The Drug Enforcement Administration (DEA) has taken a major step toward placing concentrated 7-hydroxymitragynine (7-OH) products under Schedule I of the Controlled Substances Act (CSA), while exempting natural leaf kratom that does not contain enhanced levels of 7-OH.
The agency published two notices of intent in the Federal Register this week. One notice would temporarily place in Schedule I synthetic 7-OH products containing more than 0.050% 7-OH by weight/weight, weight/volume, or volume/volume, or more than 1.0 mg of 7-OH per article. This threshold is intended to distinguish highly concentrated or synthetic 7-OH products from botanical kratom, which contains only trace amounts of naturally occurring 7-OH.
The other notice would temporarily place three synthetic 7-OH-related derivatives — mitragynine pseudoindoxyl, dihydro-7-hydroxymitragynine (MGM-15), and the 9-fluoro derivative of 7-OH (MGM-16) — in Schedule I.
Schedule I is reserved for substances deemed to have a high potential for abuse and no currently accepted medical use. Other substances in this category include heroin and lysergic acid diethylamide.
‘Encouraging’ Action
Traditional kratom products are made from the dried leaves of Mitragyna speciose, a tree native to Southeast Asia, and naturally contain dozens of bioactive alkaloids.
The most well-studied compounds in kratom are mitragynine and 7-OH. Mitragynine is the predominant alkaloid, making up about 60%-65% of dried leaves, while 7-OH is present only in trace amounts (often < 0.05% of the leaf).
Both molecules are psychoactive and are partial agonists at the Mu opioid receptor. However, concentrated 7-OH preparations are 30-40 times more potent at opioid receptors and produce rapid-onset analgesia, euphoria, respiratory depression, and classic opioid-type withdrawal.
Enhanced 7-OH products are widely sold online and in gas stations, convenience stores, and smoke shops as gummies, tablets, powders, capsules, liquid shots, and dissolvable strips, often containing substantially higher concentrations than occur naturally in kratom.
The new DEA action follows a recommendation by the FDA issued last year that 7-OH be classified as a Schedule I substance, as reported by Medscape Medical News. Around the same time, the agency issued warning letters to seven companies marketing products containing added or concentrated 7-OH.
Lief Fenno, MD, PhD, chair in the American Psychiatric Association Council on Addiction Psychiatry, called the DEA action on 7-OH “encouraging.”
“With no proven therapeutic effect and a high potential for harm, 7-OH and related molecules clearly meet the definition of a Schedule I substance. This is a first step that has the potential to reduce 7-OH accessibility and therefore improve public health,” Fenno told Medscape Medical News.
There is a 30-day public comment period on the proposal. If the temporary scheduling order takes effect, the manufacture, distribution, sale, and possession of covered high-potency 7-OH products would become subject to the criminal, civil, and administrative provisions of the CSA.
Natural Kratom Exempt
The proposal would exempt botanical kratom products containing naturally occurring 7-OH below the specified threshold, while targeting synthesized products and those with elevated concentrations of the compound.
Fenno said limiting the proposal to specific compounds rather than the kratom plant represents “a conservative strategy that deviates from precedent.” He noted that the CSA schedule restricts possession of the entire marijuana, opium, and coca plants and argued that because kratom contains 7-OH and carries risks for dependence and addiction, “the DEA’s proposal is only a partial solution to a very big problem.”
The carve-out for botanical kratom is likely to remain controversial. While kratom advocacy groups have supported distinguishing natural kratom from concentrated synthetic 7-OH products, some addiction specialists continue to warn that botanical kratom also carries risks of dependence and other adverse effects.
“Current research suggests that concentrated 7-OH products may pose greater risks than botanical kratom products. However, the safety of any kratom-derived product sold in the United States should not be assumed,” Mario San Bartolome, MD, chair in the American Society of Addiction Medicine (ASAM) Practice Management and Regulatory Affairs Committee, told Medscape Medical News. “ASAM supports evidence-based policies that mitigate the health risks associated with kratom and its constituents, including 7-OH.”
While ASAM supports the DEA proposal, San Bartolome also voiced concern about the impact the ban might have on patients who are physiologically dependent on 7-OH.
“Some of these individuals may be at risk of transitioning to a highly volatile illicit opioid market after experiencing significant withdrawal symptoms. The federal government should carefully consider how to help these individuals understand that they may experience opioid withdrawal symptoms and should therefore seek appropriate medical care,” San Bartolome said.
Enforcement of the new rule could be challenging, Fenno said.
“While the kratom plant does not fall under the DEA’s Schedule I proposal, it has separately been deemed unlawful in dietary supplements or food by the FDA,” he said. “How will the 7-OH content of kratom products be monitored, when these products aren’t allowed to be manufactured or sold to begin with? The regulatory approach needs to have teeth to bite into the American kratom crisis.”
San Bartolome had no relevant conflicts of interest. Fenno is a voting member of the Texas Opioid Abatement Fund Council and founder and officer of NumbCorp, a biotech company focused on engineering non-opioid drugs for regional pain control.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.