|Summary sheet: Kratom|
|Common names||Mitragyna speciosa, กระท่อม (Thai), ketum, kratom or kratum|
|Chemical class||Mitragynine / Indole alkaloids|
|Routes of Administration|
Mitragyna speciosa (also known as kratom) is a tropical tree of the coffee family indigenous to South East Asia. The leaves of M. speciosa contain various psychoactive alkaloids that produce mild stimulant and opioid effects. The pharmacology of kratom is complex, although it produces its major effects through action at opioid receptors in the brain.
M. speciosa is indigenous to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea, 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.
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. Strong evidence for its claimed benefits are lacking. It is highly advised to use harm reduction practices if using this substance.
- 1 Chemistry
- 2 Pharmacology
- 3 Subjective effects
- 4 Strains
- 5 Consumption and preparation
- 6 Toxicity and harm potential
- 7 Legal status
- 8 See also
- 9 External links
- 10 References
The leaves of M. speciosa contain more than 40 compounds, 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). Other active compounds in M. speciosa include raubasine, rhynchophylline, and corynantheidine, among many others.
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. 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%.
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.
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 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.
Unlike most other opioids, kratom also presents affinity for the κ-opioid, norepinephrine and serotonin 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 alkaloids (rhynchophylline and mitraphylline) which function as NMDA receptor antagonists. This may be responsible for the mild dissociating effects which occur at heavy doses.
The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.
- Stimulation & Sedation - Kratom can act as both a stimulant and a sedative depending on the strain and dos. The sedating and stimulating effects may occur simultaneously in a contradictory manner resulting in the sensation that one is both energized and relaxed. These may also occur at different times during the experience; a person may feel stimulated during the come up and sedated during the come down. Kratom is considerably more stimulating than that of traditional opioids including oxycodone, heroin, and codeine.
- Physical euphoria - Kratom reliably produces physical euphoria at higher doses. However, this euphoria is not as intense as the euphoria of opioids like heroin, or oxycodone. The sensation itself can be described as extreme feelings of intense physical comfort, warmth, love and contentment.
- Pain relief - Kratom can produce pronounced pain relief, with some users reporting that high doses of kratom produce analgesic effects equivalent to over 20 mg of hydrocodone (commonly known as "Vicodin").
- Cough suppression
- Nausea - If the dose is even slightly too high, one may feel quite ill and the nausea can last upwards of two days at the worst. For this reason, a light and healthy diet is recommended in the days prior to consuming higher doses of kratom.
- Increased perspiration
- Stomach cramps
- Appetite suppression
- Body odor alteration - Kratom can cause one's urine to acquire a very distinct and unpleasant odor for a subset of users.
- Decreased libido
- Difficulty urinating
- Orgasm suppression
- Pupil constriction
- Visual disconnection - A sense of subtle disconnection from visual input is often experienced with high doses of kratom. This is similar to a low-level version of the same effect universally experienced with dissociatives and may well be a result of NMDA antagonist properties of kratom's active metabolites.
The cognitive effects of kratom can be broken down into several components which progressively intensify proportional to dosage.
The most prominent of these cognitive effects generally include:
- Anxiety suppression
- Cognitive euphoria - In comparison to other opioids, kratom can be considered as less intense in its cognitive euphoria when compared with that of morphine or heroin.
- Dream potentiation
- Increased music appreciation
- Focus enhancement - Focus enhancement occurs at lower doses and disappears as the dose is increased and the sedative and euphoric effects take over.
- Motivation enhancement
- Sleepiness - Certain strains of kratom are noted to sometimes make users very tired. In high dosages this can get to the point where the user may be drifting in and out of consciousness or even experience what is called "nodding".
- Thought acceleration
The visual effects of kratom are pronounced compared to other opioids of its class. They can be broken down into several components which progressively intensify proportional to dosage.
- Internal hallucination - The internal hallucinations of kratom can be described as more solid than psychedelics and do not seem to be composed of visual geometry. They typically manifest themselves through hypnagogic scenarios. They are most common with high doses and can be comprehensively described in their variations as lucid in believability, fixed in style, autonomous in controllability, and equal in new experiences and memory replays in content.
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
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.
- Red Vein: 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:
- 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.
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.
- 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.
- Grapefruit juice - 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.
- 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.
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. 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.
It is strongly recommended that one use harm reduction practices when using this substance.
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. O-Desmethyltramadol (ODSMT) was present in the latter case, and has been found to be a frequent additive in certain commercial brands of kratom, 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.
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.
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.
- Depressants (1,4-Butanediol, 2M2B, barbiturates, benzodiazepines, GHB/GBL, methaqualone, and opioids) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation, sedation, respiratory depression and amnesic effects caused by one another and can lead to an unexpected loss of consciousness at high doses. There is also an increased risk of suffocating one one's vomit while unconscious. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
- Stimulants - Combining kratom and stimulants may result in unpleasant symptoms such as an abnormal heartbeat, increased perspiration, agitation, and anxiety. Kratom combined with stimulants may also result in more serious effects such as increased blood pressure, and a lowered seizure threshold.
- Australia: 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.
- 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.
- Latvia: 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.
- 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
- 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.
- 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.
- 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. 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. It is currently prohibited in the states of Tennessee, Vermont, Arkansas, Indiana Iowa, and Wisconsin.
- Kruegel, A.C., Grundmann, O., The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse, Neuropharmacology (2017), https://doi.org/10.1016/j.neuropharm.2017.08.026.
- Rech, MA; Donahey, E; Cappiello Dziedzic, JM; Oh, L; Greenhalgh, E (February 2015). "New drugs of abuse". Pharmacotherapy. 35 (2): 189–97. https://doi.org/10.1002/phar.1522. PMID 25471045.
- Gottlieb, Scott (6 February 2018). "Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency's scientific evidence on the presence of opioid compounds in kratom, underscoring its potential for abuse". US Food and Drug Administration. Retrieved 6 February 2018.
- "DEA Announces Intent to Schedule Kratom: SE Asian drug is imminent hazard to public safety". US Drug Enforcement Administration. 30 August 2016. Archived from the original on 15 September 2016. Retrieved 31 August 2016.
- Mitragyna species, a psychoactive tree from Southeast Asia with opioid activity (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/21050173
- The neuromuscular blockade produced by pure alkaloid, mitragynine and methanol extract of kratom leaves (Mitragyna speciosa Korth (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0378874110002102
- Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/23212430
- Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/11960505
- Herbal medicines for the management of opioid addiction: safe and effective alternatives to conventional pharmacotherapy? (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/22133323
- Kikura-Hanajiri, Ruri; Kawamura, Maiko; Maruyama, Takuro; Kitajima, Mariko; Takayama, Hiromitsu; Goda, Yukihiro (July 2009). "Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant "kratom" (Mitragyna speciosa) by LC-ESI-MS". Forensic Toxicology. 27 (2): 67–74. doi:10.1007/s11419-009-0070-5. ISSN 1860-8973.
- Herbal medicines for the management of opioid addiction: safe and effective alternatives to conventional pharmacotherapy? (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/22133323
- 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. https://dx.doi.org/10.1021/jacs.6b00360
- Partial agonistic effect of 9-hydroxycorynantheidine on μ-opioid receptor in the guinea-pig ileum | www.sciencedirect.com/science/article/pii/S0024320505010659 / http://sci-hub.cc/10.1016/j.lfs.2005.09.030
- Central antinociceptive effects of mitragynine in mice: contribution of descending noradrenergic and serotonergic systems (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8982722 / http://sci-hub.cc/10.1016/S0014-2999(96)00714-5
- Mitragyna alkaloids: the structure of stipulatine (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0040403901907464
- How To Make Kratom Stronger: Kratom Potentiators | http://www.politiquessociales.net/how-to-make-kratom-stronger-kratom-potentiators/
- Grapefruit juice–drug interactions (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1873672/
- Inhibition of chlorzoxazone metabolism, a clinical probe for CYP2E1, by a single ingestion of watercress (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/9728894
- Kratom and Other Mitragynines: The Chemistry and Pharmacology of Opioids from a Non-Opium Source (first search result) - https://books.google.fr/books?hl=en&lr=&id=BtPMBQAAQBAJ&oi=fnd&pg=PA195&dq=mitragynine+respiratory&ots=JbvmS24yEo&sig=tW0crj7Jqhj-4S9JOFCpwxN25nY#v=snippet&q=respiratory&f=false
- Mitragyna speciosa, a psychoactive tree from Southeast Asia with opioid activity (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/21050173
- From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/23206666
- A drug fatality involving Kratom (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/23082895
- A drug toxicity death involving propylhexedrine and mitragynine (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/21219704
- Unintentional fatal intoxications with mitragynine and O-desmethyl tramadol from the herbal blend Krypton (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/21513619
- Rosenbaum CD, Carreiro SP, Babu KM (2012). "Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines". Journal of Medical Toxicology. 8 (1): 15–32. doi:10.1007/s13181-011-0202-2. PMC . PMID 22271566.
- Here Today, Gone Tomorrow…and Back Again? A Review of Herbal Marijuana Alternatives (K2, Spice), Synthetic Cathinones (Bath Salts), Kratom, Salvia divinorum, Methoxetamine, and Piperazines (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550220/
- Kratom Legality Map | http://speciosa.org/kratom-legality-map/
- List of Prohibited Substances in Australia | https://www.odc.gov.au/ws-lps-index?search_api_views_fulltext=Mitragyna+speciosa&items_per_page=10
- Noteikumi par Latvijā kontrolējamajām narkotiskajām vielām, psihotropajām vielām un prekursoriem (I saraksts) | http://likumi.lv/doc.php?id=121086
- "Utusan Malaysia: Pinda akta daun ketum kepada Akta Dadah Berbahaya | http://translate.google.com/translate?hl=en&sl=auto&tl=en&prev=_dd&u=http%3A%2F%2Fwww.utusan.com.my%2Futusan%2FParlimen%2F20121213%2Fpa_02%2FPinda-akta-daun-ketum-kepada-Akta-Dadah-Berbahaya
- Medicines Regulations 1984 | Items 1231 & 1232 | http://www.legislation.govt.nz/regulation/public/1984/0143/latest/DLM96863.html
- Kratom in Thailand: Decriminalization and Community Control? | http://www.tni.org/sites/www.tni.org/files/download/kratom-briefing-dlr13.pdf
- Psychoactive Substances Act 2016 (Legislation.gov.uk) | http://www.legislation.gov.uk/ukpga/2016/2/contents/enacted
- Schedules of Controlled Substances: Temporary Placement of Mitragynine and 7-Hydroxymitragynine into Schedule I (Drug Enforcement Agency) | https://s3.amazonaws.com/public-inspection.federalregister.gov/2016-20803.pdf
- Bill Text: IN HB1196 | 2012 | Regular Session | Enrolled | http://legiscan.com/IN/text/HB1196/id/603106
- Bill Text: LA SB130 | 2012 | Regular Session | Chaptered | http://legiscan.com/LA/text/SB130/id/651753