{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:11:23Z","timestamp":1790626283903,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T00:00:00Z","timestamp":1500940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Suomen Akatemia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The gabapentinoid pregabalin is a rapid\u2010acting anxiolytic and analgesic, possibly suitable in supervised opioid detoxification. However, clinicians have been cautious in using it because of its unknown addictive risk and rising number of mortalities after pregabalin self\u2010medication in opioid abusers. Here, we studied interactions of pregabalin and morphine on reward functions of the dopamine system in mice and the efficacy of pregabalin on withdrawal in opioid addicts. After the treatment of mice with pregabalin and morphine, we used electrophysiology to study neuroplasticity in midbrain slices, self\u2010administration and conditioned place preference tests to investigate the rewarding potential of pregabalin and naloxone\u2010precipitated morphine withdrawal to evaluate opioid withdrawal symptoms. Further, we ran a pilot single\u2010blind, randomized, controlled trial (34 heroin addicts) to evaluate the efficacy and safety of pregabalin in the treatment of opioid withdrawal syndrome. Pregabalin alone did not induce glutamate receptor neuroplasticity of dopamine neurons in the ventral tegmental area, but pre\u2010treatment with pregabalin suppressed morphine\u2010induced neuroplasticity, hyperlocomotion and morphine self\u2010administration. Pregabalin administration after chronic morphine exposure failed to induce any rewarding effects. Instead, pregabalin suppressed withdrawal symptoms in both morphine\u2010treated mice and opioid addicts and was well tolerated. Intriguingly, pregabalin administration after a low dose of morphine strongly facilitated ventral tegmental area neuroplasticity and led to increased conditioned place preference. Pregabalin appears to have the efficacy to counteract both reinforcing and withdrawal effects of opioids, but it also has a potentiating effect when given to mice with existing opioid levels.<\/jats:p>","DOI":"10.1111\/adb.12538","type":"journal-article","created":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T10:51:49Z","timestamp":1500979909000},"page":"945-958","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Addiction\u2010related interactions of pregabalin with morphine in mice and humans: reinforcing and inhibiting effects"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4573-7175","authenticated-orcid":false,"given":"Elena","family":"Vashchinkina","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ossi","family":"Piippo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4078-5212","authenticated-orcid":false,"given":"Olga","family":"Vekovischeva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0529-4525","authenticated-orcid":false,"given":"Evgeny","family":"Krupitsky","sequence":"additional","affiliation":[{"name":"Department of Addictions St. Petersburg Bekhterev Research Psychoneurological Institute St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan","family":"Ilyuk","sequence":"additional","affiliation":[{"name":"Department of Addictions St. Petersburg Bekhterev Research Psychoneurological Institute St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5618-4206","authenticated-orcid":false,"given":"Nikholay","family":"Neznanov","sequence":"additional","affiliation":[{"name":"Department of Addictions St. Petersburg Bekhterev Research Psychoneurological Institute St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill","family":"Kazankov","sequence":"additional","affiliation":[{"name":"Murmansk Regional Addiction Hospital Murmansk Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Zaplatkin","sequence":"additional","affiliation":[{"name":"Murmansk Regional Addiction Hospital Murmansk Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0683-4009","authenticated-orcid":false,"given":"Esa R.","family":"Korpi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130100839"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.32"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/15622970802465807"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/85070"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0356-09.2009"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0380525"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.12.084"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015870"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2017.1281247"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-016-0359-y"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.8.903"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/S0022-3565(24)39009-3","article-title":"Stimulus\u2010dependent modulation of [(3)H]norepinephrine release from rat neocortical slices by gabapentin and pregabalin","volume":"295","author":"Dooley DJ","year":"2000","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.025"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(03)00173-8"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409066103"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70251-0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-016-0390-z"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02033"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-013-1578-5"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2014.04.028"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.08.030"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.89"},{"key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/ejp.728","article-title":"Pregabalin enhances the antinociceptive effect of oxycodone and morphine in thermal models of nociception in the rat without any pharmacokinetic interactions","volume":"20","author":"Jokinen V","year":"2015","journal-title":"Eur J Pain"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1305042"},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.neulet.2016.10.053","article-title":"Effects of pregabalin on spinal D\u2010serine content and NMDA receptor\u2010mediated synaptic transmission in mice with neuropathic pain","volume":"636","author":"Kato E","year":"2016","journal-title":"Neurosci Lett"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.06.012"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(16)00104-8"},{"key":"e_1_2_10_29_1","first-page":"323","article-title":"Effects of the NMDA\/glycine receptor antagonist, L\u2010701,324, on morphine\u2010 and cocaine\u2010induced place preference","volume":"51","author":"Kotlinska J","year":"1999","journal-title":"Pol J Pharmacol"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.06.057"},{"key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.17116\/jnevro20161167129-36","article-title":"A randomized single blind study of the efficacy of pregabalin in the treatment of opioid withdrawal syndrome","volume":"116","author":"Krupitsky EM","year":"2016","journal-title":"Zh Nevrol Psikhiatr Im S S Korsakova"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(96)00961-2"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(02)00086-2"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.05.054"},{"key":"e_1_2_10_35_1","doi-asserted-by":"crossref","DOI":"10.1111\/add.13843","article-title":"Risk to heroin users of polydrug use of pregabalin or gabapentin","author":"Lyndon A","year":"2017","journal-title":"Addiction"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00414-016-1358-8"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.07.004"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aer083"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00021-7"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e31822bb378"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3109\/00952990.2011.653426"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.12.024"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(95)02294-5"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.08.013"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2011.01.004"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2006.09.008"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/35079077"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4697-11.2012"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2003.10.021"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X1201140117162802"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(89)90097-3"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajad.12159"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fadb.12538","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.12538","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T17:47:04Z","timestamp":1750787224000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.12538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,25]]},"references-count":51,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1111\/adb.12538"],"URL":"https:\/\/doi.org\/10.1111\/adb.12538","archive":["Portico"],"relation":{},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,25]]},"assertion":[{"value":"2017-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}