Factor 2: scientific evidence of its pharmacological effect, if known.
In the study, it is duly noted that there are over 25 alkaloids found in kratom. Alkoloids have been found to be very therapuetic and used to treat depression.
It is no mystery that Mitragynine (MG) and 7-hydroxymitragynine (7-OH-MG) are the primary active alkaloids of kratom.
As noted previously, kratom is found to be safe because it produces very little, if any, respiratory depression. This is a key element in understanding how humans process kratom, and how it differs from other opioids.
MG was found to produce markedly less respiratory depression than codeine (Macko et al. 1972).
And lastly, the study made several mentions that 7-OH-MG alkoloid is similar in potency to morphine, however this study concluded that this reference was NOT the finding.
Although MG (Warner et al. 2016; Hassan et al. 2013) and sometimes 7-OH-MG (Matsumoto et al. 2006) have been reported as 13 times more potent than morphine, many of the references used to support this figure appear to not actually report this finding.
In summary, that although alkoloids were were present in kratom, more research is needed to truly understand how they interact with one another. Observable effects are seemingly more accurate and should be used as only a guide.
Taken together, although progress has been made in understanding the pharmacology of kratom and MG and 7-OH-MG in particular, more research is needed to fully characterize the mechanisms of action that contribute to a novel profile of some opioid- like and stimulant-like effects that may be important in the consumption of kratom products. In the absence of clarity about the pharmacological mode of action, observed effects are the most reliable guide to the impact of kratom.