Decoding the Molecular Dance: In Silico Exploration of Cannabinoid Interactions with Key Protein Targets for Therapeutic Insights

As hemp-based cannabinoids are continuously gaining popularity, synthesis and extraction methods for these compounds are ever-changing. Within the cannabinoid market, hydrogenated derivatives are also gaining popularity at an accelerated rate, with the need for in-depth analysis of these compounds pertinent to increasing the knowledge of cannabis chemistry. Our lab used Schrödinger to dock natural and synthetic cannabinoids in various CB1 and CB2 receptors, PPAR-γ, PAK1, and GPR119 complex including several enzymes, to evaluate the interacting residues within the known binding pockets, comprising the computation of binding energies, predicting ADME characteristics, and evaluating P450 sites of metabolism. The purpose of identifying active residues, sites of metabolism, and ADME characteristics for 40 various cannabinoids is to provide guidance in computer-aided drug design and rationalization in designing and synthesis of analogs

Saturated Cannabinoids: Update on synthesis strategies and biological studies of these emerging cannabinoid analogs.

Natural and non-natural hexahydrocannabinols (HHC) were first described in 1940 by Adam and in late 2021 arose on the drug market in the United States and in some European countries. A background on the discovery, synthesis, and pharmacology studies of hydrogenated and saturated cannabinoids is described. This is harmonized with a summary and comparison of the cannabinoid receptor affinities of various classical, hybrid, and non-classical saturated cannabinoids. A discussion of structure-activity relationships with the four different pharmacophores found in the cannabinoid scaffold is added to this review. According to laboratory studies in vitro, and in several animal species in vivo, HHC is reported to have broadly similar effects to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive substance in cannabis, as demonstrated both in vitro and in several animal species in vivo. However, the effects of HHC treatment have not been studied in humans, and thus a biological profile has not been established

Ultrasonic or Microwave Modified Continuous Flow Chemistry for The Synthesis of Tetrahydrocannabinol: Observing Effects Of Various Solvents And Acids

Synthesizing tetrahydrocannabinol is a lengthy process with minimal yields and little applicability on an industrial scale. To close the gap between bench chemistry and industry process chemistry, this paper introduces a small-scale flow chemistry method that utilizes a microwave or ultrasonic medium to produce major tetrahydrocannabinol isomers. This process produces excellent yields and minimal side products, which leads to more efficient large-scale production of desired cannabinoids

Antineoplastic Properties of THCV, HHC and their anti-Proliferative effects on HPAF-II, MIA-paca2, Aspc-1, and PANC-1 PDAC Pancreatic Cell Lines

Cannabinoid receptors CB1 and CB2 are the primary endogenous receptors with which cannabinoids interact, inducing physiological and psychological effects. Although interactions with other receptors including TRPV1 and GPCR55, have been recognized in earlier studies, these interactions may play a significant role in cancer remediation through the unspecified upregulation or downregulation of specific pathways. The main active constituents within the cannabis plant are cannabidiol (CBD) and tetrahydrocannabinol (THC), which have been categorized as either non-intoxicating with benefit or intoxicating with no benefit. These categories are constantly ignored, as cannabinoids have shown efficacy in the treatment of certain diseases and ailments as single-agent compounds. Tetrahydrocannabivarin (THCV), a rare cannabinoid, is a homologue of THC, with the C5 alkyl chain having three carbons rather than the standard five carbon length. THCV has garnered attention in a clinical setting as an anti-obesity drug treating glucose issues. Hexahydrocannabinol (HHC), a hydrogenated analogue of THC, is a rare cannabinoid like THCV. These cyclic cannabinoids are considered rare, because they are typically found in minimal to trace amounts within cannabis sativa and their given C. indica, and C. ruderalis sub species. Increased popularity of these rare cannabinoids has led to proposed experimentation leading to assessing the cytotoxicity of these cannabinoids toward, cancer cells of the pancreas (MIA-PaCa2, HPAF-II, and PANC1). The data evaluated through such studies led to the proposed idea of these rare cyclic cannabinoids towards the treatment of pancreatic cancer due to the modest efficacy as single agent antineoplastics compared to common single agent antineoplastics on the market, with evidence being strongly presented when compared to commercially available anticancer agents poly(ADP-ribose) polymerase (PARP) inhibitors