The endogenous cannabinoid system, or more commonly known as the endocannabinoid system, serves to regulate a wide array of physiological and psychological processes and possesses considerable potential targets for the potential treatment of numerous disease states. The endocannabinoid system is just another neurotransmitter system in our bodies just like the acetylcholine system or adrenaline system. The endocannabinoid system is composed of neurotransmitters known as endocannabinoids. Endocannabinoids are one of the most widely known, potent, and versatile signaling molecules known up to now. This is probably possible due to the two receptors (i.e., CB1 and CB2 receptors) and enzymes regulating their endogenous ligands. Cannabidiol, CBD, binds to these receptors and then alters the function of these receptors and the resulting actions of the body on which these receptors and their ligands affect. CB1 receptors are highly expressed on neurons in the central nervous system (CNS) in the inner brain areas such as the cerebral cortex and basal ganglia. CB2 receptors are most commonly are expressed on immune cells, microglia in the CNS, and macrophages, monocytes, CD4+ and CD8+ T cells, and B cells in the periphery. Additionally, CB2 receptors are also expressed on neurons, but to an extent that is almost as negligible as compared to the CB1 receptors. The abundant distribution of CB1 and CB2 receptors throughout the brain and periphery accounts for their ability to impact a diverse variety of physiological and psychological processes and other emotions such as memory, anxiety, and pain perception.
The secret of the therapeutic use of marijuana lies behind the mechanism of action of marijuana on the brain. The most particular constituent of marijuana is the tetrahydrocannabinol (THC), which is the characteristic substance behind the drug abuse. The second major constituent is cannabidiol (CBD). CBD is not psychoactive and has an effect on the brain circuits that is a lot different from the THC effect.
How Cannabis extracts act on the Brain
However, the ability of cannabinoids such as CBD to fine-tune various vital brain circuits in the nervous system has found bright prospects in the treatment of various forms of dementia including Alzheimer’s. In this regard, a study was conducted and the results were published on PubMed. The study comprised a total of 21 cases in which cannabinoids particularly CBD obtained from Cannabis plants were used as a therapeutic measure against Alzheimer’s disease.
The results of these studies, as a whole, provided strong evidence in the favour of CBD being an effective drug to check the progression of Alzheimer’s disease. CBD activated the peroxisome proliferator-activated receptor through the beta-catenin pathway to protect PC12 cells from neurotoxicity and oxidation stress that leads ultimately to cell death, thereby indirectly increasing the rate of cell survival along with reducing ROS production. CBD also indirectly reduced lipid peroxidation in the areas of the central nervous system. Lipid peroxidation is found to be the main culprit behind the uncontrolled tumor production through dangerous free radicals. Decreased lipid peroxidation, therefore, inhibited the hyperphosphorylation of the tau protein, which in turn inhibits acetylcholestrinase (the enzyme responsible for the breakdown of acetylcholine at neuromuscular junctions). All of this leads to an increased rate of neurogenesis in the hippocampus, which is a vital part of the brain involved in the formation of long-term memories. Discrepancies in this area of the brain mostly lead to various types of dementia. CBD indirectly promotes the health of the hippocampus, thereby reducing the risk of dementia in the later life of a person.
Alzheimer’s disease is not curable at the present. But certain medications do exist for easing the symptoms and research is ongoing in every corner of the world to find its cure. Aside from Alzheimer’s being not curable at the present, unfortunately, there are no drugs that can temporarily slow the worsening of dementia symptoms and the neurodegeneration of the patient.
There is not a single pharmacological agent with demonstrated therapeutic efficacy for traumatic brain injury (TBI). With recent legalization efforts and the growing popularity of medical cannabis, patients with TBI will inevitably consider medical cannabis as a treatment option. Pre-clinical TBI research suggests that cannabinoids have neuroprotective and psychotherapeutic properties. In contrast, recreational cannabis use has consistently shown to have detrimental effects. Our review identified a paucity of high-quality studies examining the beneficial and adverse effects of medical cannabis on TBI, with only a single phase III randomized control trial. However, observational studies demonstrate that TBI patients are using medical and recreational cannabis to treat their symptoms, highlighting inconsistencies between public policy, perception of potential efficacy, and the dearth of empirical evidence. We conclude that randomized controlled trials and prospective studies with appropriate control groups are necessary to fully understand the efficacy and potential adverse effects of medical cannabis for TBI.
Keywords: THC; cannabidiol; cannabinoids; medical cannabis; medical marijuana; traumatic brain injury.