Kratom has a number of interesting minor alkaloids. The whole kratom (Mitragyna speciosa) leaf contains a partial mu-opioid agonist (9-hydroxycorynantheidine), and a mu-opioid antagonist (corynantheidine). The combination of a full agonist (such as 7-OHM and mitragynine) with an antagonist or partial agonist may be compared to the use of partial opioid-agonists to interrupt opiate addiction. Buprenorphine is one such example of a partial agonist/antagonist that is FDA approved to treat addiciton. It may be that ingesting whole kratom does not have the same addictive potential as 7-OHM alone.

Kratom also contains at least one alkaloid (rhynchophylline) that is a calcium channel blocker, and reduces NMDA-induced current. There is considerable research as to the role of NMDA receptor activity in the formation of dependence, and the symptoms of withdrawal.

In 2005, Inturrisi demonstrated that co-administration of d-methadone (the isomer that lacks opioid activity, but is an NMDA antagonist) in small doses with morphine prevented the development of morphine tolerance in rats.  There is clinical evidence that administering low doses of NMDA antagonists, such as dextromethorphan can even partially alleviate symptoms of withdrawal, though the threshold for unwanted PCP-like effects in opiate-dependent patients is low. The presence of rhynchophylline in kratom should be investigated in order to determine its potential to modify the development of dependence.