Effects of SR 141716A after acute or chronic cannabinoid administration in dogs

Lichtman, Aron H.; Wiley, Jenny L.; LaVecchia, Kari L.; Neviaser, Scott T.; Arthur, David; Wilson, David M.; Martin, Billy R.

doi:10.1016/s0014-2999(98)00558-5

Cited by 70 publications

(43 citation statements)

References 32 publications

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“…Accordingly, this preparation may serve as an in vitro model for cannabinoid dependence. In line with the observation of Guagnini and colleagues77 is a finding by Lichtman and colleagues78 that one of the withdrawal signs induced by SR141716A in Δ 9 -THC tolerant dogs is diarrhoea. It is noteworthy however that SR141716A (1 μM) has been reported not to induce “withdrawal” contractions in resting (+)-WIN55212 tolerant guinea pig MPLM 76…”

Section: Gastrointestinal Signs Of Tolerance and Dependencesupporting

confidence: 77%

Cannabinoids and the gastrointestinal tract

Pertwee

2001

Gut

288

239

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The enteric nervous system of several species, including the mouse, rat, guinea pig and humans, contains cannabinoid CB1receptors that depress gastrointestinal motility, mainly by inhibiting ongoing contractile transmitter release. Signs of this depressant effect are, in the whole organism, delayed gastric emptying and inhibition of the transit of non-absorbable markers through the small intestine and, in isolated strips of ileal tissue, inhibition of evoked acetylcholine release, peristalsis, and cholinergic and non-adrenergic non-cholinergic (NANC) contractions of longitudinal or circular smooth muscle. These are contractions evoked electrically or by agents that are thought to stimulate contractile transmitter release either in tissue taken from morphine pretreated animals (naloxone) or in unpretreated tissue (γ-aminobutyric acid and 5-hydroxytryptamine). The inhibitory effects of cannabinoid receptor agonists on gastric emptying and intestinal transit are mediated to some extent by CB1 receptors in the brain as well as by enteric CB1 receptors. Gastric acid secretion is also inhibited in response to CB1 receptor activation, although the detailed underlying mechanism has yet to be elucidated. Cannabinoid receptor agonists delay gastric emptying in humans as well as in rodents and probably also inhibit human gastric acid secretion. Cannabinoid pretreatment induces tolerance to the inhibitory effects of cannabinoid receptor agonists on gastrointestinal motility. Findings that the CB1 selective antagonist/inverse agonist SR141716A produces in vivo and in vitro signs of increased motility of rodent small intestine probably reflect the presence in the enteric nervous system of a population of CB1 receptors that are precoupled to their effector mechanisms. SR141716A has been reported not to behave in this manner in the myenteric plexus-longitudinal muscle preparation (MPLM) of human ileum unless this has first been rendered cannabinoid tolerant. Nor has it been found to induce “withdrawal” contractions in cannabinoid tolerant guinea pig ileal MPLM. Further research is required to investigate the role both of endogenous cannabinoid receptor agonists and of non-CB1 cannabinoid receptors in the gastrointestinal tract. The extent to which the effects on gastrointestinal function of cannabinoid receptor agonists or antagonists/inverse agonists can be exploited therapeutically has yet to be investigated as has the extent to which these drugs can provoke unwanted effects in the gastrointestinal tract when used for other therapeutic purposes.

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Section: Gastrointestinal Signs Of Tolerance and Dependencesupporting

confidence: 77%

Cannabinoids and the gastrointestinal tract

Pertwee

2001

Gut

288

239

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“…Animal studies lend some credibility to this theory; however, results are not consistently reproducible in human studies. Additionally, many inferential hypotheses were identified that attribute different aspects of CHS to a myriad of dysregulatory issues at CB-1 receptors throughout the body (brain, gastrointestinal tract, and vasculature) [97,98,102,105,133,[135][136][137]. The experimental evidence behind these inferences illustrates the complexity of the pathophysiology of CHS and raises many additional questions.…”

Section: Pathophysiology Of Chsmentioning

confidence: 99%

“…Patients susceptible to developing CHS may have genetic variation in their metabolic enzymes resulting in toxic levels of cannabinoid metabolites [131] Very low Δ9-THC may act as a partial agonist on CB1 receptors and thus relatively antagonize the effects of full endogenous agonists on these receptors, thus precipitating sudden withdrawal and hyperemesis in sensitive patients [97,105] Very low THC causes dilation of splanchnic vasculature, resulting in CHS. Hot bathing leads to peripheral venodilation and shunts blood away from the splanchnic bed, resulting in symptom improvement [102,137] Very low validity of our findings is limited by the possibility of missing articles from our search strategy.…”

Section: Limitationsmentioning

confidence: 99%

Cannabinoid Hyperemesis Syndrome: Diagnosis, Pathophysiology, and Treatment—a Systematic Review

et al. 2016

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Cannabinoid hyperemesis syndrome (CHS) is a syndrome of cyclic vomiting associated with cannabis use. Our objective is to summarize the available evidence on CHS diagnosis, pathophysiology, and treatment. We performed a systematic review using MEDLINE, Ovid MEDLINE, Embase, Web of Science, and the Cochrane Library from January 2000 through September 24, 2015. Articles eligible for inclusion were evaluated using the G r a d i n g a n d R e c o m m e n d a t i o n s A s s e s s m e n t , Development, and Evaluation (GRADE) criteria. Data were abstracted from the articles and case reports and were combined in a cumulative synthesis. The frequency of identified diagnostic characteristics was calculated from the cumulative synthesis and evidence for pathophysiologic hypothesis as well as treatment options were evaluated using the GRADE criteria. The systematic search returned 2178 articles. After duplicates were removed, 1253 abstracts were reviewed and 183 were included. Fourteen diagnostic characteristics were identified, and the frequency of major characteristics was as follows: history of regular cannabis for any duration of time (100%), cyclic nausea and vomiting (100%), resolution of symptoms after stopping cannabis (96.8%), compulsive hot baths with symptom relief (92.3%), male predominance (72.9%), abdominal pain (85.1%), and at least weekly cannabis use (97.4%). The pathophysiology of CHS remains unclear with a dearth of research dedicated to investigating its underlying mechanism. Supportive care with intravenous fluids, dopamine antagonists, topical capsaicin cream, and avoidance of narcotic medications has shown some benefit in the acute setting. Cannabis cessation appears to be the best treatment. CHS is a cyclic vomiting syndrome, preceded by daily to weekly cannabis use, usually accompanied by symptom improvement with hot bathing, and resolution with cessation of cannabis. The pathophysiology underlying CHS is unclear. Cannabis cessation appears to be the best treatment

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“…The behavioral profile of anandamide is somewhat different, in that it produced little static ataxia and incoordination but did produce a loss of muscle tone and considerable sedation. However, the effects of both classes of compounds are reversed by CB1 receptor antagonists [Lichtman et al, 1998]. In rodents, which also have a relatively high density of CB1 receptors in the cerebellar molecular layer, D…”

mentioning

confidence: 99%

Neuroanatomical basis for therapeutic applications of cannabinoid receptor 1 antagonists

Thomas

2009

Drug Development Research

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The CB1 receptor is a Class A G-protein coupled receptor that has a high density and widespread distribution within the central nervous system. Because of its neuroanatomical distribution, the endocannabinoid system can modulate a wide variety of psychological and physiological functions. For example, CB1 receptors are found in brain regions regulating motor activity, cognitive processes, pain, satiety, appetitive behaviors and reward. In correspondence with this distribution, modulation of the endocannabinoid system has been shown to produce changes in coordination, executive function, memory, mood, perception, wakefulness, nociception and appetite. Administration of cannabinoid agonists has also been therapeutically used to reduce nausea, and is also known to decrease body temperature and neuronal excitability, pointing to additional roles for endocannabinoids in these and other physiological/neurological processes. The ongoing elucidation and characterization of the neuroanatomical circuitry within which the CB1 cannabinoid receptor and endocannabinoids are localized to modulate these psychological and physiological processes continues to suggest therapeutic applications for cannabinoid antagonists and inverse agonists. Drug Dev Res 70 : 527-554, 2009.

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Effects of SR 141716A after acute or chronic cannabinoid administration in dogs

Cited by 70 publications

References 32 publications

Cannabinoids and the gastrointestinal tract

Cannabinoids and the gastrointestinal tract

Cannabinoid Hyperemesis Syndrome: Diagnosis, Pathophysiology, and Treatment—a Systematic Review

Neuroanatomical basis for therapeutic applications of cannabinoid receptor 1 antagonists

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