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CBD Pain Freeze Cream Summary


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Boomer Wellness CBD Summary

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Adle Thomas and Roger G Pertwee

The mouse isolated vas deferens is a nerve-smooth muscle preparation that serves as a highly sensitive and quantitative functional in vitro bioassay for cannabinoid CB1 receptor agonists. Additionally, it is commonly used as a bioassay for competitive surmountable CB1 receptor antagonists, and also provides a means for distinguishing neutral CB1 antagonists from CB1 inverse agonists. The bioassay of CB1 receptor agonists relies on the ability of these ligands to produce concentration-related decreases in the amplitude of electrically evoked contractions of the vas deferens. This they do by acting on naturally expressed prejunctional neuronal CB1 receptors to inhibit release of the contractile neurotransmitters, noradrenaline and ATP, that is provoked by the electrical stimulation. The bioassay of competitive surmountable CB1 receptor antagonists involves determining the ability of these compounds to produce parallel dextral shifts in CB1 receptor agonist log concentration-response...

Endocannabinoid System 21 Cannabinoid Based Drugs

The main psychoactive substance in Cannabis extracts was isolated and synthesized in 1964 and shown to be A9-tetrahydrocannabinol (THC) (Gaoni and Mechoulam 1964). THC and cannabinoids are tricyclic ring structures containing a phenol ring with attached 5-carbon alkyl chain, a central pyran ring, and a monounsaturated cyclohexyl ring the structure and the function of THC and related compounds have been recently and extensively reviewed (Pertwee 2005 Pacher et al. 2006). Besides THC, other natural Cannabis products have been extracted and characterized such as A8-THC (also psychoactive), cannabinol, and cannabidiol (both nonpsychoactive) in addition, synthetic cannabinoid derivatives have been produced and studied such as CP55,940, HU-210, HU-211, ajulemic acid, and abnormal cannabidiol (Figure 1). The defined physiological and pharmacological effects of marijuana cannabinoids A9-THC A8-THC Cannabinol Cannabidiol A9-THC A8-THC Cannabinol Cannabidiol

Methods for the Synthesis of Cannabinergic Ligands

Synthetic Cannabinoids Synthesis

The long history of worldwide self-medication by a mixture of cannabinoids present in Cannabis sativa generated the first wave of interest among synthetic and medicinal chemists in conjunction with the co-developments of modern separation, spectroscopic, and synthetic methods during the last half century. The identification of the family of C21 tricyclic cannabinoids led to the chi-rospecific partial syntheses of these classical cannabinoids from more readily available monoterpenes, and to the total syntheses of these plant constituents, as well as an expanding list of cannabimimetic compounds. However, only a few efficacious drugs, which include Marinol (Dronabinol, (-)-A9-THC from Roxane Labs), Cesamet (Nabilone, developed by Eli Lilly) and Sativex (A9-THC and cannabidiol, developed by GW Pharmaceuticals), have resulted. Cannabinoid synthesis has seen a renewed wave of interest with the discovery and cloning of the CB1 and CB2 cannabinoid receptors and the characterizations of the...

Cannabinoid Receptors

Besides CBi and CB2, other receptors are stimulated by cannabinoid ligands. For example, the endocannabinoid, AEA, and cannabidiol have been shown to activate the transient receptor potential vanilloid 1 (TRPV1) in vascular tissues and neural circuits (Zygmunt et al. 1999). In addition, other poorly defined receptors have been suggested from studies with CB1- and CB2-knockout mice and in pharmacological studies wherein agonists for CBi and CB2 displayed split potency. For example, in rat mesenteric arteries, AEA and abnormal cannabidiol (which has low affinity for CBi receptors) induced vasodilation that was inhibited by the CBi antagonist, SR141716A however, other potent CBi agonists had no effect (Jarai et al. 1999 Offertaler et al. 2003). Studies with knockout mice also suggested a third receptor because signaling activity in brain membrane preparations occurred equally well in CB1 knockout and wild-type mice (Breivogel et al. 2001). Furthermore, in an immune cell model, IL-12...

Some Interpretational Difficulties

Although there is good evidence that cannabinoids can act via neuronal cannabinoid CB1 receptors to inhibit electrically evoked contractions of the mouse isolated vas deferens (Subheading 1.), there is also evidence that this tissue contains additional pharmacological targets with which some cannabinoids can interact to produce this inhibitory response. Thus, the endocannabi-noid anandamide appears to inhibit electrically evoked contractions of the vas deferens by acting not only on CBi receptors but also on neuronal vanilloid (TRPV1) receptors (Subheading 1.). There is also evidence that anandamide and several other established CB1 CB2 receptor agonists can act though a CB2-like cannabinoid receptor to inhibit electrically evoked contractions of this tissue preparation (17). In addition, other as yet uncharacterized neuronal and non neuronal targets for cannabinoids may be present in the mouse vas deferens (11,12). A further complication is that some cannabinoids, including the...

Assays Using Electrically Stimulated Tissues

Cannbinoid Receptor

Analysis of the recorded data involves measuring the height of the last six contractions produced during each 2-min stimulation period. This includes the period immediately before the first addition of agonist, antagonist, or vehicle is made. For experiments with antagonists (Subheading 3.3.2.), any change in contraction height produced by the antagonist is monitored to establish whether the antagonist itself has any direct effect on the amplitude of electrically evoked contractions. SRi4i7i6A and cannabidiol are both lig-ands that can significantly enhance the height of electrically evoked contractions in the mouse vas deferens (9,12). The contraction amplitudes measured just prior to the addition of the first (lowest) dose of agonist serve as the baseline amplitudes with which each subsequent set of contraction heights is compared when calculating the percentage change in contraction height produced by the agonist.


The major constituents in cannabis are termed cannabinoids, a group of more than 60 structurally related terpenophenolics. The principal psychoactive agent is tetrahydrocannabinol (THC) (Figure 3.51). This is variously referred to as A1-THC or A9-THC according to whether the numbering is based on the terpene portion, or as a systematic dibenzopyran (Figure 3.53). Both systems are currently in use. Also found, often in rather similar amounts, are cannabinol (CBN) and cannabidiol (CBD) (Figure 3.51), which have negligible psychoactive properties. These compounds predominate in the inactive resins. Many other cannabinoid structures have been characterized, including cannabigerol and cannabichromene (Figure 3.53). A range of cannabinoid acids, e.g. cannabidiolic acid, tetrahydrocannabinolic acid, and tetrahydrocannabinolic acid B (Figure 3.53) are also present, as are some analogues of the other compounds mentioned, where a propyl side-chain replaces the pentyl group, e.g....


Ab-cannabidiol Ajulemic acid suggested the existence of an endogenous ligand with similar activity and the isolation of the first of these was reported in 1992 (Devane et al. 1992). This so-called endocannabinoid was demonstrated to be the arachidonic acid derivative, -arachidonoyl ethanolamide (AEA), and since its discovery, several other similar compounds have been isolated and extensively studied including 2-arachidonoyl-glycerol (2-AG) (Mechoulam et al. 1995), 2-arachidonylglycerylether (noladin ether) (Hanus et al. 2001), and O-arachidonoyl ethanolamine (virohdamine) (Porter et al. 2002). Most of the cannabinoid-based drugs and endogenous ligands have immuno-modulating activity and most, but not all, bind to one or both of the two known can-nabinoid receptors, (see below). However, some, such as cannabidiol and HU211, have relatively low affinity for cannabinoid receptors, suggesting that other receptors or molecular mechanisms are involved in the action of these agents. A final...


Lactone Ring Aflatoxin And

The principal psychoactive component is tetrahy-drocannabinol (THC) (Figure 3.51), whilst structurally similar compounds such as cannabinol (CBN) and cannabidiol (CBD), present in similar or larger amounts, are effectively inactive. In recent years, the beneficial effects of cannabis*, and especially THC, in alleviating nausea and vomiting in cancer patients undergoing chemotherapy, and in the treatment of glaucoma and multiple sclerosis, has led to a study of cannabinoid analogues for potentially useful medicinal activity. All the cannabinoid structures contain a monoter-pene C1o unit attached to a phenolic ring having a C5 alkyl chain. The aromatic ring C5 chain cannabidiolic acid tetrahydrocannabinolic acid OH cannabidiol CBD OH cannabidiol CBD and compare terpenoid cyclization mechanisms, page 173). Cannabidiolic acid is the result of proton loss, whilst tetrahydrocannabinolic acid is the product from heterocyclic ring formation. CBD and THC are then the respective decarboxylation...

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