The marijuana-schizophrenia multifaceted nexus: Connections and conundrums towards neurophysiology

Delta-9-tetrahydrocannabinol, a component of marijuana, interacts with cannabinoid receptors in brain involved in memory, cognition, and emotional control. However, marijuana use and schizophrenia development is a complicated and contentious topic. As a result, more investigation is needed to understand this relationship. Through the functional enrichment analysis, we report the delta-9-tetrahydrocannabinol to manipulate the homeostatic biological process and molecular function of different macromolecules. Additionally, using molecular docking and subsequent processing for molecular simulations, we assessed the binding ability of delta-9-tetrahydrocannabinol with the estrogen-related protein, dopamine receptor 5, and hyaluronidase. It was found that delta-9-tetrahydrocannabinol may have an impact on the brain's endocannabinoid system and may trigger the schizophrenia progression in vulnerable people. Delta-9-tetrahydrocannabinol may interfere with the biological function of 18 proteins linked to schizophrenia and disrupt the synaptic transmission (dopamine, glutamine, and gamma-aminobutyric acid). It was discovered that it may affect lipid homeostasis, which is closely related to membrane integrity and synaptic plasticity. The negative control of cellular and metabolic processes, fatty acids binding /activity, and the manipulated endocannabinoid system (targeting cannabinoid receptors) were also concerned with delta-9-tetrahydrocannabinol. Hence, this may alter neurotransmitter signaling involved in memory, cognition, and emotional control, showing its direct impact on brain physiological processes. This may be one of the risk factors for schizophrenia development which is also closely tied to some other variables such as frequency, genetic vulnerability, dosage, and individual susceptibility.