Cannabidiol (cbd) - Prozac (Fluoxetine) Interaction

Interaction Details

Fluoxetine is classified as belonging to the following category: Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2D6.
In vitro research shows that cannabidiol inhibits CYP2D6. Theoretically, concomitant use of cannabidiol with CYP2D6 substrates might increase the risk for adverse effects from these substrates.

Interaction Rating

Likelihood of Occurrence

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

References

• Yamaori S, Okamoto Y, Yamamoto I, Watanabe K. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos 2011;39(11):2049-56.
• Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080.

Interaction Details

Fluoxetine is classified as belonging to the following category: Cytochrome P450 2C19 (Cyp2C19) Inhibitors

Theoretically, CYP2C19 inhibitors might increase cannabidiol levels.
Cannabidiol is a substrate of CYP2C19 enzymes. Theoretically, drugs that inhibit CYP2C19 enzymes might increase levels of cannabidiol, increasing its effects and adverse effects.

Interaction Rating

Likelihood of Occurrence

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

References

• Epidiolex (cannabidiol) prescribing information. Greenwich Biosciences, Inc., Carlsbad, CA, 2019. Available at: https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf (accessed 5/9/2019)

Interaction Details

Fluoxetine is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Inhibitors

Theoretically, CYP3A4 inhibitors might increase cannabidiol levels.
Cannabidiol is a substrate of CYP3A4 enzymes. Theoretically, drugs that inhibit CYP3A4 enzymes might increase levels of cannabidiol, increasing its effects and adverse effects.

Interaction Rating

Likelihood of Occurrence

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

References

• Product information for Marinol. AbbVie. North Chicago, IL 60064. August 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf.

Interaction Details

Fluoxetine is classified as belonging to the following category: Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2C9.
In vitro and animal research shows that cannabidiol inhibits CYP2C9. In human studies, cannabidiol has been associated with an increase in plasma levels of topiramate, a CYP2C9 and CYP2C19 substrate. However, this effect has not been confirmed with other CYP2C9 substrates in humans. Theoretically, concomitant use of cannabidiol with CYP2C9 substrates might increase the risk for adverse effects from these substrates.

Interaction Rating

Likelihood of Occurrence

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

References

• Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103.
• Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31.
• Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Sep;58(9):1586-92.
• Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080.

Interaction Details

Fluoxetine is classified as belonging to the following category: Fluoxetine (Prozac)

Cannabidiol might increase fluoxetine levels in certain patients.
In one case report, a 17-year-old male with autism previously stabilized on fluoxetine 20 mg daily developed insomnia, agitation, hyperactivity, yelling, and worsening symptoms of obsessive-compulsive disorder after taking cannabidiol 18 mg twice daily for 2 weeks. The patient was found to be a poor cytochrome P450 2D6 (CYP2D6) metabolizer (CYP2D6*4/*4). Fluoxetine is primarily metabolized by CYP2D6, and to a lesser extent, by CYP2C9. Although fluoxetine levels weren't measured, it was hypothesized that the lack of CYP2D6 activity resulted in fluoxetine being metabolized solely by CYP2C9, which was subsequently inhibited by cannabidiol. This would have increased levels of fluoxetine, resulting in adverse effects. Further research is needed to confirm this complex gene-drug interaction cascade.

Interaction Rating

Likelihood of Occurrence

Interaction 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.

References

• Anderson LL, Arnold JC, McGregor IS, Nation TR. A potential drug-gene-drug interaction between cannabidiol, CYP2D6*4, and fluoxetine: A case report. J Clin Psychopharmacol 2022;42(4):422-424.

Fluoxetine Overview

• Fluoxetine is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. It is also used along with olanzapine (Zyprexa) to treat depression that did not respond to other medications and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Fluoxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

Cannabidiol (cbd) - More Interactions

Cannabidiol (cbd) interacts with 1004 drugs

Interaction Rating Key

These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.