{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:15:38Z","timestamp":1790874938902,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cannabinoids are proposed in a wide array of medical indications. Yet, the evaluation of adverse effects in controlled clinical studies, following the evidence\u2010based model, has partly been bypassed. On the other hand, studies on the consequences of recreational use of cannabis and experimental studies bring some insights on the potential long\u2010term consequences of cannabinoids use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Epidemiological studies have consistently demonstrated that cannabis use is associated with a risk of persistent cognitive deficits and increased risk of schizophrenia\u2010like psychoses. These risks are modulated by the dose and duration of use, on top of age of use and genetic factors, including partially shared genetic predisposition with schizophrenia. Experimental studies in healthy humans showed that cannabis and its principal psychoactive component, the delta\u20109\u2010tetrahydrocannabinol (<jats:styled-content style=\"fixed-case\">THC<\/jats:styled-content>), could produce transient, dose\u2010dependent, psychotic symptoms as well as cognitive effects, which can be attenuated by cannabidiol (<jats:styled-content style=\"fixed-case\">CBD<\/jats:styled-content>). Studies in rodents have confirmed these effects and shown that adolescent exposure results in structural changes and impaired synaptic plasticity, impacting fronto\u2010limbic systems that are critically involved in higher brain functions. The endocannabinoid system plays an important role in brain maturation. Its over\u2010activation by cannabinoid receptor type 1 agonists (e.g., <jats:styled-content style=\"fixed-case\">THC<\/jats:styled-content>) during adolescence and the resulting changes in neuroplasticity could alter brain maturation and cause long\u2010lasting changes that persist in the adult brain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Exposure to cannabinoids can have long\u2010term impact on the brain, with an inter\u2010individual variability that could be conveyed by personal and family history of psychiatric disorders and genetic background. Adolescence and early adulthood are critical periods of vulnerability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The assessment of benefice\u2013risk balance of medical use of cannabis and cannabinoids needs to carefully explore populations that could be more at\u2010risk of psychiatric and cognitive complications.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1377","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T04:17:11Z","timestamp":1550809031000},"page":"1225-1233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Exposure to cannabinoids can lead to persistent cognitive and psychiatric disorders"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4715-9890","authenticated-orcid":false,"given":"Marie\u2010Odile","family":"Krebs","sequence":"first","affiliation":[{"name":"Inserm Laboratoire de Physiopathologie des maladies Psychiatriques UMR_S1266 Institut de Psychiatrie et Neurosciences de Paris Universit\u00e9 Paris Descartes Paris France"},{"name":"Institut de Psychiatrie (CNRS GDR 3557) Paris France"},{"name":"Facult\u00e9 de M\u00e9decine Paris Descartes Service Hospitalo Universitaire Centre Hospitalier Sainte\u2010Anne Universit\u00e9 Paris Descartes Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oussama","family":"Kebir","sequence":"additional","affiliation":[{"name":"Inserm Laboratoire de Physiopathologie des maladies Psychiatriques UMR_S1266 Institut de Psychiatrie et Neurosciences de Paris Universit\u00e9 Paris Descartes Paris France"},{"name":"Institut de Psychiatrie (CNRS GDR 3557) Paris France"},{"name":"Service d'Addictologie \u00abMoreau de Tours\u00bb Centre Hospitalier Sainte\u2010Anne Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese M.","family":"Jay","sequence":"additional","affiliation":[{"name":"Inserm Laboratoire de Physiopathologie des maladies Psychiatriques UMR_S1266 Institut de Psychiatrie et Neurosciences de Paris Universit\u00e9 Paris Descartes Paris France"},{"name":"Institut de Psychiatrie (CNRS GDR 3557) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291717001209"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(17)30280-8"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)92620-1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.187.6.510"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.325.7374.1212"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.184.2.110"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1137406"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291715002494"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2018.03.008"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-018-4885-9"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.12.002"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.01.026"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.09.020"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2015.05.004"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.28"},{"key":"e_1_2_11_18_1","unstructured":"Currie C. 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