Kratom is composed of leaves from the Mitragyna speciosa tree and are sold as a product world-wide. Kratom is used for pain opioid withdrawal, depression, anxiety, and for recreation, Mitragynine (MG) is an alkaloid found in Kratom that has been shown to decrease the consumption of alcohol and block morphine self-administration in rodents. MG's effects are thought to be mediated through. opioid receptors. Multiple studies indicate that mu opioid antagonists block the analgesic effects of MG. The mu opioid antagonist naltrexone (NTX) is indicated for the treatment of alcohol use disorder (AUD) and reduce alcohol self-administration ill animals. Prior studies show that MG alters alcohol consumption and alleviates alcohol withdrawal. Therefore, we tested MG, NTX alone and in combination on operant alcohol self-administration in rats. We found that both MG and NTX decreased alcohol self-administration yet the combination bad a greater effect than either administered alone, and did not alter locomotor activity. Similarly, MG and NTX combined enhanced cFos expression in several brain regions associated with alcohol reinforcement more than either drug alone. Our study is the first to test MG on oral operant alcohol self-administration in rats. Our finding that NTX did not block the ability of MG to decrease the reinforcing effects of alcohol was unexpected since NTX is a mu antagonist and blocks MG's analgesic effect. That combining MG and NTX decreased alcohol self-administration to a greater extent than either alone is novel and we believe the combination of the two compounds constitutes intellectual property that should be patented. Thus, we view this therapeutic combination as a much-needed potential treatment for AUD. Given that NTX is also indicated for the treatment of opioid use disorder (OUD) accumulating evidence supports the MG/NTX combination for this disorder as well.