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

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.

PMID: 17222515 [PubMed - indexed for MEDLINE]