Non-Prescribed Buprenorphine Use Mediates the Relationship between Heroin Use and Kratom Use among a Sample of Polysubstance Users

Abstract

In Asia, Mitragyna speciosa (e.g., “kratom”) has been used to mitigate alcohol and drug dependence. Some preliminary findings suggest kratom’s potential use as an informal harm-reduction method in the United States, such as an opioid substitute or as a means of lessening opioid withdrawal symptoms. To determine correlates of past-year kratom use among a sample of polysubstance users enrolled in residential recovery programs in Kentucky, an anonymous survey was completed by clients in April 2017. Logistic regression was used to identify significant associations with past-year kratom use. Of the final sample (N = 478), 10.4% reported past-year kratom use. Past-year heroin use, but not past-year prescription opioid (e.g., oxycodone, hydrocodone) use, was significantly associated with kratom use, such that individuals who reported past-year heroin use were 2.5 times more likely to also report past-year kratom use. Non-prescribed buprenorphine (i.e., Suboxone) use partially mediated the relationship between past-year heroin and kratom use by explaining 36% of the association between the two drugs. Though amphetamines were highly preferred, past-year use was negatively correlated with past-year kratom use. Rates of past-year kratom use were lower than rates of alcohol and illicit drug use. Kratom was not preferred over heroin or prescription opioids.

Introduction

Mitragyna speciosa, commonly referred to as kratom, is an evergreen tree in the Rubiaceae (coffee) family indigenous to southeast Asia, where it has been used primarily for recreational, cultural, medicinal, and occupational (e.g., increase stamina under harsh work conditions) purposes (Brown, Lund, and Murch 2017; Tanguay 2011). In the United States (U.S.), kratom has been used most often to treat symptoms related to chronic pain, anxiety, and depression (Grundmann 2017). Kratom leaves contain over two dozen alkaloids, though many of these are not believed to be pharmacologically active (Adkins, Boyer, and McCurdy 2011; Basiliere, Bryand, and Kerrigan 2018). The most abundant alkaloid, mitragynine, is a partial agonist at mu-opioid receptors; it comprises approximately 60% of the total composition of alkaloids in kratom and is believed to account for many of its psychoactive effects (Suhaimi et al. 2016). Some of these effects may not be solely mediated through opioid receptors, but also by binding to adrenergic and serotonergic receptors (Matsumoto et al. 1996). Another alkaloid, 7-hydroxymitragynine (7-OH), is present in concentrations less than 2.0% and is not thought to account for a significant proportion of kratom’s effects; it is a more potent partial agonist at mu-opioid receptors (Hemby et al. 2018; Warner, Kaufman, and Grundmann 2016). In animal assays, mitragynine was assessed as less potent than morphine, whereas 7-OH was assessed as more potent than morphine (Matsumoto 2006; Takayama et al. 2002). The potency of the entire kratom extract in humans has not yet been established.

In contrast to classical opioids like morphine or heroin, kratom alkaloids are biased agonists at G-protein coupled opioid receptors, meaning that they do not activate the β-arrestin 2 second-messenger pathway (Kruegel and Grundmann 2018). Activation of the β-arrestin 2 pathway by conventional opioid agonists has been associated with adverse effects, such as respiratory depression, and may also partly account for conventional opioids’ abuse liability (Manglik et al. 2016; Porter-Stransky and Weinshenker 2017). Kratom use as a means of easing opioid withdrawal symptoms and craving, or as a longer-term maintenance medication, has been documented in both Asia and the U.S. (Boyer et al. 2008; Grundmann 2017; Singh, Narayanan, and Vicknasingam 2016; Vicknasingam et al. 2010). Kratom has also been used to self-treat psychological symptoms, such as anxiety or depression (Grundmann 2017). As anxiety and depressive symptoms often present comorbidly with substance use disorder (SUD) and overlap with opioid withdrawal symptoms, kratom use may serve dual purposes for some users (Dyer et al. 2001).

Although kratom is not currently supported as a medical intervention by the Food and Drug Administration (FDA), its informal use as a supplement has increased in the U.S. over the past decade to an estimated 5 million users (Anwar, Law, and Schier 2016; FDA 2018a; National Institutes of Health 2018). Still, items assessing kratom use have not been included in nationally representative substance use surveys, and there is no reliable information on the extent of its uptake by people with a history of SUD. In a large, non-clinical U.S. sample, Grundmann (2017) found that of respondents who reported having used kratom to mitigate withdrawal symptoms of a current or previous drug dependency, most reported that withdrawal symptoms stemmed from iatrogenic opioid dependence, but a subset reported that the symptoms stemmed from illicit drug dependency. Kratom appears to be biphasic across the typically used dose range, stimulatory at low doses and sedative and analgesic at higher doses. Thus, kratom could appeal to people with disparate preferences, to be used either as a substitute for or supplement to other drugs, or for mitigation purposes (Kruegel and Grundmann 2018; Likhitsathian et al. 2018; Prozialeck, Jivan, and Andurkar 2012). Consistent with that idea, Singh et al. (2015) reported that long-term kratom users were taking kratom in order to maintain abstinence from a variety of substances.

Prelude to kratom: Rise of prescription opioid and heroin misuse in the U.S

Kratom use as a self-adopted, informal harm-reduction method among people with opioid use disorder (OUD) is of interest in the U.S. now, given ongoing issues of opioid misuse, overdose, and overdose-related death, which have partially stemmed from increases in opioid prescribing and diversion over the past two decades (Brady, McCauley, and Back 2015; Dart et al. 2015; Hedegaard, Warner, and Miniño 2017; Jalal et al. 2018; Kolodny et al. 2015). In 2012, the annual opioid prescribing rate peaked at 81.3 per 100 persons, and although it has since declined, it remains high with a prescribing rate of 58.5 per 100 persons as of 2017 (Centers for Disease Control and Prevention [CDC] 2017a). The response to the increase of prescription opioid misuse has included novel state and federal legislation, revised CDC opioid prescribing guidelines, prescription monitoring databases, and greater promotion of medication-assisted treatment (MAT) (e.g., buprenorphine, naloxone, naltrexone, methadone) (CDC 2018; Lin et al. 2018; Makary, Overton, and Wang 2017; McCarthy 2017; Powell and Pacula 2017). Ultimately, the various responses remain uncoordinated and underfunded (Madras 2018; Pacula and Powell 2018). In the context of strategies implemented to address prescription opioid misuse, heroin use has increased significantly (Compton, Jones, and Baldwin 2016; Kanouse and Compton 2015).

Setting

Recent trends in opioid use have impacted rural and urban areas in the southeastern U.S., including Central Appalachia (Jonas et al. 2012; Moody, Satterwhite, and Bickel 2017; Slavova et al. 2017b; Staton et al. 2018). Our study sample was drawn from part of this region, Kentucky, which has experienced elevated opioid prescribing and diversion rates (Hall, Leukefeld, and Havens 2013; Luu et al. 2018) and continues to experience a high prevalence of opioid-related morbidity and mortality (CDC 2017b; Faryar et al. 2017; Kentucky Office of Drug Control Policy 2016). In 2016, the number of opioid-related overdose fatalities in Kentucky increased to 33.5 per 100,000, ranking the state the fifth highest in the nation (CDC 2017a). Opioid use in Kentucky is nested within a context where rates of opioid prescribing are comparatively greater, even as fentanyl-adulterated heroin continues to proliferate (Slavova et al. 2017b). Further, there are few or no MAT providers in some Kentucky counties, yet even in those counties rates of buprenorphine (i.e., Suboxone) prescriptions per capita are quite high (Kentucky Cabinet for Health and Family Services 2018; Substance Abuse Mental Health Services Administration 2018). The use of diverted buprenorphine in some Kentucky communities remains a growing but underexplored phenomenon and presents as another potential indicator of the breadth of the opioid crisis, in that it either constitutes yet another form of opioid misuse, or represents medically unsupervised use of a drug for fentanyl-adulterated (Cicero, Ellis, and Chilcoat 2018; Jalal et al. 2018; Lofwall and Havens 2012). Either scenario indicates that MAT may not be accessible to opioid-using subpopulations equitably and that OUD harm-reduction intervention shortfalls persist.

It is also important to consider that many opioid users in the state are involved with the Department of Corrections (DOC), which, in Kentucky, has limited pharmacological treatment options for OUD. For instance, similar to other state DOCs and the Federal Bureau of Prisons, the KY DOC does not permit, or severely restricts, the use of buprenorphine and methadone, despite evidence of these drugs as potentially life-saving interventions for corrections-involved opioid users (Aronowitz and Laurent 2016; Brinkley-Rubinstein et al. 2018; Department of Justice 2016; Fox et al. 2015; Jones 2018). Extended-release naltrexone is now available to some KY DOC-involved persons, yet the efficacy of extended-release naltrexone among this population has not been empirically established (Jarvis et al. 2018; Kentucky Department of Corrections 2018). Insufficiently addressed OUD in the justice system may prove especially consequential, as heroin adulterated with fentanyl and carfentanil is increasingly associated with overdose fatalities (Carroll et al. 2017; Marshall et al. 2017; Merrall et al. 2010; Slavona et al. 2017a).

Due to such constraints, opioid users in Kentucky may consider alternative ways to manage or moderate OUD. As noted earlier, this potentially includes informal, even illicit, drug-substitution strategies using diverted metha-done or buprenorphine, and may also include use of mostly licit, but still unregulated, substances such as kratom (Boyer et al. 2008; Grundmann 2017; Hall, Leukefeld, and Havens 2013; Johnson and Richert 2014; Singh et al. 2015; Swogger et al. 2015; Vicknasingam et al. 2010; Wiecko, Thompson, and Parham 2017). Among people with OUD involved with the DOC, kratom may have the additional appeal of not being detectable on standard drug screens, although possession or suspected use of kratom can result in probation/parole revocation in Kentucky, similar to heroin possession or suspected use.

Purpose

Current understanding of kratom’s pharmacology, coupled with self-reported subjective effects in humans, suggests that people with preference for or dependence on opioids may be more likely to initiate kratom use than individuals with a history primarily characterized by other drug use (Hassan et al. 2013; Ismail et al. 2016; Prozialeck, Jivan, and Andurkar 2012). Kratom is sold as a dietary supplement in 44 states and may be purchased online or from local vendors, including in Kentucky (Grundmann 2017; Smith and Lawson 2017), making it a potentially attractive substitute for classical opioids among some users. The aim of this exploratory investigation was to further examine survey data pertaining to lifetime and past-year substance use reported by a sample of polysubstance users enrolled in residential, peer-led recovery programs in Kentucky (Smith and Lawson 2017) in order to determine concomitants of past-year kratom use and to better understand drug preferences of past-year kratom users.

Methods

Clients in five peer-led, drug-free, residential recovery centers participated in this study. These centers were chosen based upon their varied locations in the state. Two were located in a metro area of ≥1 million population, two in a metro area of 250,000 to 1 million, and one was an Appalachian-based program in a non-metro area adjacent to a metro area with an urban population of 2,500–19,999 (U.S. Department of Agriculture 2013). The programs use a 12-step curriculum and constitute a controlled environment in which clients are subject to drug monitoring (Walker et al. 2018). A convenience sample was obtained by having a researcher meet with clients during regular program hours. Clients interested in participating in the study were informed that the study would not impact their standing in the program or with the DOC, which was a referral source for approximately 85% of clients. There was no compensation for participation. Of the 511 clients recruited, 503 chose to participate. This study was approved by the University of Louisville Institutional Review Board.

Measures and procedures

An anonymous self-administered paper survey was provided to clients who consented to participate. Those who were approached but chose not to participate (N = 8) worked on their regularly assigned recovery materials during the data collection session. Participants completed the survey in a large communal area (e.g., dining area, meeting room). A researcher remained in the room until all participants had completed their surveys. The researcher was available to answer questions or to clarify survey items as needed. Participants deposited their surveys into a closed box upon completion. Typical survey completion time was 15 minutes. Individuals in this sample had been enrolled in the recovery program for an average of 3.5 months at the time data were collected in April 2017.

The content of the survey was informed by published literature on kratom and by prior professional work with this population. This process also included pilot testing the survey with 10 participants from one all-male recovery program and conducting a brief focus group. Because of the straightforward nature of the survey, only minor revisions were made subsequent to the pilot testing and focus group.

Demographic data collected were age, highest level of education attained, sex, race, marital status, and past-year employment.

Past-year substance use was measured by asking participants to indicate if they had used alcohol, marijuana, synthetic cannabinoids, synthetic cathinones (e.g., bath salts), cocaine, amphetamines, sedatives (e.g., Valium), barbiturates, inhalants, club drugs (e.g., ecstasy), and hallucinogens at least once in the past 12 months. Past-year opioid use was measured by asking participants to report use of opioid agonist drugs other than kratom by placing a check mark next to each relevant substance used in the past 12 months. Opioid drug options presented to participants included: “Heroin,” “Prescription opioids that were not prescribed to you (e.g., OxyContin, Percocet, methadone),” and “Suboxone not prescribed to you.” Past-year kratom use was assessed by asking participants to indicate if they had used kratom at least once in the past 12 months. Additional questions pertaining to lifetime kratom use were also asked (see Smith and Lawson 2017).

Lastly, drug preference was assessed by asking participants to “List the three drugs that you most preferred using in the order you most preferred using them.”

Analytic plan

Descriptive statistics were used to characterize the demographics and drug preferences of past-year kratom users. Multiple logistic regression was used to determine concomitants of past-year kratom use. To avoid model overfitting, only variables significantly associated at the p < .05 level in bivariate tests were included in the final models. Model 1 examined demographic and polydrug-use correlates of past-year kratom use. Model 2 added past-year non-prescribed buprenorphine as a mediator to examine the potential influence of opioid harm reduction on these associations. Analyses were completed with Stata V15.1. Collinearity was not an issue as indicated by variance inflation factors. Model-fit statistics supported the appropriateness of the models.

Results

A total of 503 participants took the survey, but 25 surveys were not included in the analyses due to missing data. Participants in the final sample (N = 478) were, on average, 35 years old, White (84.9%), single (49.4%), had at least a high-school diploma or equivalent (92.2%), and worked full-time (32.6%). Most participants had a history of DOC involvement, with approximately 88% having been incarcerated at least once since 2010. Among these, the average length of total time incarcerated between 2010–2017 was 1.8 years. The average number of arrests for the same time period was 5.6.

Approximately 10% of the sample reported past-year kratom use (N = 49). Other past-year drug use significantly associated with past-year kratom use included heroin, prescription opioids, non-prescribed buprenorphine, marijuana, cocaine, and amphetamines. Summary statistics are presented in Table 1. No differences in rates of past-year kratom use were observed between programs. Frequencies for the top three most preferred substances among past-year kratom users appear in Table 2. Heroin was a preferred drug for the majority of kratom users (71.5%), as were amphetamines (63.4%); others preferred prescription opioids (35.0%). Non-prescribed buprenorphine was preferred by 12.4% of kratom users. Only 6.25% listed kratom among their top three preferred substances, and within that 6.25%, all ranked kratom third. In other words, no respondent rated kratom as his or her most preferred drug.

Table 1.

Summary statistics of relevant variables (N = 478).

	Total Sample (%)	Kratom Users	p-Value*
Dependent Variable
Past-year kratom use	10.4
Independent Correlates
Age	35.0	31.1	.002
Education level			.558
Below high school	7.7	4.1
High school/GED	52.3	48.9
Associates/Vocational	25.9	28.6
Bachelors	9.0	14.3
Masters	5.0	4.1
Gender (Male)	57.7	65.3	.265
Race (White)	84.8	87.8	.544
Marital status (Single)	49.0	59.2	.134
Employment status			.066
Full-time	33.3	22.4
Part-time	14.3	24.5
Unemployed	22.6	30.6
Incarcerated	24.7	20.4
Other (disabled/student)	5.1	2.0
Past-year drug use
Heroin	55.6	81.6	.001
Prescription opioids	63.6	77.5	.032
Sedatives	46.0	53.1	.297
Marijuana	65.3	81.6	.011
Cocaine	44.1	57.1	.053
Amphetamines	66.1	89.8	.001
Non-prescribed buprenorphine	52.1	83.7	.001

^*Chi-square tests of significance conducted on all variables, with t-test conducted for the continuous variable of age

Table 2.

Frequencies of drug preferences for past-year kratom users (N = 49).

	(%)
Heroin	71.5
Amphetamines	63.4
Prescription opioids	35.0
Sedatives	23.0
Cocaine/crack	22.7
Alcohol	22.6
Marijuana	20.7
Non-prescribed buprenorphine	12.4
Synthetic cannabinoids	8.25
Nicotine	8.25
Kratom	6.25
Club drugs	4.16
Synthetic cathinones	4.08

Table 3 presents the results from the logistic regression examining concomitants of past-year kratom use. Model 1 showed that respondents who reported past-year kratom use were more likely to report past-year heroin use (AOR = 2.51, 95% CI = 1.12–5.65). Past-year prescription opioid use showed no such association. Individuals who reported past-year amphetamine use (AOR = 0.35, 95% CI = 0.12–1.00), were less likely to have used kratom in the past year.

Table 3.

Logistic regression examining correlates of past-year kratom use (N = 478).

	Model 1*			Model 2*
	Std. Coef	AOR (95% CI)	p-value	Std. Coef.	AOR (95% CI)	p-value
Age	−0.04	0.96 (0.92–1.00)	0.08	−0.03	0.97 (0.93–1.01)	0.12
Heroin use	0.92	2.51 (1.12–5.65)	0.03	0.69	2.00 (0.86–4.63)	0.10
Prescription opioid use	−0.23	0.80 (0.36–1.78)	0.58	−0.51	0.60 (0.26–1.39)	0.23
Marijuana use	0.47	1.60 (0.72–3.57)	0.24	0.42	1.52 (0.68–3.42)	0.31
Cocaine use	0.20	1.23 (0.65–2.31)	0.53	0.20	1.22 (0.64–2.30)	0.55
Amphetamines use	1.04	2.82 (1.00–7.97)	0.05	0.75	2.11 (0.72–6.21)	0.17
Non-prescribed buprenorphine use	-	-	-	1.16	3.20 (1.32–7.77)	0.01

Notes: AOR = Adjusted Odds Ratio

^*Model 1 examined demographic and polydrug-use correlates of past-year kratom use. Model 2 added past-year non-prescribed buprenorphine as a mediator.

Model 2 showed that past-year use of non-prescribed buprenorphine partially mediated the relationship between past-year heroin use and kratom use, explaining approximately 36% of the association between the two drugs. Sobel tests (not shown) confirmed the significance of the mediation (p < .01).

Discussion

In this study, past-year kratom use was positively associated with heroin use, but not with prescription opioid use. The increased odds of past-year kratom use partially explained by use of non-prescribed buprenorphine may indicate that some people who use heroin and/or who may have OUD are trying both buprenorphine and kratom as a means of drug substitution or to ease withdrawal symptoms, as both motivations have been observed in other studies (Assanangkornchai et al. 2007; Furst 2014; Jayadeva et al. 2017; Swogger et al. 2015; Vicknasingam et al. 2010).

That a portion of the relationship between past-year heroin use and kratom use was mediated by non-prescribed buprenorphine use suggests that a subset of polysubstance users in Kentucky are contemporaneously using opioid agonists with complex mechanisms of action, but whose subjective psychoactive effects may be less robust than classical opioids, including heroin (Khanna and Pillarisetti 2015; Walsh et al. 1994; Wiecko, Thompson, and Parham 2017). Kratom and buprenorphine carry less likelihood for injection compared to heroin, which is noteworthy given the adverse consequences associated with injection drug practices (Staton-Tindall et al. 2015; Zibbell et al. 2015). In the U.S., kratom is typically purchased in powdered form and consumed as self-prepared beverages or capsules, or by swallowing the powder followed by drinking a liquid (Grundmann 2017; Smith and Lawson 2017). However, since the time that data were collected, there has been an increase in the marketing and sale of prepared kratom drinks, though these are also not readily injectable. The active alkaloids with known opioid receptor-binding capabilities found in leaf or powder kratom products sold in the U.S. are not water soluble such that they could be administered intravenously by the typical user. However, one case report documented intravenous administration of kratom extract by an individual with a history of opioid dependence and MAT utilization (Lydecker et al. 2017). While buprenorphine has the potential to be misused intravenously, despite its ceiling effect, there are few documented instances of this, suggesting that this method of administration has not become widely adopted among intravenous drug users (Daniulaityte, Falck, and Carlson 2012; Yeo, Chan, and Chia 2006).

Past-year prescription opioid use was not significantly associated with past-year kratom use. This may reflect modest decreases in the availability of prescription opioids state-wide, increases in street prices, and proliferation of abuse-deterrent formulations (Havens et al. 2014; Walter, Knothe, and Lötsch 2016). However, rates of prescription opioid use among this sample were higher (63.6%) than heroin (52.1%) and non-prescribed buprenorphine (52.1%), hinting that the relationships observed here may not so much reflect issues of prescription opioid availability. The perception of drug types may be relevant insofar as people who use prescription opioids, but not heroin, may be less likely to believe they are in need of a harm-reduction strategy due to potentially greater perceived safety of pharmaceutical drugs compared to heroin (Kolodny et al. 2015; Pollini et al. 2011).

Yet, some evidence suggests that opioid-dependent individuals, regardless of their opioid of choice, will seek out drug substitutes and life-saving strategies in pragmatic ways, particularly as treatment services in the U.S. remain inadequate for addressing OUD long-term (Madras 2018; Wiecko, Thompson, and Parham 2017; Yokell et al. 2012). For instance, capturing the frustrating complexity of the “opioid epidemic,” a recent case report in the U.S. documented a veteran with OUD who reportedly first used kratom to ease prescription opioid withdrawal symptoms and then used diverted buprenorphine to ease kratom withdrawal symptoms after becoming dependent on kratom (Jayadeva et al. 2017). Case reports have also documented the medical use of buprenorphine to treat kratom dependence and withdrawal symptoms among pregnant women with a history of OUD (Smid et al. 2018). Similar to other psychoactive substances, kratom has a potential for misuse and dependence, as well as a potential for therapeutic benefit (Grundmann 2017; Hassan et al. 2013; Singh et al. 2015, 2017). That 6.25% of past-year kratom users in this sample preferred kratom to other drugs indicates that kratom may indeed have appeal and abuse liability for a small subset of users. Dose-dependent kratom withdrawal effects (e.g., pain, anxiousness, irritability, sleep disturbance) are reported to be minor to moderate and dissipate over time, but may still incline some individuals to adopt a drug substitution strategy when use is discontinued or may necessitate MAT (Saingam et al. 2016; Singh et al. 2018a, 2018c).

Although short-term use of kratom for addressing symptoms of opioid withdrawal may have utility, the viability of kratom use long-term as an opioid replacement may pose challenges. More research in this area is needed. Yet, if the reduction of harm is taken as a foundational goal amidst what Jalal et al. (2018) assess as a nearly 40-year exponential increase of accidental drug-related mortalities, all strategies adopted by drug users demonstrating some promise to mitigate risk, particularly the risk of death, need to be taken seriously and require further exploration. Some reports have documented kratom-related side effects and morbidities (e.g., hepatotoxicity, seizure, insomnia, dehydration) and fatalities; however, no causal contribution of kratom has been sufficiently established, as prior health conditions and concomitant drug use are regular features of kratom-linked mortalities (Domingo et al. 2017; Fluyau and Revadigar 2017; Nelsen et al. 2010; Tatum et al. 2018; Tayabali et al. 2018). Indeed, other evidence suggests that regular, long-time kratom users showed few differences compared to healthy controls (Singh et al. 2018a, 2018b). Still, concomitant use of kratom with other substances is concerning, as 7-OH may produce adverse drug interactions (Haron and Ismail 2015).

Uncertain kratom policy

It is important to consider these findings within the current U.S. policy context in which kratom’s legal status remains uncertain and drug policy remains complex (Griffin 2014; Griffin and Webb 2018). As kratom use has proliferated in the U.S., it has received increased public and government attention (Griffin and Webb 2018). Intense debate and scrutiny of kratom’s safety may be attributable to several factors, including kratom’s unique pharmacology, reports of adulterated kratom products, sensationalized media coverage, and potential conflation of kratom with synthetic or novel psychoactive substances (Chien, Odonkor, and Amorapanth 2017; Dolengevich-Segal et al. 2017; Griffin and Webb 2018; Kronstrand et al. 2011; Lydecker et al. 2016; Singh, Narayanan, and Vicknasingam 2016). Kratom has remained on the Drug Enforcement Administration’s (DEA) “Drugs of Concern” list since 2013, despite insufficient scientific information regarding its pharmacology and side effects in humans (Castillo 2018; Federal Register 2016). DEA placement under Schedule I, the most restrictive category, will create more obstacles for research on kratom’s potential medicinal uses (Lanier et al. 2017). Since the FDA issued a public health advisory on the “deadly risks associated with kratom,” it has halted numerous shipments of kratom from entering the U.S. and has designated it as both an “opioid” and “drug of abuse” (FDA 2018a, 2018b). Meanwhile, scientists and kratom advocates continue to voice concerns about potentially hasty prohibitory decisions in light of inconclusive data, seeking FDA regulation of kratom products pending further information (American Kratom Association 2019; Grundmann et al. 2018; Henningfield, Fant, and Wang 2018).

Among people using kratom to reduce opioid use or abstain from heroin or prescription opioids, the inability to readily access kratom due to prohibitions may increase willingness to seek professional OUD treatment. Yet, the high rates of non-prescribed buprenorphine use among individuals in this sample indicates that some people using heroin or prescription opioids may procure harm-reduction medications illicitly and independently of formal medical channels. In other words, denied access to kratom, people with a history of illicit drug use may still procure prohibited drugs. For example, Daniulaityte, Falck, and Carlson (2012) found that among a community sample of young adults, non-prescribed buprenorphine was informally used to treat opioid withdrawal symptoms, as an occasional opioid replacement, and as a longer-term replacement. In Asia, kratom’s prohibition does not seem to have resulted in decreased use (Ahmad and Aziz 2012), though, as Griffin and Webb (2018) note, kratom’s continued presence in the region may reflect years of indigenous use as much as specific preference for kratom. Should kratom become prohibited in the U.S., individuals using it as a means of mitigating opioid dependence may feel that their choices for OUD management have been reduced. Since shortfalls remain in the availability of scientifically-informed OUD interventions in the U.S. (Epstein, Heilig, and Shaham 2018), any decrease in accessible harm-reduction avenues for people with OUD is concerning.

Limitations

There are several limitations to this cross-sectional study. First, respondents were asked to report past-year “kratom use,” which did not capture variability of strain type and product brands (Griffin, Daniels, and Gardner 2016). Dosing variability was also not captured, and thus cannot help explicate findings. Without laboratory testing, it is impossible to verify that reported kratom use represented actual use of kratom rather than use of adulterated products marketed as kratom. Similarly, “fentanyl” was not listed as a survey item, but it is likely that some respondents had consumed fentanyl in the past-year period. This study did not assess whether kratom was routinely co-ingested with other substances. Temporal order of use was not established, therefore making it possible that past-year kratom use predated instances of past-year use of traditional opioids and buprenorphine. That this convenience sample included a large portion of corrections-referred individuals mandated to participate in 12-Step modalities limits generalizability; however, most drug treatment programs have high proportions of corrections-referred participants. The narrow geographic region in which data were collected also limits generalizability. Lastly, self-report includes the possibility of poor recall; however, this methodology is considered valid and reliable for data collection among substance-using populations (Darke 1998; Denis et al. 2012; Zanis, McLellan, and Randall 1994).

Conclusion

Among this sample of polysubstance users in drug-free residential recovery programs, kratom was used in the past year by a minority of individuals, but among users, it was correlated with heroin use and was partially mediated by non-prescribed buprenorphine use. Globally, kratom has been used to help some individuals abstain from illicit drugs and alcohol long-term (Saingam et al. 2013; Singh, Narayanan, and Vicknasingam 2016). For some, kratom may be a useful opioid agonist replacement therapy that reduces the risk of opioid-related overdose or death, or as an aid to alleviate opioid withdrawal symptoms. Although long-term use of kratom in its current form may pose challenges due to issues of tolerance, it may more readily serve short-term purposes in reducing the well-known risks associated with heroin, should kratom be used as a substitute for heroin. Currently, there are insufficient data to make strong claims about kratom’s risks or effectiveness as an opioid agonist substitute, and more research is needed. In addition to controlled biomedical experiments, nationally representative surveys are required, not only to help estimate the prevalence of current and former kratom users, but also to explore the self-reported effects associated with kratom use, including dependence. Longitudinal studies collecting both detailed self-report and biological specimens will be important in examining kratom’s effectiveness and side effects over time, its safety profile, and a person’s willingness to continue using it as a replacement for more potent drugs.