The role of cannabinoids in the treatment of cancer

Abstract

The aim of this review article is to summarize current knowledge about the role of cannabinoids and cannabinoid receptors in tumor disease modulation and to evaluate comprehensively the use of cannabinoids in cancer patients. METHOD: According to the PRISMA protocol, we have included data from a total of 105 articles. RESULTS: Cannabinoids affect cancer progression by three mechanisms. The most important mechanism is the stimulation of autophagy and affecting the signaling pathways leading to apoptosis. The most important mechanism of this process is the accumulation of ceramide. Cannabinoids also stimulate apoptosis by mechanisms independent of autophagy. Other mechanisms by which cannabinoids affect tumor growth are inhibition of tumor angiogenesis, invasiveness, metastasis, and the modulation of the anti-tumor immune response. CONCLUSION: In addition to the symptomatic therapy of cancer patients, the antitumor effects of cannabinoids (whether in monotherapy or in combination with other cancer therapies) have promising potential in the treatment of cancer patients. More clinical trials are needed to demonstrate the antitumor effect of cannabinoids (Tab. 1, Fig. 1, Ref. 167).

Cannabinoids Inhibited Pancreatic Cancer via P-21 Activated Kinase 1 Mediated Pathway

“…Cannabinoids act through different types of receptors including cannabinoid receptors 1&2 (CB1 and CB2) and another G-protein coupled receptor, GPR55 [13,14]. It is recognised that THC binds to CB1 and CB2 while CBD acts as an antagonist of GPR55, which cause inhibition of ERK-and AKT-dependent pathways to promote apoptosis and to suppress proliferation of cancer cells [16,17].…”

“…Cannabinoids appear in part to exhibit their anti-cancer effects through modulation of tumour immune responses. Both CBD and THC have been reported to cause changes in T helper cell profiles leading to suppression of cytotoxic T cell function [13,16]. The anti-inflammation effects of cannabinoids contribute to the immunosuppressive tumour microenvironment on one hand, but can also prevent carcinogenesis by suppressing chronic inflammation [20,21] on the other hand.…”

“…The anti-inflammation effects of cannabinoids contribute to the immunosuppressive tumour microenvironment on one hand, but can also prevent carcinogenesis by suppressing chronic inflammation [20,21] on the other hand. The immunosuppressive effects of cannabinoids are mainly mediated by CB2 receptors which are extensively expressed in immune cells [13]. However, cannabinoids can also elicit anti-tumour immune responses via different mechanisms.…”

“…THC suppressed PC growth via cannabinoid receptor 2 (CB2) [11] while CBD inhibited PC growth synergistically with gemcitabine through antagonizing the G protein-coupled receptor GPR55 [12]. The mechanism(s) involved in the anti-cancer effects of cannabinoids include direct inhibition on cancer cells and through modulation of tumour immune response [13,14]. Depending on the components and dosages of cannabinoids used and types of receptors activated, cannabinoids execute stimulation or inhibition of anti-tumour immunity [13,14].…”

“…The mechanism(s) involved in the anti-cancer effects of cannabinoids include direct inhibition on cancer cells and through modulation of tumour immune response [13,14]. Depending on the components and dosages of cannabinoids used and types of receptors activated, cannabinoids execute stimulation or inhibition of anti-tumour immunity [13,14]. However, the role of cannabinoids in regulation of PD-L1 (a key immune checkpoint molecule that negatively regulate T cell activation via a distinct mechanism) expression by cancer cells has not been clearly investigated.…”