More than an opioid: dissociable analgesic and behavioral effects of kratom in planarians

Kratom (Mitragyna speciosa) is a psychoactive plant with stimulant, sedative, and analgesic properties, yet the mechanisms underlying its behavioral effects remain incompletely understood. In particular, it is unclear whether kratom's effects across behavioral domains are uniformly mediated by opioid receptor signaling. The present study used the planarian flatworm (Dugesia dorotocephala) to characterize the effects of kratom and to determine the extent to which these effects are opioid-dependent using the antagonist naloxone. In study 1, kratom produced dose-dependent reductions in locomotion and nociceptive responding, with higher doses nearly abolishing movement. In study 2, kratom significantly reduced locomotion, but this effect was not reversed by naloxone. In contrast, kratom-induced reductions in nociceptive curling were reversed by naloxone, indicating opioid receptor involvement. Together, these findings demonstrate a dissociation between opioid-dependent and opioid-independent effects of kratom, with analgesic effects mediated by opioid receptors and behavioral effects mediated by nonopioid mechanisms. These results highlight the multimodal pharmacology of kratom and support the use of planarians as a tractable model for investigating its neurobehavioral mechanisms.