Mitragynine attenuates morphine withdrawal effects in rats—a comparison with methadone and buprenorphine

Background: Opiate addiction is a major health problem in many countries. A crucial component of the medical treatment is the management of highly aversive opiate withdrawal signs, which may otherwise lead to resumption of drug taking. In a medication-assisted treatment (MAT), methadone and buprenor...

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Main Authors: Hassan, Rahimah, Cheah, Pike See, Sreenivasan, Sasidharan, M. Mansor, Sharif, Muller, Christian P., Hassan, Zurina
Format: Article
Language:English
Published: Frontiers Research Foundation 2020
Online Access:http://psasir.upm.edu.my/id/eprint/86772/
http://psasir.upm.edu.my/id/eprint/86772/1/Mitragynine%20attenuates%20morphine%20withdrawal%20effects%20in%20rats.pdf
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author Hassan, Rahimah
Cheah, Pike See
Sreenivasan, Sasidharan
M. Mansor, Sharif
Muller, Christian P.
Hassan, Zurina
author_facet Hassan, Rahimah
Cheah, Pike See
Sreenivasan, Sasidharan
M. Mansor, Sharif
Muller, Christian P.
Hassan, Zurina
author_sort Hassan, Rahimah
building UPM Institutional Repository
collection Online Access
description Background: Opiate addiction is a major health problem in many countries. A crucial component of the medical treatment is the management of highly aversive opiate withdrawal signs, which may otherwise lead to resumption of drug taking. In a medication-assisted treatment (MAT), methadone and buprenorphine have been implemented as substitution drugs. Despite MAT effectiveness, there are still limitations and side effects of using methadone and buprenorphine. Thus, other alternative therapies with less side effects, overdosing, and co-morbidities are desired. One of the potential pharmacotherapies may involve kratom's major indole alkaloid, mitragynine, since kratom (Mitragyna speciosa Korth.) preparations have been reported to alleviate opiate withdrawal signs in self-treatment in Malaysian opiate addicts. Methods: Based on the morphine withdrawal model, rats were morphine treated with increasing doses from 10 to 50 mg/kg twice daily over a period of 6 days. The treatment was discontinued on day 7 in order to induce a spontaneous morphine abstinence. The withdrawal signs were measured daily after 24 h of the last morphine administration over a period of 28 abstinence days. In rats that developed withdrawal signs, a drug replacement treatment was given using mitragynine, methadone, or buprenorphine and the global withdrawal score was evaluated. Results: The morphine withdrawal model induced profound withdrawal signs for 16 days. Mitragynine (5–30 mg/kg; i.p.) was able to attenuate acute withdrawal signs in morphine dependent rats. On the other hand, smaller doses of methadone (0.5–2 mg/kg; i.p.) and buprenorphine (0.4–1.6 mg/kg; i.p.) were necessary to mitigate these effects. Conclusions: These data suggest that mitragynine may be a potential drug candidate for opiate withdrawal treatment.
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spelling upm-867722021-11-16T04:27:18Z http://psasir.upm.edu.my/id/eprint/86772/ Mitragynine attenuates morphine withdrawal effects in rats—a comparison with methadone and buprenorphine Hassan, Rahimah Cheah, Pike See Sreenivasan, Sasidharan M. Mansor, Sharif Muller, Christian P. Hassan, Zurina Background: Opiate addiction is a major health problem in many countries. A crucial component of the medical treatment is the management of highly aversive opiate withdrawal signs, which may otherwise lead to resumption of drug taking. In a medication-assisted treatment (MAT), methadone and buprenorphine have been implemented as substitution drugs. Despite MAT effectiveness, there are still limitations and side effects of using methadone and buprenorphine. Thus, other alternative therapies with less side effects, overdosing, and co-morbidities are desired. One of the potential pharmacotherapies may involve kratom's major indole alkaloid, mitragynine, since kratom (Mitragyna speciosa Korth.) preparations have been reported to alleviate opiate withdrawal signs in self-treatment in Malaysian opiate addicts. Methods: Based on the morphine withdrawal model, rats were morphine treated with increasing doses from 10 to 50 mg/kg twice daily over a period of 6 days. The treatment was discontinued on day 7 in order to induce a spontaneous morphine abstinence. The withdrawal signs were measured daily after 24 h of the last morphine administration over a period of 28 abstinence days. In rats that developed withdrawal signs, a drug replacement treatment was given using mitragynine, methadone, or buprenorphine and the global withdrawal score was evaluated. Results: The morphine withdrawal model induced profound withdrawal signs for 16 days. Mitragynine (5–30 mg/kg; i.p.) was able to attenuate acute withdrawal signs in morphine dependent rats. On the other hand, smaller doses of methadone (0.5–2 mg/kg; i.p.) and buprenorphine (0.4–1.6 mg/kg; i.p.) were necessary to mitigate these effects. Conclusions: These data suggest that mitragynine may be a potential drug candidate for opiate withdrawal treatment. Frontiers Research Foundation 2020-05-07 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/86772/1/Mitragynine%20attenuates%20morphine%20withdrawal%20effects%20in%20rats.pdf Hassan, Rahimah and Cheah, Pike See and Sreenivasan, Sasidharan and M. Mansor, Sharif and Muller, Christian P. and Hassan, Zurina (2020) Mitragynine attenuates morphine withdrawal effects in rats—a comparison with methadone and buprenorphine. Frontiers in Psychiatry, 11. pp. 1-13. ISSN 1664-0640 https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00411/full 10.3389/fpsyt.2020.00411
spellingShingle Hassan, Rahimah
Cheah, Pike See
Sreenivasan, Sasidharan
M. Mansor, Sharif
Muller, Christian P.
Hassan, Zurina
Mitragynine attenuates morphine withdrawal effects in rats—a comparison with methadone and buprenorphine
title Mitragynine attenuates morphine withdrawal effects in rats—a comparison with methadone and buprenorphine
title_full Mitragynine attenuates morphine withdrawal effects in rats—a comparison with methadone and buprenorphine
title_fullStr Mitragynine attenuates morphine withdrawal effects in rats—a comparison with methadone and buprenorphine
title_full_unstemmed Mitragynine attenuates morphine withdrawal effects in rats—a comparison with methadone and buprenorphine
title_short Mitragynine attenuates morphine withdrawal effects in rats—a comparison with methadone and buprenorphine
title_sort mitragynine attenuates morphine withdrawal effects in rats—a comparison with methadone and buprenorphine
url http://psasir.upm.edu.my/id/eprint/86772/
http://psasir.upm.edu.my/id/eprint/86772/
http://psasir.upm.edu.my/id/eprint/86772/
http://psasir.upm.edu.my/id/eprint/86772/1/Mitragynine%20attenuates%20morphine%20withdrawal%20effects%20in%20rats.pdf