no human data with CBD; the CYP2D6 route

   No human study was found that looked at CBD together with atomoxetine. In the lab, CBD slowed CYP2D6, the enzyme that breaks down atomoxetine. However, in healthy volunteers given a single dose of a CBD-dominant cannabis extract, the breakdown of dextromethorphan, which was given to measure this enzyme's activity, did not change. In other words, the lab effect was not seen in this human study; whether atomoxetine levels change was not measured.

   Source: PMID 21821735, PMID 37313955, Atomoxetine prescribing information §7

4. Official drug information

   Prescribing information for approved CBD

   The US (Epidiolex, 05/2026) and European (Epidyolex) prescribing information do not mention methylphenidate or atomoxetine by name; CES1 and CYP2D6 are not listed among the enzymes CBD affects. The prescribing information lists decreased appetite and weight loss among CBD's common side effects and states that in children this may slightly slow growth in height; the prescribing information for methylphenidate and atomoxetine also calls for close monitoring of weight and height in children.

   Source: FDA Epidiolex label §7.2 (05/2026), EMA Epidyolex prescribing information 4.4 and 4.5 and 4.8, Methylphenidate prescribing information §5.7, Atomoxetine prescribing information §5.11

5. Controlled study

   THC and methylphenidate: increases in heart rate added up (2015)

   In a double-blind, crossover study, 16 healthy adults with no mental illness who occasionally used cannabis took 10 mg of oral THC (dronabinol) or placebo together with 0, 10 or 40 mg of methylphenidate in six separate sessions. The effects of THC and methylphenidate on heart rate added up: in the sessions with THC, peak heart rate averaged 89 beats per minute without methylphenidate, 96 with 10 mg of methylphenidate and 102 with 40 mg of methylphenidate. Only 40 mg of methylphenidate raised blood pressure. In one participant, a prolonged fast heartbeat (over 100 per minute) occurred with 40 mg of methylphenidate and THC together and was monitored by a doctor. Drug levels were not measured in the study, and CBD was not tested.

   Source: PMID 25175495

6. Case series

   Atomoxetine and dronabinol: side effects common in a small study (2023)

   In an open-label study (no placebo group) in which atomoxetine was tried together with dronabinol, a synthetic form of THC, to treat sleep apnea, 15 patients first took atomoxetine alone for one week, then atomoxetine (40–80 mg) and dronabinol (2.5–10 mg) in weekly increasing doses for three weeks. According to the results in the study registry, insomnia, nausea, raised blood pressure, excessive suspiciousness (paranoia), a feeling of detachment from oneself, fast heartbeat and, in one patient, suicidal thoughts were reported during the periods when the two were taken together. Side effects were also common in the first week on atomoxetine alone (in 9 of 15 patients; most often insomnia). Of the 15 patients, 5 did not complete the study: one in the first week and four during the combined periods. Because there was no placebo group and the doses were raised step by step, it cannot be clearly told which side effects came from dronabinol; the authors note that side effects were common and could sometimes be harmful. The study was funded by the company developing this combination; the patients did not have ADHD, and atomoxetine levels were not reported.

   Source: PMID 36805833, ClinicalTrials.gov NCT05101122

7. Controlled study

   Amphetamine derivatives and guanfacine: no CBD data; three studies with THC

   No human studies were found looking at CBD together with amphetamine derivatives (such as dextroamphetamine and lisdexamfetamine) and guanfacine. There are three double-blind studies with THC. In a 1976 study, when a THC cigarette was smoked 1.5 hours after oral dextroamphetamine (equivalent to 10 mg in a 70 kg person), heart rate and blood pressure rose in an additive way. In 15 people who smoked cannabis every day, 2 mg of guanfacine a day was well tolerated together with smoked cannabis and lowered blood pressure slightly (2019). In a pilot study with heavy cannabis users, 3 mg of guanfacine a day for 6 days reduced the negative effect of 20 mg of oral THC on working memory and attention; THC's increase in heart rate did not change (2018). These studies were not designed to study ADHD treatment; they looked at the effects seen when the drugs are taken together, not at drug-level interactions.

   Source: PMID 782773, PMID 29659126, PMID 28641496

What is monitored?

• Methylphenidate side effects: if after starting CBD or increasing the amount you notice more complaints such as a racing heartbeat (palpitations), headache, trouble sleeping, anxiety or decreased appetite, tell your doctor. (Methylphenidate prescribing information §6, PMID 36467779)
• Weight and height in children: Both ADHD medicines and CBD can reduce appetite and can slow weight gain and growth in height in children. Your doctor monitors weight and height regularly; tell them if you notice a marked change in your child's appetite or weight. (Methylphenidate prescribing information §5.7, Atomoxetine prescribing information §5.11, EMA Epidyolex prescribing information 4.4)
• Liver symptoms: Atomoxetine can rarely cause severe liver damage; CBD can also raise liver enzymes. If you notice itching, dark urine, yellowing of the eyes or skin, tenderness in the upper right part of the belly, or unexplained flu-like symptoms, tell your doctor right away. (Atomoxetine prescribing information §5.2, FDA Epidiolex label §5.1 and §17 (05/2026))
• Mood and behavior: The prescribing information for atomoxetine warns about the risk of suicidal thoughts in children and teenagers; the prescribing information for approved CBD contains a similar warning. If you notice an unusual change in mood or behavior, tell your doctor right away. (Atomoxetine prescribing information (Boxed Warning) and §5.1, FDA Epidiolex label §5.3 (05/2026))

Frequently asked questions

References

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