The Science

Background

MEDICAL CANNABIS OVERVIEW

For the last two decades, the number of clinical studies providing evidence demonstrating the therapeutic benefits of cannabis have been increasing. Cannabis-derived medicine brings renewed hope to patients suffering with diseases such as chronic neuropathic pain, cancer, epilepsy, chronic obstructive pulmonary disease (COPD), acquired immune deficiency syndrome (AIDS) and diabetes(3). Furthermore, with the current opioid crisis affecting North America, medical cannabis has been a promising alternative to opioid pain medications(1). Specifically, in the USA in 2017, the hospitalization rate for opioid painkiller dependence/abuse and for opioid overdoses declined on average by 23% and 13% respectively in states where marijuana was permitted for medicinal purposes(2).

Due to emerging research and anecdotal reports, we believe that cannabis therapies are the future of medicine. As such, it is imperative that we promote access to education and awareness on the results of such research.

THE ENDOCANNABINOID SYSTEM

The endocannabinoid system is a signaling pathway that occupies the central nervous system (CNS; brain and spinal cord), peripheral nervous system (PNS) and immune pathways (3, 4). This network is comprised of two major receptors: cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). The binding of cannabinoids to these receptors affect the release of neurotransmitters and cytokine signalling molecules, causing a cascade that influences a number of physiological processes such as immune response, pain sensation, cardiovascular function, bone development, digestion, metabolism, wake/sleep cycles, learning, pain response, and regulation of stress and appetite (3-5).

Cannabinoid ligands are categorized into three groups based on their origin:
1. Endocannabinoids are produced endogenously within the human body and include compounds such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG).

2. Phyto-cannabinoids are produced in the vegetative matter of plants, specifically cannabis and hemp, and include two of the most widely studied cannabinoids THC and CBD.

3. Synthetic cannabinoids are developed chemically within a laboratory setting to mimic those naturally created (5, 6).

Medical and Therapeutic Benefits

Δ9- TETRAHYDROCANNABINOL

THC is one of the primary cannabinoids found in the cannabis plant and is largely responsible for the psychoactive effects brought on from cannabis use (3, 20, 21). Over the years, based on anecdotal and scientific evidence, THC has demonstrated its potential therapeutic benefit toward a number of conditions and symptoms including nausea, vomiting, insomnia, pain, muscle spasticity, tremors, and bronchospasm often brought on by a range of medical conditions (Table 1) (3, 20-23). Emerging research indicates a high level of therapeutic potential for a variety of health concerns, in some cases even at doses substantially lower than those required to feel the psychoactive effects of THC (24). For example, evidence at lab-scale has confirmed that THC and its derivatives might be capable of reducing tumor cell growth (23), as well as symptoms induced by cancers (3, 21, 25). In conjugation with other cannabinoids, THC might be therapeutic against a number of neurological disorders, including multiple sclerosis (MS)(3, 21, 26, 27), Huntington’s disease, Parkinson’s disease (28), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (29), as well as anxiety, stress, and depression (3, 21, 25).

CANNABIDIOL

CBD is another abundant cannabinoid found in cannabis. Unlike THC, CBD does not have the same psychoactive effect. Research is beginning to demonstrate that CBD possesses therapeutic effects via blockage of neurotransmitter reuptake and through its ability to bind several other targets, including serotonin receptors(4, 6, 12). CBD has shown great promise in patients suffering from epilepsy by significantly reducing the frequency of re-occurring seizures (3, 22, 30), as well as several other conditions and related symptoms (see Table 1). There is also evidence to suggest that CBD may help with diabetes (31), varying symptoms of cancer (31), mood disorders including post-traumatic stress disorder (PTSD), attention deficit disorder (ADD), obsessive-compulsive disorder (OCD) (12, 22), and inflammatory diseases such as arthritis and inflammatory bowel disease (IBS) (3, 32-35). CBD may also help with weight management and promote cessation of addictions to smoking (tobacco cigarettes) (31, 36-38).Due to its lack of psychoactive stimulus, CBD is often a desirable choice for many individuals seeking cannabinoid therapies.

Table 1: POTENTIAL THERAPEUTIC USES OF CANNABINOIDS AND THEIR SPECIFIC TARGETED SYMPTOMS, as suggested based on information collected via clinical trials(1), pre-clinical trials(2), in vitro assays(3), or anecdotal reports(4).

It is important to note that the medical benefits of cannabinoids are not limited to the information displayed in this chart. The endocannabinoid system has been shown to affect all regions of the human body and as such is thought to be involved in other physiological process unrelated to the nervous system. Other potential targets of cannabinoid therapeutics include liver disease (39), pancreatic disease(40), obesity(36), and osteoporosis(41). In addition, some research presented in this table is not yet conclusive and/or are among preliminary findings that have yet to be confirmed by further investigation.

Pharmacology and Toxicology

TOXICOLOGY OF CANNABIS

Cannabinoids have demonstrated a promising safety profile as both THC and CBD demonstrate low toxicity both in short and long term use. To date, there has been zero evidence to support a death caused exclusively from a cannabis overdose(42).

Currently there may lack applicability of available research regarding chronic effects of cannabis use. Although recreational use of cannabis is done primarily one via inhalation, the majority of clinical studies that investigate medical cannabis are done through administration via means other than smoking (ex. capsules, sprays). With this, it is estimated that the lethal dose of THC when administered intravenously is 30 mg/kg of body weight (3). While research is working toward elucidating the effects of long-term cannabis use in humans, it has been demonstrated to be relatively well tolerated in animals without serious deterioration in general health. Some mild effects, however, include increased heart rate, reddened eyes, a dry mouth, and psychoactive effects including mild euphoria, enhanced sensory perception, fatigue, dysphonia and anxiety(3).

Smoking cannabis during pregnancy is linked to lower birth weight in the offspring; the relationship between smoking cannabis during pregnancy and other pregnancy and childhood outcomes is unclear(42). There have been several studies on the effect of cannabis use on hepatitis C-related liver fibrosis, but the results have been mixed(42). While acute exposure to cannabis results in increased heart rate, chronic exposure is associated with bradycardia and hypotension, cannabis use is not associated with lung, head and neck cancers; but is associated with testicular cancer(42, 43). Adverse neuropsychological effects (learning, memory) has also been associated with long-term and early onset cannabis use(42, 43).

The potential toxic effects of CBD specifically have been extensively reviewed(44) with a recent update of the literature (44, 45). The following are some of the relevant findings to date from in vitro and animal studies: