Cannabinoids have been widely taken to achieve a feeling of high and to reduce stress. Endogenous cannabinoids are naturally occurring substances in the brain that are involved in motivation, mood, pain, sleep, and neurological disorders. Research has more recently focused on the cannabinoid signaling pathway in the brain, the receptors being eCB ligands, and how cannabinoids can be utilized in treatment of various disorders.
In the article by Patel et al., "Endocannabinoids at the synapse and beyond: implications for neuropsychiatric disease pathophysiology and treatment," the function of endocannabinoids is presented and how eCBs can be used to treat neuropsychiatric disease, epilepsy, developmental disorders, and obesity. The article discusses the physiological mechanisms underlying stress and how chronic stress can lead to depression and anxiety disorders as well as substance use disorders. It is described how endocannabinoids have an important role in the HPA axis, an area crucial for regulation of the stress response. ECBs regulate GABAergic and glutamatergic transmission in neurons of the PVN, which is part of the HPA axis. GABA is an inhibitory neurotransmitter while glutamate innervates excitatory responses in the brain. Signaling of these chemicals occurs in the amygdala, an area associated with assessment of valanced stimuli and managing stress and emotion. 2-AG (an endogenous cannabinoid ligand receptor) signaling in the basolateral amygdala increases expression of the neurotransmitters.
The therapeutic potential of cannabinoids is further debated in “Cannabinoids: Therapeutic Use in Clinical Practice”, by Pagano et al., mentioning implications in cancer and neurodegenerative diseases. Cannabinoids can reduce pain and inflammation, namely in cancer. The side effects of cancer or cancer treatment such as chemotherapy includes emesis, nausea, pain, and muscle spasms. Many patients are prescribed opioids, but cannabinoids can be used as analgesics acting through CB1 receptors, the main cannabinoid receptor. Another function is the anti-emetic properties of the drug. It can decrease activity of excitatory transmitters in areas involved in nausea and vomiting, limiting these responses. Furthermore, neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and multiple sclerosis have shown symptom improvements through the use of cannabinoids. AD is caused by accumulation of beta amyloid plaques and tau protein, leading to neuroinflammation. The concentration of CB1 receptors decreases with an increase in 2-AG in the hippocampus. Studies show neuroinflammation and beta amyloid could decrease with the use of cannabinoids. PD is characterized by changes in the endocannabinoid system, including an increase in activity of CB1 receptors in the basal ganglia. Patients of studies using cannabinoids reported improvements in motor control, tremors, sleep, pain, and even associated mood disorders.
The two articles describe the emerging effects of cannabinoids and emphasize the importance of further studies to determine how various disorders could be improved with cannabinoid treatment. It could be concluded this treatment can be beneficial in people with muscular and movement disorders and show improvements in some anxiety and mood disorders; however, there is still much room for progression in science as many findings are inconclusive and contradictory.
References:
Pagano, C., Navarra, G., Coppola, L., Avilia, G., Bifulco, M., & Laezza, C. (2022). Cannabinoids: Therapeutic use in clinical practice. International journal of molecular sciences, 23(6), 3344.
Sheyer, A., Yasmin, F., Naskar, S., Patel, S. Endocannabinoids at the synapse and beyond: implications for neuropsychiatric disease pathophysiology and treatment. Neuropsychopharmacology (2023) 48:37–53; https://doi.org/10.1038/s41386-022-01438-7
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