The effects of cannabidiol and Δ9-tetrahydrocannabinol, alone and in combination, in the maximal electroshock seizure model

Dlugosz, Lukasz; Zhou, Han Zhong; Scott, Bradley; Burnham, McIntyre

doi:10.1016/j.eplepsyres.2023.107087

Cited by 5 publications

(7 citation statements)

References 35 publications

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“…While CBD or CBDA alone does not seem to affect locomotor activity (Calapai et al, 2022), its regulation of NDMAR via CB1Rs and 5‐HT1ARs is likely one of the mechanisms that reverses MK‐801‐indcued hyperlocomotion (Rodríguez‐Muñoz et al, 2016; Yuen et al, 2005). Previous research showed that NMDAR antagonism can induce immobility in the FST (Langen et al, 2012), and our study corroborates the findings that compounds such as CBD and HU‐580 can significantly reduce immobility behaviour (Dlugosz et al, 2023; Sales et al, 2019, 2020). Moreover, CBD (Felipe et al, 2013; Leweke et al, 2021; Osborne et al, 2017) and CBDA (Kim et al, 2023) improve or rescue cognitive performance in psychiatric and neurological disorders.…”

Section: Discussionsupporting

confidence: 90%

Therapeutic‐like activity of cannabidiolic acid methyl ester in the MK‐801 mouse model of schizophrenia: Role for cannabinoid CB1 and serotonin‐1A receptors

Richardson,

Clarke,

Blundell

et al. 2024

Eur J of Neuroscience

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Schizophrenia is a psychotic disorder with an increasing prevalence and incidence over the last two decades. The condition presents with a diverse array of positive, negative, and cognitive impairments. Conventional treatments often yield unsatisfactory outcomes, especially with negative symptoms. We investigated the role of prefrontocortical (PFC) N‐methyl‐D‐aspartate receptors (NMDARs) in the pathophysiology and development of schizophrenia. We explored the potential therapeutic effects of cannabidiolic acid (CBDA) methyl ester (HU‐580), an analogue of CBDA known to act as an agonist of the serotonin‐1A receptor (5‐HT1AR) and an antagonist of cannabinoid type 1 receptor (CB1R). C57BL/6 mice were intraperitoneally administered the NMDAR antagonist, dizocilpine (MK‐801, .3 mg/kg) once daily for 17 days. After 7 days, they were concurrently given HU‐580 (.01 or .05 μg/kg) for 10 days. Behavioural deficits were assessed at two time points. We conducted enzyme‐linked immunosorbent assays to measure the concentration of PFC 5‐HT1AR and CB1R. We found that MK‐801 effectively induced schizophrenia‐related behaviours including hyperactivity, social withdrawal, increased forced swim immobility, and cognitive deficits. We discovered that low‐dose HU‐580 (.01 μg/kg), but not the high dose (.05 μg/kg), attenuated hyperactivity, forced swim immobility and cognitive deficits, particularly in female mice. Our results revealed that MK‐801 downregulated both CB1R and 5‐HT1AR, an effect that was blocked by both low‐ and high‐dose HU‐580. This study sheds light on the potential antipsychotic properties of HU‐580, particularly in the context of NMDAR‐induced dysfunction. Our findings could contribute significantly to our understanding of schizophrenia pathophysiology and offer a promising avenue for exploring the therapeutic potential of HU‐580 and related compounds in alleviating symptoms.

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Section: Discussionsupporting

confidence: 90%

Therapeutic‐like activity of cannabidiolic acid methyl ester in the MK‐801 mouse model of schizophrenia: Role for cannabinoid CB1 and serotonin‐1A receptors

Richardson,

Clarke,

Blundell

et al. 2024

Eur J of Neuroscience

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show abstract

“…While CBD and CBDA alone do not seem to affect locomotor activity (Calapai et al, 2022), its regulation of NDMAR via CB1R and 5-HT1AR is likely to be one of the mechanisms that reverses hyperlocomotion (Rodríguez-Muñoz et al, 2016;Yuen et al, 2005). Previous research was able to show that NMDAR antagonism can induce immobility in the FST (Langen et al, 2012), and our study corroborates the findings that compounds such as CBD and HU-580 can significantly reduce immobility behavior (Sales et al, 2019;Sales et al, 2020;Dlugosz et al, 2023). Moreover, CBD (Felipe et al, 2013;Osborne et al, 2017;Leweke et al, 2021) and CBDA (Kim et al, 2023) have been shown to improve or rescue cognitive performance in psychiatric and neurological disorders.…”

Section: Discussionsupporting

confidence: 88%

Therapeutic-like activity of cannabidiolic acid methyl ester (HU-580) in the MK-801 mouse model of schizophrenia: role for cannabinoid CB1 and serotonin-1A receptors

Richardson,

Clarke,

Bambico

2023

Preprint

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Schizophrenia is an incurable psychotic illness. Those diagnosed have limited pharmacological treatment options, many of which do not provide long term relief and come with unpleasant side effects. The endocannabinoid and serotonergic systems are important neuromodulators in psychotic illness. We hypothesize that cannabidiolic acid methyl ester (HU-580) that exerts action on both these systems could have therapeutic potential by antagonizing cannabinoid receptor-1 (CB1R) and agonizing 5-hydroxytryptamine receptor-1A (5-HT1AR). We employed behavioural and brain protein analyses in male and female mice exposed to MK-801, which precipitated schizophrenia-related reactivity across a number of behavioural dimensions. C57BL/6 mice were subjected to a battery of behavioral tests, and we found that subchronic treatment of MK-801 (once daily for seven days) induced positive-like, negative-like, and cognitive-related behavioral deficits; primarily in females. Sub-chronic treatment of MK-801 (once daily for 17 days) induced positive- and negative-like behavioral deficits in females. Low-dose (0.01ug/kg) but not high-dose (0.05 ug/kg) treatment rescued female mice from schizophrenia-related behavioral deficits. Altogether, these data suggest that HU-580 may have dose-dependent antipsychotic-like potential that rely on mechanisms that recruit CB1R and 5-HT1AR.

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“…Its anticonvulsant properties have gained attention, potentially offering a more accessible and cost-effective alternative to CBD. Studies have shown that THC's antiseizure properties can be achieved through CBD alone or in combination with THC [71]. However, the advantages of combining THC with CBD might be limited for focal-onset seizures [72].…”

Section: Discussionmentioning

confidence: 99%

“…In their study, they assessed the efficacy of CBD and THC individually, as well as in combination (CBD+THC at a ratio of 15:1) in the maximal electroshock (MES) model in mice. The findings suggest that treatment options for generalized-onset seizures may involve CBD alone or the combination of CBD+THC [71]. However, it was noted that the advantages of combining THC with CBD might be more limited when treating focal-onset seizures [72].…”

Section: δ9-tetrahydrocannabinol (Thc)mentioning

confidence: 99%

Evaluating the Efficacy of Cannabinoids in Epilepsy: A Critical Examination of Hard Evidence

Pepito,

Plaza,

Rallos

et al. 2023

Int. J. Res. Publ. Rev.

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Epilepsy, a prevalent neurological disorder, affects one-third of individuals with seizures resistant to standard antiepileptic drugs. Cannabis sativa, a plant that is reportedly used for seizure treatment, contains non-psychoactive cannabidiol (CBD) and psychoactive Δ9-tetrahydrocannabinol (THC). Although anecdotal accounts point to favorable results, there are insufficient reliable human data. This research examines the pharmacological basis of cannabis sativa, its anti-seizure benefits, centered around the effects of THC and CBD. This also covers the safety profile of cannabis, answering issues with safe usage and negative effects.Methodologically, clinical trials and systematic reviews from databases were examined. Since an imbalance in neural impulses causes epilepsy, treating it can be difficult. Due to the drawbacks of traditional antiepileptic medications, there is interest in complementary therapies like cannabis-based medicine. Epilepsy results from an imbalance in neuronal impulses, making its treatment challenging. Conventional antiepileptic drugs have limitations, leading to interest in alternative treatments, including cannabis-based therapies. CBD interacts with adenosine, TRPV1 receptors, and GPR55 receptors, potentially reducing seizures. Clinical evidence supports CBD's efficacy in managing seizures, especially in Dravet syndrome and Lennox-Gastaut syndrome. THC, the psychoactive component, has analgesic effects. The review underscores the importance of thorough studies to establish cannabinoids, particularly CBD, as safe and effective options for epilepsy treatment, acknowledging their potential to revolutionize seizure control and improve patients' quality of life.

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The effects of cannabidiol and Δ9-tetrahydrocannabinol, alone and in combination, in the maximal electroshock seizure model

Cited by 5 publications

References 35 publications

Therapeutic‐like activity of cannabidiolic acid methyl ester in the MK‐801 mouse model of schizophrenia: Role for cannabinoid CB1 and serotonin‐1A receptors

Therapeutic‐like activity of cannabidiolic acid methyl ester in the MK‐801 mouse model of schizophrenia: Role for cannabinoid CB1 and serotonin‐1A receptors

Therapeutic-like activity of cannabidiolic acid methyl ester (HU-580) in the MK-801 mouse model of schizophrenia: role for cannabinoid CB1 and serotonin-1A receptors

Evaluating the Efficacy of Cannabinoids in Epilepsy: A Critical Examination of Hard Evidence

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