Tag Archives: cannabinoid receptors

Weed Could Block H.I.V.’s Spread. No, Seriously.

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“But the U.S. government won’t let scientists try out this promising treatment on humans… proving that an illegal drug can stop a deadly disease in humans—without testing it on them—is impossible…

THC is one of 500 active ingredients in marijuana. And marijuana, despite many studies proving its medical value, is sill classified by the government as a Schedule 1 Substance.

In the face of mounting evidence that it is beneficial in treating diseases… it remains a controlled substance.

During HIV infection, one of the earliest effects is that the virus spreads rapidly throughout the body and kills a significant part of cells in the gut and intestine. This activity damages the gut in a way that allows the HIV to leak through the cell wall of the intestines and into the bloodstream.

When THC is introduced into this environment, it activates the CB2 receptors in the intestines to build new, healthy bacterial cells that block the virus from leaking through the cell walls. In other words, the body works hard to keep bad stuff in the intestines and the good stuff out.

Put another way: HIV kills the cells that protect the walls— THC brings them back. Reducing the amount of the virus in the lower intestines could then help keep uninfected people uninfected.”

More: http://www.thedailybeast.com/articles/2014/02/15/weed-can-block-h-i-v-s-spread-no-seriously.html

Inhibition of adenylate cyclase by delta 9-tetrahydrocannabinol in mouse spleen cells: a potential mechanism for cannabinoid-mediated immunosuppression.

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“The ability of delta 9-Tetrahydrocannabinol (delta 9-THC) to modulate adenylate cyclase activity in mouse spleen cells was investigated…

delta 9-THC treated spleen cells demonstrated a 33% inhibition and a 66% inhibition in intracellular cAMP… respectively…

These studies suggest that inhibition of immune function by delta 9-THC may be mediated through the inhibition of intracellular cAMP early after antigen stimulation.”

http://www.ncbi.nlm.nih.gov/pubmed/1321935

Anandamide, a naturally-occurring agonist of the cannabinoid receptor, blocks adenylate cyclase at the frog neuromuscular junction.

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“Anandamide (arachydonylethanolamide) is a naturally-occurring ligand of the canabinoid receptor. When anandamide binds to its receptor, adenylate cyclase is inhibited…

The conclusions are that the motor nerve terminal has a cannabinoid receptor.

The binding of anandamide to this receptor seems to block adenylate cyclase.”

http://www.ncbi.nlm.nih.gov/pubmed/7953630

The peripheral cannabinoid receptor: adenylate cyclase inhibition and G protein coupling.

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“Two cannabinoid receptors, designated neuronal (or CB1) and peripheral (or CB2), have recently been cloned. Activation of CB1 receptors leads to inhibition of adenylate cyclase and N-type voltage-dependent Ca2+ channels.

Here we show, using a CB2 transfected Chinese hamster ovary cell line, that this receptor binds a variety of tricyclic cannabinoid ligands as well as the endogenous ligand anandamide.

Activation of the CB2 receptor by various tricyclic cannabinoids inhibits adenylate cyclase activity and this inhibition is pertussis toxin sensitive indicating that this receptor is coupled to the Gi/G(o) GTP-binding proteins…

These results characterize the CB2 receptor as a functional and distinctive member of the cannabinoid receptor family.”

http://www.ncbi.nlm.nih.gov/pubmed/7498464

 

Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model.

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“Extensive structure-activity relationship studies have demonstrated that specific requirements within the cannabinoid structure are necessary to produce potent analgesia.

A three-point association between the agonist and the receptor mediating analgesia consists of: 1) the C ring hydroxyl, 2) the phenolic A ring hydroxyl, and 3) the A ring alkyl hydrophobic side chain. Potent tricyclic and bicyclic structures were synthesized as “nonclassical” cannabinoid analgetics that conform to this agonist-receptor three-point interaction model.

At the cellular level, centrally active cannabinoid drugs inhibit adenylate cyclase activity in a neuroblastoma cell line. The structure-activity relationship profile for inhibition of adenylate cyclase in vitro was consistent with this same three-point association of agonists with the receptor.

A correlation exists between the potency of drugs to produce analgesia in vivo and to inhibit adenylate cyclase in vitro.

Based on the parallels in structure-activity relationships and the enantioselective effects, it is postulated that the receptor that is associated with the regulation of adenylate cyclase in vitro may be the same receptor as that mediating analgesia in vivo.

A conceptualization of the cannabinoid analgetic receptor is presented.”

http://www.ncbi.nlm.nih.gov/pubmed/3352594

Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase.

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“A putative endogenous cannabinoid ligand, arachidonylethanolamide (termed “anandamide”), was isolated recently from porcine brain.

Here we demonstrate that this compound is a specific cannabinoid agonist and exerts its action directly via the cannabinoid receptors.

Anandamide specifically binds to membranes from cells transiently (COS) or stably (Chinese hamster ovary) transfected with an expression plasmid carrying the cannabinoid receptor DNA but not to membranes from control nontransfected cells.

Moreover, anandamide inhibited the forskolin-stimulated adenylate cyclase in the transfected cells and in cells that naturally express cannabinoid receptors (N18TG2 neuroblastoma) but not in control nontransfected cells. As with exogenous cannabinoids…

These data indicate that anandamide is an endogenous agonist that may serve as a genuine neurotransmitter for the cannabinoid receptor.”

http://www.ncbi.nlm.nih.gov/pubmed/8515284

Thermal isomerization of cannabinoid analogues.

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“Thermal isomerization of CBC(an) to THC(an) [nonaromatic analogues of plant cannabinoids cannabichromene (CBC) and Delta(1)-tetrahydrocannabinol (THC), respectively] is predicted in silico and demonstrated experimentally. Density functional theory calculations support a similar isomerization mechanism for the corresponding plant cannabinoids. Docking studies suggest that THC(an), although nonaromatic, has a CB(1) receptor binding affinity similar to that of natural THC.”

http://www.ncbi.nlm.nih.gov/pubmed/19919138

The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis.

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“The non-psychotropic cannabinoid cannabichromene is known to activate the transient receptor potential ankyrin-type1 (TRPA1) and to inhibit endocannabinoid inactivation, both of which are involved in inflammatory processes. We examined here the effects of this phytocannabinoid on peritoneal macrophages and its efficacy in an experimental model of colitis…

CONCLUSION AND IMPLICATIONS:

Cannabichromene exerts anti-inflammatory actions in activated macrophages – with tonic CB1 cannabinoid signalling being negatively coupled to this effect – and ameliorates experimental murine colitis.”

http://www.ncbi.nlm.nih.gov/pubmed/23373571

Potential protective effects of cannabidiol on neuroanatomical alterations in cannabis users and psychosis: a critical review.

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“…different cannabis compounds may exert opposite effects on the neuroanatomical changes underlying psychosis. In particular, cannabidiol (CBD) was shown to prevent THC associated hippocampal volume loss… This finding is further supported by several animal experiments supporting neuroprotective properties of CBD mainly via anti-oxidative effects, CB2 receptors or adenosine receptors… mechanisms by which CBD may reduce brain volume loss, including antagonism of THC, interactions with endocannabinoids, and mechanisms that specifically underlie antipsychotic properties of CBD.”

http://www.ncbi.nlm.nih.gov/pubmed/22716143

(+)-Cannabidiol analogues which bind cannabinoid receptors but exert peripheral activity only.

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“We have tested a series of (+)-cannabidiol derivatives… for central and peripheral (intestinal, antiinflammatory and peripheral pain) effects in mice…

We conclude that centrally inactive (+)-cannabidiol analogues should be further developed as antidiarrheal, antiinflammatory and analgesic drugs for gastrointestinal and other peripheral conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/15588739