Functionalization of β-Caryophyllene Generates Novel Polypharmacology in the Endocannabinoid System.

Posted on May 19, 2014 by David

“The widespread dietary plant sesquiterpene hydrocarbon β-caryophyllene is a CB2 cannabinoid receptor-specific agonist showing anti-inflammatory and analgesic effects in vivo…

Our study shows that by removing the conformational constraints induced by the medium-sized ring and by introducing functional groups in the sesquiterpene hydrocarbon 1, a new scaffold with pronounced polypharmacological features within the endocannabinoid system could be generated.

The structural and functional repertoire of cannabimimetics and their yet poorly understood intrinsic promiscuity may be exploited to generate novel probes and ultimately more effective drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/24831513

“Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception…β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis… The combined injection of morphine and BCP may be an alternative in treating chemogenic pain.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

Analgesic effects of 1′,1′ dimethylheptyl-delta8-THC-11-oic acid (CT3) in mice.

Posted on March 21, 2014 by David

“The metabolic pathway leading to carboxylic acid derivatives of cannabinoids was discovered more than twenty years ago. While these compounds showed no cannabimimetic activity, subsequent work documented several biological responses both in vitro and in vivo for the THC acids.

These include inhibition of eicosanoid synthesis, antiedema effects, antagonism to PAF actions, inhibition of leucocyte adhesion and anti nociception.

In this report we present data further characterizing the analgesic properties of the title substance which is a potent synthetic member of this group. CT3 was effective in the mouse…”

http://www.ncbi.nlm.nih.gov/pubmed/9698045

Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists.

Posted on March 21, 2014 by David

“The cannabinoid receptor type 2 (CB2) is a class A GPCR that was cloned in 1993 while looking for an alternative receptor that could explain the pharmacological properties of Δ(9)-tetrahydrocannabinol.

CB2 was identified among cDNAs based on its similarity in amino acid sequence to the CB1receptor and helped provide an explanation for the established effects of cannabinoids on the immune system.

In addition to the immune system, CB2 has widespread tissue expression and has been found in brain, peripheral nervous system, and gastrointestinal tract.

Several “mixed” cannabinoid agonists are currently in clinical use primarily for controlling pain, and it is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects.

Thus, selective CB2 receptor agonists represent high value putative therapeutics for treating pain and other disease states. In this Perspective, we seek to provide a concise update of progress in the field.”

http://www.ncbi.nlm.nih.gov/pubmed/23865723

HIV Cure: Medical Cannabis Or ‘Weed’ Explored To Help Stop HIV Infection Using THC Component; Laws Prevent Clinical Trials On Humans

Posted on March 1, 2014 by David

“Medical cannabis is used as an appetite stimulant, antiemetic, antispasmodic and sometimes as analgesic to help treat chronic, non-cancerous pain, vomiting or nausea caused by chemotherapy. In some cases, it is also used to aid treating symptoms of AIDS patients…

Marijuana or “weed” is now among the several ingredients that researchers are looking into to helping stop further spread of HIV infection.”

More: http://au.ibtimes.com/articles/539079/20140217/hiv-cure-medical-cannabis-weed-explored-help.htm#.UxJCyPBX-uY

Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes.

Posted on February 27, 2014 by David

“The inhibition of adenylate cyclase activity by cannabimimetic compounds in a membrane fraction from cultured neuroblastoma cells has been examined. The inhibition was shown to be concentration-dependent over a nanomolar range for both delta 9-tetrahydrocannabinol and its synthetic analog…

This study points to the similarities between the enzyme inhibition by cannabimimetic compounds and by muscarinic cholinergic compounds. It is inferred that the cannabimimetic compounds must act via regulatory mechanisms similar to those operating for receptor-mediated inhibition of adenylate cyclase.”

http://www.ncbi.nlm.nih.gov/pubmed/2984538

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

Posted on February 26, 2014 by David

“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

The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain.

Posted on February 25, 2014 by David

“The therapeutic effects of the cannabinoid anandamide and the putative CB2 agonist palmitoylethanolamide were tested in a model of persistent visceral pain (turpentine inflammation of the urinary bladder)…

The results confirm the analgesic potential of endogenous ligands at cannabinoid receptor sites.

The anti-nociceptive effect of the putative CB2 receptor agonist, palmitoylethanolamide, is particularly interesting since it is believed to be a peripherally mediated effect.

This observation might be exploited to separate central psychotropic effects from peripheral analgesic actions of the cannabinoids, under inflammatory conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/9696473

Activation of cannabinoid receptor 2 inhibits experimental cystitis.

Posted on February 25, 2014 by David

“Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1and CB2). Both CB1 and CB2 are present in bladders of various species, including human, monkey, and rodents, and it appears that CB2 is highly expressed in urothelial cells…

The results of the current study indicate that CB2 is a potential therapeutic target for treatment of bladder inflammation and pain in patients.”

http://www.ncbi.nlm.nih.gov/pubmed/23515618

The endocannabinoid anandamide inhibits voltage-gated sodium channels nav1.2, nav1.6, nav1.7, and nav1.8 in Xenopus oocytes.

Posted on February 24, 2014 by David

“Anandamide is an endocannabinoid that regulates multiple physiological functions by pharmacological actions, in a manner similar to marijuana. Recently, much attention has been paid to the analgesic effect of endocannabinoids in terms of identifying new pharmacotherapies for refractory pain management, but the mechanisms of the analgesic effects of anandamide are still obscure…

Anandamide inhibited the function of α subunits in neuronal sodium channels Nav1.2, Nav1.6, Nav1.7, and Nav1.8.

These results help clarify the mechanisms of the analgesic effects of anandamide.”

http://www.ncbi.nlm.nih.gov/pubmed/24557103

Targeting the cannabinoid system for pain relief?

Posted on February 18, 2014 by David

“Marijuana has been used to relieve pain for centuries, but its analgesic mechanism has only been understood during the past two decades. It is mainly mediated by its constituents, cannabinoids, through activating central cannabinoid 1 (CB1) receptors, as well as peripheral CB1 and CB2receptors.

CB2-selective agonists have the benefit of lacking CB1 receptor-mediated CNS side effects. Anandamide and 2-arachidonoylglycerol (2-AG) are two intensively studied endogenous lipid ligands of cannabinoid receptors, termed endocannabinoids, which are synthesized on demand and rapidly degraded…

In addition to the antinociceptive properties of exogenous cannabinoids and endocannabinoids, involving their biosynthesis and degradation processes, we also review recent studies that revealed a novel analgesic mechanism, involving 2-AG in the periaqueductal gray (PAG), a midbrain region for initiating descending pain inhibition…”

http://www.ncbi.nlm.nih.gov/pubmed/24529672

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