Cannabidiol potentiates Δ9-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats

Klein, Charlotte; Karanges, Emily A; Spiro, Adena S.; Wong, Alexander; Spencer, Jarrah R.; Huynh, Thanh; Gunasekaran, Nathan; Karl, Tim; Long, Leonora E.; Huang, Xu‐Feng; Liu, Kelly H.; Arnold, Jonathon C.; McGregor, Iain S.

doi:10.1007/s00213-011-2342-0

Cited by 180 publications

(148 citation statements)

References 56 publications

(94 reference statements)

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“…It must be noted that CBD's reversal of THC-induced laziness in slackers is a modest effect, an issue underscored by the small number (8 slackers) used. However, other studies have also shown that CBD-THC interactions produce only modest physiologic and psychological changes 36 that are sensitive to numerous factors, including the specific THC/CBD doses used, their ratio, and timing of coadministration. 37 Understanding the mechanism by which CBD partially ameliorates THC's effects may provide insight into why this effect is not as robust as expected.…”

Section: Discussionmentioning

confidence: 99%

“…Recent in vitro evidence suggests that CBD may inhibit the effects of THC through negative allosteric modulation of the CB 1 receptor, 38 whereas human neuroimaging studies indicate that THC and CBD differentially influence brain activity while performing cognitive or emotional tasks. [39][40][41] And while both additive 36 and antagonistic 18,42 associations have been reported between these agents in rodents, to date no studies have provided a direct mechanism as to how CBD moderates THC's behavioural effects.…”

Section: Discussionmentioning

confidence: 99%

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Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats

Silveira

Adams

Morena

et al. 2017

JPN

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats

Silveira

Adams

Morena

et al. 2017

JPN

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“…Findings to date suggest minimal CBD impact on apparent positive subjective effects induced by psychostimulants or THC [70,71,78]. Moreover, no animal studies have been published to date regarding CBD's effects on nicotine or alcohol.…”

Section: Cbd In Preclinical Addiction Modelsmentioning

confidence: 99%

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

et al. 2015

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Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ 9 -tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from Bmedical CBD^and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.

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“…CBD has also been shown to attenuate THC-induced memory impairment [80]. However, in mice and rats, CBD inhibits metabolism of THC, so that pretreatment with CBD can increase brain concentrations of THC and thereby potentiate its behavioral effects [82]. In a series of functional magnetic resonance imaging experiments in which CBD and THC were administered to healthy human subjects, the 2 compounds produced largely opposite patterns of activation during tasks involving memory, emotional processing, salience, and response inhibition in key brain regions implicated in schizophrenia, such as the striatum, prefrontal cortex, and hippocampus [3,81].…”

Section: Cbdmentioning

confidence: 99%

Cannabinoids and Schizophrenia: Risks and Therapeutic Potential

Manseau

Goff

2015

Neurotherapeutics

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A convergence of evidence shows that use of Cannabis sativa is associated with increased risk of developing psychotic disorders, including schizophrenia, and earlier age at which psychotic symptoms first manifest. Cannabis exposure during adolescence is most strongly associated with the onset of psychosis amongst those who are particularly vulnerable, such as those who have been exposed to child abuse and those with family histories of schizophrenia. Schizophrenia that develops after cannabis use may have a unique clinical phenotype, and several genetic polymorphisms may modulate the relationship between cannabis use and psychosis. The endocannabinoid system has been implicated in psychosis both related and unrelated to cannabis exposure, and studying this system holds potential to increase understanding of the pathophysiology of schizophrenia. Anandamide signaling in the central nervous system may be particularly important. Δ 9 -Tetrahydrocannabinol in cannabis can cause symptoms of schizophrenia when acutely administered, and cannabidiol (CBD), another compound in cannabis, can counter many of these effects. CBD may have therapeutic potential for the treatment of psychosis following cannabis use, as well as schizophrenia, possibly with better tolerability than current antipsychotic treatments. CBD may also have antiinflammatory and neuroprotective properties. Establishing the role of CBD and other CBD-based compounds in treating psychotic disorders will require further human research.

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Cannabidiol potentiates Δ9-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats

Abstract: CBD can potentiate the psychoactive and physiological effects of THC in rats, most likely by delaying the metabolism and elimination of THC through an action on the CYP450 enzymes that metabolise both drugs.

Cited by 180 publications

References 56 publications

Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats

Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

Cannabinoids and Schizophrenia: Risks and Therapeutic Potential

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