The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations
Open accessAbstract
The neuropharmacology of marijuana, including its effects on selective serotonin reuptake inhibitor (SSRI)/antidepressant metabolism and the subsequent response and tolerability in youth, has received limited attention. We sought to (1) review clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) interactions between cannabinoids and selected SSRIs, (2) use PK models to examine the impact of cannabinoids on SSRI exposure (area under curve (AUC)) and maximum concentration (CMAX) in adolescents, and (3) examine the frequency of adverse events reported when SSRIs and cannabinoids are used concomitantly. Cannabinoid metabolism, interactions with SSRIs, impact on relevant PK/PD pathways and known drug–drug interactions were reviewed. Then, the impact of tetrahydrocannabinol (THC) and cannabidiol (CBD) on exposure (AUC24) and CMAX for escitalopram and sertraline was modeled using pediatric PK data. Using data from the Food and Drug Administration Adverse Events Reporting System (FAERS), the relationship between CBD and CYP2C19-metabolized SSRIs and side effects was examined. Cannabis and CBD inhibit cytochrome activity, alter serotonergic transmission, and modulate SSRI response. In PK models, CBD and/or THC increases sertraline and es/citalopram concentrations in adolescents, and coadministration of CBD and CYP2C19-metabolized SSRIs increases the risk of cough, diarrhea, dizziness, and fatigue. Given the significant SSRI–cannabinoid interactions, clinicians should discuss THC and CBD use in youth prescribed SSRIs and be aware of the impact of initiating, stopping, or decreasing cannabinoid use as this may significantly affect es/citalopram and sertraline exposure.
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THC and/or CBD increase SSRI concentrations in adolescents.
“THC and/or CBD increase SSRI concentrations in adolescents, and coadministration of CBD and SSRIs increases the risk of cough, diarrhea, dizziness, and fatigue [106].”
From Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits (2025) · cites this paper as [106]
Section 2.4 reports that a pharmacokinetic model predicts increased escitalopram and sertraline exposure in adolescents using THC or low-dose CBD. The Conclusions say these cannabinoids likely increase concentrations of those two SSRIs. The claim omits the modeling and uncertainty and extends the finding to SSRIs generally. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCoadministration of CBD and SSRIs increases the risk of cough, diarrhea, dizziness, and fatigue.
“THC and/or CBD increase SSRI concentrations in adolescents, and coadministration of CBD and SSRIs increases the risk of cough, diarrhea, dizziness, and fatigue [106].”
From Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits (2025) · cites this paper as [106]
The Abstract reports increased risk of cough, diarrhea, dizziness, and fatigue with CBD and CYP2C19-metabolized SSRIs. Section 2.8 reports higher rates of those effects in adverse-event data, but the paper limits its analysis to selected SSRIs; the claim omits that qualification and says SSRIs generally. (LLM, conf=0.87)
Experimental — accuracy not yet measured
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- Authors
- Vaughn, S., Strawn, J., Poweleit, E., Sarangdhar, M., & Ramsey, L.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Vaughn, Samuel
- Venue
- Journal of Personalized Medicine
- Publisher
- MDPI AG
- Published
- 2021-06-29
- Volume
- 11
- Issue
- 7
- Pages
- 615
- ISSN
- 2075-4426 (ISSN-L)
- PMC
- PMC8307883
- OpenAlex
- W3174116238
- Cited by
- 40
- References
- 65
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 13 · 2023: 11 · 2022: 1 · 2021: 2
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Personalized Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD099775)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Keywords
- cannabis, cannabinoids, adolescents, antidepressants, selective serotonin reuptake inhibitors, drug-drug interactions, tetrahydrocannabinol, cannabidiol, escitalopram, sertraline, CYP2C19, pharmacokinetics, pharmacodynamics, adverse events, serotonergic neurotransmission
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