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Kratom For Opiate Withdrawal: A Popular “Natural” Intervention

Kratom (Mitragyna speciosa) is a tropical evergreen tree from the coffee family (Rubiaceae) native to Indonesia, Papa New Guinea, Thailand and other parts of Southeast Asia.  The kratom tree produces leaves containing psychoactive compounds, and when ingested, these compounds are capable of eliciting opioidergic and/or stimulatory effects.  Although it is estimated that kratom leaves contain upwards of 40 distinct psychoactive compounds, indole alkaloids are hypothesized to facilitate a majority of its psychoactive effect, namely: mitragynine, 7-hydroxymitragynine, and mitraphylline.

Historically, records suggest that kratom has been utilized in traditional medicine since the early 19th century for the management of chronic pain and as a recreational intoxicant.  These days, kratom is lauded by alternative health practitioners and/or those with an aversion to the pharmaceutical industry as being a safe and effective treatment for chronic pain.  Some also claim that kratom is a much-needed experimental intervention for the management of neuropsychiatric conditions such as depression and anxiety.

That said, usage of kratom is perhaps most ubiquitous among individuals with a history of opioid dependence and/or persons attempting to detoxify from potent opiates (e.g. heroin) or prescription opioids (e.g. hydrocodone) – which is somewhat ironic because kratom is very similar to opiates.  The strategic administration of certain kratom strains during opioid detoxification is understood to attenuate many debilitating withdrawal symptoms.  Nevertheless, anyone who considers using kratom for the management of opiate withdrawal symptoms should be cognizant of its mechanism of action, the symptoms that it may reduce, and the potential risks/benefits associated with its usage.

How Kratom May Help with Opiate Withdrawal (Symptom Management)

The primary means by which kratom may provide benefit during opioid withdrawal is through completely abolishing and/or attenuating the severity of symptoms that emerge following the discontinuation of an opiate or opioid.  By reducing the significance of withdrawal symptoms from another opiate, it’s generally easier for an individual to completely detoxify from the [problematic] agent and refrain from future administration.  The specific opiate withdrawal symptoms that kratom is capable of managing will likely be subject to significant individual variation.

Not every person discontinuing an opiate will have the same history of opiate usage, nor will they be detoxifying from the same substance.  Additionally, complex factors such as: psychological support, genetics, co-administered substances, neurochemistry, health conditions, etc. – can influence the intensity of opiate withdrawal, as well as the extent to which kratom is beneficial during detox.  Moreover, there are many different strains of kratom available, meaning one strain may work well for a certain set of opiate withdrawal symptoms better than another.

To get even more complicated, kratom is not a standardized substance, meaning even if you consume equal amounts from the same strain, alkaloid contents may vary based on growing conditions, leaf positioning, the specific leaf, etc.  For this reason, variation in reduction of opiate withdrawal symptoms should be expected among kratom users.  One person may report significant reduction in anxiety, depression, and/or restlessness, yet another individual might consider kratom to be completely useless in terms of managing his/her opiate detoxification.  Included below is a list of opiate withdrawal symptoms that may improve as a result of kratom administration.

  • Agitation: When discontinuing any potent opiate or opioid, it is common to experience agitation. The agitation experienced is often described as an inner restlessness and/or excitement which makes it difficult to sit still, think clearly, and/or relax.  Agitation may be accompanied by other opiate detoxification symptoms such as anxiety and restlessness.  While most people may try to cope with agitation by engaging in relaxation exercises and/or lightly exercising – these strategies are not always sufficiently effective.  To completely eliminate the agitated feelings, sometimes a medication is needed.  It makes a lot of sense that kratom would attenuate agitation experienced during opiate withdrawal because it stimulates opioid receptors.
  • Anger: Some individuals experience extreme anger during opiate withdrawal whereby they become argumentative with others and/or engage in acts of physical violence. The anger is likely explained in part by the fact that the user’s brain is no longer receiving the opiate to which it had adapted and expected.  Without administration of the opiate, the former-opiate user’s neurochemistry becomes imbalanced and unpleasant emotions like anger surface.  Since kratom contains alkaloids that stimulate opioid receptors in the brain, its administration should induce relaxation to counteract withdrawal-related anger.
  • Anxiety: A debilitating symptom of withdrawal that can persist for weeks or months after opiate discontinuation is anxiety. In some cases, the anxiety occurring during opiate withdrawal is mild and can be managed with simplistic interventions like getting enough sleep, taking warm baths/showers to induce relaxation, and/or by administering dietary supplements.  That said, among high-dose and/or long-term opiate users, anxiety that occurs during withdrawal might be severe enough to interfere with occupational performance, social relationships, or routine “every day” functioning.  Furthermore, if the anxiety is extreme, various physical symptoms of anxiety (e.g. headache) may potentiate the severity of preexisting opiate withdrawal symptoms, thereby making detoxification more difficult.  Administration of properly-dosed kratom has potential to induce an anxiolytic and/or sedating effect that protects against detoxification-related anxiety.
  • Cravings: Some research suggests heroin is the single most addictive recreational drug, and that other prescription opioids (including those utilized as “replacement therapies”) are still among the top 10 most addictive drugs. In any regard, most drugs that act upon opioid receptors in the brain are addictive and users tend to experience incessant cravings during detoxification.  The cravings can be so difficult to resist, that many users need to check into a detox facility to successfully avoid relapse.  One way some individuals may manage their cravings for an opioid is through intermittent administration of kratom.  Kratom stimulates opioid receptors in the brain to transiently satisfy and negate overwhelming cravings for more potent, illicit opiates (e.g. heroin).
  • Depression: A major reason opiates appeal to recreational drug users is that their stimulation of the mu-opioid receptor (MOR) in the brain induces feelings of euphoria and relaxation. Over time, the individual builds up a tolerance to stimulation of the mu receptor whereby receptors are upregulated and euphoria is no longer attained unless the opiate dosage is increased.  Should an individual eventually discontinue the opiate to which tolerance was developed, a rebound effect in the form of dysphoria or depression is likely to ensue.  Though withdrawal-related dysphoria is more complex than the upregulation of mu opioid receptors, this likely plays a causative role.  For this reason, any agent that agonizes opioid receptors, including kratom, should ameliorate depression and improve mood.
  • Fever: During opiate withdrawal, some individuals will develop a fever. The fever is often low-grade and manageable with over-the-counter medications.  That said, in select cases, the fever might be moderate-to-high grade, especially during the peak of withdrawal.  The recommended course of action in dealing with opiate withdrawal-related fever is to consult a medical professional.  Nonetheless, various anecdotal accounts mention that kratom can alleviate detox-related fevers, possibly through an antipyretic effect.
  • Headaches: A symptom of opiate withdrawal that affects many individuals is headache. The headaches experienced during opiate detoxification are often severe and can strike at unpredictable times.  Some persons will report ongoing headaches throughout the day, whereas others will experience throbbing migraines.  It isn’t fully understood as to why headaches occur in opiate withdrawal, but abrupt changes in neurochemistry and corresponding alterations in cerebral blood flow may be culpable.  Although withdrawal-related headaches can be reduced with proper hydration, electrolyte/nutrient intake, proper sleep, over-the-counter medications, and relaxation – sometimes they are unmanageable.  Individuals using kratom during opiate detoxification often notice that headaches subside.  Sedating strains of kratom tend to reverse tension-type headaches [via vasodilation], whereas mildly stimulating strains may attenuate migraines [via vasoconstriction].
  • Insomnia: Opiates are understood to facilitate a sedative effect whereby it becomes easier for many users to fall asleep and/or stay asleep throughout the night.  When opiates are discontinued, especially after a long-term of regular usage, a rebound effect occurs within the CNS whereby excitatory activity increases.  The excitatory activity can directly cause insomnia or cause symptoms such as agitation, anxiety, and restlessness – each of which might lead to insomnia.  Although the insomnia is generally transient and diminishes in severity the longer a person remains abstinent from opiates, some may want to treat it.  Individuals pursuing kratom during withdrawal have reported success with sedating strains for the management of insomnia.
  • Irritability: Any individuals who discontinue opiates after an extended duration of usage are likely to experience irritability. For some the irritability becomes so intense that they cannot control how they respond to the irritable emotion.  Intense irritability can lead to verbally attacking others, aggression, and in some cases may escalate to physical violence.  Irritability may be even more prominent and/or difficult to manage among individuals with underlying neuropsychiatric disorders who cease opiates.  Since kratom is essentially a natural opioid replacement therapy, and there are various strains of kratom that promote sedation, it’s reasonable to think that it may reduce irritability during opiate withdrawal.
  • Mood swings: Opiate withdrawal can often seem like an emotional rollercoaster. One moment you may feel as though you’re making progress with restoring normative neurochemistry and a balanced mood, yet the next it may seem as if you’re sinking back into a depressive abyss.  Generally, mood swings are characterized as sudden and/or unpredictable changes in one’s emotional state.  While many pharmaceutical drugs are often useful for the management of mood swings, anecdotal accounts indicate that various strains of kratom are effective for the attenuation of withdrawal-related mood swings.
  • Pain: Most individuals who use opioids for a long-term have been diagnosed with chronic pain. While opioids are effective for long-term pain management, sometimes tolerance occurs such that little or zero pain relief is attained by patients after an extended duration of administration.  Though the dosage of an opioid medication can be increased for greater pain relief, side effects typically become more severe with each dosage increase.  Furthermore, some individuals experience unwanted long-term effects as a result of regular long-term opioid administration.  Diminishing returns on pain relief from increased dosing and long-term effects are viable reasons for ceasing prescription opioid usage.  That said, when many opt to discontinue prescription opioids, they experience a resurgence of their pain condition and a rebound effect from opioid cessation such that the intensity of pain is amplified.  Though the pain may be manageable with other pharmaceutical medications, some report amelioration of rebound pain from the administration of kratom.
  • Restlessness: Those that have discontinued an opiate know how difficult it can be to manage restlessness throughout the entire body, but especially in the legs (i.e. RLS). This restlessness can interfere with sleep and is often associated with agitation, anxiety, and inability to concentrate.  Although some restlessness is to be expected during opiate withdrawal, if it becomes extreme, individuals may wish to pursue treatment for the restlessness.  Medications such as pregabalin and gabapentin are can be useful for counteracting opiate withdrawal-induced restlessness, however, not everyone has access to these drugs – especially persons outside of the United States.  Kratom, an herbal mu-opioid receptor (MOR) agonist, should induce similar effects to the opiate that was discontinued ultimately reversing the symptom of restlessness during withdrawal.
  • Sleep disturbances: As was already mentioned, a prominent symptom of opiate withdrawal is insomnia, or the inability to fall and/or stay asleep throughout the night.  That said, other sleep disturbances may occur during withdrawal besides insomnia.  Some may experience weird dreams, nightmares, and/or feel as if their sleep is “lighter” than usual.  Others may report night sweats, frequent awakenings throughout the night, and/or tossing and turning.  While sleep medications can work well for managing sleep disturbances implicated in opiate withdrawal, certain strains of kratom can also prove useful for enhancing sleep quality.
  • Spasms: Involuntary contractions of muscles, or spasms, can occur in select individuals during opiate withdrawal.  The spasms may be intermittent and/or infrequent, or may occur regularly.  In some cases, spasms can be accompanied by bursts of mild-to-moderate pain and/or cramping.  There are numerous reasons spasms might occur during opiate withdrawal, including: excitatory activity in the CNS, electrolyte imbalances, and/or dehydration.  Assuming a person is consuming a balanced diet, getting plenty of rest, and staying hydrated – the spasms can be minimized.  Still, spasms can require a greater duration of time to subside after opiate discontinuation.  Knowing that certain kratom strains can downregulate CNS activity, it’s reasonable to suspect that it could help some individuals cope with discontinuation-related muscle spasms.
  • Tension: There are numerous reasons as to why muscle tension may occur during opiate withdrawal. Muscle tension may be caused by psychological stress, constriction of blood vessels, dehydration, and/or increased excitatory activity within the CNS.  To manage the muscle tension, some individuals opt to take muscle relaxants provided by a medical professional.  Others may attempt to fight through the tension, hoping that it will subside as soon as possible.  If kratom is administered during opiate detoxification, it should effectively manage muscle tension through stimulation of opioid receptors to promote sedation.
  • Tremor: Shaking and/or quivering during opioid withdrawal are commonly referred to as tremor. Any long-term users who discontinue opioids rapidly and/or “cold turkey” will probably experience tremor.  The tremor can be disconcerting such that it may cause anxiety and stress, especially if it interferes with one’s ability to perform academic or occupational tasks.  Although the tremor should gradually abate over time, some will want the tremor treated.  In the event that kratom is administered during opiate withdrawal, it is likely capable of attenuating tremor.

How Kratom Works to Alleviate Withdrawal Symptoms (Mechanisms of Action)

It has been stated that the mechanism of action of kratom isn’t fully understood.  Despite its unelucidated pharmacodynamics, the prominent alkaloidal constituents of kratom function predominantly as mu-opioid receptor (MOR) agonists and kappa-opioid receptor (KOR) antagonists.  Agonism of the mu-opioid receptor plus simultaneous antagonism of the kappa-opioid receptor indicates that kratom exerts similar neurophysiological effects to the opioid replacement drug buprenorphine.

The significance of the opioidergic modulation facilitated by kratom vary based on the strain of kratom and specific plant (due to alkaloidal differences and lack of standardization) and the dosage administered.  Nonetheless, it’s relatively easy to understand why kratom would attenuate opiate withdrawal symptoms: kratom is largely replacing the mu-opioid receptor agonism that was formerly delivered by the discontinued opiate/opioid.  Below are descriptions of kratom’s mechanism of action explained in regards to how they might reduce symptoms of opiate withdrawal.

Mu-opioid receptor (MOR) agonist: At high doses, kratom delivers a pronounced opiate-like effect comparable to conventional opiates such as morphine.  Kratom contains 7-hydroxymitragynine (7-HMG) and mitragynine, each of which act as partial agonists of mu-opioid receptors.  Interestingly, animal data indicate that the 7-HMG constituent of kratom delivers approximately a 13-fold greater antinociceptive effect compared to morphine; it is unclear as to whether the comparative potency of 7-HMG to morphine in animals would be similar in humans.

In any regard, a majority of the therapeutic benefit derived from the administration of kratom during opiate withdrawal stems from its ability to agonize mu-opioid receptors.  Agonism of mu-opioid receptors alters neuronal excitability and the downstream release of neurotransmitters, ultimately inducing many neurophysiological effects such as: analgesia, constipation, hypotension, itchiness, mood enhancement, nausea, pupillary constriction, and sedation.  That said, persons with a long-term history of opiate usage, dependence, and/or tolerance are unlikely to report these effects.

Instead, long-term opiate users detoxifying from opiates are likely to report that kratom helps them feel “normal.”  This is because over a long-term, central mu-opiate receptors are upregulated in response to the ongoing agonism elicited by a previously-utilized opiate.  When certain strains of kratom are administered at higher doses, mu-opioid receptors are stimulated sufficiently to negate many symptoms of opiate withdrawal without inducing intoxication.

Essentially, kratom is acting as an herbal opiate replacement therapy by providing mu-opioid receptor agonism.  Experiences with kratom during opiate withdrawal will be subject to variation and contingent upon:  preexisting density of mu-opioid receptors, dosage of kratom administered, and its strain.  If kratom is administered at a dose and/or strain such that mu-opioid receptors are stimulated slightly less than occurred with a previous opiate, individuals will note that kratom ameliorates many detox-related symptoms yet withdrawal is still experienced.

Those who administer kratom at a dose and/or strain such that mu-opioid receptor stimulation is relatively equal to that provided by the previous substance, individuals will report zero withdrawal.  This is because the individual simply switched from their previous opiate to kratom as a source of mu-opioid receptor stimulation, suggestive of the fact that they are not undergoing a legitimate withdrawal or detox.  Finally, if kratom is administered at a dose and/or strain such that mu-opioid receptor stimulation exceeds the agonism provided by a prior opiate, users might report that kratom is more effective for pain management than their previous opiate.

Most will report that opiate withdrawal symptoms such as: anxiety, diarrhea, hypertension, mood swings, rapid breathing, and restlessness – diminish with kratom administration.  The reduction in opiate withdrawal symptoms from kratom usage is mostly attributable its mu-opioid receptor agonism.  Those who fail to derive benefit from kratom during opiate detox are unlikely utilizing a strain and/or dose that provides adequate mu-opioid receptor stimulation.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/27192616

Kappa-opioid receptor (KOR) antagonist:  Research by Takayama, Ishikawa, Kurihara, et al. (2002) indicates that mitragynine, the primary alkaloid within kratom, exhibits a high affinity for the kappa opioid receptors.  Kappa opioid receptors are naturally stimulated by dynorphins, endogenous ligands capable of influencing appetite, circadian rhythm, mood, and pain perception.  As kappa-opioid receptors are antagonized by alkaloidal constituents of kratom, a host of favorable neurophysiological effects may occur that make opiate withdrawal symptoms easier to manage.

Perhaps the most prominent benefit to be derived from kappa-opioid receptor antagonism is mood enhancement.  The binding of dynorphins to kappa opioid receptor sites is understood to induce negative psychological states such as depression.  Oppositely, if dynorphins are blocked from activating kappa opioid receptors, a person’s mood typically improves.

Predictably, clinical trials are investigating kappa opioid receptor antagonists for depression, with some showing substantial promise.  It has also been suggested that kappa opioid receptor antagonism might alleviate symptoms of anxiety.  Since depression and anxiety are commonplace for many individuals during opiate detoxification, most would agree that the kappa opioid receptor antagonism provided by kratom is likely to prove therapeutic among those withdrawing.

Antagonism of the kappa opioid receptors is also understood to enhance dopaminergic activity, whereby users experience some degree of pleasure or reward.  This may help counteract a preexisting “reward deficiency syndrome” that some opioid users are suspected to exhibit.  The rewarding effect of kappa opioid receptor antagonism facilitated by alkaloids within kratom is likely to attenuate cravings and minimize likelihood of relapse during opiate withdrawal.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/11960505/
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/11316510/
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/27192616

Other mechanisms of kratom’s action…

Among individuals who find kratom useful during opiate detoxification, the majority of its therapeutic effect is derived from agonism of mu-receptors with simultaneous antagonism of kappa-receptors.  Still, it may be somewhat myopic to assume that no other mechanisms of kratom’s action aid in the management of detox-related symptoms.  Kratom interacts with delta-opioid receptors (DORs), NMDA receptors, alpha-2 adrenergic receptors, adenosine A2A receptors, D2 receptors, and various serotonergic receptors (5-HT2A, 5-HT2C, and 5-HT7) – each of which might contribute to its therapeutically-valuable effects during opiate withdrawal.

Delta-opioid receptor (DOR) antagonist:  Delta-opioid receptors are predominantly expressed within the basal ganglia and neocortex regions of the brain and are endogenously activated by ligands known as “enkephalins.”  At low doses, the alkaloidal constituents of kratom antagonize kappa-opioid and delta-opioid receptors.  As of current, it isn’t fully understood how the delta-opioid receptor antagonism induced by alkaloids within kratom might prove therapeutic during opiate detox.

Some believe that delta-opioid receptor antagonism could attenuate rewards and/or reinforcement associated with opiate administration, possibly helping users overcome dependence and/or minimizing likelihood of a relapse.  That said, since high doses of kratom modulate mu-receptors and kappa-receptors to a significantly greater extent than delta-receptors, it’s unlikely that substantial benefit is attained from delta-receptor antagonism in regards to overcoming dependence.  Furthermore, if the antagonism of delta-opioid receptors facilitated by alkaloids within kratom were more substantial, this would probably have a negative effect on mood.

Perhaps delta-opioid receptor antagonism offsets some of the euphoria and/or pleasure derived from mu-opioid receptor agonism with simultaneous kappa-receptor antagonism, thereby slightly reducing the addition potential of kratom.  Another means by which modest delta-opioid receptor antagonism may prove beneficial during opiate withdrawal is through the regulation of respiration.  When delta-opioid receptors are mildly activated, respiration increases, yet when overly active, respiration decreases.

Individuals exhibiting abnormal respiration during opiate detoxification may benefit from delta-opioid receptor antagonism.  More research is needed to understand whether the negligible antagonism of delta-opioid receptors provides any benefit to those enduring opiate withdrawal.  Nevertheless, the possibility that modest delta-opioid receptor antagonism reduces certain symptoms of withdrawal necessitates consideration.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/27192616
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/20026960
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/16809477

NMDA antagonist: Research indicates that alkaloid constituents of kratom, specifically rhynchophylline and mitraphylline, function as NMDA receptor antagonists.  When administered at high doses, the NMDA receptor blockade provided by rhynchophylline and mitraphylline may be substantial enough to induce a dissociative effect.  It is possible that a subset of kratom users consider this dissociative effect to be therapeutic during opiate detoxification such that it serves as a psychological escape from the dreaded withdrawal symptoms of an opiate.

That said, there are many other therapeutic effects that may be derived from the NMDA receptor antagonism provided by the alkaloids within kratom.  For example, Hewitt (2000) notes that NMDA receptor antagonism is useful for the treatment of chronic pain by generating an antinociceptive effect and delaying tolerance to opioids.  One might hypothesize that the NMDA receptor antagonism elicited by alkaloids within kratom augment mu-opioid receptor agonism to counteract the resurgence of pain among persons subject to opiate detox.

In addition to reducing pain thresholds, the NMDA receptor antagonism facilitated by rhynchophylline and mitraphylline might improve one’s mood.  Assuming an individual experiences depression during detox and/or has a history of depression, research by Dang, Ma, Zhang, et al. (2014) indicates that NMDA receptor antagonists such as ketamine provide a rapid-onset antidepressant effect.  Perhaps high doses of certain strains of kratom modulate NMDA receptor function such that a depressed mood is normalized during detox.

Other opiate withdrawal symptoms that may improve from NMDA receptor antagonism include: anxiety, insomnia, and irritability.  Furthermore, it should be noted that NMDA receptor antagonism induces synaptogenesis or the growth of new synapses, thereby reorganizing connectivity within the brain – possibly also aiding in management of withdrawal.  While the extent to which alkaloid-mediated NMDA antagonism provides therapeutic benefit during opiate detox is unknown, it warrants consideration.

  • Source: http://www.sciencedirect.com/science/article/pii/S0040403901907464
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/26511390
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Alpha-2 receptor agonist: A possibly overlooked mechanism by which kratom may ameliorate opiate withdrawal symptoms is through agonism of the postsynaptic alpha-2 adrenergic receptor.  An investigation by Matsumoto, Mizowaki, Takayama, et al. (1997) discovered that mitragynine within kratom stimulated central postsynaptic alpha-2 adrenergic receptors in mice.  Whether mitragynine exerts a similar affinity for the alpha-2 adrenergic receptors in humans [as it does in mice] is unclear, however, most report alpha-2 receptor agonism as a putative mechanism of kratom’s action.

Assuming mitragynine agonizes alpha-2 adrenergic receptors in humans, this may facilitate therapeutic effects analogous to that of clonidine, an alpha-2 receptor agonist commonly prescribed for the management of opiate withdrawal.  Alpha-2 adrenergic receptors are G protein-coupled receptors (GPCRs) primarily subject to activation by endogenous catecholamines such as norepinephrine and epinephrine.  Agonism of the alpha-2 adrenergic receptor can modulate: arterial constriction, blood pressure, and executive function.

In some cases, alpha-2 receptor agonism can alleviate anxiety, mitigate fatigue, regulate blood pressure, and enhance cognition – each of which may prove helpful during severe opiate detoxification.  That said, since kratom likely acts upon other pharmacological targets with higher affinity than 5-HT2A receptors (e.g. opioid receptors), and its exact affinity for 5-HT2A receptors remains unknown, the 5-HT2A-mediated therapeutic effects may be notably less than those associated with clonidine.  Still, the fact that mitragynine agonizes 5-HT2A receptors cannot be ruled out as making a [modest] contribution to therapeutic effects of kratom during opiate withdrawal.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/9164589

5-HT2A antagonist:  Research conducted by Matsumoto, Mizowaki, Takayama, et al. (1997) revealed that mitragynine, kratom’s principal alkaloid, functions as a 5-HT2A receptor antagonist in mice.  Mitragynine’s antagonism of the 5-HT2A receptor inhibited head-twitch responses resulting from the administration of the drug 5-MeO-DMT.  Understanding that head-twitch responses in mice are correlated with hallucinogenic effects of drugs in humans, it is logical to surmise that the mitragynine constituent of kratom exerts an anti-hallucinogenic effect.

Since most individuals won’t hallucinate during opiate withdrawal, the anti-hallucinogenic effects resulting from 5-HT2A antagonism are likely irrelevant to this discussion.  Nonetheless, the potential benefit resulting from 5-HT2A receptor antagonism during opiate withdrawal may be most significant in regards to treating insomnia and/or enhancing sleep quality.  Evidence to support this speculation is derived from a paper by Vanover and Davis (2010) in which researchers noted that 5-HT2A receptor antagonism bolsters slow-wave sleep, reduces waking after sleep onset, and improves overall sleep maintenance.

In addition to attenuating insomnia and other sleep disturbances, 5-HT2A antagonism facilitated by kratom may reduce dependence to opiates by interfering with dopamine-mediated reinforcement.  A report by de Angelis (2002) mentions that 5-HT2A antagonists normalize irregular dopaminergic activity implicated in dependence.  It is possible that 5-HT2A antagonism might make kratom inherently less addictive than other opiates.

Furthermore, it should be clear that 5-HT2A antagonism may induce antidepressant, anxiolytic, and anti-obsessive effects.  For this reason, it’s not farfetched to assume that 5-HT2A antagonism provided by mitragynine contributes to mood elevation and anxiety reduction among persons subject to opiate detox.  Although more research is needed to substantiate the hypothesis that mitragynine exerts a noticeable effect upon 5-HT2A receptors in humans, assuming this is a legitimate pharmacological target, it probably contributes [in some respect] to the therapeutic value of kratom during opiate withdrawal.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/9164589
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/23616706
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/23616706
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/12054060

Adenosine A2A antagonist: It is understood that alkaloids within kratom bind to the adenosine A2A receptor, however, it remains unknown as to whether their effect upon the adenosine A2A receptor is agonistic or antagonistic.  Most hypotheses suggest that kratom acts as an adenosine A2A receptor antagonist, a mechanism that might explain its stimulating properties.  When alkaloids of kratom bind to the adenosine A2A receptor and block agonism from adenosine, they inhibit the corresponding drowsiness, fatigue, and/or somnolence that would normally result.

Additionally, the blockade of adenosine A2A receptors affects the neurotransmission of glutamate, dopamine, and GABA such that following the administration of an antagonist, excitatory neurotransmission (dopamine and glutamate) increases and inhibitory neurotransmission (GABA) decreases.  Predictable effects resulting from A2A blockade-mediated increases in excitatory transmission could include increased energy and/or enhanced cognition, each of which may counteract withdrawal-related fatigue and cognitive impairment.

Adenosine A2A blockade also has potential to attenuate withdrawal-related depression and anxiety.  Researchers Yamada, Kobayashi, and Kanda (2014) report that adenosine A2A antagonists reduce depression-like and anxiety-like behaviors in animal models.  Among those who experience less depression and anxiety after taking kratom during opiate detoxification, adenosine A2A antagonism may have been partially responsible.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/25175973

Note: In addition to the numerous aforestated mechanisms of action associated with alkaloidal constituents of kratom, it is clear that these alkaloids interact with other pharmacological targets, including: D2 receptors, 5-HT2C receptors, and 5-HT7 receptors.  That said, it is unknown how the alkaloids interact with these targets (e.g. agonism, antagonism, etc.).  Without knowing how the alkaloids interact with these targets, it’s impossible to explain how action on these receptors would contribute to therapeutically-relevant effects during opiate withdrawal.  Moreover, it is necessary to mention that the alkaloids within kratom exhibit anti-inflammatory and antioxidant properties – each of which have unclear mechanisms, but may help attenuate opiate withdrawal symptoms.

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Various Strains of Kratom (Mitragyna speciosa)

It is well-understood that not all strains of kratom induce the exact same psychological and physical effects.  Certain strains of kratom are cultivated to facilitate an opioidergic effect, some to induce more of a stimulatory effect, and others to combine opioidergic and stimulatory properties.  Strains of kratom are often loosely categorized based upon vein color of leafs (e.g. red, white, green), as well as the country in which they were cultivated.

Kratom enthusiasts claim that the vein color of leafs correlate well with the general psychological and physical effects likely to be experienced by users.  For example, red vein kratom is said to induce sedation with minimal stimulation, whereas white vein kratom is said to induce stimulation with minimal sedation.  Below are descriptions of 3 basic types of kratom strains along with their hypothesized general effects.

  • Red vein: Kratom leaves with red veins are suggested to facilitate anxiolytic, opioidergic, and/or sedative effect. Many find that “red vein” kratom alleviates insomnia, reduces pain, subjectively improves sleep quality, enhances mood, and acts as a muscle relaxant.  Due to the opioidergic effects of red vein kratom, this is the type most commonly utilized for the management of opiate withdrawal symptoms.  It should be noted that there are various strains of red vein kratom leaves that are engineered to generate different effects.  Some are aimed more at mood enhancement and/or relaxation, whereas others are geared more towards pain reduction.
  • White vein: Kratom leaves with white veins are suggested to facilitate a stimulatory effect. Individuals using white vein kratom may be more likely to report enhanced alertness, arousal, motivation, vigilance, and/or wakefulness.  It is suspected that the stimulatory effect of white vein kratom is most noticeable when administered at a low or low-to-moderate dose.  White vein kratom is not often sought out by individuals to help manage opioid detoxification, however, some may find that it helps mitigate excessive fatigue and/or drowsiness.
  • Green vein: Kratom leaves with green veins generally are capable of providing stimulant-like and opioid-like effects simultaneously. The green vein type of kratom leaf provides less stimulation than white vein types and less sedation than the red vein types.  A subset of green vein kratom leaves may provide more stimulation than sedation, yet others may induce greater sedation and less stimulation.  Moreover, at lower doses, more stimulation should be expected, and at higher doses, more sedation should be expected from mu-opioid receptor agonism.

Note:  Understand that there may be more vein colors of kratom than those listed above and realize that vein color does not always accurately predict the effects a user will experience.  The effects of kratom a person experiences will be contingent upon the user’s genetics, neurochemistry, and the dosage they decide to administer.

Benefits of Using Kratom for Opiate Withdrawal (Possibilities)

There are many benefits that individuals associate with the strategic usage of kratom during opiate withdrawal.  Arguably the most substantial benefit resulting from kratom administration during opiate withdrawal is that it significantly attenuates the severity of withdrawal symptoms, thereby making the process more manageable for the user while minimizing likelihood of relapse.  Another benefit associated with kratom usage during opiate withdrawal is that the substance can be legally purchased in most states at a low cost, without doctor visits nor supervision.

  • Administration options: Some individuals may like the numerous ways in which kratom can be prepared and administered.  Most commonly, kratom leaves are steeped in boiling water and consumed in the form of a tea.  That said, kratom leaves can also be pulverized into a powder to be blended in beverages (e.g. orange juice) or foods (e.g. applesauce).  Kratom powder is sometimes even added to unflavored capsules and swallowed like most medications.
  • Anecdotal support: There are countless anecdotes online from former opiate/opioid users claiming that kratom is of substantial therapeutic value during opiate/opioid withdrawal.  What’s more, some of these anecdotes claim that kratom is superior to medically-recommended opioid replacement therapies (e.g. buprenorphine) for managing opiate withdrawal and/or transitioning to sobriety.  Although countless anecdotal accounts highlighting kratom’s therapeutic value during opiate withdrawal are not valid replacements for randomized controlled trials, the sheer number of favorable anecdotes is reason to suspect that kratom benefits at least a subset of the populace to manage opiate withdrawal symptoms.
  • “As-needed”: Many individuals like the fact that they can administer kratom on an “as needed” basis, or only when their withdrawal symptoms are most severe. Following ingestion, kratom is said to deliver a therapeutic effect for a duration of 4 to 6 hours.  This differs from other pharmaceutical medications such as serotonergic antidepressants which are taken once per day to deliver an effect that lasts ~24 hours.  Those who don’t need round-the-clock symptom reduction and/or don’t want to be under the influence of a drug for the entire day – may perceive kratom as a superior option.
  • Drug testing: Another beneficial aspect of utilizing kratom for the management of opiate detoxification symptoms is that it won’t show up on most drug tests. No standardized drug tests (e.g. SAMHSA-5) are engineered to detect kratom, and most extended-panel tests have no reason to test for kratom.  Even if a heavy user were to be tested, evidence suggests that kratom stays in your system for less than 2 weeks.  The lack of detection on a drug test may be perceived as favorable over agents like methadone which are known to appear on extended-panel screenings.
  • Preliminary efficacy: Though kratom hasn’t undergone extensive testing as a potential treatment for opiate withdrawal symptoms, preliminary evidence suggests that it’s likely to be effective. For example, an animal model study by Khor, Jamil, Adenan, and Shu-Chien (2011) discovered that mitragynine, the primary alkaloid within kratom, mitigated abnormal behavior in zebrafish following detoxification from morphine.  Moreover, kratom prevented onset of withdrawal symptoms in a patient following discontinuation of high-dose intravenous hydromorphone.  All existing evidence indicates that kratom is likely effective for the management of opiate withdrawal.
  • Fewer medical expenses: If a person attends a rehab facility for rapid detoxification from an opiate and/or to overcome an addiction, the corresponding expense for 30 days of attendance may exceed $20,000.  For most individuals, spending $20,000 to attend a detoxification facility is a poor choice because there’s always risk of relapse after exiting the facility – thereby rendering the expense a complete waste.  That said, even if an individual doesn’t attend an inpatient detox facility, working with a medical doctor in an outpatient setting is still expensive for most.  Each doctor visit may cost upwards of $100, and prescription medications for the management of opiate withdrawal symptoms often cost $100 to $200 per month.  In the event that you have a minimalistic health insurance policy with a high deductible, you may end up paying a considerable amount of money “out-of-pocket.”  Although kratom isn’t picked up by insurance, those using it save money by averting costs associated with doctor visits and pharmaceutical drug prescriptions.
  • Less sedation: Many strains of kratom are understood to stimulate the mu-opioid receptor to prevent opiate withdrawal symptoms without inducing as much sedation as conventional opioid replacement therapies. Excessive sedation is understood to impair cognitive performance and motor skills.  Since kratom may not induce as much sedation as other interventions, users may have an easier time completing cognitively-demanding tasks and/or operating machinery.  Moreover, some strains of kratom can actually induce psychostimulation such that wakefulness, vigilance, and cognition is enhanced.  This is believed to stem from kratom’s interaction with adenosine A2A receptors.
  • Lower potency (?): A subset of individuals claim that kratom has a lower affinity for the mu-opioid receptor than conventional opioid replacement therapies, suggestive of the fact that it’s less potent. Although kratom has not been proven to be of lower potency than standard prescription medications utilized during detoxification, it’s possible that it is.  Hypothetically speaking, if kratom alkaloids are less potent (on average) than most medications used to manage opiate withdrawal symptoms, its lower potency may be advantageous such that likelihood of abuse and/or addiction would be reduced.
  • Low cost: Most kratom consumers consider it to be an affordable herbal drug. Those who use the minimal effective dose of kratom to manage opiate withdrawal will probably spend between $50 and $100 per month on their supply.  This is a lower out-of-pocket expense than many pharmaceutical medications if one lacks quality health insurance.
  • “Natural” appeal: Throughout the world, a subset of individuals remain convinced that medical professionals and/or pharmaceutical companies are conspiring against them with some sort of hidden agenda to push expensive, toxic pills to treat medical conditions.  These individuals may also believe that doctors avoid recommending natural substances like kratom because it’ll hurt their kickbacks from big pharma.  Although this way of thinking is largely delusional, it is impossible to convince certain individuals otherwise.  Assuming someone detoxifies from an opiate and refuses to use conventional medications because they aren’t “natural,” kratom may serve as a much-needed alternative option for stabilization and relapse prevention.
  • Unique mechanism of action: The mechanism of action associated with kratom is unique compared to most medications commonly prescribed to patients during opiate withdrawal. Although kratom’s pharmacodynamics are somewhat akin to buprenorphine, they differ such that kratom interacts with neurochemical systems that buprenorphine does not, including:  adenosine, NMDA, serotonin, and norepinephrine.  Considering the unique neurochemical influence of kratom, one might suspect that kratom could be more effective than other interventions for the management of opiate withdrawal symptoms.
  • Various strains: Another benefit of using kratom to manage symptoms of opiate withdrawal is that not all strains generate the same psychological effects. Some strains induce stimulation and increased vigilance, whereas others are more sedating.  In other words, different strains may be rotated throughout a person’s opiate withdrawal depending on the most prominent withdrawal symptoms.  For example, one strain may be ingested to reduce insomnia and/or enhance sleep in the early stages of withdrawal, whereas another may be ingested to reduce fatigue in later stages.

Drawbacks of Using Kratom for Opiate Withdrawal (Possibilities)

Though there are numerous potential benefits associated with administering kratom during opiate withdrawal, there are also potential drawbacks to consider.  Perhaps the most substantial drawback is that kratom may be downright ineffective for the management of severe opiate withdrawal symptoms, possibly increasing likelihood of relapse compared to conventional opioid replacement medications.  Other drawbacks of using kratom during opiate withdrawal include: abuse potential, cost, unestablished dosing guidelines, side effects, and discontinuation symptoms.

  • Abuse / addiction potential: Although kratom is legal and/or unregulated in many states, it has significant potential for abuse and may prove addictive for a subset of users. At high dosages, kratom exerts similar effects to other opiates/opioids through agonism of the mu-opioid receptor.  Since kratom is unregulated by medical professionals, persons with a history of opiate abuse are free to purchase kratom and administer large quantities to attain a pleasurable intoxication.  This is problematic because, if the quantity of kratom ingested stimulates mu-opioid receptors greater than the opiate/opioid from which an individual is withdrawing, it may exacerbate opiate addiction and/or dependence rather than guiding the former user toward sobriety.  While many kratom users claim that it’s less addictive than conventional pharmaceutical medications, there’s zero evidence to legitimize these claims.  Moreover, experiments by Yusoff, Suhaimi, Vadivelu, et al. (2016) in mice mention that the mitragynine constituent of kratom has an addictive profile similar to morphine. (Source: https://www.ncbi.nlm.nih.gov/pubmed/25262913).
  • Comparative efficacy: It is unknown as to how kratom compares to conventional pharmaceutical medications that are used to help manage opiate withdrawal symptoms. While kratom may be useful during opiate detoxification to attenuate withdrawal symptoms, it may be less effective than conventional pharmaceutical interventions.  For example, if compared head-to-head with buprenorphine-containing medications, kratom may be significantly less effective.  For this reason, someone quitting a potent opiate like heroin after an extended term should be encouraged to utilize a proven intervention to manage withdrawal.
  • Contraindications: A serious concern associated with using kratom is that, due to lack of research, most contraindications are unknown. It’s logical to assume that kratom is contraindicated among persons with known kratom allergies, as well as among pregnant and/or nursing women.  One might suspect that kratom is contraindicated among persons with blood pressure abnormalities, hepatic impairment, and renal impairment.  Since contraindications are unknown, using kratom with any diagnosable medical condition could provoke adverse and/or life-threatening reactions.
  • Dependence: The reason kratom alleviates severe opiate detoxification symptoms is because it exerts opioidergic effects. It is very possible that an individual with opioid dependence may discontinue opioids only to use high-dose kratom as an alternative means of fueling their opioid dependence.  Furthermore, it’s possible that some individuals may become dependent upon the unique effects of kratom, such that when they attempt to discontinue kratom, they struggle with deleterious withdrawal symptoms.  Although many anecdotes claim that kratom dependence is unlikely, these claims are often biased and/or subjective.
  • Dosing guidelines: As of current, there are zero scientifically-substantiated dosing guidelines of kratom during opiate withdrawal.  With buprenorphine-based medications, doctors know the safe and effective dosages to administer because they’ve been tested in randomized controlled trials.  Kratom has never undergone any sort of formalized testing to determine a safe and effective dose for the attenuation of opiate withdrawal symptoms.  Furthermore, when considering the myriad of kratom strains and lack of standardization, universally safe and/or effective dosing guidelines are impossible to establish.  Most people using kratom are simply following the guidelines established by others online.  Although online recommendations may be helpful, they may be unsafe and/or ineffective due to individuality (severity of dependence, genetics, neurochemistry), strain of kratom, and/or modality of preparation/administration.
  • High cost: Among those who administer low daily doses of kratom for the management of opiate withdrawal symptoms, the cost of a monthly supply should be relatively affordable. As a hypothetical example, let’s assume someone administers 14 grams of Red Vein Bali kratom per day in two divided doses of 7 grams.  The cost of Red Vein Bali kratom is around $125 per kilogram from online vendors.  Accounting for the rate of usage (14 grams per day) and the cost of this particular kratom strain, we can estimate that the user would need to spend approximately $52.50 per month on his/her supply.  While this may be more affordable for some individuals than the cost of doctor visits and corresponding prescription medications, others may realize the exact opposite – that kratom is more expensive.  In the event that someone has quality health insurance coverage and/or has met their deductible, the cost of doctor visits and prescription medications may be negligible for the patient, making conventional medical care cheaper than kratom.  It is also important to mention that some individuals may: purchase kratom from a more expensive vendor, prefer a higher-priced strain than Red Vein Bali, and/or administer a large quantity per day (e.g. 30 grams/day).  As an example, let’s assume that someone purchases 1 lb. of Thai Red Vein kratom (instead of Red Vein Bali) for $180 (a price currently listed through online vendors) and only derives therapeutic benefit from administering 30 grams per day.  In this case, the kratom supply would only last around 15 days, costing the user just under $12 per day.  Those who plan on using kratom for an extended duration may find that kratom is significantly more expensive than conventionally recommended medical care.  Furthermore, even if the doctor visits and/or medications are initially more expensive than kratom, over the course of a calendar year (with regular checkups and prescription refills) you may meet your health insurance deductible whereby the cumulative annual expenses associated with medical care are significantly lower than kratom.  Moreover, the only formalized case report of a kratom user confirmed that the individual was spending upwards of $15,000 per year on his kratom supply – an expense many would consider unaffordable.
  • Impurities: Assuming someone knows a reputable kratom vendor and/or has done some upfront research, likelihood of ingesting impure kratom should be low. That said, since kratom is classified as a dietary supplement, it is not subject to FDA regulation to protect the consumer.  It is possible that various kratom vendors may sell semi-pseudo-kratom (some legitimate kratom mixed with fillers), ultimately taking advantage of the consumer’s trust.  Impurities may be most common in powdered forms of kratom due to the fact that fillers can be easily disguised in powder.  Unless consumers get their kratom supply tested to ensure that it’s 100% kratom, there’s a chance their supply could contain impurities that were added with the intention of saving the retailer money.  Any impurities and/or fillers in kratom may be harmful to the consumer.  A small percentage of kratom sold online has been discovered to be laced with pharmaceutical drugs (e.g. tramadol) and other chemicals, possibly putting the consumer at serious risk of an adverse reaction.
  • Interactions: Like most drugs, kratom may interact pharmacokinetically and/or pharmacodynamically with co-administered substances (e.g. illicit drugs, pharmaceutical medications, supplements, etc.), possibly triggering serious adverse reactions.  Since kratom hasn’t been subject to extensive scientific research in humans, the substances most likely to interact with kratom remain unknown.  It should be stated that in a single case report, tonic-clonic seizures occurred as a likely interaction effect as a result of administering modafinil (150 mg) along with kratom.  Although it’s possible that this individual experienced a seizure solely from the modafinil, however, it’s most likely that the combination of kratom plus modafinil yielded a pharmacodynamic interaction to trigger tonic-clonic seizures.  In any regard, since there are many strains of kratom, each containing different quantities of alkaloids, pharmacodynamic interactions occurring with one strain of kratom may differ from those of another.  Among persons taking kratom to manage opiate withdrawal, the strains administered are most often opioidergic and/or sedating.  If these strains of kratom are co-administered with an opioid, serious pharmacodynamically-mediated adverse interaction effects may occur (e.g. respiratory depression) resulting from the synergistic mu-opioid receptor agonism.  Furthermore, anyone using CNS depressants (e.g. alcohol, barbiturates, benzodiazepines, etc.) along with kratom may be at risk for adverse interactions due to potentiation of CNS depression.  That said, someone administering a stimulating strain of kratom may be protected against some CNS depressant-related interaction effects.  In addition to the potential unwanted pharmacodynamic-mediated interactions, kratom users may experience pharmacokinetic-mediated interactions.  The alkaloids within kratom are thought to undergo hepatic metabolism, primarily facilitated by CYP2D6 isoenzymes and possibly CYP2C9 and CYP3A4.  Should an individual ingest kratom along with an agent that inhibits or induces the CYP2D6 enzyme, this may provoke a serious adverse reaction such that the person experiences a potent, rapid-onset of effect to increase likelihood of CNS depression.  Adverse pharmacokinetically-mediated interactions may be even more likely among persons with a preexisting CYP2D6 polymorphism whereby metabolism of substances through this pathway is expedited.
  • Intoxication: While most individuals using kratom to help manage opioid withdrawals will not experience intoxication or a “high” – some might. The degree of intoxication following kratom administration will be largely predicated upon the significance of a person’s opiate dependence and/or tolerance, the strain and dose of kratom ingested, as well as individual neurochemistry and genetics.  Assuming someone were to purchase a potent opioidergic strain of kratom and ingest a mega-dose, it’s possible that the degree of mu-opioid receptor agonism would exceed the opiate/opioid that the person had previously discontinued.  As a result, this individual may report some intoxication.  The intoxication resulting from kratom may be pleasurable, which can be problematic in terms of addiction and dependence.  Kratom-induced intoxication may also be unwanted such that it might impair cognitive function and/or physical reflexes, whereby it negatively affects academic, athletic, or occupational performance.
  • Legal status: A notable drawback associated with using kratom to manage opioid withdrawal symptoms is that it is not legal in every state (within the U.S.) nor is it legal in every country around the world. In the event that you are caught in possession of kratom in a state and/or country in which it is classified as illegal, you might end up imprisoned and/or paying a hefty fine.  While legal penalization for the purchase, possession, and/or usage of kratom may seem unnecessarily harsh or unfair, there are legal alternatives (e.g. pharmaceutical medications).  Assuming you live in an area in which kratom is either already illegal or on the verge of being classified as a controlled-substance, you may want to avoid kratom altogether so that you won’t be penalized by the legal system.
  • Long-term effects: There is currently a lack of information regarding the long-term effects of kratom usage. While many individuals using kratom to manage opiate withdrawal symptoms only plan to administer it for a short-term (e.g. weeks or months), others may decide to use it for a longer-term (e.g. years) or indefinitely as an opioid replacement therapy.  Since kratom isn’t well-researched, it’s possible that long-term kratom administration induces deleterious neurological and/or physiological changes.  While most deleterious long-term effects resulting from kratom are likely to reverse following kratom withdrawal, some may be permanent.  For example, it is reasonable to hypothesize that long-term kratom administration among teenagers and/or young adults may interfere with normative brain development and cause permanent neurodevelopmental deficits.
  • Non-standardized: Unlike pharmaceutical medications, kratom is not subject to standardization. The aim of standardization in the medical community is to ensure that consumers are getting a product in which the chemistry is consistent from batch to batch.    Because kratom is not subject to standardization, users cannot be guaranteed that they’ll experience the same [predictable or reliable] neurobiological effect even if equivalent quantities are ingested.  Even if the quantity of kratom leaves ingested is consistent for each dose, alkaloidal composition could be variable.  Hypothetically, an individual could ingest 5 grams of “red vein” kratom and experience a particular effect that differs from the effect experienced following a subsequent ingestion of the same “red vein” kratom at the same quantity.  Perhaps the second dose was more stimulating than the first dose – or vice-versa.  The differing effects may be explained, in part, by intra-plant or intra-leaf differences in alkaloidal constituents, whereby resulting neurobiological effects are slightly (or perhaps significantly) different.  Unpredictable or inconsistent reactions to kratom due to lack of alkaloidal standardization may be perceived as unfavorable over pharmaceutical medications that are of reliable chemical consistency.
  • Potency: Based on the fact that the mitragynine within kratom acts as a partial mu-opioid receptor agonist (as opposed to a full agonist), the potency of its opioidergic effect should be less substantial than that resulting from opiates (e.g. heroin) and opioids (e.g. oxycodone).  That said, it remains unclear as to whether kratom is more or less potent than pharmaceutical opioid replacement therapies (e.g. buprenorphine).  It’s possible that kratom is less potent than buprenorphine, but it is also possible that buprenorphine is less potent than certain strains of kratom.  Until more research is conducted and the pharmacodynamics of each are compared, we must acknowledge that kratom might be more potent than expected.  What’s likely is that the significance of opioidergic effect derived from kratom is contingent upon the dosage ingested, as well as the specific strain of kratom.  It’s probable that the ingestion of high-dose kratom (e.g. 10 grams per dose) will provide a more significant opioidergic effect than lower doses of buprenorphine-based replacement therapies (e.g. 2 mg/0.5 mg Suboxone).  Since the dosing of kratom is not regulated by medical professionals, it’s also likely that some individuals will ingest doses of kratom that facilitate a [substantially] more potent opioidergic effect than the opiate/opioid from which they detoxified, thereby potentiating the severity of their preexisting opioidergic dependence – rather than helping them overcome it.
  • Questionable efficacy: Countless anecdotal accounts on the internet suggest that kratom is therapeutically valuable during opiate withdrawal.  That said, there are anecdotes suggestive that many substances are therapeutically valuable in certain scenarios, yet when these substances are tested in scientifically-substantiated trials, they are often no more efficacious than a placebo control.  To determine whether a substance is efficacious for the treatment for any medical condition, it necessitates evaluation in robustly-designed, large-scale, randomized controlled trials (RCTs).  As of current, there haven’t been any randomized controlled trials that’ve investigated the efficacy of kratom for the management of opiate withdrawal symptoms.  For this reason, it is impossible to know whether kratom is more effective than a placebo for mitigating symptoms of opiate detoxification.  Knowing that the therapeutic usefulness of kratom during opiate withdrawal remains unknown, many would agree that it’s smarter to pursue evidence-based interventions to increase likelihood of relief.
  • Safety concerns: Using kratom during opiate withdrawal may be downright unsafe for certain individuals.  The medical conditions that are contraindicated with kratom remain unknown, and the substances (medications, supplements, etc.) that interact with kratom are largely undetermined.  Individuals who use kratom without consulting a medical professional may experience serious and/or unexpected adverse reactions as a result.  Additionally, kratom isn’t subject to FDA regulatory standards and can be sold by anyone online, each of which are safety concerns because certain products may be contaminated and/or laced with unknown chemicals.  Moreover, it is possible that a subset of individuals who use kratom to manage opioid detoxification will end up addicted and/or dependent upon kratom.
  • Side effects: Although some will find kratom to be more tolerable than pharmaceutical interventions during opiate withdrawal, others may struggle to tolerate the side effects of kratom more than the side effects of pharmaceutical interventions.  Common kratom side effects have been documented by researchers including: cognitive deficits, constipation, dizziness, drowsiness, dry mouth, fatigue, impaired motor skills, itchiness, sedation, and sweating.  In the event that you experience a few of the aforestated side effects such as cognitive deficits, drowsiness, and impaired motor skills – the implications could be profoundly negative.  For example, your academic and/or occupational performance may suffer from the side effect of cognitive deficits and/or “brain fog,” plus you may be unable to safely operate a motor vehicle as a result of the drowsiness plus motor impairment.  Though less common, extreme adverse reactions to kratom have been reported, including: delusions, hallucinations, paranoia, and vomiting.
  • Superior options: Since the safety and efficacy of kratom for the management of opiate withdrawal haven’t been evaluated, yet other medications have demonstrated both safety plus efficacy in randomized controlled trials, we must acknowledge that kratom is [currently] an inferior intervention for patients detoxifying from opiates. Kratom may be equally as effective (or possibly more effective) than medically-recommended interventions for opiate detox, however, there’s no evidence to legitimize this hypothesis.  Any intervention that’s supported by randomized controlled trials is superior to one that has never been tested, because the one that hasn’t been tested may be ineffective or unsafe, possibly leaving a patient to suffer and/or compromising his/her health.  Agents like buprenorphine, clonidine, gabapentin, methadone, etc. should be considered superior to kratom for the management of opiate withdrawal because they have a track-record of safety and efficacy.
  • Tolerance onset: Anyone transitioning from opiates/opioids to kratom may initially derive substantial benefit from the pharmacological effect of kratom. The pharmacology of kratom differs from opiates/opioids such that kratom modulates many targets and neurotransmitter systems (e.g. adenosine, norepinephrine, serotonin) besides just the mu-opioid receptor.  As a result, users may actually prefer kratom over the previously discontinued opiate/opioid.  Though some individuals use kratom as nothing more than a temporary bridge from opiates to abstinence, others may decide that they should use kratom as a long-term maintenance therapy.  With regular daily usage of kratom, users will develop tolerance, sometimes at a fast pace.  Just because kratom is a natural plant does not mean that there’s some sort of “biological free lunch” whereby users are able to reap continuous benefits from the exact same dose – this is a misnomer.  Over an extended duration of ingestion (e.g. months), daily kratom users will come to realize that the same starting dose of kratom is no longer as beneficial as in the past.  This diminishing and/or lack of benefit after an extended-term of use is attributable to tolerance.  The underpinnings of tolerance likely involve mu-opioid receptor upregulation, kappa-opioid receptor downregulation, and altered expression of hepatic enzymes in response to regular kratom ingestion.  When tolerance is established, kratom users may incrementally increase their intake over time, and as a result of increased intake:  preexisting dependence is potentiated, side effects become more severe, and future withdrawal becomes more challenging.
  • Withdrawal symptoms: Although kratom may significantly attenuate the severity of opiate withdrawal symptoms, discontinuation of kratom commonly yields debilitating and unwanted withdrawal symptoms of its own. Research by Singh, Müller, and Vicknasingam (2014) suggests that kratom withdrawal symptoms are both physical and psychological, including:  anger, anxiety, appetite fluctuation, depression, diarrhea, fever, hot flashes, muscle spasms, pain, restlessness, runny nose, sleep disturbances, and watery eyes.  When acknowledging the fact that kratom exerts an opioidergic effect, it’s reasonable to assume that, unless a kratom user gradually tapers his/her dose over an extended duration (e.g. months), kratom cessation be difficult for many users to manage – especially among persons who adapted to the regular ingestion of high doses.  (Source: https://www.ncbi.nlm.nih.gov/pubmed/24698080).

Kratom for Opiate Withdrawal Symptoms (Review of Research)

To determine the therapeutic usefulness of kratom during opiate withdrawal, it is necessary to examine scientific literature for relevant studies in which kratom was administered to patients while detoxifying from opiates.  Randomized controlled trials with large sample sizes are preferred, as these will provide the most accurate data regarding the safety, tolerability, and efficacy of kratom in the management of opiate withdrawal symptoms.  At this time, there are zero randomized controlled trials that have investigated the efficacy of kratom for the management of opiate withdrawal.

Despite the lack of randomized controlled trials, there are case reports in which kratom was highlighted as providing therapeutic benefit to patients during opiate withdrawal.  Furthermore, a study in animal models showcased kratom’s ability to attenuate symptoms of opiate detoxification.  Although preliminary evidence is promising, more robust data supporting the efficacy of kratom during opiate withdrawal are needed before it can be recommended as a safe and/or practical intervention.

2011: Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish.

A study by Khor, Jamil, Adenan, and Shu-Chien (2011) noted that opiate addiction is often challenging to treat due to the severity of detoxification symptoms.  These symptoms can be so overwhelming and/or unmanageable for certain patients, that relapse is inevitable.  One plant-based intervention that individuals with opiate dependence and/or addiction frequently reference as aiding in the management of detoxification syndrome is Mitragyna speciosa, popularly referred to as “kratom.”

Based on preliminary case studies and anecdotal reports implying that kratom alleviates opiate withdrawal syndrome, researchers conducted a series of experiments in which kratom was administered to an animal model (zebrafish) of opiate withdrawal.  For the study, researchers exposed adult zebrafish to chronic administration of morphine (1.5 mg/L) for a duration of 2 weeks.  Following the 2-week phase of chronic morphine administration, all adult zebrafish underwent abrupt detoxification.

Approximately 24 hours after withdrawal, the zebrafish underwent various experiments designed to measure:  anxiety-like behavior, cortisol concentrations, and expression of stress-related genes.  In a tank diving test, the zebrafish exhibited substantial increases in anxiety-like behaviors after abrupt detoxification, as was evidenced by reduced exploration and irregular movements.  Researchers also noted that the zebrafish exhibited elevated whole-body cortisol concentrations plus mRNA expression of corticotropin releasing factor (CRF) receptors and prodynorphin – biomarkers indicative of heightened stress.

After an initial evaluation of morphine detoxification symptoms in the zebrafish, researchers administered mitragynine [the most abundant alkaloid within kratom] to determine whether it might attenuate symptoms.  Mitragynine appeared to reduce anxiety-like behavior as evidenced by increased exploration and fewer abnormal movements post-administration.  Moreover, mitragynine mitigated mRNA expression of CRF receptors and prodynorphin, suggestive of the fact that it reduced neurophysiological stress responses.

Overall, the results from this study support the idea that mitragynine is of therapeutic value during opiate detoxification.  In this zebrafish model, mitragynine reduced biomarkers of stress plus attenuated overt anxiety-like and restlessness-like behavior associated with abrupt opiate detoxification.  That said, since results from an animal model cannot be extrapolated to humans, human trials are needed to evaluate mitragynine in a detoxification setting.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/22205946

2008: Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth).

A case report presented by Boyer, Babu, Adkins, et al. (2008) discussed the usage of kratom by a 43-year-old male in effort to manage chronic pain and evade symptoms of opiate detoxification.  The aforementioned individual had a history chronic pain associated with thoracic outlet syndrome.  To attenuate thoracic outlet syndrome-related pain, the patient was prescribed hydromorphone by a medical professional.

The patient eventually developed tolerance to hydromorphone whereafter he resorted to hydromorphone abuse and misuse involving the crushing of pills for subcutaneous injection at a dosage of 10 mg per day.  As a result of this unauthorized abuse and misuse, the patient would inevitably run out of his hydromorphone supply prior to medically-sanctioned refills.  To elude opiate withdrawal syndrome in the days and/or weeks without hydromorphone, the patient turned to kratom.

He consumed kratom up to 4 times per day in the form of a brewed tea, claiming that it reduced chronic pain and enhanced mental alertness without inducing drowsiness that he experienced while taking hydromorphone.  Since the patient was said to have experienced social stress resulting from his hydromorphone usage, and kratom worked well as an alternative, he opted to discontinue hydromorphone and utilize kratom as a standalone therapy.  In effort to potentiate mental alertness while taking kratom, the patient administered adjunct modafinil (100 mg), a eugeroic medication.

Within 20 minutes of ingesting 100 mg of modafinil, the patient experienced a 5-minute generalized tonic-clonic seizure and received medical attention.  The patient had no history of seizures or head injury and denied recently ingesting alcohol and illicit drugs that may have provoked the seizure.  Medical professionals conducted a drug screening and the results solely revealed the presence of modafinil.

Additionally, computerized tomography (CT) and magnetic resonance imaging (MRI) scans of the patient appeared normal.  Following emergency medical care, the patient was directed to a doctor specializing in addiction and directed to cease kratom in favor of buprenorphine/naloxone maintenance therapy.  It is worth noting that, had this patient never experienced a seizure, there may be no formal accounts of kratom usage in formal medical literature.

In any regard, this case report suggests that, in select individuals, long-term kratom administration may be safe and therapeutically effective for the management of chronic pain and as an opioid replacement therapy.  It was suspected that kratom’s mechanism of action targeting mu-opioid receptors, kappa-opioid receptors, and alpha-2 adrenergic receptors yields effects that are similar to conventional opioid replacement medications (e.g. buprenorphine) and adjuncts (e.g. clonidine).  Still, although kratom continues to garner mainstream attention as an herbal alternative to medically-regulated opioid replacement drugs, more research is needed to elucidate its safety and tolerability – especially when administered with other substances.

  • Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670991/

2007: Self-treatment of opioid withdrawal with a dietary supplement, Kratom.

Boyer, Babu, and Macalino (2007) investigated the increasing popularity of kratom as a form of self-treatment for opioid detoxification syndrome.  For this investigation, researchers monitored discussions within an online community among individuals diagnosed with chronic pain who purchase opioid analgesics from internet pharmacies.  Within 1 year of monitoring users of DrugBuyers.com, a website dedicated to the sale of opioids, researchers discovered many users recommending kratom for the treatment of opioid withdrawal.

Considering that kratom was frequently recommended by users as being a useful intervention during opioid detoxification, it’s reasonable to suspect that it provides some degree of benefit.  Since the discussions take place on a website that sells opioid analgesics and not kratom, it is unlikely that the recommendations were fabricated to generate kratom sales.  Although kratom cannot be formally endorsed by medical professionals due its unknown safety profile and efficacy, the lack of medical endorsement isn’t stopping individuals from administering it during opioid detox.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/17882605

Limitations associated with research of Kratom for opiate withdrawal

Upon examination of the available literature in which kratom was investigated as a potential intervention for the management of opioid withdrawal symptoms, it is apparent that there are some serious limitations.  Arguably the most notable limitation in determining whether kratom is safe and/or efficacious for the management of opioid detoxification is that it hasn’t been tested in any human trials.  The primary alkaloid within kratom, mitragynine, was solely evaluated in one animal model study involving zebrafish subject to abrupt opioid cessation.  In addition to the lack of human trials, limitations that may emerge with continued research of kratom include: unknown comparative potency [to conventional opiates/opioids], unknown optimal dosage, lack of standardization, and profit-motivated bias.

  • Anecdotal reports: There is currently only one case report in medical literature documenting an individual who successfully utilized kratom to inhibit opioid discontinuation syndrome and treat a chronic pain condition. In this particular case, the long-term usage of kratom appeared safe and was [subjectively] efficacious in preventing hydromorphone withdrawal after a period of abuse.  While this anecdotal report supports the idea that kratom may be useful to counteract and/or manage opioid withdrawal symptoms, a standalone anecdote is low-quality evidence to support the usefulness of kratom.  Moreover, exact details of kratom usage in case reports such as: the strain, dosage, dosage adjustments, etc. – remain unknown and/or are taken at the word of the patient, possibly with incomplete detail.
  • Animal models: There is solely one animal model study in which mitragynine, an opioidergic alkaloid of kratom, was investigated for the management of opioid detoxification syndrome. The study involved daily administration of morphine to a group of adult zebrafish for a 2-week term followed by abrupt discontinuation.  Based on neurophysiological testing conducted by researchers, the fish exhibited morphine withdrawal symptoms.  When mitragynine was administered, the mitragynine attenuated the severity of the measured morphine withdrawal symptoms.  Although an animal model study is useful for strengthening of the hypothesis that administration of kratom may attenuate opioid withdrawal in humans, it is necessary to consider that the effects of a substance in animal models is not always applicable to humans.  It’s possible that the mitragynine is highly effective in zebrafish yet negligibly therapeutic in humans undergoing morphine detox.
  • Comparative potency: The marketing of kratom as a “dietary supplement” leads many to automatically conclude that kratom must be less potent than prescription opioids. As of current, the potency of kratom is unknown when compared to the potency of opioids and/or opiates that an individual discontinues prior to making the transition to kratom.  The potency of kratom’s opioidergic effect is likely variable based upon the specific strain/leaf purchased and the quantity ingested.  Kratom is not standardized which makes it difficult to compare to a standardized pharmaceutical medication such as hydrocodone.  Nonetheless, it’s possible that the potency of certain kratom strains is nearly equivalent to, or even superior to that of opioid medications.  Perhaps the reason many find it helpful during opiate withdrawal is because it’s preventing the withdrawal by delivering a potent opioidergic effect.  The lack of comparative potency makes it unclear as to whether kratom warrants usage during opioid detoxification.
  • Dosage calibration: Even if we were to assume that all strains of kratom are less potent and/or deliver a weaker opioidergic effect than all prescription opioids, it is currently unknown as to what the optimal dosage of kratom would be. Furthermore, since all strains and leafs of kratom can differ in alkaloidal constituents, the dose taken from one strain or leaf may deliver a substantially more potent effect than the same dosage of another.  Currently, most individuals are using kratom at dosages based upon how it subjectively makes them feel after ingestion.  It is possible that some individuals are using such high dosages, that the opioid receptor modulation derived from kratom exceeds the modulation derived from the opioid that they discontinued.  Unless kratom is standardized and/or a kratom-mimetic substance is developed by a pharmaceutical company, it will be difficult to recommend a safe and/or effective dose of kratom for individuals attempting to manage opioid withdrawal.
  • Lack of incentive: Despite the fact that there are kratom retailers online, there’s little incentive for these retailers to invest money in scientific research of kratom. Kratom cannot be patented and therefore no pharmaceutical company would waste research dollars to test the usefulness of kratom among those detoxifying from opiates.  Really the only financial incentive for studying kratom would be to prove its efficacy [for the treatment of a medical condition] to increase kratom sales.  Since anyone can sell kratom, retailers don’t stand to see a good return on investment from research (unless they research a patented formula/extract).  Perhaps a crowdfunding campaign by kratom enthusiasts for randomized controlled trials (RCTs) of would be one way to overcome the lack of incentive.
  • Lack of standardization: It is known that there are many different strains of kratom on the market. Different strains tend to facilitate different effects and may vary from other strains in regards to potency.  In other words, someone who ingests “Maeng Da” kratom may report variance in subjective effects and/or magnitude of effects than if that same individual had ingested an equivalent quantity of “Red Vein Thai” kratom.  Additionally, even if a person were to ingest the exact same quantity of “Red Vein Thai” kratom on a daily basis, it’s possible that certain days may yield more substantial effects than others – even at the same dose.  This is because the alkaloids may differ between kratom plants even if both are classified as “Red Vein Thai.”  To get even more technical, it’s possible that there may be significant differences in alkaloid concentrations within leaves of the exact same kratom plant.  In brief, there’s likely inter-species, intra-species, intra-yield, and intra-plant variability in alkaloids.  Until a standardized kratom extract is studied, trial outcomes may be subject to inaccuracies.
  • Safety concerns: Statistical data indicate that kratom is generally regarded as safe. Most kratom users don’t experience adverse reactions, unpredictable side effects, nor end up with health complications that are attributable to kratom ingestion.  That said, if kratom is to be studied for its therapeutic potential among those attempting to detoxify from opiates, it will first need to be proven safe and non-toxic to animal models.  Assuming animal model data shows kratom is safe, researchers will need to determine contraindications and/or possible interactions associated with kratom in humans.  These safety concerns need to be addressed before it undergoes testing in humans for the management of opioid withdrawal.
  • Zero human trials: It is necessary to emphasize that there are zero randomized controlled trials in which kratom was tested in humans for the treatment of a medical condition. Although a lack of clinical trials does not automatically negate kratom’s therapeutic potential, it does mean that kratom cannot be endorsed by professionals as a safe, effective, and reliable intervention for the management of opioid discontinuation syndrome.  Human trials are needed to understand whether kratom may prove therapeutically beneficial in select populations.

Verdict: Kratom is likely of therapeutic value during opiate withdrawal

Professionals understand that abruptly detoxifying from an opioid, especially after an extended duration of regular usage, yields severe withdrawal symptoms.  In many cases these symptoms are so debilitating, that many persons are prone to relapse.  Considering that the alkaloidal constituents of kratom exert a partial agonist effect upon mu-opioid receptors (MOR) and an antagonist effect upon kappa-opioid receptors (KOR), it’s logical to assume that kratom attenuates the severity of opiate withdrawal symptoms for many.

Although the precise causative neurological and physiological underpinnings responsible for triggering withdrawal symptoms are debatable, most would agree with the hypothesis that many withdrawal symptoms arise, in part, because a person’s neurobiology had adapted to regular mu-opioid receptor agonism [and corresponding downstream neurochemical effects] facilitated by regular opiate administration.  When the opiate is discontinued, the user’s neurochemistry is transiently stuck in a state of disarray [as compared to homeostasis] whereby the density of mu-opioid receptors is high, and a myriad of downstream signaling cascades exhibit abnormalities.

The administration of kratom following opioid cessation is likely beneficial because its alkaloidal constituents ameliorate the degree of neurochemical imbalance implicated in triggering symptoms of withdrawal.  Though kratom probably won’t deliver the exact same effect nor as potent of an effect as most opioids, it is capable of partially agonizing the mu-opioid receptor such that it bridges the gap between the nonexistent agonism (following cessation) and the full agonism (that a user had regularly derived from his/her former opiate).

In other words, the partial agonism of mu-opioid receptors elicited by kratom helps the person’s neurochemistry to establish a medium of mu-opioid receptor activation, such that withdrawal symptoms aren’t so overwhelming that they trigger relapse.  The individual detoxifying from an opiate will still [likely] experience some withdrawal symptoms, but they should be less severe due to the effect of kratom.  Once a person has stabilized on kratom and survived the first few weeks and/or months of opiate detoxification, the dosage of kratom can gradually be reduced via downward titration.

This gradual downward titration gives the user’s neurochemistry to slowly recalibrate itself to functioning with less opioidergic modulation.  Eventually, assuming an individual doesn’t have a chronic pain condition, the goal will be to fully cease kratom usage and remain abstinent from all opioidergic influence.  Most obviously, kratom is being utilized in an analogous manner to opioid replacement drugs like buprenorphine.

Interestingly, although kratom is not medically endorsed for the management of opioid withdrawal symptoms, its mechanism of action is strikingly similar to that of buprenorphine.  That said, in comparison to buprenorphine, kratom does not have as much scientific support for the treatment of opioid withdrawal symptoms as buprenorphine.  Evaluation of the scientific literature in 2016 only yielded 1 animal model trial, 1 case report, and 1 general report describing the usage of kratom and/or its alkaloids for the management of opioid detoxification symptoms.

Still, despite the paucity of formalized documentation discussing the usefulness of kratom in opiate detoxification, existing documentation unanimously supports the hypothesis that kratom attenuates opiate withdrawal symptoms.  Straying from the scientifically formalized information, a considerable number of self-reports logged by individuals on the internet testify that kratom is: as effective, more effective, and/or more tolerable than FDA-approved and/or medically-accepted strategies for the management of opiate withdrawal.

Though personal anecdotes cannot be regarded as quality data, they warrant recognition, especially considering that clinical trials of kratom for the treatment of opiate withdrawal symptoms may never occur due to lack of financial motive.  In summary, when contemplating that: kratom exerts an opioidergic effect, preliminary evidence indicates that kratom attenuates opiate withdrawal symptoms, and there are countless testimonials from kratom users who claim that it was highly therapeutic during opiate withdrawal – it’s not a stretch to believe that kratom may be a useful intervention among those detoxifying from opiates.  That said, at this time, kratom cannot be recommended over medically-accepted opioid replacement therapies that have demonstrated safety, efficacy, and tolerability in large-scale randomized controlled trials (RCTs).

Have you tried Kratom for opiate withdrawal?

If you’ve personally taken kratom to help manage opiate/opioid withdrawal symptoms, be sure to share your experience in the comments section below.  Hypothetically, assuming you had to rate the efficacy of kratom for the management of opiate/opioid withdrawal symptoms on a scale of 1 to 10 (with “1” being completely ineffective and “10” being maximally effective), which number would you assign it?  Document the specific symptoms of opiate/opioid withdrawal that kratom has most effectively attenuated (e.g. anxiety, dizziness, restlessness, etc.).

Feel free to provide some additional details regarding your kratom usage, such as:  the strains of kratom utilized (e.g. Red Vein Bali), average intake (per dose and per day), frequency of ingestion (e.g. 4 doses, one every 5 hours), cumulative duration of regular administration (e.g. 6 months), and mode of administration (e.g. capsules, tea, powder).  Did you administer kratom as a monotherapy or as an adjunct intervention?  If you administered kratom as an adjunct intervention, how can you be sure that any perceived therapeutic benefit you’re attributing to kratom is not more attributable to co-administered substances?

To help others get a better understanding of your situation, cite the total duration over which you had been using opiates/opioids prior to the initiation of kratom, as well as the significance of your dependence.  If you’ve previously used pharmaceutical medications to manage opiate/opioid withdrawal, how does kratom compare?  Realize that while kratom can be therapeutically useful for many individuals during opiate/opioid withdrawal, it is not yet an evidence-based intervention, and therefore cannot be endorsed by the medical community.

Nonetheless, some individuals choose to avoid the conventional medical system and will continue using kratom regardless of professional advice.  Anyone who uses kratom regularly is encouraged to work with a licensed medical professional and, at the very least, receive regular medical checkups to ensure personal safety.  Though kratom seems promising as an opioid replacement option, further research is needed to ensure that it’s legitimately useful and safe for individuals undergoing opiate/opioid detox.

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