1. Introduction
Mitragyna speciosa, colloquially known as kratom, is a tree that grows natively in several Southeast Asian countries, including Indonesia, Malaysia, and Thailand. In these countries, the human consumption of kratom dates back several centuries and has had medicinal and recreational motives [1,2]. Locals ingest the crude plant products either by directly chewing on the leaves, or by using the leaves as an ingredient in tea and other drink concoctions [3]. Through these routes of administration, the plant’s analgesic properties have been utilized to combat chronic pain, whereas its energizing effects have been popular among farming communities where kratom is used to prolong physical labor [4]. There are also records describing the use of kratom during religious ceremonies [5]. Although several parts of the tree have been analyzed for their phytochemical composition, only the leaves of Mitragyna speciosa are used for medicinal and recreational purposes [6]. However, in its native Southeast Asia, no distinction is made between kratom strains of different colors, nor are they advertised to be associated with distinct effects [7].
Interestingly, some of the different effects associated with kratom use appear to be dose-dependent, with low to moderate doses (1-5 g) inducing stimulation and awareness, and with moderate to high doses inducing analgesia and sedation [8]. While much of kratom’s pharmacology remains unexplored, mitragynine is widely regarded as one of kratom’s essential psychoactive ingredients. This indole alkaloid is generally found to be the most abundant alkaloid in kratom, accounting for about ⅔ of the plant’s alkaloid composition [2]. Other noteworthy kratom alkaloids resemble mitragynine, with some being similar in their molecular formulas and with others being formulaically identical but geometrically rearranged. Examples include mitragynine’s oxidized derivative 7-hydroxymitragynine and several mitragynine diastereomers including speciogynine, speciociliatine and mitraciliatine [9].
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Mitragynine has been studied most extensively in recent years by means of animal models and in vitro studies The indole alkaloid has been shown to exert activity at the µ-opioid receptor as a partial agonist, and at the α2 adrenergic receptor as an agonist [10]. Synergistic activity at both receptors has been shown to exhibit antinociceptive effects in animals. The in vivo metabolite of mitragynine, 7-hydroxymitragynine, is a specific and selective partial agonist at the µ-opioid receptor associated with analgesic effects. The minor alkaloids paynantheine and speciogynine have been shown to agonize serotonin receptors, specifically 5-HT1A and 5-HT2B receptors, in vitro and in animal models [11]. This activity has been associated with potential mood-enhancing effects as observed in behavioral animal models of depression and anxiety [12,13].
In the West, kratom is marketed and sold as different strains, which are generally named after two properties: first, the leaf vein coloring of the plant products (e.g., red, green, or white) and second, the country or region the plant was harvested (Malaysia, Sumatra, Thailand, etc.). This gives rise to strain names such as red Malay, white Thai, and green Thai. Importantly, the marketing of kratom strains posits that different strains can produce distinct (and sometimes contradictory) pharmacological effects. For example, online vendors report that the kratom strain “Maeng-Da” (originating from Thailand), is an excellent energy booster and mood enhancer, whereas the kratom strain “Sumatra” (originating from Indonesia), is a good stress reliever [14]. Similarly, with regards to the different color denominations, the marketing of kratom products and anecdotal reports from kratom users, both commonly state that red kratom strains tend to be anxiolytic and calming whereas white and green strains tend to be stimulating and energizing. Representative effect descriptions of red, green, and white kratom strains are summarized in Table 1.
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Presumably, these reported differences between kratom strains could be mediated by variations in their alkaloid profiles, in a manner analogous to cannabis strains producing distinct effects due to variations in cannabinoid profiles [15]. Indeed, findings from analytical chemistry suggest that different strains of kratom can vary in their alkaloid content [16]. Moreover, one study analyzed the elemental ingredients of kratom samples (e.g., calcium) by means of discriminant function analysis, and found that the samples could be reliably classified according to origin, sub-origin, and strain [17]. While such findings support the notion that the ingredients of different kratom products can vary substantially, thus far no empirical research has explored whether kratom products sold as different strains are reliably associated with distinct effect profiles. One phytochemical study did examine the metabolomic profile of young and mature kratom leaves and identified five unique alkaloids between the young and mature leaves while 76 secondary metabolites were present in both leaf samples, albeit in different concentrations [18]. While the major alkaloid mitragynine is present in approximately equal amounts in both young and mature leaves, some of the other indole alkaloids, including speciogynine, speciociliatine, and 7-hyroxymitragynine, are present in higher abundance in mature leaves. In most kratom leaf materials available on the US market, mature leaves are used.
Another study examined the seasonal and geographical differences between red- and green-veined kratom in parts of Thailand [19]. Though mitragynine remained the most abundant alkaloid, the total alkaloid concentration was much lower in the fall (October) sample compared to winter (January) and summer (June) samples. Regional differences indicate that total alkaloid content does also vary. Despite these phytochemical differences in composition, it is not clear whether the reported effect differences between kratom strains might just reflect a placebo or expectancy effect elicited by marketing, customer reviews or hear-say [20].
Therefore, the current study strived to investigate the notion that kratom products marketed as red, green, and white kratom strains can produce distinct pharmacological effects in humans. This was investigated by means of an online questionnaire which asked respondents about their motivations to use different kratom strains and the subjective effects they experienced when consuming them. It is important to note that most of the participants of this study were customers of the same kratom web shop (Super Speciosa, Super Organics LLC, St. Petersburg, FL, USA), which means that the results produced by this study might have limited generalizability to kratom products of other vendors. However, in addition to the survey results, a second source of data utilized in the current study was Certificates of Analyses (COAs) showing the alkaloid content of the kratom products consumed by those who indicated using kratom from the specific vendor surveyed in this study. These data were obtained through an independent laboratory unaffiliated with Super Speciosa, and therefore, the COAs allowed for the investigation of potential correlations between the alkaloid content of different kratom strains and the self-reported subjective effects produced by those strains.
Source: https://t-tees.com
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