Gut bacteria, endocannabinoid system, and marijuana addiction: Novel therapeutic implications

Gut bacteria plays a leading role in the pharmacological actions of both synthetic and natural product derived drugs. Their interactions are complex and bidirectional. This complexity with psychotropic phyto-compounds like delta-9-tetrahydrocannabinol (∆9-THC) (source: cannabis) has been found for modulating various brain functions including anxiety, depression, and cognition through an intricate cell-signaling network known as endocannabinoid system (ECS). This is a prominent neuromodulatory system that defines the host's health and disease. As a habit-forming weed, cannabis is associated with severe neuropsychiatric complications upon withdrawal. This is due to the dysregulation of monoamines (particularly dopamine and GABA) in the mesocorticolimbic circuit and hypothalamic-pituitary-adrenal axis. No notable pharmacotherapies are found for the treatment of cannabis dependence. Here, we postulate the connections between gut bacteria, CNS, ECS, and marijuana dependence, which would be an insight to overcome marijuana withdrawal symptoms.