The Role of Cannabinoids in Allergic Diseases: Collegium Internationale Allergologicum (CIA) Update 2020

Abstract

The human endocannabinoid system (ECS) is a complex signalling network involved in many key physiological processes. The ECS includes the cannabinoid receptors, the endocannabinoid ligands, and the enzymes related to their synthesis and degradation. Other cannabinoids encompass the phytocannabinoids from Cannabis sativa L. (marijuana) and the synthetic cannabinoids. Alterations in the ECS are associated with different diseases, including inflammatory and immune-mediated disorders such as allergy. Allergy is a global health problem of increasing prevalence with high socioeconomic impact. Different studies have convincingly demonstrated that cannabinoids play a role in allergy, but their actual contribution is still controversial. It has been shown that cannabinoids exert anti-inflammatory properties in the airways and the skin of allergic patients. Other studies reported that cannabinoids might exacerbate asthma and atopic dermatitis mainly depending on CB2-mediated signalling pathways. A better understanding of the molecular mechanisms involved in the mode of action of specific cannabinoids and cannabinoid receptors on relevant immune cells under different biological contexts might well contribute to the design of novel strategies for the prevention and treatment of allergic diseases. Future research in this promising emerging field in the context of allergy is warranted for the upcoming years.

Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids

“…2-AG belongs to the endocannabinoid system consisting of endocannabinoid ligands, endocannabinoid receptors, and enzymes related to their synthesis and degradation. While many studies depict the roles of the endocannabinoid system in allergic diseases, their actual contribution remains controversial [ 250 ]. 2-AG binds to and activates GPCRs such as the cannabinoid receptor 1 and 2 (CB 1 , CB 2 ).…”

“…2-AG binds to and activates GPCRs such as the cannabinoid receptor 1 and 2 (CB 1 , CB 2 ). Moreover, 2-AG may be converted to arachidonic acid via the monoacylglycerol lipase (MGL) pathway leading to eicosanoid production [ 250 ]. Human leukocytes were found to differentially express CB 1 and CB 2 receptors as well as MGL [ 251 , 252 , 253 ].…”

“…Similar findings were observed in human eosinophils in vitro, where MGL inhibition prevented the migration of primed eosinophils in response to 2-AG, suggesting potential anti-inflammatory actions of MGL inhibitors in lung inflammation and allergy [ 66 ]. The involvement of the endocannabinoid system in allergic diseases was comprehensively described by Angelina et al in a recent Collegium Internationale Allergologicum update [ 250 ].…”

The Interplay between the Immune and the Endocannabinoid Systems in Cancer

“…Although the detailed mechanisms of cannabinoid-PPAR interactions are not completely elucidated, there is some evidence that PPAR are also involved in immune cell regulation. [ 70 ].…”

“…The enzymes involved in the degradation of ECs are fatty acid-amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) [ 23 , 74 , 75 , 76 , 77 ]. FAAH and MAGL represent possible therapeutic targets for the treatment of several disorders [ 70 ]. In some tissues, ECs can also undergo oxidative catabolism through the lipoxygenase, cyclooxygenase 2 (COX-2), and cytochrome P450 isoenzymes [ 78 ].…”