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 . 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.
1. Maule WJ. Medical uses of marijuana (Cannabis sativa): fact or fallacy?
2. Zuardi AW. History of cannabis as a medicine: a review.
3. Touw M. The religious and medicinal uses of Cannabis in China, India and Tibet.
4. Kalant H. Medicinal use of cannabis: history and current status.
5. Mikuriya TH. Marijuana in medicine: past, present and future.
6. Pisanti S, Bifulco M. Modern history of medical cannabis: from widespread use to prohibitionism and back.
7. Mechoulam R. Cannabinoids as therapeutic agents.
8. Svizenska I, Dubovy P, Sulcova A. Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures
9. Console-Bram L, Marcu J, Abood ME. Cannabinoid receptors: nomenclature and pharmacological principles
10. Szulakowska A, Milnerowicz H. Cannabis sativa in the light of scientific research. Adv Clin Exp Med. 2007;16(6):807–15.
11. Kendall DA, Yudowski GA. Cannabinoid receptors in the central nervous system: their signaling and roles in disease.
12. Identification and functional characterization of brainstem cannabinoid CB2 receptors.
13. Onaivi ES. Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain.
14. Henstridge CM. Off-target cannabinoid effects mediated by GPR55.
15. Bisogno T. Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid.
16. Bisogno T. Phosphatidic acid as the biosynthetic precursor of the endocannabinoid
17. Cravatt BF. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides.
18. Dinh TP. Brain monoglyceride lipase participating in endocannabinoid inactivation.
19. Endo- and synthetic cannabinoids: promising chemotherapeutic agents in the treatment of breast and prostate carcinomas.
20. Schurman LD, Lichtman AH. Endocannabinoids: a promising impact for traumatic brain injury.
21. Pagotto U. The emerging role of the endocannabinoid system in endocrine regulation and energy balance.
22. Cunha P. Endocannabinoid system in cardiovascular disorders
23. Shoenfeld Y. Cannabinoids and autoimmune diseases: a systematic review.
24. Laprairie RB.Cannabinoid receptor ligand bias: implications in the central nervous system.
25. Di Marzo V. Targeting the endocannabinoid system: to enhance or reduce?
26. Is lipid signaling through cannabinoid 2 receptors part of a protective system?
27. Hasenoehrl C. The gastrointestinal tract: a central organ of cannabinoid signaling in health and disease.
28. Ligresti A. From phytocannabinoids to cannabinoid receptors and endocannabinoids.
29. Bridgeman MB. Medicinal cannabis: history, pharmacology, and implications for the acute care setting.
30. Pyszniak M. Endocannabinoid system as a regulator of tumor cell malignancy: biological pathways and clinical significance.
31. Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptor agonists.
32. Nikan. Ligands for cannabinoid receptors, promising anticancer agents.
33. Tegeder I. Endocannabinoids as guardians of metastasis.