Effects of Cannabidiol on Innate Immunity: Experimental Evidence and Clinical Relevance

Abstract

Cannabidiol (CBD) is the main non-psychotropic cannabinoid derived from cannabis (Cannabis sativa L., fam. Cannabaceae). CBD has received approval by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of seizures associated with Lennox–Gastaut syndrome or Dravet syndrome. However, CBD also has prominent anti-inflammatory and immunomodulatory effects; evidence exists that it could be beneficial in chronic inflammation, and even in acute inflammatory conditions, such as those due to SARS-CoV-2 infection. In this work, we review available evidence concerning CBD’s effects on the modulation of innate immunity. Despite the lack so far of clinical studies, extensive preclinical evidence in different models, including mice, rats, guinea pigs, and even ex vivo experiments on cells from human healthy subjects, shows that CBD exerts a wide range of inhibitory effects by decreasing cytokine production and tissue infiltration, and acting on a variety of other inflammation-related functions in several innate immune cells. Clinical studies are now warranted to establish the therapeutic role of CBD in diseases with a strong inflammatory component, such as multiple sclerosis and other autoimmune diseases, cancer, asthma, and cardiovascular diseases.

The Polypharmacological Effects of Cannabidiol

“…Anti-inflammatory and immunosuppressive effects of cannabis have been known since 3000 years ago, when it was used as an antipyretic and to treat rheumatism [ 190 ]. Recently, in vitro and in vivo models have suggested that CBD seems to produce these effects by acting directly on the cells and tissues of the immune system [ 32 , 152 ], where CBD acts as an agonist of TRPV1 in vitro activating phagocytosis in microglia [ 45 ] and in vivo decreasing inflammation in both inflammatory bowel disease and allergic contact dermatitis models [ 175 , 176 ]. CBD is an agonist of A 2A R, showing reduction of inflammation in a murine model of acute lung injury and inflammatory response induced for lipopolysaccharide (LPS) [ 174 ].…”

“…Due to the broad spectrum of possible medical applications of CBD, many naturally occurring and synthetic CBD derivatives have been described in the scientific literature and numerous patents for its potential clinical use [ 30 ]. Recently, the FDA approved the use of pure CBD ( Table 1 ) [ 12 , 31 , 32 , 33 ] for the treatment of medically refractory seizures in patients with Dravet syndrome (DS) or Lennox–Gastaut syndrome (LGS), conditions more prevalent in children. There are currently ongoing clinical trials for the use of CBD in other conditions such as autism [ 34 , 35 ], schizophrenia [ 36 ], and other diseases.…”

Perturbation of 3D nuclear architecture, epigenomic aging and dysregulation, and cannabinoid synaptopathy reconfigures conceptualization of cannabinoid pathophysiology: part 2—Metabolome, immunome, synaptome

“…Many other immune actions of cannabinoids are described which have been reviewed ( 143 – 156 ). Both immunosuppressive ( 143 – 145 , 157 , 158 ) and immunostimulatory ( 142 , 159 – 161 ) actions have been described.…”

“…Both immunosuppressive ( 143 – 145 , 157 , 158 ) and immunostimulatory ( 142 , 159 – 161 ) actions have been described. Cannabidiol appears to be mainly immunosuppressive in its actions ( 156 , 162 ). CB1R activation is often immunostimulatory ( 159 – 161 ).…”

Effects of combined cannabidiol (CBD) and hops (Humulus lupulus) terpene extract treatment on RAW 264.7 macrophage viability and inflammatory markers

“…They offer a promising alternative to the use of more aggressive treatments with common corticosteroids, as they modulate various biochemical pathways in the body, including those involved in inflammatory processes [ 4 – 6 ]. Notably, the non-psychotropic phytocannabinoid cannabidiol (CBD) shows promising potential as an alternative treatment option, due to its high abundance in the cannabis plant, its extensive anti-inflammatory and anti-oxidative potency, and little to no side effects observed from either topical or systemic administration [ 7 – 12 ]. Several in vitro and ex vivo studies have demonstrated that CBD possesses anti-inflammatory properties.…”