Introduction to Medical Cannabis

There are many ideas and questions around the use of cannabis for medical purposes that need answers from reliable sources. Luckily, we have had the opportunity to work along with Dr. Mafer Arboleda, an expert in medical cannabis, anesthesiologist and specialist in chronic pain and palliative care. 

What is medical cannabis? 

It refers to the use of preparations or active principles of the cannabis plant, mainly cannabinoids, as a complementary therapy to alleviate certain symptoms associated to specific medical conditions.

Medical cannabis use requires close supervision and guidance from a well-trained healthcare practitioner. This is a customized treatment that involves a comprehensive medical history to determine if the patient is a candidate to receive cannabinoid-based medicines.  We should always keep in mind that medical cannabis is not the panacea or miracle drug and that needs to be administered according to medical conditions and requirements of each specific patient.

* This is not intended to be an inclusive list, so we only mention the most studied aspects for an informative purpose.

Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are two of the most abundant and studied compounds of the Cannabis sativa plant; they also have different properties and therapeutic applications.

THC reduces chronic pain (mainly neuropathic pain), enhances sleep quality, increases appetite (i.e., in HIV/AIDS and cancer population) and alleviates secondary effects of chemotherapy such as nausea and vomiting. On the other hand, CBD has shown important anti-inflammatory effects, is anxiolytic (specifically in Social Anxiety Disorders, anxiety associated to chronic pain, cancer and Parkinson’s disease), antioxidant, is neuroprotective and has been studied for the treatment of drug-resistant epilepsy such as Lennox-Gastaut and Dravet syndromes. 

Sativa and Indica are the two principal cultivars (‘varieties’ or ‘strains’) of the cannabis plant. 

Cannabis taxonomy has been the subject of a long debate. Cannabis sativa, subspecie sativa differs subspecie indica mainly on its phenotypic characteristics and geographical origins:

• Sativa possibly originated in the Himalayan mountains but is currently found in western Asia and countries along the equator. It can be recognized by tall plants with widely spaced branches and long thin leaves. 
• Indica is believed to have evolved from mountainous regions of South Asia (Afghanistan, India, Bangladesh, Pakistan, Bhutan, etc.). Indica cultivars are characteristically short plants with broader leaves.

Interestingly, as anecdotal data primarily from non-medical (“recreational”) use, consumers report sativa-predominant varieties to elicit uplifting, cerebral effects versus indica-predominant varieties that are associated with relaxation and analgesic effects.  However, such anecdotal reporting has not been validated by any randomized controlled trial. It is also widely accepted that all commercial cultivars in North America are hybrids of sativa and indica. Traditionally, the phenotype and origin of the plant is unlikely to determine its therapeutic effects.  This will depend only on the chemovar classification and main cannabinoid component.

Myths vs facts about medical cannabis

• It has no adverse effects? – Both THC and CBD could produce adverse effects. Most are related to THC and are dose dependent. Such adverse effects can often be avoided with careful dose titration and close follow-up. 
• Cannabis can produce addiction? – Chronic or habitual use of cannabis for non-medical purposes (“recreational use”) and primarily high amounts of THC can lead to the development of cannabis use disorder (CUD). Specific predictors for this risk of development of CUD include males, early-onset cannabis users, and childhood traumatic events.

No clinical studies have yet been published related to the risk of development of CUD during medical cannabis use.

Cannabis cures cancer? – No clinical evidence to support its use as a curative therapy in cancer patients or in other medical conditions. However, it can improve cancer-related symptoms and / or side effects to treatments such as chemotherapy-induced nausea and vomiting.

We are aware that terminology can be difficult, especially in an unknown field, so here are some definitions that will make it easier to understand.

*This part and conclusion are from the book Cannabinoids and Pain, chapter five, written by Maria Fernanda Arboleda, MD and Erin Prosk, MSc.

The Endocannabinoid System (ECS):
The ECS is an interesting biological system composed of cannabinoid receptor proteins, such as CB1 and CB2, as well as endogenous lipid-based neurotransmitters known as endocannabinoids, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG). THC acts as a partial agonist of the G protein-coupled cannabinoid receptors, CB1 and CB2, producing the majority of psychoactive and specific therapeutic effects of cannabis. Conversely, CBD is a non-intoxicating phytocannabinoid that exerts other therapeutic properties.

The ECS has been widely studied and has been identified as an important modulatory system to support homeostasis of many body functions including appetite, sleep, mood, memory, and pain sensation, among others.

Cannabinoid-based medicines or treatments
A general term used to describe therapeutic cannabis or cannabinoid-based products where cannabinoids are the primary active pharmaceutical ingredient. This term is applied regardless of origin as plant-derived or synthetic cannabinoids. 

Cannabinoid-based medicines may be approved or unapproved medical treatments, but generally are regulated and legally accessible though availability of products is varied in different countries and jurisdictions. 

Pharmaceutical or prescription cannabinoids
Cannabinoid-based treatments have been approved as medical treatments for specific indications. They must be prescribed by a licensed healthcare practitioner according to applicable local regulations and are available through pharmacies. In Canada, there are two products authorized as cannabinoid-based pharmacological treatments, nabilone (Cesamet®) and nabiximols (Sativex®), whereas in the USA, nabilone, dronabinol (Marinol®), and Epidiolex® are available. 

Medical cannabis 

Cannabis-based treatments that have not been approved as medical treatments but have been legalized and regulated for patient access.  Medical cannabis is differentiated from nonmedical cannabis by a unique access program and a required medical authorization. Medical cannabis products may be available in many forms such as dried cannabis, cannabis extracts, oil, capsules, edibles, or topical products. 

Cultivars (varieties, strains) 

Distinct cultivars of the cannabis plant, having unique genetic signature and expressing distinct chemical composition. Colloquially referred to as strains. 

Phytocannabinoids 

Cannabinoids that are produced by the cannabis plant, primarily in the female flowers. More than 100 unique cannabinoids have been identified. 

Delta-9-tetrahydrocannabinol (THC)
THC is the primary cannabinoid in almost all strains of cannabis, and almost all therapeutic effects of cannabis can be attributed to THC. THC is the primary psychoactive and intoxicating agent and is responsible for most adverse effects related to cannabis use. This is why dosage and dose titration is so important. 

Cannabidiol (CBD) 

CBD is usually the secondary cannabinoid found in cannabis; however recent research into its anti-epileptic, anxiolytic, and anti-inflammatory properties has encouraged the selective breeding of cannabis cultivars with high concentration of CBD and minimal THC concentration. 

Cannabinol (CBN) 

The degradation molecule of both THC and CBD, CBN is often found in significant concentration in cannabis products that have been stored for several months. The effects of CBN have not been well-studied; however preclinical evidence suggests that it may produce sedating, mild psychoactive, and mild analgesic effects. 

Cannabigerol (CBG) 

The precursor compound, CBG is a non-psychoactive cannabinoid found in higher concentration in immature cannabis plants. In addition, CBG is often found in higher concentrations in hemp plants and other low-THC cultivars. The effects have not been well-studied in humans. 

THC-A, CBD-A, etc. 

Acidic forms of cannabinoids, existing in the natural plant or in “fresh” or “raw” unprocessed prior to decarboxylation via drying or manufacturing such as for oral administration products. 

Terpenes 

Aromatic compounds that exist in unique profiles in different cultivars. May provide some therapeutic benefit and may contribute to the varying effects of different cultivars of cannabis. 

Some of the most common terpenes found in cannabis are D-limonene (commonly found in citrus essential oils), beta-myrcene, linalool (common to lavender), alpha-pinene, and beta caryophyllene (common to black pepper).

Entourage effect 

A proposed theory that cannabinoids and terpenes act synergistically to produce specific pharmacological effects and may contribute to  the tolerability of certain cannabis cultivars. 

Cannabinoid receptors 

The group of receptor proteins that bind with endocannabinoids and phytocannabinoids. The most well-described are the G protein-coupled receptors CB1 and CB2, located in the central and peripheral nervous systems. Additionally, other receptors are known to bind endocannabinoids, often termed orphan cannabinoid receptors. 

Endocannabinoids 

The endogenous cannabinoids produced by the body and active at cannabinoid receptors. The most well-known endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG) though several hundreds have been identified. 

Cannabis Products and Accessories 

Marijuana, Marihuana 

The historical slang term marihuana or marijuana usually refers to dried cannabis of high THC concentration. The term has recently been dropped from legal and regulatory legislation in Canada in favor of the term cannabis; however, the use of the term continues globally and within social discussion. 

Cannabis extracts 

Highly concentrated preparations of cannabis which are produced via a variety of manufacturing techniques, such as cannabinoid and terpenoid supercritical CO2 extraction, and highly flammable solvents such as ethanol, isopropyl  alcohol, butane, or hexane. 

Concentrates (Hashish, Shatter, Dab, Wax)
Slang terms for highly concentrated preparations of cannabis utilizing various methodologies. The potency of concentrates can be up to 90% THC by weight.  Various methods of administration are used to inhale these products, but electronic pen-style vaporizers and glass bongs are common.  

Concentrates have gained popularity among “recreational” cannabis consumers and should not be recommended for medical purposes 

Pipe or Bong 

A pipe is a glass or metal device designed to combust or inhale cannabis smoke. Similarly, a bong is a glass smoking device which combines water with the cannabis smoke and may increase the cannabinoid potency.  These are not recommended for medical purposes. 

Vaporizer 

An electronic device designed to heat dried cannabis or cannabis extracts to specific temperatures allowing for vaporization and required decarboxylation of active ingredients. Importantly, vaporizer temperatures stay well below the temperature of combustion limiting. Some vaporizers for dried cannabis have been recognized as medical devices and may be eligible for insurance coverage. 

Recently, the use of unregulated, illicit cannabis extract vaporizers (also known as electronic cigarettes or vape pens) has produced serious adverse events including lung toxicity and even death. 

According to Dr. Mafer Arboleda, understanding the general information about the cannabis plant and the basic terminology that describes medical cannabis and related uses is key for effective communication with patients and medical professionals. Once the main concepts are familiarized, clinicians are ready to move forward to explore other important areas of understanding such as the pharmacology of cannabinoid-based treatments and practical considerations for its safe use. 

The cannabis plant has a fascinating history and unique, still understudied pharmacology.  There is much discovery to be made to understand further therapeutic potential and relationship with the human body. 

References 

Grinspoon, P. (2018, January 9). Medical marijuana – Harvard Health Blog. Harvard Health Blog; Harvard Medical School. https://www.health.harvard.edu/blog/medical-marijuana-2018011513085 

Arboleda M.F., Prosk E. (2021) Cannabis Terminology. In: Narouze S.N. (eds)

Cannabinoids and Pain. Springer, Cham. https://doi.org/10.1007/978-3-030-69186-8_5