Available online at www.sciencedirect.com Journal of Ethnopharmacology 116 (2008) 173–178 Inhibitory effects of kratom leaf extract (Mitragyna speciosa Korth.) on the rat gastrointestinal tract Somsmorn Chittrakarn a,∗ , Kitja Sawangjaroen a , Supaporn Prasettho a , Benjamas Janchawee a , Niwat Keawpradub b a Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand b Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand Received 14 November 2006; received in revised form 11 November 2007; accepted 15 November 2007 Available online 28 November 2007 Abstract Kratom (Mitragyna speciosa Korth.) is an indigenous plant of Thailand used traditionally in folk medicine although it is claimed to cause addiction. It is used to treat diarrhea, however, there is no scientific evidence to support the use. The aim of this study is to investigate the effect of methanolic extract of kratom leaves on the rat gastrointestinal tract. Kratom extract at 50, 100, 200 and 400 mg/kg (p.o.) caused a dose dependent protection against castor oil-induced diarrhea in rats and also inhibited intestinal transit. The antidiarrheal effect was not antagonized by naloxzone. The inhibition of intestinal transit by kratom extract was significantly different from the control when treated with a single dose for 1 day. For longer-term treatments of 15 and 30 days, kratom extract did not decrease the intestinal transit time indicating that adaptation had occurred. Kratom extract at a dose level of 200 and 400 mg/kg for 30 days and morphine at 3 mg/kg (i.p.) caused a decrease in the increment of body weight that was significantly different from the control and kratom extract at lower doses (50 and 100 mg/kg). However it had no effect on the level of plasma cholecystokinin. The results suggested that methanolic kratom extract exhibited its antidiarrheal effect on rat gastrointestinal tract. The effects may occur via pathways in addition to the action on opioid receptors. High does of kratom extract decreased the increment of body weight similar to the effect of morphine. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Mitragyna speciosa; Kratom; Diarrhea; Intestinal transit; Body weight; Cholecystokinin; CCK 1. Introduction Mitragyna speciosa Korth., family Rubiaceae, is found in tropical and sub-tropical regions of Asia. It is a tree indige- nous to Thailand, where it is mostly called kratom. It can be found throughout the country but is grown mostly in the south- ern region. To our knowledge, there are two varieties of kratom in Thailand, one with red veins in the leaf, the other with green veins. The red veined variety is supposed to have the stronger biological activities. Kratom has been traditionally used in Thai- land and Malaysia. In addition to being used in its own right, as a narcotic drug, it is often used as a substitute for opium when opium is unavailable, or drug users are trying to moder- ∗ Corresponding author. Tel.: +66 74 288178; fax: +66 74 446678. E-mail address: somsmorn.c@psu.ac.th (S. Chittrakarn). ate their opium addiction. A kratom user mostly likes to chew fresh leaves. When preparing fresh leaves, the vein is removed. Kratom has been reported to be a central nervous system stim- ulant rather than a depressant. It also helps to increase work efficiency and tolerance to hard work under a scorching sun (Suwanlert, 1975). Although the growing and harvesting of kratom is prohibited in Thailand, it is still used in traditional medicine and its use is still widespread especially where the kratom trees grow naturally. Over 25 alkaloids have been isolated from kratom leaves. Mitragynine is the major alkaloid found in this plant. Mitrag- ynine has been demonstrated to produce an antinociceptive effect through an action on supraspinal opioid receptors and descending noradrenergic and serotonergic systems (Matsumoto et al., 1996). Mitragynine inhibited the vas deferens contraction elicited by nerve stimulation, probably through its blockage of neuronal Ca 2+ channels (Matsumoto et al., 2005). Mitragynine 0378-8741/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2007.11.032