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 Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the principal active component of cannabis, would alter BDNF levels in humans.


METHODS
Healthy control subjects (n = 14) and light users of cannabis (n = 9) received intravenous administration of (0.0286 mg/kg) Delta(9)-THC in a double-blind, fixed order, placebo-controlled, laboratory study. Serum sampled at baseline, after placebo administration, and after Delta(9)-THC administration was assayed for BDNF using ELISA.


RESULTS
Delta(9)-THC increased serum BDNF levels in healthy controls but not light users of cannabis. Further, light users of cannabis had lower basal BDNF levels. Delta(9)-THC produced psychotomimetic effects, perceptual alterations, and "high" and spatial memory impairments.


CONCLUSIONS
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.
D'Souza
Deepak Cyril
DC
Schizophrenia Biological Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA. deepak.dsouza@yale.edu
Pittman
Brian
B
Perry
Edward
E
Simen
Arthur
A
D000293:Adolescent; D000328:Adult; D001519:Behavior / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008385:Marijuana Smoking / Q000523:psychology; D008569:Memory Disorders / Q000139:chemically induced / Q000523:psychology; D008875:Middle Aged; D010465:Perception / Q000187:drug effects; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D006213:Hallucinogens; D013759:Dronabinol