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Three studies were conducted to evaluate the early phase (acute, day 1) and late phase (days 2\u201312) effects of SJP-005 on discontinuation-induced morphine withdrawal.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Sprague-Dawley rats received subcutaneous morphine twice daily for 18 days and ceased on day 19. Twice daily, oral dosages of placebo or SJP-005 (1 mg\/kg ketotifen and 15 mg\/kg ibuprofen) were administered starting 4 days before (study 1), 2 days before (study 2), or immediately after (study 3) morphine cessation. Functional observations were made up to 12 h after treatment cessation on day 19 (early phase), and immediately after treatment on days 20\u201330 (late phase). Treatment effects (mean overall score, and individual symptoms) were compared with placebo using ANOVA, and Tukey\u2019s tests in case of multiple comparisons.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Across the studies, the number of withdrawal signs on day 19 (early phase) and days 20\u201330 (late phase) was lower with SJP-005 compared with placebo. The effects of SJP-005 when treatment was initiated 2 days before morphine cessation by discontinuation were most pronounced and statistically significant in the late phase (<jats:italic>F<\/jats:italic><jats:sub>(1,18)<\/jats:sub> = 14.10, <jats:italic>p<\/jats:italic> = 0.001). In particular, a significant reduction was observed in hypersensitivity to touch (<jats:italic>F<\/jats:italic><jats:sub>(1,18)<\/jats:sub> = 13.65, <jats:italic>p<\/jats:italic> = 0.002). A 50% reduction in withdrawal symptoms was observed 9.0 days after placebo versus 4.5 days after SJP-005. After 9.0 days, all withdrawal symptoms were absent in the SJP-005 group, while symptoms in the placebo group were still evident on day 18.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Compared to placebo, SJP-005 significantly reduced the incidence and duration of discontinuation-induced morphine withdrawal symptoms when treatment was initiated 2 days before morphine cessation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00213-021-05771-5","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T07:16:55Z","timestamp":1612855015000},"page":"1449-1460","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Functional observation after morphine withdrawal: effects of SJP-005"],"prefix":"10.1007","volume":"238","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-2096","authenticated-orcid":false,"given":"Joris C.","family":"Verster","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Scholey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Dahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline M.","family":"Iversen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"5771_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1080\/21556660.2019.1704416","volume":"9","author":"D Alam","year":"2020","unstructured":"Alam D, Tirado C, Pirner M, Clinch T (2020) Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials. 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He has acted as a consultant\/expert advisor to Arepa Nootroptics, Bayer, Coca-Cola, Danone, Naturex, Nestl\u00e9, Pfizer, Sanofi, and Sen-Jam Pharmaceutical, and has received travel\/hospitality\/speaker fees from Bayer, Sanofi, and Verdure Sciences. Over the past 36 months, J.C.V. has held grants from Janssenand Sequential Medicine, and acted as a consultant\/expert advisor to More Labs, Red Bull, Sen-Jam Pharmaceutical, Toast!, Tomo, and ZBiotics. J.M.I. is the founder and Head of Clinical Development of Sen-Jam Pharmaceutical. T.A.D. is the partner and Head of Product Development and Regulatory Affairs of Sen-Jam Pharmaceutical. The independent studies were conducted by Calvert Laboratories, Inc, without involvement of the authors and the funder. The funder was involved in the design of the studies, interpretation of data, writing of the manuscript, and in the decision to publish the results.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}