Effects of Tetrahydrocannabinol and Cannabidiol on Brain-Derived Neurotrophic Factor and Tropomyosin Receptor Kinase B Expression in the Adolescent Hippocampus

This study found changes in BDNF mRNA expression within the hippocampus of adolescent mice exposed to THC and CBD. THC represses transcript expression for some BDNF variants, and this effect is rescued when CBD is co-administered. These effects were seen in both males and females, but sex differences were observed in specific BDNF isoforms. While a statistically significant reduction in CB1 receptor protein in the ventral dentate gyrus was seen, no other changes in protein levels were observed.

Mice of both sexes were injected daily from P28 to P49 with 3 mg/kg THC, CBD, or a combination of THC/CBD. Brains were harvested on P50, and the dorsal and ventral hippocampi were analyzed for levels of BDNF, TrkB, and several synaptic markers using quantitative polymerase chain reaction, western blotting, and image analyses.

The objective of this study was to examine the effects of the phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), on the expression of BDNF, its receptor TrkB, and other synaptic markers in the adolescent mouse hippocampus. Materials and

THC treatment statistically significantly reduced transcript levels of BDNF in adolescent female (BDNF I) and male (BDNF I, II, IV, VI, and IX) hippocampi. These changes were prevented when CBD was co-administered with THC. CBD by itself statistically significantly increased expression of some transcripts (BDNF II, VI, and IX for females, BDNF VI for males). No statistically significant changes were observed in protein expression for BDNF, TrkB, phospho-TrkB, phospho-CREB (cAMP response element-binding protein), and the synaptic markers, vesicular GABA transporter, vesicular glutamate transporter, synaptobrevin, and postsynaptic density protein 95. However, CB1 receptors were statistically significantly reduced in the ventral hippocampus with THC treatment. Conclusions: This study found changes in BDNF mRNA expression within the hippocampus of adolescent mice exposed to THC and CBD. THC represses transcript expression for some BDNF variants, and this effect is rescued when CBD is co-administered. These effects were seen in both males and females, but sex differences were observed in specific BDNF isoforms. While a statistically significant reduction in CB1 receptor protein in the ventral dentate gyrus was seen, no other changes in protein levels were observed.