Pharmacokinetic modeling shows THC and CBD inhibit enzymes that metabolize common SSRIs, potentially increasing escitalopram and sertraline concentrations in adolescents, with CBD co-use linked to more side effects.
Pediatric psychiatrists, adolescent medicine providers, pharmacologists, and parents of teens on antidepressants.
CBD co-use with SSRIs linked to increased dizziness, diarrhea, cough, and fatigue
What the researchers found
CBD and THC inhibit cytochrome enzymes (particularly CYP2C19) that metabolize SSRIs. PK models showed increased sertraline and escitalopram exposure in adolescents when co-administered with cannabinoids. FAERS data showed co-administration of CBD with CYP2C19-metabolized SSRIs increased the risk of cough, diarrhea, dizziness, and fatigue.
Why it matters
With both cannabis use and antidepressant prescribing increasing among adolescents, clinicians need to understand how these substances interact to avoid unexpected increases in medication levels and side effects.
The numbers in context
Modeled interactions for escitalopram and sertraline with CBD and THC. FAERS analysis identified increased signals for cough, diarrhea, dizziness, and fatigue with CBD + CYP2C19-metabolized SSRIs.
How the study worked
Three-part approach: (1) review of cannabinoid-SSRI pharmacokinetic and pharmacodynamic interactions, (2) pediatric PK modeling of THC/CBD effects on escitalopram and sertraline exposure, and (3) analysis of FDA Adverse Events Reporting System (FAERS) data for CBD-SSRI side effect signals.
What this study cannot tell us
PK modeling rather than clinical measurement of actual drug levels. FAERS data is based on voluntary reporting and cannot confirm causation. Limited to two SSRIs.
How to read the evidence
Combines PK modeling with adverse event database analysis, but lacks direct clinical measurement of drug levels in co-using patients.
When this study was published
Published in 2021.
The bigger picture
Drug interactions between cannabinoids and psychiatric medications represent an underappreciated clinical concern, especially in adolescents who may not disclose cannabis use to prescribers.
Questions still open
- How significant are these interactions at typical recreational cannabis doses vs. therapeutic CBD doses? Should routine screening for cannabis use be standard before prescribing SSRIs to teens?
Common questions
How do cannabis and CBD affect antidepressant levels?
What side effects were seen when CBD was used with SSRIs?
Read the original research
The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations.
Journal of personalized medicine, 11(7)
Citation
Vaughn, Samuel E; Strawn, Jeffrey R; Poweleit, Ethan A; Sarangdhar, Mayur; Ramsey, Laura B. (2021). The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations.. Journal of personalized medicine, 11(7). https://doi.org/10.3390/jpm11070615
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