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Modulatory Effects of Cannabis Sativa Co-administration with Tramadol and Codeine on Cognitive Function in Male Rats.

A. Ademosun, O. Ajeigbe, Bodun Oluwaseun Lawrence, G. Oboh

Neurotoxicology August 1, 2023 DOI: 10.1016/j.neuro.2023.08.005 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Controlled animal experiment Peer reviewed
Sample size 48
Population Male Wistar rats
Interventions Codeine Tramadol Cannabis sativa
Dose CDE 2 mg/kg bw, TMD 10 mg/kg bw, CNB 200 mg/kg bw
Duration 28 days
Measures acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO), NTPdase, adenosine deaminase (ADA), malondialdehyde
Topics Cannabis
Key findings Prolonged oral administration of codeine, tramadol, and Cannabis sativa, alone or in combination, suppressed cognitive function and lowered brain acetylcholinesterase, butyrylcholinesterase, monoamine oxidase, and antioxidant enzyme activities in rats relative to controls (P<0.05), while raising NTPdase, adenosine deaminase, and malondialdehyde levels. The authors attribute the neurotoxicity to reduced cholinesterase activity leading to neurotransmitter poisoning.

Abstract

Most teenagers mix up various psychoactive cocktail substances in combinations to get intoxicated. The role of the mixture combination of codeine (CDE), tramadol (TMD), and Cannabis sativa (CNB) on brain cognition, purinergic, cholinergic, and antioxidant enzyme activities remains unknown. This study sought to assess the mechanism of action of combinations of CDE+ TMD+ CNB on the function and activities of the brain of male Wistar rats. Forty-eight male Wistar rats were divided into 8 groups, n = 6. Group 1 served as a control, groups 2, 3, and 4 were exposed to CDE (2mg/kg bw), TMD (10mg/kg bw), and CNB (200mg/kg bw), while groups 5, 6, 7, and 8 were co-administered with CDE+TMD, CNB+ TMD, CNB+CDE, and CNB+TMD+CDE orally for 28 days. This study revealed the effect of prolonged administration of CNB, TMD, and CDE on the suppression of cognitive function, acetyl-cholinesterase (AChE), butyl-cholinesterase (BChE), monoamine oxidase (MAO) enzyme activities, and antioxidant enzyme activities in rats' brains when compared against control rats (P< 0.05). However, the activities of ectonucleosides (NTPdase), adenosine deaminase (ADA), and malondialdehyde levels produced in the brain of rats were significantly elevated (P< 0.05). This study reported the mechanism behind the neurotoxicity of CNB, TMD, and CDE on rats' cognitive, cholinergic, purinergic, and antioxidant enzymes as a consequence of the drastic reduction in cholinesterase enzyme activities leading to neurotransmitter poisoning.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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