"The Two Sides of the Same Coin"-Medical Cannabis, Cannabinoids and Immunity: Pros and Cons Explained

Abstract

Cannabis, as a natural medicinal remedy, has long been used for palliative treatment to alleviate the side effects caused by diseases. Cannabis-based products isolated from plant extracts exhibit potent immunoregulatory properties, reducing chronic inflammatory processes and providing much needed pain relief. They are a proven effective solution for treatment-based side effects, easing the resulting symptoms of the disease. However, we discuss the fact that cannabis use may promote the progression of a range of malignancies, interfere with anti-cancer immunotherapy, or increase susceptibility to viral infections and transmission. Most cannabis preparations or isolated active components cause an overall potent immunosuppressive impact among users, posing a considerable hazard to patients with suppressed or compromised immune systems. In this review, current knowledge and perceptions of cannabis or cannabinoids and their impact on various immune-system components will be discussed as the "two sides of the same coin" or "double-edged sword", referring to something that can have both favorable and unfavorable consequences. We propose that much is still unknown about adverse reactions to its use, and its integration with medical treatment should be conducted cautiously with consideration of the individual patient, effector cells, microenvironment, and the immune system.

Keywords: endocannabinoids; medical cannabis; phytocannabinoids.

Figure 2

Cannabinoids regulate immune responses. Schematic diagram of cannabis immuno-modulation properties on different effector cells of the immune system. The arrows in the chart above represent the adjacent cellular process’s increase (up arrow) and decrease (down arrow). Cannabis consumption expressed above includes all forms of cannabis-based products (smoking, ingestion, or the direct use of THC and CBD). For specific details on each component and its effects, refer to the review’s specific immune cell type section. See Table 1 for a detailed summary of the effects of particular cannabinoids on specific immune cells.

Figure 1

A schematic representation of the main components of the endocannabinoid system. Receptors, endogenous cannabinoids, and cannabis-based components. THC, tetrahydrocannabinol; CBD, cannabidiol; 2-AG, 2-arachidonoylglycerol; O-AEA, virodhamine; AEA, anandamide; ARA-S, N-arachidonoyl serine; 2-AGE, 2-arachidonoyl glycerol ether; NADA, N-arachidonoyl dopamine; TRPV2, transient receptor potential cation channel subfamily V member 2; CB1, cannabinoid receptor 1; CB2, cannabinoid receptor 2; GPR55, G protein-coupled receptor 55; TRPV1, transient receptor potential cation channel subfamily V member 1; TRPM8, transient receptor potential cation channel melastatin 8; PPAR-α, peroxisome proliferator-activated receptor-alpha; PPAR-γ, peroxisome proliferator-activated receptor-gamma.