Δ9-Tetrahydrocannabinol discrimination in rats as a model for cannabis intoxication

Balster, Robert L.; Prescott, William R.

doi:10.1016/s0149-7634(05)80051-x

Cited by 124 publications

(89 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, these effects serve as an animal model of the subjective effects of marijuana in humans (Balster and Prescott, 1992). In drug discrimination studies, combined administration of THC and CBD has resulted in varied effects including no effect, lack of antagonism, or time course potentiation.…”

Section: Cbd and Thc Interactions In Drug Discriminationmentioning

confidence: 99%

See 1 more Smart Citation

Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Δ9-tetrahydrocannabinol

Vann

Gamage

Warner

et al. 2008

Drug and Alcohol Dependence

114

View full text Add to dashboard Cite

Cannabis sativa (marijuana plant) contains myriad cannabinoid compounds; yet, investigative attention has focused almost exclusively on Δ 9 -tetrahydrocannabinol (THC), its primary psychoactive substituent. Interest in modulation of THC's effects by these other cannabinoids [e.g., cannabidiol (CBD)] has been stimulated anew by recent approval by Canada of Sativex (a 1:1 dose ratio combination of CBD:THC) for the treatment of multiple sclerosis. The goal of this study was to determine the degree to which THC's abuse-related effects were altered by co-administration of CBD. To this end, CBD and THC were assessed alone and in combination in a two-lever THC discrimination procedure in Long-Evans rats and in a conditioned place preference/aversion (CPP/ A) model in ICR mice. CBD did not alter the discriminative stimulus effects of THC at any CBD:THC dose ratio tested. In contrast, CBD, at CBD:THC dose ratios of 1:1 and 1:10, reversed CPA produced by acute injection with 10 mg/kg THC. When administered alone, CBD did not produce effects in either procedure. These results suggest that CBD, when administered with THC at therapeutically relevant ratios, may ameliorate aversive effects (e.g., dysphoria) often associated with initial use of THC alone. While this effect may be beneficial for therapeutic usage of a CBD:THC combination medication, our discrimination results showing that CBD did not alter THC's discriminative stimulus effects suggest that CBD:THC combination medications may also produce THC-like subjective effects at these dose ratios.

show abstract

Section: Cbd and Thc Interactions In Drug Discriminationmentioning

confidence: 99%

“…While the THC drug discrimination represents an excellent model of the subjective intoxication produced by marijuana (Balster and Prescott, 1992), THC has other types of stimulus effects that may not be assessed adequately in this procedure. Specifically, THC may produce rewarding or aversive effects.…”

Section: Place Conditioning Effects Of Thc and Cbdmentioning

confidence: 99%

Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Δ9-tetrahydrocannabinol

Vann

Gamage

Warner

et al. 2008

Drug and Alcohol Dependence

114

View full text Add to dashboard Cite

show abstract

“…The presence or absence of discriminable interoceptive CNS effects of a compound can be evaluated in animals with two-lever choice drug-discrimination procedures. Discriminative-stimulus effects of THC in animals show a high degree of pharmacological specificity and provide a reliable animal model of subjective effects of marijuana or THC in humans (Balster and Prescott, 1992;Barrett et al, 1995;Wiley et al, 1995b). Usually, only other cannabinoids that are active at central cannabinoid CB1 receptors reliably produce THC-like discriminative effects in animals (Barrett et al, 1995;Wiley et al, 1995b;Jarbe et al, 2001).…”

Section: Subjective and Motivational Effects Of Cannabinoidsmentioning

confidence: 99%

“…route of administration, which does not favor rapid entry into the brain before metabolic breakdown, may explain the difficulties encountered in demonstrating THC-like discriminative effects of anandamide in animals. Among noncannabinoid drugs, only pentobarbital and diazepam have been found to produce partial generalization to a cannabinoid training stimulus (Mokler et al, 1986;Balster and Prescott, 1992;Barrett et al, 1995;Wiley and Martin, 1999;Alici and Appel, 2004). Since this effect of diazepam is not blocked by the cannabinoid CB 1 receptor antagonist rimonabant (SR 141716), it is probably mediated by an interaction through the GABAergic system (Wiley and Martin, 1999).…”

Section: Subjective and Motivational Effects Of Cannabinoidsmentioning

confidence: 99%

Self-administration of cannabinoids by experimental animals and human marijuana smokers

Justinová

Goldberg

Heishman

2005

Pharmacology Biochemistry and Behavior

115

View full text Add to dashboard Cite

Drug self-administration behavior has been one of the most direct and productive approaches for studying the reinforcing effects of psychoactive drugs, which are critical in determining their abuse potential. Cannabinoids, which are usually abused by humans in the form of marijuana, have become the most frequently abused illicit class of drugs in the United States. The early elucidation of the structure and stereochemistry of delta-9-tetrahydrocannabinol (THC) in 1964, which is now recognized as the principal psychoactive ingredient in marijuana, activated cannabinoid research worldwide. This review examines advances in research on cannabinoid self-administration behavior by humans and laboratory animals. There have been numerous laboratory demonstrations of the reinforcing effects of cannabinoids in human subjects, but reliable self-administration of cannabinoids by laboratory animals has only recently been demonstrated. It has now been shown that strong and persistent self-administration behavior can be maintained in experimentally and drugnaïve squirrel monkeys by doses of THC comparable to those in marijuana smoke inhaled by humans. Furthermore, reinforcing effects of some synthetic CB 1 cannabinoid agonists have been recently reported using intravenous and intracerebroventricular self-administration procedures in rats and mice. These findings support previous conclusions that THC has a pronounced abuse liability comparable to other drugs of abuse under certain experimental conditions. Self-administration of THC by squirrel monkeys provides the most reliable animal model for human marijuana abuse available to date. This animal model now makes it possible to study the relative abuse liability of other natural and synthetic cannabinoids and to preclinically assess new therapeutic strategies for the treatment or prevention of marijuana abuse in humans.

show abstract

“…Studies employing this model have demonstrated that activation of CB1-Rs induces interoceptive effects in gerbils , pigeons , rodents (Balster and Prescott, 1992), and monkeys (Wiley et al, 1995). Cannabinoid DS effects show high pharmacological specificity, as they are selectively blocked by CB1-R antagonists, although a partial overlap has been reported with diazepam (Mokler et al, 1986;Wiley and Martin, 1999), phencyclidine (Doty et al, 1994), and pentobarbital (Alici and Appel, 2004).…”

mentioning

confidence: 99%

Neurobiological mechanisms of cannabinoid addiction

Fattore

Fadda

Spano

et al. 2008

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Please cite this article as: Fattore, L., Fadda, P., Spano, M.S., Pistis, M., Fratta, W., Neurobiological mechanisms of cannabinoid addiction, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 2 AbstractThe endocannabinoid system is implicated in the regulation of a variety of physiological processes, among which conditioning, motivation, habit forming, memory, learning, and cognition play pivotal roles in drug reinforcement and reward. In this article we will give a synopsis of last developments in research on cannabinoid actions on brain reward circuits coming from behavioral, neurochemical and electrophysiological studies. Central cannabinoid-induced effects as measured by animal models of addiction, in vivo cerebral microdialysis, in vitro and in vivo electrophysiological recording techniques, will be reviewed.Brain sites that have been implicated in the mediation of addictive cannabinoid properties include primarily the ventral tegmental area, the nucleus accumbens, and the medial prefrontal cortex, although the amygdala, the substantia nigra, the globus pallidus, and the hippocampus have also been shown to be critical structures mediating motivational and reinforcing effects of cannabinoids. Putative neurobiological mechanisms underlying these effects will be delineated.

show abstract

Δ9-Tetrahydrocannabinol discrimination in rats as a model for cannabis intoxication

Cited by 124 publications

References 28 publications

Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Δ9-tetrahydrocannabinol

Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Δ9-tetrahydrocannabinol

Self-administration of cannabinoids by experimental animals and human marijuana smokers

Neurobiological mechanisms of cannabinoid addiction

Contact Info

Product

Resources

About