Blockade of Effects of Smoked Marijuana by the CB1-Selective Cannabinoid Receptor Antagonist SR141716

Huestis, Marilyn A.; Gorelick, David A.; Heishman, Stephen J.; Preston, Kenzie L.; Nelson, Richard Alan; Moolchan, Eric T.; Frank, Richard A.

doi:10.1001/archpsyc.58.4.322

Cited by 433 publications

(267 citation statements)

References 40 publications

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“…Most behavioral, cognitive, and psychotropic effects of cannabis result from the effects of Δ9-THC at brain CB 1 Rs. The subjective "high" produced by cannabis can be blocked by pretreatment with the CB 1 R antagonist rimonabant [74]. Δ9-THC impairs short-term working memory in several rodent models, which can be reversed by preapplication of a CB 1 R antagonist [75][76][77][78].…”

Section: δ9-thcmentioning

confidence: 99%

Cannabinoids and Epilepsy

et al. 2015

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Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabisbased antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro-and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.

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Section: δ9-thcmentioning

confidence: 99%

Cannabinoids and Epilepsy

et al. 2015

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“…In a study investigating the ability of the CB1 receptor antagonist, rimonabant, to reverse the effects of D 9 THC, Marilyn Heustis and her colleagues found that even very high doses of rimonabant (90 mg) were only modestly effective in reducing most of the subjective components of the 'high' elicited by smoking of a cannabis cigarette. 18 Interestingly, the autonomic effect (tachycardia) elicited by cannabis was more effectively antagonized by rimonabant than the subjective effects, 18 suggesting that the former might be mediated by fatty acid amides and the latter mediated by 2-AG.…”

Section: Interaction Of Endogenous and Exogenous Cannabinoidsmentioning

confidence: 99%

Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength

Mackie

2006

Int J Obes

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The CB1 cannabinoid receptor has attracted much recent interest because of the observation that CB1 receptor antagonists have efficacy in treating metabolic syndrome and obesity. CB1 receptors also mediate most of the psychotropic effects of D 9 -tetrahydrocannabinol (D 9 THC), the principal psychoactive component of cannabis. In addition, they are one component of an interesting and widespread paracrine signaling system, the endocannabinoid system. The endocannabinoid system is comprised of cannabinoid receptors, endogenous cannabinoids, and the metabolic pathways responsible for their synthesis and degradation. The details of the endocannabinoid system have been most thoroughly studied in the brain. Here it has been shown to be intimately involved in several forms of neuronal plasticity. That is, activation of CB1 receptors by endocannabinoids produces either short-or long-term changes in the efficacy of synaptic transmission. The behavioral consequences of these changes are many, but some of the most striking and relevant to the current symposium are those associated with endogenous reward and consumptive behavior.

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“…The CB1 receptor mediates the positive subjective and reinforcing effects of cannabis (Cooper and Haney, 2008), and the subjective effects of cannabis are attenuated by the CB1 receptor antagonist, rimonabant (Huestis et al, 2001(Huestis et al, , 2007. Further study of rimonabant has, however, been discontinued following evidence that its chronic administration produced side effects such as depression and anxiety (Taylor, 2009), and the manufacturers of other CB1 receptor antagonists approved for testing in humans withdrew their clinical development after rimonabant use was suspended.…”

Section: Introductionmentioning

confidence: 99%

Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers

Haney

Ramesh

Glass

et al. 2015

Neuropsychopharmacol

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Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n = 18 M and 5 F) or placebo (0 mg; n = 26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4-6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects ('good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1-51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of 'good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder.

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Blockade of Effects of Smoked Marijuana by the CB1-Selective Cannabinoid Receptor Antagonist SR141716

Abstract: SR141716 blocked acute psychological and physiological effects of smoked marijuana without altering THC pharmacokinetics. These findings confirm, for the first time in humans, the central role of CB1 receptors in mediating the effects of marijuana.

Cited by 433 publications

References 40 publications

Cannabinoids and Epilepsy

Cannabinoids and Epilepsy

Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength

Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers

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