Evidence map›Paper›PMID 29869197›Full record

ArticleMolecular neurobiology2019

Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex.

Amanda J Sales, Manoela V Fogaça, Ariandra G Sartim, Vitor S Pereira, Gregers Wegener, Francisco S Guimarães, Sâmia R L Joca

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04732169 (Cannabidiol for Treatment Resistant Depression), which is not on this map. Cited by 95 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04732169 phase4withdrawnnot on this mapstarted 2021, after this paper: background citation

Cannabidiol for Treatment Resistant Depression

TypeinterventionalSponsorUniversity of Alabama at BirminghamRan2021 to 2021Enrolled0ConditionsTreatment Resistant DepressionArmsActive study drug ( oral CBD), matching placebo
3 · Its place in the literature

Who cites it

95 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2020
    Pooled it
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  14. New cannabidiol structure-related terpeneFuture medicinal chemistry · 2025
    Article
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  19. Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  20. Article

35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Amanda J SalesDepartment of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.ORCID http://orcid.org/0000-0003-0816-1792
Manoela V FogaçaDepartment of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Ariandra G SartimDepartment of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Vitor S PereiraTranslational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital, Risskov, Denmark.
Gregers WegenerTranslational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital, Risskov, Denmark.
Francisco S GuimarãesDepartment of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Sâmia R L JocaDepartment of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. samia@usp.br.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Currently available antidepressants have a substantial time lag to induce therapeutic response and a relatively low efficacy. The development of drugs that addresses these limitations is critical to improving public health. Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is a promising compound since it shows large-spectrum therapeutic potential in preclinical models and humans. However, its antidepressant properties have not been completely investigated. Therefore, the aims of this study were to investigate in male rodents (i) whether CBD could induce rapid and sustained antidepressant-like effects after a single administration and (ii) whether such effects could be related to changes in synaptic proteins/function. Results showed that a single dose of CBD dose-dependently induced antidepressant-like effect (7-30 mg/kg) in Swiss mice submitted to the forced swim test (FST), 30 min (acute) or 7 days (sustained) following treatment. Similar effects were observed in the Flinders Sensitive and Flinders Resistant Line (FSL/FRL) rats and the learned helplessness (LH) paradigm using Wistar rats. The acute antidepressant effects (30 min) were associated with increased expression of synaptophysin and PSD95 in the medial prefrontal cortex (mPFC) and elevated BDNF levels in both mPFC and hippocampus (HPC). CBD also increased spine density in the mPFC after 30 min, but not 7 days later. Intracerebroventricular injection of the TrkB antagonist, K252a (0.05 nmol/μL), or the mTOR inhibitor, rapamycin (1 nmol/μL), abolished the behavioral effects of CBD. These results indicate that CBD induces fast and sustained antidepressant-like effect in distinct animal models relevant for depression. These effects may be related to rapid changes in synaptic plasticity in the mPFC through activation of the BDNF-TrkB signaling pathway. The data support a promising therapeutic profile for CBD as a new fast-acting antidepressant drug.

Indexed as

AnimalsAntidepressive AgentsBehavior, AnimalBrain-Derived Neurotrophic FactorCannabidiolDepressionHippocampusMaleMicePrefrontal CortexSignal TransductionAntidepressive AgentsBrain-Derived Neurotrophic FactorCannabidiolAntidepressantBDNFCannabidiolPrefrontal cortex

Identifiers

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.