Medical Cannabis 101

How Cannabis Works

 

Our bodies naturally accept cannabis as medicine! To understand how this works, we first need to understand the vast system in our bodies called the endocannabinoid system. It is within this system that our bodies naturally create chemicals similar to those found in cannabis. It is theorized that the purpose of this system is to maintain homeostasis in the body (1). Deficiencies within this system can lead to a variety of health problems (2). When our bodies are deficient in these naturally occurring substances, we can "supplement" with cannabis. Just as deficiencies within this system can lead to health issues, maintaining a healthy endocannabinoid system can help prevent and treat and variety of ailments (3).

The endocannabinoid system spans throughout the entire body. It is comprised of receptors on cells, two of which are known as CB1 and CB2, as well as chemicals anandamide and 2-AG (4). Think of CB1 and CB2 receptors as "targets"; when endocannabinoids hit these targets, this affects the internal processes of these cells. The endocannabinoid system effectively regulates various cell functions and processes throughout the body (5). This all sounds very complicated, and it is. However, we begin to get a better understanding of this system and how important it is when we discuss exactly what the endocannabinoid system controls within the body.

The endocannabinoid system plays a crucial role in perceiving and responding to stress, controls energy metabolism, regulates the entire nervous system, regulates how we perceive pain, controls inflammation, controls intestinal processes, regulates liver function, reproductive function, cardiac function, bone development, motor functions and immune system functions and responses. It even plays a role in how our bodies fight against cancer (6,7,8,14) !

It is theorized that there are over 100 different cannabinoids produced within cannabis plants9. The two most studied, and the ones we will discuss within, are THC and CBD. THC, whose chemical name is tetrahydrocannabinol, is an intoxicating compound known to produce the "high" that users experience when using cannabis. The plant actually produces what is known as THCA, a non-intoxicating compound, that when it is heated via combustion or vaporization converts into THC. Similarly, plants naturally produce CBDA, and again when heated this compound coverts to CBD. THC, besides causing intoxication, can also alleviate neuropathic pain, reduce muscle spasticity, decrease nausea, and increase appetite (1,7,10). There are many other potential health benefits currently being studied around the world. CBD, or cannabidiol, has been shown to offer a multitude of potential health benefits as well, all without producing an intoxicating effect (11). It is theorized that CBD can act as an anti-inflammatory, anti-epileptic, neuroprotectant, and anxiolytic, and is currently being studied in a multitude of other clinical applications (12).  

There are other active compounds in cannabis known as terpenes (13).  Terpenes are aromatic compounds found in cannabis products that give each strain its own individual smell and taste.  Most of these compounds are not unique to cannabis, but they can have profound effects on the patient when present in cannabis formulations (6). It is theorized that patient's different experiences with different strains of cannabis may be primarily due to varied concentrations of various terpenes found in each individual strain (7,9).

 

Methods of Consumption

Below we will outline the most common ways to consume cannabis and outline the typical time of onset and duration of effect.

 

 

 

Inhalation(19)

Typical onset: seconds-10 minutes

Duration: 1-4 hours

Smoking is the most common way patients consume cannabis. It has a moderate bioavailability. Doses can be easily titrated to effect and its rapid onset are considered recognized benefits. Smoking can cause general lung irritation, so vaporizing is considered an easy and safer alternative to smoking. Many patients perceive effects within a few puffs, which allows patients to have a high degree of control over dosing.

Ingesting(19)

Typical onset:  30-90+ minutes

Duration: 6-8 hours

Edible cannabis products have a delayed onset. This is where following the motto "start low and go slow" is imperative. Most cannabis naïve patients should begin with low doses, and titrate dose based on effect after 2 hours. THC is converted by the liver to a much more psychoactive form following ingestion, which can cause patients to have considerable adverse effects if too high of a dose is consumed(19,20).

Sublingual(19)

Typical onset: 15-60 minutes

Duration: 1-4 hours

Sublingual dosing has become a common way of ingesting cannabis products. The bioavailability is high. The effects start rapidly and last longer than smoking. Sublingual dosing is more reliable and more consistent than edible products. 

Topical(19)

Topical preparations of cannabis can be very helpful to patients and  cause no psychoactivity or "high". They can be used to help decrease pain and inflammation locally. They can be applied fairly liberally and often.

Suppository(19,21)

While not a dosage form used in most patients, suppositories are another way to utilize cannabis. Anecdotal patient reports suggest little to no intoxication from this form of administration(21). More research is needed to determine the specific bioavailability of cannabis via suppository. Suppositories can be utilized in patients who want to target the lower torso specifically, or by patients who have damaged or altered upper GI tracts.

 

Possible Side Effects and Drug Interactions

Side effects are possible with cannabis use. The severity of symptoms can range from very mild to very intense depending on a variety of factors. It should be noted that lethal overdoses of cannabis do not occur(22) and severe side effects are very rare(19). The majority of side effects that can occur will cause patient discomfort for a relatively short period of time and then pass. The response to medical cannabis and potential severity of side effects can vary widely from patient to patient. To mitigate potential side effects the motto "start low and go slow" should be used(19). You can always increase your dose of cannabis, but once taken, you can't "take it away". Side effects can range from dry eyes, dry mouth, dizziness, drowsiness, increased heart rate, decreased blood pressure, decreased blood sugar, lack of balance, increased appetite, decreased motor function, decreased cognitive abilities, and short-term memory loss to panic attacks and exacerbations of psychosis symptoms(19,23)

It should be noted that many of the "more severe" side effects occur in patients that ingest high dose edible products. The liver converts delta-9-tetrahydrocannabinol (what we call THC) to 11-hydroxy-delta-9-tetrahydrocannabinol. 11-hydroxy-THC is estimated to be over 3 times more potent than THC, which explains the increased potential for side effects with edible products(24).

If you are currently taking prescription drugs or supplements you should discuss cannabis use with your physician and/or pharmacist. There are potential drug interactions possible with a variety of pharmaceuticals when combined with cannabis. To assess the possibility of potential drug interactions, your doctor or pharmacist will need to know that THC is metabolized by CYP3A4 and CYP2C9, and CBD is metabolized by CYP3A4, CYP2C9, and CYP2C19(25). Pharmaceuticals that "inhibit" these systems can increase THC and CBD levels, while pharmaceuticals that "induce" these systems can decrease THC and CBD levels. It should also be noted that THC is a CYP1A2 inducer, and CBD is an inhibitor of CYP3A4 and CYP2D6(25).

Many classes of medications fall into these categories for potential interactions with cannabis.  Consuming cannabis while taking these medications is not contraindicated, however proper monitoring and potential dosage adjustment should be discussed and monitored by a physician. Examples of common drug classes that may have potential drug interactions are as follows (this list is not inclusive):

  • SSRI's

  • Benzodiazepines

  • Chemotherapy

  • Anti-Retrovirals

  • Antidiabetic drugs

  • Immunosuppressants

  • Antibiotics

  • Antifungal drugs

  • Blood pressure and/or cholesterol drugs

If you are currently taking a medication that is designated as having a "narrow therapeutic index", it is even more critical that you tell your physician about your medical cannabis use. These types of medications have an even higher chance of needing to be dose adjusted when used with cannabis. Examples are as follows (this list is not inclusive):

  • Phenobarbital, Carbamazepine, Valproic Acid and anti-convulsants in general

  • Warfarin or blood thinners in general

  • Digoxin

  • Lithium or other anti-psychotics and/or mood stabilizers in general

  • Cyclosporine or other immunosuppressive drugs in general

  • Levothyroxine or other thyroid medications in general

  • Theophylline

 

Sources

  1. Jarvis, Sabrina, Sean Rassmussen, and Blaine Winters. “Role of the Endocannabinoid System and Medical Cannabis.” The Journal for Nurse Practitioners 13.8 (2017): 525–531.

  2. Russo E. (2018). Clinical Endocannabinoid Deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol. Lett. 29 192–200.

  3. Mouhamed, Yara et al. “Therapeutic Potential of Medicinal Marijuana: An Educational Primer for Health Care Professionals.” Drug, Healthcare and Patient Safety Volume 10 (2018): 45–66.

  4. Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown” Current medicinal chemistry vol. 17,14 (2010): 1468-86.

  5. Lisboa, S.F. et al. “The Endocannabinoid System and Anxiety.” Vitamins and Hormones (2017): 193–279.

  6. Chakravarti, Bandana, Janani Ravi, and Ramesh K. Ganju. “Cannabinoids as Therapeutic Agents in Cancer: Current Status and Future Implications.” Oncotarget 5.15 (2014): n. pag.

  7. Fine, Perry G., and Mark J. Rosenfeld. “The Endocannabinoid System, Cannabinoids, and Pain.” Rambam Maimonides Medical Journal 4.4 (2013): n. pag.

  8. Battista, Natalia et al. “The Endocannabinoid System: An Overview.” Frontiers in Behavioral Neuroscience 6 (2012): n. pag.

  9. Russo, Ethan B. “Taming THC: Potential Cannabis Synergy and Phytocannabinoid-Terpenoid Entourage Effects.” British Journal of Pharmacology 163.7 (2011): 1344–1364.

  10. Rudroff, Thorsten, and Jacob Sosnoff. “Cannabidiol to Improve Mobility in People with Multiple Sclerosis.” Frontiers in Neurology 9 (2018): n. pag.

  11. Suryadevara, Uma et al. “Pros and Cons of Medical Cannabis Use by People with Chronic Brain Disorders.” Current Neuropharmacology 15.6 (2017): n. pag.

  12. “Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?” Journal of epilepsy research vol. 7,2 61-76. 31 Dec. 2017, doi:10.14581/jer.17012

  13. Oláh, Attila, Zoltán Szekanecz, and Tamás Bíró. “Targeting Cannabinoid Signaling in the Immune System: ‘High’-Ly Exciting Questions, Possibilities, and Challenges.” Frontiers in Immunology 8 (2017): n. pag.

  14. Schwarz, Rico, Robert Ramer, and Burkhard Hinz. “Targeting the Endocannabinoid System as a Potential Anticancer Approach.” Drug Metabolism Reviews 50.1 (2018): 26–53.

  15. Bicas, J.L. et al. “Evaluation of the Antioxidant and Antiproliferative Potential of Bioflavors.” Food and Chemical Toxicology 49.7 (2011): 1610–1615.

  16. “Cannabinoids in the management of difficult to treat pain” Therapeutics and clinical risk management vol. 4,1 (2008): 245-59.

  17. Dahham, Saad et al. “The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene β-Caryophyllene from the Essential Oil of Aquilaria Crassna.” Molecules 20.7 (2015): 11808–11829.

  18. Fernandes, Elizabeth S. et al. “Anti-Inflammatory Effects of Compounds Alpha-Humulene and (−)-Trans-Caryophyllene Isolated from the Essential Oil of Cordia Verbenacea.” European Journal of Pharmacology 569.3 (2007): 228–236.

  19. Goldstein, Bonni. Cannabis Revealed: How the World's Most Misunderstood Plant Is Healing Everything from Chronic Pain to Epilepsy. Bonni Goldstein, 2016.

  20. Romero-Sandoval, E. Alfonso, Ashley L. Kolano, and P. Abigail Alvarado-Vázquez. “Cannabis and Cannabinoids for Chronic Pain.” Current Rheumatology Reports 19.11 (2017): n. pag.

  21. Israel, Solomon. “Legal Cannabis Suppositories Are Coming to Canada, but with Strict Potency Limits.” Are Recreational Cannabis Lounges in Canada's Future? - The Leaf Cannabis News, 8 Aug. 2018, www.theleafnews.com/news/legal-cannabis-suppositories-are-coming-to-canada-but-with-strict-potency-limits-490368621.html.

  22. "Cannabis and Cannabinoids.” National Cancer Institute, www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#link/_88_toc.

  23. Vigil, Jacob M. et al. “Associations Between Medical Cannabis and Prescription Opioid Use in Chronic Pain Patients: A Preliminary Cohort Study.” Ed. Kent E. Vrana. PLOS ONE 12.11 (2017): e0187795.

  24. Lemberger, Louis et al. “Comparative Pharmacology of Δ9-Tetrahydrocannabinol and Its Metabolite, 11-OH-Δ9-Tetrahydrocannabinol.” Journal of Clinical Investigation 52.10 (1973): 2411–2417.

  25. Fugh-Berman, Adriane, et al. “Medical Cannabis Adverse Effects and Drug Interactions.” Medical Cannabis Adverse Effects and Drug Interactions, Government of the District of Columbia Department of Health,

 

 
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