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Chronic use of marijuana decreases cannabinoid receptor binding and mRNA expression in the human brain.

Villares 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

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.

Published 16 February 2007 in Neuroscience, 145(1): 323-34.
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