This study examined the probable effects of graded doses of Cannabis sativa (C. sativa) extract on the gene expressions of monoamine oxidase B and serotonin receptor 2C (HTR2C) in an attempt to correlate the duration of use with neurodegeneration tendencies in chronic marijuana users. Male Wistar rats weighing between 90 g ± 100 g were treated with graded doses of petroleum ether extract of C. sativa (12.5, 25 and 50 mg/kg body weight) orally. The exposure was monitored at 4, 8, and 12 weeks for each of the doses employed, after which the brain was removed. The gene expressions were determined by reverse transcriptase polymerase chain reaction. Cannabis considerably (p < 0.05) reduced the relative expression of MAOB at 4 weeks. At 8 weeks, cannabis upregulated the relative expression of the MAOB gene by 60%. Following 12 weeks of exposure to the 50mg/kg body weight dose of C. sativa, 80% increase in the expression of MAOB was observed compared to the control group. C. sativa (50 mg/kg body weight) extract at 8 weeks resulted in about 47.7% decrease in the expression of the gene, however, prolonged exposure (12 weeks) to the extract significantly (p < 0.05) increased the relative expression of HTR2C. Cannabis-induced dysregulation of the MAOB genes may be one mechanism linking chronic use of cannabis to cognitive decline and improved likelihood of developing neurological diseases. Alterations observed in HTR2C gene expression as a result of exposure to high doses of C. sativa extract may partly account for the depression and aggressive tendencies observed in chronic users.
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