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Abstract Substances from the Cannabis sativa species, especially cannabidiol (CBD) and Delta-9-tetrahydrocannabinol (Δ9-THC), have attracted medical attention in recent years. The actions of these two main cannabinoids modulate the cholinergic nervous system (CholNS) involving development, synaptic plasticity, and response to endogenous and environmental damage, as a characteristic of many neurodegenerative diseases. The dynamics of these diseases are mediated by specific neurotransmitters, such as the GABAergic nervous system (GNS) and the CholNS. The nematode Caenorhabditis elegans is an important experimental model, which has different neurotransmitter systems that coordinate its behavior and has a transgene strain that encodes the human β-amyloid 1–42 peptide in body wall muscle, one of the main proteins involved in Alzheimer´s disease. Therefore, the objective of this study was to evaluate the protective potential of terpenoids found in C. sativa in the GNS and CholNS of C. elegans. The effect of two C. sativa oils with variations in CBD and THC concentrations on acetylcholinesterase (AChE) activity, lipid peroxidation, and behavior of C. elegans was evaluated. C. sativa oils were efficient in increasing pharyngeal pumping rate and reducing defecation cycle, AChE activity, and ROS levels in N2 strains. In the muscle:Abeta1-42 strain, mainly when using CBD oil, worm movement, body bends, and pharyngeal pumping were increased, with a reduced AChE activity. Consequently, greater investments in scientific research are needed, in addition to breaking the taboo on the use of the C. sativa plant as an alternative for medicinal use, especially in neurodegenerative diseases, which have already shown positive initial results.

The use of terpenoid compounds in different neural-related conditions is becoming useful for several illnesses. Another possible activity of these compounds is the reduction of nervous impairment. Cannabis sativa plants are known for their concentration of two important terpenoids, the delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD and THC have central peripheral activities already described and their usage in different brain diseases, such as Alzheimer's and multiple sclerosis. Aluminum (Al) is known as an important neurotoxic compound, the physiological action of Al is not known already, and in high concentrations can lead to intoxication and cause neurotoxicity. Here we evaluated the potential effect of two different doses of CBD- and THC-rich based oils against Al-induced toxicity, in the zebrafish model. We evaluated behavioral biomarkers of the novel tank test (NTT) and social preference test (SPT), and biochemical markers: the activity of the enzyme acetylcholinesterase (AChE) and the antioxidant enzymes-catalase, superoxide dismutase, and glutathione-S-transferase. CBD- and THC-based oils were able to increase the AChE activity helping the cholinergic nervous system actuate against Al toxicity which was reflected by the behavioral biomarkers changes. We concluded that the oils have a protective effect and might be used with proposals for neurological and antioxidant impairment avoidance caused by Al intoxications., (© 2023. The Author(s).)