Medical Cannabis: A guide to the clinical and legal landscapes

Botanical or synthetic? It is important to distinguish between synthetic and plant-based cannabinoids, for you and your patients' benefit. Pharmaceutical (synthetic) THC is just that: THC alone. Whole-plant Cannabis, on the other hand, has hundreds of additional chemicals—most notably, phytocannabinoids and terpenoids. Data on the mechanisms of action and interactions of these additional chemicals are limited.

Although clinical trials have been undertaken with synthetic cannabinoids, there is increasing understanding and interest in the medical community of whole-plant Cannabis as a distinct entity. For example, nabiximols is a novel development in plant-based Cannabis products. Available as an oromucosal spray, a dose provides THC and CBD at 2.7 mg/100 mcL. Nabiximols is not approved by the US Food and Drug Administration (FDA) but is widely used in Canada and Europe.

^{PHOTO: ANTHONY RODRIGUEZ 2019; PHOTO MANIPULATION: JOHN DENAPOLI}

A third class of Cannabis comprises nonregulated synthetic cannabinoids that have no medically recognized benefit. They are solely a drug of abuse; common names include “K2” and “Spice.” These cannabinoids are outside of the scope of our discussion, but patients and providers should be aware of these cannabinoids because they are street-available. Unsuspecting patients might not know the difference between abusive and therapeutic formulations.⁸

Delivery and strength. Common forms of plant-based Cannabis include leaf that is smoked or vaporized, oral tincture, pill, and oil concentrate that can be vaporized. All forms come in a range of THC:CBD ratios—from as high as 90% THC content to 0% THC and all CBD-based content. Patients who are naïve to Cannabis might be concerned about formulations with a high THC concentration because of the psychoactive effects of this substance. Given the minimal CNS activity of CBD, a tolerable therapeutic starting point often is a THC:CBD ratio of 1:1, which contains a lower percentage of THC.⁴

Physiologic effects. THC is a partial agonist of CB₁ and CB₂ receptors; CBD functions as an antagonist at both receptors. The primary effects of THC result from activation of CB₁ receptors, which exist in various areas of the cerebrum and cerebellum, as well as in the spinal cord.⁷ THC exerts its psychotropic effects at CB₁ sites in the central nervous system; CBD can antagonize these THC effects at CB₁ receptors. CBD also has anti-inflammatory and other effects that are mediated through peripherally distributed CB₂ receptors.⁹

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