Chronic pain is one of the most common conditions that medical cannabis is prescribed for. Chronic pain refers to persistent pain that lasts for several months or longer, often resulting from conditions such as arthritis, neuropathy, fibromyalgia, or back injuries. Conventional treatment approaches for chronic pain may include opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and physical therapy. However, these treatments can be ineffective for some individuals and may come with undesirable side effects or risks of dependency.
The Endocannabinoid System and Pain
In recent years, research has shown promising evidence regarding the use of medical cannabis for managing chronic pain. Cannabis contains more than 100 active compounds, known as cannabinoids, with two primary cannabinoids being delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These cannabinoids interact with the body’s endocannabinoid system, which plays a role in pain regulation.
The endocannabinoid system consists of cannabinoid type 1 (CB1) and type 2 receptors (CB2) which play roles in pain perceptions and pain sensation [4]. Here’s a snapshot of how these cannabinoid receptors impact chronic pain:
- CB1 is most abundant in the nervous system
- CB1 inhibits pain sensation (nociception) by blocking signals in the spinal column
- CB1 stimulates the body’s pain-relieving (analgesic) pathways
- CB2 is abundant in the immune system
- CB2 inhibits the release of inflammatory factors from immune cells (glial cells, neurons)
- CB2 inhibits pain sensation by mediation immune cells (neuroprotective)
Cannabinoids like THC and CBD are able to bind to cannabinoid receptors because they are the botanical version of endocannabinoids. The endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) are naturally produced in the body. Both types of cannabinoids can act on biological pathways outside of the endocannabinoid system in addition to, or in conjunction with, their interactions with cannabinoid receptors. Serotonin 3A (5-HT3A), and transient receptor potential subfamily V member 1 (TRPV1) cation channels are an example of this [4].
How Cannabinoids Combat Pain Outside of the Endocannabinoid System
Synaptic junctions are the spaces between nerve cells where signals get passed. One way that CBD can reduce pain is by increasing endocannabinoid concentration at synaptic junctions [4]. It does this by inhibiting the breakdown of fatty acids that transport endocannabinoids to these junctions. Another way that CBD can relieve pain is by inhibiting serotonin 3A (5-HT3A) receptors. These serotonin receptors transmit pain sensation signals, especially the sensation of neuropathic (shooting or burning) pain [3]. They also play a role in hyperalgesia (increased pain sensitivity).
TRP cation channels like TRPV1 are another important target for treating chronic pain with medical cannabis. These channels play a crucial role in pain sensation which involves psychological and physiological aspects [2].THC has been found to inhibit pain sensation by blocking TRP cation channels [4].
How Cannabinoids Reduce Inflammation
In addition to pain sensation, inflammation can play a major role in chronic pain. Activation of CB1 and/or CB2 promotes an anti-inflammatory state in the body [1]. This anti-inflammatory state occurs when cannabinoids suppress the immune system from synthesizing a type of signal protein called a cytokine. In addition to cytokines, cannabinoids also suppress a number of other inflammatory factors that originate in the immune system (nitric oxide, TNF-a, gamma interferon-induced protein 10 (CXCL10), chemokines, and others).
Overall, when CB1 and CB2 are activated pro-inflammatory cytokines that increase inflammation are suppressed, and anti-inflammatory cytokines that decrease inflammation are elevated [1]. In this way, cannabinoids can act on anti-inflammatory mechanisms that nonsteroidal anti-inflammatory drugs (NSAIDs) and other drugs cannot take advantage of. THC has even been found to be 80 times more potent than aspirin and twice as potent as hydrocortisone in terms of potential anti-inflammatory action. However, both THC and CBD can reduce inflammation via the immune system. They target different aspects but can be used individually or together.
Considerations for Using Medical Cannabis for Pain Management
Medical cannabis can be consumed in various forms, including orally inhaling dried cannabis flowers, ingesting cannabis-infused edibles or capsules, applying topical creams or oils, or using sublingual sprays. Each method of consumption has different onset times and durations of effects, allowing patients and healthcare providers to choose the most suitable option based on individual needs.
While medical cannabis shows promise for chronic pain management, it’s important to note that further research is still needed to understand its efficacy, safety, and long-term effects. The use of medical cannabis should always be approached with caution and under the guidance of a qualified healthcare professional.
References
- da Nóbrega Marinho, A. M., & da Silva-Neto, R. W. G. Anti-inflammatory effects of cannabinoids. Cannabis and Cannabinoids, 31.
https://sbed.org.br/wp-content/uploads/2023/06/BrJPain_Suplemento1_Cannabis_2023_ing.pdf#page=33
- González-Ramírez, R., Chen, Y., Liedtke, W. B., & Morales-Lázaro, S. L. (2017). TRP channels and pain. Neurobiology of TRP channels, 1, 125-147.
- Nasirinezhad, F., Hosseini, M., Karami, Z., Yousefifard, M., & Janzadeh, A. (2016). Spinal 5-HT3 receptor mediates nociceptive effect on central neuropathic pain; possible therapeutic role for tropisetron. The journal of spinal cord medicine, 39(2), 212-219.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072495/
- Tait, J., Erridge, S., Holvey, C., Coomber, R., Usmani, A., Sajad, M., … & Sodergren, M. H. (2023). Clinical outcome data of chronic pain patients treated with cannabis-based oils and dried flower from the UK Medical Cannabis Registry. Expert Review of Neurotherapeutics, 1-11.
https://www.tandfonline.com/doi/pdf/10.1080/14737175.2023.2195551
