R Street Comments on Placement of 7-OH on Schedule I

July 31, 2026

U.S. Department of Health and Human Services
Office of the Assistant Secretary for Health
200 Independence Avenue SW
Washington, DC 20201

Response to HHS-OASH-2026-0232: Temporary Placement of 7-Hydroxymitragynine Above a Specified Threshold in Schedule I

Submitted to the Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Re: Docket No. HHS-OASH-2026-0232

Assistant Secretary Brian Christine:

My name is Dr. Jeffrey S. Smith, and I am a Resident Senior Fellow at the R Street Institute, a nonprofit, nonpartisan public policy research organization headquartered in Washington, D.C. R Street supports pragmatic, evidence-based policy solutions that emphasize free markets, limited government, and individual liberty. In that capacity, I have conducted extensive research on substance regulation and the role of informed personal choice in public health. I submit this comment in response to the Office of the Assistant Secretary for Health’s request for information concerning the Drug Enforcement Administration’s proposed threshold for temporarily placing 7-hydroxymitragynine (7-OH) in Schedule I of the Controlled Substances Act.

I. INTRODUCTION AND SUMMARY

The available evidence supports prompt action to reduce harms associated with concentrated and semisynthetic 7-hydroxymitragynine, commonly called 7-OH. It does not support temporary Schedule I placement at the proposed threshold. Those are not contradictory conclusions. 7-OH acts at the mu-opioid receptor, concentrated products have been associated with tolerance, dependence, and withdrawal, and animal studies demonstrate respiratory depression. At the same time, the present record does not identify a human dose or product concentration at which 7-OH suddenly becomes an “imminent hazard to public safety.” It also does not show that Schedule I control would protect public health more effectively than targeted product regulation, premarket review of chemically converted products, and improved surveillance.

The HHS request for information asks two narrow questions. First, it asks whether data support the proposed threshold or an alternative threshold and, specifically, what amount or concentration of 7-OH constitutes an imminent hazard. Second, it asks whether other ways of expressing a threshold would better serve that purpose.^[1] The scientific answer to the first question is that current evidence does not establish an imminent-hazard boundary at 0.050% by weight, 1.00 mg per article, or any other single numerical value. The answer to the second question is that neither percentage by weight nor milligrams per “article” are sufficient measures of risk. If HHS develops an interim product classification-framework rather than a criminal scheduling threshold, it should combine milligrams per serving, milligrams per package, concentration, alkaloid ratios, route of administration, manufacturing method, and validated laboratory testing.

The proposed 0.050% threshold equals 0.5 mg of 7-OH per gram of material. That calculation is straightforward, but its biological meaning is not. A concentration is not a dose. A dose is not a complete measure of exposure. Exposure is not the same as demonstrated population risk. Route of administration, speed of absorption, frequency of redosing, co-use with alcohol or sedatives, product composition, and individual vulnerability all influence risk. A scientifically defensible threshold must be derived from evidence connecting a measured exposure to a health outcome. That link has not yet been established for 7-OH in humans.

For those reasons, HHS should advise the Attorney General and the Drug Enforcement Administration not to issue the temporary scheduling order on the present record. HHS should instead lead an expedited, risk-based process that distinguishes botanical kratom from concentrated 7-OH products and from synthetic or semisynthetic derivatives, imposes enforceable safeguards on the products that remain available, and generates the dose-response evidence needed for future decisions.

II. RESPONSE TO QUESTION 1: CURRENT EVIDENCE DOES NOT ESTABLISH THE PROPOSED THRESHOLD OR A SCIENTIFICALLY DEFENSIBLE ALTERNATIVE SCHEDULE I THRESHOLD

The evidence establishes hazard, but not the proposed dividing line. Science distinguishes hazard from risk. Hazard asks whether a substance can cause harm. Risk asks how likely that harm is under specified conditions of use. The evidence supports the conclusion that 7-OH has opioid-related hazards. It does not identify 1.00 mg per article or 0.050% by weight as the point at which those hazards become an imminent threat.

Preclinical studies demonstrate why concentrated 7-OH warrants concern. In one rat self-administration study, 7-OH substituted for morphine, while mitragynine did not, indicating greater reinforcing potential for 7-OH in that model.^[2] Another rodent study using intracranial self-stimulation did not find rewarding effects for either mitragynine or 7-OH.^[3] These findings are not necessarily incompatible because the experiments measured different aspects of reinforcement, but together they show that the preclinical evidence is not reducible to one simple potency statement. More recent comparative research found that intravenously administered 7-OH reduced breathing frequency and ventilation, while mitragynine increased respiratory frequency. Naloxone reversed the respiratory depression caused by 7-OH.^[4] This is an important warning signal, but an intravenous dose in a rat cannot be converted directly into a human oral threshold of 1.00 mg per consumer product.

The human literature is even less suited to deriving the proposed threshold. Recent reports describe clinically meaningful dependence and withdrawal after repeated use of concentrated or rapidly delivered 7-OH. One patient using a sublingual film developed tolerance within days and progressed to using a film every one to two hours before treatment with buprenorphine.^[5] Another report described withdrawal after use escalated to 360 mg per day.^[6] A retrospective series of nine patients found that eight stabilized after buprenorphine initiation, but the authors did not claim that the series established a population incidence rate or a toxic dose threshold.^[7] These observations are clinically important. They support warnings, treatment guidance, and tighter control of high-dose products. They do not establish that a product containing 1.01 mg presents an imminent hazard while one containing 0.99 mg does not.

The Drug Enforcement Administration’s own notice states that no controlled human clinical trials have established safe consumption limits or standardized dosing for concentrated 7-OH products.^[8] The absence of a validated safety limit does not mean that low doses are proven safe. It means that a criminal threshold cannot be presented as if it were derived from a known human dose-response curve. Uncertainty can justify precautionary product controls. It does not justify assigning scientific precision to a number that the available studies have not validated.

1. FDA’s assessment supports hazard identification, not numerical threshold derivation

FDA’s own 2025 scientific assessment identifies the central evidentiary gap. FDA found no clinical study in which isolated or purified 7-OH had been administered to humans, described the available human pharmacokinetic evidence as sparse and variable, and noted that much of it came from uncontrolled studies that are difficult to interpret. FDA also concluded that the public health burden could not be quantified because surveillance systems did not estimate the prevalence of 7-OH use and were only beginning to distinguish enhanced 7-OH products from botanical kratom and other kratom-derived products.^[9] These are not minor caveats. They are the data elements needed to connect a product’s concentration or quantity to an imminent public health hazard.

FDA’s compositional evidence helps explain why 0.050% may be useful as an enrichment screen. FDA cited an analysis of 13 commercial kratom products containing 0.01% to 0.04% 7-OH by weight and other reports finding less than 0.05%. It also cited 341 consumer-supplied products in which 7-OH ranged from below 0.005% to 0.21%, with a mean of 0.01%.^[10] These findings help distinguish typical botanical composition from some enhanced products. They do not demonstrate that 0.050% is the concentration at which a human health outcome begins, becomes severe, or becomes imminent. FDA did not map those product concentrations to verified doses and clinical outcomes.

2. A supportive eight-factor assessment still does not validate the proposed numbers

A structured, non-peer-reviewed eight-factor assessment prepared for DEA, FDA, and the National Institute on Drug Abuse reaches a more restrictive legal conclusion. It concludes that 7-OH likely meets the criteria for Controlled Substances Act control and may constitute an imminent public health threat.^[11] That conclusion deserves engagement rather than dismissal. It confirms the importance of opioid-receptor pharmacology, reinforcing effects in some animal models, respiratory depression, dependence, withdrawal, and the rapid growth of concentrated products. Those findings are most probative of hazard and abuse potential under Factors 1, 2, 3, and 7. The RFI’s numerical threshold question additionally requires evidence linking product composition and human exposure to the scope, significance, and immediacy of public health harm addressed by Factors 4, 5, and 6.

The same assessment also acknowledges that the severity of the population risk remains unclear, that surveillance cannot reliably separate 7-OH products from kratom, that the level and prevalence of dependence and withdrawal have received little study, and that no reliable estimate exists for the number of consumers using 7-OH for therapeutic or harm-reduction purposes. It further notes a route mismatch: much of the strongest respiratory evidence involves intravenous administration in animals, while real-world use is primarily oral.^[12] Most importantly for this RFI, the assessment does not derive either 0.050% or 1.00 mg from human dose-response evidence. A substance-wide conclusion about abuse potential or the need for control cannot substitute for evidence validating the particular quantitative line that HHS has asked the public to evaluate.

Abuse-potential assessment should be treated as a relative and comparative process, not as a binary label. Under that framework, a finding that 7-OH is more reinforcing or more respiratorily depressant than mitragynine in a particular model is important, but it does not identify the oral dose or product concentration at which an imminent hazard begins. Product class, formulation, route, speed of delivery, dose, frequency, and comparator all matter.^[13]

3. Product studies identify a high-risk market segment, not a hazard boundary at 0.050% or 1.00 mg

Market studies strongly support separating concentrated and semisynthetic 7-OH products from botanical kratom. They do not validate the proposed cutoff. Hill and colleagues identified 304 online 7-OH and mitragynine pseudoindoxyl products sold during a six-month period. Most were 7-OH-only products in chewable or sublingual tablets, shots, or gummies, and many made claims related to pain, anxiety, focus, or relaxation.^[14] That study documented product proliferation, routes of administration, and marketing practices. It did not test whether 1.00 mg is the threshold for an imminent hazard.

Chemical analyses reveal a similarly important but different problem. Brown and colleagues tested products labeled as “kratom extracts” and found 22 to 75 mg of 7-OH per gram, label-to-content discrepancies, alkaloid profiles inconsistent with kratom leaf, and unidentified constituents.^[15] Those measured concentrations were 44 to 150 times the proposed 0.5 mg per gram concentration threshold. Avula and colleagues likewise found label inaccuracies, oxidation byproducts, and evidence that more than 98% of the 7-OH-labeled products they analyzed were semisynthetic. Labeled amounts ranged from 0.001 to 33.6 mg per serving.^[16] These studies provide a compelling basis for identity standards, batch testing, manufacturing controls, and separate treatment of semisynthetic products. They provide little evidence about the risk transition near 0.5 mg per gram because the problematic products that were chemically characterized were often far above that level.

The data therefore support using composition to identify a product category. They do not support using the same number as a bright line for criminal Schedule I control. A compositional action level can answer, “Is this product materially enriched beyond botanical conditions?” An imminent-hazard threshold must answer a different question, “At what exposure does the evidence show a sufficiently serious and immediate public safety risk to warrant emergency scheduling?” The present literature answers the first question much better than the second.

4. Botanical kratom is a necessary comparator, even though the RFI is not a referendum on kratom generally

The RFI states that HHS is not soliciting broad comments on the safety or utility of kratom-derived products.^[17] Nevertheless, controlled botanical studies are relevant to the threshold because DEA’s proposal expressly covers botanical material above 0.050% 7-OH by dry weight. A threshold cannot be evaluated scientifically without understanding what it separates.

Controlled studies of botanical leaf powder report a different exposure pattern from concentrated 7-OH products. In a randomized pilot study, 40 adults received placebo or a single botanical kratom dose from 1 to 12 g. The material contained trace 7-OH. There were no deaths or serious adverse events, although nausea, vomiting, somnolence, pupillary constriction, and increased ratings of drug liking occurred, especially at higher doses.^[18] In a separate randomized study, 116 kratom-naive adults received placebo or dried leaf powder at doses up to 4 g, including 15 consecutive daily doses in some cohorts. No participant met the study’s threshold for clinically meaningful opioid withdrawal, and no serious adverse events or deaths were reported.^[19] These findings do not prove that botanical kratom is harmless, and they should not be generalized to all products. They do show why product composition and formulation matter.

Human pharmacokinetic research also shows that the body converts mitragynine to 7-OH after botanical or extract consumption. In a study of concentrated kratom extract, blood concentrations of both mitragynine and 7-OH increased with dose, and the relationship between the two varied with single versus repeated dosing.^[20] A product test therefore measures the 7-OH present before use, not the user’s complete biological exposure after metabolism. That does not make product testing unimportant. It means the test result should be interpreted as one part of a broader exposure model rather than as a complete measure of pharmacologic risk.

5. Surveillance data show a growing problem but cannot identify a 1.00 mg threshold

Poison center, adverse-event, and forensic data are essential warning systems. However, they are not controlled dose-response studies. The distinction matters because reports often lack a retained product for laboratory confirmation, a verified amount used, an exposure denominator, or complete information about co-used substances.

The National Poison Data System shows a clear increase in kratom-related reports. Poison centers received 14,449 reports from 2015 through 2025, including 3,434 in 2025. Multiple-substance reports had higher rates of hospitalization and serious outcomes than single-substance reports, and 79% of reported deaths involved multiple substances.^[21] These data demand better surveillance and prevention. They also aggregate products that may include botanical leaf, extracts, concentrated 7-OH, semisynthetic derivatives, and mislabeled mixtures. The study therefore cannot determine which 7-OH concentration or dose produced an outcome.

The DEA notice reports more specific 7-OH poison center and adverse-event signals, but those data have similar limitations. A 7-OH-specific poison center code was only recently introduced, and the agency acknowledges limitations in forensic identification and tracking.^[22] Case reports and surveillance signals can establish that a problem exists. Without verified product content and dose, they cannot locate the problem at 0.050% or 1.00 mg.

Recent state comparisons should also be interpreted with care. One observational analysis found lower rates of poison center reports and severe outcomes in states that banned kratom than in unrestricted states.^[23] Another found lower rates of kratom detection in fatal overdoses in controlled-substance states than in regulated states or states without statewide policy.^[24] These studies are relevant counterevidence to claims that bans never reduce visible harms. They do not establish causation, isolate concentrated 7-OH, measure illicit purchases, determine whether consumers switched to other substances, or show that Schedule I control at 1.00 mg is superior to enforceable product regulation. Much of the observation period also preceded the recent expansion of semisynthetic 7-OH products.

6. The scientifically supportable answer is that no single imminent-hazard threshold can currently be identified

Based on the available literature, HHS should answer Question 1 directly: Current data do not establish that 0.050% by weight or 1.00 mg per article is the point at which 7-OH constitutes an imminent hazard to public safety. Current data also do not support a different single numerical Schedule I threshold. This conclusion should not be misread as a finding that any particular lower dose is safe. It only shows that the evidence necessary to establish a bright-line Schedule I threshold has not been generated.

The 0.050% value may have practical utility as a provisional identity or enrichment screen, especially when combined with an alkaloid ratio and manufacturing information. If used that way, it should trigger laboratory confirmation, product classification, additional safety requirements, or premarket review. It should not, on the current record, automatically trigger Schedule I criminal controls.

HHS should commission the evidence needed to revisit the question. The research program should use chemically characterized materials and include controlled pharmacokinetic and pharmacodynamic studies, human abuse-potential assessment, respiratory measures, repeated-dose and withdrawal evaluation, interaction studies with alcohol, benzodiazepines, opioids, and other depressants, and post-market surveillance that retains products for testing. Reviews of the field have repeatedly called for chemically defined preparations, validated methods, and exposure-to-effect research that distinguish botanical products from enriched or semisynthetic derivatives.^[25]

III. RESPONSE TO QUESTION 2: THRESHOLDS SHOULD BE EXPRESSED THROUGH MULTIPLE COMPLEMENTARY MEASURES

1. Milligrams per serving and per package should be the primary exposure measures

For a consumer product, the most understandable and health-relevant starting point is the amount of 7-OH in a defined serving. Labels should state milligrams of 7-OH per unit, per recommended serving, and per total package. These quantities should be based on independent batch testing, not a manufacturer’s formulation target. Serving and package definitions must be standardized so that a company cannot avoid a limit by relabeling one tablet as two servings or selling multiple units as one undefined “article.”

Milligrams per serving still cannot establish a universal safety threshold because absorption, metabolism, frequency, and individual susceptibility differ. It is nevertheless more informative than concentration alone because it approximates the quantity a consumer takes at one time. Milligrams per package captures another risk: the total amount immediately available for repeated dosing, accidental ingestion, or use by multiple people.

The proposed concentration and total-content prongs can classify products differently. At 0.050% by weight, a 2 g product contains 1.00 mg of 7-OH. A 100 g product at only 0.010% contains 10 mg and could exceed the total-content prong if the package is treated as the “article,” even though its concentration is one-fifth of the proposed concentration line. This is not technical curiosity. It means that the legal result can depend on whether “article” is interpreted as a tablet, serving, bottle, retail package, or bulk container. HHS should define each of those units and explain which exposure concept the total-content test is intended to represent.

2. Concentration and alkaloid ratios should be used to identify enrichment and product class

Percentage by weight or milligrams per gram remain useful for quality control and product identity. For botanical material, HHS should pair absolute concentration with the ratio of 7-OH to mitragynine and, where analytically feasible, the ratio of 7-OH to total alkaloids. A product with a botanical-looking label but an unusually high 7-OH concentration, a high 7-OH-to-mitragynine ratio, or a missing botanical alkaloid fingerprint should be classified as enriched, converted, or otherwise nonbotanical. Brown and colleagues demonstrated the value of this approach by showing that products marketed as kratom extracts lacked the expected leaf profile and contained exceptionally high 7-OH concentrations.^[26]

A ratio is an identity measure, not a complete exposure measure. A product can have a botanical-looking ratio but still deliver a large total dose if the serving is large or concentrated. Conversely, a very small product can exceed a percentage cutoff while delivering a low absolute amount. HHS should therefore reject the premise that percentage, absolute quantity, or ratio can serve alone.

Weight/weight, weight/volume, and volume/volume percentages should not be presented as interchangeable expressions. Solids and powders should be reported as milligrams per gram on a defined dry-weight basis. Liquids should be reported as milligrams per milliliter, with density and sample-homogeneity requirements where conversion is necessary. A volume/volume percentage is not self-explanatory for a dissolved, nonvolatile such as 7-OH. HHS should either justify and precisely define that expression or remove it from the threshold framework.

3. Route of administration and speed of delivery should be part of the threshold framework

Products intended for swallowing should not be treated as equivalent to sublingual films, buccal pouches, nasal products, or inhaled products. Faster delivery can increase the intensity of effect and encourage repeated use. The reported case involving a sublingual 7-OH film illustrates why formulation is relevant to dependence risk.^[27] The proliferation of tablets, films, gummies, liquids, and other dosage forms also shows that a rule written only around chemical concentration will miss important product-level differences.^[28]

A risk-based framework should therefore treat non-swallowed and rapid-delivery 7-OH products as a separate, higher-scrutiny category. Such products should not enter ordinary consumer channels without route-appropriate pharmacokinetic, safety, and abuse-liability evidence.

4. Measurement must be standardized before a threshold can be enforced fairly

Any threshold requires a validated analytical system. HHS should specify the chemical form being measured, the sample preparation method, dry-weight determination, treatment of liquids and heterogeneous products, extraction efficiency, calibration materials, limits of detection and quantification, and acceptable measurement uncertainty near the cutoff. The proposal covers isomers, esters, ethers, salts, and salts of those forms without explaining whether laboratories should report the mass of each compound, convert each result to a 7-OH-equivalent amount, or apply a different rule. Laboratories should participate in proficiency testing, and enforcement decisions should include an uncertainty or guard-band rule so that normal analytical variation does not convert a borderline result into a criminal violation.

Validated liquid chromatography and tandem mass spectrometry methods can quantify multiple kratom alkaloids, including 7-OH, and can support regulatory testing.^[29] The product studies also demonstrate the need to test for mitragynine pseudoindoxyl, oxidation products, residual processing chemicals, adulterants, and contaminants rather than measuring 7-OH alone.^[30] A threshold that ignores related compounds and process byproducts can create an incentive to reformulate around the named analyte without reducing risk.

Accordingly, the best response to Question 2 is a measurement matrix rather than a single expression. Milligrams per serving and package should measure consumer exposure. Milligrams per gram or milliliter should measure concentration. Alkaloid ratios and chemical fingerprints should distinguish botanical from enriched or converted products. Route and formulation should identify rapid-delivery risk. Manufacturing records and testing for related compounds should establish what the product actually is. None of these measures, alone or together, can substitute for the missing human dose-response evidence, but they can support proportionate product regulation while that evidence is developed.

5. Ancillary consequences that directly affect the threshold decision

Schedule I would impose a blunt legal consequence on an uncertain scientific boundary. Although the RFI is narrow, the consequence of the threshold is not. DEA states that the temporary order would apply Schedule I regulatory controls and civil and criminal sanctions to manufacture, distribution, importation, exportation, research, chemical analysis, and possession of covered products. The order could last two years and be extended for a third year, and a temporary scheduling order is not subject to judicial review.^[31] These consequences make the scientific validity and administrability of the threshold central, not collateral.

Schedule I is a legal control category, not a scientific ranking that automatically means a substance is more dangerous than every drug in Schedules II through V. Applying that category to products on one side of a measurement boundary requires greater confidence than the current evidence provides. A label discrepancy, an ambiguous definition of “article,” or ordinary laboratory uncertainty should not determine whether possession is lawful or criminal.

6. Scheduling would not end research, but it would make the needed research harder

Researchers can study Schedule I substances, but they must navigate additional registration, protocol, security, recordkeeping, procurement, and material-handling requirements. Experience with cannabis research shows that controlled-substance status, limited access to representative study products, and funding constraints can delay the studies needed to answer urgent public health questions.^[32] The eight-factor assessment supplied with this comment raises the same concern for 7-OH and warns that Schedule I requirements could impede urgently needed safety, pharmacology, and therapeutic research.^[33] The 7-OH evidence base is at precisely the stage where rapid access to well-characterized products, reference standards, market samples, and clinical participants is most important.

The appropriate statement is not that scheduling makes research impossible. It is that scheduling adds friction, cost, and delay while the consumer market can move toward unobserved or illicit channels. HHS should not impose those barriers before it has established that the proposed threshold is valid and that less restrictive tools cannot address the measured risks.

7. Prohibition can displace rather than eliminate supply and can criminalize consumers

No study has measured what a federal 7-OH scheduling order would do to consumer behavior, product substitution, illicit manufacturing, or overdose risk. Predictions should therefore be stated as risks, not certainties. Existing evidence nevertheless shows why displacement deserves serious consideration. In a study of leading internet kratom vendors, only 27% blocked sales to Rhode Island and 65% blocked sales to Indiana when those jurisdictions prohibited kratom, demonstrating uneven compliance in an online market.^[34] A federal order may reduce mainstream retail availability, but demand, internet sales, and chemical reformulation may not disappear.

Criminalization also has consequences beyond product access. Drug-law enforcement and criminal records can affect employment, housing, family stability, public benefits, and health care, with disproportionate effects on already disadvantaged communities.^[35] These are public health effects of the threshold because a result above the line would not merely require a new warning label. It could expose consumers and sellers to federal criminal sanctions.

Notably, the eight-factor assessment that supports control also recommends risk mitigation before scheduling, additional public input, transition time and assistance for current consumers, coordination among public health agencies, and enforcement priorities that avoid focusing on individual possession.^[36] It expressly warns of possible relapse to more dangerous opioids and the emergence of an illicit 7-OH market, while acknowledging that the evidence about consumer motivations and benefits is largely anecdotal. Those recommendations reinforce the central point of this comment: an emergency order should not precede a product-specific risk assessment, a valid measurement system, and a credible transition plan.

8. A legal, tightly regulated channel provides more points of public health control

The current market problems point toward enforceable product rules. HHS, FDA, DEA, Congress, and the states should establish legally distinct categories for botanical kratom, concentrated 7-OH products, and synthetic or semisynthetic derivatives. Botanical products should meet identity, contaminant, labeling, and age-access standards. Concentrated 7-OH products should face stricter potency, serving-size, package-size, warning, packaging, and surveillance requirements. Synthetic and semisynthetic products, rapid-delivery formulations, and products above defined enrichment triggers should require premarket authorization or an equivalent review before sale. This category-based approach is consistent with recent scientific recommendations to apply different evidence standards to whole-leaf, enriched, and semisynthetic products.^[37]

All legal products should disclose 7-OH and mitragynine per serving and package, carry clear warnings about dependence and co-use with alcohol or sedatives, use child-resistant packaging, and avoid candy-like or youth-directed presentation. Recent marketplace research identified gummies, candies, brightly colored formulations, and cartoon imagery among mitragynine and 7-OH products could appeal to children.^[38] Retail sale should be limited to adults, serious adverse events should be reported, batch certificates should be available to regulators and consumers, and disease-treatment claims should be prohibited unless authorized by FDA.

Regulation should also address treatment. Clinicians and poison centers need guidance that distinguishes botanical kratom from concentrated 7-OH and related derivatives. Naloxone education is warranted because preclinical and case evidence indicates opioid-mediated respiratory risk, and clinicians should have practical guidance for recognizing and treating dependence and withdrawal. A regulated market makes it easier to obtain product information, trace a batch, issue a recall, enforce an age limit, and connect a reported event to laboratory findings. An illicit market weakens each of those controls.

IV. CONCLUSION

The scientific record supports concern about concentrated and semisynthetic 7-OH. It supports immediate action against inaccurate labels, undisclosed potency, rapid-delivery formulations, child-appealing products, unsafe manufacturing, and unapproved medical claims. It supports treatment guidance and better surveillance. It does not establish that 0.050% by weight or 1.00 mg per article marks an imminent-hazard boundary, and it does not establish a different single numerical threshold that would make temporary Schedule I placement scientifically defensible.

HHS should report that conclusion clearly to the Attorney General. The proposed percentage may be useful as a provisional product-identity or enrichment trigger, but it should not be converted into a criminal scheduling line without human dose-response evidence, validated measurement standards, and analysis of less restrictive alternatives. The better path is a risk-proportionate framework that measures what consumers actually receive, distinguishes product classes, requires premarket evidence for synthetic and rapid-delivery products, preserves access to research materials, and adjusts controls as surveillance improves.

Forgoing temporary scheduling is not a decision to ignore risk. It is a decision to regulate the measured risks directly, to avoid overstating what the science can presently prove, and to build the evidence needed for durable public health policy.

Respectfully submitted,

Jeffrey S. Smith
Resident Senior Fellow, Healthier Communities
R Street Institute
jsmith@rstreet.org