Cannabinoids, Phenolics, Terpenes and Alkaloids of Cannabis

Mohamed M. Radwan, Suman Chandra, Shahbaz Gul and Mahmoud A. ElSohly





Molecules, 2021, 26, 2774.

Doi : 10.3390/molecules26092774

 

Abstract :

Cannabis sativa is one of the oldest medicinal plants in the world. It was introduced
into western medicine during the early 19th century. It contains a complex mixture of secondary metabolites, including cannabinoids and non-cannabinoid-type constituents. More than 500 compounds have been reported from C. sativa, of which 125 cannabinoids have been isolated and/or identified as cannabinoids. Cannabinoids are C21 terpeno phenolic compounds specific to Cannabis.

The non-cannabinoid constituents include: non-cannabinoid phenols, flavonoids, terpenes, alkaloids and others. This review discusses the chemistry of the cannabinoids and major non-cannabinoid constituents (terpenes, non-cannabinoid phenolics, and alkaloids) with special emphasis on their chemical structures, methods of isolation, and identification.

Keywords : Cannabis sativa; cannabinoids; non-cannabinoid phenols; flavonoids; terpenes; alkaloids

 

1. Introduction

Cannabis sativa L. belongs to the plant family Cannabaceae, which only has one genus
(Cannabis) with only one highly variable species, C. sativa. This is one of the oldest plants
grown for food, fiber, and medicine. It grows in all habitats, ranging from sea level to
temperate to alpine foothills. The plant originated in Western Asia and introduced to
western medicine during the early 19th century. Cannabis has a long history of being used as a medicine to treat a variety of ailments, including asthma, epilepsy, fatigue, glaucoma, insomnia, nausea, pain, and rheumatism [1].

Cannabis is primarily a dioecious plant (male and female flowers occur on individual plants); it is only occasionally found as a hermaphrodite (male and female flowers on the same plant). It flowers under a short photoperiod (below 12 h of light) and continues growing vegetatively during the longer photoperiod days.

The plant is a chemically complex species, due to its numerous natural constituents [2]. Cannabinoids, a specific chemical class found in cannabis, are produced in the glandular trichomes of the plant. Among the cannabinoid constituents of cannabis, D9 tetrahydrocannabinol (D9-THC), which is naturally present in the form of an acid (D9 tetrahydrocannabinolic acid, D9-THCA), is the main psychoactive constituent of the plant. Decarboxylation of the acid with age or heat is required to formthe pharmacologically active D9-tetrahydrocannabinol [3].

Cannabidiol (CBD), another cannabinoid of current interest, is reported to be active as an
antiepileptic agent, particularly for the treatment of intractable pediatric epilepsy [4,5].
Other than D9-THC and CBD, tetrahydrocannabivarin (THCV), cannabinol (CBN),
cannabigerol (CBG), and cannabichromene (CBC) are four other major cannabinoids also
identified in C. sativa. Modern studies report that the pharmacological effects of phytocannabinoidsresult from their ability to interact with cannabinoid receptors and/or withother kinds of pharmacological targets, including non-cannabinoid receptors [6].

Thus far, more than 500 constituents have been reported from Cannabis, out of which 125 are classified as cannabinoids. The non-cannabinoid constituents include non–cannabinoid phenols, flavonoids, terpenes, alkaloids and others.

The present review discusses the chemistry of all identified major Cannabis constituents including cannabinoid and non-cannabinoid constituents (non–cannabinoid phenols, flavonoids, terpenes, and alkaloids), with special emphasis on the chemical structures, methods of isolation, and identification. This review also updated the chemistry of 125 cannabinoids, 42 phenolics, 34 flavonoids, 120 terpenes and 2 alkaloids. The last review on cannabis chemistry was published by our group in 2017 as a chapter book which focused on the new constituents reported between 2005 and 2017 only but, in this review, we provided a chemical account on the chemistry of major constituents (323 compounds) of cannabis from 1940 up to now along with their structures. For the reader, this review should provide almost all the information of cannabinoids and non cannabinoids, their methods of isolation, identification and structures in one place. In addition, these 323 compounds include 12 new compounds (five cannabinoids, one cannabispiran, three flavonoids, and three terpenes). The inclusion of all the 323 chemical structures along with all other details makes this review unique.

2. Cannabinoids: (125 Compounds)

Cannabinoids are a group of compounds with a characteristic C21 terpenophenolic backbone. This nomenclature can be applied to parent cannabinoids, cannabinoid derivatives, and transformation products. These cannabinoids can be further classified into 11 cannabinoid sub-classes, namely; cannabichromene (CBC), cannabidiol (CBD), cannabielsoin (CBE), cannabigerol (CBG), cannabicyclol (CBL), cannabinol (CBN), cannabinodiol (CBND), cannabitriol (CBT), (-)-D8-trans-tetrahydrocannabinol (D8 THC), (-)-D9-transtetrahydrocannabinol (D9-THC), and miscellaneous-type cannabinoids.

(…)

molecules-26-02774