Examining The Psychoactive Differences Between Kratom Strains

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]

Interestingly, the different effects associated with kratom use appear to be dose-dependent, with low to moderate doses (1 - 5 gram) inducing stimulation and awareness, and with moderate to high doses inducing analgesia and sedation.[6] While much of kratom's pharmacology remains unexplored, mitragynine (MG) 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 MG, with some being similar in their molecular formulas and with others being formulaically identical but geometrically rearranged. Examples include MG's oxidized derivative 7-hydroxymitragynine (7-HMG) and several MG diastereomers including speciogynine, speciociliatine and mitraciliatine.[7]

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 unique (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.[8] Similarly, with regards to the different color denominations, the marketing of kratom products and anecdotal reports from kratom users 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.

Presumably, these reported differences between kratom strains could be mediated by variations in their alkaloid profiles, in a manner analogous to cannabis strains producing unique effects due to variations in cannabinoid profiles.[9] Indeed, findings from analytical chemistry suggest that different strains of kratom can vary in their alkaloid content.[10] 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.[11] 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. . Thus, the differences between kratom strains might just reflect a placebo or expectancy effect due to marketing, customer reviews or hear-say.[12]

Therefore, the current study strived to investigate the notion that kratom products marketed as red, green, and white kratom strains can produce unique 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 some 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.

2. Materials and Methods

2.1. Power Calculation

An online sample size calculator (https://www.surveymonkey.com/mp/sample-size-calculator/) was used to estimate the required number of survey respondents. Given that the hypotheses of the current study were novel and given that the main outcome measure was designed for this study specifically, the sample size calculation could not be based on prior research findings. However, the calculation assumed that the overall kratom use population is about 5 million people in the U.S., which is a conservative estimate based on kratom imports from Indonesia.[13] Given this assumption and given a 95% percent confidence interval, the required sample size was estimated to be 385. However, since not all kratom users consume all strains of kratom, the required sample size per strain was estimated to be about 150 responses. Under the assumption that 70% of responses were to be valid responses, it was estimated that the current study would require 315 valid responses (105 responses per strain) to have sufficient statistical power.

2.2. Participants

The target population of this survey were people who use kratom regularly. Recruitment of study participants was achieved in collaboration with the kratom vendor Super Speciosa (https://superspeciosa.com/). The survey link was distributed as part of newsletters sent to clientele of Super Speciosa. No incentives of any kind were given for study participation. Survey responses were obtained between July 22^nd 2022 and September 12^th 2022, after which a total of 644 responses were obtained.

2.3. Procedure

The study was conducted using the online survey platform Qualtrics (Qualtrics, Provo, UT). The survey consisted of a questionnaire which asked participants about their experiences with different kratom strains. The questionnaire was designed to be completed in approximately 5 – 15 minutes. On the first page of the survey, participants were provided with an informed consent form explaining the purpose of the study and the risks and benefits of participation. Participants were required to indicate their agreement to participate in the study by checking a box on the informed consent page. Participants were informed that withdrawing from the study was possible at any time and that the survey data could not be traced back to any individual.

2.4. Questionnaire design

The questionnaire consisted of different blocks which are summarized below. A Qualtrics export of the full survey can be found in Appendix A.

2.4.1. Block 1: General Health

Participants were asked to indicate their height (in ft. and inches) on visual sliders and were asked in open-ended format what their body weight was (in lbs). Subsequently, participants were asked in multiple-choice format about the frequency with which they smoke (i.e., cigarettes or nicotine-containing e-liquids) and the frequency of their alcohol consumption. Participants were then asked if they were currently prescribed antidepressants, anxiety medication, antipsychotics, opioids and/or other prescription medications. Lastly, respondents were asked whether a physician had ever diagnosed them with any of the following conditions: post-traumatic stress disorder (PTSD), depression, social anxiety, generalized anxiety disorder, schizophrenia (or other psychotic disorders), bipolar disorder, personality disorder, attention deficit or hyperactivity disorder (ADD/ADHD), addiction and substance disorder, fibromyalgia, rheumatoid arthritis, chronic pain. These specific diagnoses and medical prescriptions were included as items because prior literature suggested they are commonly relevant in the population of kratom users.[14]

2.4.2. Block 2: Kratom Strain Color

This block consisted solely of the following multiple-choice question: “Which color(s)/strain(s) of kratom do you generally consume? “. This question aimed to ascertain if the kratom products consumed by the respondent were green, white and/or red kratom strain products. The subsequent blocks of questions were repeated once, twice, or thrice, depending on whether the respondent consumed one (e.g., only red), two (e.g., red and green) or three (red, green, and white) different kratom strains (Figure 1).

2.4.3. Block 3: Kratom Dosing Regimen

Block 3 of the survey was repeated for each kratom strain consumed by the respondent. Respondents were asked whether they purchased the given strain of kratom at Super Speciosa or at a different vendor. Respondents were asked what type of formulations (power, tablets, capsules and/or tea) they purchased of the given strain. On visual sliders (ranging from 0 to 20, with the items being gram, capsules, tablets, tea bags, teaspoons of powder, and tablespoons of powder), the respondents then indicated what serving size they typically consume of the given strain of kratom, at what frequency per week/month they consume the strain and what number of servings they consume in a typical day. Lastly, respondents were asked at what time of day (morning, afternoon, evening or at night) they generally consumed the given strain of kratom, and whether they consume their kratom before, after or with a meal.

2.4.4. Block 4: Ranking Motivations to use Kratom

Block 4 of the survey was repeated for each kratom strain consumed by the respondent. The respondents were given a list of 13 prewritten statements indicating potential motivations to consume kratom. The respondents were asked to rank these motivations in the order most applicable to their consumption of the given strain of kratom (i.e., red, white, or green kratom products). This questionnaire was designed as an extended version of the 18-item reasons for drug-use scale by Boys and colleagues.[15] The added items included motives related to social context, self-exploration, and escapism, as derived from qualitative interviews.[16] The full list of motivational statements can be found in Appendix A.

2.4.5. Block 5: Self-reported Effects of different Kratom Strains

Block 5 of the survey was repeated for each kratom strain consumed by the respondent. Respondents were shown a randomized list of items describing subjective drug effects (e.g., feeling happier), and were asked to indicate on a visual analog scale (VAS) ranging 0 – 100 to what extent they experienced the given drug effect. The meaning of the range of values on the VAS was exemplified with the following 4 labels: ‘The effect is not present or not applicable to my situation’ (i.e., 0), ‘The effect is present to some degree’ (i.e., 1-25, ‘The effect is clearly present’ (i.e., 26-75), and ‘The effect is present with great intensity’ (i.e., 76-100). The full list of items is shown in Appendix A.

2.5. Data Analysis

The survey data were analyzed using descriptive statistics and inferential statistics. Descriptive statistics were used to summarize the demographic characteristics of the participants and the reported effects of each kratom strain. Inferential statistics were used to test for differences in reported effects between different kratom strains. Correlational analysis of nominal data was conducted using a Chi-square or Friedman test while Student’s t-test and one-way ANOVA analysis followed by post-hoc Bonferroni comparison were used for interval data. Statistical significance is defined as α≤0.05. Statistical analyses were conducted using SPSS software (version 26, IBM, Armonk, NY).

3. Results

3.1. General Demographic Information

Table 2 summarizes the general demographic information of the survey population. The survey population was comprised mostly of middle-aged adults, with most respondents being within the age range of 35-44 years (29.70%), followed by 25-34 years (20.00%), and 45-54 years (22.80%). In terms of gender, the sample was relatively balanced, with slightly more respondents identifying as male (56.60%) compared to female (41.10%), and a small percentage identifying as non-binary (1.50%).

Most participants had received at least some college education (40.10%) or a bachelor's degree (24.80%). Most participants were employed for wages (64.00%), with a sizeable percentage being retired (11.40%) or unable to work (8.90%). Nearly half of the respondents were married (44.50%), while one third had never been married (32.10%). In terms of ethnicity and nationality, the survey population was overwhelmingly Caucasian (86.40%) and American (85.98%), with limited representation of other ethnicities and nationalities. The annual household income distribution was varied, with the largest proportion of participants reporting an income of $100,000-$149,999 (16.00%), and with some respondents preferring not to disclose their income (7.50%). Most respondents reported never or rarely smoking and/or vaping (62.70%), while a considerable percentage reported daily use (32.80%). Most respondents rarely or never consumed alcohol (76.10%).

3.2. Clinical Profile

Table 3 displays the clinical profile and medication use of the survey population. In this sample, 29.0% used antidepressants, 14.3% anxiety medications, 3.3% antipsychotics, 7.1% opioid pain killers, and 9.3% stimulants. 23.8% of respondents reported using other prescription medications, while 44.6% were not taking any prescription medications. The most prevalent clinical diagnoses were depression (42.7%), generalized anxiety disorder (32.8%), and chronic pain (38.8%). Less prevalent diagnoses included PTSD (20.8%), social anxiety disorder (17.9%), ADD/ADHD (19.9%), addiction/substance use disorder (14.3%), fibromyalgia (8.7%), and rheumatoid arthritis (7.9%). Schizophrenia, bipolar disorder, and personality disorder were reported by 1.6%, 8.7%, and 3.0% of participants, respectively, while 22.0% reported not being diagnosed with any of the listed diagnoses.

3.3. Between-Strain Comparison Of Motivations

Respondents were shown 13 randomly ordered motivational statements and were asked to rank these statements in the order most applicable to their use of a given kratom strain. Table 4 shows the average positions (between 1 – 13) at which each motivational statement was ranked for respondents consuming red (N=184), green (N=288), or white (N=131). A Chi-squared test was conducted for each motivational statement to detect between-strain differences in the average ranking position.

Significant differences were found for the statements “to treat a medical condition” (p=0.049), “to help you relax or sleep” (p=<0.001), “to improve your mood or to feel less sadness/depression” (p=0.007), “to help you concentrate work or study” (p=0.001), “to induce or enhance a spiritual experience” (p=0.021), and “to be more sociable or to get more enjoyment out of social events” (p=0.005).

For the statement "to treat a medical condition," red kratom users ranked it highest (position 3.51, SD=3.37), while green strain users ranked it lowest (position 4.25, SD=3.51). White kratom users ranked the statement at position 4.18 (SD=3.38). For the statement "to help you relax or sleep," red kratom users ranked it highest (position 3.83, SD=2.54), while white strain users ranked it lowest (position 6.06, SD=2.99). Green kratom users ranked the statement at position 5.15 (SD=2.68). For the statement "to improve mood or feel less sadness/depression," green kratom users ranked it highest (position 5.28, SD=4.00), while red strain users ranked it lowest (position 6.34, SD=3.88). White kratom users ranked the statement at position 5.45 (SD=3.96). For the statement "to help concentrate on work or study," white kratom users ranked it highest (position 5.30, SD=3.49), while red strain users ranked it lowest (position 6.97, SD=3.15). Green kratom users ranked the statement at position 5.72 (SD=3.15). For the statement "to induce or enhance a spiritual experience," red kratom users ranked it highest (position 6.70, SD=3.15), while green strain users ranked it lowest (position 7.40, SD=3.13). White kratom users ranked the statement at position 6.93 (SD=3.24). For the statement "to be more sociable or enjoy social events more," white kratom users ranked it highest (position 6.50, SD=2.72), while red strain users ranked it lowest (position 7.26, SD=2.46). Green kratom users ranked the statement at position 6.39 (SD=2.54).

Moreover, for white strain users, there was a significant correlation (Figure 2) between the amount of kratom consumed and the position at which the statement “to help you concentrate on work or study” was ranked, i.e., white kratom users who consumed higher doses tended to rank this statement higher. In contrast, for the statement “to help you relax or sleep”, users of white kratom strains ranked this significantly lower with higher dose use compared to the red and green strains. These were the only significant correlations found between dosing amount and average ranking position across all the motivational statements.

3.4. Self-Reported Subjective Effects of different Kratom Strains

Table 5 presents the self-reported effects of different kratom strains (green, red, and white) on various physiological outcomes and aspects of mood and cognition. Participants were asked to indicate on a visual slider (0 – 100) the extent to which they experienced a given drug effect when consuming a particular kratom strain. For every drug effect, a cross-strain comparison was made by means of an ANOVA. Out of the 39 VAS items, only 6 showed statistical significance in their cross-strain omnibus ANOVA, namely ‘being better able to concentrate’ (p < 0.01), ‘feeling more energetic’ (p < 0.01), ‘feeling more stimulated’ (p < 0.01), ‘feeling more constipated than usual’ (p < 0.01), ‘being better able to stay up all night’ (p < 0.01), ‘being better able to fall asleep’ (p = 0.0364).

Tukey's multiple comparison tests revealed significant differences between kratom strains for the following drug effects: ‘being better able to concentrate’, with green strains (x̄=60.98) being rated to improve concentration more than red strains (x̄=49.79, p<0.01), and white strains (x̄=69.42) being rated to improve concentration more than red strains (p<0.01) and green strains (p=0.04); ‘feeling more energetic’, with green strains (x̄=64.46) being rated as more energizing than red strains (x̄=52.93, p<0.01), and white strains (x̄=66.5) being rated as more energizing than red strains (p<0.01); ‘feeling more stimulated’, with green strains (x̄=52.94) being rated as less stimulating than white strains (x̄=62.61, p=0.01), and with red strains (x̄=48.79) being rated as less stimulating than white strains (p<0.01); ‘feeling more constipated than usually’, with green strains (x̄=26.45) being rated as causing less constipation than red strains (x̄=39.39, p<0.01) and white strains (x̄=41.74, p=0.01); ‘being better able to stay up all night’, with green strains (x̄=26.45) being rated as less effective in maintaining wakefulness compared to white strains (x̄=41.14, p<0.01), and with red strains (x̄=18.43) being rated as less effective in maintaining wakefulness compared to white strains (p<0.01).

3.5. Certificates of Analyses (COAs)

Analysis of Alkaloid Content of Super Speciosa Products was conducted by Santé Laboratories, which operate independently from Super Speciosa. The certificates of analyses (COAs) showing the alkaloid content of the products of Super Speciosa included in the survey were obtained by means of liquid chromatography quadrupole Time-of-Flight Mass Spectrometry (LC-MS-QTOF). As shown in Table 6, the presence of mitragynine, paynantheine, speciogynine and speciocilliatine was measured for each product, as well as the total alkaloid content. The examined products were White Maeng Da, Red Maeng Da, Green Bali, White Thai, Green Maeng Da and Red Bali. A one-way ANOVA revealed that the products did not differ significantly from one another in terms of their mitragynine (p=0.362), paynantheine (p=0.917), speciogynine (0.803), or speciociliatine content (p=0.762), and there was no significant difference in total alkaloid content (0.500).

4. Discussion

Kratom products are sold in the west as different strains, often denoted by the coloring of the plant product and the region where the plant was cultivated. Anecdotal reports of kratom users as well as the marketing of kratom products, both suggest that the effects induced by kratom are strain-dependent, presumably due to variations in the alkaloid content of different strains.[17] Given the absence of published research investigating the differences between kratom strains, the current study sought to investigate by means of an online questionnaire whether different color strains of kratom can induce unique pharmacological effects in humans, and whether use of the different color strains is driven by distinct motivations.

The survey population can be described as primarily working middle-aged, Caucasian, American individuals with some level of post-secondary education. Given that the respondents were customers of an American based online vendor, it is unsurprising that the survey population is predominantly American. However, the lack of ethnic diversity in the sample should be considered when interpreting the results of this study.

In the current survey, motivations for using either red, green, or white kratom strains were investigated by asking survey respondents to rank 13 pre-written motivational statements in the order most applicable to their use of the respective strains. Interestingly, there are notable congruencies between the respondents’ ranking of these statements and the way that different color strains are commonly marketed. For example, red kratom users ranking the motivation "to help you relax or sleep" at the highest position is consistent with product descriptions claiming that red strains are calming, anxiolytic and beneficial in treating insomnia. Likewise, the motivation "to improve your mood or to feel less sadness/depression" being ranked highest by green kratom users, is in line with marketing claims that green strains are the best for promoting overall well-being. As for white strain users, the finding that "to help you concentrate on work or study” was ranked highest, is congruent with descriptions of white strains being nootropic, stimulating and energizing. Interestingly, part of these congruencies extended to the results of VAS scales in which the respondents indicated to what extent 39 drug effects were present when they consumed red, green, or white kratom strains. Although all measures in the current study were self-report measures subject to reporting biases, there is a clear conceptual difference between self-reported motivations to use different kratom strains and self-reported effects of different kratom strains, in the sense that the former construct describes intention and reasoning, while the latter construct describes actual - albeit retrospectively observed - experiences.

It is therefore interesting that there was a consistent strain hierarchy for the items pertaining to concentration, wakefulness, sleepiness, stimulation, and energy on the VAS. For all items, the results indicated that white strains were experienced to be the most stimulating and energizing, while green strains were experienced to be less stimulating and energizing than white strains, but more stimulating and energizing than red strains. It can be argued that this hierarchy closely matches the aforementioned marketing claims and anecdotal reports of users consuming different kratom strains.

Interestingly however, the COAs of the different kratom products did not show any significant differences in alkaloid content between the kratom strains consumed by the survey population. Therefore, it seems that the significant between-strain differences in self-reported effects, are unlikely to be explained by variations in alkaloid content. It is possible that the observed differences were a placebo or expectancy effect induced by marketing information and/or by hearsay. In this case, the observed effect differences do not have a tangible pharmacological origin. However, an alternative explanation is that the observed differences are pharmacologically ‘real’, but that they are explained either by variations in alkaloids that were not measured, or by other substituents of kratom, e.g. terpenes.[17] Yet another possible explanation is differential metabolism and thus exposure of kratom alkaloids and other constituents as a variable of interindividual metabolic differences. This has not been evaluated to date, but we do know that several kratom alkaloids may induce or inhibit metabolic enzymes.[2,18]

It is important to note that some respondents of this survey were clientele of the same kratom online vendor, which poses both a limitation and a strength of this study. Namely, the homogeneity of the sample likely impairs generalizability of the current results to other vendors or other kratom products. Moreover, with the survey population being comprised predominantly of working middle-aged, Caucasian, American individuals with some level of post-secondary education, the survey population was lacking in ethnic and national diversity. On the other hand, having a homogeneous survey population presumably increased the statistical power of this study when compared to a hypothetical study in which the same number of respondents would have been recruited from different vendors.It is noteworthy that although more than one-third of the survey population was diagnosed with chronic pain, only 7.1% percent of respondents reported taking opioid pain medication. This adds credence to the claim that kratom has the potential to be a substitute for traditional analgesics, which is a notion that is increasingly being investigated by scientific and governmental institutions.[6,19]

In conclusion, the current study found that despite a lack of detectable differences in alkaloid content across red, green, and white kratom strains, users nonetheless reported distinct subjective experiences associated with each strain, and these experiences mirrored the strains' respective marketing descriptions, suggesting a strong influence of user expectations and marketing claims on the individual’s experience of different kratom strains. To assess the generalizability of these results, future survey studies should target more diverse populations while covering kratom strains from different vendors. Moreover, controlled, double-blind studies comparing the effects of kratom strains could experimentally prove whether the reported effect differences are caused by a placebo effect or by other factors, such as variations in terpenes or minor alkaloids that are not commonly quantified.