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Review
. 2022 Apr 25:13:894960.
doi: 10.3389/fphar.2022.894960. eCollection 2022.

Cannabis for Medical Use: Versatile Plant Rather Than a Single Drug

Shiri Procaccia  1 , Gil Moshe Lewitus  1 , Carni Lipson Feder  1 , Anna Shapira  1 , Paula Berman  1 , David Meiri  1
Affiliations
Review

Cannabis for Medical Use: Versatile Plant Rather Than a Single Drug

Shiri Procaccia et al. Front Pharmacol. .

Abstract

Medical Cannabis and its major cannabinoids (-)-trans-Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are gaining momentum for various medical purposes as their therapeutic qualities are becoming better established. However, studies regarding their efficacy are oftentimes inconclusive. This is chiefly because Cannabis is a versatile plant rather than a single drug and its effects do not depend only on the amount of THC and CBD. Hundreds of Cannabis cultivars and hybrids exist worldwide, each with a unique and distinct chemical profile. Most studies focus on THC and CBD, but these are just two of over 140 phytocannabinoids found in the plant in addition to a milieu of terpenoids, flavonoids and other compounds with potential therapeutic activities. Different plants contain a very different array of these metabolites in varying relative ratios, and it is the interplay between these molecules from the plant and the endocannabinoid system in the body that determines the ultimate therapeutic response and associated adverse effects. Here, we discuss how phytocannabinoid profiles differ between plants depending on the chemovar types, review the major factors that affect secondary metabolite accumulation in the plant including the genotype, growth conditions, processing, storage and the delivery route; and highlight how these factors make Cannabis treatment highly complex.

Keywords: cannabis; chemovar; phytocannabinoids; secondary metabolites; terpenoids.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Phytocannabinoids are divided into subclasses according to their structure. Prenylation of olivetolic acid with the isoprenoid geranyl pyrophosphate forms CBGA. Less frequently, instead of olivetolic acid other molecules with different length alkyl side-chain serve as precursors. The acid forms THCA, CBDA and CBCA are synthesized in the Cannabis plant from CBGA. The neutral forms and other subclasses of phytocannabinoids are the result of chemical processes such as decarboxylation, isomerization and others. The shared core of olivetolic acid by the different subclasses is depicted in red. Subclass 11 includes phytocannabinoids identified by mass spectrometry in different Cannabis chemovars, whose structures have not been elucidated yet.
FIGURE 2
FIGURE 2
Minor phytocannabinoids are associated with Type I, Type III and Type IV chemovars. Heatmap presenting the concentration of phytocannabinoids (% weight per weight) divided by chemovars. Type I chemovars defined THCA >20% (n = 13), Type III chemovars defined CBDA >15% (n = 9), Type II defined THCA >4% and CBDA >10% (n = 13), type IV defined CBGA >6% (n = 4). Groups of unique phytocannabinoids are depicted by a surrounding black square.
FIGURE 3
FIGURE 3
Venn diagram of the distribution of particular phytocannabinoids to specific chemovars. Examples of unique phytocannabinoids per chemovar type are shown in the appropriate subgroup.
See this image and copyright information in PMC

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