

Mitragyna speciosa (also known as kratom) is a tropical tree of the coffee family indigenous to South East Asia.[1] The leaves of M. speciosa contain various psychoactive alkaloids that produce mild stimulant and opioid effects.[1] The pharmacology of kratom is complex, although it produces its major effects through action at opioid receptors in the brain.[1]

M. speciosa is indigenous to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea,[2] where it has been used in traditional medicines for centuries. Traditionally, fresh or dried kratom leaves are chewed or made into tea. Starting in the 2000s, kratom began to receive significant attention due to increased use in Western cultures as an alternative medicine. It is readily available for purchase from a large number of internet vendors, most commonly as dried and powdered leaves.[1]

User reports indicate that the effects of kratom vary depending on the dose used. Lower doses are reported to produce a caffeine-like stimulant effect. Higher doses produce opioid effects like pain relief, sedation, and euphoria. Many users claim kratom is useful in treating opioid addiction as a weaning agent, particularly during the initial withdrawal phase. Kratom exists in a variety of strains with different characteristics, some more opioid-like than others.

Kratom’s mood-elevating effects have raised concerns about the plant’s potential for dependence and abuse. In some jurisdictions, its sale and importation have been restricted, and several public health authorities have raised alerts.[3][4] Strong evidence for its claimed benefits are lacking. It is highly advised to use harm reduction practices if using this substance.

Chemistry

The leaves of M. speciosa contain more than 40 compounds,[5] including many indole alkaloids such as mitragynine, mitraphylline, and 7-hydroxymitragynine (which is currently the most likely candidate for the primary active chemical in the plant).[6][7] Other active compounds in M. speciosa include raubasine, rhynchophylline, and corynantheidine, among many others.[8]

The amount of active alkaloids in the leaves highly depends on many factors. One major factor is the location of the tree. When trees are grown in Southeast Asia, the levels tend to be higher but when grown elsewhere (even in greenhouses) the levels tend to be low or non-existent.[9] One analysis of products marketed as kratom leaf found mitragynine at levels of 1–6% and 7-hydroxymitragynine at levels of 0.01–0.04%.[10]

Pharmacology

Kratom behaves as an opioid receptor agonist similar in function to morphine and other opiates, although its pharmacological action and subjective effects differ significantly from those of traditional opiates.[11]

Opioids exert their effects by binding to and activating the opioid receptors. They structurally mimic endogenous endorphins which are naturally found within the body and also work upon the opioid receptor system. The way in which opioids structurally mimic these natural endorphins results in their euphoric, pain-relieving and anxiolytic effects. This is because endorphins are responsible for reducing pain, causing sedation, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or general excitement.

Mitragynine and 7-hydroxymitragynine[12] bind as partial agonists to the μ-opioid receptors and antagonistic to the κ- and δ-opioid receptors. They have high binding affinities to the µ- and κ-receptors. The binding affinity to the δ-receptors is high for 7-hydroxymitragynine, but weak for mitragynine.[13]

Unlike most other opioids, kratom also presents affinity for the norepinephrine and serotonin[14] receptor systems where it functions as an agonist. Its action on norepinephrine and serotonin also likely contributes to kratom's stimulating properties.

Additionally, kratom contains the alkaloid (rhynchophylline, which functions as an NMDA receptor antagonist.[15] This may be responsible for the mild dissociating effects which occur at heavy doses.

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), a literature which relies on collected anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be taken with a healthy amount of skepticism. It is worth noting that these effects will not necessarily occur in a consistent or reliable manner, although higher doses (common+) are more likely to induce the full spectrum of reported effects. Likewise, adverse effects become much more likely with higher doses and may include serious injury or death.

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

Strains

The image above shows the differences in appearance between the leaves of red, green and white vein kratom strains.

Similar to cannabis, there are many different strains of Mitragyna speciosa available from vendors. The strains below have varying degrees of depressant, stimulating, and opioid characteristics. The strains are named and identified after the country/region where the Mitragyna speciosa tree originated as well as the color of the veins of the leaf (red, green, or white).

Below are the general effects and similarities of the various vein colors. Note that the effects vary across all strains and that the effects are dependent on the dose taken. Not all white strains, for example, will produce the same effects and each strain may work differently in one individual than it does on another.

White Vein: Leaves with a white vein are reported to be energetic and stimulating, promoting alertness, motivation, and wakefulness in low to moderate doses.

Leaves with a white vein are reported to be energetic and stimulating, promoting alertness, motivation, and wakefulness in low to moderate doses. Red Vein: Red vein kratom is sedating and relaxing, making it better suited for managing insomnia or pain.

Red vein kratom is sedating and relaxing, making it better suited for managing insomnia or pain. Green Vein: Green vein strains are a mix of both. They are not as stimulating as white vein nor as sedating as red vein.

Consumption and preparation

There are several different ways that kratom is typically ingested:[16]

Traditionally, kratom users in Thailand would commonly chew whole kratom leaves in order to achieve its stimulating and pain-relieving effects while performing manual labor. However, the amount of leaves needed to be chewed to induce optimal effects is quite high. In addition, kratom leaves are very bitter and few users would find this method bearable.

Kratom tea is one popular method of consumption. Powdered or crushed kratom leaves are steeped in hot water to extract the alkaloids. Many users choose to place the leaf matter directly into the water without using a tea bag as it ensures that no alkaloids are wasted. Kratom tea is very bitter, so flavorings like honey, peppermint oil, or lemon juice can be added to mask the bitterness.

Toss and wash is done by placing kratom powder in the back of the mouth, avoiding contact with the taste buds as much as possible, and washing the powder down with a drink. A sweet or acidic drink is typically used to mask the bitter taste of the kratom. Since kratom powder is relatively hydrophobic, it will not always be washed down entirely with the liquid, which can leave a bitter taste and residual kratom powder in the back of the mouth. This can cause coughing or choking if not done correctly, although most people can perform this without any issues.

Mixing with olive oil is a method that some users have found particularly helpful using powdered kratom. Kratom dissolves very easily in olive oil, and the lipids in the oil suppress the bitter taste of the kratom. Due to the fact that this method dissolves the majority of the powder, the chances of accidentally inhaling the powder or having it get stuck in the throat are minimal.

Placing kratom in gelatin capsules is a tested ingestion method for avoiding the bitter and unpleasant taste of kratom. Typically, "00" size gelatin or vegetable capsules are filled with kratom powder. This is normally done using a capsule making machine so that many capsules can be filled at once. This also makes it easier to pack the powder down into the capsules, allowing around 0.5 grams of powder in each capsule. Some users dislike having to swallow a large amount of capsules when dosing, but this is an effective method for users who cannot tolerate kratom's bitter taste.

Extracting kratom is done to reduce the amount of powder one must ingest to feel the effects of kratom. A safe, multisolvent kratom extract recipe can be found at the multisolvent heatless extraction of Kratom tutorial. This extraction reduces the amount of kratom needed to cause the desired effects and can reduce the dosage needed immensely. After drying, the extract can be placed in gelatin capsules on its own or mixed with raw kratom to create a full blend of effects. This is particularly helpful in opiate withdrawal.

Smoking, vaporizing, or insufflating kratom is not seen as a viable means of administration, as the amount of alkaloids needed to produce effects would only be obtained by smoking or snorting an excessive amount of leaf material. In addition, certain kratom alkaloids may be destroyed during the process of combustion.

Potentiation

The effects of kratom can be potentiated using the techniques below.

Antacids - Taking up to four 750mg antacid tablets approximately 30 - 60 minutes before dosing kratom can increase the intensity of its effects. This works because antacids raise the pH level in the stomach, which increases the absorption of kratom. [17]

- Taking up to four 750mg antacid tablets approximately 30 - 60 minutes before dosing kratom can increase the intensity of its effects. This works because antacids raise the pH level in the stomach, which increases the absorption of kratom. Turmeric / Curcumin and Black pepper - A tablespoon or 7 grams of turmeric and a large pinch of black pepper will greatly increase the potency of kratom as well as lengthen its duration if taken approximately 1 hour before ingestion. This works because turmeric functions as an MAOI. Although turmeric is mostly inactive by itself, black pepper increases its bioavailability by 2000% percent. [17]

and - A tablespoon or 7 grams of turmeric and a large pinch of black pepper will greatly increase the potency of kratom as well as lengthen its duration if taken approximately 1 hour before ingestion. This works because turmeric functions as an MAOI. Although turmeric is mostly inactive by itself, black pepper increases its bioavailability by 2000% percent. Grapefruit juice - Drinking a large glass of grapefruit juice approximately 2 hours before ingesting kratom can greatly potentiate its intensity. [17] This works because grapefruit juice functions as a CYP3A4 enzyme inhibitor which results in altered drug metabolism. [18]

- Drinking a large glass of grapefruit juice approximately 2 hours before ingesting kratom can greatly potentiate its intensity. This works because grapefruit juice functions as a CYP3A4 enzyme inhibitor which results in altered drug metabolism. DXM - Taking 30 - 60 mg of DXM approximately 45 - 60 minutes before ingesting kratom is said to potentiate its effects.

- Taking 30 - 60 mg of DXM approximately 45 - 60 minutes before ingesting kratom is said to potentiate its effects. Watercress - Ingesting watercress approximately 45 minutes before kratom is said to potentiate its effects. This works because watercress functions as a cytochrome P450 CYP2E1 enzyme inhibitor which results in altered drug metabolism.[19]

Preparation methods

Preparation methods for this compound within our tutorial index include:

Toxicity and harm potential

Kratom has a low toxicity relative to dose. Like most opioids, safe usage of kratom is not known to cause any dangerous long-term complications. Heavy dosages of kratom can result in increased respiratory depression, leading onto fatal or dangerous levels of anoxia (oxygen deprivation). This is significantly less powerful than the respiratory depression of heroin or morphine. This occurs because the breathing reflex is suppressed by agonism of µ-opioid receptors proportional to the dosage consumed.

It is likely impossible to achieve this using kratom in its standard leaf form as the nausea ceiling makes it difficult to consume high enough dosages without vomiting. A pure extract or tincture, however, may be potent enough to cause lethal respiratory depression at appropriate dosages, although oral administration of pure mitragynine to mice in dosages up to 920 mg/kg did not produce lethal respiratory depression.[20] However, kratom can be fatal when it is combined with other depressants such as alcohol or benzodiazepines.

Side effects associated with chronic kratom use include loss of appetite and weight loss, constipation, decreased libido, apathy, and darkening of the skin color of the face. Chronic use has been associated with bowel obstruction.[21][22]

It is strongly recommended that one use harm reduction practices when using this substance.

Lethal dosage

The lethal dosage of kratom is unknown but thought to be far above the active dosage. The precise dosage likely depends on a variety of factors including strain, potency, tolerance and method of consumption. It is unlikely that one could ingest a lethal dosage of kratom powder as the nausea will force one to vomit at around 8 - 9 grams; however, it could be possible to ingest a lethal dosage of a kratom if purer forms such as a resin or pure alkaloids are used.

Three case reports document deaths involving kratom. Other drugs were used in all cases, and in one, kratom was speculated to possibly be the primary cause of death.[23][24] O-Desmethyltramadol (ODSMT) was present in the latter case, and has been found to be a frequent additive in certain commercial brands of kratom,[25] there were nine cases of death reported in Sweden in 2010 and 2011 relating to use of Krypton, which was kratom mixed with O-Desmethyltramadol.[26]

Dependence and abuse potential

As with other opioids, the kratom produces dependence with chronic use and has a high abuse potential. When dependence has developed, cravings and withdrawal symptoms may occur if a person suddenly stops their usage.[27]

Tolerance to many of the effects of kratom develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Kratom presents cross-tolerance with all other opioids, meaning that after the consumption of kratom all opioids will have a reduced effect.

Dangerous interactions

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The list below includes some known dangerous combinations (although it cannot be guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from TripSit.

Alcohol - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely

- Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely Amphetamines - Stimulants increase respiration rate which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the user and cause respiratory arrest.

- Stimulants increase respiration rate which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the user and cause respiratory arrest. Benzodiazepines - Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position blackouts/memory loss likely.

- Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position blackouts/memory loss likely. Cocaine - Stimulants increase respiration rate, which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.

- Stimulants increase respiration rate, which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest. DXM - Generally considered to be toxic. CNS depression, difficulty breathing, heart issues, and liver toxicity have been observed. Additionally if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.

- Generally considered to be toxic. CNS depression, difficulty breathing, heart issues, and liver toxicity have been observed. Additionally if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects. GHB/GBL - The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position

- The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position Ketamine - Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.

- Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. MAOIs - Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.

- Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases. MXE - MXE can potentiate the effects of opioids but also increases the risk of respiratory depression and organ toxicity.

- MXE can potentiate the effects of opioids but also increases the risk of respiratory depression and organ toxicity. Nitrous - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are common.

- Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are common. PCP - PCP may reduce opioid tolerance, increasing the risk of overdose.

- PCP may reduce opioid tolerance, increasing the risk of overdose. Tramadol - Increased risk of seizures. Tramadol itself is known to induce seizures and it may have additive effects on seizure threshold with other opioids. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present

- Increased risk of seizures. Tramadol itself is known to induce seizures and it may have additive effects on seizure threshold with other opioids. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present Grapefruit - While grapefruit is not psychoactive, it may affect the metabolism of certain opioids. Tramadol, oxycodone, and fentanyl are all primarily metabolized by the enzyme CYP3A4, which is potently inhibited by grapefruit juice[28]. This may cause the drug to take longer to clear from the body. it may increase toxicity with repeated doses. Methadone may also be affected[28]. Codeine and hydrocodone are metabolized by CYP2D6. People who are on medicines that inhibit CYP2D6, or that lack the enzyme due to a genetic mutation will not respond to codeine as it can not be metabolized into its active product: morphine.

Legal status

[29] This map shows the legal status of kratom within each US state. It is currently a controlled substance within Wisconsin, Arkansas, Tennessee, Indiana, Rhode Island, and Vermont.

]

Australia: As of January 2015, kratom is a controlled and prohibited narcotic substance which requires a permit and license to import into the country. [30]

As of January 2015, kratom is a controlled and prohibited narcotic substance which requires a permit and license to import into the country. Canada: As of October 2016, it is illegal to market kratom for any use in which it is ingested. However, kratom may be marketed for other uses, such as incense. [31]

As of October 2016, it is illegal to market kratom for any use in which it is ingested. However, kratom may be marketed for other uses, such as incense. Europe: As of September 2011, kratom, mitragynine, and 7-hydroxymitragynine are controlled substances in a number of EU Member States such as Denmark, Latvia, Lithuania, Poland, Romania and Sweden. [32]

As of September 2011, kratom, mitragynine, and 7-hydroxymitragynine are controlled substances in a number of EU Member States such as Denmark, Latvia, Lithuania, Poland, Romania and Sweden. Germany: Kratom is not a controlled substance under the BtMG. [33] It is legal, as long as it is not sold for human consumption, according to §2 AMG. [34] This legal opinion was approved by court descision of the OLG Köln (Higher Regional Court Cologne), as of September 11, 2015. [35]

Kratom is not a controlled substance under the BtMG. It is legal, as long as it is not sold for human consumption, according to §2 AMG. This legal opinion was approved by court descision of the OLG Köln (Higher Regional Court Cologne), as of September 11, 2015. Latvia: Kratom and its primary active constituent mitragynine are Schedule I controlled substances according to an amendment on August 16th, 2012. [36]

Kratom and its primary active constituent mitragynine are Schedule I controlled substances according to an amendment on August 16th, 2012. Malaysia: The use of kratom leaves is prohibited in Malaysia under Section 30 (3) Poisons Act 1952, and the user may be, penalized with a maximum compound of MYR 10,000 (USD 3,150) or up to 4 years imprisonment. [37]

The use of kratom leaves is prohibited in Malaysia under Section 30 (3) Poisons Act 1952, and the user may be, penalized with a maximum compound of MYR 10,000 (USD 3,150) or up to 4 years imprisonment. New Zealand: Kratom and its primary active constituent mitragynine, after an amendment on August 6, 2015, are Schedule I controlled substances under Medicines Regulations 1984 [38]

Kratom and its primary active constituent mitragynine, after an amendment on August 6, 2015, are Schedule I controlled substances under Medicines Regulations 1984 Switzerland: Mitragynine and 7-Hydroxymitragynine are controlled substances specifically named under Verzeichnis A. [39]

Mitragynine and 7-Hydroxymitragynine are controlled substances specifically named under Verzeichnis A. Thailand: Possession of kratom leaves is illegal in Thailand, despite the tree being native to the country. The Thai government passed the kratom Act 2486 which made planting the tree illegal and requires existing trees to be cut down. As of October 2, 2013, the justice ministry of Thailand suggested removal of kratom from the narcotic drug list relating to Category 5 of the Narcotic Drug Law of 1979, though still recommended regulating kratom in other ways. [40]

Possession of kratom leaves is illegal in Thailand, despite the tree being native to the country. The Thai government passed the kratom Act 2486 which made planting the tree illegal and requires existing trees to be cut down. As of October 2, 2013, the justice ministry of Thailand suggested removal of kratom from the narcotic drug list relating to Category 5 of the Narcotic Drug Law of 1979, though still recommended regulating kratom in other ways. United Kingdom: It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016. [41]

It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016. United States: On August 31, 2016, the DEA issued a statement indicating its intention to place kratom on Schedule I of the U.S. Controlled Substances Act in the temporary scheduling category.[42] This ban would have come into effect on September 30th, 2016, but was withdrawn on October 13th, 2016. A public comment period, which closed on December 1st, 2016. Following the comment period, the DEA will have to issue a new statement of intent to place kratom in Schedule I.[43] While there are states that have pledged to not pursue legislation to ban kratom, many others have passed or have pending legislation to ban kratom. It is currently prohibited in the states of Tennessee, Rhode Island, Vermont, Arkansas, Indiana[44] Iowa,[45] and Wisconsin.

See also

References



