Cannabis sativa (cannabis) has been used for medicinal, spiritual, and nonmedicinal purposes since antiquity, mainly as dried plant material.1, 2, 3 With legalization and regulation in Canada, several US states, and other jurisdictions, smoked cannabis flowers are one of many different products and modes of administration used among consumers. In addition to flowers, various cannabis extracts, oils, and high-potency concentrates are not only smoked but vaporized, encapsulated, or cooked and consumed, or administered intranasally and topically (Table 1). The diversity of products has outpaced their scientific evaluation for risk. As the complexity and variability of cannabis products impacts safety, the objective of this review is to summarize available data about the phytochemistry and potential for pharmacokinetic interactions of different cannabis products with health products (ie, biologics, drugs, nonprescription products, and natural health products). Because, when combined with other bioactive substances, cannabis products may present risk of interaction, the reviewed data are pertinent for both medical and nonmedical consumers. For more detailed information, the reader is directed to the Health Canada information document) and other publications.1, 2, 4, 5, 6, 7, 8
Cannabis Chemistry
Most cannabis products may contain several hundred substances among 18 different chemical classes including terpenes, flavonoids, and alkaloids, in addition to more than 100 reported cannabinoids, which are the most characteristic compounds of cannabis.2, 3, 8 Pyrolysis can produce many more substances, many of which have not been characterized chemically and pharmacologically.3, 8 As with other botanical products, they can be characterized with a few marker substances, but the large number of compounds and the nascency of the cannabis industry has led to very few products being properly standardized. For example, the presence and relative amounts of the various substances may differ among cannabis varieties, lots, extracts, smoke, and vapor.
Phytocannabinoids (as opposed to endocannabinoids or synthetic cannabinoids) have been categorized into several classes.9 ∆9–tetrahydrocannabinol (THC) and cannabidiol (CBD) are generally the most abundant, well-studied, sought after by consumers, and, together with their acid forms (THCA and CBDA), the only ones subject to regulations under the Cannabis Act. Cannabinoids are present in the plant primarily as carboxylic acids that undergo decarboxylation and transformation to their neutral form when heated above 120°C (eg, smoking, vaping, baking). The rate of decarboxylation is temperature-dependent, occurring slowly at 98°C and increasing up to 200°C, where the reaction occurs in seconds. Other cannabinoids of interest are: cannabinol (CBN), cannabichromene, cannabigerol, tetrahydrocannabivarin, cannabidivarin, and cannabichromevarin.
The chemical composition of cannabis is largely determined by plant genetics, but is also affected by cultivation, harvesting, drying, and other manufacturing factors. Accordingly, the substance profile of any one product will likely differ qualitatively and quantitatively from the next.
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-Brian C. Foster, PhDa, Hanan Abramovici, PhDb, Cory S. Harris, PhDc
This article originally appeared in the November 2019 issue of The American Journal of Medicine.
