Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine

Pedrazzi, João Francisco Cordeiro; Issy, Ana Carolina; Gomes, Felipe V.; Guimarães, Francisco Silveira; Del‐Bel, Elaine

doi:10.1007/s00213-015-3945-7

Cited by 67 publications

(53 citation statements)

References 60 publications

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“…A second potential target for CBD is the FAAH enzyme which is located intracellularly (Leweke et al, 2012;Pedrazzi et al, 2015). In the case of URB597, there is in vitro evidence to suggest that it can penetrate the plasma membrane to directly inhibit FAAH, albeit in a pH-sensitive manner (Paylor et al, 2006).…”

Section: Potential Mechanisms Of Antipsychotic Effectmentioning

confidence: 99%

“…Recent work has shown in Swiss mice that intra-accumbal administration of CBD (60 nmol) inhibited disruption of PPI induced by systemic injections of amphetamine (10 mg/kg) (Pedrazzi et al, 2015). This study also reported that a systemic injection of the FAAH inhibitor, URB597 (0.3-1 mg/kg), was able to inhibit amphetamine-induced disruption of PPI and this was indirect evidence in support of the role of CBD as an inhibitor of AEA reuptake.…”

Section: Speciesmentioning

confidence: 99%

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Does cannabidiol have a role in the treatment of schizophrenia?

Gururajan

Malone

2016

Schizophrenia Research

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Section: Potential Mechanisms Of Antipsychotic Effectmentioning

confidence: 99%

Section: Speciesmentioning

confidence: 99%

Does cannabidiol have a role in the treatment of schizophrenia?

Gururajan

Malone

2016

Schizophrenia Research

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“…In male Swiss mice, cannabidiol (15, 30, or 60 mg/kg) did not affect PPI or startle amplitude (Pedrazzi et al, 2015). On the other hand, Long et al (2006) reported that C57BL/6JArc mice acutely treated with cannabidiol (1 and 15, but not 5 mg/kg) showed increased startle amplitudes while PPI remained unaffected.…”

Section: Antipsychotic Potential Of Cannabidiol: Insights From Preclimentioning

confidence: 99%

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence

et al. 2016

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There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9-THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

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“…While the precise neuroanatomical regions responsible for CBD's actions are not known, considerable evidence implicates the nucleus accumbens (NAc) as an important site for CBD's modulatory effects on various cognitive and behavioral phenomena (Guimarães et al, 2004;Bhattacharyya et al, 2009;Valvassori et al, 2011;Mijangos-Moreno et al, 2014;Pedrazzi et al, 2015). For example, CBD attenuates THCinduced dysregulation of the ventral striatum during verbal recall tasks (Bhattacharyya et al, 2009) and increases c-fos and adenosine levels in rodent NAc (Guimarães et al, 2004;Mijangos-Moreno et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…For example, CBD attenuates THCinduced dysregulation of the ventral striatum during verbal recall tasks (Bhattacharyya et al, 2009) and increases c-fos and adenosine levels in rodent NAc (Guimarães et al, 2004;Mijangos-Moreno et al, 2014). In addition, CBD blocks amphetamine-induced oxidative stress in the NAc (Valvassori et al, 2011) and intra-NAc CBD attenuates amphetamineinduced deficits in prepulse inhibition (Pedrazzi et al, 2015;Renard et al, 2016b). Nevertheless, the precise functional and pharmacological mechanisms by which CBD may produce these effects in the mesolimbic system are not currently understood.…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System

Norris

Loureiro

Kramar

et al. 2016

Neuropsychopharmacol

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Emerging evidence suggests that the largest phytochemical component of cannabis, cannabidiol (CBD), may possess pharmacotherapeutic properties in the treatment of neuropsychiatric disorders. CBD has been reported to functionally interact with both the mesolimbic dopamine (DA) and serotonergic (5-HT) receptor systems. However, the underlying mechanisms by which CBD may modulate emotional processing are not currently understood. Using a combination of in vivo electrophysiological recording and fear conditioning in rats, the present study aimed to characterize the behavioral, neuroanatomical, and pharmacological effects of CBD within the mesolimbic pathway, and its possible functional interactions with 5-HT and DAergic transmission. Using targeted microinfusions of CBD into the shell region of the mesolimbic nucleus accumbens (NASh), we report that intra-NASh CBD potently blocks the formation of conditioned freezing behaviors. These effects were challenged with DAergic, cannabinoid CB1 receptor, and serotonergic (5-HT 1A ) transmission blockade, but only 5-HT 1A blockade restored associative conditioned freezing behaviors. In vivo intra-ventral tegmental area (VTA) electrophysiological recordings revealed that behaviorally effective doses of intra-NASh CBD elicited a predominant decrease in spontaneous DAergic neuronal frequency and bursting activity. These neuronal effects were reversed by simultaneous blockade of 5-HT 1A receptor transmission. Finally, using a functional contralateral disconnection procedure, we demonstrated that the ability of intra-NASh CBD to block the formation of conditioned freezing behaviors was dependent on intra-VTA GABAergic transmission substrates. Our findings demonstrate a novel NAc → VTA circuit responsible for the behavioral and neuronal effects of CBD within the mesolimbic system via functional interactions with serotonergic 5-HT 1A receptor signaling.

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Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine

Abstract: These results corroborate findings indicating that CBD induces antipsychotic-like effects. In addition, they pointed to the nucleus accumbens as a possible site of these effects. The increase of anandamide availability may be enrolled in the CBD effects.

Cited by 67 publications

References 60 publications

Does cannabidiol have a role in the treatment of schizophrenia?

Does cannabidiol have a role in the treatment of schizophrenia?

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence

Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System

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