Abstract The medicinal use of Cannabis sativa L. can be traced back thousands of years to ancient China and Egypt. While marijuana has recently shown promise in managing chronic pain and nausea, scientific investigation of cannabis has been restricted due its classification as a schedule 1 controlled substance. A major breakthrough in understanding the pharmacology of cannabis came with the isolation and characterization of the phytocannabinoids trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This was followed by the cloning of the cannabinoid CB1 and CB2 receptors in the 1990s and the subsequent discovery of the endocannabinoid system. In addition to the major phytocannabinoids, Δ9-THC and CBD,...

Abstract Study Objectives This randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the safety and efficacy of 2 weeks of nightly sublingual cannabinoid extract (ZTL-101) in treating chronic insomnia (symptoms ≥3 months). Methods Co-primary study endpoints were safety of the medication based on adverse event reporting and global insomnia symptoms (Insomnia Severity Index [ISI]). Secondary endpoints included: self-reported (sleep diary), actigraphy-derived, and polysomnography measurements of sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), sleep efficiency (SE); and self-reported assessments of sleep quality (sSQ) and feeling rested upon waking. Adjusted mean differences between placebo and ZTL-101 were calculated. Results...

Abstract This narrative review represents an output from the International Association for the Study of Pain's global task force on the use of cannabis, cannabinoids, and cannabis-based medicines for pain management, informed by our companion systematic review and meta-analysis of preclinical studies in this area. Our aims in this review are (1) to describe the value of studying cannabinoids and endogenous cannabinoid (endocannabinoid) system modulators in preclinical/animal models of pain; (2) to discuss both pain-related efficacy and additional pain-relevant effects (adverse and beneficial) of cannabinoids and endocannabinoid system modulators as they pertain to animal models of pathological or injury-related persistent pain; and (3) to...

Abstract Background: Epidermolysis bullosa (EB) patient anecdotes and case reports indicate that cannabinoid-based medicines (CBMs) may alleviate pain and pruritus and improve wound healing. CBM use has not been characterized in the EB patient population. Objectives: To evaluate CBM use among EB patients, including CBM types, efects on symptoms (e.g., pain and pruritus), disease process (e.g., blistering, wounds, and infammation), well-being (e.g., sleep, appetite) and concomitant medications. Methods: English-speaking EB patients or caregivers completed an online international, anonymous, cross-sectional survey regarding CBM use. Respondents reported the types of CBMs, subsequent efects including perceived EB symptom alteration, changes in medication use, and side efects. Results:...

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 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 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...