Marijuana use among adolescents is associated with deleterious alterations in mature BDNF

With increases in marijuana use and legalization efforts, it is imperative to establish its impact on the developing brain. Therefore, we investigated whether exposure to marijuana alters brain derived neurotropic-factor (BDNF), given its critical role in brain development and plasticity. We then examined whether onset age of cannabis use was associated with more severe changes. A single site, cohort study following 500 urban healthy American adolescents. Changes in plasma m-BDNF levels were longitudinally assessed, and a multi-method approach was implemented to ascertain marijuana use. Multivariate and general linear model (GLM) regression modeling were utilized to test the main hypothesis, controlling for confounders.

Group-based trajectory modeling identified four distinct groups, characterized by naive (60% control), starters (14%), chronic users (20%), and experimenting/quitters (6%). Compared to controls, those initiating marijuana use had similar pre-existent m-BDNF (1939.2 ± 221 vs. 2640.7 ± 1309 ng/ml, p=0.4) After adjusting for confounding factors, GLM analyses revealed that, compared to controls, younger adolescents increased BDNF levels when experimenting and during moderate marijuana use. Older adolescents had a steeper increase in endogenous BDNF levels, particularly when escalating use. Multivariate analyses confirmed marijuana use as a predictor of m-BDNF (p = 0.001).

This is the first study demonstrating BDNF alterations were not a precondition. Rather, BDNF alteration was secondary to marijuana use, serving as cautionary evidence of marijuana's deleterious effects. Findings suggest that when marijuana use escalates, the BDNF pathway becomes more deregulated. Analyses confirm that age of marijuana use onset influences the magnitude of these changes.