British Journal of Clinical Pharmacology: Cannabidiol

Cannabidiol as potential anticancer drug
British Journal of Clinical Pharmacology
Volume 75, Issue 2, pages 303–312, February 2013

Cannabidiol as potential anticancer drug

Volume 75, Issue 2, pages 303–312, February 2013

Medical cannabidiol – is there anything it can’t do?

Abstract

Over the past years, several lines of evidence support an antitumourigenic effect of cannabinoids including Δ9-tetrahydrocannabinol (Δ9-THC), synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of Δ9-THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non-psychoactive cannabinoid compounds with structural affinity for Δ9-THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents…

The endocannabinoid system: a brief overview

The endocannabinoid system (eCB) is a recently discovered signalling system comprising the cannabinoid CB1 and CB2 receptors, their intrinsic lipid ligands, endocannabinoids (eCBs), such as the N-arachidonoylethanolamide (anandamide, AEA) and the 2-arachidonoylglycerol (2-AG), and the associated enzymatic machinery (transporters, biosynthetic and degradative enzymes).

The cannabinoid CB1 and CB2 receptors are both G protein-coupled receptors: CB1 receptors are highly distributed in the central nervous system (CNS), with low to moderate expression in periphery, whereas CB2 receptors are high in the immune system, with much lower and more restricted distribution in the CNS [1, 2].

Endogenous ligands for the cannabinoid receptors were discovered soon after their characterization. The two major known endogenous ligands are anandamide (AEA) and 2-AG [3–6]. Both are arachidonic acid derivatives produced from phospholipid precursors through activity-dependent activation of specific phospholipase enzymes [7]. Later on, a number of other eCB ligands have been discovered, including N-arachidonoyldopamine, N-arachidonoylglycerolether and O-arachidonoylethanolamine…snip

Cannabinoids in the treatment of cancer

Cannabinoids are currently used in cancer patients to palliate wasting, emesis and pain that often accompany cancer. A significant advancement in cannabinoid use in cancer treatment came from the discovery of a potential utility of these compounds for targeting and killing cancer cells. In 1975 Munson et al. [17] demonstrated that the administration of Δ9-THC, Δ8-THC and cannabinol inhibited the growth of Lewis lung adenocarcinoma cells in vitro as well as in vivo after oral administration in mice. The interest in anticarcinogenic properties of cannabinoids was even renewed after the discovery of the eCB system and the cloning of the specific cannabinoid receptors.

Since then, several cannabinoids have been shown to exert anti-proliferative and pro-apoptotic effects in various cancer types (lung, glioma, thyroid, lymphoma, skin, pancreas, uterus, breast, prostate and colorectal carcinoma) both in vitro and in vivo[18–26]. Moreover, other antitumourigenic mechanisms of cannabinoids are currently emerging, showing their ability to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization…snip

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