Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses

Abstract

For thousands of years, Cannabis sativa has been utilized as a medicine and for recreational and spiritual purposes. Phytocannabinoids are a family of compounds that are found in the cannabis plant, which is known for its psychotogenic and euphoric effects; the main psychotropic constituent of cannabis is Δ9-tetrahydrocannabinol (Δ9-THC). The pharmacological effects of cannabinoids are a result of interactions between those compounds and cannabinoid receptors, CB1 and CB2, located in many parts of the human body. Cannabis is used as a therapeutic agent for treating pain and emesis. Some cannabinoids are clinically applied for treating chronic pain, particularly cancer and multiple sclerosis-associated pain, for appetite stimulation and anti-emesis in HIV/AIDS and cancer patients, and for spasticity treatment in multiple sclerosis and epilepsy patients. Medical cannabis varies from recreational cannabis in the chemical content of THC and cannabidiol (CBD), modes of administration, and safety. Despite the therapeutic effects of cannabis, exposure to high concentrations of THC, the main compound that is responsible for most of the intoxicating effects experienced by users, could lead to psychological events and adverse effects that affect almost all body systems, such as neurological (dizziness, drowsiness, seizures, coma, and others), ophthalmological (mydriasis and conjunctival hyperemia), cardiovascular (tachycardia and arterial hypertension), and gastrointestinal (nausea, vomiting, and thirst), mainly associated with recreational use. Cannabis toxicity in children is more concerning and can cause serious adverse effects such as acute neurological symptoms (stupor), lethargy, seizures, and even coma. More countries are legalizing the commercial production and sale of cannabis for medicinal use, and some for recreational use as well. Liberalization of cannabis laws has led to increased incidence of toxicity, hyperemesis syndrome, lung disease cardiovascular disease, reduced fertility, tolerance, and dependence with chronic prolonged use. This review focuses on the potential therapeutic effects of cannabis and cannabinoids, as well as the acute and chronic toxic effects of cannabis use on various body systems.

Keywords: Cannabis sativa; abuse; cannabinoid receptors; cannabinoids; endocannabinoids; hemp; marijuana; therapeutics; toxicity; Δ-9-tetrahydrocannabinol (THC).

Figure 1

Chemical structures of Δ-9-tetrahydrocannabinol (THC, (1)), cannabidiol (2), Δ9- cannabinol (3), cannabigerol (4), cannabichromen (5) tetrahydrocannabinol-4-oic acid (THCA, (6)), anandamide (AEA, (7)) 2-arachidonoylglycerol (2-AG, (8)), N-arachidonoyldopamine (NADA, (9)), 2-arachidonoyl glyceryl ether (2-AGE, (10)), O-arachidonoylethanolamine (11), oleic acid amide (OA, (12)), Δ9-tetrahydrocannabiphorol (Δ9-THCP, (13)) and cannabidiphorol (CBDP, (14)).

Figure 2

The biosynthesis pathway of tetrahydrocannabinol (THC) and cannabidiol (CBD) from the coupling of olivetolic acid and geranyl diphosphate.

Figure 3

The endocannabinoid system; (a) distribution of endocannabinoids receptors through human body; (b) binding of endogenous anandamide (AEA), 2-arachidonoylsn-glycerol (2-AG), and exogenous Δ⁹-tetrahydrocannabinol (Δ⁹-THC) with cannabinoid receptors type 1 (CB1) and type 2 (CB2).

Figure 4

Chemical structures of some synthetic agonist and antagonist cannabinoid; (−)-11-hydroxy-D8--THC dimethyl heptyl (HU-210) (15), CP55940 (16), R-(+)-WIN55212 (17), SR141716A (18), SR144528 (19), arachidonyl-2′-chlorethylamide (ACEA) (20), and allosteric modulators; Org29647 (21), Org27759 (22), and Org27569 (23), GAT211 (24), ZCZ011 (25), RTI-371 (26) and PSNCBAM-1 (27), cannabidiol-dimethylheptyl (CBD-DMH /or HU-219 (28)) and compound C2 (29).

Figure 5

Chemical structures of the analgesic cannabinoids; dronabinol (30), nabilone (31), ajulemic acid (AJA (32)), HU-308 (33), AM1241 (34), JWH-133 (35), GW405833 (36) and rimonabant (37) a CB1 receptor inverse agonist that reduce appetite.