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The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing fearful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man. Fourteen healthy males were studied with fMRI twice, one month apart, following an oral dose of either delta-9-THC (10\u2009mg) or placebo, while they performed a fear-processing task. Baseline availability of the CB1 receptor was studied using PET with [\n                    <jats:sup>11<\/jats:sup>\n                    C]MePPEP, a CB1 inverse agonist radioligand. Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. Both these effects were positively correlated with CB1 receptor availability in the right amygdala. These results suggest that the acute effects of cannabis on anxiety in males are mediated by the modulation of amygdalar function by delta-9-THC and the extent of these effects are related to local availability of CB1 receptors.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-14203-4","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T08:36:19Z","timestamp":1509352579000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8688-8025","authenticated-orcid":false,"given":"Sagnik","family":"Bhattacharyya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Egerton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euitae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lula","family":"Rosso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Riano Barros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9530-4848","authenticated-orcid":false,"given":"Alexander","family":"Hammers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico E.","family":"Turkheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver D.","family":"Howes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"McGuire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,3]]},"reference":[{"key":"14203_CR1","unstructured":"UNODC. 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Sagnik Bhattacharyya is currently supported by a NIHR Clinician Scientist Award (NIHR CS-11-001) and the MRC (MR\/J012149\/1).\u00a0Euitae Kim was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) grant, funded by the Ministry of Health & Welfare, Republic of Korea (Grant no.HI15C3104). This work was supported by the Wellcome EPSRC Centre for Medical Engineering at King\u2019s College London (WT 203148\/Z\/16\/Z).\u00a0The authors acknowledge infrastructure support from the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King\u2019s College London. The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy\u2019s & St Thomas\u2019 NHS Foundation Trust in partnership with King\u2019s College London and King\u2019s College Hospital NHS Foundation Trust.\u00a0The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Philip McGuire and Sagnik Bhattacharyya have received research funding from GW pharmaceuticals unrelated to this work. The other authors disclose no competing financial interests and potential conflict of interest relevant to the subject matter of the manuscript.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"15025"}}