Effect of low doses of ?9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats

Parker, Linda A.; Burton, Page; Sorge, Robert E.; Yakiwchuk, Christine; Mechoulam, Raphael

doi:10.1007/s00213-004-1825-7

Cited by 154 publications

(149 citation statements)

References 36 publications

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“…Alone, CBD, a cannabinoid void of THC-like psychoactivity, produced no preference or aversion at any of the four doses tested. These results are consistent with a previous report in which 5 mg/kg CBD alone failed to alter preference in a place conditioning procedure in rats (Parker et al, 2004). However, in that study both CBD and THC potentiated cocaine and amphetamine induced extinction of place preference learning.…”

Section: Place Conditioning Effects Of Thc and Cbdsupporting

confidence: 93%

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

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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.

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Section: Place Conditioning Effects Of Thc and Cbdsupporting

confidence: 93%

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

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“…The design of the present experiments cannot discriminate between these two potential mechanisms; however, a memory deficit explanation is less tenable in light of the finding in experiment 1 that the highest dose of CBD (10 mg/kg) did not modify the expression of gaping. Furthermore, at a dose of 5 mg/kg CBD neither affected the acquisition nor retrieval of a floor-amphetamine association in a conditioned place preference task (Parker et al 2004a) or of a flavor-lithium association in a conditioned taste avoidance task (Parker et al 2002). Finally, Varvel et al (2007) reported that mice pre-treated with the FAAH inhibitor, OL-135, as well as FAAH knockout mice with elevated central AEA levels, did not display memory impairment or motor disruption in a spatial memory task (Morris water maze); in fact, the FAAH knockouts displayed a significant increase in acquisition rate.…”

Section: Discussionmentioning

confidence: 84%

The effect of cannabidiol and URB597 on conditioned gaping (a model of nausea) elicited by a lithium-paired context in the rat

et al. 2007

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Rationale Anticipatory nausea (AN) experienced by chemotherapy patients is resistant to current anti-nausea treatments. In this study, the effect of manipulation of the endocannabinoid (EC) system on a rat model of nausea (conditioned gaping) was determined. Objective The potential of cannabidiol (CBD) and the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (URB) to reduce conditioned gaping in rats were evaluated. Materials and methods In each experiment, rats received four conditioning trials in which they were injected with lithium chloride immediately before placement in a distinctive odor-laced context. During testing, in experiment 1, rats were injected with vehicle (VEH), 1, 5 or 10 mg/kg CBD 30 min before placement in the context previously paired with nausea and in experiment 2, rats were injected with VEH, 0.1 or 0.3 mg/kg URB 2 h before placement in the context. Additional groups evaluated the ability of the CB 1 antagonist/inverse agonist, SR141716A, to reverse the suppressive effects of URB. Experiment 3 measured the potential of URB to interfere with the establishment of conditioned gaping.Results When administered before testing, CBD (1 and 5, but not 10 mg/kg) and URB (0.3, but not 0.1 mg/kg) suppressed conditioned gaping. The effect of URB was reversed by pre-treatment with the CB 1 antagonist/inverse agonist, SR141716A. When administered before conditioning, URB also interfered with the establishment of conditioned gaping. Conclusions Manipulations of the EC system may have therapeutic potential in the treatment of AN.

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“…This is in keeping with similar indications observed in rats in which cannabidiol reversed apomorphine-induced stereotypy (Zuardi et al, 1991) and in a female schizophrenic patient in whom cannabidiol markedly reduced psychotic symptoms (Zuardi et al, 1995). The dose range of cannabidiol (1, 5, and 15 mg/kg) used in the present study is lower than doses previously determined to reverse the effects of psychoactive drugs in rats (Zuardi et al, 1991;Moreira and Guimaraes, 2005); however, it has previously been shown to be active in extinguishing conditioned place preference learning induced by amphetamine and cocaine (Parker et al, 2004). The lack of effect of either capsazepine or cannabidiol per se on PPI and startle response suggests that these drugs do not directly interfere with normal sensorimotor gating in the mouse.…”

Section: Discussionmentioning

confidence: 62%

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

Long

Malone

Taylor

2005

Neuropsychopharmacol

154

102

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Cannabidiol, a nonpsychoactive constituent of the Cannabis sativa plant, has been reported to act as an agonist of the vanilloid 1 channel in the transient receptor potential family (TRPV1) and also to inhibit the hydrolysis and cellular uptake of the endogenous cannabinoid anandamide. Cannabidiol has also been reported to have potential as an antipsychotic. We investigated the effect of cannabidiol on sensorimotor gating deficits in mice induced by the noncompetitive NMDA receptor antagonist, MK-801. Sensorimotor gating is deficient in psychotic disorders such as schizophrenia and may be reliably measured by prepulse inhibition (PPI) of the startle response in rodents and humans. MK-801 (0.3-1 mg/kg i.p.) dose dependently disrupted PPI while cannabidiol (1-15 mg/kg i.p.), when administered with vehicle, had no effect on PPI. Cannabidiol (5 mg/kg i.p.) successfully reversed disruptions in PPI induced by MK-801 (1 mg/kg i.p.), as did the atypical antipsychotic clozapine (4 mg/kg i.p.). Pretreatment with capsazepine (20 mg/kg i.p.) prevented the reversal of MK-801-induced disruption of PPI by cannabidiol, providing preliminary evidence that TRPV1 receptors are involved in the reversal of MK-801-induced sensorimotor gating deficits by cannabidiol.

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Effect of low doses of ?9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats

Abstract: These results are the first to show that both delta9-THC, which acts on both CB 1 and CB2 receptors, and CBD, which does not bind to CB1 or CB2 receptors, potentiate the extinction of conditioned incentive learning.

Cited by 154 publications

References 36 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

The effect of cannabidiol and URB597 on conditioned gaping (a model of nausea) elicited by a lithium-paired context in the rat

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

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