Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans

Background  Acute and chronic exposure to cannabinoids has been associated with cognitive deficits, a higher risk for schizophrenia and other drug abuse. However, the precise mechanism underlying such effects is not known. Preclinical studies suggest that cannabinoids modulate brain-derived neurotrophic factor (BDNF). Accordingly, we hypothesized that Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the principal active component of cannabis, would alter BDNF levels in humans. Materials and methods  Healthy control subjects (n = 14) and light users of cannabis (n = 9) received intravenous administration of (0.0286 mg/kg) Δ⁹-THC in a double-blind, fixed order, placebo-controlled, laboratory study. Serum sampled at baseline, after placebo administration, and after Δ⁹-THC administration was assayed for BDNF using ELISA. Results  Δ⁹-THC increased serum BDNF levels in healthy controls but not light users of cannabis. Further, light users of cannabis had lower basal BDNF levels. Δ⁹-THC produced psychotomimetic effects, perceptual alterations, and “high” and spatial memory impairments. Implications  The effects of socially relevant doses of cannabinoids on BDNF suggest a possible mechanism underlying the consequences of exposure to cannabis. This may be of particular importance for the developing brain and also in disorders believed to involve altered neurodevelopment such as schizophrenia. Larger studies to investigate the effects of cannabinoids on BDNF and other neurotrophins are warranted.