Synthetic cannabinoids WIN55,212-2 and JWH133 were also tested in glioblastoma cells expressing high levels of CB2 receptors by Ellert-Miklaszewska et al. in their research article. These authors used five different glioma cell lines and patients-derived cells that were highly resistant to standard chemotherapy due to a lack of tumour suppressor p53 and/or PTEN. Interestingly, the observed cannabinoid-induced autophagy and apoptotic cell death were enhanced bythe inactivation of specific autophagy genes, suggesting cannabinoid use as a potential new therapeutic strategy for glioblastoma . The latest tumour is the topic of the work by Kolbe et al., who tested the effects of cannabidiol and ∆9 -tetrahydrocannabinol , the main cannabinoids found in the cannabis plant, on patient-derived glioblastoma cells. Cell cycle analysis revealed a decrease in cell cycle marker Ki67 via G protein-coupled orphan GPR55 receptor upon treatment with THC, pointing to the potential therapeutic action of THC in GPR55-expressing glioblastomas .

The review by Andradas et al. takes stock of the situation of cannabinoid’s treatment in paediatric oncology. They report few, and yet only preliminary, results on cannabinoids’ effects on children’s tumours, and unfortunately even less data on their safety and side effects. Remarkably, the few available studies are greatly diversified in terms of methodologies, types of compounds and formulations used, thus leading to controversial observations and a lack of confirmations . Moreover, Andradas et al. reported bad news on this subject in their paper on the role of cannabinoids in the treatment of children’s brain cancers medulloblastoma and ependymoma. Despite positive results in vitro, THC and CBD treatment of mouse models of these tumours failed to have any impact on traditional chemotherapy or on the animals’ survival . Bar-Sela et al. reported unfavourable outcomes for cancer patients, who were cannabis consumers, treated with immunotherapy in their observatory study. Their findings suggest that cannabinoids’ immunomodulatory effects might interfere with immunotherapy and call for caution on their use in those patients . Then, Taylor et al. review the current knowledge of the involvement of endocannabinoid system and its various constituents in reproductive events and in gynaecological cancers.

The latter are malignancies originating from either the reproductive tract or the products of conception, or secondary tumours. The review article highlights how targeting the endocannabinoid system could lead to new approaches to the diagnosis and treatment of these cancers in the female reproductive system . Another review analyses the complex involvement of the various components of the endocannabinoid system in susceptibility to cancer, prognosis, and response to treatment, focusing on the relationship of this lipid signalling system with cancer biology in different paradigms, such as gastrointestinal, gynaecological, prostate, thoracic, thyroid, and brain cancers, as well as melanoma. Interestingly, Moreno et al. noted that the same component of the endocannabinoid system can exert both pro- and anti-tumoural actions in different tumour subtypes . Finally, Afrin et al. discuss the action of non-THC cannabinoids in cancer. In their study, these authors evidenced the paucity of clinical data using cannabinoids, and the need for further preclinical investigations in order to establish the ‘pros’ and ‘cons’ of using whole cannabis extracts . Taken together, we hope to offer the reader at least a compass to navigate the mare magnum of the cannabinoid and endocannabinoid literature in the context of cancer.

Cannabis was used during the Han Chinese dynasty to treat inflammatory disorders and malaria . Other ancient people used Cannabis for healing and recreation in several regions of the world . In the western world, the importance of Cannabis was recognized in the mid-19th century, when an Irish physician, William B. O’Shaughnessy, and a French psychiatrist, Jacques-Joseph Moreau, reported that Cannabis had some beneficial effects . Cannabis was also used for religious and textile purposes . More recently, Cannabis was used as a recreational drug and the emergent problem of opiate dependency caused legal restrictions in 1925. In 1941, the American National Formulary and Pharmacopoeia included these compounds among illicit drugs . In recent years, there have been legislative changes to allow the use of Cannabis for some medical and/or recreational purposes . In this review we describe the interplay between endocannabinoids and immune systems in the cancer context.These compounds can also be stored in intracellular vesicles or organelles .