THE ENDOCANNABINOID SYSTEM
The Endocannabinoid System is a signaling pathway that occupies the central nervous system (CNS; brain and spinal cord), peripheral nervous system (PNS) and immune pathways [1,2]. This network is comprised of two major receptors Cannabinoid Receptor 1 (CB1) and Cannabinoid Receptor 2 (CB2) that, when activated via cannabinoid ligation, affect neurotransmitter release and subsequently influences a number of physiological factors such as immune response, cardiovascular function, bone development, digestion and metabolism, as well as several other processes including wake/sleep cycles, learning, pain response, and regulation of stress and appetite [1,2,3].
+ Cannabinoid ligands are categorized into three groups based on their origin:
+ Endocannabinoids are produced endogenously within the human body and include compounds such as Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG).
+ Phyto-cannabinoids are produced in the vegetative matter of plants, specifically cannabis and hemp, and include the most widely studied cannabinoids THC and CBD.
+ Synthetic cannabinoids are developed chemically within a laboratory setting[3, 4].
SIGNALLING THROUGH CANNABINOID RECEPTORS
CB1 and CB2 receptors are expressed throughout the body wherein CB1 dominate the CNS while CB2 receptors exist predominantly in the peripheral tissues including the immune system and related organs. A number of cannabinoids including endogenous AEA and phyto-supplied THC have a high affinity for CB1 and interactions with this receptor creates a signalling cascade that is largely responsible for the physical and psychotropic effects brought on by cannabis use [1,2]. In contrast, CB2 receptor activation does not yield psychoactive effects, and rather elicits a range of therapeutic benefits including those against pain, and neurodegenerative happenings associated with disease including Multiple Sclerosis (MS) and Huntington’s disease .
Conversely, cannabinoid such as CBD affect CB1 and CB2 indirectly by preventing the breakdown and reuptake of other Cannabinoids allowing for their accumulation and subsequent method of action. Furthermore, CBD activates several non-cannabinoid receptors including the serotonin receptors that are responsible for mood, sleep and memory [2,4,15], and are the target of many pharmaceutical drugs involved in antidepressant, anxiolytic, and neuroprotective effects.
Therapeutic & Medical Benefits
TETRAHYDROCANNABINOL (THC)THC is one of the primary cannabinoids found in the cannabis plant and is largely responsible for the psychological and psychoactive effects brought on from cannabis use [1,8,10]. Over the years based on anecdotal and scientific evidence, THC has demonstrated its potential therapeutic benefit toward a number of conditions and symptoms including nausea, vomiting, insomnia, pain, muscle spasticity, tremors, and bronchospasm often brought on by a range of medical conditions (Table 1) [1,8,9,10,11]. Emerging research indicates a high level of therapeutic potential for a variety of health concerns, in some cases even at doses substantially lower than those required to feel the psychoactive effects of THC.
CANNABIDIOL (CBD)CBD is another major cannabinoid found in cannabis. Unlike THC, CBD does not administer the same psychoactive effect(s) Research is beginning to demonstrate that CBD possesses therapeutic effects through its ability to target several other receptors, including 5-HT1A serotonin receptors, and its blockage of neurotransmitter uptake [2, 4, 15]. It has become increasingly evident that CBD greatly benefits patients suffering from epilepsy by significantly reducing the frequency of re-occurring seizures [1, 6, and 9]. There are several other conditions and related symptoms that have shown to benefit from CBD related therapy (see Table 1). Because of the lack of accompanying psychoactive responses, CBD is often a desirable choice for many individuals seeking cannabinoid therapies without the side effect of impairment.
However, THC has also been shown to effectively treat anxiety, stress, and depression, as well as symptoms of Multiple Sclerosis (MS) [1,10,12,13], Parkinson’s disease [14,15], and those induced from cancers including glaucoma [1,7,1