Chronic use of marijuana decreases cannabinoid receptor binding and mRNA expression in the human brain.
Chronic exposure to Cannabis sativa (marijuana) produced a significant down-regulation of cannabinoid receptor in the postmortem human brain. The significant decrease in maximal binding capacity was not accompanied by changes in the affinity constant. [3H]SR141716A binding was reduced in the caudate nucleus, putamen and in the accumbens nucleus. A significant decrease of binding sites was seen in the globus pallidus. Also in the ventral tegmental area and substantia nigra pars reticulata quantitative analysis of the density of receptors shows a significant reduction in [3H]SR141716A binding. In Cannabis sativa user brains, compared with normal brains [3H]SR141716A binding was reduced only in the hippocampus. The density of cannabinoid receptor 1 mRNA-positive neurons was significantly lower in Cannabis sativa users than in control brains for the caudate nucleus, putamen, accumbens nucleus and hippocampal region (CA1-CA4, areas of Ammon's horn). No hybridization was seen in the mesencephalon and globus pallidus.
Villares
J
J
Universidade Federal de São Paulo, Aging and Neurodegenerative Diseases Brain Bank Laboratory, Department of Psychobiology, Rua Botucatu n. 862, Biological Science Building, São Paulo SP, Brazil, CEP 04023-062. villares@psicobio.epm.br
D000293:Adolescent; D000328:Adult; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002188:Cannabis; D016022:Case-Control Studies; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D002189:Marijuana Abuse / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010880:Piperidines / Q000493:pharmacokinetics; D011180:Postmortem Changes; D011720:Pyrazoles / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism*; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant; D014316:Tritium / Q000493:pharmacokinetics
D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid; D014316:Tritium; D000077285:Rimonabant