Abstract
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.
Highlights
Introduction conditions of the Creative CommonsAnxiety and depressive disorders, the most common mental health conditions in children and adolescents [1], are frequently treated with selective serotonin reuptake inhibitors (SSRIs) [2,3,4]
We focus primarily on es/citalopram and sertraline as (1) these SSRIs are primarily metabolized by CYP2C19, (2) CPIC has issued genotype-specific dosing guidelines for these medications, and (3) CBD appears to have a greater interaction with
Concurrent or low-dose mg/day) use with escitalopram or sertraline was simulated the totalatbody clearance reduced by 25%
Summary
The most common mental health conditions in children and adolescents [1], are frequently treated with selective serotonin reuptake inhibitors (SSRIs) [2,3,4]. As CYP2D6, CYP2C19 metabolize manyand neuropsychiatric medications These alleles are classified normal and function, decreased function, no function [14]. Inherits of two alleles, phenotypes depend on metabolizers inheriting duplications of functional patients), normal Four metabolic phenotypes have been predicted for tensive) metabolizers inheriting at least one normal function allele (19–63%), intermediate. There are five predicted phenotypes for CYP2C19: CYP2C19 is highly polymorphic, with over 30 identified allelic variants These can be grouped in broadtwo functional groups. Predicted phenotypes for CYP2C19: ultrarapid metabolizers carrying increased function of patients), rapid ultrarapid metabolizers carrying two increased function alleles Les (9–47%), intermediate metabolizers carrying one normal or increased function allele.
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