Cannabidiol in Humans The Quest for Therapeutic Targets

Reference: Cannabidiol in Humans. The Quest for Therapeutic Targets
Simon Zhornitsky and Stéphane Potvin

Cannabidiol in Humans

Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients. A systematic search was performed in the electronic databases PubMed and EMBASE using the key word “cannabidiol”. Both monotherapy and combination studies (e.g., CBD + Δ9-THC) were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington’s disease (one study), insomnia (one study), and epilepsy (one study). Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of Δ9-THC. Moreover, some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and/or intensify Δ9-THC-induced effects, whereas others suggest that it may inhibit Δ9-THC-induced effects. Finally, preliminary clinical trials suggest that high-dose oral CBD (150–600 mg/d) may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed.

The cannabis plant has been used by humans for thousands of years in medicine for its sedative/hypnotic, antidepressant, analgesic, anticonvulsant, antiemetic, anti-inflammatory, anti-spasmodic and appetite-stimulating effects [1]. The plant is composed of a complex chemical mixture that includes phytocannabinoids, terpenoids, flavanoids, steroids and enzymes [2]. Phytocannabinoids—the most cannabis-specific of these constituents—bind to receptor sites normally activated by endogenous cannabinoids such as anadamide and 2-arachidonylglycerol (2-AG)..

Cannabidiol in Humans