Antianxiety effect of cannabidiol in the elevated plus-maze

Guimarães, F. S.; Chiaretti, T. M.; Graeff, F. G.; Zuardi, A. W.

doi:10.1007/bf02244012

Cited by 379Cannabis and Cannabinoid ResearchMedicinal Plant Extracts EffectsPsychedelics and Drug Studies

Antianxiety effect of cannabidiol in the elevated plus-maze

Guimarães, F. S., Chiaretti, T. M., Graeff, F. G., Zuardi, A. W.·1990·Psychopharmacology

DOI 10.1007/bf02244012

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Abstract

In order to assess the presence of anxiolytic properties in cannabidiol (CBD) the drug was tested in an elevated plus-maze model of anxiety, in rats. Doses of 2.5, 5.0 and 10.0 mg/kg significantly increased the entry ratio (open/total number of entries), an anxiolytic-like effect. CBD at a dose of 20.0 mg/kg was no longer effective. None of the doses of CBD used changed total number of entries, a measure of total exploratory activity. Diazepam (2.0 mg/kg) also caused an anxiolytic-like effect in this model. These results indicate that CBD causes a selective anxiolytic effect in the elevated plus-maze, within a limited range of doses.

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In rats, CBD induces anxiolytic-like effects at lower doses (2.5-10 mg/kg) that completely disappear at higher doses.
“Using this model and covering a full dose-response curve, they showed that in rats CBD does induce anxiolytic-like effects at lower doses (2.5–10 mg/kg) that completely disappear at higher doses (19).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [19]

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“However, these effects were predominantly evident after acute treatment regimes (Campos and Guimaraes 2008; Campos et al. 2013; Guimaraes et al. 1990; Long et al. 2010; Moreira et al. 2006; Onaivi et al. 1990) whereas our behavioural testing commenced only after 3-week CBD treatment.”
Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage
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Cannabidiol reduces ethanol consumption, motivation and relapse in mice
Viudez‐Martínez, A., García‐Gutiérrez, M. S., Navarrón, C. M., Morales‐Calero, M. I., Navarrete, F., Torres‐Suárez, A. I., & Manzanares, J. (2017) · Addiction Biology · doi:10.1111/adb.12495 · Cited by 152 · see citing works
“Several studies showed that CBD presents anxiolytic (Guimaraes et al. 1990; Moreira et al. 2006; Resstel et al. 2006; Lemos et al. 2010; de Mello Schier et al. 2014), antidepressant (El-Alfy et al. 2010; Zanelati et al. 2010; Schiavon et al. 2016), antipsychotic (Zuardi et al. 1991; Moreira &…”
Background
Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: involvement of 5HT1A receptors and previous stressful experience
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“For instance, Guimaraes et al. (1990) showed that CBD in doses of 2.5, 5 and 10 mg/kg had an anxiolytic effect in the Fig. 3 Mean (€SEM) number of vomiting episodes (top section )o r latency to the first vomiting episode (bottom section) displayed by the various groups pretreated with SR-141716 prior to pretreatment w…”
BackgroundInfluential
Endocannabinoid system dysfunction in mood and related disorders
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“Anxiolytic effects of CBD have been demonstrated in animal models utilizing the elevated plus maze (46).”
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Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia
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Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors
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“These apparently opposite results were subsequently explained by Guimaraes et al. (1990), who verified that CBD produces inverted Ushaped dose response curves in the elevated plus-maze.”
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“These apparently opposite results were subsequently explained by Guimarães et al. (1990), who verified that CBD causes an inverted U-shaped dose-related anxiolytic response curve in the elevated plus-maze, with the anxiolytic doses ranging from 2.5 to 20 mg/kg. Subsequent studies employing diverse…”
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Effects of cannabidiol (CBD) in neuropsychiatric disorders: A review of pre-clinical and clinical findings
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“Cannabidiol produces anxiolytic effects in both preclinical and clinical studies (Crippa et al., 2004; Guimarães et al., 1990) and blunts the anxiogenic effects of THC (Zuardi et al.”
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Repeated Cannabidiol treatment reduces cocaine intake and modulates neural proliferation and CB1R expression in the mouse hippocampus
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Cannabidiol, extracted fromCannabis sativa, selectively inhibits inflammatory hypermotility in mice
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“, 2008) in cultured cells and (2) anti-anxiety (Guimarães et al., 1990; Moreira et al., 2006), hypnotic (Carlini and Cunha, 1981), anticonvulsant (Carlini and Cunha, 1981), neuroprotective (Dirikoc et al.”
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Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats
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Anti-Aversive Effects of Cannabidiol on Innate Fear-Induced Behaviors Evoked by an Ethological Model of Panic Attacks Based on a Prey vs the Wild Snake Epicrates cenchria crassus Confrontation Paradigm
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“In the elevated plus-maze, this drug produces an anxiolytic-like effect in an inverted U-shaped dose-response curve, with higher doses no longer being effective (”
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Cannabidiol in Inflammatory Bowel Diseases: A Brief Overview
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Self-citation
Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT 1A receptors
Gomes, F. V., Reis, D. G., Alves, F. H., Corrêa, F. M., Guimarães, F. S., & Resstel, L. B. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881110389095 · Cited by 97 · see citing works
“In agreement with this proposal, acute administration of CBD has been shown to induce anxiolytic-like effects in several animal models (Guimarães et al., 1990; Moreira et al., 2006; Resstel et al., 2006b).”
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Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings.
Trigo, J. M., Lagzdins, D., Rehm, J., Selby, P., Gamaleddin, I., Fischer, B., Barnes, A. J., Huestis, M. A., & Le Foll, B. (2016) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2016.02.020 · Cited by 97 · see citing works
“Human research suggests that CBD may have anti-psychotic properties (Zuardi et al., 2006), while some pre-clinical studies suggest that CBD may have anxiolytic (Guimaraes et al., 1990) properties.”
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Cannabidiol Therapy for Refractory Epilepsy and Seizure Disorders
Golub, V. M., & Reddy, D. S. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-57369-0_7 · Cited by 98 · see citing works
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“Acute anxiolytic properties of CBD have been demonstrated in several preclinical studies that employed various paradigms such as the Vogel conflict test (Moreira et al. 2006), the elevated plus maze (Guimaraes et al. 1990) and fear conditioning (Lemos et al. 2010; Resstel et al. 2006).”
Background
Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms
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“Importantly, preclinical evidence suggests that CBD may attenuate the effects of experimentally induced stress in lab animals following both acute (Guimarães et al. 1990; Campos and Guimarães 2008; Gomes et al. 2011; Gomes et al. 2012) and chronic treatments (Campos et al.”
BackgroundInfluential
Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats
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“The pharmacological property of the anxiolytic effect of CBDhas been demonstrated in both animal researches (Guimaraes et al., 1990; Mechoulam et al., 2002; Pickens, 1981) and human studies (Crippa et al., 2004; Fusar-Poli et al., 2010), and becomes significant for therapeutic purposes.”
Method

Effects of cannabidiol and Δ9-tetrahydrocannabinol in the elevated plus maze in mice
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Sex-dependent differences in the anxiolytic-like effect of cannabidiol in the elevated plus-maze
Fabris, D., Carvalho, M. C., Brandão, M., Prado, W. A., Zuardi, A., Crippa, J., de Oliveira, A. D., Lovick, T., & Genaro, K. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811221125440 · Cited by 38 · see citing works

Authors: Guimarães, F. S., Chiaretti, T. M., Graeff, F. G., & Zuardi, A. W.
Affiliations: Universidade de São Paulo (BR)
ORCID: Guimarães, F. S.
Graeff, F. G.
Zuardi, A. W.
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 1990-04
Volume: 100
Issue: 4
Pages: 558-559
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/bf02244012
OpenAlex: W2052034283
Cited by: 379
References: 8
Citations by year: 2026: 10 · 2025: 24 · 2024: 21 · 2023: 25 · 2022: 34 · 2021: 31 · 2020: 26 · 2019: 21 · 2018: 21 · 2017: 21 · 2016: 15 · 2015: 10 · 2014: 8 · 2013: 12 · 2012: 20
FWCI: 1.26
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Keywords: cannabidiol, anxiolytic effects, elevated plus maze, anxiety, exploratory activity, dose-response relationship, diazepam, rats
MeSH terms: Animals, Cannabidiol, Cannabinoids, Diazepam, Dose-Response Relationship, Drug, Injections, Intraperitoneal, Male, Rats, Inbred Strains, Anti-Anxiety Agents, Rats

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Antianxiety effect of cannabidiol in the elevated plus-maze

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