Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer

Abstract

Cannabis has been used to relieve the symptoms of disease for thousands of years. However, social and political biases have limited effective interrogation of the potential benefits of cannabis and polarised public opinion. Further, the medicinal and clinical utility of cannabis is limited by the psychotropic side effects of ∆9-tetrahydrocannabinol (∆9-THC). Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-related nausea and vomiting, respectively. An increasing number of preclinical studies have established that ∆9-THC can inhibit the growth and proliferation of cancerous cells through the modulation of cannabinoid receptors (CB1R and CB2R), but clinical confirmation remains lacking. In parallel, the anti-cancer properties of non-THC cannabinoids, such as cannabidiol (CBD), are linked to the modulation of non-CB1R/CB2R G-protein-coupled receptors, neurotransmitter receptors, and ligand-regulated transcription factors, which together modulate oncogenic signalling and redox homeostasis. Additional evidence has also demonstrated the anti-inflammatory properties of cannabinoids, and this may prove relevant in the context of peritumoural oedema and the tumour immune microenvironment. This review aims to document the emerging mechanisms of anti-cancer actions of non-THC cannabinoids.

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…Inglet et al [133] recently comprehensively outlined clinical data supporting the use of cannabis-based treatments in a variety of disease states, including cancer. Afrin et al [27] also presented completed, ongoing, and recruiting clinical trials looking at the effects of cannabis-based treatment in cancer patients. Completed clinical trials that incorporated THC as treatment for various cancers are presented below.…”

“…To date, there are many studies surrounding the anti-cancer potential of cannabidiol. Two recent reviews by Afrin et al and Kis et al [27,136] thoroughly highlighted research studies investigating the anti-cancer effects of cannabidiol. Treatment with CBD exhibited a multitude of beneficial anti-cancer effects in lung, breast, colon, prostate, melanoma, leukemia, cervical, brain, neuroblastoma and multiple myeloma cancer cells (Reviewed in [27,136]), and we highlight these studies here.…”

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

“…The interest associated with cannabinoids administration is related to their palliative effects useful for the treatment of cancer pain, but also for their activity as anticancer compounds able to induce inhibition of cancer cell growth and increasing cancer cell death. CBD anticancer effects, recently reviewed, were investigated in in vitro and in vivo models of glioma, leukaemia, breast, lung, thyroid, colon carcinoma, myeloma, and melanoma [ 25 ]. CBD activities are mediated through the binding to different receptors (CB1, CB2, and Gpr55 receptors), and some members of TRP channels family (as TRPV1-2-3-4, TRPM8 and TRPA1), but also by a receptor-independent mechanism [ 38 , 39 ].…”

“…Advantages of using cannabinoids in cancer therapy have been evaluated in in vitro and in vivo models of several human cancers. Their potential use for cancer in current clinical trials has been recently reviewed [ 25 ]. Indeed, cannabinoids can reduce cancer cell viability, proliferation, metastasis, and they induce cancer cell death in human glioblastoma multiforme, multiple myeloma, colorectal cancer, endometrial cancer, prostate carcinoma, and melanoma [ 26 , 27 , 28 , 29 ].…”

“…Similar findings were shown in a study with the CB1 ligand SR141716 combined with GEM, where was evidenced a reduced tumor growth in treated mice with respect to control and single agent treated mice [ 34 ]. As to O 2 /O 3 , CBD exerts a synergistic activity with different chemotherapeutic drugs [ 25 , 26 ]. So, the aim of this research was to investigate, for the first time, the anticancer effect of CBD and O 2 /O 3 , alone and in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, by examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death.…”