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.

The Impact of Early Life Exposure to Cannabis: The Role of the Endocannabinoid System

“…Indeed, while the route of administration and variability within and between subjects influence the pharmacokinetics of these compounds, both ∆ 9 -THC and CBD have been detected in the lungs, heart, brain, liver, adipose tissue, and breast milk, and can readily cross the placenta [76]. ∆ 9 -THC is the most potent psychoactive component found in cannabis extracts that causes a state of euphoria (generically referred to as the "high") and possesses therapeutic utility, treating nausea and emesis, appetite, spasticity, pain, and anxiety [77,78]. These effects are largely attributed to agonist activity at CB1 and CB2 receptors.…”

“…CBD is another phytocannabinoid that modulates pain, spasticity, and inflammation, while lacking the psychoactive properties typically seen with ∆ 9 -THC. In fact, CBD is thought to have a protective effect as co-administration of CBD with ∆ 9 -THC has been shown to alleviate the psychotic effects of ∆ 9 -THC by allosterically modulating and indirectly antagonizing CB receptors [77,79]. While CBD can be metabolized into various derivatives of 7-carboxy-CBD, most CBD is excreted in the feces unchanged [80].…”

“…While CBD can be metabolized into various derivatives of 7-carboxy-CBD, most CBD is excreted in the feces unchanged [80]. Due to the medicinal efficacy of cannabis, ∆ 9 -THC and CBD, many synthetic analogues have been synthesized to mimic the benefits of these cannabinoids including WIN-55,212, JWH-018, JWH-122, UR-144, CP55940, ajulemic acid, dronabinol and HU308 [77,81].…”

“…AEA and ∆ 9 -THC are partial agonists with high affinity to CB1/CB2, while 2-AG is a full agonist at both receptors with moderate affinity [81]. Contrastingly, CBD has been proposed to function as an antagonist and has weak CB receptor affinity [77]. Some synthetic cannabinoids were created to be more potent than AEA, 2-AG and ∆ 9 -THC, and possess greater affinity and efficacy at cannabinoid receptors (reviewed in [81]).…”

Pros and Cons of the Cannabinoid System in Cancer: Focus on Hematological Malignancies

“…Despite this, some agonists, such as arachidonyl-2 -chlorethylamide (ACEA) compound, show CB1R high selectivity. In addition, allosteric modulators that bind to different sites other than the ligand orthosteric site affect the stimulus of cannabinoid receptor by either enhancing or reducing its activity [24].…”