Kratom Guide | Ibogaine For Kratom

Extracts & Alkaloid Medium Lethal Dose (LD50)

In contemporary markets, beyond raw leaf material, kratom is often available in concentrated extracts. These extracts are produced by isolating and concentrating the active alkaloids, primarily mitragynine and 7-hydroxymitragynine (7OH), from the plant material.

Extraction processes can vary, leading to products that are significantly more potent than the raw leaf, often labeled with a “X” factor (e.g., 10x, 25x, 50x), indicating the approximate concentration factor relative to the original leaf material. The higher concentration of alkaloids in extracts means that smaller quantities can produce more pronounced effects, but also carry a significantly higher risk of adverse effects and overdose due to their increased potency and reduced predictability of alkaloid content.

The lethal medium dose (LD50) represents the dose at which 50% of a test population dies. Regarding the LD50 for kratom alkaloids, it is crucial to note that this data is primarily derived from animal studies and in vitro analyses, as direct human LD50 values are unethical to determine.

Mitragynine (MG): In rodent models, the reported oral LD50 for pure mitragynine ranges from approximately 477 mg/kg to 760 mg/kg in mice and rats. Intravenous (IV) LD50 values are considerably lower, demonstrating higher acute toxicity via this route. For instance, an IV LD50 of 29.8 mg/kg has been reported in mice. These figures highlight that while mitragynine has a relatively high therapeutic index in animal models compared to some classical opioids, its toxicity is dose-dependent.
7-Hydroxymitragynine (7-OHMG): Due to its significantly higher potency, the LD50 for 7-hydroxymitragynine is expected to be substantially lower than that of mitragynine. However, precise standalone LD50 data for 7-OHMG is less commonly cited in the literature compared to MG, often being studied in the context of its synergistic or additive effects with other alkaloids. Its greater affinity for the mu-opioid receptor suggests a higher potential for dose-dependent adverse effects, including respiratory depression, which is the primary cause of opioid-related fatalities.

It is vital to emphasize that these animal LD50 values do not directly translate to humans. Human toxicity and potential lethality are influenced by numerous factors including individual variability (metabolism, body weight, pre-existing conditions), co-ingestion of other substances (especially central nervous system depressants), and the purity and concentration of the product. The risk of adverse events, including respiratory depression, increases significantly with higher doses, particularly with concentrated extracts, and when kratom is combined with other substances like alcohol, benzodiazepines, or other opioids.

What to take into consideration before using Kratom:

1. Your Motivation and Expectations:

Why are you considering Kratom? Are you seeking pain relief, increased energy, mood enhancement, or an alternative for opioid withdrawal?
How did you hear about it? Information sources vary widely in their scientific accuracy and objectivity.
What do you find appealing about it? Understanding your attraction to Kratom can help you consider alternative, evidence-based options.

2. Lack of Regulation and Scientific Evidence:

Not FDA Approved: In the United States, Kratom is not an FDA-approved medication for any medical use. This means its safety, effectiveness, and consistency of product quality are not guaranteed.
Varying Potency: The amount of active compounds (mitragynine and 7-hydroxymitragynine) in Kratom leaves and products can vary significantly. This makes it difficult to predict the effects of a given dose.
Contaminants: Unregulated Kratom products may contain contaminants like heavy metals or harmful bacteria (e.g., Salmonella). Some products have even been found to contain other drugs, like tramadol.

3. Potential Side Effects and Risks:

Common Side Effects: Nausea, vomiting, constipation, dry mouth, increased urination, sweating, itching, decreased appetite, and drowsiness.
Serious Side Effects (especially with high doses or long-term use): Liver damage, seizures, confusion, hallucinations, delusions, high blood pressure, rapid heartbeat, and respiratory depression.
Addiction and Withdrawal: Kratom can be addictive and lead to physical dependence. Withdrawal symptoms, similar to those of opioids, can occur when use is stopped, including muscle pain, insomnia, irritability, and diarrhea.
Drug Interactions: Kratom can interact with other medications, potentially leading to serious adverse effects, including liver problems and death.
Pregnancy and Breastfeeding: It is considered unsafe during pregnancy, as babies exposed to Kratom may experience withdrawal symptoms. There’s insufficient information about its safety during breastfeeding.
Underlying Health Conditions: Individuals with alcohol use disorder, epilepsy, heart conditions, or mental disorders may be at increased risk of adverse effects.

Legal Status &
Research Landscape

The legal status of kratom varies significantly across countries and even within regions of the same country, as is the obvious case of the United States, reflecting an ongoing debate about its safety, efficacy, and potential for abuse. Regulatory bodies worldwide are grappling with how to classify and regulate kratom, often leading to bans in some areas while remaining unregulated or lightly regulated in others.

Scientific research into Mitragyna speciosa is expanding rapidly. Studies are exploring its potential therapeutic applications, particularly for pain management and opioid withdrawal, as well as investigating its toxicity, abuse potential, and long-term effects. The complex pharmacology of kratom, with its multiple alkaloids interacting with various receptor systems, presents both challenges and opportunities for future pharmacological development.

However, they truly only present challenges for those struggling with problematic Kratom use. In paticular, at Ibogaquest, we have noticed that this quality of kratom makes it harder to quit than some of the toughest opiates we have treated for. It is because of this that we developed a unique detox protocol.

Learn About Our Program

Mitragyna Speciosa:
A Concise Botanical
and Pharmacological Overview

Kratom, derived from the leaves of Mitragyna speciosa, is a tropical evergreen tree indigenous to Southeast Asian countries including Thailand, Malaysia, Indonesia, and Papua New Guinea. Belonging to the Rubiaceae family, which also encompasses the coffee plant (Coffea arabica), kratom has been traditionally utilized for centuries by indigenous populations for its various reported effects.

However, as with many plants, it has suffered rapid industrialization over the past decade. This has led to a modern usage of the word kratom and it now means a lot of different things, from teas, to pills to gummies, other edibles and concentrated extracts like power drinks and shots.

Traditional Context and Ethnobotany

The historical use of Mitragyna speciosa is deeply embedded in the cultural and economic practices of its native regions. For centuries, traditional laborers, particularly farmers, fishermen, and manual workers, have consumed kratom leaves to mitigate fatigue and enhance stamina during long, arduous workdays under challenging climatic conditions. This application often involved chewing fresh leaves, sometimes with salt to facilitate absorption, or brewing them into a tea. The stimulant-like effects at lower doses were highly valued for improving productivity and endurance.

Beyond its role as a work aid, kratom also held significance in traditional medicine. Indigenous practitioners utilized it for a spectrum of therapeutic purposes. These included:

Pain management: Its analgesic properties were leveraged to alleviate chronic pain conditions.
Fever reduction: Used as a traditional antipyretic.
Cough suppression: Employed as a remedy for respiratory ailments.
Diarrhea treatment: Its constipating effects were utilized to manage gastrointestinal distress.
Opioid withdrawal management: Perhaps one of its most notable traditional uses was to alleviate the symptoms of opioid withdrawal and to help individuals reduce their reliance on opium, serving as a substitute during the historical prevalence of opium use in the region. The strongest evidence of kratom’s success in treating opium dependence is it’s first recorded prohibition. The government in Thailand prohibited its use in 1943 because it was affecting its monopoly on the opium trade which it regulated and taxed.
Mood enhancement and anxiolysis: In social settings or for personal well-being, it was also consumed for its purported mood-elevating and anxiety-reducing effects.

The method of preparation often depended on the desired outcome; for instance, dried leaves might be crushed and mixed with food, or brewed as a decoction. The traditional knowledge surrounding kratom’s preparation, dosage, and application was passed down through generations, reflecting a nuanced understanding of its effects within the context of local health practices

Phytochemistry: The Alkaloid Spectrum

The primary compounds responsible for kratom’s effects are a diverse class of indole alkaloids. Over 40 different alkaloids have been identified in Mitragyna speciosa, with the most abundant and pharmacologically significant being mitragynine (MG) and 7-hydroxymitragynine (7-OHMG).

Mitragynine (MG): This is the most prevalent alkaloid, typically constituting 60-70% of the total alkaloid content in the leaves. MG acts as a partial agonist at mu-opioid receptors, albeit with a distinct binding profile and downstream signaling compared to classical opioid agonists like morphine. It also interacts with other receptor systems, including alpha-2 adrenergic receptors and serotonin 5-HT2A receptors, contributing to its complex pharmacological effects. MG’s binding affinity for the mu-opioid receptor is lower than that of morphine, but its unique signaling properties are a subject of ongoing research.
7-Hydroxymitragynine (7-OHMG): Although present in much smaller quantities (typically less than 2% of total alkaloids), 7-OHMG is considered significantly more potent than mitragynine, with a higher binding affinity for the mu-opioid receptor. It is believed to be a major contributor to the analgesic and opioid-like effects observed, particularly at higher doses. It’s also a metabolite of mitragynine, formed through cytochrome P450 enzymes in the liver.

Other notable alkaloids present in varying concentrations include paynantheine, speciogynine, and mitraphylline, each potentially contributing to the plant’s overall effects through diverse mechanisms, including interactions with serotonin, dopamine, and adrenergic systems.

Pharmacological Mechanisms and Effects

Unlike traditional opioids that primarily activate the G-protein coupled signaling pathway, leading to analgesia but also respiratory depression and constipation, mitragynine exhibits biased agonism.

The interaction of kratom’s alkaloids, particularly mitragynine and 7-hydroxymitragynine (7OH, or simply OH), with opioid receptors is central to its reported effects. Unlike traditional opioids that primarily activate the G-protein coupled signaling pathway, leading to analgesia but also respiratory depression and constipation, mitragynine exhibits biased agonism. This means it preferentially activates certain intracellular signaling pathways (e.g., β-arrestin-2 recruitment is reduced compared to morphine), which may theoretically lead to a more favorable side effect profile, though this area requires further elucidation.

At lower doses (typically 1-5 grams of dried leaf), users report stimulant-like effects, including increased energy, alertness, and sociability. This is often attributed to the interaction with alpha-2 adrenergic receptors and indirect modulation of monoamine neurotransmitters.

At higher doses (typically 5-15 grams), the effects shift towards more opioid-like properties, including analgesia, sedation, and anxiolysis. This is primarily mediated by increased activation of mu-opioid receptors by mitragynine and especially 7-hydroxymitragynine.

The nature of kratom addiction presents a unique challenge. Its onset is often described as a "slow burn," characterized by discrete and subtle progression, which can lead individuals to become deeply dependent before fully recognizing the severity of their condition. Despite common perceptions that it may be less harmful than other substances, kratom can lead to significant psychological and physiological dependence. This often leaves individuals grappling with severe withdrawal symptoms and a profound need for effective interventions.