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This pilot study sought to assess the safety and pharmacokinetics (PK) of co\u2010administration of<jats:styled-content style=\"fixed-case\">RPR<\/jats:styled-content>102681 and cocaine, and to confirm the DA release mechanism of<jats:styled-content style=\"fixed-case\">RPR<\/jats:styled-content>102681.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixteen cocaine\u2010dependent participants were randomized to either placebo or<jats:styled-content style=\"fixed-case\">RPR<\/jats:styled-content>102681 at 3 ascending doses; cocaine was co\u2010administered at steady state of<jats:styled-content style=\"fixed-case\">RPR<\/jats:styled-content>102681. [<jats:sup>11<\/jats:sup>C]raclopride positron emission tomography scans were conducted at baseline and at each<jats:styled-content style=\"fixed-case\">RPR<\/jats:styled-content>102681 dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">RPR<\/jats:styled-content>102681 was well tolerated, and safe to co\u2010administer with cocaine.<jats:styled-content style=\"fixed-case\">RPR<\/jats:styled-content>102681 did not alter the PK of either cocaine or its metabolite benzoylecgonine and showed no intrinsic abuse liability. There was a trend toward reduction of cocaine craving scores. In contrast to animal studies,<jats:styled-content style=\"fixed-case\">RPR<\/jats:styled-content>102681 significantly increased the binding potential of [<jats:sup>11<\/jats:sup>C]raclopride in the ventral striatum (<jats:italic>t<\/jats:italic>test,<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) and caudate nucleus (<jats:italic>t<\/jats:italic>test,<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001) in a small subset of patients, suggesting that it may reduce intrasynaptic striatal DA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, this pilot study suggests that<jats:styled-content style=\"fixed-case\">RPR<\/jats:styled-content>102681 would be unlikely candidate, as an agonist medication for the treatment for cocaine addiction but worth investigating further for possible role in reducing craving.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12994","type":"journal-article","created":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T07:11:24Z","timestamp":1529478684000},"page":"136-146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A cholecystokinin B receptor antagonist and cocaine interaction, phase I study"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5866-8498","authenticated-orcid":false,"given":"Ahmed","family":"Elkashef","sequence":"first","affiliation":[{"name":"Medications Development Division The National Institute on Drug Abuse National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James Robert","family":"Bra\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Section of High Resolution Brain Positron Emission Tomography Imaging Division of Nuclear Medicine and Molecular Imaging The Russell H. 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