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Although preclinical evidence suggests glutamatergic dysfunction following cannabis exposure in several brain regions including the hippocampus, evidence from human studies have been inconsistent. We investigated the effect of persistent cannabis use on the brain levels of <jats:italic>N<\/jats:italic>\u2010acetyl aspartate (NAA) and myoinositol, the metabolite markers of neurons and glia, the site of the main central cannabinoid CB1 receptor, and the levels of glutamate, the neurotransmitter directly affected by CB1 modulation. We investigated cannabis users (CUs) who started using during adolescence, the period of greatest vulnerability to cannabis effects and focused on the hippocampus, where type 1 cannabinoid receptors (CBR1) are expressed in high density and have been linked to altered glutamatergic neurotransmission. Twenty\u2010two adolescent\u2010onset CUs and 21 nonusing controls (NU), completed proton magnetic resonance spectroscopy, to measure hippocampal metabolite concentrations. Glutamate, NAA, and myoinositol levels were compared between CU and NU using separate analyses of covariance. CU had significantly lower myoinositol but not glutamate or NAA levels in the hippocampus compared with NU. Myoinositol levels in CU positively correlated with glutamate levels, whereas this association was absent in NU. Altered myoinositol levels may be a marker of glia dysfunction and is consistent with experimental preclinical evidence that cannabinoid\u2010induced glial dysfunction may underlie cannabinoid\u2010induced memory impairments. Future studies using appropriate imaging techniques such as positron emission tomography should investigate whether glial dysfunction associated with cannabis use underlies hippocampal dysfunction and memory impairment in CUs.<\/jats:p>","DOI":"10.1111\/adb.12827","type":"journal-article","created":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T05:33:53Z","timestamp":1567488833000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Adolescent\u2010onset heavy cannabis use associated with significantly reduced glial but not neuronal markers and glutamate levels in the hippocampus"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3192-2433","authenticated-orcid":false,"given":"Grace","family":"Blest\u2010Hopley","sequence":"first","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisling","family":"O'Neill","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Giampietro","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lythgoe","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Egerton","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8688-8025","authenticated-orcid":false,"given":"Sagnik","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"},{"name":"South London and Maudsley NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,2]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"Unodc.Market analysis of plant\u2010based drugs. 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