Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol

Gomes, Felipe V.; Llorente, Ricardo; Bel, Elaine Aparecida Del; Viveros, María-Paz; López‐Gallardo, Meritxell; Guimarães, Francisco Silveira

doi:10.1016/j.schres.2015.01.015

Cited by 127 publications

(99 citation statements)

References 63 publications

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“…The meaning of this finding is still unknown. Imipramine and CBD presented protective effects under of different animal models of neurodegenerative conditions, such as brain ischemia (Pazos et al, 2012;Schiavon et al, 2010;Schiavon et al, 2014), Alzheimer's disease (Cheng et al, 2014), Parkinson's disease (LastresBecker et al, 2005), and schizophrenia (Gomes et al, 2015). The proneurogenic activity of CBD observed in the SVZ, therefore, might be related to its reparative and/or neuroprotective effects.…”

Section: Discussionmentioning

confidence: 99%

“…Preclinical studies have shown that CBD also exhibits a profile that is similar to atypical antipsychotic drugs. Cannabidiol reduced stereotyped behavior (Zuardi et al, 1991), reversed the disruption of prepulse inhibition (Long et al, 2006;Gururajan et al, 2011), and restored MK-801-induced behavioral deficits in the social interaction and novel object recognition tests (Gomes et al, 2015). In the clinical setting, CBD attenuated some aspects of schizophrenia without producing extrapyramidal side effects (Zuardi et al, 1995;Zuardi et al, 2006;Leweke et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

Schiavon

Bonato

Milani

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

116

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

Schiavon

Bonato

Milani

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

116

View full text Add to dashboard Cite

“…Cannabidiol (dosage range: 1–50 mg/kg) itself seems to have no effect on social interaction of untreated Sprague Dawley (Malone et al, 2009; Gururajan et al, 2012), Wistar rats (van Ree et al, 1984; Deiana et al, 2015), C57BL/6JArc mice (Long et al, 2010; Gomes et al, 2015b), and wild type-like littermates of Nrg1 TM HET mice (Long et al, 2012). However, in Wistar rats 1 mg/kg cannabidiol increased social interaction behavior, whereas higher dosages (5, 15, 30, 60 mg/kg) had no effect (Almeida et al, 2013).…”

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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“…In terms of psychotropic profiles, THC is associated with transient and long-term psychotomimetic effects Murray et al, 2007), whereas clinical and preclinical research has shown that CBD can produce antipsychotic and anxiolytic effects (Crippa et al, 2011;Campos et al, 2012;Fogaca et al, 2014;Zuardi et al, 2006Zuardi et al, , 2012Mechoulam et al, 2007;Leweke et al, 2012;Renard et al, 2016a;Schubart et al, 2014;Gomes et al, 2015). In addition, CBD may modulate emotional memory processing and decrease symptoms associated with emotional memory disorders such as post-traumatic stress disorder (PTSD; Blessing et al, 2015,Betthauser et al, 2015.…”

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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Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol

Cited by 127 publications

References 63 publications

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

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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