title: Effect of cannabis on glutamate signalling in the brain: A systematic review of human and animal evidence.
abstract: Use of cannabis or delta-9-tetrahydrocannabinol (Δ9-THC), its main psychoactive ingredient, is associated with 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.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, United Kingdom.
authors.forename: Marco
authors.initials: M
authors.lastname: Colizzi
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Pertwee
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, United Kingdom. Electronic address: sagnik.2.bhattacharyya@kcl.ac.uk.
authors.forename: Sagnik
authors.initials: S
authors.lastname: Bhattacharyya
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002188:Cannabis; D013759:Dronabinol / Q000494:pharmacology*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans
chemical_list: D018683:Excitatory Amino Acid Agents; D018698:Glutamic Acid; D013759:Dronabinol
keywords: Cannabinoid receptor type 1; Cannabis; Delta-9-tetrahydrocannabinol; Glutamate signalling; Glutamatergic synaptic transmission