Abstract The President of the International Association for the Study of Pain established a task force on cannabis and cannabinoid analgesia to systematically examine the evidence on (1) analgesic pharmacology of cannabinoids and preclinical evidence on their efficacy in animal models of injury-related or pathological persistent pain; (2) the clinical efficacy of cannabis, cannabinoids, and cannabis-based medicines for pain; (3) harms related to long-term use of cannabinoids; as well as (4) societal issues and policy implications related to the use of these compounds for pain management. Here, we summarize key knowledge gaps identified in the task force outputs and propose a research agenda for...

Abstract There is an urgent need for developing effective drugs to combat the obesity and Type 2 diabetes mellitus epidemics. The endocannabinoid system plays a major role in energy homeostasis. It comprises the cannabinoid receptors 1 and 2 (CB1 and CB2), endogenous ligands called endocannabinoids and their metabolizing enzymes. Because the CB1 receptor is overactivated in metabolic alterations, pharmacological blockade of the CB1 receptor arose as a promising candidate to treat obesity. However, because of the wide distribution of CB1 receptors in the central nervous system, their negative central effects halted further therapeutic use. Although the CB2 receptor is mostly peripherally expressed, its role...

Abstract Despite the importance of pain as a warning physiological system, chronic neuropathic pain is frequently caused by damage in the nervous system, followed by persistence over a long period, even in the absence of dangerous stimuli or after healing of injuries. Chronic neuropathic pain affects hundreds of millions of adults worldwide, creating a direct impact on quality of life. This pathology has been extensively characterized concerning its cellular and molecular mechanisms, and the endocannabinoid system (eCS) is widely recognized as pivotal in the development of chronic neuropathic pain. Scientific evidence has supported that phyto-, synthetic and endocannabinoids are efficient for pain management, while...

Abstract Up to 20% of pregnant women ages 18–24 consume cannabis during pregnancy. Moreover, clinical studies indicate that cannabis consumption during pregnancy leads to fetal growth restriction (FGR), which is associated with an increased risk of obesity, type II diabetes (T2D), and cardiovascular disease in the offspring. This is of great concern considering that the concentration of Δ9- tetrahydrocannabinol (Δ9-THC), a major psychoactive component of cannabis, has doubled over the last decade and can readily cross the placenta and enter fetal circulation, with the potential to negatively impact fetal development via the endocannabinoid (eCB) system. Cannabis exposure in utero could also lead to FGR...

Abstract Chronic kidney disease (CKD) concerns millions of individuals worldwide, with few therapeutic strategies available to date. Recent evidence suggests that the endocannabinoid system (ECS) could be a new therapeutic target to prevent CKD. ECS combines receptors, cannabinoid receptor type 1 (CB1R) and type 2 (CB2R), and ligands. The most prominent receptor within the kidney is CB1R, its endogenous local ligands being anandamide and 2-arachidonoylglycerol. Therefore, the present review focuses on the therapeutic potential of CB1R and not CB2R. In the normal kidney, CB1R is expressed in many cell types, especially in the vasculature where it contributes to the regulation of renal hemodynamics. CB1R...

Abstract Clinical reports of cannabis use prevalence during pregnancy vary widely from 3% to upwards of 35% in North America; this disparity likely owing to underestimates from self-reporting in many cases. The rise in cannabis use is mirrored by increasing global legalization and the overall perceptions of safety, even during pregnancy. These trends are further compounded by a lack of evidence-based policy and guidelines for prenatal cannabis use, which has led to inconsistent messaging by healthcare providers and medically licensed cannabis dispensaries regarding prenatal cannabis use for treatment of symptoms, such as nausea. Additionally, the use of cannabis to self-medicate depression and anxiety during...

Abstract Introduction Cannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. There is a growing body of evidence from cell culture and animal studies in support of cannabinoids possessing anticancer properties. Method A database search of peer reviewed articles published in English as full texts between January 1970 and April 2021 in Google Scholar, MEDLINE, PubMed and Web of Science was undertaken. References of relevant literature were searched to identify additional studies to construct a narrative literature review of oncological effects of cannabinoids in pre-clinical and clinical studies in various cancer types. Results Phyto-, endogenous and synthetic cannabinoids demonstrated...

Abstract The legalization of cannabis in many parts of the United States and other countries has led to a need for a more comprehensive understanding of cannabis constituents and their potential for drug-drug interactions. Although (−)-trans-Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) are the most abundant cannabinoids present in cannabis, THC metabolites are found in plasma at higher concentrations and for a longer duration than that of the parent cannabinoids. To understand the potential for drug-drug interactions, the inhibition potential of major cannabinoids and their metabolites on major hepatic cytochrome P450 (P450) enzymes was examined. In vitro assays with P450-overexpressing cell microsomes demonstrated that...

Abstract The CB1 cannabinoid receptor is a G-protein coupled receptor highly expressed throughout the central nervous system that is a promising target for the treatment of various disorders, including anxiety, pain, and neurodegeneration. Despite the wide therapeutic potential of CB1, the development of drug candidates is hindered by adverse effects, rapid tolerance development, and abuse potential. Ligands that produce biased signaling—the preferential activation of a signaling transducer in detriment of another—have been proposed as a strategy to dissociate therapeutic and adverse effects for a variety of G-protein coupled receptors. However, biased signaling at the CB1 receptor is poorly understood due to a lack of...

Abstract Plant-based, synthetic, and endogenous cannabinoids have been shown to control a diverse array of biological processes, including regulation of cell fate across cancers. Their promise as broad-based antitumor agents in preclinical models has led to the initiation of pilot clinical trials. Session 5 of the National Cancer Institute’s Cannabis, Cannabinoids and Cancer Research Symposium provides an overview of this research topic. Overall, the presentations highlight cannabinoid signal transduction and specific molecular mechanisms underlying cannabinoid antitumor activity. They also demonstrate the broad-based antitumor activity of the plant-based, synthetic, and endogenous cannabinoid compounds. Importantly, evidence is presented demonstrating when cannabinoids may be contraindicated as a...