7-Hydroxymitragynine (7-OH)
Holistic Alternative Recovery Trust
HART Statement on 7-OH
The Holistic Alternative Recovery Trust (HART) was formed in 2023 to provide education to consumers about the safety and efficacy of holistic alternative recovery solutions and to advocate before Congress and state legislatures to promote responsible regulations of plant-based recovery products.
The U.S. opioid crisis is the leading public health challenge of the new millennium. There are more than 200 opioid overdoses and poisonings every day —and drug overdose is now the number one cause of death for 18-45-year-olds. To address this unprecedented crisis, policymakers and public health officials need to identify new tools for the toolbox.
Our Proposal
Opioids, effective for acute and chronic pain, pose significant risks like addiction and respiratory depression, which is a serious breathing slowdown leading to organ damage or death. The World Health Organization reported around 600,000 drug-related deaths in 2019, 80% involving opioids. In the U.S., there were approximately 70,630 drug overdose deaths in 2019, with almost half linked to synthetic opioids.
We propose examining 7-hydroxymitragynine (7-HMG), a compound in Kratom, for harm reduction and pain management. Emerging evidence suggests that it can be used as a safer alternative to traditional opiates. This report provides a brief overview of current scientific knowledge on Kratom and opioid research.
Interested in becoming an advocate?
HART believes that 7-hydroxymitragynine (7-OH), a metabolite of mitragynine, the most abundant alkaloid found in kratom, could provide a new set of tools to combat opioid misuse and improve public health. Proper regulation of this substance would also expand access to safe options for managing stress and decreasing reliance on harmful, illicit substances, while also supporting the transition from dependence on these substances.
7-OH products marketed by HART members comply with FDA’s adulteration standard for dietary supplements, in that they do not present a significant or unreasonable risk of illness or injury under the conditions of use recommended or suggested in labeling, or under ordinary conditions of use. Based on monitoring of consumer feedback and adverse event reports by HART members, there also do not appear to be safety signals with products currently on the market.
Unfortunately, there are current efforts in a number of state legislatures to ban 7-OH, which are largely driven by a kratom organization that views 7-OH as a threat to its market share. That group has paid scientists hundreds of thousands of dollars to make broad policy pronouncements based on very preliminary research and theory. This article describes the conflicted actors seeking to gain competitive advantage through the legislative process.
7-OH can be an invaluable harm reduction tool that should remain an option for the hundreds of thousands of consumers that rely on it. This was a key factor in HHS’ decision to reject efforts to ban kratom and 7-OH, stating that, by contrast, “there is significant risk of immediate adverse public health consequences for potentially millions of users if kratom and its components” were controlled as Schedule 1 drugs.
HART advocates for the responsible availability of 7-OH products and remains committed to promoting evidence-based strategies and maintaining public trust. As new data emerges, we commit to using this information to guide best practices that uphold our commitment to consumer safety and public health.
HART strongly supports robust regulation and is pursuing legislation federally, and in the states, to mandate that all 7-OH products are manufactured safely, are marketed transparently, and are kept out of the hands of children. In the meantime, HART is continuing its investment in self-regulation and the science supporting 7-OH’s safety.
Science
We have engaged Pinney Associates and their specialists in central nervous system (CNS) active drugs, to advise HART on the research approach needed to better understand 7-OH pharmacology, safety, addiction-related risks, and other health effects. HART is committed to working with researchers, regulators, and public health stakeholders to investigate the safety profile and efficacy of 7-OH, including through the evaluation of how 7-OH is used across different consumer populations, potential adverse health effects, additional toxicological/safety data, and abuse potential studies.
Findings from this review will be shared through scientific conferences and peer-reviewed publications, as well as disseminated to regulatory authorities, healthcare providers, and consumers. HART believes that this transparency will enable stakeholders to make informed decisions about the potential benefits and risks of 7-OH.
Self-Regulation
HART recognizes that supporting its public health mission and protecting consumers depends on science-based product standards and accurately labeled products. Clear standards for product quality, marketing, and research are vital to earning public trust and supporting informed choices. HART is committed to advancing a regulated 7-OH industry that places consumer health and well-being first while maintaining product safety and quality. We also welcome the opportunity to work with FDA to enhance the current regulatory framework through additional product performance standards and labeling recommendations.
In pursuit of these objectives, HART is committed to promoting self-regulation, with the guidance of former White House Drug Czar Jim Carroll. HART endorses the following principles:
1. Collaboration and Compliance with Legal and Regulatory Requirements
HART member companies must comply with all laws and regulations applicable to the marketing, distribution, and sale of their products, including obtaining regulatory approval in local jurisdictions where this is required. We also support federal restrictions that prohibit 7-OH products from being marketed to diagnose, cure, treat, mitigate, or prevent disease and implementation of adverse event reporting systems to facilitate ongoing safety monitoring. In addition, manufacturers must accurately label 7-OH products to include 7-OH content, recommended serving sizes, daily intake limit recommendations, appropriate warnings, and usage instructions. Health-related claims must be substantiated by credible scientific evidence and comply with FTC truth-in-advertising requirements. Companies must also adhere to current Good Manufacturing Practices (cGMPs) for dietary supplements to help ensure products are free from contaminants and consistently meet quality standards, as well as testing to verify the consistency, purity, and potency of 7-OH products, with test results made publicly available.
2. Prioritizing Consumer Safety
HART endorses a consumer-focused approach that includes regularly revising industry standards based on emerging scientific data, regulatory updates, and consumer feedback. HART also encourages active engagement with healthcare providers to develop continuing education initiatives that highlight the latest scientific findings on 7-OH and help healthcare professionals advise patients on their safe and responsible use. Additionally, HART advocates for systems that provide insights into consumption and provide active monitoring for early signs of misuse, abuse or dependence to inform risk mitigation strategies.
3. Preventing Underage Access
HART member companies will ensure their products are sold only with age verification and ID-checking measures to prohibit the sale of 7-OH products to individuals under 21. HART also recommends its member companies implement child-resistant packaging for all 7-OH products to reduce the risk of accidental ingestion. Additionally, HART member companies should avoid marketing and advertising in any form to individuals under 21.
4. Commitment to Sound Scientific Research
HART commits to rigorous scientific investigations conducted under vigorous standards (i.e., adhering to Good Laboratory Practices (cGLP) and/or Organization for Economic Cooperation and Development (OECD) guidelines) to assess the safety and potential risks of 7-OH. HART also commits to the transparent dissemination of research findings through scientific conferences and peer-reviewed articles to regulatory authorities, healthcare providers, and consumers to enable informed decision-making.
5. Establishing Industry Best Practices and Guidelines
HART recommends timely and transparent dissemination of research findings and interpretations to industry and encourages using this data to facilitate conversations within industry and with legal and regulatory authorities to develop consensus documents, such as best-practice manuals or industry product performance standards that the industry can follow.
6. Differentiation from Kratom Products
Although 7-OH is a kratom metabolite, pure 7-OH products should not be confused with natural kratom products or other kratom derivatives. HART maintains that isolated or concentrated 7-OH products should be clearly distinguished from natural kratom products and labeled accordingly.
Key Findings
- 7-HMG's Pain-Relieving Role: 7-HMG, derived from Mitragynine, is crucial for Kratom's pain relief effects. Animal studies show a significant portion of Mitragynine converts to 7-HMG in-vivo, contributing to its analgesic properties.
- Tolerability in Animal Studies: Research on dogs indicates that 7-HMG, even in high doses, is well tolerated without adverse effects, suggesting a large therapeutic window.
- Unique Mechanism of Action: 7-HMG and other Kratom alkaloids potentially avoid typical opioid side effects like respiratory depression. This is due to their 'biased agonism', which selectively activates pain-relief pathways without triggering harmful effects.
- Addiction Potential: Existing studies on the addiction potential of 7-HMG are inconclusive. Some research indicates no abuse potential, while others suggest it could be addictive. Studies demonstrating abuse potential have been conducted using rodents as models. This has yet to be examined in humans.
Our Conclusion
We propose considering 7-hydroxymitragynine (7-HMG) for use in harm reduction clinics and as an over-the-counter medication. Its safety profile and effective pain relief potential make it a promising alternative to traditional opioids. This approach could improve access to safer pain management, potentially reducing opioid misuse.