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Inhibition of monoamine oxidase activity by cannabinoids

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Abstract

Brain monoamines are involved in many of the same processes affected by neuropsychiatric disorders and psychotropic drugs, including cannabinoids. This study investigated in vitro effects of cannabinoids on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters and affecting brain development and function. The effects of the phytocannabinoid Δ9-tetrahydrocannabinol (THC), the endocannabinoid anandamide (N-arachidonoylethanolamide [AEA]), and the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN) on the activity of MAO were measured in a crude mitochondrial fraction isolated from pig brain cortex. Monoamine oxidase activity was inhibited by the cannabinoids; however, higher half maximal inhibitory concentrations (IC50) of cannabinoids were required compared to the known MAO inhibitor iproniazid. The IC50 was 24.7 μmol/l for THC, 751 μmol/l for AEA, and 17.9 μmol/l for WIN when serotonin was used as substrate (MAO-A), and 22.6 μmol/l for THC, 1,668 μmol/l for AEA, and 21.2 μmol/l for WIN when phenylethylamine was used as substrate (MAO-B). The inhibition of MAOs by THC was noncompetitive. N-Arachidonoylethanolamide was a competitive inhibitor of MAO-A and a noncompetitive inhibitor of MAO-B. WIN was a noncompetitive inhibitor of MAO-A and an uncompetitive inhibitor of MAO-B. Monoamine oxidase activity is affected by cannabinoids at relatively high drug concentrations, and this effect is inhibitory. Decrease of MAO activity may play a role in some effects of cannabinoids on serotonergic, noradrenergic, and dopaminergic neurotransmission.

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Acknowledgements

This research was supported by grant no. MSM0021620849 given by Ministry of Education, Youth and Sports of the Czech Republic, and by pharmaceutical company Zentiva Group, a.s. Praha. The author would like to thank Zdeněk Hanuš for his technical assistance.

Conflict of interest

Dr. Fišar's work has been funded in part by the Zentiva Group, a.s. Praha.

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Fišar, Z. Inhibition of monoamine oxidase activity by cannabinoids. Naunyn-Schmied Arch Pharmacol 381, 563–572 (2010). https://doi.org/10.1007/s00210-010-0517-6

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