Mitragyna speciosa is a tropical plant with narcotic effects. The antinociceptive effects of
its crude extracts, bioactive compounds and structurally modified derivatives have been examined in
rodent models. This review aims to summarize the evidence on the antinociceptive effects of M.
speciosa and its derivatives and explore whether they can offer an alternative to morphine in pain
management. Methanolic and alkaloid extracts of M. speciosa were shown to attenuate the nociceptive
response in rodents. Mitragynine and 7-hydroxymitragynine offered better antinociceptive effects than
crude extracts. Structurally modified derivatives of 7-hydroxymitragynine, such as MGM-9, MGM-
15, MGM-16, demonstrated superior antinociceptive effects compared to morphine. M. speciosa and
its derivatives mainly act on the opioid receptor, but receptor subtypes specificity differs between each
compound. The tolerance and adverse side effects of M. speciosa and its derivatives are similar with
morphine. The affinity of MGM-9 on kappa-opioid receptor could potentially limit the effects of drug
dependence. In conclusion, M speciosa derivatives can offer alternatives to morphine in controlling
chronic pain. Structural modification of mitragynine and 7-hydroxymitragynine can generate
compounds with higher potency and lesser side-effects. Human clinical trials are required to validate
the use of these compounds in clinical setting.
Keywords: Analgesia, ketum, morphine, narcotic, nociception, opioid, pain.
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