Marc T. Swoggera,⁎, Zach Walshb
a Department of Psychiatry, University of Rochester Medical 300 Center, Crittenden Blvd., Rochester, NY, USA
b Department of Psychology, University of British Columbia, 3333 University Way, Kelowna, BC, Canada
A R T I C L E I N F O
Keywords:
Kratom
Mitragyna speciosa
Substitution
Harm reduction
A B S T R A C T
Background: Kratom (Mitragyna speciosa) is a psychoactive plant native to Southeastern Asia that is receiving
increased international attention as a potential therapeutic agent. While much of the limited scientific research
on kratom is focused on its analgesic potential, kratom use also has important risks and benefits in the domain of
mental health.
Methods: We conducted a comprehensive systematic review of all studies on kratom use and mental health
published between January 1960 and July 2017.
Results: Findings indicate kratom’s potential as a harm reduction tool, most notably as a substitute for opioids
among people who are addicted. Kratom also enhances mood and relieves anxiety among many users. For many,
kratom’s negative mental health effects – primarily withdrawal symptoms – appear to be mild relative to those of
opioids. For some users, however, withdrawal is highly uncomfortable and maintaining abstinence becomes
difficult.
Conclusion: Results inform clinicians working in the mental health and substance use fields, policy-makers, and
researchers about the mental health effects of this plant.
1. Introduction
Kratom (Mitragyna speciosa; also known as krathom or ketum) is a
psychoactive plant in the Rubiaceae, or coffee, family that has been
used medicinally for centuries in Southeastern Asia (Cinosi et al., 2015;
Pendell, 2010). In Thailand and Malaysia, individuals use kratom across
diverse contexts; as an opium substitute and to relieve symptoms of
opioid withdrawal, medicinally to relieve pain, diarrhea, and cough,
and by manual laborers to enhance stamina and energy (Tanguay,
2011; Prozialeck et al., 2012). People chew raw leaves of the kratom
plant, boil them and serve as a tea, or smoke or vaporize them. Recent
years have witnessed the expansion of kratom use beyond Asia; kratom
leaves, powders, gums, capsules, and extracts are widely accessed via
the internet and retail outlets across North America and Europe
(Prozialeck et al., 2012; Singh et al., 2016), leading to novel concerns
regarding the potential for adverse consequences of use (Boyer et al.,
2008; Ward et al., 2011). In the absence of robust scientific data, some
warnings about kratom from government and press sources exhibit
features of drug hysteria (Hart, 2013), threatening researchers’ ability
to study the plant and the public’s ability to evaluate pros and cons of
kratom use, making this a critical time for collecting and evaluating
evidence for the risks and benefits of this substance. Some of the most
important potential risks and benefits of kratom are in the mental
health realm. For this reason, we conducted a systematic review of all
identified studies on kratom use and mental health.
As with many psychoactive substances before it, several factors have
led to baseless and potentially unwarranted fears about kratom in North
America; these include the marketing of kratom as a “legal high”
(Cinosi et al., 2015), the confusion between kratom and other novel
psychoactive substances (e.g., synthetic cannabis, bath salts), and sensationalized
media coverage of putative harms (e.g., “Kratom: The
supplement that will kill Godzilla”; Bloom, 2016). In the medical literature,
the number of published case studies that have highlighted
adverse events coincident with kratom use including liver toxicity and
death (Kapp et al., 2011; McIntyre et al., 2015; Neerman et al., 2012;
Nelsen et al., 2010; Sheleg and Collins, 2011) is disproportionately high
relative to the number of rigorous investigations. Case studies present a
relatively low level of evidence due to overrepresentation of extreme
events, unknown validity and generalizability, and other potential
biases (Merriam, 2009). These limitations render a causal linkage between
kratom and serious adverse events impossible. Nonetheless, results
of these studies have contributed to the issuance of dire public
warnings. For example, the U.S. Centers for Disease Control and Prevention
(CDC) and Drug Enforcement Administration (DEA) have explicitly
warned that kratom may cause psychosis or death (Anwar et al.,
2016; DEA, 2016) and the DEA has recommended criminalizing kratom
https://doi.org/10.1016/j.drugalcdep.2017.10.012
Received 29 May 2017; Received in revised form 3 October 2017; Accepted 7 October 2017
⁎ Corresponding author at: University of Rochester Medical Center, Department of Psychiatry, 300 Crittenden Blvd, Rochester, NY, 14642, USA.
E-mail address: marc_swogger@urmc.rochester.edu (M.T. Swogger).
Drug and Alcohol Dependence 183 (2018) 134–140
Available online 07 December 2017
0376-8716/ © 2017 Elsevier B.V. All rights reserved.
T
possession and distribution despite robust public opposition to “cruel
and irresponsible” governmental policy (Swogger, 2016) and the clear
failure of such measures to do public good (Mallea, 2014).1
Kratom is understudied and, as such, the risks and benefits of
kratom use have not been characterized in detail. Whereas caution in
light of this lack of research is warranted, recent public discourse and
policy approaches related to kratom exhibit characteristics associated
with a drug hysteria (see Hart, 2013), including the promulgation of
sensationalistic and biased information and the pursuit of regulatory
approaches that appear overmatched to apparent risks. Indeed, dangers
of drug hysterias include the tendency toward the adoption of blunt and
reactive strategies that risk inhibiting scientific study and thus deprive
the public of useful medicine. Drug hysteria also creates harmful stigma
around users and increases the risk of ineffective and harsh policies that
lead to unnecessary incarceration. The need for evidence-based policy
to manage the growing adoption of kratom in North America and
Europe makes this a critical time for evaluating risks and benefits.
Moreover, the potential salutary role of kratom use in the context of
opioid use, coupled with increasing demand for effective options for
reducing harms associated with problematic opioid use, make the investigation
of kratom a critical research priority. Understanding the
influence of kratom use on mental health and well-being is important
for evaluating the therapeutic potential of kratom in the context of
harmful opioid use and other psychopathology, as psychological factors
are key determinants of the acceptability kratom-based medicines.
Increased scientific attention is beginning to organize and clarify the
state of knowledge about kratom. Thorough reviews describe the
longstanding uses of kratom in Southeastern Asia and detail modes of
consumption, side effects (including withdrawal), and kratom’s legal
and social status in different parts of the world (Aziz, 2014; Hassan
et al., 2013; Singh et al., 2016). They indicate kratom’s potential to help
with a variety of problems, perhaps most notably pain (Ahmad and
Aziz, 2012; Grundman, 2017). Importantly, kratom use also impacts
several domains of mental health. The nascent scientific literature on
kratom’s beneficial impact on mood and as a substitute for opioids
deserves careful attention, as do the potential mental health risks of
kratom use. To this end, the present work is the first to systematically
review the literature on kratom and mental health. In this review, we
aim to inform clinicians practicing in mental health or substance use
treatment settings who may encounter kratom use in the course of their
clinical work, policy-makers interested in understanding the potential
public health impact of kratom use, and researchers who will base their
scientific investigations on this preliminary knowledge.
2. Methods
2.1. Search strategy
We conducted a search for literature that addresses kratom use and
mental health. In order to ensure coverage of all relevant studies and
guided by recent, high-quality mental health review papers (e.g.,
Walker et al., 2015; Walsh et al., 2017), we chose search terms that
comprise the broad emotional, psychological, and social domains of
mental health (Ryff and Keyes, 1995). Electronic databases (Psycinfo,
Medline) were used to identify all published studies using human
samples between January 1960 and February 2017 on Mitragyna speciosa
OR kratom and anxiety, posttraumatic stress, social, dependence,
abuse, harmful substance use, tobacco, cocaine, alcohol, opiates,
opioids, heroin, amphetamine, depression, bipolar, mania, mood, psychosis,
schizophrenia, neuropsychology, cognitive, IQ, intelligence,
violence, aggression, therapeutic, substitution, suicide, self-harm.
2.2. Inclusion/Exclusion criteria
Identified studies were inspected for redundancy and retained for
further review if they contained original data on kratom use and mental
health. We established two a priori exclusion criteria to ensure that we
reviewed only studies of adequate quality that would contribute
meaningfully. First, we excluded case studies due to limitations on both
internal and external validity, a tendency to over-represent extreme
events, and an unacceptable potential for researcher effects (Merriam,
2009). Additionally, we excluded studies that did not supply adequate
information for a review of study methods.
3. Results
Our search yielded 49 results. After eliminating redundant results,
theoretical and review papers without novel empirical data (n=19),
case studies (n=9), and papers determined to contain no data relevant
to mental health (n=6), we examined 15 studies. We then eliminated
studies (n=2) whose methods were inadequately reported for us to
evaluate their limitations. Thirteen studies were retained for full review.
The combined sample for these studies is 28,745, of which 25,189
were drawn from two large surveys. All studies were cross-sectional or
retrospective in design, with 9 of 13 reporting results of surveys from
Thailand and Malaysia, two reporting on calls to US poison control
centers, one study based on submissions to a US-based website that
provides user reports of a variety of psychoactive substances, and an
anonymous online survey made available through the American Kratom
Association Web page (Table 1). Based on the content of these articles,
we organize the review around the categories of harm reduction, mood,
and adverse effects.
3.1. Harm reduction
Substitution is a form of harm reduction involving the use of a
substitute compound in order to replace or decrease the use of another
substance that is deemed undesirable (Lucas et al., 2016). The consequences
of substitution can be observed at the individual and public
health levels. Long-acting opioids like methadone or buprenorphine are
prescribed as substitutes for potentially more dangerous compounds
(e.g., oxycodone, heroin) and there is evidence that cannabis can be
successfully substituted for alcohol, opioids, and cocaine (Bachhuber
et al., 2014; Lucas and Walsh, 2017; Lucas et al., 2016; Socias et al.,
2017). Consistent with older descriptions of kratom use in Asia, recent
research indicates that kratom is being used as a harm-reducing, substitute
substance.
One study that signals the substitution potential of kratom was
conducted in Northern Malaysia and used convenience sampling to
identify 136 kratom users (99% male) in areas of where heavy kratom
use was reported (Vicknasingam et al., 2010). Of these people, seventyseven
percent had lower secondary education or less and the mean age
(38.7; SD=10.9) was older than other reviewed samples. Many individuals
(46%) were using other substances concomitantly with
kratom and most (76%) had a prior drug use history. Results indicated
that a 90% were using kratom as a substitute for opioids; 84% indicated
that kratom helped with their opioid withdrawal symptoms. Another
Malaysian survey (Singh et al., 2015) used snowball sampling to engage
293 adult males who had used kratom for a minimum of six months
prior to the interview. This sample consisted largely (87%) of manual
laborers who were younger (mean age=28) and more educated (66%
upper secondary education) than the Vicknasingam et al. (2010)
sample. Fifty-two percent reported kratom use for three years or more.
Fifteen percent indicated that they had used kratom in an effort to reduce
or eliminate addictions to illicit substances (e.g., opioids, cannabis)
and/or to ameliorate opioid withdrawal symptoms (Singh et al.,
2015).
Across the world, nearly half of 8049 respondents (56.9% male and
1 The DEA has withdrawn its notice of intent to schedule kratom following a public
backlash and pending further gathering of information on the substance and consequences
of its use.
M.T. Swogger, Z. Walsh Drug and Alcohol Dependence 183 (2018) 134–140
135
Table 1
Study characteristics − kratom use and mental health.
Publication Sample Location Design Summary
Ahmad and Aziz (2012) n=562;>99% male; most daily users; 94% upper secondary education
or above
Northern Malaysia cross-sectional kratom used for stamina, recreation, performance; most users reported inability to abstain
Anwar et al. (2016) 660 poison control calls over 5 years; predominantly male (72% where
gender was reported)
United States retrospective some callers reported acute irritability/agitation
Grundman (2017) 8049 survey respondents; 57% male; 82% some college; 66% >1 year
kratom use
United States cross-sectional users reported improved mood and relaxation; successful substitution for opioids; 9%
reported withdrawal symptoms following non-use
Kittiranapaiboon et al. (2014) 17,140 survey respondents; 50% male 537 were illicit substance users
(59% kratom)
Thailand cross-sectional regular kratom use without comorbid alcohol or mental disorder did not increase suicide
risk over that of non-substance users
Forrester (2013) 14 poison control calls over 1.5 years; 79% male Texas retrospective agitation, confusion, hallucinations reported; comorbid substances limit conclusions
Saingam et al. (2012) 34 male “continuous” users; 3–50 years of use Rural Thailand qualitative acute consequences include enhanced energy, “happiness”; dependence seen for long-term
use
Saingam et al. (2014) 1118 males, 526 with kratom use histories; 67% regular users (3 times
per week for minimum 3 months)
Rural Thailand cross-sectional more than half of regular users developed withdrawal, including muscle spasams, pain,
insomnia, hot flashes, decreased appetite
Saingam et al. (2016) Same sample as Saingam et al. (2014); 526 males; 67% regular users Rural Thailand cross-sectional 4 dimensions of withdrawal symptoms: craving/fatigue, musculoskeletal and insomnia,
mood; autonomic nervous system/physical sickness
Singh. et al. (2014) 293 males; most laborers, all>6 months use; mean use frequency=3.5
times per day
Northern Malaysia cross-sectional significant cravings and withdrawal following non-use
Singh et al. (2015) Same sample as (Singh et al., 2014); 293 males; most laborers,
all>6 months use; mean use=3.5 times per day
Northern Malaysia cross-sectional chronic and heavy kratom use does not significantly impair social functioning
Swogger et al. (2015) 161 users of a Western drug information website; 89% males among
those who reported gender
Various; mostly
Western
qualitative pros: successful substitution for opiates, mood elevation, social enhancement; Cons: 10%
reported withdrawal symptoms following non-use
Trakulsrichai et al. (2013) 52 kratom exposure cases at posion center; 85% male; 67% kratom only
substance of use
Thailand cross-sectional good prognosis for kratom exposure; modest withdrawal symptoms
Vicknasingam et al. (2010) 136 active substance users, 99% male; mean age=39;>75%
had<9 years of education
Northern Malaysia cross-sectional 90% used kratom as substitute for opioids; 84% report success in relieving opioid
withdrawal; other benefits were increased energy and sexual desire
43.1% female) to a U.S.-based, online kratom survey indicated that
kratom enabled them to reduce or discontinue the use of opioids
(Grundman, 2017). In this sample, 51% were between 31 and 50 years
old, greater than 80% had some college or more education, and 56.6%
had used kratom for greater than one year. Kratom use for harm reduction
purposes (i.e., reducing withdrawal from opioids or other unwanted
drugs) was more likely in participants between the ages of
21–30 years (OR: 1.89, CI: 1.02–3.51), those with self-insurance (OR:
1.57, CI: 1.18–2.10), Medicaid (OR: 2.11, CI: 1.49–3.00), Medicare (OR:
2.41, CI: 1.53–3.79), or no insurance (OR: 1.97, CI: 1.51–2.59). A
minimum dose of 5 g was perceived as effective for decreasing the use
of opioids. Those less likely to use kratom for substitution were females
(OR: 0.63, CI: 0.51–0.78), married participants (OR: 0.69, CI:
0.54–0.87), and retired individuals (OR: 0.26, CI: 0.07–0.93) and those
unable to work (OR: 0.29, CI: 0.16–0.51).
In a study of 161, self-selected respondents (approximately 89%
male) to a US-based internet forum, over 10% reported using kratom to
successfully decrease or abstain from a substance that was unwanted or
considered to be causing harm (Swogger et al., 2015). Whereas opioids
− both heroin and pharmaceuticals − were the most frequent substances
to be replaced, kratom was also used to replace antidepressants,
including selective serotonin reuptake inhibitors (SSRIs).
3.2. Mood
Kratom has been reported to have an energizing effect at lower
doses (Saingam et al., 2012) and a calming effect at higher doses (Singh
et al., 2016). In the Malaysian sample of 293 male kratom users, described
above, 29% reported using kratom to enhance energy or fight
fatigue and 6% to improve mood or ease boredom (Singh et al., 2014).
In another Malaysian sample, approximately 28% of primarily male
kratom users indicated that they felt increased energy and alertness and
approximately 26% indicated euphoria, relaxation, or contentment as a
result of kratom ingestion (Ahmad and Aziz, 2012). Similarly, 30% of
the 161 individuals who reported their experiences to a US-based drug
information website indicated that kratom produced an enhanced sense
of well-being and nearly 9% reported an increase in energy (Swogger
et al., 2015). Relaxation and reduced anxiety also appeared in the
narratives of 24% of the sample in a US-based qualitative study
(Swogger et al., 2015). However, none of these studies clearly delineated
the nature of kratom’s apparent anxiolytic effect and thus did
not speak to the extent to which kratom decreases anxiety without
unwanted sedation. Generally, sedation has been reported by very low
percentages of participants; 0.6% (Ahmad and Aziz, 2012), 3.1%
(Swogger et al., 2015), and, combined with dizziness, 4.8% (Grundman,
2017). Drowsiness and sedation were reported by 19.4% of 660 people
who called U.S. poison control centers from 2010 to 2015 (Anwar et al.,
2016). The higher level of sedation in the poison control study may be
due to the self-selected sample or the fact that over 40% had used other
substances concurrently with kratom. It is interesting to note that approximately
9% of Swogger et al.’s sample indicated enhanced sociability
and/or empathy following kratom ingestion, suggesting that
kratom may exert anxiolytic effects without accompanying apathy and
impaired social motivation.
Sixty-six percent of respondents to a large Western survey indicated
they use kratom to relieve negative moods or mental states, including
anxiety, depression, and posttraumatic stress (Grundman, 2017).
Kratom use for this purpose was significantly related to female gender
(OR: 1.3, CI: 1.16–1.46), being a homemaker (OR: 1.34, CI: 1.05–1.71)
or student (OR: 1.86, CI:1.34–2.59), and on either Medicaid (OR: 1.36,
CI: 1.08–1.73), Medicare (OR: 1.35, CI: 1.05–1.74), or having no insurance
(OR:1.31, CI: 1.10–1.57). Being age 41 or older, being married,
having a Bachelor’s degree, and earning $75,000 or more were negatively
associated with mood-related use. In this study, Kratom was
perceived by 79.4% of users to increase energy. Moreover, 75.6% of
users indicated relief from depressed mood and 74.3% reported
decreased anxiety. Benefits for energy were reported at low doses
(≤1 g) and benefits for depression and anxiety were dose-dependent
up to 5 g, with higher doses correlating with greater perceived benefits
(Grundman, 2017). Kratom’s positive potential in the areas of mood
and anxiety notwithstanding, kratom withdrawal can lead to the opposite
effects, including depressed mood, hostility, and heightened
anxiety (Ahmad and Aziz, 2012; Singh et al., 2014). A significant
portion (23.8%) of callers to U.S. poison centers during a 5-year period
reported agitation or irritability after ingesting kratom, though other
substances may have contributed to these experiences (Anwar et al.,
2016).
3.3. Adverse effects
Several studies described kratom-related adverse effects (Ahmad
and Aziz, 2012; Anwar et al., 2016; Forrester, 2013; Grundman, 2017;
Saingam et al., 2016; Singh et al., 2014; Singh et al., 2015; Swogger
et al., 2015; Trakulsrichai et al., 2013). Evidence related to negative
psychosocial effects converges to indicate that regular use can result in
tolerance, withdrawal symptoms upon cessation of use, and difficulty in
abstaining from kratom (Ahmad and Aziz, 2012; Grundman, 2017;
Singh et al., 2014; Swogger et al., 2015). Interestingly, a comprehensive
survey of 530 predominantly male, regular kratom users in Malaysia
(94% daily, with a mean history of 4.6 [SD=3.8] years of use) reported
lower user education level was protective for uncontrolled use
(Ahmad and Aziz, 2012). Another study of 293 male, frequent kratom
users in Malaysia found that 73% experienced withdrawal symptoms
for approximately one to three days after discontinuing use (Singh
et al., 2014). The U.S.-based studies reported lower rates of withdrawal
symptoms: nearly 9% and 10%, respectively (Grundman, 2017;
Swogger et al., 2015).
While the incidence of withdrawal appears to vary according to the
sample, the evidence converges across studies to characterize the nature
of withdrawal symptoms. Results of a factor analysis of symptoms of
kratom withdrawal conducted among 526 kratom-using males in
Thailand (67% of whom reported kratom use ≥ 3 three times per
week), describe the withdrawal syndrome across four symptom dimensions:
1) craving and fatigue, 2) musculoskeletal system and insomnia,
3) mood symptoms, and 4) autonomic nervous system/physical
sickness (Saingam et al., 2016). These categories of kratom withdrawal
symptoms are consistent with evidence from ethnically and culturallydiverse
samples indicating that prominent withdrawal symptoms include
fatigue and cravings, tremor, cramping, muscle aches and insomnia,
anxiety and tension, depressed mood, and nausea, hot flashes,
sweating, diarrhea, vomiting, and watering eyes and nose (Grundman,
2017; Singh et al., 2014; Swogger et al., 2015; Trakulsrichai et al.,
2013).
Kratom withdrawal symptoms resemble the opioid withdrawal
syndrome (Miranda and Taca, 2017). Extant data suggest that kratom’s
withdrawal syndrome is uncomfortable, but generally milder and of
shorter duration than is characteristic of opioid withdrawal (Singh
et al., 2015; Swogger et al., 2015). Symptoms of withdrawal are not
insignificant, however; among the 9% of respondents to a U.S.-based
survey who had experienced kratom withdrawal within 12–48 h of nonuse,
most rated the severity of symptoms at either ‘2′ (40.4%), ‘3′
(36.1%), or ‘4′ (11.5%) on a 5-point Likert scale, with ‘1′ as most severe
(Grundman, 2017). Preliminary survey data among Western respondents
indicates that withdrawal and other negative effects were
more highly reported by people who were partnered but not married
(OR: 1.37, CI: 1.12–1.68), had Medicare (OR: 1.69, CI: 1.31–0.218),
Medicaid (OR: 1.6, CI: 1.27–2.00), or no insurance (OR: 1.64, CI:
1.37–1.95), and earned between $35,000 to $49,999 (OR: 1.38, CI:
1.11–1.73). By contrast, being self- employed (OR: 0.77, CI: 0.65–0.92),
a student (OR: 0.72, 0.53–0.99), or having a Bachelor’s (OR: 0.46, CI:
0.30–0.72) or advanced degree (OR: 0.41, CI: 0.25–0.66) was associated
with lower odds for consuming Kratom for a prescription drug
dependency (Grundman, 2017).
Apart from kratom dependence, available studies give no indication
that kratom causes psychopathology. In Grundmann’s large survey,
only about 3% of respondents indicated they had sought mental health
treatment “because of kratom consumption.” Approximately 4% of interviewees
in a Malaysian study that directly asked about hallucinations
during kratom use endorsed them (Ahmad and Aziz, 2012). One study
(Forrester, 2013) reported psychotic-like symptoms among a small
number of callers to a U.S. poison center (i.e., hallucinations following
the ingestion of kratom), though the extent to which these reported
hallucinations are directly attributable to kratom rather than concurrent
use of other substances, existing psychopathology, or drug
naiveté is unclear.
We searched for scientific information on kratom use and self-andother
directed aggression. Although few studies directly assessed aggression,
reports of this outcome were notably absent from studies that
indirectly enabled such reporting (e.g., Anwar et al., 2016; Saingam
et al., 2012; Swogger et al., 2015; Trakulsrichai et al., 2013). No studies
indicated increased self-or-other directed aggression following acute
ingestion. Approximately 1% of Malaysian interviewees indicated that
they had engaged in aggression or experienced hostility while in kratom
withdrawal (Ahmad and Aziz, 2012). Consistent with above results,
findings of a large epidemiological study (n=17,140; Thai National
Mental Health Survey; Kittiranapaiboon et al., 2014) provide indirect
support for the proposition that kratom use does not increase risk for
self-directed aggression. Specifically, an aggregated group of users of
illicit substances (n=537), of whom nearly 60% used regularly used
kratom, did not differ from a non-substance-using group with regard to
suicide risk on the Mini International Neuropsychiatric Interview, Suicidality
Module (Kittiranapaiboon and Khamwongpin, 2005). This
study has several limitations; most notably that analyses combine
kratom users with other drug users (e.g., 24% were methamphetamine
users) and do not provide an analysis of risk associated with any particular
substance except alcohol. However, while the study found that
drug users who also used alcohol or had mental health problems were
at higher risk for suicide than individuals without mental illness or
alcohol problems, preliminary findings indicate no increased suicide
risk related to kratom in healthy individuals.
4. Discussion
We conducted a comprehensive systematic review of the scientific
literature on kratom use and mental health. Perhaps our most robust
finding is that the study of kratom’s effects on humans, and mental
health in particular, is in its infancy. This was revealed by a lack of
rigorous, well-controlled, prospective studies; the kind that will eventually
lead to a sophisticated and nuanced clinical understanding of the
benefits and harms of kratom use. Females were excluded or underrepresented
in most of the studies. Moreover, the integration of a scant
literature is complicated by the diversity of samples and methodologies;
for example, frequent users of kratom in Southeast Asia, where use is
embedded in complex cultural traditions, differ in myriad ways from
potentially drug naïve individuals who call into a U.S. poison centers.2
Despite these challenges and limitations, we were able to draw some
conclusions about kratom use and mental health from converging evidence
across 13 studies.
With regard to adverse effects, kratom use carries risk for physiological
dependence, though this risk has not been adequately quantified.
Additional research is necessary to estimate the incidence of
kratom dependence in various populations, which varies widely in the
extant literature. There is good evidence that kratom dependence is
typically less severe than opioid dependence, with which kratom shares
some mechanisms of action (Hassan et al., 2013). Moreover, unlike
opioids, kratom use does not appear to result in significant respiratory
depression (Kruegel et al., 2016) and is thus far less likely to cause fatal
overdose. The perception that kratom is a milder and less dangerous
opioid-like psychoactive substance is supported by the uptake of
kratom use as an opiate substitute (Vicknasingam et al., 2010) and is
consistent with data on the unimpaired social functioning of regular
kratom users (Singh et al., 2015). For future research on the effects of
heavy kratom use, a scale designed to measure kratom dependence has
shown good preliminary reliability and validity (the Krathom Dependence
Scale; Saingam et al., 2014).
Findings indicate that kratom has potential as a harm reduction tool
in the context of problematic opioid use. Substitution therapy has demonstrated
substantial effectiveness as a harm reduction strategy for
problematic opioid use, as evidenced by the widespread proliferation
and success of methadone maintenance therapy and the emergence of
buprenorphine treatment to decrease or eliminate the use of potentially
more harmful opioids (Li et al., 2016). However, extant approaches do
not meet the needs of all those who struggle with opioid addiction,
making the development of additional options an important target
(Stitzer et al., 2017). As an example of the utility of substitution agents
at the public health level, opioid deaths have decreased following an
increase in legal medical cannabis availability in select U.S. states
(Bachhuber et al., 2014). As a catastrophic North American opioid
epidemic continues, a natural experiment into the harm reducing potential
of kratom as a substitute for opioids is well underway. Across the
U.S., daily visits to the American Kratom Association webpage average
greater than 9000, including an average of 2262 unique visitors
(Grundman, 2017). Proposed restriction of legal access to kratom can
be reasonably expected to have unintended negative public health
consequences by removing a harm reduction tool.
Regarding kratom’s effect on mood and anxiety, kratom appears to
be more akin to a stimulant than an antidepressant medication, based
on the relatively rapid onset and limited duration of action. There is
good evidence that, in the short-term, low doses of kratom can boost
energy and enhance mood, whereas higher doses may have anxiolytic
effects (Ahmad and Aziz, 2012; Saingam et al., 2012; Singh et al., 2014;
Swogger et al., 2015). There is also preliminary evidence that kratom
has empathogenic effects and can lead to enhanced sociability (Swogger
et al., 2015). If these findings are replicated, kratom might be studied as
a potential anxiolytic that does not lead to emotional blunting or feelings
of disconnection associated with widely used anxiolytics (Ashton,
1986; Price et al., 2009). Clinicians who work with people who are
already using kratom to manage anxiety might encourage adding evidence-
based psychosocial treatment strategies (e.g., gradual exposure
to feared stimuli, mindfulness meditation) in order to enhance self-efficacy
and increase experiential acceptance and functionality in a
lasting way (Hofman and Smits, 2008; Kishita et al., 2016). Only anecdotal
reports are available that address the long-term, moderate use
of kratom use to enhance mood (see Henningfield, 2016; Erowid,
2017), and clinical trials are necessary to more carefully evaluate kratom’s
impact on mood and anxiety over the course of weeks or months.
Clinicians should be aware of the potential for dependence in heavy
users. Withdrawal symptoms may include depression, irritability, and
anxiety.
Discrepant findings in existing data appear to be closely tied to
cultural and demographic moderators of kratom use patterns and consequences.
In the West, females are more likely than males to use
kratom for emotional help (Grundman, 2017), probably due to their
higher incidence of mood disorders relative to males (Seney and Sibille,
2014). By contrast, males have a higher incidence of substance use
disorders (SAMHSA, 2014), potentially increasing the likelihood of
kratom use for substitution. Data from North America indicates that
higher education is associated with less incidence of withdrawal
2 The dangers of comparison are highlighted by the fact that Texas Poison Center study
(Forrester, 2013) included at least two individuals who inhaled kratom. This is a method
of consumption that is largely recognized as unpleasant and/or dangerous in informed
samples and highlights the importance of education.
M.T. Swogger, Z. Walsh Drug and Alcohol Dependence 183 (2018) 134–140
138
(Grundman, 2017). By contrast, Malaysian individuals with higher
education had more difficulty abstaining from kratom than less educated
people. Ahmad and Aziz (2012) speculate that, because individuals
with lower education are more likely to be laborers who
regularly use low doses of kratom for energy, they may be less likely to
become dependent than individuals with more education who use high
doses for recreation. The incidence of kratom withdrawal varies widely
in existing studies (9%–73%), indicating the importance of rigorous and
sophisticated research that elucidates moderators of kratom use patterns
and outcomes.
In general, this comprehensive review of a preliminary, scant, and
diverse literature yields no indication that kratom use carries significant
mental health risks beyond the possible development of kratom dependence,
which is generally mild compared to that of opioids. A low
proportion of Malaysian participants in one study endorsed hallucinations
following acute use, although it is unclear whether these were true
hallucinations or a nonspecific labeling of kratom’s visual effects. These
have been reported as pleasant among individuals experimenting with
kratom in the U.S. (Swogger et al., 2015). Most studies did not examine
psychosis directly. It is notable, given CDC and DEA warnings in the
U.S., that psychotic symptoms were not described in most studies that
enabled their reporting (Anwar et al., 2016; Saingam et al., 2012;
Swogger et al., 2015; Trakulsrichai et al., 2013). The lack of evidence
for psychosis or other psychopathology combines with the very low
percentage of people in North America who report seeking mental
health care as a result of kratom use (Grundman, 2017) to indicate
minimal to no short-term risk of psychosis due to kratom. Similarly, we
found no evidence for kratom-induced risk for self-or-other directed
aggression. In one investigation, approximately 1% of Malaysian interviewees
endorsed aggression during kratom withdrawal (Ahmad and
Aziz, 2012). As with all reviewed studies, the design does not enable
causal inferences and no aggressive behavior was found among participants
of the other studies that enabled its reporting (Anwar et al.,
2016; Saingam et al., 2012; Swogger et al., 2015; Trakulsrichai et al.,
2013). Importantly, our review was limited to mental health consequences
and other sources should be reviewed for data on other
health correlates of kratom use.
In conclusion, kratom use appears to have several important mental
health benefits that warrant further study. Kratom dependence is a risk
for some people, though the dependence syndrome appears to be mild
in its psychosocial and physiological effects relative to that of opioids.
More and better research, including well-controlled, prospective studies
is necessary to further elucidate kratom’s potential for good and harm
and the moderators of its effects. Studies that address kratom’s mental
health effects in women and across understudied cultures and ethnicities
are particularly needed. Moreover, there are no good data on
kratom use in the severely mentally ill or on interactions between
kratom and other substances. The extent to which the adverse effects of
kratom are accepted by the public and policy makers in the North
America (akin to caffeine, for example) will depend largely on the results
of further research and the further development of sociocultural
norms around this relative newcomer to the pharmacopeia of North
America and Europe.
Conflict of interest
No conflicts declared
Contributors
Dr. Swogger conducted the research for and wrote initial drafts. Dr.
Walsh provided additional text and substantive input that contextualized
findings within the broader literature. All authors approved
of the submission.
Role of funding source
Nothing declared
References
Anwar, M., Law, R., Schier, J., 2016. Notes from the field: kratom (Mitragyna speciosa)
exposures reported to poison centers — United States, 2010–2015. MMWR. Morb.
Mortal. Wkly. Rep. 65, 748–749. http://dx.doi.org/10.15585/mmwr.mm6529a4.
Ahmad, K., Aziz, Z., 2012. Mitragyna speciosa use in the northern states of Malaysia: a
cross-section. J. Ethnopharmacol. 7, 446–450. http://dx.doi.org/10.1016/j.jep.2012.
03.009.
Ashton, H., 1986. Adverse effects of prolonged benzodiazepine use. Adverse Drug React.
Bull. 118, 440–443.
Aziz, Z., 2014. Kratom: the epidemiology, use and abus, addiction potential, and legal
status. kratom and other mitragynines. In: Raffa, Robert B. (Ed.), The Chemistry and
Pharmacoogy of Opioids from a Non-opium Source. CRC Press, Boca Raton, FL, pp.
309–320. http://dx.doi.org/10.1201/b17666-22.
Bachhuber, M.A., Saloner, B., Cunningham, C.O., Barry, C.L., 2014. medical cannabis
laws and opioid analgesic overdose mortality in the United States, 1999–2010. JAMA
Intern. Med. 174, 1668. http://dx.doi.org/10.1001/jamainternmed.2014.4005.
Bloom, J., 2016. Kratom: The Supplement That Will Kill Godzilla Topic. Retrieved 20
March 2017, from http://theminiaturespage.com/plus/msg.mv?id=162672.
Boyer, E.W., Babu, K.M., Adkins, J.E., Mccurdy, C.R., Halpern, J.H., 2008. Self-treatment
of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction 103,
1048–1050. http://dx.doi.org/10.1111/j.1360-0443.2008.02209.x.
Cinosi, E., Martinotti, G., Simonato, P., Singh, D., Demetrovics, Z., Roman-Urrestarazu,
A., Bersani, F.S., Vicknasingam, B., Piazzon, G., Li, J.H., Yu, W.J., Kapitany-Foveny,
M., Farkas, J., Di Giannantonio, M., Corraza, O., 2015. Following the roots of kratom
(Mitragyna speciosa): the evolution of an enhancer from a traditional use to increase
work and productivity in Southeast Asia to a recreational psychoactive drug in
western countries. BioMed Res. Int. 2015, 1–11. http://dx.doi.org/10.1155/2015/
968786.
Drug Enforcement Administration, August 30, 2016. “DEA announces intent to schedule
kratom. Retrieved March 20, 2017, from https://www.dea.gov/divisions/hq/2016/
hq083016.shtml.
Erowid, 2017. Erowid experience vaults: kratom (also mitragyna speciosa) reports.
Retrieved February 14, 2017, from https://erowid.org/experiences/subs/exp_
Kratom_General.shtml.
Forrester, M.B., 2013. Kratom exposures reported to texas poison centers. J. Addict. Dis.
32, 396–400. http://dx.doi.org/10.1080/10550887.2013.854153.
Grundman, O., 2017. Patterns of kratom use and health impact in the US: results from an
online survey. Drug Alcohol Depend. 176, 63–70. http://dx.doi.org/10.1016/j.
drugalcdep.2017.03.007.
Hart, C., 2013. High Price: A Neuroscientist’s Journey of Self-discovery That Challenges
Everything You Know About Drugs and Society. HarperCollins, NY.
Hassan, Z., Muzaimi, M., Navaratnam, V., Yusoff, N.H., Suhaimi, F.W., Vadivelu, R.,
Vicknasingam, B.K., Amato, D., von Horsten, S., Ismail, N.I.W., Jayabalan, N., Hazim,
A.I., Mansor, S.M., Müller, C.P., 2013. From kratom to mitragynine and its derivatives:
physiological and behavioral effects related to use, abuse, and addiction.
Neurosci. Biobehav. Rev. 37, 138–151. http://dx.doi.org/10.1016/j.neubiorev.2012.
11.012.
Henningfield, J.E., 2016. Assessment of Kratom Under the CSA Eight Factors and
Scheduling Recommendations. Retrieved March 20, 2017 from http://216.30.191.
148/HL-AKA-Eight_Factor_and_Recommendations_by_PinneyAssoc.pdf
(November 28).
Hofman, S.G., Smits, J.A.J., 2008. Cognitive behavioral therapy for adult anxiety disorders:
a meta-analysis of randomized, placebo-controlled, trials. J. Clin. Psychiatry
68, 621–632.
Kapp, F.G., Maurer, H.H., Auwarter, V., Winkelman, M., Hermanns-Clausen, M., 2011.
Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). J.
Med. Toxicol. 7, 227–231. http://dx.doi.org/10.1007/s13181-011-0155-5.
Kishita, N., Takei, Y., Stewart, I., 2016. A meta-analysis of third-wave mindfulness-based
cognitive-behavioral therapies for older adults. Int. J. Geriatr. Psychiatry. 11
(November), 2016. http://dx.doi.org/10.1002/gps.4621. (Published online).
Kittiranapaiboon, P., Suttajit, S., Junsirimongkol, B., Likhitsathian, S., Srisurapanont, M.,
2014. Suicide risk among Thai illicit drug users with and without mental/alcohol use
disorders. Neuropsychiatr. Dis. Treat. 13, 453–458. http://dx.doi.org/10.2147/ndt.
s56441.
Kruegel, A.C., Gassaway, M.M., Kapoor, A., Varadi, A., Majumdar, S., Filizola, M., Javitch,
J.A., Sames, D., 2016. Synthetic and receptor signaling explorations of the Mitragyna
alkaloids: mitragynine as an atypical molecular framework for opioid receptor
modulators. J. Am. Chem. Soc. 138, 6754–6764. http://dx.doi.org/10.1021/jacs.
6b00360.
Li, X., Shorter, D., Kosten, T.R., 2016. Buprenorphine prescribing: to expand or not to
expand. J. Psychiatr. Pract. 22, 183–192. http://dx.doi.org/10.1097/PRA.
0000000000000154.
Lucas, P., Walsh, Z., Crosby, K., Callaway, R., Belle-Isle, L., Kay, R., Capler, R., Holtzman,
S., 2016. Substituting cannabis for prescription drugs, alcohol and other substances
among medical cannabis patients: the impact of contextual factors. Drug Alcohol Rev.
35, 326–333. http://dx.doi.org/10.1111/dar.1232.
Mallea, P., 2014. The War on Drugs: a Failed Experiment. dundurn., Toronto, Canada.
McIntyre, I.M., Trochta, A., Stolberg, S., Campman, S.C., 2015. mitragynine ‘kratom’ related
fatality: a case report with postmortem concentrations. J. Anal. Toxicol. 39,
M.T. Swogger, Z. Walsh Drug and Alcohol Dependence 183 (2018) 134–140
139
152–155. http://dx.doi.org/10.1093/jat/bku1.
Merriam, S.B., 2009. Qualitative Research: A Guide to Design and Implementation.
Jossey-Bass, San Francisco, CA.
Miranda, A., Taca, A., 2017. Neuromodulation with percutaneous electrical nerve field
stimulation is associated with reduction in signs and symptoms of opioid withdrawal:
a multisite, retrospective assessment. Am. J. Drug Alcohol Abuse 16, 1–8. http://dx.
doi.org/10.1080/00952990.2017.1295459.
Neerman, M.F., Frost, R.E., Deking, J., 2012. A drug fatality involving kratom. J. Forensic
Sci. 58, S278–S279. http://dx.doi.org/10.1111/1556-4029.12009.
Nelsen, J.L., Lapoint, J., Hodgman, M.J., Aldous, K.M., 2010. Seizure and coma following
kratom (Mitragynina speciosa korth) exposure. J. Med. Toxicol. 6, 424–426. http://
dx.doi.org/10.1007/s13181-010-0079-5.
Pendell, D., 2010. Pharmakognosis: Plant Teachers and the Poison Path. North Atlantic
Books, Berkeley, CA.
Price, J., Cole, V., Goodwin, G.M., 2009. Emotional side-effects of selective serotonin
reuptake inhibitors: qualitative study. Br. J. Psychiatry 195, 211–217. http://dx.doi.
org/10.1192/bjp.bp.108.051110.
Prozialeck, W.C., Jivan, J.K., Andurkar, S.V., 2012. Pharmacology of kratom: an emerging
botanical agent with stimulant, analgesic, and opioid-like effects. J. Am. Osteopath.
Assoc. 112, 792–799.
Ryff, C.D., Keyes, C.L.M., 1995. The structure of psychological well–being revisited. J.
Pers. Soc. Psychol. 69, 719–727. http://dx.doi.org/10.1192/bjp.bp.108.051110.
(SAMHSA) Substance Abuse and Mental Health Services Administration, 2014. Results
from the 2013 National Survey on Drug Use and Health: Summary of National
Findings. Substance Abuse and Mental Health Services Administration, Rockville, MD
HHS Publication No. (SMA) 14–4863. NSDUH Series H-48.
Saingam, D., Assanangkornchai, S., Geater, A.F., Balthip, Q., 2012. Pattern and consequences
of krathom (Mitragyna speciosa Korth) use among mail villagers in
southern Thailand: a qualitative study. Int. J. Drug Policy 24, 351–358.
Saingam, D., Assanangkornchai, S., Geater, A.F., Lerkiatbundit, S., 2014. Validation of
Kratom (Mitragyna speciosa Korth) dependence scale (KDS): a dependence screen for
internationally emerging psychoactive substance. Subst. Abuse. 35, 276–283.
Saingam, D., Assanangkornchai, S., Geater, A.F., Lerkiatbundit, S., 2016. Factor analytical
investigation of krathom (Mitragyna speciosa Korth) withdrawal syndrome in
Thailand. J. Psychoactive Drugs 48, 76–85. http://dx.doi.org/10.1080/02791072.
2016.1156791.
Seney, M.L., Sibille, E., 2014. Sex difference in mood disorders: perspectives from humans
and rodent models. Biol. Sex Differ. 5, 17. http://dx.doi.org/10.1186/s13293-014-
0017-3.
Sheleg, S.V., Collins, G.B., 2011. A coincidence of addiction to kratom and severe primary
hypothyroidism. J. Addict. Med. 5, 300–301. http://dx.doi.org/10.1097/adm.
0b013e318221fbfa.
Singh, D., Müller, C.P., Vicknasingam, B.K., 2014. Kratom (Mitragyna speciosa) dependence,
withdrawal symptoms and craving in regular users. Drug Alcohol Depend.
139, 132–137. http://dx.doi.org/10.1016/j.drugalcdep.2014.03.017.
Singh, D., Müller, C.P., Vicknasingam, B.K., Mansor, S.M., 2015. Social functioning of
kratom (mitragyna speciosa) users in Malaysia. J. Psychoactive Drugs 47, 125–131.
http://dx.doi.org/10.1080/02791072.2015.1012610.
Singh, D., Narayanan, S., Vicknasingam, B., 2016. Traditional and non-traditional uses of
Mitragynine (Kratom): a survey of the literature. Brain Res. Bull. 126, 41–46. http://
dx.doi.org/10.1016/j.brainresbull.2016.05.004.
Socias, M.E., Kerr, T., Wood, E., Dong, H., Lake, S., Hayashi, K., DeBeck, K., Jutras-Aswad,
D., Montaner, J., Milloy, M.J., 2017. Intentional cannabis use to reduce crack cocaine
use in a Canadian center: a longitudinal analysis. Addict. Behav. 72, 138–143. http://
dx.doi.org/10.1016/j.addbeh.2017.04.006.
Stitzer, M.L., Schwartz, R.P., Bigelow, G.E., 2017. Prescription opioids: new perspectives
and research on their role in chronic pain management and addiction. Drug Alcohol
Depend. 173, S1–S3. http://dx.doi.org/10.1016/j.drugalcdep.2016.11.018.
Swogger, M.T., Hart, E., Erowid, F., Erowid, E., Trabold, N., Yee, K., Parkhurst, K.A.,
Priddy, B.M., Walsh, Z., 2015. Experiences of kratom users: a qualitative analysis. J.
Psychoactive Drugs 47, 360–367. http://dx.doi.org/10.1080/02791072.2015.
1096434.
Swogger, M.T., 2016. A ban too far. New Sci. 232, 20–21. http://dx.doi.org/10.1016/
s0262-407931929-7.
Tanguay, P., 2011. Kratom in Thailand, Decriminalization and Community Control. Series
on Legislative Reform of Drug Policies. Nr 13. Transnational Institute. International
Drug Policy Consortium (IPDC).
Trakulsrichai, S., Tongpo, A., Sriapha, C., Wongvisawakorn, S., Rittilert, P., Kaojarern, S.,
Wananukul, W., 2013. Kratom abuse in ramathibodi poison center, Thailand: a fiveyear
experience. J. Psychoactive Drugs 45, 404–408. http://dx.doi.org/10.1080/
02791072.2013.844532.
Vicknasingam, B., Narayanan, S., Beng, G.T., Mansor, S.M., 2010. The informal use of
Ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular
Malaysia and implications for drug substitution therapy. Int. J. Drug Policy. 21,
283–288. http://dx.doi.org/10.1016/j.drugpo.2009.12.003.
Walker, E.R., McGee, R.E., Druss, B.G., 2015. Mortality in mental disorders and global
disease burden implications: a systematic review and meta-analysis. JAMA Psychiatry
72, 334–341. http://dx.doi.org/10.1001/jamapsychiatry.2014.2502.
Walsh, Z., Gonzalez, R., Crosby, K., Thiessen, M.S., Carroll, C., Bonn-Miller, M.O.1, 2017.
Medical cannabis and mental health: a guided systematic review. Clin. Psychol. Rev.
51, 15–29. http://dx.doi.org/10.1016/j.cpr.2016.10.002.
Ward, J., Rosenbaum, C., Hernon, C., Mccurdy, C.R., Boyer, E.W., 2011. Herbal medicines
for the management of opioid addiction. CNS Drugs 25, 999–1007. http://dx.doi.org/
10.2165/11596830-000000000-00000.
M.T. Swogger, Z. Walsh Drug and Alcohol Dependence 183 (2018) 134–140
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