August 30, 2020 Archives • 2020 • vol.2 • 302-313 http://pharmacologyonline.silae.it ISSN: 1827-8620 TIME-COURSE EFFECTS OF Cannabis sativa ON BRAIN ACETYLCHOLINESTERASE (AChE) ACTIVITY AND EXPRESSION OF DOPA DECARBOXYLASE GENE (DDC) Oluwatosin Adebisi Dosumu 1 Odunayo Anthonia Taiwo 1,2* , Oluseyi Adeboye Akinloye 1 , Eniola Oluwayemisi Oni 3 , Oluwafemi Paul Owolabi 1 , Oluwafemi Adeleke Ojo 4* 1 Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria. 2 Department of Biochemistry, Chrisland University, Owode, Abeokuta, Nigeria. 3 Department of Microbiology, Federal University of Agriculture, Abeokuta, Nigeria. 4 Department of Biochemistry, Landmark University, Omu-Aran, Nigeria *odunayotaiwo25@gmail.com; ojo.adeleke@lmu.edu.ng Abstract Cannabis sativa affects almost every system in the body of animals and humans resulting in impairments, especially of attention, memory, and ability to process complex information which may be a result of inhibition or activation of activities and expressions of neurotransmitters involved in these biological functions. The effects of doses of Cannabis sativa extract on brain acetylcholine esterase (AChE) activity and the expression of dopa decarboxylase gene (DDC) an enzyme involved in the biosynthetic pathway of Serotonin (a neurotransmitter) was investigated to correlate the duration of use with associated cholinergic neurotoxicity and behavioral implications. Male Wistar rats weighing between 90g ± 10 g were treated with graded doses of petroleum ether extract of C. sativa (12.5, 25, and 50 mg/kg body weight) orally for 4, 8, and 12 weeks. AChE activity was measured in the brain of the treated animals using the colorimeter method while the expression of DDC was obtained using reverse transcriptase-polymerase chain reaction (RT-PCR) method. There was a significant (p<0.05) increase (about 16.6 %) in the brain AChE activity in rats treated with the different doses of C. sativa at 4 weeks. A significant (p<0.05) decrease in the enzyme activity by 29.9 % and 24.5 % was however observed after 8 weeks’ administration of 25 and 50 mg/kg doses of C. sativa respectively. Administration of all measured doses of C. sativa for 12 weeks resulted in significant(p<0.05) increase in brain AChE activity by 17.3 % and 28.7 % and 39.3 % respectively, Upregulation of about 35.9 % and 30.6 % was recorded in the expression of DDC with the administration of only 50 mg/kg after 4 and 8 weeks, no significant(p>0.05) difference was however observed after 12 weeks exposure to all doses of the extract. The important implication of our study is that prolonged cannabis exposure increases AChE activity in the brain and ultimately could decrease brain level of acetylcholine thereby affecting cognition and neurotransmission. Alteration of the expression of DDC in the brain after exposure to different doses for varying duration could also account for different behavioral tendencies observed in users. Keywords: C. sativa, acetylcholine esterase, serotonin, neurotransmission, cognition, gene expression.