{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:15:48Z","timestamp":1781108148622,"version":"3.54.1"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,5,28]]},"abstract":"<jats:p>Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin\u2019s rapid metabolism to 6-acetylmorphine and morphine. We recently developed a \u201cdynamic\u201d vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin\u2019s metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin\u2019s psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance.<\/jats:p>","DOI":"10.1073\/pnas.1219159110","type":"journal-article","created":{"date-parts":[[2013,5,7]],"date-time":"2013-05-07T00:00:47Z","timestamp":1367884847000},"page":"9036-9041","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":96,"title":["Dynamic vaccine blocks relapse to compulsive intake of heroin"],"prefix":"10.1073","volume":"110","author":[{"given":"Joel E.","family":"Schlosburg","sequence":"first","affiliation":[{"name":"Committee on the Neurobiology of Addictive Disorders and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro F.","family":"Vendruscolo","sequence":"additional","affiliation":[{"name":"Committee on the Neurobiology of Addictive Disorders and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T.","family":"Bremer","sequence":"additional","affiliation":[{"name":"Departments of Chemistry, Immunology, and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan W.","family":"Lockner","sequence":"additional","affiliation":[{"name":"Departments of Chemistry, Immunology, and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie L.","family":"Wade","sequence":"additional","affiliation":[{"name":"Committee on the Neurobiology of Addictive Disorders and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlee A. 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