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Gastro Intestinal Reflux Disease (GERD)

J Neurosci. 2009 Feb 4;29(5):1554-64.

CB1 receptors mediate the analgesic effects of cannabinoids on colorectal distension-induced visceral pain in rodents.

Brusberg M, Arvidsson S, Kang D, Larsson H, Lindström E, Martinez V.

Biosciences, AstraZeneca R&D Mölndal, Mölndal SE-431 83, Sweden.

Activation of cannabinoid receptors (CB(1), CB(2) and GPR(55)) produces analgesic effects in several experimental pain models, including visceral pain arising from the gastrointestinal tract. We assessed the role of CB(1), CB(2), and GPR(55) receptors and the endogenous cannabinoid system on basal pain responses and acute mechanical hyperalgesia during colorectal distension (CRD) in rodents. The effects of cannabinoid receptor agonists and antagonists on pain-related responses to CRD were assessed in rats and in wild-type and CB(1) receptor knock-out mice. The dual CB(1/2) agonist, WIN55,212-2, and the peripherally acting CB(1)-selective agonist, SAB-378, inhibited pain-related responses to repetitive noxious CRD (80 mmHg) in a dose-related manner in rats. The analgesic effects of WIN55,212-2 and SAB-378 were blocked by the selective CB(1) antagonist SR141716, but were not affected by the selective CB(2) antagonist SR144528. SR141716, per se, increased the responses to repetitive noxious CRD, indicative of hyperalgesia, and induced pain-related responses during non-noxious CRD (20 mmHg), indicative of allodynia. The cannabinoid receptor agonists anandamide, virodhamine and O-1602 had no effect. At analgesic doses, WIN55,212-2 did not affect colonic compliance. In accordance to the rat data, WIN55,212-2 produced analgesia, whereas SR141716 induced hyperalgesia, during noxious CRD (55 mmHg) in wild-type but not in CB(1)-knock-out mice. These data indicate that peripheral CB(1) receptors mediate the analgesic effects of cannabinoids on visceral pain from the gastrointestinal tract. The allodynic and hyperalgesic responses induced by SR141716 suggest the existence of an endogenous cannabinoid tone and the activation of CB(1) receptors during noxious CRD.

PMID: 19193902 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/19193902

 


 

Mayo Clin Proc. 2009;84(1):76-8.

Cannabinoid Hyperemesis Relieved by Compulsive Bathing.

Chang YH, Windish DM.

Yale Internal Medicine Primary Care Office, 64 Robbins Street, Waterbury, CT 06708, USA.

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Cannabinoid hyperemesis is a clinical syndrome characterized by repeated vomiting and associated learned compulsive hot water bathing behavior due to long-term marijuana use. Research has identified type 1 cannabinoid receptors in the intestinal nerve plexus that have an inhibitory effect on gastrointestinal motility. This inhibitory effect may lead to hyperemesis in marijuana users. The thermoregulatory role of endocannabinoids may be responsible for the patient's need to take hot showers. We report 2 cases of cannabinoid hyperemesis that demonstrate this unusual adverse effect of marijuana use.

PMCID: PMC2664574, PMID: 19121257 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664574/

 


 

Br J Pharmacol. 2008 Nov;155(5):681-9. Epub 2008 Jul 14.

Inhibitory Effect of Salvinorin A, from Salvia Divinorum, on Ileitis-Induced Hypermotility: Cross-Talk Between Kappa-Opioid and Cannabinoid CB(1) Receptors.

Capasso R, Borrelli F, Cascio MG, Aviello G, Huben K, Zjawiony JK, Marini P, Romano B, Di Marzo V, Capasso F, Izzo AA.

Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.

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BACKGROUND AND PURPOSE: Salvinorin A, the active component of the hallucinogenic herb Salvia divinorum, inhibits intestinal motility through activation of kappa-opioid receptors (KORs). However, this compound may have target(s) other than the KORs in the inflamed gut. Because intestinal inflammation upregulates cannabinoid receptors and endogenous cannabinoids, in the present study we investigated the possible involvement of the endogenous cannabinoid system in salvinorin A-induced delay in motility in the inflamed gut.

EXPERIMENTAL APPROACH: Motility in vivo was measured by evaluating the distribution of a fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; direct or indirect activity at cannabinoid receptors was evaluated by means of binding, enzymic and cellular uptake assays.

KEY RESULTS: Salvinorin A as well as the KOR agonist U-50488 reduced motility in croton oil treated mice. The inhibitory effect of both salvinorin A and U-50488 was counteracted by the KOR antagonist nor-binaltorphimine and by the cannabinoid CB(1) receptor antagonist rimonabant. Rimonabant, however, did not counteract the inhibitory effect of salvinorin A on motility in control mice. Binding experiments showed very weak affinity of salvinorin A for cannabinoid CB(1) and CB(2) and no inhibitory effect on 2-arachidonoylglycerol and anandamide hydrolysis and cellular uptake.

CONCLUSIONS AND IMPLICATIONS: The inhibitory effect of salvinorin A on motility reveals a functional interaction between cannabinoid CB(1) receptors and KORs in the inflamed--but not in the normal--gut in vivo.

PMCID: PMC2584932, PMID: 18622408 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2584932/