The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects

Hallak, Jaime E. C.; Dursun, Serdar; Bosi, Daniel C.; Macedo, Ligia Ribeiro Horta de; Machado‐de‐Sousa, João Paulo; Abrão, João; Crippa, José Alexandre S; McGuire, Philip; Krystal, John H.; Baker, Glen B.; Zuardi, Antônio Waldo

doi:10.1016/j.pnpbp.2010.11.002

Cited by 74 publications

(58 citation statements)

References 38 publications

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“…Interestingly, both rimonabant and AM251 significantly reversed the disruption of PPI produced by phencyclidine, similar to the effects of clozapine, indicating that rimonabant may exhibit an atypical antipsychotic profile presumably mediated by the CB 1 receptor. However, human studies failed to demonstrate any significant efficacy of CB 1 receptor antagonists on psychotic symptoms either in the ketamine model of schizophrenia or in schizophrenic patients (Hallak et al 2011;Meltzer et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cerebral type 1 cannabinoid receptors is associated with impaired auditory mismatch negativity generation in the ketamine model of schizophrenia

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Inhibition of cerebral type 1 cannabinoid receptors is associated with impaired auditory mismatch negativity generation in the ketamine model of schizophrenia

et al. 2011

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“…CBD also has low potency for inhibiting the uptake of striatal dopamine [36]; it modulates allosterically μ and δ opioid receptors [37] and enhances adenosine signaling through uptake inhibition [36,38]. Although more studies are needed to further understand the impact of CBD on glutamatergic neurotransmission, its protective effects on glutamate toxicity and its pharmacologic interaction with ketamine [39,40], an Nmethyl-D-aspartate receptor (NMDA) antagonist, are also well documented.…”

Section: Cbd and Neurobiological Targets/effectsmentioning

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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“…An initial investigation in healthy subjects showed that CBD induced a non-significant trend to reduce ketamine-induced dissociative effects, but, at the same time, augmented the activating effects of ketamine (28) 300 and 600 mg (acute) no effect [106] [102]. Because only a single dose of CBD was used, additional studies are needed to characterize the effects of CBD in this model [102]. The therapeutic use of CBD in psychotic patients was tested for the first time in 1995.…”

Section: Cannabidiol and Psychosismentioning

confidence: 99%

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Campos

Moreira

Gomes

et al. 2012

Phil. Trans. R. Soc. B

342

227

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Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound D 9 -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamidemediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARg receptors agonism, intracellular (Ca 2þ ) increase, etc.), on CBD behavioural effects.

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The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects

Cited by 74 publications

References 38 publications

Inhibition of cerebral type 1 cannabinoid receptors is associated with impaired auditory mismatch negativity generation in the ketamine model of schizophrenia

Inhibition of cerebral type 1 cannabinoid receptors is associated with impaired auditory mismatch negativity generation in the ketamine model of schizophrenia

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

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

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