In this article we will look at a case study of a man who used kratom to treat opioid withdrawal. We’ll also explore the scientific evidence behind the mechanisms of major kratom (mitragyna speciosa) alkaloids.

The Deleterious Effects of Opiates

Mu-opioid receptor agonists remain the gold standard in pain therapy, but the therapeutic use of these agents is associated with serious side effects including potentially lethal respiratory depression (Kruegel et al., 2016). Opiates exhibit their addictive properties due to inducing euphoria upon use, and upon cessation causing dysphoria. Chronic opiate use causes structural and functional changes in important brain regions that control impulse, reward and motivation. This combination of the euphoric properties of the drug, and the physical dependence and withdrawal that results from structural changes in the brain creates a recipe for disaster that subsequently leads to addiction (Kolodny et al., 2015).

Kratom Case Report

There is some clinical evidence that kratom withdrawal differs significantly from prescription opioid withdrawal. An addiction case report discusses a patient using kratom for the self-treatment of opiate withdrawal. A finding of the report showed that kratom attenuates severe opioid withdrawal, yet cessation of kratom use itself appears to be associated with only modest abstinence symptoms.

The patient had ceased hydromorphone injection abuse, and managed his chronic pain and withdrawal using kratom. He reported significant pain relief from kratom as well as an improvement in alertness. In addition, he did not experience sedation that often accompanies opioid use. The patient immediately ceased kratom use upon discharge from the hospital. He described a withdrawal period much less intense than that from prescription opioids. (Boyer et al., 2008).

The Bias of Kratom Alkaloids

In Kruegel et al’s article (2016), two novel μ-opioid receptor modulators are introduced. These compounds show promise in inducing analgesia without the severe side effects associated with synthetic opiates. The experiment was done on human embryonic kidney cells that expressed the opioid receptor subtypes.

This study showed that two compounds found in kratom, mitragynine and 7-hydroxymitragynine are functionally selective (biased) human μ-opioid receptor agonists. What this effectively means is that the molecules preferentially activate only certain downstream signaling pathways. This functional selectivity gives the potential to separate the benefits of μ-opioid receptor activation (analgesia) from the negative side effects usually associated with classical opiates.

When agonists bind to the μ-opioid receptor, two mechanisms involved in activation are G-protein signaling and β-arrestin signaling. Mu-opioid receptor agonists that are biased towards G protein signaling over β-arrestin signaling display less respiratory depression, tolerance development, and constipation while remaining potent analgesics. Mitragynine and 7-hydroxymitragynine were found to elicit no β-arrestin binding, even in the presence of G-protein-coupled receptor kinase 2 (GRK2), a known enhancer of β-arrestin signaling. This selectivity for G-protein signaling could explain the reduced respiratory depression of mitragynine in comparison to codeine (Kruegel et al., 2016).

Schematic of G protein biased signaling by mitragyna alkaloids (Kruegel et al., 2016)

Antidepressant Activity

In addition to their MOR (mu-opioid receptor) activity, 7-hydroxymitragynine and mitragynine are KOR ( kappa-opioid receptor) antagonists, a mechanism which has been shown to elicit antidepressant effects in animals. In a rodent model of depression (forced swim test), mitragynine was shown to exhibit antidepressant activity. This provides evidence that mitragyna alkaloids may serve as lead compounds for novel antidepressants. The authors concluded that Mitragyna alkaloids show promise in the potential treatment of mood disorders (Kruegel et al., 2016).


The scientific research behind kratom is promising. More research needs to be done to explore the different effects of all the kratom alkaloids. In time we can get a greater understanding of this miraculous plant and how it works.

Disclaimer: This page is for general information and not to be considered as medical advice. This information is not intended to diagnose, prescribe, treat, or cure any medical condition. Kreed Botanicals and its editors do not provide medical advice. 


  1. Kruegel, A. C., Gassaway, M. M., Kapoor, A., Váradi, A., Majumdar, S., Filizola, M., … & Sames, D. (2016). Synthetic and receptor signaling explorations of the Mitragyna alkaloids: mitragynine as an atypical molecular framework for opioid receptor modulators. Journal of the American Chemical Society, 138(21), 6754-6764.
  2. Kolodny, A., Courtwright, D. T., Hwang, C. S., Kreiner, P., Eadie, J. L., Clark, T. W., & Alexander, G. C. (2015). The prescription opioid and heroin crisis: a public health approach to an epidemic of addiction. Annual review of public health, 36, 559-574.
  3. 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). Addiction103(6), 1048-1050.

Pharmacology Terms

Agonist  An agent that activates (or stabilizes the active state of) a receptor. In this context, opioids are agonists that activate opioid receptors to produce biological effects.

Receptor – A biological molecule whose function is modulated (changed in some way) by chemical combination with the drug. Another term for a drug receptor is “drug target”. 

Antagonist – An agent that interferes with the action of an agonist.

G proteins – Protein family that acts as molecular switches inside cells, and are involved in transmitting signals from extracellular stimuli to the interior of the cell.

Receptor Modulator-A substance that binds to and modulates a receptor, usually as an agonist, antagonist, or combination of both.

β-arrestins –  Multifunctional, versatile adapter proteins that are best known for their ability to desensitize G protein-coupled receptors (GPCRs), but also regulate a diverse array of cellular functions.

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