Cannabinoids in asthma, allergic diseases and viral infections
The human endogenous cannabinoid system (ECS) is involved in many
physiological processes. It consists of the cannabinoid receptors
(CBRs), the endogenous ligands (anandamide and 2-arachidonoylglycerol)
and the proteins related to their synthesis and
degradation.132 Cannabinoid receptor 1 (CB1) and 2
(CB2) are the main CBRs. CB1 is largely expressed in the central nervous
system but also in peripheral tissues and immune cells. CB2 is mainly
expressed in immune cells but also in other cell types such as
progenitor neurons. The biosynthesis and inactivation of
endocannabinoids involve five main enzymes:
N‑acyl-phosphatidylethanolamine-hydrolysing phospholipase D (NAPE-PLD),sn ‑1‑specific diacylglycerol lipase-α (DGLα), DGLβ, fatty acid
amide hydrolase (FAAH) and monoacylglycerol lipase (MGL). The main
product of endocannabinoids inactivation is the AA (Fig.
1) .133,134 The role of cannabinoids in allergic
diseases is still a bit controversial.135 Sukawaraet al demonstrated that endocannabinoids limited mast cell
maturation and activation in human airway mucosa and skin through
CB1.136,137 Tetrahydrocannabinol (THC) and cannabidiol
(CBD) attenuated airway allergic inflammation, decreased cytokine
production, cell infiltration, mucus secretion and bronchial
hyperresponsiveness in mice.138-140 Similarly, the
synthetic agonist CP55,940 induced lung protection in ovalbumine
(OVA)-induced asthma guinea pig models via CB1 and
CB2.141 In keratinocytes, CB1 prevented
transepithelial water loss and skin inflammation, cell infiltration and
cytokine production in atopic dermatitis mouse
model.142 Anandamide and different CB1 agonists also
accelerated skin barrier recovery and reduced pro-inflammatory cytokine
production and cell recruitment.143,144 Several
cannabinoids have also shown a protective role in allergic contact
dermatitis by reducing inflammatory responses.145-147CB1 activation may also induce bronchodilation in the
airways.141,148 In human bronchial epithelial cells,
the synthetic agonist WIN55212-2 restored the epithelial barrier
disruption induced by RV.149 In addition, WIN55212-2
decreased the immediate anaphylactic reaction in a mouse model of peanut
allergy, and promoted the generation of allergen-specific regulatory T
cells.150 Currently, different studies suggest the
therapeutic potential of cannabinoids in COVID-19
pandemic.151-153 In contrast, Frei et al showed
that CB2 activation enhanced migratory responsiveness of eosinophils in
an OVA-asthma mouse models.154 Accordingly, the lack
of CB2 decreased allergic inflammation in asthma and dermatitis mouse
model.155 This result correlated with increased number
of NK cells and reduced number of ILC2s in the lung of CB2 knockout
mice, demonstrating that NK cells are negative regulators of
ILC2s.156 Interestingly, it has been described that
mRNA expression levels of CB1 are upregulated in tonsils and peripheral
blood of patients with allergic rhinitis, atopic dermatitis, and food
allergy, but the functional relevance remains
unknown.157 These studies suggest that the ECS could
be explored as a potential therapeutic target in the treatment of
asthma, allergic and skin diseases and viral infections.