Effect of cannabis on glutamate signalling in the brain: A systematic review of human and animal evidence
Neuroscience and Biobehavioral Reviews
number of words: 168 Article body number of words: 7081 2 HIGHLIGHTS Use of cannabis or its main active ingredient Δ9-THC is associated with psychosis Evidence of the effects of Δ9-THC or cannabis on the dopamine system in man is equivocal Chronic cannabis use reduces glutamate or its metabolites levels in human brain Δ9-THC alters glutamate signalling in animal brain 3 ABSTRACT Use of cannabis or delta-9-tetrahydrocannabinol (Δ9-THC), its main psychoactive ingredient, is associated
... psychotic symptoms or disorder. However, the neurochemical mechanism that may underlie this psychotomimetic effect is poorly understood. Although dopaminergic dysfunction is generally recognized as the final common pathway in psychosis, evidence of the effects of Δ9-THC or cannabis use on dopaminergic measures in the brain is equivocal. In fact, it is thought that cannabis or Δ9-THC may not act on dopamine firing directly but indirectly by altering glutamate neurotransmission. Here we systematically review all studies examining acute and chronic effects of cannabis or Δ9-THC on glutamate signalling in both animals and man. Limited research carried out in humans tends to support the evidence that chronic cannabis use reduces levels of glutamate-derived metabolites in both cortical and subcortical brain areas. Research in animals tends to consistently suggest that Δ9-THC depresses glutamate synaptic transmission via CB1 receptor activation, affecting glutamate release, inhibiting receptors and transporters function, reducing enzyme activity, and disrupting glutamate synaptic plasticity after prolonged exposure.