Beyond the stigma: cannabinoids as a therapeutic

With the growing prevalence of marijuana use and legalization across the globe, cannabinoids, the active compounds found in cannabis – otherwise known as marijuana – are increasingly chosen to treat chronic pain and mental health conditions. In fact, cannabis has been used for centuries, dating back to 2700 B.C. in China and 1000 B.C. in India. Cannabinoids interact with our endocannabinoid system to regulate metabolism, neuronal functions, and inflammation. Recently, there is growing evidence that cannabinoids have therapeutic applications in managing chronic pain, anxiety, and symptoms associated with autoimmune conditions, such as multiple sclerosis and inflammatory bowel disease. Despite this, research on the health effects from the long-term use of cannabis is still lacking.

Anxiety

Anxiety is one of the most common reasons for medical cannabis use. Anxiety and mood disorders are common mental health conditions that persistently affect your emotional state, driving changes in behaviour, ability to perform routine activities, and impacting the overall quality of life. A systematic review on the effect of cannabidiol treatment for anxiety found that cannabinoids reduced anxiety in both animals and humans. Currently, there is still limited and sometimes conflicting evidence regarding the clinical efficacy of cannabis for alleviation of anxiety and mood disorders, despite many individuals self-reporting beneficial effects. Part of this discrepancy could be due to the formulation or route of administration of cannabinoids. Clinical trials are currently underway to provide further insight into the advantages and appropriate use of cannabis in reducing anxiety.

Pain

Chronic pain is one of the most challenging conditions to manage or cure. In ancient China, cannabis was used as an anesthetic. In fact, the Chinese characters used for cannabis refer to numbness. Evidence from animal studies have revealed that cannabinoids interact with cannabinoid receptors and pain sensing systems to provide pain relief. In the clinic, cannabinoids have been shown to elicit a decrease in neuropathic pain, a chronic condition resulting from nerve damage. These promising results have inspired the use of cannabis for managing pain resulting from autoimmune conditions as well.

Multiple Sclerosis

Multiple sclerosis (MS) is a chronic neurological condition where the immune system attacks the insulating layers of the nerves in the central nervous system. This condition induces symptoms such as pain as well as cognitive and motor dysfunction. Interestingly, MS patients display increased expression of cannabinoid receptors and changes in cannabinoid metabolism. Activating cannabinoid receptors can alleviate neuropathic pain, reduce muscle spasms, and improve sleep in MS patients. It is unclear whether the drug has any effect on MS progression, however, in an open-label study by Sorosina et al., use of cannabinoids was found to downregulate markers of immune activation in blood of MS patients.

Inflammatory bowel disease

Many patients with inflammatory bowel disease (IBD) utilize cannabinoids to manage the pain elicited by their chronic condition. Cannabis has a plethora of effects on the gut, modulating gastric function, intestinal motility, pancreatic function, liver metabolism, immune activation, and sensory functions through cannabinoid receptors expressed throughout the gastrointestinal tract. In both mouse and human studies, cannabinoids promoted mucosal healing, reduced inflammation, and provided symptomatic relief, such as abdominal pain, diarrhea, and nausea. However, long-term use of cannabis correlates with increased complications and surgery in IBD, highlighting the need for further research on the use of cannabinoids in IBD management.

The use of cannabinoids is associated with both physical and mental health risks, including respiratory problems, cardiovascular dysfunction, gastrointestinal distress, anxiety, and cognitive function. Frequent cannabis use has also been correlated with higher risk of psychosis and schizophrenia, and longitudinal data suggests an association with age-related cognitive decline. A study from Meier et al. 2012 demonstrated cognitive impairment over 20 years, and recent work from Colorado by Gowin et al. found that cannabis use was associated with lower brain activity and working memory. Alarmingly, a study of 222,600 mother-child pairs found that maternal gestational cannabis use increases the risk of behaviour disorders in children, emphasizing the need for this type of research to enable informed use of cannabis.

Of note, these rising concerns are associated with recreational and not medicinal use of cannabis, which vary greatly in cannabinoid profiles and routes of administration. For example, medicinal use primarily involves oral administration with purified active compounds of cannabinoids, while recreational use is predominantly through smoking. Additionally, various cannabinoid compounds are also licensed for medicinal use. Two cannabinoids naturally found in cannabis plants that have been approved by Health Canada for use in clinic include cannabidiol (CBD) and tetrahydrocannabinol (THC). For example, nabilone, a form of THC, is approved for management of severe nausea and vomiting associated with cancer treatments, while Epidiolex, an oral solution of CBD, is approved for treatment of seizures. Cannabinoid combination therapies are also available, such as the buccal spray Sativex, which contains a mixture of THC and CBD and is approved for adults with neuropathic pain associated with MS. Thus, deconvoluting variables related to clinical versus recreational use will be necessary to evaluate the safety and efficacy associated with long-term use of cannabinoids.

An additional challenge in performing these investigations is that the societal stigma associated with cannabis use could affect participant recruitment. Furthermore, research progress has been impeded due to lack of a safety profile for cannabinoids, accepted clinical use, and drug access due to the differences in drug legalization frameworks around the world. The choice in selecting cannabinoids as a treatment, particularly for chronic pain and psychiatric conditions, is often due to the lack of treatments that have worked in alleviating their conditions. For some, it has been a miracle drug, where no other option has been effective. Providing a well-rounded understanding of the benefits and risks of cannabis, regarding the route of administration, dose, formulation, and duration of use, would empower individuals to make informed decisions about their health.