Alkaloids in Kratom

Kratom, scientifically known as Mitragyna speciosa, is a tropical tree native to Southeast Asia. One of the most significant elements contributing to its unique biological effects is the presence of alkaloids, particularly Mitragynine. Constituting around 60 percent of the alkaloid content in a typical kratom leaf, Mitragynine interacts with an individual's mu opioid receptors, thereby stimulating an array of responses in the human body.

Mitragyna speciosa's complexity extends beyond the mere presence of Mitragynine. The plant encompasses a variety of other alkaloids that jointly contribute to kratom's multifaceted effects. These alkaloids interact synergistically, affecting different receptors in the body and often intensifying, negating, or modulating each other's outcomes. This interplay of compounds crafts the unique experience for each kratom user, making it valuable not only as a source of traditional medicine but also an area of ongoing scientific curiosity.

 

What are kratom alkaloids?

Kratom alkaloids are naturally occurring compounds found in the plant Mitragyna speciosa, best known for their opiate-like effects, which offer potential therapeutic benefits, especially in pain management. They exhibit agonistic activities, primarily at the μ-opioid receptor, which is responsible for the pain-relieving properties of many prescribed painkillers. The majority of these alkaloids serve as agonists for these receptors, producing similar activity to reduce pain sensation.

However, the complex chemical makeup of kratom alkaloids has other effects as well, some of which can contribute to the range of potential adverse effects and risks associated with kratom use. Despite such adverse outcomes, it's the unique blend of upwards of 40 individual alkaloids within each leaf that contributes to the diverse array of effects associated with kratom consumption, from its known analgesic effects to mood enhancement, anxiety reduction, and more. The simultaneous activation and inhibition of various neural pathways by these alkaloids make kratom a subject of great medical and ethnobotanical interest.

What makes up the chemical composition of kratom alkaloids?

Kratom leaves are naturally rich in compounds known as alkaloids, which are responsible for the plant's distinctive effects. Central to the chemical composition of these kratom alkaloids are two primary substances: mitragynine and 7-hydroxymitragynine. Combined, these compounds make up about sixty-six percent of the total alkaloid content found in a single leaf. They are partial agonists at the mu-opioid receptor, a type of opioid receptor in the human nervous system, and show a certain level of opioid activity.

Furthermore, these alkaloids demonstrated varied interactions at other opioid receptors. The intricate activities of mitragynine and 7-hydroxymitragynine are not restricted purely to opioid agonism but rather span to antagonism at the kappa- and delta-opioid receptors. This unique combination of receptor interactions and binding profiles sets kratom alkaloids apart from traditional opioids and other psychoactive plants. The complexities of these chemicals and their interactions with the human body drive the ongoing scientific interest and the potential applicability of kratom in medical scenarios.

Where is the natural source of kratom alkaloids found?

Kratom alkaloids originate from a tropical tree native to Southeast Asia known as Mitragyna speciosa, often abbreviated as M. speciosa. The tree is recognized for its broad, oval-shaped leaves, which when harvested, are used to extract the potent alkaloids. These alkaloids, primarily mitragynine and 7-hydroxymitragynine, are largely credited with the plant’s analgesic effects, making it frequently utilized in the treatment of pain, especially chronic pain.

In recent years, the popularity of M. speciosa, mainly in the form of dietary supplements, has extended beyond its native region, reaching Western countries. Here, it's largely sold in head shops, online platforms, and natural food stores. Users often grind and brew the leaves, much similar to traditional tea preparation. While it's hailed for its therapeutic effects, it's drawn a fair share of controversy with its use and safety profile. Since it occupies a grey area of legality in various jurisdictions, kratom's accessibility may fluctuate, posing challenges for individuals who rely on it as a natural alternative for pain relief.

How do kratom alkaloids affect the body biologically?

Kratom extracts are composed of over 40 individual alkaloids, each with their unique impact on the human body's biological structure. This is due largely to their complex molecular make-up, which lends to the myriad of effects experienced by consumers. According to a journal titled 'Medicinal Chemistry', their potency is primarily attributed to the two primary alkaloids – mitragynine and 7-hydroxymitragynine – amid the chemical structure. These compounds interact with the body's opioid receptors in the brain to elicit responses such as pain reliefs, among others.

In a study by Kruegel et al., the analgesic activity of kratom alkaloids was closely examined, offering critical insights into these naturally occurring compounds. The research discovered that kratom alkaloids function as partial agonists on mu-receptors and competitive antagonists on delta-receptors in the body. This interaction with the central nervous system often results in users experiencing mild euphoria, enhanced mood, and reduced anxiety symptoms. However, the effects can widely differ based on factors such as user's physiology, dosage, and the specific strain of the Kratom in use.

What are the pharmacological properties associated with kratom alkaloids?

Research conducted by McCurdy and his team have indicated that kratom alkaloids, specifically 'Mitragynine pseudoindoxyl', mimic the pharmacological effects of opium, making it an attractive natural substitute for opium. A popular strain of kratom, 'Maeng Da', is particularly high in this alkaloid, making it sought after for both its potency and therapeutic effects. The opiate-like effects are due to the alkaloid’s ability to bind with opioid receptors in the brain, thereby reducing the perception of pain.

Aside from these pain-relieving properties, a comprehensive study by Kruegel et al. showed that these natural products also carry a host of other pharmacological benefits. Particularly, they found that kratom alkaloids can act as powerful antioxidants, anti-inflammatory agents and even help to regulate mood and enhance focus. This versatility of kratom alkaloids is contributing to its growing popularity among researchers and health-conscious consumers alike. However, no matter its potential benefits, it is crucial to use these substances responsibly to mitigate potential risks and complications.

What methods are used for extracting kratom alkaloids?

The extraction of alkaloids from kratom entails complex procedures incorporating certain specific variables, such as flow rate, to manipulate the precise yield composition. Multiple scientific studies have demarcated various approaches to this end. Obeng et al., for instance, utilized an acid-base extraction technique which included a combination of methanol and chloroform, maintaining a delicate balance between flow rate and solvent composition to achieve optimal results.

On the other hand, reports by Matsumoto et al. demonstrated an alternative extraction protocol involving ultra-sonication, pointing to the versatility of methodologies available for alkaloid extraction from kratom. Hassan et al., following a different path, implemented purification via column chromatography resulting in an isolated and concentrated alkaloid sample. Meanwhile, Hanapi et al. focused on the application of a simple soaking process in relating to commercial kratom products. The variance in methodologies reflects the wide scientific interest in kratom alkaloids and the potential benefits they may hold.

Is there psychoactive potential in kratom alkaloids?

Kratom alkaloids, specifically mitragynine congeners, have been studied extensively for their varying effects on the human nervous system. Noted pharmacologist Christopher R. McCurdy has observed the potential for psychoactive interactions within the brain's chemistry, particularly involving the serotonin and adrenergic receptors. Evidence from studies led by McCurdy suggests that these alkaloids may have an affinity for these receptors, leading to possible psychoactive outcomes.

In their natural form, kratom alkaloids are derived from the Mitragyna Speciosa Korth, a tree native to Southeast Asia. The relationship between this tree's chemistry and the human body is complex and intricately linked. The psychotropic potential of kratom alkaloids lies in their ability to stimulate serotonin and adrenergic receptors in the brain, offering the potential to alter mood and cognition. As research continues, stronger correlations may be discovered further solidifying the psychoactive potential of kratom alkaloids.

What are the medicinal uses of kratom alkaloids?

Kratom alkaloids have been under the lens of medical research for quite some time for their therapeutic potential. Scholars like McCurdy CR and Abhisheak Sharma have highlighted in their works, the use of Mitragyna speciosa (commonly known as kratom) for its possible analgesic properties. A study published in the Journal of Natural underlines the traditional consumption of kratom as a mild stimulant by the natives of Southeast Asia. However, it's the alkaloids present in them that provide the soothing and numbing effect, alleviating various types of pain conditions.

In another study, Kruegel and Flores-Bocanegra explained their findings regarding the opioid-like effects of kratom alkaloids. This characteristic feature makes them an area of interest for researchers exploring alternatives to conventional opioid drugs, focusing on the reduction of dependency and adverse effects. An article in J. Ethnopharmacol, showcases the promising results of kratom alkaloids in reducing withdrawal symptoms in opioid-dependent individuals. Yet, much investigation is needed to thoroughly understand these compounds' safety, potency and overall impact on human health.

What potential risks are associated with kratom alkaloids?

While kratom alkaloids have been lauded for their varied biological effects, they're not without potential downsides. One aspect that has drawn significant concern is the possibility of addiction. Regular usage of kratom alkaloids can lead to physical dependence over time. The compounds interact with opioid receptors in the brain, producing a sense of euphoria similar to opioid drugs. This may encourage repeated use and could spiral into addiction, with users experiencing withdrawal symptoms upon discontinuation.

Another risk associated with kratom alkaloids lies in their psychoactive properties. Excessive consumption can lead to a range of psychiatric disorders, including psychosis, mood swings, and hallucinations. There's also the risk of physical side effects, such as nausea, constipation, and liver damage. Furthermore, as kratom products are not regulated by the FDA, the risk of contamination or ingestion of harmful substances increases. Therefore, it's crucial to understand these potential risks before deciding to use kratom alkaloids for their potential benefits.

Sources

Ramanathan, S., et al. (2021). "Kratom Alkaloids: Interactions With Enzymes, Receptors, and Cellular Barriers." Retrieved from: https://www.frontiersin.org/articles/10.3389/fphar.2021.751656/full

Prozialeck, W. C., et al. (2020). "Kratom—Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review."Retrieved from: https://pubmed.ncbi.nlm.nih.gov/31994019/

Hemby, S. E., et al. (2018). "Alkaloid Profiles and Activity in Different Mitragyna speciosa Strains." Retrieved from: https://www.researchgate.net/publication/344962803_Alkaloid_Profiles_and_Activity_in_Different_Mitragyna_speciosa_Strains

Avery, B. A., et al. (2020). "Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions." Retrieved from: https://www.researchgate.net/publication/344962803_Alkaloid_Profiles_and_Activity_in_Different_Mitragyna_speciosa_Strains

Christopher R. McCurdy, Abhisheak Sharma, Kirsten E. Smith, Charles A. Veltri, Stephanie T. Weiss, Charles M. White, Oliver Grundmann. (2024) "An update on the clinical pharmacology of kratom: uses, abuse potential, and future considerations" Retrieved from: https://www.tandfonline.com/doi/full/10.1080/17512433.2024.2305798?src=