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Cannabinoids in SCI

What is Cannabis

Cannabis is a term that refers to the products of cannabis (hemp) plants, a group of plants from central Asia that are now cultivated around the world. Cannabis sativa, Cannabis indica, and Cannabis ruderalis are three well known types of cannabis, but many strains or varieties exist, including pure and hybrid types. Common preparations of cannabis include marijuana, which is the dried leaves and flowering tops of the plant, and hashish, which is its condensed resin. Cannabis has been used for thousands of years as a medicine and as a recreational drug (Atakan 2012).

Cannabis is a controlled substance in most regions of the world because of its psychoactive effects (Habibi et al. 2018). In some regions, cannabis is approved for medical or spiritual uses only. Dried cannabis and oil were made legal in Canada for recreational purposes in October 2018 (Cannabis Act 2018); and edibles and concentrates (e.g., foods, oils, tinctures) were made legal and available through authorized vendors in October 2019.

How Does Cannabis Work?

Cannabis contains cannabinoids, which are agents that act on the endocannabinoid system; an ancient, evolutionary conserved system that regulates our bodies in many ways, most of them still poorly understood (Rodriguez et al. 2005). Cannabinoids occur naturally in cannabis plants (phytocannabinoids) but can also be synthesized in a lab (synthetic cannabinoids). Synthetic cannabis must be approved by Health Canada (or other governing agency) and prescribed by a physician to ensure quality control (Health Canada 2018). For example, cannabis grown through licensed vendors is regulated in Canada to ensure safe agricultural practices, and cannabinoid concentrations (Health Canada 2016).

There are more than 60 cannabinoids present in cannabis. Commonly known as THC, Delta-9-tetrahydrocannabinol is possibly the most well-known, and is responsible for many of the psychoactive effects, such as creating a “high” or sense of euphoria. Cannabidiol (CBD) is a primary non-psychoactive cannabinoid that plays an important role in modulating the psychoactive effects of THC. The mechanism of action of CBD is not completely clear, but it seems that CBD has similar effects to THC in some domains (e.g., potential antiemetic, anti-inflammatory, and immunomodulatory properties) and opposite effects in others (e.g., potential antipsychotic and sedating properties: Atakan 2012). Most of these effects are dependent on dose, and the ratio of THC to CBD. High THC to low CBD ratio products tend to have a stronger psychoactive effect in comparison to those with more balanced ratios (i.e., 1:1: Atakan 2012). However, there is a tipping point, where the psychoactive effects of THC are enhanced in higher absolute CBD doses (Atakan 2012).

Modes of Administration

Cannabis may be inhaled, ingested, or (less commonly) applied topically, rectally, or intravenously. The risks associated with smoking cannabis are like those for smoking tobacco (Health Canada 2018). Smoking with a vaporizer distributes fewer toxic substances to the lungs, but is associated with the risk of vaping-associated pulmonary injury (Werner et al. 2020). The additive Vitamin E acetate is strongly associated with vape injury, though there may be contribution of other chemicals (Werner et al. 2020). The issue with edibles, oils, concentrates, and drinks is that they have varying doses of THC and if not regulated, may contain toxic by-products such as mold, bacteria, pesticides and traces of heavy metals (McPartland 2017). This risk is thought to be significantly lower in products from governmental sources, due to stringent quality control measures. Cannabinoids are usually taken through inhalation or orally; other routes of administration such as rectally, sublingual administration, transdermal administration, eye drops and aerosols are rarely studied and of little relevance (Bridgeman and Abazia 2017). All routes of administration, such as orally, rectally, and parenterally, are free of the risk of chronic inflammatory disease and upper respiratory cancer. Topically, THC is not well absorbed through the skin, thus the time of onset and duration of action are unknown. There are some reports of rash and itching when the skin comes into contact with cannabis products (Manini et al. 2015).

The cannabinoid type, administration route, and concentration are separate factors that together account for the effects it has on the body. Inhaling cannabis makes it act faster than ingesting it, but the duration of effect is shorter. There is no standard cannabis dosing regimen for people with SCI. Experienced users who use cannabis for medical purposes reported using 1-3 g/day (Health Canada 2018). Generally, products containing only THC tend to have a stronger psychoactive effect than products containing THC and CBD in equal concentrations. Oil containing only CBD has no psychoactive effects. Products containing only CBD are taken for a range of ailments, but there is limited safety and efficacy data and no research in SCI. People who have never used cannabis tend to experience more side effects and are advised to start with low doses and select a high CBD to relatively low THC concentration product (Health Canada 2018).

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