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Weed Through the Evidence: Medical Marijuana for Chronic Pain

Introduction 

Join us as we weed through current research on cannabis and chronic pain. It is all smoke and mirrors? Is the research half-baked, or can cannabis help you help your patients? 

 

Cannabis Through the Ages, An Ultra-Brief but Very Fascinating History 

To be honest, a lot of this was mind-blowing for me, I had no idea that marijuana has such a long history of medical applications!

  • Cannabis is one of the earliest plants to be domesticated by humans - dating approximately 36 million years ago in Central Asia1
  • One of the earliest formal records of medicinal use dates back to China, 2737 B.C.1
  • Western physicians recommended cannabis for various ailments starting in the mid-1800s1.
  • Numerous pharmaceutical companies such as Eli Lilly, Merck, and Bristol-Meyers marketed cannabis extracts1.
  • The sociopolitical climates of the 1920s, with anti-alcohol legislation, lead to the outlawing of marijuana in 19701
  • The sociopolitical climate of the 21st century has witnessed the legalization of marijuana across many states (USA)1 and many other nations such as Canada and Trinidad and Tobago. 

The Cannabaceae Family

So I wrote this whole blog, very excited about all the science and left this section for last as I thought it would be simple. Little did I know, this little section is a deep and winding rabbit hole full of confusion, disagreements and misinformation! Who would have imagined that that finding a phylogenetic tree for the cannabis family would be such a nightmare! I know many have heard of Cannabis sativa, indica and maybe even ruderalis, but I at least, have never heard of afghanica!  So without further ado, allow me to introduce you to the Cannabaceae family:


Figure 1: Cannabaceae family. Source.

Marijuana and hemp are two strains of the same plant species, Cannabis sativa


Figure 2: The Cannabis sativa plant family. Source

If you feel like jumping down that rabbit hole and learning more about the Cannabis family, this is a nice place to start. Otherwise, keep reading below to learn about the endocannabinoid system and the pharmacological effects of phytocannabinoids.

The Endocannabinoid (ECS) System

The Cannabis mechanism of action tends to be through the endocannabinoid system. 

  • The endocannabinoid (ECS) system is involved in the maintenance of homeostasis2 in all vertebrates1
  • Its functions can be summarized as "relax, eat, sleep, protect, and forget1."
  • The ECS has been implicated in numerous disease states such as chronic inflammatory conditions, regulation of immune homeostasis in the gut, to anxiety and migraines2
  • The body produces endogenous cannabinoids2 (figure 3).
  • Phytocannabinoids (plant-derived), as well as synthetic cannabinoids, are also extracted and produced2 (figure 3).           

Cannabinoids

Figure 3: Cabbabinoids: Endocannabinoids, Phytocannabinoids and Synthetic Cannabinoids. From VanDolah, H.J., Bauer, B.A. and Mauck, K.F., 2019.

 

Endocannabinoid Receptors

  • The main receptors for cannabinoids are CB-1 and CB-21 (with endogenous ligands AEA and 2-AG shown in figure 3).

Learning the distribution of these receptors in the body is essential for understanding the implications of cannabis in patient pain1

  • CB-1: G-protein coupled receptors located in the central nervous system (CNS) and peripheral nervous system (PNS), adipocytes, leukocytes, spleen, heart, lung, GI tract, kidney, bladder, reproductive organs, skeletal muscle, bone, joints and skin1.
  • CB-1 expression is low in the brainstem, medulla, and thalamus. This may likely explain the low risk of mortality from respiratory depression due to cannabis overdose
  • CB-2: Found mostly in the immune system and in lesser amounts in bone, liver and nerve cells1
  • Some evidence shows that these receptors also have analgesic effects on induced nerve damage and pain1.

The Pharmacological Effects of Phytocannabinoids

The figure below (figure 4) lists some of the pharmacological effects of phytocannabinoids. However, the field of cannabis research would benefit from larger human studies and RCTs:

Figure 4: The Pharmacological Effects of Phytocannabinoids. From Mayaah, Z.H., Takahara, S., Ferdaoussi, M., Dyck, J.R.B, 2020.

Check out Embodia's collection of pain sciences continuing education physiotherapy courses by following our big yellow button below. 

Check out our Pain Sciences courses!

 

We also have a course on hand that's quite relevant to today's topic of discussion: Management of Pain in Older Adults in the Opioid and Cannabis Era. If you work with older adults, you may find this online continuing education physiotherapy course quite useful. 

Data and Such (In Case You Aren't Buying It)

But back to the topic at hand. If you love data, check out the table below, composed of recent (2015-2020) primary research articles and reviews spanning various categories in the field of chronic pain:

Target Importance Evidence

Combating opioid addiction

 

Greatest public health challenge facing health providers3

500% increase in opioid-related deaths across North America over the last year. With more than 500 000 reported fatalities, over 1/3 of which were related to prescription medication3.

Acute and chronic musculoskeletal pain is a leading reason for opioid prescription3.

CBD: 53% of patients with chronic pain reduced or eliminated their opioids within 8 weeks after adding a CBD-rich hemp extract to their regimens. 94% of users reported quality of life improvements. (n=131, 30-65 years, chronic pain, have been on opioids for at least 1 year)4

Systematic review and meta-analysis: Moderate evidence to support cannabinoids in treating chronic non-cancer pain at 2 weeks. Similar results were observed at later time points, but the confidence effect is low (36 trials, 4006 participants)3

Rheumatic diseases:

fibromyalgia, rheumatoid arthritis, osteoarthritis, systemic sclerosis 

 

Chronic pain in the adult population is estimated at 30% in some countries; rheumatic diseases are a leading cause for chronic pain5

Review: Cannabis and cannabinoids show great potential for the treatment of rheumatic diseases (fibromyalgia in particular). Recommend larger studies for longer time periods5

Headaches:

Migraines, cluster headaches

Migraines affect 1 in 7 adults worldwide7.

Headache disorders are painful and disabling, can cause substantial personal suffering, impaired quality of life, and high financial cost7.

Review: Supporting literature suggests a role for medicinal cannabis and cannabinoids in treating migraines and cluster headaches, although evidence is primarily limited to case-based, anecdotal, or laboratory-based research6.
Neuropathic pain

Common known causes of neuropathic pain include the following9 common issues affecting our society:

- Alcoholism 
- Amputation
- Chemotherapy
- Diabetes
- Facial nerve problems
- HIV infection or AIDS
- Multiple myeloma
- Multiple sclerosis
- Nerve or spinal cord compression from herniated discs or from arthritis in the spine
- Shingles
- Spine surgery
- Syphilis
- Thyroid problems

Review: Full-spectrum cannabis extract has better analgesic effectiveness than CBD or THC alone. Preclinical studies using full-spectrum cannabis have demonstrated several convincing anti-inflammatory and analgesic effects; it may be a promising therapeutic agent8.


Of course, we don't need to mention that our table is very much non-exhaustive.

Mechanism: ECS Molecular Biology

For all you molecular bio nerds who get excited at the mere thought of a molecular mechanism and sleep sounder after seeing one (kinase, kinase, kinase...that may just be an inside joke with me, myself and I though). Regardless, if anyone loves mechanisms as much as I do, this one's for you!

In figure 5 below, we see the modulation of the ECS by phytocannabinoids. Pictured are CB-1 and CB-2 receptors in the presynaptic neuron of CNS and PNS. The green shaded compounds are common phytocannabinoids and other herbal inclusions in hemp oils that affect the ECS. THC works by agonism of the CB-1 receptors. BCP = beta-caryophyllene, TRPV = transient receptor potential vanilloid. 

We won't get into the details of this modulation, because this is a blog, not a primary research paper, however, if you'd like to go deeper, check out the paper by VanDolah, Bauer and Mauck Clinicians’ Guide to Cannabidiol and Hemp Oils, it's free!

Modulation of the Endocannabinoid System by Phytocannabinoids

Figure 5: Modulation of the Endocannabinoid System by Phytocannabinoids. From VanDolah, H.J., Bauer, B.A. and Mauck, K.F., 2019.

There's so much more to say but we must say goodbye now. This blog only touched the tip of the iceberg with regard to cannabis and medicine. This is an evolving, rapidly changing field that shows great promise for the treatment of chronic pain and may be able to help your patients if it is not helping them already. 

 

References

1. Temple, L.M. (2016). Medical marijuana and pain management. Disease-a-Month, 62: 346-52. DOI: 10.1016/j.disamonth.2016.05.014

2. VanDolah, H.J., Bauer, B.A., Mauck, K.F. (2019). Clinicians' guide to cannabidiol and hemp oils. Mayo Clinic Proc., 94(9): 1840-51. DOI: 10.1016/j.mayocp.2019.01.003

3. Johal, H., Devji, T., Chang, Y., Simon, J., Vannabouathong, C., Bahandari, M. (2020). Cannabinoids in chronic non-cancer pain: A Systematic Review and Meta-Analysis. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders, 13: 1-13. DOI: 10.1177/1179544120906461

4. Capano, A.,  Weaver, R., and Burkman, E. (2020). Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. Postgraduate Medicine, 132:1, 56-61, DOI: 10.1080/00325481.2019.1685298

5. Gonen, T. and Amital, H. (2020). Cannabis and cannabinoids in the treatment of rheumatic diseases. Rambam Maimonides Medical Journal, 11(1): e0007. DOI: 10.5041/RMMJ.10389

6. Baron E.P. (2015). Comprehensive review of medicinal marijuana, cannabinoids, and therapeutic implications in medicine and headache: What a long strange trip its been...Headache: The Journal of Head and Face Pain, 55(6): 885-916. DOI: 10.1111/head.12570

7. World Health Organization. (2014). How common are headaches? Retrieved from https://www.who.int/news-room/q-a-detail/how-common-are-headaches 

8. Mayaah, Z.H., Takahara, S., Ferdaoussi, M., Dyck, J.R.B (2020). The molecular mechanisms that underpin the biological benefits of full-spectrum cannabis extract in the treatment of neuropathic pain and inflammation. BBA - Molecular Basis of Disease, 1866. DOI: 10.1016/j.bbadis.2020.165771

9. WedMD. 2019. Neuropathic pain management. Retrieved from https://www.webmd.com/pain-management/guide/neuropathic-pain#1

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Blog writer, editor: Nataliya Zlotnikov 

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