To date, over 545 different compounds have been identified and isolated from the Cannabis sativa L. (Cannabaceae) plant, of which include over 100 different cannabinoids. These compounds differ greatly in their chemical structure; thus, consumption of the cannabis plant can induce a wide range of effects. Although cannabis has been used for a wide range of therapeutic and recreational purposes, this article will focus primarily focused on therapeutic benefits associated with cannabis use.
Cannabis sativa. Image Credit: Filip Jedraszak / Shutterstock
The over-prescription of opioids and other addictive pain killers has led many industrialized countries around the world, particularly the United States, to experience epidemics of opioid overdoses that unfortunately continues to rise. Although chronic pain management, particularly that which has an idiopathic origin, remains an unresolved global health dilemma, a considerable amount of scientific data has demonstrated that cannabis may be useful for this purpose.
For example, a 2017 online survey of female patients suffering from endometriosis found that a majority of these women experienced a significant reduction in their pain following the use of cannabis. Another study conducted in 2019 found that elderly patients who were diagnosed with wither chronic pain, neuropathy or Parkinson’s disease experienced a significant relief in their symptoms, as well as a reduced dependence on opioids when using a CBD formulation.
Despite the fact that the United States Food and Drug Administration (FDA) has not officially declared cannabis to be an approved treatment for chronic pain, states like Colorado and Michigan that have legalized medical marijuana have found that severe pain is the primary reason for the prescription of cannabis in these areas.
Commercial Medical Marijuana Growing Operation. Image Credit: Canna Obscura / Shutterstock
Chemotherapy-Induced Nausea and Vomiting
Nausea and vomiting related to chemotherapy present a significant burden to affected patients. Cannabinoids have shown some usefulness as antiemetics for cancer patients undergoing chemotherapy. While the precise mechanisms of action are poorly understood, researchers believe that the ability of cannabinoids to act on non-seratonergic receptors, such as the CB1 receptor, accounts for their ability to delay nausea and vomiting in patients.
Two synthetic tetrahydrocannabinol (THC) preparations known as nabilone and dronabinol have shown some success in treating nausea and vomiting in some studies but not others, and improvements in symptoms have been modest. Some of the major limitations of current THC-rich cannabinoids that are used to treat chemotherapy induced nausea and vomiting (CINV) include their poor bioavailability, delayed onset of action and unpredictable gastrointestinal absorption. Furthermore, the altered neurological states, such as disorientation, paranoia and euphoria that can often result from exposure to THC, are often unwanted side effects that limit the clinical practicality of this specific treatment option.
In an effort to overcome these limitations and reduce the potential for abusing such THC preparations, a number of scientific studies have developed formulations that provide a self-titrating dose of both THC and CBD. For example, the University of Sydney is currently conducting a CannabisCINV trial aimed towards investigating the efficacy of a novel oral capsule formulation that has enhanced guideline-consistent antiemetics with TN-TC11M, which is an oral THC/CBD extract.
Many of the biological actions of cannabinoids, which is a term used to refer to the over 100 biologically active chemicals present within the cannabis plant, are mediated by their interaction with two primary cannabinoid receptors known as type 1 (CB1) and type 2 (CB2).
Within the central nervous system (CNS), both CB1 and CB2 receptors can be found primarily within neurons and microglia, respectively. More specifically, CB1 receptors can be found on both glutamatergic and GABAergic interneurons, both of which play a role in the inhibition of synaptic transmission.
Several experimental studies have confirmed the ability of cannabinoids to act as both a non-competitive antagonist against CB1 receptors as well as an inverse agonist to CB2 receptors, thereby demonstrating the ability of cannabis and its chemical constituents to target these pathways for therapeutic purposes.
To this end, cannabis has been used as a possible treatment for a number of neurological disorders including epilepsy, amyotrophic lateral sclerosis (ALS), Huntington’s disease, Parkinson’s disease, dementia and traumatic brain injury, to name a few.
The use of cannabis for the treatment of seizures and epileptic conditions has shown particularly promising results.
Although THC has demonstrated significant anticonvulsant effects in some seizure models, the psychotropic properties of this cannabis compound have led researchers to turn towards other cannabinoids for seizure treatment. For example, cannabidiol (CBD) has been widely evaluated for its anti-seizure activity in various seizure models. These studies have found that CBD successfully reduces the occurrence of seizures that were induced by maximal electroshock and pentylentetrazole in both mice and rates. In mice alone, CBD has successfully shown anti-convulsant activity against seizures induced by cocaine, mercaptopropionic acid, bicuculline, picrotoxin and isoniazid.
Despite the promising results of these animal studies, many clinical applications of cannabis and its chemical constituents for seizure treatment have relied mainly on patient reporting of symptoms. Additionally, these clinical studies often lack appropriate control groups to determine whether the results provide statistically and clinically meaningful differences between patients who do and do not use cannabis-derived products.
Although the action of cannabis on cannabinoid receptors has been postulated as the molecular actions behind this plant’s anti-convulsant profile, further research must still be conducted to fully evaluate its precise mechanisms of action.
In addition to chronic pain, cancer, chemotherapy-induced vomiting and neurological conditions like epilepsy, cannabis has been used to self-medicate for a wide variety of different maladies.
To treat weight loss, there is limited data to support the use of cannabis to treat patients with AIDS wasting syndrome or anorexia nervosa; however, cannabis does not appear to be effective in treating cancer-associated anorexia-cachexia syndrome.
There is currently insufficient evidence to support the role of cannabis in the treatment of irritable bowel syndrome, spasticity associated with multiple sclerosis and spinal cord injury, depression, anxiety, Tourette’s Syndrome, posttraumatic Stress Disorder (PTSD), schizophrenia, schizophreniform psychosis, dystonia, glaucoma, drug addiction, or sleep disorders.
- National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington (DC): National Academies Press (US); 2017 Jan 12. 4, Therapeutic Effects of Cannabis and Cannabinoids. Available from: https://www.ncbi.nlm.nih.gov/books/NBK425767/
- Palace, Z.J.; Reingold, D.A. (2019) Medical Cannabis in the Skilled Nursing Facility: A Novel Approach to Improving Symptom Management and Quality of Life. Journal of the American Medical Directors Association 20(1); 94–98. DOI: 10.1016/j.jamda.2018.11.013.
- Goncalves, J., Rosado, T., Soares, S., Simao, A. Y., Caramelo, D., Luis, A., et al. (2019). Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects and Analytical Determination. Medicines 6(1); 31. DOI: 10.3390/medicines6010031.
- Mersiades, A. J., Tognela, A., Haber, P. S., Stockler, M., Lintzeris, N., et al. (2018). Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: a study protocol for a pilot and definitive randomized double-blind placebo-controlled trial (CannabisCINV). BMJ Open 8(9). DOI: 10.1136/bmjopen-2017-020745.
- Perucca, E. (2017). Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last? Journal of Epilepsy Research 7(2); 61-76. DOI: 10.14581/jer.17012.
Full story is available here.