Co-administration of cannabidiol and ketamine induces antidepressant-like effects devoid of hyperlocomotor side-effects

Sartim, Ariandra Guerini; Marques, João Mazzoncini de Azevedo; Silveira, Kennia Moura; Gobira, Pedro H.; Guimarães, Francisco Silveira; Wegener, Gregers; Joca, Sâmia Regiane Lourenço

doi:10.1016/j.neuropharm.2021.108679

Cited by 14 publications

(7 citation statements)

References 70 publications

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“…Moreover, the antidepressant effect of CBD at similar doses used in our study has been associated with the elevation of neuroplasticity indices, including BDNF, potentially through NMDA and AMPA activation (Silote et al, 2019). A recent study has shown that CBD's antidepressant effect relies on AMPA receptor activation (Sartim et al, 2021), supporting the abovementioned mechanistic explanation. Noteworthy, we have shown that repeated CBD administration did not act additively following repeated KET administration in this manner, but on the contrary, it depressed KET-induced effects in terms of NMDA subunit expression, which is associated with this schizophrenialike profile.…”

Section: Discussionsupporting

confidence: 84%

CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration

et al. 2021

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Clinical evidence and experimental studies have shown the psychotomimetic properties induced by ketamine. Moreover, acute or chronic ketamine (KET) administration has been widely used for modeling schizophrenia-like symptomatology and pathophysiology. Several studies have reported the antipsychotic potential of cannabidiol (CBD), while there is limited information on the cannabidiol effect on KET-induced schizophrenia-like impairments. Therefore, the goal of the present study was to evaluate neuroplastic changes induced by repeated KET administration, which is used as an experimental model of schizophrenia—with a behavioral focus on positive-like symptomatology– and to assess the modulatory role of CBD treatment. The present findings have shown a robust increase in motor activity in KET-treated rats, following a 10-day period of chronic administration at the sub-anesthetic dose of 30 mg/kg (i.p), that was reversed to normal by subsequent chronic CBD treatment. Concerning the expression of glutamate receptors, the current findings have shown region-dependent KET-induced constitutional alterations in NMDA and AMPA receptors that were modified by subsequent CBD treatment. Additionally, repeated KET administration increased ERK1/2 phosphorylation state in all regions examined, apart from the ventral hippocampus that was modulated by subsequent CBD treatment. The present results show, for the first time, a stimulated motor output coupled with a specific glutamatergic-related status and ERK1/2 activation following chronic KET administration that were attenuated by CBD treatment, in a region-dependent manner. These findings provide novel information concerning the antipsychotic potential of CBD using a specific design of chronic KET administration, thus contributing to experimental approaches that mirror the symptomatology and pathophysiology of schizophrenia.

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Section: Discussionsupporting

confidence: 84%

CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration

et al. 2021

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“…NBQX antagonizes the antidepressant effects of both substances. Interestingly, previous treatment with CBD (10 mg/kg) reduced ketamine-induced increases in motor activity but preserved ketamine-induced antidepressant effects [ 79 ]. These results suggest that AMPA signaling is, as happens for ketamine, responsible for CBD antidepressant activity and that on the basis of prevention of hyperactivity induced by ketamine, CBD could be explored as a potential adjuvant for mood disorders.…”

Section: Resultsmentioning

confidence: 99%

“… Higher dose of S-ketamine showed antidepressant effects with increase in motor activity. [ 79 ] i.p. = intraperitoneal; i.m.…”

Section: Resultsmentioning

confidence: 99%

“…CBD is also implicated in the activation and upregulation of PPARγ, a receptor known to be associated with the appearance of oral dyskinesia [ 75 ]. Moreover, CBD also showed potential antidepressant effects without any changes in locomotor activity [ 79 ], thus suggesting the possibility of using CBD in these diseases without concern for motor activity. Furthermore, CBD was also shown to produce anti-anxiety effects without a negative influence on motor activity [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

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Effects of Cannabidiol on Locomotor Activity

Calapai

Cardia

Calapai

et al. 2022

Life

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Cannabidiol (CBD) is the second cannabinoid, in order of importance after Δ9-tetrahydrocannabinol (THC), from Cannabis sativa. Unlike THC, CBD does not cause psychotomimetic effects, and although these compounds have the same chemical formula, their pharmacological characteristics are not equivalent. Preclinical studies suggest that CBD has anti-inflammatory, analgesic, anxiolytic, antiemetic, anticonvulsant, and antipsychotic properties and influences the sleep–wake cycle. The evaluation of effects on spontaneous motor activity is crucial in experimental pharmacology, and the careful measurement of laboratory animal movement is an established method to recognize the effects of stimulant and depressant drugs. The potential influence of CBD on locomotor activity has been investigated through numerous in vivo experiments. However, there is no clear picture of the impact of CBD on these issues, even though it is administered alone for medical uses and sold with THC as a drug for pain caused by muscle spasms in multiple sclerosis, and it was recently licensed as a drug for severe forms of infantile epilepsy. On this basis, with the aim of developing deeper knowledge of this issue, scientific data on CBD’s influence on locomotor activity are discussed here. We conducted research using PubMed, Scopus, Google Scholar, and a search engine for literature between January 2009 and December 2021 on life sciences and biomedical topics using the keywords “motor activity”, “locomotor activity”, and “locomotion” in combination with “cannabidiol”. In this article, we discuss findings describing the effects on locomotor activity of the CBD precursor cannabidiolic acid and of CBD alone or in combination with THC, together with the effects of CBD on locomotor modifications induced by diseases and on locomotor changes induced by other substances.

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“…Administration of ketamine was shown to enhance the release of dopamine and glutamate in the brain striatal region (Hons et al, 2010). Ketamine, an NMDAR antagonist induces hyper locomotion by increasing the number of lines crossed and reducing the ambulation time in mice (Sartim et al, 2021;Zhang et al, 2021). The crude extract of Cissampelos owariensis alongside its fractions were screened for their effect on behavioural studies.…”

Section: Bioactivity Of Crude Extract/fractions/compoundmentioning

confidence: 99%

Isolation and structure elucidation of cyclohexanepentol, an anti-psychotic agent from Cissampelos owarensis (P. Beauv.) leaves

Arowona¹,

Sonibare²,

Yeye³

et al. 2023

njpr

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Background: In Nigeria, an estimated 20 – 30% of our population is believed to suffer from mental disorders. Cissampelos owariensis has been used in Southwest Nigerian traditional medicine to treat mental illness.Objectives: This study evaluated the anti-psychotic potential of Cissampelos owariensis crude extract, fractions, sub-fractions and isolated compound, using in vivo and in vitro antipsychotic assays.Material and Methods: Crude extract and fractions of the leaves were investigated against ketamine induced hyper-locomotion and stereotype behaviours in mice. Extrapyramidal effect of bioactive fraction was tested using catalepsy model. D - amino acid oxidase assay was used to test for anti-psychotic property of chromatographic sub-fractions and isolated compound. Percentage inhibition of pooled sub-fractions and compound was measured at an excitation and emission wavelengths of 355 and 460 nm, respectively. Characterization of isolated compound was done using Infrared and Nuclear Magnetic Resonance spectroscopy. One-way ANOVA, followed by Dunnett’s posthoc test at α0.05, was used for data analysis.Results: Crude extract of Cissampelos owariensis (125 mg/kg) and fractions showed reduction in hyper-locomotion at different doses. The extract (125 mg/kg) and ethylacetate fraction (500 mg/kg) significantly antagonized stereotypy in mice. The ethyl acetate fraction did not induce catalepsy but rather reversed the cataleptic effect induced by haloperidol. Phytochemical investigation led to the identification of Cyclohexanepentol, which possesses comparable anti-psychotic activity with Risperidone.Conclusion: This paper presents for the first time, anti-psychotic principle from C. owariensis and validates its ethno-medicinal use.

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Co-administration of cannabidiol and ketamine induces antidepressant-like effects devoid of hyperlocomotor side-effects

Cited by 14 publications

References 70 publications

CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration

CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration

Effects of Cannabidiol on Locomotor Activity

Isolation and structure elucidation of cyclohexanepentol, an anti-psychotic agent from Cissampelos owarensis (P. Beauv.) leaves

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