Cannabis and CBD can increase antidepressant levels in adolescents through drug interactions

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.

Vaughn, Samuel E et al.·Journal of personalized medicine·2021·Preliminary EvidenceReview
RTHC-03593ReviewPreliminary Evidence2021RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Review
Evidence
Preliminary Evidence
Sample
Not reported

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
CBD co-use with SSRIs linked to increased dizziness, diarrhea, cough, and fatigue
Evidence Grade:
Combines PK modeling with adverse event database analysis, but lacks direct clinical measurement of drug levels in co-using patients.
Study Age:
Published in 2021.
Original Title:
The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations.
Published In:
Journal of personalized medicine, 11(7) (2021)
Database ID:
RTHC-03593

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

Summarizes existing research on a topic.

What do these levels mean? →

Frequently Asked Questions

How do cannabis and CBD affect antidepressant levels?

Both THC and CBD inhibit liver enzymes (especially CYP2C19) that break down SSRIs like escitalopram and sertraline, potentially causing higher-than-expected medication levels.

What side effects were seen when CBD was used with SSRIs?

FDA adverse event data showed increased reports of cough, diarrhea, dizziness, and fatigue when CBD was combined with CYP2C19-metabolized SSRIs.

Read More on RethinkTHC

Cite This Study

RTHC-03593·https://rethinkthc.com/research/RTHC-03593

APA

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

MLA

Vaughn, Samuel E, et al. "The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations.." Journal of personalized medicine, 2021. https://doi.org/10.3390/jpm11070615

RethinkTHC

RethinkTHC Research Database. "The Impact of Marijuana on Antidepressant Treatment in Adole..." RTHC-03593. Retrieved from https://rethinkthc.com/research/vaughn-2021-the-impact-of-marijuana

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.