Research Topic

The Pharmacology of Kratom and Its Alkaloids

About this Research Topic

Kratom (Mitragyna speciosa) has gained interest in recent years due to its increased use in Western countries as a natural product consumed for pain relief, mitigation of withdrawal symptoms from opioid and other drug dependences, and for a range of other acute and chronic conditions. Several of its indole alkaloids have been shown to bind to opioid receptors in a unique manner which led to the ban of kratom and its alkaloids in several countries. However, the pharmacology explored to date presents with distinct properties to classical opioids such as morphine. In addition, the leaf exerts stimulant at low and sedative, analgesic effects at high doses which to date is poorly explained. Aside from the primary alkaloid mitragynine, many of the leaf compounds remain pharmacologically unexplored.

The advances in our understanding of kratom pharmacology have been focused on mitragynine and its derivative 7-hydroxymitragynine in recent years. The primary research was centered on the opioid pharmacology, even though mitragynine appears to interact with a range of other receptors as well. Although this is certainly warranted and there is more research desired on the most abundant alkaloid, the leaf material contains a range of other compounds, including at least 38 more indole alkaloids. The differential effects of taking kratom as a natural product compared to taking pure mitragynine have not been compared in human studies but appear to differ in animals. From an observational perspective, it is desirable to investigate other compounds present in kratom leaf that either act in a similar manner to mitragynine or exert novel pharmacological effects that explain the overall reported beneficial and detrimental outcomes reported in surveys and case studies of kratom exposure and use. Both pre-clinical and clinical observational studies can provide answers to the spectrum of pharmacological activity exerted by kratom as well as isolated compounds. In addition, semi-synthetic derivatives can address critical questions related to the biased opioid receptor signaling reported for mitragynine and 7-hydroxymitragynine as well as potentially leading to feasible lead and drug candidate structures for the treatment of pain and substance use disorders.

This Research Topic is centered on the pharmacology of kratom, its currently known compounds, as well as unidentified ingredients that may contribute to its complex pharmacology. Because of a lack of clinical trials, feasible investigations into effects of kratom as a whole or any of its components may also be conducted using other tools such as surveys, case studies, or observational study designs. Submission of Reviews and Original Research articles, as well as Opinion and Perspective papers covering new insights regarding the following are encouraged:

• Novel pharmacological investigations into known or yet unidentified compounds of Mitragyna speciosa. These may relate to the opioid activity but must provide new insights to either the molecular mechanism or the downstream effects mediated by binding to specific receptors.
• Clinical investigations such as observational studies, case reports, and surveys that provide new insights into the effects of kratom on health in humans, i.e. adverse effects/toxicity, neurological effects/altered mental status. These may also relate to uses of kratom for withdrawal from substance dependence or as a mitigation strategy in the prevention of escalating opioid use.
• Potential interactions of kratom or its constituents with other substances and drugs that can be of clinical significance. This includes CYP enzyme interactions, other metabolic enzymes, pharmacokinetic alterations, or alike processes.


Keywords: opioid, SUD, antidepressant, drug interactions, natural product


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Kratom (Mitragyna speciosa) has gained interest in recent years due to its increased use in Western countries as a natural product consumed for pain relief, mitigation of withdrawal symptoms from opioid and other drug dependences, and for a range of other acute and chronic conditions. Several of its indole alkaloids have been shown to bind to opioid receptors in a unique manner which led to the ban of kratom and its alkaloids in several countries. However, the pharmacology explored to date presents with distinct properties to classical opioids such as morphine. In addition, the leaf exerts stimulant at low and sedative, analgesic effects at high doses which to date is poorly explained. Aside from the primary alkaloid mitragynine, many of the leaf compounds remain pharmacologically unexplored.

The advances in our understanding of kratom pharmacology have been focused on mitragynine and its derivative 7-hydroxymitragynine in recent years. The primary research was centered on the opioid pharmacology, even though mitragynine appears to interact with a range of other receptors as well. Although this is certainly warranted and there is more research desired on the most abundant alkaloid, the leaf material contains a range of other compounds, including at least 38 more indole alkaloids. The differential effects of taking kratom as a natural product compared to taking pure mitragynine have not been compared in human studies but appear to differ in animals. From an observational perspective, it is desirable to investigate other compounds present in kratom leaf that either act in a similar manner to mitragynine or exert novel pharmacological effects that explain the overall reported beneficial and detrimental outcomes reported in surveys and case studies of kratom exposure and use. Both pre-clinical and clinical observational studies can provide answers to the spectrum of pharmacological activity exerted by kratom as well as isolated compounds. In addition, semi-synthetic derivatives can address critical questions related to the biased opioid receptor signaling reported for mitragynine and 7-hydroxymitragynine as well as potentially leading to feasible lead and drug candidate structures for the treatment of pain and substance use disorders.

This Research Topic is centered on the pharmacology of kratom, its currently known compounds, as well as unidentified ingredients that may contribute to its complex pharmacology. Because of a lack of clinical trials, feasible investigations into effects of kratom as a whole or any of its components may also be conducted using other tools such as surveys, case studies, or observational study designs. Submission of Reviews and Original Research articles, as well as Opinion and Perspective papers covering new insights regarding the following are encouraged:

• Novel pharmacological investigations into known or yet unidentified compounds of Mitragyna speciosa. These may relate to the opioid activity but must provide new insights to either the molecular mechanism or the downstream effects mediated by binding to specific receptors.
• Clinical investigations such as observational studies, case reports, and surveys that provide new insights into the effects of kratom on health in humans, i.e. adverse effects/toxicity, neurological effects/altered mental status. These may also relate to uses of kratom for withdrawal from substance dependence or as a mitigation strategy in the prevention of escalating opioid use.
• Potential interactions of kratom or its constituents with other substances and drugs that can be of clinical significance. This includes CYP enzyme interactions, other metabolic enzymes, pharmacokinetic alterations, or alike processes.


Keywords: opioid, SUD, antidepressant, drug interactions, natural product


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

24 January 2021 Abstract
24 May 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

24 January 2021 Abstract
24 May 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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