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Remyelination occurs when the CNS attempts to recover from myelin loss and requires the activation of oligodendrocyte precursor cells. With the rationale that CB1 receptor is expressed in oligodendrocytes and marijuana consumption alters CNS myelination, we study the effects of the cannabinoid agonist WIN55212.2 in (1) an <jats:italic>in\u00a0vitro<\/jats:italic> model of oligodendrocyte differentiation and (2) the cuprizone model for demyelination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The synthetic cannabinoid agonist WIN55212.2 at 1\u00a0<jats:italic>\u03bc<\/jats:italic>M increased the myelin basic protein mRNA and protein expression <jats:italic>in\u00a0vitro<\/jats:italic>. During cuprizone\u2010induced acute demyelination, the administration of 0.5\u00a0mg\/kg WIN55212.2 confers more myelinated axons, increased the expression of retinoid X receptor alpha, and declined nogo receptor expression. Controversially, 1\u00a0mg\/kg of the drug increased the number of demyelinated axons and reduced the expression of nerve growth factor inducible, calreticulin and myelin\u2010related genes coupling specifically with a decrease in 2\u2032,3\u2032\u2010cyclic nucleotide 3\u2032 phosphodiesterase expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The cannabinoid agonist WIN55212.2 promotes oligodendrocyte differentiation <jats:italic>in\u00a0vitro<\/jats:italic>. Moreover, 0.5\u00a0mg\/kg of the drug confers neuroprotection during cuprizone\u2010induced demyelination, while 1\u00a0mg\/kg aggravates the demyelination process.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12506","type":"journal-article","created":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T10:32:52Z","timestamp":1454581972000},"page":"387-395","source":"Crossref","is-referenced-by-count":34,"title":["The Cannabinoid CB1\/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation <i>In Vitro<\/i> and Neuroprotection During the Cuprizone\u2010Induced Central Nervous System Demyelination"],"prefix":"10.1111","volume":"22","author":[{"given":"Jordi","family":"Tomas\u2010Roig","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"},{"name":"Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) G\u00f6ttingen 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