Glossary

Also2-percent cap, alkaloid cap

The 2% cap is a common regulatory threshold in state kratom laws, prohibiting retail products where 7-hydroxymitragynine exceeds 2% of total alkaloid content. It was first adopted by Utah in 2019 and now appears in the Kratom Consumer Protection Act versions passed in Arizona, Colorado, Texas, and others. Oklahoma uses a stricter 1% cap; independent audits have found shelf products at 80-96% 7-OH, far above any cap.

/SEV-en hy-DROX-ee my-truh-JY-neen/·Also7-OH, 7-hydroxy, 7-HMG, seven-oh

7-Hydroxymitragynine is an indole alkaloid produced in small quantities in the leaves of Mitragyna speciosa and generated via oxidation of mitragynine. It acts as a partial agonist at the μ-opioid receptor and is roughly 46 times more potent than mitragynine and 13 times more potent than morphine at that receptor. Natural leaf contains approximately 0.01-2% 7-OH by alkaloid mass; concentrated and semi-synthetic preparations raise that fraction dramatically.

An agonist is a molecule that binds to a receptor and activates it, producing a biological response. A full agonist produces the maximum possible response at the receptor; a partial agonist produces a sub-maximal response even at full occupancy. 7-hydroxymitragynine and mitragynine are both partial agonists at the μ-opioid receptor, while morphine is a full agonist.

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An alkaloid is a nitrogen-containing organic compound produced by plants, fungi, and other organisms, often with marked pharmacological activity in humans. Examples include morphine, caffeine, nicotine, and the kratom alkaloids mitragynine and 7-hydroxymitragynine. Kratom leaves contain more than 40 identified alkaloids.

AlsoAKA

The American Kratom Association is a consumer advocacy nonprofit that lobbies against kratom prohibition and promotes the Kratom Consumer Protection Act model legislation. AKA maintains a Good Manufacturing Practice (GMP) standards program and publishes position statements on 7-hydroxymitragynine regulation, generally supporting caps on concentrated 7-OH while opposing outright kratom bans.

An antagonist is a molecule that binds to a receptor and blocks activation by agonists, without producing a biological response itself. Naloxone is a μ-opioid receptor antagonist and will reverse the effects of 7-hydroxymitragynine at that receptor. Antagonists are the basis of opioid overdose reversal protocols.

Alsofunctional selectivity

Biased agonism is a mechanism where a drug preferentially activates some signaling pathways downstream of a receptor while avoiding others. At the μ-opioid receptor, G-protein-biased agonists can produce analgesia with reduced β-arrestin signaling, which is associated with respiratory depression. Mitragynine and some 7-OH analogs have been studied as G-protein-biased agonists, a property the kratom industry cites as a safety argument.

Bioavailability is the fraction of an administered dose of a compound that reaches systemic circulation in active form. Oral bioavailability of 7-hydroxymitragynine is limited by first-pass hepatic metabolism; sublingual, rectal, and injected routes bypass that metabolism and raise effective dose. Product form therefore matters: shots and chewables generally produce faster onset and higher peak blood levels than swallowed tablets.

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Buprenorphine is a synthetic partial agonist at the μ-opioid receptor, used medically for chronic pain and for opioid use disorder (under brand names Suboxone, Subutex, Sublocade). Pharmacologically, 7-hydroxymitragynine and buprenorphine share the partial-agonist mechanism and a ceiling effect on respiratory depression; clinically, buprenorphine is regulated as a Schedule III controlled substance while 7-OH status varies by state.

AlsoC&D

A cease-and-desist order is an administrative directive from a government authority ordering a person or business to stop a specified activity, on pain of further enforcement. State attorneys general in Alabama, California, Louisiana, and others have issued statewide cease-and-desist orders against retailers selling kratom or 7-OH products. A C&D is not a court ruling but typically precedes litigation or seizure.

A ceiling effect describes the plateau in a drug's response beyond which additional dose does not proportionally increase effect. Partial agonists at the μ-opioid receptor, including 7-hydroxymitragynine and buprenorphine, exhibit a ceiling on both analgesia and respiratory depression. The ceiling reduces but does not eliminate overdose risk, especially when combined with other CNS depressants.

AlsoCOA

A Certificate of Analysis is a document issued by an independent laboratory reporting the quantified results of testing a product batch. For 7-OH products, a reputable COA reports mitragynine and 7-hydroxymitragynine content by weight, heavy metals, microbial load, and residual solvents. Consumers should verify COAs come from accredited third-party labs and correspond to the specific product batch.

AlsoCSA

The Controlled Substances Act is the 1970 federal statute that establishes the five schedules under which the DEA regulates drugs based on potential for abuse and accepted medical use. Kratom and 7-hydroxymitragynine are not currently scheduled federally; in July 2025 the HHS and FDA recommended scheduling 7-OH under the CSA. State controlled-substances acts operate in parallel and can schedule compounds the federal government does not.

Cross-tolerance occurs when tolerance to one drug reduces sensitivity to another drug acting at the same receptor system. Because 7-hydroxymitragynine acts at the μ-opioid receptor, heavy 7-OH users often develop partial cross-tolerance to classical opioids and vice versa. Clinically, this matters for both pain management and overdose risk when switching between substances.

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CYP3A4 is a hepatic cytochrome P450 enzyme that metabolizes an estimated 50% of prescription drugs, including kratom alkaloids. Mitragynine is oxidized to 7-hydroxymitragynine in part by CYP3A4 activity. Drugs that inhibit CYP3A4 (including grapefruit juice, ketoconazole, and some antidepressants) can substantially raise 7-OH exposure and potentiate effects.

AlsoDrug Enforcement Administration

The Drug Enforcement Administration is the U.S. federal agency responsible for enforcing the Controlled Substances Act and scheduling drugs. In 2016, the DEA attempted an emergency scheduling of mitragynine and 7-hydroxymitragynine as Schedule I but withdrew the proposal after public comment. In July 2025 the HHS recommended the DEA schedule 7-OH as Schedule I; the DEA had not finalized that action as of April 2026.

Emergency scheduling is an expedited administrative mechanism that allows the DEA (federally) or state authorities (via state boards of pharmacy or attorneys general) to temporarily classify a substance as a controlled substance when public safety is asserted to be at imminent risk. Florida (August 2025) and Ohio (December 2025) used state-level emergency rules to restrict 7-hydroxymitragynine. Emergency rules typically last 90 to 180 days pending a permanent rulemaking process.

An enhanced extract is a kratom preparation in which the natural leaf matrix is supplemented with additional alkaloids — most commonly mitragynine or 7-hydroxymitragynine isolates — to raise potency beyond what a simple extract would yield. Enhanced products sit between conventional full-spectrum extracts and pure isolates. State laws that cap 7-OH as a percentage of alkaloid content generally prohibit enhanced products that exceed the cap.

An extract is a concentrated preparation produced by removing alkaloids from raw kratom leaf using solvent, water, or mechanical means. Extracts typically contain 5-45% total alkaloid content versus 1-2% in dried leaf. Form factors include powders, resins, tinctures, shots, and tablets; potency and 7-OH ratio vary substantially between products and batches.

AlsoFood and Drug Administration

The Food and Drug Administration is the U.S. federal agency responsible for regulating food, drugs, and dietary supplements. The FDA has issued public warnings against kratom since 2016 and has not approved kratom or 7-hydroxymitragynine for any medical use. In July 2025 the FDA publicly recommended scheduling 7-OH as a Schedule I controlled substance.

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Fentanyl is a synthetic full agonist at the μ-opioid receptor, roughly 50-100 times more potent than morphine, and the leading cause of U.S. overdose deaths. Comparisons between fentanyl and 7-hydroxymitragynine are frequently made in policy discussions; the two differ materially because fentanyl is a full agonist without a meaningful ceiling on respiratory depression. Counterfeit fentanyl contamination of the illicit drug supply is a distinct public-health problem unrelated to legal 7-OH products.

AlsoGKC

The Global Kratom Coalition is an industry association representing kratom manufacturers and retailers that advocates for regulated legal access to kratom while supporting restrictions on synthetic and concentrated 7-hydroxymitragynine. GKC audits and reports on retail compliance with state potency caps, notably publishing an August 2025 Oklahoma audit that found products up to 92% 7-OH on shelves. Its position frequently aligns with but sometimes diverges from the American Kratom Association.

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Glucuronidation is a phase-II metabolic conjugation reaction in which glucuronic acid is attached to a molecule to increase water solubility and enable renal elimination. 7-hydroxymitragynine is extensively glucuronidated in the liver, which shortens its half-life relative to many classical opioids. UGT enzyme polymorphisms and induction can therefore alter individual 7-OH exposure substantially.

AlsoDepartment of Health and Human Services

The U.S. Department of Health and Human Services is the cabinet-level department that oversees the FDA, CDC, and NIH. On July 29, 2025, HHS forwarded to the DEA a formal recommendation to schedule 7-hydroxymitragynine as a Schedule I controlled substance under the Controlled Substances Act. HHS scheduling recommendations are advisory to the DEA but carry substantial weight.

Hot-water extraction is the traditional method of preparing kratom by steeping or boiling crushed leaf in water, yielding a tea that concentrates mitragynine and 7-hydroxymitragynine while leaving behind much of the plant material. Traditional Southeast Asian kratom tea is made this way. Commercial extracts typically use more efficient solvent-based methods to achieve higher alkaloid yields.

An indole alkaloid is an alkaloid whose structure contains an indole ring system — a fused benzene and pyrrole ring. Mitragynine and 7-hydroxymitragynine are indole alkaloids, as are serotonin, psilocybin, and reserpine. The indole scaffold is common in neuroactive plant compounds.

An isolate is a single purified alkaloid separated from its plant source, typically at or above 95% purity. 7-hydroxymitragynine isolate is produced either by purification from kratom leaf or by semi-synthetic oxidation of mitragynine. Products sold as '7-OH' tablets or gummies generally contain isolate, not full-spectrum extract.

Alsoκ-opioid receptor, KOR

The kappa-opioid receptor is one of the three classical opioid receptor subtypes (μ, δ, κ). Kratom alkaloids have measurable affinity for the κ-opioid receptor in addition to μ, which some researchers associate with kratom's dysphoric effects at high doses. 7-hydroxymitragynine's activity at κ is substantially weaker than at μ.

/KRAY-tum or KRAT-um/·Alsoketum, biak-biak, thang

Kratom is the common name for Mitragyna speciosa, a tropical evergreen tree in the Rubiaceae (coffee) family native to Southeast Asia. Its leaves have been used traditionally in Thailand, Malaysia, and Indonesia as a stimulant and analgesic. In U.S. consumer markets, 'kratom' refers to dried leaf, powders, teas, and extracts derived from the plant.

AlsoKCPA

The Kratom Consumer Protection Act is a model regulatory framework for kratom and 7-hydroxymitragynine products, promoted primarily by the American Kratom Association and adopted in varying forms by Arizona, Colorado, Georgia, Nevada, Oklahoma, Texas, Utah, and others. Typical KCPA provisions include a minimum age of 18 or 21, product labeling and testing requirements, prohibition of synthetic alkaloids, and a cap on 7-hydroxymitragynine concentration — usually 2% of total alkaloid content.

Kratom tea is the traditional Southeast Asian preparation of Mitragyna speciosa leaves steeped or boiled in water, historically consumed by agricultural laborers as a mild stimulant and analgesic. Traditional tea contains natural-ratio alkaloids dominated by mitragynine, with 7-hydroxymitragynine in trace amounts. It differs substantially from commercial 7-OH-concentrated products.

/my-truh-JY-nuh spee-see-OH-suh/

Mitragyna speciosa is the botanical name for the kratom tree, a tropical evergreen in the Rubiaceae (coffee) family native to Thailand, Malaysia, Indonesia, Papua New Guinea, and the Philippines. Its leaves are the source of the alkaloids mitragynine and 7-hydroxymitragynine. The plant grows to 25 meters in the wild and has been cultivated regionally for centuries.

/my-truh-JY-neen/·AlsoMG

Mitragynine is the most abundant alkaloid in kratom leaves, typically accounting for roughly 66% of total alkaloid content. It is a partial agonist at the μ-opioid receptor and is the metabolic precursor from which 7-hydroxymitragynine is generated by oxidation (in planta, in the liver, and in semi-synthetic manufacturing). Mitragynine is substantially less potent at the μ-opioid receptor than its 7-hydroxy metabolite.

Alsopseudoindoxyl, MP

Mitragynine pseudoindoxyl is a rearrangement product of 7-hydroxymitragynine with strong μ-opioid receptor activity and relatively weak β-arrestin recruitment — a signaling profile that has drawn research interest as a potentially safer analgesic. It is structurally distinct from 7-OH despite being derived from it. The compound exists only in trace amounts in raw leaf and is a research compound rather than a commercial product.

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Morphine is the prototypical opioid analgesic, a full agonist at the μ-opioid receptor isolated from the opium poppy (Papaver somniferum) in 1804. 7-hydroxymitragynine is frequently compared to morphine on a potency basis: at the μ-opioid receptor, 7-OH is roughly 13 times more potent than morphine. Morphine has no meaningful ceiling on respiratory depression and is a Schedule II controlled substance in the U.S.

Alsoμ-opioid receptor, MOR, mu receptor

The mu-opioid receptor is the G-protein-coupled receptor responsible for most of the analgesic, euphoric, and respiratory-depressant effects of opioid drugs. It is the primary target of 7-hydroxymitragynine, mitragynine, morphine, fentanyl, and buprenorphine. Partial agonism at this receptor — as seen with 7-OH and buprenorphine — produces a ceiling effect on respiratory depression that full agonists lack.

/nal-OX-own/·AlsoNarcan

Naloxone is a μ-opioid receptor antagonist used to rapidly reverse opioid overdose, marketed as Narcan and Kloxxado. Because 7-hydroxymitragynine acts at the μ-opioid receptor, naloxone will reverse acute 7-OH effects; it is the standard of care for suspected 7-OH overdose. Naloxone has a short half-life and a single dose may be insufficient if the offending compound has a longer duration of action.

The opioid receptors are a family of G-protein-coupled receptors in the central and peripheral nervous system, comprising three classical subtypes — mu (μ), delta (δ), and kappa (κ) — plus the non-classical nociceptin receptor. Kratom alkaloids act primarily at the μ subtype with weaker activity at δ and κ. Endogenous ligands include endorphins, enkephalins, and dynorphins.

A partial agonist is a receptor ligand that produces a sub-maximal response even at 100% receptor occupancy. 7-hydroxymitragynine, mitragynine, and buprenorphine are all partial agonists at the μ-opioid receptor; morphine, heroin, and fentanyl are full agonists. The partial-agonist mechanism is pharmacologically important because it creates a ceiling effect on respiratory depression — the primary cause of opioid overdose death.

AlsoPost-Acute Withdrawal Syndrome

Post-Acute Withdrawal Syndrome is a constellation of protracted symptoms — anxiety, insomnia, mood instability, anhedonia, and impaired concentration — that can persist for weeks to months after the acute phase of opioid withdrawal has resolved. PAWS is well-documented for classical opioids and is reported anecdotally by former heavy 7-hydroxymitragynine users. It complicates long-term recovery and frequently drives relapse.

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Paynantheine is the second-most-abundant alkaloid in kratom leaves, typically accounting for approximately 9% of total alkaloid content. It acts as a smooth muscle relaxant and is pharmacologically distinct from mitragynine at the opioid receptor. Its contribution to the overall effect profile of traditional kratom is modest compared with mitragynine.

Alsodependence

Physical dependence is a physiological adaptation to repeated drug exposure in which the body requires continued use to function normally and produces withdrawal symptoms upon cessation. Regular 7-hydroxymitragynine use can produce physical dependence consistent with its action at the μ-opioid receptor. Dependence is distinct from addiction, though the two frequently co-occur.

Respiratory depression is a dose-dependent reduction in breathing rate and depth, mediated at the μ-opioid receptor and the primary mechanism of fatal opioid overdose. Partial agonists like 7-hydroxymitragynine produce a ceiling on respiratory depression that full agonists like fentanyl and morphine do not. Combining 7-OH with other CNS depressants — alcohol, benzodiazepines, GHB — removes that protection and is associated with reported 7-OH-related deaths.

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Rubiaceae is the coffee family, a large family of flowering plants containing over 13,000 species. Mitragyna speciosa (kratom) is a Rubiaceae, as are Coffea arabica (coffee) and Cinchona officinalis (the source of quinine). The family is known for producing pharmacologically active indole alkaloids.

AlsoSchedule 1

Schedule I is the most restrictive classification under the U.S. Controlled Substances Act, reserved for substances with a high potential for abuse and no currently accepted medical use. Heroin, LSD, and MDMA are Schedule I federally. Several states have classified 7-hydroxymitragynine as Schedule I under state law (Alabama, Arkansas, California, Connecticut, Indiana, Louisiana, Rhode Island, Vermont, Wisconsin), and the FDA recommended federal Schedule I status in July 2025.

A semi-synthetic compound is produced by chemical modification of a naturally occurring precursor, rather than being extracted directly or synthesized de novo. Most commercial 7-hydroxymitragynine on the U.S. retail market is semi-synthetic — produced by oxidation of mitragynine isolated from kratom leaf. Several state kratom laws explicitly prohibit semi-synthetic alkaloid products.

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Speciogynine is the third-most-abundant alkaloid in kratom leaves, generally accounting for approximately 7% of total alkaloid content. It has smooth-muscle relaxant properties and limited opioid receptor activity. Its clinical significance in overall kratom effects is minor.

A synthetic compound is produced entirely by chemical synthesis from non-natural precursors, without using the source plant. Fully synthetic 7-hydroxymitragynine is less common than semi-synthetic product but is chemically identical. Several state laws either prohibit 'synthetic kratom alkaloids' outright or treat synthetic and semi-synthetic preparations under the same restriction.

Third-party lab testing is analytical verification of product content and purity by an independent laboratory unaffiliated with the manufacturer. For 7-OH products, reputable brands commission third-party testing for alkaloid composition, heavy metals, microbial load, and residual solvents. Results are published as a Certificate of Analysis; consumers should match the COA lot number to the product batch purchased.

Tolerance is the reduction in a drug's effect that occurs with repeated exposure, requiring a higher dose to achieve the original response. Tolerance to 7-hydroxymitragynine develops rapidly with daily use, consistent with its μ-opioid receptor activity. Escalating doses to overcome tolerance raise the risk of both acute adverse effects and eventual physical dependence.

Toss-and-wash is a consumption method in which dry kratom powder is placed directly into the mouth and washed down with water or juice. It is one of the oldest forms of kratom consumption in Western markets and largely predates modern tablet, gummy, and shot formats. The method applies to leaf powder rather than concentrated 7-OH products.

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Tramadol is a synthetic opioid analgesic with weak μ-opioid receptor agonism and additional serotonin-norepinephrine reuptake inhibition. It is sometimes compared to kratom on pharmacology because kratom alkaloids share the weak-μ-agonist profile and some incidental monoaminergic activity. Tramadol is a Schedule IV controlled substance in the U.S.

Withdrawal is the cluster of physiological and psychological symptoms that emerge when a physically dependent person stops or substantially reduces drug exposure. 7-hydroxymitragynine withdrawal resembles classical opioid withdrawal: muscle aches, gastrointestinal distress, sweating, anxiety, insomnia, and craving. Acute symptoms typically begin within 12-24 hours of last use, peak at 48-72 hours, and resolve over 5-10 days; protracted PAWS symptoms can persist longer.