ArticlePsychopharmacology2015
Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist.
Article in Psychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Somatic and anxiety-like behaviors in male and female rats during withdrawal from the non-selective cannabinoid agonist WIN 55,212-2.Pharmacology, biochemistry, and behavior · 2024Article
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- Novel Noninvasive Approaches to the Treatment of Obesity: From Pharmacotherapy to Gene Therapy.Endocrine reviews · 2022Review
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- Overcoming the Psychiatric Side Effects of the Cannabinoid CB1 Receptor Antagonists: Current Approaches for Therapeutics Development.Current topics in medicinal chemistry · 2019Review
- Assessment of rimonabant-like adverse effects of purported CB1R neutral antagonist / CB2R agonist aminoalkylindole derivatives in mice.Drug and alcohol dependence · 2018Article
- Characterization of structurally novel G protein biased CBPharmacological research · 2017Article
- Synthetic Pot: Not Your Grandfather's Marijuana.Trends in pharmacological sciences · 2017Review
- Tripping with Synthetic Cannabinoids ("Spice"): Anecdotal and Experimental Observations in Animals and Man.Current topics in behavioral neurosciences · 2017Review
- Pharmacological characterization of repeated administration of the first generation abused synthetic cannabinoid CP47,497.Journal of basic and clinical physiology and pharmacology · 2016Article
- Screening Medications for the Treatment of Cannabis Use Disorder.International review of neurobiology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
rationalePrevious reports shows rimonabant's inverse properties may be a limiting factor for treating cannabinoid dependence. To overcome this limitation, neutral antagonists were developed, to address mechanisms by which an inverse agonist and neutral antagonist elicit withdrawal.
objectiveThe objective of this study is to introduce an animal model to study cannabinoid dependence by incorporating traditional methodologies and profiling novel cannabinoid ligands with distinct pharmacological properties/modes of action by evaluating their pharmacological effects on CB1-receptor (CB1R) related physiological/behavioral endpoints.
methodsThe cannabinergic AM2389 was acutely characterized in the tetrad (locomotor activity, analgesia, inverted screen/catalepsy bar test, and temperature), with some comparisons made to Δ(9)-tetrahydrocannabinol (THC). Tolerance was measured in mice repeatedly administered AM2389. Antagonist-precipitated withdrawal was characterized in cannabinoid-adapted mice induced by either centrally acting antagonists, rimonabant and AM4113, or an antagonist with limited brain penetration, AM6545.
resultsIn the tetrad, AM2389 was more potent and longer acting than THC, suggesting a novel approach for inducing dependence. Repeated administration of AM2389 led to tolerance by attenuating hypothermia that was induced by acute AM2389 administration. Antagonist-precipitated withdrawal signs were induced by rimonabant or AM4113, but not by AM6545. Antagonist-precipitated withdrawal was reversed by reinstating AM2389 or THC.
conclusionsThese findings suggest cannabinoid-precipitated withdrawal may not be ascribed to the inverse properties of rimonabant, but rather to rapid competition with the agonist at the CB1R. This withdrawal syndrome is likely centrally mediated, since only the centrally acting CB1R antagonists elicited withdrawal, i.e., such responses were absent after the purported peripherally selective CB1R antagonist AM6545.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.