Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not CB1 and CB2 receptors

Silva, Naielly Rodrigues da; Gomes, Felipe V.; Sonego, Andreza Buzolin; Silva, Nicole Rodrigues da; Guimarães, Francisco Silveira

doi:10.1016/j.phrs.2020.104749

Cited by 61 publications

(46 citation statements)

References 67 publications

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“…In this study, the high dose of CBD showed the same efficacy as the antipsychotic drug clozapine [193]. Moreover, social interaction and novelty object recognition tests revealed protective effects of CBD when administered after the end of the MK-801 chronic administration, in which 5-HT 1A receptors appear to play a relevant role [194]. Despite these promising results, in other rodent studies, CBD slightly modulated the PPI impairment induced by MK-801, without normalizing locomotor hyperactivity or social interaction [184,186].…”

Section: Results From Animal Studiessupporting

confidence: 52%

Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

et al. 2020

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The potential therapeutic use of some Cannabis sativa plant compounds has been attracting great interest, especially for managing neuropsychiatric disorders due to the relative lack of efficacy of the current treatments. Numerous studies have been carried out using the main phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD displays an interesting pharmacological profile without the potential for becoming a drug of abuse, unlike THC. In this review, we focused on the anxiolytic, antidepressant, and antipsychotic effects of CBD found in animal and human studies. In rodents, results suggest that the effects of CBD depend on the dose, the strain, the administration time course (acute vs. chronic), and the route of administration. In addition, certain key targets have been related with these CBD pharmacological actions, including cannabinoid receptors (CB1r and CB2r), 5-HT1A receptor and neurogenesis factors. Preliminary clinical trials also support the efficacy of CBD as an anxiolytic, antipsychotic, and antidepressant, and more importantly, a positive risk-benefit profile. These promising results support the development of large-scale studies to further evaluate CBD as a potential new drug for the treatment of these psychiatric disorders.

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Section: Results From Animal Studiessupporting

confidence: 52%

Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

et al. 2020

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“…Thus, the allosteric 5-HT 1A receptor modulation by CBD may also be an additional relevant mechanism of action. This hypothesis is consistent with the preclinical finding that CBD attenuates cognitive impairments in a schizophrenia-like animal mode and that these effects can be blocked by a 5-HT 1A receptor antagonist but not by CB 1 and CB 2 receptor antagonists ( Rodrigues da Silva et al, 2020 ). Thus, the allosteric 5-HT 1A receptor modulation by CBD may also be an additional relevant mechanism of action.…”

Section: Discussionsupporting

confidence: 90%

Cannabidiol and Amisulpride Improve Cognition in Acute Schizophrenia in an Explorative, Double-Blind, Active-Controlled, Randomized Clinical Trial

et al. 2021

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Cannabidiol (CBD), a principal phytocannabinoid constituent, has demonstrated antipsychotic properties in recent clinical trials. While it has also been suggested a promising candidate for the treatment of neurodegenerative disorders, it failed to demonstrate efficacy in cognitive impairments associated with schizophrenia as an add-on treatment (600 mg/day for 6 weeks) in 18 chronically ill patients co-treated with a variety of psychopharmacologic drugs. Here, we report on the results of parallel-group, active-controlled, mono-therapeutic, double-blind, randomized clinical trial (CBD-CT1; ClinicalTrials.gov identifier: NCT00628290) in 42 acute paranoid schizophrenic patients receiving either CBD (up to 800 mg/day) or amisulpride (AMI, up to 800 mg/day) for four weeks in an inpatient setting with neurocognition as a secondary objective. Twentynine patients (15 and 14 in the CBD and AMI group, respectively) completed two cognitive assessments at baseline and the end of the treatment period. We investigated the following cognitive domains: pattern recognition, attention, working memory, verbal and visual memory and learning, processing speed, and verbal executive functions. When applying the Bonferroni correction for multiple testing, p < 0.0004 would indicate statistical significance. There was no relevant difference in neurocognitive performance between the CBD and the AMI group at baseline, and we observed no post-treatment differences between both groups. However, we observed improvements within both groups from pre-to post-treatment (standardized differences reported as Cohen’s d) in visual memory (CBD: 0.49, p = 0.015 vs. AMI: 0.63, p = 0.018) and processing speed (CBD: 0.41, p = 0.004 vs. AMI: 0.57, p = 0.023). Furthermore, CBD improved sustained attention (CBD: 0.47, p = 0.013, vs. AMI: 0.52, p = 0.085), and visuomotor coordination (CBD: 0.32, p = 0.010 vs. AMI: 0.63, p = 0.088) while AMI led to enhanced working memory performance in two different paradigms (Subject Ordered Pointing Task–AMI: 0.53, p = 0.043 vs. CBD: 0.03, p = 0.932 and Letter Number Sequencing–AMI: 0.67, p = 0.017 vs. CBD: 0.08 p = 0.755). There was no relevant correlation between changes in neurocognitive parameters and psychotic symptoms or anandamide serum levels. This study shows that both CBD and AMI improve neurocognitive functioning with comparable efficacy in young and acutely ill schizophrenia patients via an anandamide-independent mechanism.

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“…Moreover, in a spontaneously hypertensive rat strain (an animal model of schizophrenia), intra-peritoneal CBD prevented both hyperlocomotion and deficits in PPI (105). CBD attenuated also hyper-locomotion, social interaction and cognitive impairments induced in rodents by the NMDA receptor antagonist MK-801 (106,107).…”

Section: Psychosismentioning

confidence: 90%

Cannabidiol and the central nervous system: translating into clinics

Saviano¹,

Raucci²,

Tallarico³

et al. 2021

Pharm Adv

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Cannabis plants contain more than a hundred cannabinoids of which we have only limited knowledge about their effects and exact mechanisms of action. Cannabidiol (CBD) represents one of the most studied; it was discovered at the beginning of the last century while only recently has attracted greater attention. CBD mechanism of action is still unclear and debated; in the plant only the (-) enantiomer can be found and it seems that only the (+) enantiomer is able to bind to the cannabinoid receptors although evidence of a modulation of the endocannabinoid system exists. Furthermore, several other mechanisms have been proposed which may be differently relevant for different disease spanning from ion channels to immune responses and modulation of inflammation. It is a highly lipophilic drug with a peculiar pharmacokinetic which has led to the use and proposal of different formulations and routes of administration; of note, CBD has a complex interaction with cytochromes and is at high risk of drug-drug interaction with many drugs. Nowadays, CBD has been studied for potential efficacy in several pathologies and central nervous system (CNS) diseases are the most promising with clinical studies already in the started and some formulations with CBD already authorized for the treatment of spasticity in multiple sclerosis and seizures in some specific epileptic syndromes such as Lennox-Gastaut or Dravet. This review article is summarizing the relevant studies and perspectives of CBD use in the most relevant areas of CNS disorders also including a detailed description of its proposed mechanism(s) of action, pharmacokinetic characteristics and safety profile.

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Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not CB1 and CB2 receptors

Cited by 61 publications

References 67 publications

Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

Cannabidiol and Amisulpride Improve Cognition in Acute Schizophrenia in an Explorative, Double-Blind, Active-Controlled, Randomized Clinical Trial

Cannabidiol and the central nervous system: translating into clinics

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