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Cannabidiol Inhibits the Proliferation and Invasiveness of Prostate Cancer Cells

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Prostate cancer is the fifth leading cause of cancer death in men, responsible for over 375,000 deaths in 2020. Novel therapeutic strategies are needed to improve outcomes. Cannabinoids, chemical components of the cannabis plant, are a possible solution. Preclinical evidence demonstrates that cannabinoids can modulate several cancer hallmarks of many tumor types. However, the therapeutic potential of cannabinoids in prostate cancer has not yet been fully explored. The aim of this study was to investigate the antiproliferative and anti-invasive properties of cannabidiol (CBD) in prostate cancer cells in vitro. CBD inhibited cell viability and proliferation, accompanied by reduced expression of key cell cycle proteins, specifically cyclin D3 and cyclin-dependent kinases CDK2, CDK4, and CDK1, and inhibition of AKT phosphorylation. The effects of CBD on cell viability were not blocked by cannabinoid receptor antagonists, a transient receptor potential vanilloid 1 (TRPV1) channel blocker, or an agonist of the G-protein-coupled receptor GPR55, suggesting that CBD acts independently of these targets in prostate cancer cells. Furthermore, CBD reduced the invasiveness of highly metastatic PC-3 cells and increased protein expression of E-cadherin. The ability of CBD to inhibit prostate cancer cell proliferation and invasiveness suggests that CBD may have potential as a future chemotherapeutic agent.

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Studies Pertaining to the Emerging Cannabinoid Hexahydrocannabinol (HHC)

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We report studies pertaining to two isomeric hexahydrocannabinols (HHCs), (9R)-HHC and (9S)-HHC, which are derivatives of the psychoactive cannabinoids Δ9- and Δ8-THC. HHCs have been known since the 1940s, but have become increasingly available to the public in the United States and are typically sold as a mixture of isomers. We show that (9R)-HHC and (9S)-HHC can be prepared using hydrogen-atom transfer reduction, with (9R)-HHC being accessed as the major diastereomer. In addition, we report the results of cannabinoid receptor studies for (9R)-HHC and (9S)-HHC. The binding affinity and activity of isomer (9R)-HHC are similar to that of Δ9-THC, whereas (9S)-HHC binds strongly in cannabinoid receptor studies but displays diminished activity in functional assays. This is notable, as our examination of the certificates of analysis for >60 commercially available HHC products show wide variability in HHC isomer ratios (from 0.2:1 to 2.4:1 of (9R)-HHC to (9S)-HHC). These studies suggest the need for greater research and systematic testing of new cannabinoids. Such efforts would help inform cannabis-based policies, ensure the safety of cannabinoids, and potentially lead to the discovery of new medicines.

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Fibromyalgia and the endocannabinoid system

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Authors: John M. McPartland Published in Science Direct November 2009 Introduction Fibromyalgia has been characterized as an ‘endocanna- binoid (eCB) deficiency syndrome’, along with other refractory maladies such as irritable…

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The synthetic cannabinoid WIN55212‐2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies

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Author: Anna Porcella Chiara Maxia Gian Luigi Gessa Luca Pani Published in European Journal of Neuroscience March 1980 Abstract The search for new ocular hypotensive agents represents a frontier of current…

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Changes in endocannabinoid and palmitoylethanolamide levels in eye tissues of patients with diabetic retinopathy and age-related macular degeneration

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Author: I. Matias, J.W. Wang, A. Schiano Moriello, A. Nieves, D.F. Woodward,V. Di Marzo Published in Science Direct December 2006 Abstract Cannabinoid receptors and the endocannabinoids (anandamide (N-arachidonoylethanolamine—AEA) and 2-arachidonoylglycerol (2-AG)),…

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