Dissociable changes in spike and wave discharges following exposure to injected cannabinoids and smoked cannabis in Genetic Absence Epilepsy Rats from Strasbourg.

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Title: Dissociable changes in spike and wave discharges following exposure to injected cannabinoids and smoked cannabis in Genetic Absence Epilepsy Rats from Strasbourg.
Authors: Roebuck, Andrew J. (AUTHOR), Greba, Quentin (AUTHOR), Onofrychuk, Timothy J. (AUTHOR), McElroy, Dan L. (AUTHOR), Sandini, Thaísa M. (AUTHOR), Zagzoog, Ayat (AUTHOR), Simone, Jonathan (AUTHOR), Cain, Stuart M. (AUTHOR), Snutch, Terrance P. (AUTHOR), Laprairie, Robert B. (AUTHOR), Howland, John G. (AUTHOR)
Source: European Journal of Neuroscience. Feb2022, Vol. 55 Issue 4, p1063-1078. 16p. 1 Color Photograph, 6 Graphs.
Subjects: Cannabinoids, Cannabis (Genus), Smoking, Epilepsy, Smoke, Test anxiety
Geographic Terms: Strasbourg (France)
Abstract: There is significant interest in the use of cannabinoids for the treatment of many epilepsies including absence epilepsy (AE). Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model many aspects of AE including the presence of spike‐and‐wave discharges (SWDs) on electroencephalogram (EEG) and behavioral comorbidities, such as elevated anxiety. However, the effects of cannabis plant‐based phytocannabinoids have not been tested in GAERS. Therefore, we investigated how SWDs in GAERS are altered by the two most common phytocannabinoids, Δ9‐tetrahydrocannabinol (THC) and cannabidiol (CBD), and exposure to smoke from two different chemovars of cannabis. Animals were implanted with bipolar electrodes in the somatosensory cortex and EEGs were recorded for 2 hr. Injected THC (1–10 mg/kg, i.p.) dose‐dependently increased SWDs to over 200% of baseline. In contrast, CBD (30–100 mg/kg, i.p.) produced a ~50% reduction in SWDs. Exposure to smoke from a commercially available chemovar of high‐THC cannabis (Mohawk, Aphria Inc.) increased SWDs whereas a low‐THC/high‐CBD chemovar of cannabis (Treasure Island, Aphria Inc.) did not significantly affect SWDs in GAERS. Pre‐treatment with a CB1R antagonist (SR141716A) did not prevent the high‐THC cannabis smoke from increasing SWDs, suggesting that the THC‐mediated increase may not be CB1R‐dependent. Plasma concentrations of THC and CBD were similar to previously reported values following injection and smoke exposure. Compared to injected CBD, it appears Treasure Island did not increase plasma levels sufficiently to observe an anti‐epileptic effect. Together these experiments provide initial evidence that acute phytocannabinoid administration exerts the biphasic modulation of SWDs and may differentially impact patients with AE. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Dissociable changes in spike and wave discharges following exposure to injected cannabinoids and smoked cannabis in Genetic Absence Epilepsy Rats from Strasbourg.
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. Feb2022, Vol. 55 Issue 4, p1063-1078. 16p. 1 Color Photograph, 6 Graphs.
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  Data: There is significant interest in the use of cannabinoids for the treatment of many epilepsies including absence epilepsy (AE). Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model many aspects of AE including the presence of spike‐and‐wave discharges (SWDs) on electroencephalogram (EEG) and behavioral comorbidities, such as elevated anxiety. However, the effects of cannabis plant‐based phytocannabinoids have not been tested in GAERS. Therefore, we investigated how SWDs in GAERS are altered by the two most common phytocannabinoids, Δ9‐tetrahydrocannabinol (THC) and cannabidiol (CBD), and exposure to smoke from two different chemovars of cannabis. Animals were implanted with bipolar electrodes in the somatosensory cortex and EEGs were recorded for 2 hr. Injected THC (1–10 mg/kg, i.p.) dose‐dependently increased SWDs to over 200% of baseline. In contrast, CBD (30–100 mg/kg, i.p.) produced a ~50% reduction in SWDs. Exposure to smoke from a commercially available chemovar of high‐THC cannabis (Mohawk, Aphria Inc.) increased SWDs whereas a low‐THC/high‐CBD chemovar of cannabis (Treasure Island, Aphria Inc.) did not significantly affect SWDs in GAERS. Pre‐treatment with a CB1R antagonist (SR141716A) did not prevent the high‐THC cannabis smoke from increasing SWDs, suggesting that the THC‐mediated increase may not be CB1R‐dependent. Plasma concentrations of THC and CBD were similar to previously reported values following injection and smoke exposure. Compared to injected CBD, it appears Treasure Island did not increase plasma levels sufficiently to observe an anti‐epileptic effect. Together these experiments provide initial evidence that acute phytocannabinoid administration exerts the biphasic modulation of SWDs and may differentially impact patients with AE. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/ejn.15096
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      – Code: eng
        Text: English
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        PageCount: 16
        StartPage: 1063
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      – SubjectFull: Cannabinoids
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      – SubjectFull: Smoking
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      – SubjectFull: Epilepsy
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      – SubjectFull: Smoke
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      – SubjectFull: Test anxiety
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      – SubjectFull: Strasbourg (France)
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              Text: Feb2022
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