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

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.

Endocannabinoid System: Chemical Characteristics and Biological Activity

“…Diverse classes of secondary metabolites from different parts of the plant have been identified, with a wide range of applications (nutraceuticals, cosmetics, aromatherapy, and pharmacotherapy) that are beneficial to humans. However, in the past, studies were focused on the two most abundant phytocannabinoids, THC and CBD, thus resulting in greater knowledge about their pharmacological activities and increasing interest in the numerous possibilities of the medicinal actions of the plant [ 109 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ]. CBD has been gaining prominence in pharmacological research since the 1970s.…”

An Individuality of Response to Cannabinoids: Challenges in Safety and Efficacy of Cannabis Products

“…Furthermore, in defining the safe dose of cannabis products, focusing on a specific active compound such as THC or cannabidiol (CBD) is insufficient for predicting the effects. Due to the differential profiles of the 140 other phytocannabinoids, a wide range of effects can be observed [ 8 ]. Such variation leads to challenges in setting health-based guidance values and standardized cannabis units for safety control [ 9 , 10 ].…”

Beyond cannabinoids: Application of NMR-based metabolomics for the assessment of Cannabis sativa L. crop health

“…Since then, several cultures have employed cannabis preparations to treat a variety of ailments ( Russo, 2014 ). Since our understanding of its therapeutic potential is continuously improving, the interest in cannabis as a source of compounds for use in medicinal preparations has increased notably ( Procaccia et al., 2022 ). Furthermore, the non-pharmacological uses of the plant and its derivatives, particularly as a source of fibers and as a recreational drug, are well known.…”

“…These compounds are present mostly as carboxylic acids in the plant, namely Δ 9 -tetrahydrocannabinolic and cannabidiolic acids (THCA and CBDA), and are transformed to the neutral molecules through non-enzymatic decarboxylation ( Flores-Sanchez and Verpoorte, 2008 ). However, the biological effects of C. sativa do not depend only on the levels of THC and CBD ( Procaccia et al., 2022 ). Indeed, nearly 150 phytocannabinoids which can be classified in different structural subclasses have been isolated from this plant ( Hanuš et al., 2016 ), and several of these compounds, sometimes referred to as minor cannabinoids, have pharmacological potential ( Franco et al., 2020 ).…”