Therapeutic Effects of Cannabinoids and Their Applications in COVID-19 Treatment

Abstract

Cannabis sativa is one of the first medicinal plants used by humans. Its medical use remains controversial because it is a psychotropic drug whose use has been banned. Recently, however, some countries have approved its use, including for recreational and medical purposes, and have allowed the scientific study of its compounds. Cannabis is characterized by the production of special types of natural products called phytocannabinoids that are synthesized exclusively by this genus. Phytocannabinoids and endocannabinoids are chemically different, but both pharmacologically modulate CB1, CB2, GRP55, GRP119 and TRPV1 receptor activities, involving activities such as memory, sleep, mood, appetite and motor regulation, pain sensation, neuroinflammation, neurogenesis and apoptosis. Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids with greater pharmacological potential, including anti-inflammatory, neuroprotective and anticonvulsant activities. Cannabidiol is showing promising results for the treatment of COVID-19, due to its capability of acting on the unleashed cytokine storm, on the proteins necessary for both virus entry and replication and on the neurological consequences of patients who have been infected by the virus. Here, we summarize the latest knowledge regarding the advantages of using cannabinoids in the treatment of COVID-19.

Keywords: COVID-19; clinical trials; phytocannabinoids; refractory epilepsy; synthetic cannabinoids.

Figure 1

Chemical structure of endocannabinoid derivates from arachidonic acid, including anandamide (AEA), 2–arachidonoyl glycerol (2–AG), 2-arachidonoyl–glycerol (2–AGE), O-arachidonoyl-ethanolamine (virodamine) and N-arachidonoyl-dopamine (NADA).

Figure 2

Biosynthesis and hydrolysis of N–Arachidonoylethanolamine (AEA) pathway. Abbreviations in red mean the enzymes: NAT: N–acyltransferase; sPLA2: soluble phospholipase A2; PLC: phospholipase C; ABHD4: α/β–hydrolase domain 4; GDE1: glycerophosphodiesterase; NAPE–PLD: NAPE–specific phospholipase D; PTPN22: non–receptor protein tyrosine phosphatase 22; FAAH: fatty acid amide hydrolase.

Figure 3

Biosynthesis and hydrolysis of 2–Arachidonoyl ethanolamine (2–AG) and arachidonic acid (AA). Abbreviations in red mean the enzymes: PLC: Phospholipase C–β; DAGL: Diacylglycerol lipase; MAGL: monoacylglycerol lipase.

Figure 4

Chemical structures of the phytocannabinoids Δ9–tetrahydrocannabinol (Δ9-THC), Δ8–THC, cannabinol (CBN) and cannabidiol (CBD).

Figure 5

The CBD functions in SARS-CoV2 infection. Cannabinol could limit the severity of SARS-CoV2 infection by decreasing ACE-2 receptors, cytokine mitigation and lung inflammation and fibrosis through PPARγ receptors.