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It is one of the most recent and exciting findings in scientific research. The ECS is known to regulate various physiological processes such as restfulness and sleep, thermoregulation, immune response, specific inflammatory effects, gastrointestinal functions and cognitive work. To state it plainly, the endocannabinoid system is chiefly responsible for maintaining the homeostasis of the body.
Endocannabinoids and the receptors they affect are distributed all through the body, hence further research studies on the ECS are warranted to define and fully understand such a complex system and the extent of its role.
Conversely, it is vital to know that the body produces cannabinoids in a natural process. These endocannabinoids are namely, anandamide and 2-AG. They share chemical structures similar to exogenous cannabinoids derived from plants such as Cannabidiol or CBD. Both endogenous and exogenous cannabinoids exert their effects on receptors CB1 and CB2, two G protein-coupled receptors that are located mainly in the central and peripheral nervous systems.
Lab studies show that higher levels of cannabidiol in cannabis appeared to protect against memory impairment. This may be due to the antagonistic (or perhaps inverse agonist) effects of cannabidiol at the CB1 receptor. Moreover, CB1 knockout mice (mice with inactivated CB1) have been shown to exhibit reduced forgetting on memory tasks.
While endogenous cannabinoids have been shown to enhance hippocampal long-term potentiation similar to endocannabinoids, exogenous THC prevents or reduces consolidation of newly learned memories while Cannabidiol, through its antagonism of THC activity, may reverse this anti-consolidation effect.
Another research on Ischemic mice treated with CBD exhibited an increase in the hippocampal brain derived neurotrophic factor (BDNF) protein levels. CBD also stimulated neurogenesis and promoted dendritic restructuring in the hippocampus of animals with ischemic brain injuries.
Cannabidiol is also clinically proven to have great antioxidant effects and acts as a natural neuroprotective agent, restoring damaged brain cells and minimizing the effects of oxidative stress and neuroinflammation caused by free radicals from aging, stress, poor diet and other environmental toxins.
Certain types of nonpsychoactive cannabinoids like CBD can potentiate glycine receptors (GlyRs), an important target for nociceptive regulation at the spinal level. However, more research is still required to explore the potential and mechanism of glycinergic cannabinoids for chronic pain treatment.
Cannabidiol (CBD), and its modified derivatives significantly suppress chronic inflammatory and neuropathic pain without causing apparent analgesic tolerance in rodents. The cannabinoids significantly potentiate glycine currents in dorsal horn neurons in rat spinal cord slices. The analgesic potency of 11 structurally similar cannabinoids is positively correlated with cannabinoid potentiation of the α3 GlyRs. In contrast, the cannabinoid analgesia is neither correlated with their binding affinity for CB1 and CB2 receptors nor with their psychoactive side effects.
Analysis through Nuclear Magnetic Resonance reveals a direct interaction between CBD and S296 in the third transmembrane domain of purified α3 GlyRs which consequently mediate glycinergic cannabinoid-induced suppression of chronic pain. Recent clinical studies have demonstrated that CBD can be an effective therapeutic option for patients with neuropathic pain and other types of injuries.
Bodybuilders, athletes and fitness enthusiasts are revealing that a dose of CBD oil helps them to get the most out of their intense workouts by lowering the pain threshold. They also believe that CBD helps to reduce the time needed for post-workout recovery, helping them to avoid the risks of injuries. Some even hail CBD as a “performance enhancing drug”. If this is certainly the case, we can vouch that CBD is a lot safer compared to synthetic hormones frequently used in the sporting industry to improve athletic performance.
The effect of CBD on amygdala activation during a simulated response to fear was correlated with its reduction of autonomic arousal, and associated decrease in anxiety. The documented effects of CBD on neural activation in the amygdala and striatal regions of the brain may indicate a potential beneficial effect of CBD in the treatment of psychotic and anxiety symptoms.
Moreover, CBD acts through a range of other mechanisms. One route is through the inhibition of the uptake and hydrolysis of our own endocannabinoid, Anadamide. Recent data also suggest that CBD can modulate CB1 receptors, leading to the amelioration of existing psychiatric conditions such as depression and seasonal affective disorder.
CBD’s mood boosting effects may also be attributed to its modest affinity agonist at the human 5-HT1a receptor, a major receptor of the Serotonin pathway which is popularly thought to be a contributor to feelings of well-being and happiness.
HT1A receptor activation has been shown to increase dopamine release in the medial prefrontal cortex, striatum, and hippocampus, and may be useful for improving the symptoms of schizophrenia and Parkinson's disease. These include mood swings, violent tendencies and extreme irritability.
As mentioned before, some of the atypical antipsychotics are 5-HT1A receptor partial agonists, and this property has been shown to enhance their clinical efficacy. Enhancement of dopamine release in these areas may also play a major role in CBD’s antidepressant and anxiolytic effects.
Aside from CB1 and CB2 receptors, CBD can also regulate- directly or indirectly, the activity of: