Furthermore, a number of N-acylethanolamines structurally similar to ECs, so-called EC-like substances, such as N-palmitoylethanolamine (PEA) and N-oleylethanolamine (OEA), have been described, which use the biosynthesis and degradation enzymes of ECs, but do not trigger cannabinoid receptor activation (reviewed in ref. However, the available data on their biological role are very limited. Scientific attention has also been paid in recent years to substances with structural similarities to the aforementioned ECs, such as the cannabinoid receptor ligands 2-arachidonoyl glycerol ether (noladin ether), O-arachidonoylethanolamine (virodhamine), N-arachidonoyldopamine and oleic acid amide (oleamide) (reviewed in ref. Other components of the EC system discovered in the 1990s are N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), two endogenously synthesised agonists at cannabinoid receptors. While CB 1 receptors are primarily localised in the central nervous system, CB 2 receptors are mostly expressed on cells of the immune system. The entry of the endocannabinoid (EC) system into modern research as a potential target of pharmacotherapeutic intervention began with the discovery and cloning of specific G i/o protein-coupled cannabinoid receptors, termed CB 1 and CB 2. Although the isolation of a substance called ‘cannabinol’ from the exuded resin of Indian hemp dates back to a communication published in 1899, it was not until the 1960s that Raphael Mechoulam and his collaborators published a series of studies that elucidated the chemical structure and activity of Δ 9-tetrahydrocannabinol (THC), cannabidiol (CBD), and other cannabinoids. O’Shaughnessy, who published a groundbreaking study on hemp in 1839 with his work ‘On the preparations of the Indian hemp or gunjah’. The introduction of cannabis into European medicine can be attributed to the Irish physician William B. Further evidence for a millennia-old use is based on cannabis-containing grave goods found in archaeological investigations of an Ukok ‘princess’ from the Pazyryk culture or the remains of cannabis fruits identified in archaeobotanical investigations at the Laoguanshan cemetery from the Han dynasty in Chengdu, South China. Accordingly, the psychoactive effect of cannabis is already mentioned in the Pen-ts’ao ching, the oldest pharmacopoeia in the world. The use of the cannabis plant for medicinal and ritual purposes dates back several thousand years. This review provides an up-to-date overview of the potential of cannabinoids as inhibitors of tumour growth and spread as demonstrated in preclinical studies. Research in recent years has yielded several compounds that exert promising effects on tumour cells and tissues in addition to the psychoactive Δ 9-tetrahydrocannabinol, such as the non-psychoactive phytocannabinoid cannabidiol and inhibitors of endocannabinoid degradation. Further studies showed that cannabinoids could be potential combination partners for established chemotherapeutic agents or other therapeutic interventions in cancer treatment. Accordingly, there is considerable evidence for cannabinoid-mediated inhibition of tumour cell proliferation, tumour invasion and metastasis, angiogenesis and chemoresistance, as well as induction of apoptosis and autophagy. As a result of these efforts, a large body of data suggests that the anticancer effects of cannabinoids are exerted at multiple levels of tumour progression via different signal transduction mechanisms. From this perspective, cannabinoid compounds have been successfully tested as a systemic therapeutic option in a number of preclinical models over the past decades. Drugs that target the endocannabinoid system are of interest as pharmacological options to combat cancer and to improve the life quality of cancer patients.
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