3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD)

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background:

          The potential benefits of cannabis and its major non-intoxicating component cannabidiol (CBD) are attracting attention, including as a potential treatment in neurodevelopmental disorders such as autism spectrum disorder (ASD). However, the neural action of CBD, and its relevance to ASD, remains unclear. We and others have previously shown that response to drug challenge can be measured using functional magnetic resonance imaging (fMRI), but that pharmacological responsivity is atypical in ASD.

          Aims:

          We hypothesized that there would be a (different) fMRI response to CBD in ASD.

          Methods:

          To test this, task-free fMRI was acquired in 34 healthy men (half with ASD) following oral administration of 600 mg CBD or matched placebo (random order; double-blind administration). The ‘fractional amplitude of low-frequency fluctuations’ (fALFF) was measured across the whole brain, and, where CBD significantly altered fALFF, we tested if functional connectivity (FC) of those regions was also affected by CBD.

          Results:

          CBD significantly increased fALFF in the cerebellar vermis and the right fusiform gyrus. However, post-hoc within-group analyses revealed that this effect was primarily driven by the ASD group, with no significant change in controls. Within the ASD group only, CBD also significantly altered vermal FC with several of its subcortical (striatal) and cortical targets, but did not affect fusiform FC with other regions in either group.

          Conclusion:

          Our results suggest that, especially in ASD, CBD alters regional fALFF and FC in/between regions consistently implicated in ASD. Future studies should examine if this affects the complex behaviours these regions modulate.

          Related collections

          Most cited references35

          • Record: found
          • Abstract: found
          • Article: not found

          Frequencies contributing to functional connectivity in the cerebral cortex in "resting-state" data.

          In subjects performing no specific cognitive task ("resting state"), time courses of voxels within functionally connected regions of the brain have high cross-correlation coefficients ("functional connectivity"). The purpose of this study was to measure the contributions of low frequencies and physiological noise to cross-correlation maps. In four healthy volunteers, task-activation functional MR imaging and resting-state data were acquired. We obtained four contiguous slice locations in the "resting state" with a high sampling rate. Regions of interest consisting of four contiguous voxels were selected. The correlation coefficient for the averaged time course and every other voxel in the four slices was calculated and separated into its component frequency contributions. We calculated the relative amounts of the spectrum that were in the low-frequency (0 to 0.1 Hz), the respiratory-frequency (0.1 to 0.5 Hz), and cardiac-frequency range (0.6 to 1.2 Hz). For each volunteer, resting-state maps that resembled task-activation maps were obtained. For the auditory and visual cortices, the correlation coefficient depended almost exclusively on low frequencies (<0.1 Hz). For all cortical regions studied, low-frequency fluctuations contributed more than 90% of the correlation coefficient. Physiological (respiratory and cardiac) noise sources contributed less than 10% to any functional connectivity MR imaging map. In blood vessels and cerebrospinal fluid, physiological noise contributed more to the correlation coefficient. Functional connectivity in the auditory, visual, and sensorimotor cortices is characterized predominantly by frequencies slower than those in the cardiac and respiratory cycles. In functionally connected regions, these low frequencies are characterized by a high degree of temporal coherence.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The visual word form area: expertise for reading in the fusiform gyrus.

            Brain imaging studies reliably localize a region of visual cortex that is especially responsive to visual words. This brain specialization is essential to rapid reading ability because it enhances perception of words by becoming specifically tuned to recurring properties of a writing system. The origin of this specialization poses a challenge for evolutionary accounts involving innate mechanisms for functional brain organization. We propose an alternative account, based on studies of other forms of visual expertise (i.e. bird and car experts) that lead to functional reorganization. We argue that the interplay between the unique demands of word reading and the structural constraints of the visual system lead to the emergence of the Visual Word Form Area.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome

              Medicinal cannabis use is booming despite limited preclinical evidence and mechanistic insight. Recent clinical trials of cannabidiol (CBD) in Dravet syndrome (DS) support its clinical efficacy for reduction of seizure frequency and invite study of its benefits for additional DS symptoms. We demonstrate here that treatment with CBD is beneficial for seizure frequency, duration, and severity and for autistic-like social deficits in a mouse model of DS. CBD rescue of DS symptoms is associated with increased inhibitory neurotransmission, potentially mediated by antagonism of the lipid-activated G protein-coupled receptor GPR55. These studies lend critical support for treatment of seizures in DS with CBD, extend the scope of CBD treatment to autistic-like behaviors, and provide initial mechanistic insights into CBD’s therapeutic actions. Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence of its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures and autistic-like social deficits in a well-validated mouse genetic model of Dravet syndrome (DS), a severe childhood epilepsy disorder caused by loss-of-function mutations in the brain voltage-gated sodium channel Na V 1.1. The duration and severity of thermally induced seizures and the frequency of spontaneous seizures were substantially decreased. Treatment with lower doses of CBD also improved autistic-like social interaction deficits in DS mice. Phenotypic rescue was associated with restoration of the excitability of inhibitory interneurons in the hippocampal dentate gyrus, an important area for seizure propagation. Reduced excitability of dentate granule neurons in response to strong depolarizing stimuli was also observed. The beneficial effects of CBD on inhibitory neurotransmission were mimicked and occluded by an antagonist of GPR55, suggesting that therapeutic effects of CBD are mediated through this lipid-activated G protein-coupled receptor. Our results provide critical preclinical evidence supporting treatment of epilepsy and autistic-like behaviors linked to DS with CBD. We also introduce antagonism of GPR55 as a potential therapeutic approach by illustrating its beneficial effects in DS mice. Our study provides essential preclinical evidence needed to build a sound scientific basis for increased medicinal use of CBD.
                Bookmark

                Author and article information

                Journal
                J Psychopharmacol
                J. Psychopharmacol. (Oxford)
                JOP
                spjop
                Journal of Psychopharmacology (Oxford, England)
                SAGE Publications (Sage UK: London, England )
                0269-8811
                1461-7285
                25 June 2019
                September 2019
                : 33
                : 9
                : 1141-1148
                Affiliations
                [1 ]Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
                [2 ]South London and Maudsley NHS Foundation Trust Pharmacy, London, UK
                [3 ]Department of Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
                Author notes
                [*]Gráinne McAlonan, Sackler Centre for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, 16 De Crespigny Park, SE5 8AF, UK. Email: grainne.mcalonan@ 123456kcl.ac.uk
                [*]

                Authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-2761-6628
                https://orcid.org/0000-0002-0258-5917
                https://orcid.org/0000-0003-3625-3467
                Article
                10.1177_0269881119858306
                10.1177/0269881119858306
                6732821
                31237191
                ef57bc74-fa51-4075-82e9-1581ef580470
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Funding
                Funded by: autistica, FundRef https://doi.org/10.13039/100011706;
                Award ID: MR/N026063/1
                Funded by: EU-AIMS, ;
                Award ID: FP7/2007
                Funded by: GW Pharmaceuticals, ;
                Funded by: national institute for health research, FundRef https://doi.org/10.13039/501100000272;
                Award ID: Studentship to CMP
                Funded by: medical research council, FundRef https://doi.org/10.13039/501100000265;
                Award ID: MR/N026063/1
                Funded by: seventh framework programme, FundRef https://doi.org/10.13039/501100004963;
                Award ID: FP7/2007–2013
                Funded by: European Innovative Medicines Initiative Joint Undertaking, ;
                Award ID: 115300 and 777394,
                Categories
                Original Papers

                Pharmacology & Pharmaceutical medicine
                cannabidiol,autism spectrum disorder,low-frequency fluctuations,functional connectivity,cannabis sativa

                Comments

                Comment on this article