Beyond the Leaf: A Risk-Based Framework for Kratom, 7-OH, and Synthetic Derivatives

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Kratom policy should not be a referendum on whether kratom is good or bad. It should be a practical effort to reduce harm in a market that already exists. Although current scientific evidence supports concern, especially for concentrated 7-OH extracts and synthetic or semi-synthetic products, it also supports caution against overgeneralization.

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Executive Summary

Kratom policy is advancing quickly, but the science and the marketplace do not support treating all kratom-related products as one category. Botanical kratom, 7-hydroxymitragynine (7-OH) extracts/concentrates, and synthetic/semi-synthetic kratom-derived products differ in composition, route of administration, potency, likely risk, and appropriate regulatory response.

These differences call for a tiered approach. Botanical kratom products should remain available to adults under enforceable standards for safety, labeling, contaminants, age restriction, and retail compliance. However, 7-OH extracts and concentrates should face stricter potency, warning, testing, and product-form requirements. Synthetic and semi-synthetic products should be subject to premarket review or an equivalent authorization process because chemical conversion and novel analog development introduce risks that ordinary botanical standards cannot address.

Building on these distinctions, this paper recommends a risk-proportionate framework for kratom products. The goal of this framework is not to normalize every product in the marketplace, but to move the market away from undisclosed potency, youth access, contamination, synthetic escalation, and unapproved medical claims, while preserving less harmful options for adults who might otherwise turn to more dangerous substances or unregulated supply chains.

Introduction

Kratom policy is moving faster than kratom science. Although policymakers do not need to wait for the science to settle before considering kratom-related legislation, it is important to understand the distinctions between different types of kratom products and their associated risks—and build a framework that can adapt as those distinctions become clearer. The single biggest misstep in current policy debates is treating botanical kratom, concentrated 7-hydroxymitragynine (7-OH) extracts, and synthetic or semi-synthetic 7-OH products as the same thing. They are related, but not interchangeable, and those differences matter for toxicology, consumer behavior, enforcement, and public health.

Kratom is the common name for Mitragyna speciosa, a tree native to Southeast Asia. Traditional uses include chewing leaves, brewing tea, or making simple leaf preparations. However, in the United States, manufacturers sell kratom as powders, capsules, tablets, beverages, and extracts. The major alkaloid (a naturally occurring organic chemical compound) in kratom leaf is mitragynine, though the plant contains dozens of related alkaloids with different pharmacologic profiles.^[1] Adults report using kratom for a variety of reasons, including energy, focus, pain, anxiety, mood, sleep, self-management of opioid withdrawal, or reduction in opioid use.^[2]

7-hydroxymitragynine, often called 7-OH or 7-HMG, is a related but distinct
compound. It appears in trace amounts in ordinary kratom leaf and is formed when the body metabolizes mitragynine.^[3] 7-OH has stronger activity on the mu-opioid receptor (i.e., structures in the brain that regulate pain, reward, and mood) than mitragynine, and recent clinical reports describe dependence and withdrawal associated with concentrated 7-OH products.^[4] Consumers may use 7-OH products to seek the same effects as botanical kratom, but the results can be very different. A concentrated 7-OH tablet, strip, liquid, pouch, or powder can deliver a higher dose of a more potent opioid-active compound more quickly than ordinary kratom leaf powder.^[5]

Synthetic and semi-synthetic 7-OH products move even further from botanical kratom. These products are made or modified through chemical processes that enrich, convert, or mimic kratom alkaloids. Some of these products include semi-synthetic 7-OH and mitragynine pseudoindoxyl derivatives marketed as kratom-related products even though they have a higher risk profile than whole-leaf and naturally derived products.^[6] People may seek these products out because they are potent, legal (or perceived as legal), easy to purchase, and marketed as enhanced kratom or alternatives to opioids. However, these features make this category of product more likely to create physical, clinical, and regulatory problems.

A ban or Schedule I approach for all kratom products may appear easier and more decisive, but it would be a blunt instrument that could push consumers toward illicit markets, remove incentives for testing and labeling, hinder further study of potential harms and benefits, and blur distinctions between a leaf powder with low 7-OH content and a high-potency synthetic 7-OH product.^[7] A better path is risk-proportionate regulation: Preserve adult access to compliant botanical products, impose stricter rules on 7-OH extracts and concentrates, and require premarket review or equivalent authorization for synthetic and semi-synthetic products.

Why Product Distinctions Matter

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Composition varies by plant genetics, geography, and growing conditions, as well as processing, extraction, storage, and manufacturing methods.^[8] Traditional leaf material contains mitragynine as the dominant alkaloid, and 7-OH is typically present at much lower levels. Commercial products can differ widely in alkaloid profile, dosage, route of administration, and label accuracy.^[9]

That variation changes the risk analysis of different products and product categories. Botanical kratom leaf powder is pharmacologically complex. Mitragynine has partial mu-opioid receptor activity, so botanical kratom products can produce stimulant-like effects at lower doses and opioid-like effects at higher doses.^[10] However, controlled human work on orally administered botanical kratom suggests that policymakers should not automatically equate ordinary leaf powder with high-potency opioid products. Specifically, a pilot dose-finding study evaluated the pharmacodynamic, safety, and pharmacokinetic outcomes of oral botanical kratom.^[11] A separate controlled abuse-potential study assessed single and repeated doses of dried leaf powder in healthy kratom-naïve adults.^[12] The results of these studies did not imply that botanical kratom is harmless, but they did suggest that it differs from concentrated 7-OH products.

Route of administration sharpens the distinction. When consumed via tea or capsule, botanical kratom is absorbed through the gastrointestinal pathway and typically takes effect gradually. However, some newer 7-OH products are designed for sublingual, buccal, nasal, or inhaled use, which may bypass first-pass metabolism and potentially produce faster, more intense effects.^[13] This rapid onset, especially when coupled with higher concentrations, can increase dependence liability for many psychoactive substances. Thus, a product designed to deliver high-dose 7-OH rapidly likely presents a higher potential for harm than a package of powdered whole-leaf kratom. From a policy perspective, this means that the two products should not be regulated as if they were the same.

These differences also matter for enforcement because regulators cannot apply risk-proportionate rules if they cannot tell one category of product from another. Identifying the presence and quantity of kratom and its alkaloids requires sophisticated, standardized testing methods and validated analytical approaches that state and federal governments must develop to support new legislation.^[14] Without them, regulators cannot distinguish ordinary botanical kratom from elevated 7-OH or a synthetic analog, nor can they identify contaminants, inaccurate labeling, or the degree of risk an individual product presents. Building that analytical capacity is therefore not a precondition for regulation but a core component of it.

What Safety Evidence Shows

Kratom has been associated with adverse events, poison center reports, dependence, withdrawal, and deaths.^[15] However, the most severe outcomes tend to involve polysubstance use, products with unknown composition, or products that may not represent ordinary botanical kratom.^[16]

National Poison Data System data show a substantial and recent uptick in the annual number of kratom-related reports.^[17] U.S. poison centers documented 14,449 kratom exposures among people aged 12 years and older from 2015 through 2025.^[18] Although the annual number of reports ranged between 1,300 and 1,500 for most of the early 2020s, the 2025 total (3,434) represented a 125 percent increase over 2024 (1,523) and an approximately 1,200 percent increase over the 258 reports recorded in 2015.^[19] During this 10-year period, poison centers documented 233 kratom-associated deaths, nearly 80 percent of which (184) involved multiple substances.^[20] One recent case involving kratom and tianeptine (a supplement not approved by the FDA but used by some as an antidepressant) described acute hypoxemic respiratory failure and respiratory depression after self-reported combined ingestion, illustrating both the risks of polysubstance exposure and the difficulty of assigning causality to a single product.[^21]

A few caveats are essential when interpreting poison center data. Because these data are voluntary and self-reported, they may undercount milder events that go unreported, and they may include repeat calls for the same event/product or misclassified substances. In addition, they may disproportionately capture more serious or unusual cases. They also cannot accurately attribute causation, meaning the presence of kratom in a reported fatal overdose does not necessarily mean that kratom was the primary cause of death.^[22]

These same interpretive limits apply to other overdose data sources, but the broader pattern is still informative. A separate analysis of the State Unintentional Drug Overdose Reporting System (SUDORS) for 2020 through 2024 showed how kratom detection in fatal overdoses varied in relation to state policy.^[23] The analysis found that kratom was detected 3.27 times as often in regulated states and 4.19 times as often in states without statewide kratom policies as it was in states where kratom was designated as a controlled substance.^[24] This is an ecologic association: It measures how often kratom appeared in postmortem toxicology, not whether kratom caused those deaths, and it cannot establish that scheduling itself produced the differences. Even so, the pattern is consistent with what pharmacology and case reports suggest: Where higher-potency and less-standardized kratom products are more accessible, the substance shows up more often in toxicology.

The safety concerns around concentrated 7-OH are more concrete. Recent case reports and case series suggest that some individuals using purified or concentrated 7-OH products are taking high doses and experiencing acute withdrawal and substance use disorder.^[25] Published clinical evidence remains limited but now includes an inpatient case report and a nine-patient retrospective case series involving problematic purified 7-OH use. In the case series, eight of nine patients were successfully initiated and stabilized on buprenorphine, and eight reported symptomatic improvement at a median six-week follow-up.^[26] Although these reports are not population-level estimates, they are still clinically meaningful because they describe a pattern that is pharmacologically plausible and increasingly visible in treatment settings: A product that delivers a high dose of a potent mu-opioid receptor agonist should be expected to carry dependence and withdrawal risk.

Derivative products such as mitragynine pseudoindoxyl and other semi-synthetic analogs are also elevating these concerns. Reviews and case reports describe these substances as more potent kratom derivatives that may be even more active at mu receptors and also produce opioid-like withdrawal and other harms.^[27] One study evaluated a semi-synthetically enhanced kratom preparation containing 56.31 percent 7-OH using computational predictions and two standard laboratory assays to assess for genetic damage. Such studies illustrate the broader testing battery needed to evaluate whether an enriched or chemically modified product can damage DNA or chromosomes.^[28] The preparation was negative on one assay and was predicted to have low genotoxic potential overall, but the second assay produced a weak positive chromosomal-damage signal at the highest tested concentration, where cytotoxicity (cell death) exceeded 50 percent, making the biological significance difficult to interpret. These findings address genotoxicity only and do not establish safety regarding dependence, respiratory effects, interactions, misuse, or long-term exposure. Still, they illustrate broad safety concerns and the importance of manufacturer testing and transparent labeling.

Lessons From Cannabis, Hemp, and Novel Cannabinoid Regulation

The kratom and 7-OH debate is not the first time policymakers have struggled to regulate a botanical, its extracts, and its chemically modified derivatives. Cannabis and hemp regulation offers a useful parallel. The policy failure was not legalizing hemp; it was that legal categories did not adequately distinguish between plant material, nonintoxicating cannabidiol (CBD), full-spectrum extracts, and chemically converted intoxicants.^[29]

A closer look at the 2018 law shows how those categories broke down in practice. The Agriculture Improvement Act of 2018 legalized hemp by defining it as Cannabis sativa containing no more than 0.3 percent delta-9 tetrahydrocannabinol (or “THC,” the primary intoxicating component in cannabis) by dry weight.^[30] The goal was to permit industrial hemp, which is used in paper, textiles, and more, and nonintoxicating CBD, which is typically used to enhance relaxation and improve well-being.^[31] But the law’s treatment of hemp derivatives, extracts, cannabinoids, and isomers created space for manufacturers to chemically convert CBD into delta-8 THC, delta-10 THC, hexahydrocannabinol, THC-O-acetate, and related products.^[32] Like delta-9 THC, these substances can produce intoxicating effects, but because of their source, manufacturers can still market the products as hemp-derived.^[33] Consequently, products appeared in convenience stores, vape shops, gas stations, and online markets, often outside the age-gated, tested, and labeled systems that state cannabis programs had built.^[34]

As a result, FDA and poison control data documented adverse events and pediatric exposures involving delta-8 THC products, and laboratory analyses raised concerns about residual solvents, heavy metals, and reaction byproducts from nonstandardized synthesis.^[35] CBD product studies also found substantial labeling inaccuracy and occasional contamination with unlabeled cannabinoids.^[36] States responded with a patchwork of bans, restrictions, potency caps, and efforts to fold intoxicating hemp products into cannabis regulatory systems. That patchwork created consumer confusion, enforcement gaps, and incentives for online arbitrage.^[37]

Botanical kratom should mean unconverted Mitragyna speciosa leaf or simple preparations that remain within specified alkaloid limits. 7-OH extracts and concentrates should be a separate category because they intentionally elevate a more potent opioid-active alkaloid. Synthetic or semi-synthetic kratom-derived products should be treated as a third category because chemical conversion and novel analog development introduce risks that ordinary botanical standards cannot address.

The cannabis experience also shows why blanket scheduling can undermine the science needed for better policy. Cannabis’ decades-long Schedule I status slowed research, limited access to representative products, and made it harder for regulators to evaluate the products consumers were actually using.^[38] Furthermore, once regulators categorized the drug as Schedule I, loosening those restrictions to allow more research and legal or medical access became slow and arduous. Because kratom science is still developing—especially with regard to 7-OH extracts and synthetic analogs—policymakers should not repeat a model that suppresses research while demand and product innovation move to less visible markets.

Lessons From the DSHEA: Why Post-Market Enforcement Is Not Enough

The Dietary Supplement Health and Education Act of 1994 (DSHEA) is the federal framework most closely associated with the channel through which many kratom products are sold. The DSHEA gives manufacturers substantial premarket responsibility, making it a poor fit for concentrated, synthetic, or semi-synthetic compounds that enter the market quickly and are often sold before regulators can evaluate safety. Under the DSHEA, dietary supplements generally do not receive premarket approval. For new dietary ingredients, manufacturers must notify the FDA and provide safety information, but the process is not an affirmative approval system and has limited deterrent effect when manufacturers do not comply.^[39]

The limits of post-market enforcement are well documented. Ephedra (a stimulant used to treat colds, fevers, headaches, and other ailments), DMAA (an amphetamine derivative/stimulant used in fat burners and workout performance supplements), and tianeptine (an atypical tricyclic compound that can produce euphoric, opioid-like highs) each show how products can remain available and easily accessible for years while the FDA develops the evidentiary and legal record needed to act.^[40] The FDA’s Tainted Products database similarly shows that many adulterated supplements are identified only after market entry, often without a voluntary recall and sometimes with repeat violations.^[41] This is not a criticism of enforcement efforts; it is a design problem. A framework that relies mainly on post-market removal is too slow for novel psychoactive compounds sold through retail and online channels.

The kratom and 7-OH market is already testing these limits. The FDA has long taken the position that kratom is not a lawful dietary ingredient absent an adequate new dietary ingredient notification, and it has objected to submitted notifications on safety or identity grounds.^[42] Yet these products remain widely available, and some newer products are not even conventional swallowed supplements. A 2026 analysis identified sublingual strips, buccal pouches, and vaping products marketed as kratom-derived products, with 7-OH being prominent in many formulations.^[43] These different delivery forms matter because they may change exposure, onset, and abuse liability. They also highlight why a framework built for swallowed botanical supplements cannot carry the whole regulatory burden for products with different routes of delivery.

Manufacturer Responsibility and the Wellness-Medical Boundary

Any regulatory framework established around kratom/7-OH products must clarify manufacturer responsibility. Current good manufacturing practice (GMP) regulations for dietary supplements require manufacturers to verify ingredients, establish written procedures, document batch records, investigate complaints, and ensure that finished products meet labeled specifications for identity, purity, strength, and composition.^[44] In practice, these regulations help ensure that consumers receive a product that matches its label.

More recent work has also identified large numbers of products marketed as enhanced formulations that contain elevated 7-OH levels and that inconsistently use terms such as “extract,” “alkaloids,” “full spectrum,” or “enhanced”—both of which make dose comparison difficult.^[46] As a result, consumers cannot make informed decisions about the products they are purchasing.

Manufacturers must also be held to truthful marketing. Even though many adults use kratom for health-related reasons, including pain management or substance withdrawal, these products are not FDA-approved medications. Under the Federal Food, Drug, and Cosmetic Act, companies cannot make disease-treatment claims that suggest a product is a medication without undergoing the agency’s approval process.^[47] The DSHEA permits limited structure/function claims, but it does not permit a manufacturer to market a product as a treatment for opioid use disorder, pain, anxiety disorders, depression, or other diseases without going through the appropriate FDA pathway.^[48]

FDA enforcement has repeatedly upheld this standard. Warning letters and agency actions have cited kratom and 7-OH product claims related to pain relief, opioid withdrawal, anxiety, and opioid substitution as evidence of unapproved drug marketing.^[49] The policy implication is straightforward: Regulators should allow truthful content disclosures and safety warnings while prohibiting unapproved medical claims. Such steps are critical to protect consumers without ignoring the fact that many adults use kratom for health-related reasons.

Third-party certification can help operationalize these responsibilities. The American Kratom Association’s voluntary GMP Standards Program, for example, applies third-party audits, manufacturing standards, restrictions on disease claims, and a ceiling on 7-OH content as a share of total alkaloids.^[50] Voluntary programs cannot replace law, but they can provide a model for enforceable retailer and platform rules. Retailers can also choose (or be required) to sell only products from registered manufacturers with batch-specific certificates of analysis and recognized certification. They can also be required to ensure that buyers meet minimum age requirements.

Policy Recommendations

The most constructive kratom policy would create legal categories that reflect product risk, applying lighter requirements to lower-risk botanical products and progressively stricter ones to more potent or chemically altered products. The following 10 recommendations translate that framework into specific, actionable steps for policymakers.

Policy Implementation Considerations

A workable statute should be built for enforcement, not just messaging. State agencies need authority to inspect products, obtain certificates of analysis, remove mislabeled products from the market, and penalize repeat violations. Retailers need clear rules that can be applied at the point of sale. Manufacturers need a predictable pathway for compliant products. Consumers need labels that make sense. A label that lists “total alkaloids” but hides 7-OH per serving does not help consumers compare products; a label that discloses 7-OH content, mitragynine content, serving size, total servings, warnings, and testing information does.

Policymakers should structure the regulatory model in a way that rewards ethical manufacturers and disincentivizes irresponsible ones. If compliant manufacturers pay for testing while noncompliant sellers face no meaningful enforcement, the market will drift toward less expensive, riskier products. Testing requirements should therefore be paired with retailer obligations. Retailers should be required to purchase only from registered manufacturers, maintain batch documentation, and remove products that exceed potency limits or lack valid testing. Online sellers should also be required to meet the same standards as brick-and-mortar retailers, including age verification and state-specific shipping restrictions.

Policymakers should invest in data collection before and after implementing any statute. States should track poison center calls, emergency department encounters, medical examiner findings, product seizures, age-compliance checks, and adverse-event reports by product category. If severe events cluster around concentrated 7-OH or specific delivery forms, regulators can tighten those standards without eliminating lower-risk products that meet safety requirements. If contamination or labeling problems persist, enforcement can focus efforts on those issues. This type of feedback loop would be more useful than a static ban because it would allow policy to follow the evidence as the market changes.^[58]

Congress should establish a limited federal framework defining the major product categories and setting minimum standards for age restrictions, testing, labeling, manufacturer registration, retail compliance, and enforcement. States should remain free to adopt stronger requirements or respond to local surveillance findings, provided that state definitions remain compatible with the federal categories. A patchwork of conflicting definitions and limits makes compliance more difficult and encourages sellers to route products to less-restrictive jurisdictions. Legislation should therefore define botanical kratom, 7-OH extracts and concentrates, and synthetic or semi-synthetic products in consistent terms. Regulators should develop federal definitions through a transparent process informed by analytical chemistry, pharmacology, public-health surveillance, state experience, and stakeholder standards, including relevant American Kratom Association proposals. Regulations should also set a floor for age limits, testing, labeling, retail compliance, and enforcement while allowing states to respond to local surveillance data. The overarching, shared objective should be to move the market away from undisclosed potency, youth access, contamination, synthetic escalation, and unapproved medical claims.

Conclusion

Kratom policy should not be a referendum on whether kratom is good or bad. It should be a practical effort to reduce harm in a market that already exists. Although current scientific evidence supports concern, especially for concentrated 7-OH extracts and synthetic or semi-synthetic products, it also supports caution against overgeneralization. Botanical kratom, 7-OH extracts, and synthetic products differ in composition, pharmacology, consumer use, route of administration, manufacturing process, and apparent risk.

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Policymakers should define three product categories, require independent testing and accessible certificates of analysis, cap 7-OH content in products sold as botanical kratom, restrict youth access, prohibit unapproved medical claims, strengthen surveillance, provide clinicians with guidance for dependence and withdrawal, require premarket notification or authorization for synthetic and high-risk products, and condition legal retail on manufacturer registration and certification.

A risk-regulated market will not eliminate every adverse event—no realistic policy can. But it can give consumers more accurate information, give clinicians better tools, give regulators clearer enforcement authority, and give responsible manufacturers incentives to compete on safety and transparency rather than potency alone. For policymakers, the question is not whether to act. The question is whether to act precisely enough to reduce real risks while preserving less harmful options for adults. The available evidence points toward precision, transparency, and harm reduction rather than bans and scheduling.

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The sources included in this paper were verified and active at the time of publication.

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[5] Reif et al. https://pubmed.ncbi.nlm.nih.gov/41189061; Kirsten E. Smith et al., “Complicating Factors Surrounding Concurrent Use of Kratom and a Novel 7-hydroxymitragynine Product Among a Participant Enrolled in a Kratom Clinical Trial,” Journal of Addiction Medicine (Oct. 31, 2025). https://pubmed.ncbi.nlm.nih.gov/41177541; C Michael White et al., “Nonswallowed Kratom-Derived Products: Unlawful Dietary Supplements That Endanger Public Health,” Public Health Reports 141:3 (May-June 2026), pp. 335-338. https://pubmed.ncbi.nlm.nih.gov/41587771. 

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[8] Yathindra Marimuthu et al., “Variations of Mitragynine Content in Kratom Leaves From Southeast Asia: An Updated Review,” Chemistry and Biodiversity 23:6 (June 2026), article e02332. https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202502332; Todd et al. https://pmc.ncbi.nlm.nih.gov/articles/PMC7645423.

[9] Avula et al. https://www.sciencedirect.com/science/article/pii/S0031942226001044; Cinzia Citti et al., “Kratom: The analytical challenge of an emerging herbal drug,” Journal of Chromatography A 1703 (Aug. 16, 2023). https://www.sciencedirect.com/science/article/pii/S0021967323003205; Todd et al. https://pmc.ncbi.nlm.nih.gov/articles/PMC7645423.

[10] Green et al. https://linkinghub.elsevier.com/retrieve/pii/S0278584624002835.

[11] Chad J Reissig et al., “A Pilot, Dose-Finding, Pharmacodynamic and Pharmacokinetic Study of Orally Administered Botanical Kratom,” Journal of Clinical Psychopharmacology 46:4 (July-August 2026), pp. 386-398. https://pubmed.ncbi.nlm.nih.gov/41837407.

[12] Marion Coe et al., “Assessment of Abuse Potential-Related Effects of Oral Dried Kratom Leaf Powder in Healthy Normal Participants Following Single and Multiple Daily Doses,” Drug Testing and Analysis (May 17, 2026), pp. 1-11. https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/dta.70089.

[13] Rakshit S. Tanna et al., “Clinical Pharmacokinetic Assessment of Kratom (Mitragyna speciosa), a Botanical Product with Opioid-Like Effects, in Healthy Adult Participants,” Pharmaceutics 14:3 (March 11, 2022). https://www.mdpi.com/1999-4923/14/3/620; Marilyn A Huestis et al., “Human Mitragynine and 7-Hydroxymitragynine Pharmacokinetics after Single and Multiple Daily Doses of Oral Encapsulated Dried Kratom Leaf Powder,” Molecules 29:5 (Feb. 23, 2024). https://pmc.ncbi.nlm.nih.gov/articles/PMC10934259; White et al. https://pubmed.ncbi.nlm.nih.gov/41587771; Scott Alsbrook et al., “From kratom to 7-hydroxymitragynine: evolution of a natural remedy into a public-health threat,” Pharmaceutical Biology 63:1 (December 2025), pp. 896-911. https://www.tandfonline.com/doi/full/10.1080/13880209.2025.2590311; Jean Kim and Orlando De Jesus, “Medication Routes of Administration,” StatPearls, Aug. 23, 2023. https://www.ncbi.nlm.nih.gov/books/NBK568677.

[14] Avula et al. https://www.sciencedirect.com/science/article/pii/S0031942226001044; Citti et al. https://www.sciencedirect.com/science/article/pii/S0021967323003205.

[15] Grant Comstock et al., “Association between state-level kratom regulations and poison center-reported severe medical outcomes and healthcare use: A United States national analysis,” Addiction (April 21, 2026). https://onlinelibrary.wiley.com/doi/10.1111/add.70416; Christian M Iuteri et al., “Case–control study of mitragynine deaths in Florida,” Journal of Analytical Toxicology 50:5 (May 2026). https://academic.oup.com/jat/article/doi/10.1093/jat/bkag017/8524763; Eleanor Blair Towers et al., “Increases in Kratom-Related Reports to Poison Centers—National Poison Data System, United States, 2015–2025,” MMWR Morbidity and Mortality Weekly Report 75:11 (March 26, 2026), pp. 139-145. https://pmc.ncbi.nlm.nih.gov/articles/PMC13020857.

[16] Kaulin Duncan et al., “Management of a Kratom and Tianeptine Overdose,” Journal of Pharmacy Practice (May 26, 2026), pp. 1-3. https://journals.sagepub.com/doi/10.1177/08971900261456021; Iuteri et al. https://academic.oup.com/jat/article/doi/10.1093/jat/bkag017/8524763.

[17] Towers et al. https://pmc.ncbi.nlm.nih.gov/articles/PMC13020857.

[18] Ibid.

[19] Ibid.

[20] Ibid.

[21] Duncan et al. https://journals.sagepub.com/doi/10.1177/08971900261456021.

[22] Lekshmi Rita-Venugopal, “Association Between State Kratom Policy Status and Kratom-Involved Overdose Deaths in the United States, 2020–2024: Analysis of the State Unintentional Drug Overdose Reporting System (SUDORS),” Substance Use and Misuse (May 14, 2026), pp. 1-6. https://www.tandfonline.com/doi/full/10.1080/10826084.2026.2670611.

[23] Ibid.

[24] Ibid.

[25] Wightman and Hu. https://pubmed.ncbi.nlm.nih.gov/40758956; Fenske et al. https://pubmed.ncbi.nlm.nih.gov/42225057.

[26] Wightman and Hu. https://pubmed.ncbi.nlm.nih.gov/40758956.

[27] Gour et al. https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/dta.3952; Smith et al., “Complicating Factors Surrounding Concurrent Use of Kratom and a Novel 7-hydroxymitragynine Product Among a Participant Enrolled in a Kratom Clinical Trial.” https://pubmed.ncbi.nlm.nih.gov/41177541.

[28] Nathaphat Harnkit et al., “Genotoxicity risk assessment of a 7-hydroxymitragynine-enriched Kratom preparation: An integrated in silico and in vitro approach,” Toxicology Reports 16 (Jan. 14, 2026). https://pmc.ncbi.nlm.nih.gov/articles/PMC12856349.

[29] Alyssa F. Harlow et al., “Closing the Loophole on Hemp-Derived Cannabis Products: A Public Health Priority,” JAMA 328:20 (Nov. 4, 2022), pp. 2007-2008. https://jamanetwork.com/journals/jama/fullarticle/2798426; Eric C Leas, “The Hemp Loophole: A Need to Clarify the Legality of Delta-8-THC and Other Hemp-Derived Tetrahydrocannabinol Compounds,” American Journal of Public Health 111:11 (November 2021), pp. 1927-1931. https://pmc.ncbi.nlm.nih.gov/articles/PMC8630489.

[30] Agriculture Improvement Act of 2018, Pub. L. No. 115-334, § 10113, 132 Stat. 4490, 4908 (2018) (codified at 7 U.S.C. § 1639o(1)). https://www.govinfo.gov/content/pkg/PLAW-115publ334/pdf/PLAW-115publ334.pdf.

[31] Julie Moltke and Chandni Hindocha, “Reasons for cannabidiol use: a cross-sectional study of CBD users, focusing on self-perceived stress, anxiety, and sleep problems,” Journal of Cannabis Research 3 (Feb. 18, 2021), pp. 1-2. https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-021-00061-5; Meghann Wheeler et al., “CBD (Cannabidiol) Product Attitudes, Knowledge, and Use Among Young Adults,” Substance Use & Misuse 55:7 (Feb. 24, 2020), p. 1138. https://www.tandfonline.com/doi/full/10.1080/10826084.2020.1729201.

[32] Harlow et al. https://jamanetwork.com/journals/jama/fullarticle/2798426; Leas. https://pmc.ncbi.nlm.nih.gov/articles/PMC8630489.

[33] Ibid.

[34] Matthew C Nali et al., “Assessing Characteristics and Compliance of Online Delta-8 Tetrahydrocannabinol Product Sellers,” Cannabis and Cannabinoid Research 9:4 (Aug. 16, 2024), pp. e1132-e1141. https://pmc.ncbi.nlm.nih.gov/articles/PMC11386993.

[35] “5 Things to Know about Delta-8 Tetrahydrocannabinol—Delta-8 THC,” U.S. Food & Drug Administration, May 4, 2022. https://www.fda.gov/consumers/consumer-updates/5-things-know-about-delta-8-tetrahydrocannabinol-delta-8-thc; Harlow et al. https://jamanetwork.com/journals/jama/fullarticle/2798426.

[36] Marcel O Bonn-Miller et al., “Labeling Accuracy of Cannabidiol Extracts Sold Online,” JAMA 318:17 (Nov. 7, 2017), pp. 1708-1709. https://pmc.ncbi.nlm.nih.gov/articles/PMC5818782; Barry E. Gidal et al., “Product labeling accuracy and contamination analysis of commercially available cannabidiol product samples,” Frontiers in Pharmacology 15 (March 17, 2024). https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1335441/full.

[37] Harlow et al. https://jamanetwork.com/journals/jama/fullarticle/2798426; Nali et al. https://pmc.ncbi.nlm.nih.gov/articles/PMC11386993.

[38] Ziva D Cooper et al., “Challenges for Clinical Cannabis and Cannabinoid Research in the United States,” JNCI Monographs 2021:58 (December 2021), pp. 114-122. https://academic.oup.com/jncimono/article/2021/58/114/6446199; National Academies of Sciences, Engineering, and Medicine, The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research (National Academies Press, 2017). https://www.nationalacademies.org/publications/24625.

[39] Pieter A. Cohen, “The FDA and Adulterated Supplements—Dereliction of Duty,” JAMA Network Open 1:6 (Oct. 12, 2018), article e183329. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2706489; “New Dietary Ingredients in Dietary Supplements – Background for Industry,” U.S. Food & Drug Administration, Feb. 9, 2023. https://www.fda.gov/food/new-dietary-ingredient-ndi-notification-process/new-dietary-ingredients-dietary-supplements-background-industry.

[40] Cohen. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2706489; “Updated review of available information pertaining to 1,3-dimethylamylamine: lack of general recognition of safety for its use in foods,” U.S. Food & Drug Administration, Aug. 24, 2021. https://www.fda.gov/media/169554/download; “FDA and Kratom,” U.S. Food & Drug Administration, Dec. 2, 2025. https://www.fda.gov/news-events/public-health-focus/fda-and-kratom; Keith R. Martin, “Navigating the Nomenclature of a Purported ‘Dietary Supplement’: A Cautionary Tale for Consumers and Practitioners Regarding Tianeptine or ‘Gas Station Heroin,’” Health 15 (Dec. 26, 2023), pp. 1338-1351. https://www.memphis.edu/healthsciences/pdfs/2023-kr-martin.pdf.

[41] Jenna Tucker et al., “Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With U.S. Food and Drug Administration Warnings,” JAMA Network Open 1:6 (Oct. 12, 2018). https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2706496.

[42] “Import Alert 54-15,” U.S. Food & Drug Administration, Feb. 21, 2025. https://www.accessdata.fda.gov/cms_ia/importalert_1137.html; “FDA and Kratom.” https://www.fda.gov/news-events/public-health-focus/fda-and-kratom; Stephen Daniells, “Sixth time still not a charm: FDA again rejects NDIN for kratom,” NutraIngredients, Feb. 2, 2022. https://www.nutraingredients-usa.com/Article/2022/02/02/Sixth-time-still-not-a-charm-FDA-again-rejects-NDIN-for-kratom.

[43] White et al. https://pubmed.ncbi.nlm.nih.gov/41587771.

[44] “Backgrounder on the Final Rule for Current Good Manufacturing Practices (CGMPs) for Dietary Supplements,” U.S. Food and Drug Administration, June 22, 2007. https://www.fda.gov/food/dietary-supplements-guidance-documents-regulatory-information/backgrounder-final-rule-current-good-manufacturing-practices-cgmps-dietary-supplements.

[45] Preston K. Manwill et al., “Kratom (Mitragyna speciosa) Validation: Quantitative Analysis of Indole and Oxindole Alkaloids Reveals Chemotypes of Plants and Products,” Planta Medica 88:09/10 (August 2022), pp. 838-857. https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1795-587; Prozialeck et al. https://pmc.ncbi.nlm.nih.gov/articles/PMC7881941.

[46] Paula N Brown et al., “Elevated 7-Hydroxymitragynine Levels Found in Products Misbranded as Kratom,” Journal of AOAC International 109:1 (Jan. 1, 2026), pp. 124-130. https://pmc.ncbi.nlm.nih.gov/articles/PMC12733965; Smith et al., “Complicating Factors Surrounding Concurrent Use of Kratom and a Novel 7-hydroxymitragynine Product Among a Participant Enrolled in a Kratom Clinical Trial.” https://pubmed.ncbi.nlm.nih.gov/41177541.

[47] Federal Food, Drug, and Cosmetic Act, 21 U.S.C. §§ 321(g)(1), 355 (2018).

[48] “Small Entity Compliance Guide on Structure/Function Claims,” U.S. Food & Drug Administration, January 2002. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-structurefunction-claims-small-entity-compliance-guide; “Structure/Function Claims,” U.S. Food & Drug Administration, March 28, 2024. https://www.fda.gov/food/nutrition-food-labeling-and-critical-foods/structurefunction-claims.

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[50] “American Kratom Association’s Good Manufacturing Practice Standards Program,” American Kratom Association, last accessed June 29, 2026. https://www.americankratom.org/gmp-standards-program.

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