Physicians Guide

The investigation of cannabis-derived products for medical use


Medical cannabis

Medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms.

Herbal cannabis has been used for thousands of years for medical purposes. With elucidation of the chemical structures of Tetrahydrocannabinol (THC) and Cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored.  
Cannabinoids can be administered orally, sublingually, or topically, mixed with food, or made into tea.

Initially, the term ‘cannabinoids’ was used to designate a group of specific compounds present in the Cannabis sativa plant, which is known for its psychoactive effects and which has been used in medicine since ancient times [1, 2]. For example, in traditional Chinese medicine, cannabis was used for neuralgias, convulsions and migraines [3, 4].
In the nineteenth century, the use of cannabis became very popular in Europe and USA, where ethanolic extracts of cannabis (known as cannabis tincture) were also utilized to treat various disorders such as convulsions in infants, tetanus, cholera and rabies, among others. However, these disappeared from therapeutic use in the first half of the twentieth century owing to an inability to prepare standardized cannabis preparations, which resulted in the risk of producing over- or
under-dosed formulations [4–7].
The most relevant cannabinoids are Δ9- tetrahydrocannabinol (Δ9-THC), the most abundant cannabinoid and the one mainly responsible for the psychoactive properties of cannabis, and cannabidiol (CBD), the second most abundant and lacking psychoactive activity. However, the discovery of specific receptors for these compounds in the 1990s demonstrated that membrane receptors mediated cannabinoid effects. This discovery led to the search for endogenous ligands that activate them, which are called endogenous cannabinoids or endocannabinoids. Today, the term cannabinoids not only include plant cannabinoids, also known as Phyto cannabinoids, but also endocannabinoids and the synthetic analogues of both groups.

However, it has been demonstrated that CB2 receptors are also present in the CNS (but only in glial cells, not in nerve cells), especially under certain circumstances, such as in inflammation [12, 13]. It has to be taken into account that some effects of cannabinoids, including endocannabinoids, are mediated by non-cannabinoid receptors such as other G-protein-coupled receptors GPR55 and GPR19, transient receptor potential vanilloid channels and peroxisome proliferator-activated receptors [14]. In fact, the GPR55 receptor has been postulated to be part of the endocannabinoid system (ECS).
With respect to endocannabinoids, the most relevant compounds are N-arachidonoyl ethanolamine, commonly known as anandamide (AEA), and 2-arachydonoilglycerol (2-AG). Both are synthesized on demand.

Cannabinoid receptors, endocannabinoids and the enzymes responsible for their biosynthesis and degradation constitute the ECS. In recent decades, the ECS has attracted considerable interest as a potential therapeutic target in numerous pathological conditions. Its involvement in several physiological processes is well known, such as in energy balance, appetite stimulation, blood pressure, pain relief, embryogenesis, nausea and vomiting control, memory, learning and immune response, among others [21–24], as well as in pathological conditions where it exerts a protective role in the development of certain disorders. As a result, it has been reported that changes in endocannabinoid levels may be related to neurological diseases such as Parkinson’s disease (PD), Huntington’s disease (HD) or multiple sclerosis (MS), as well as anorexia and irritable bowel syndrome [25–29].
Considering the importance of the ECS and the therapeutic potential of cannabinoids in a vast number of medical conditions, several clinical studies with cannabinoid- based medications are ongoing. Specifically, some cannabinoid-based medications have already been approved for the treatment of nausea and vomiting associated with chemotherapy, anorexia, pain related to cancer, and spasticity and pain associated with MS. A preclinical and clinical data of cannabinoid use in therapeutics, especially of indications with high evidence will be provided in the other posts.

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