The Stop Gas Station Heroin coalition reviewed the beagle study commissioned by CBD American Shaman, a Missouri-based company that reports generating the majority of its revenue from the sale of “7” products in over 200 retail locations, to evaluate the effects of escalating oral doses of their formulations of 7 (semi-synthetic 7-hydroxymitragynine), and Pseudo (semi-synthetic mitragynine pseudoindoxyl).
Commissioned to support an Investigational New Drug (IND) submission, the study’s clear conflicts of interest are as alarming as its findings. Consider that CBD American Shaman, the sponsor of the research, has falsely marketed and sold these products as dietary supplements since 2022. Moreover, the study was released by the Holistic Alternative Recovery Trust (HART), an advocacy group comprised of members with a vested interest in 7-OH products.
This study raises serious concerns about the safety of 7 and Pseudo products, especially with regard to CBD American Shaman’s marketed “serving size” of 7.5 mg per serving, or half a tablet. More concerning is that in reality users consume significantly greater amounts of these products, and misuse risks include tolerance and addiction.
Critically, the study’s findings suggest that doses of more than 0.3 mg exceed a conservative threshold for human safety. This figure is based on adverse effects observed in dogs at 10 mg doses, scaled to a human-equivalent dose using FDA-recommended methods.
In other words, CBD American Shaman’s marketed serving size is more than 25 times greater than what could be considered reasonably safe based on the study’s own preclinical data, and many more times greater if measured against normal consumption of these products.
Lastly, what HART is ignoring, irrespective of the science they put forward, is that 7 and Pseudo have been chemically formulated and put into the market with the intent to cure, treat and mitigate disease; that is in relation to chronic pain, and opioid use disorder. Despite marketing their products as natural botanicals, they are producing unapproved new pharmaceutical drugs, which is illegal.
In order to protect Americans, they should be conducting rigorous peer reviewed science that is published in a journal and vetted as a part of a robust IND submission that proves the efficacy and safety of 7 and Pseudo in comparison to the prescription drugs they are attempting to mimic. Without this critical research and approval from the FDA for prescribed use of 7 and Pseudo, these products should not be on the market.
The study’s design, results, and implications are expanded upon below:
The original study design sought to give 10, 20, 40 mg of 7-OH or mitragynine psuedoindoxyl twice daily for 7 days for beagles ranging from 8–10.2 kg. However, at the lowest dose of 10 mg, a Serious Adverse Event (SAE) occurred causing the study to be halted).
What does this mean?
- A 10 mg dog for a ~10 kg dog dose ≈ 0.5 mg/kg in humans, or ~32.4 mg in a 60 kg human, potentially enough to cause a similar SAE. [1]
- Based on this data, using a reasonable safety factor of 100 (per FDA guidance), the results would mean the maximum dose they could administer is 0.3 mg for humans. This maximum dose of 0.3 mg is equivalent to about 4% of the suggested serving size, and 2% of a single tablet sold by American Shaman.
After the SAE, the sponsor adjusted its protocol to 1/10 of the original doses (1, 2, 4 mg per day in dogs), which is 1/20 of the daily dose. However, even at doses at 1 mg, 2 mg and 4 mg per day, adverse events (AEs) were still 2.5–2.7x more common than placebo. Specific AEs include GI disturbances, including blood and mucus in feces. All episodes of drooling appeared in dogs only after the daily dose was escalated to 4 mg.
What does this mean?
- 1 mg, 2 mg and 4 mg doses in dogs can be converted to Human Equivalent Dose (HED) of 0.05 mg/kg, 0.1 mg/kg and 0.2 mg/kg.
- For a 60 kg human, the dose that can cause adverse events could be as low as 3.24–12.96 mg.
- The sponsor (CBD American Shaman)’s current human product doses, as well as many 7 and Pseudo products in market already far exceed the Human Equivalent Dose that could cause an adverse event, and many times more than what would be considered a safe dose.
Missing pieces in research design and unfinished reports:
The presented study of 7 and Pseudo in dogs was incomplete, missing key safety endpoints, and inappropriately designed to assess safe use of the test articles. Some of these are described below
- Short duration: Only seven days of exposure per dose, not representative of daily chronic use observed in real-world conditions.
- Within-group dose escalation confounds data: The middle and high doses were only given to dogs acclimated to lower doses of the test article.
- No assessment of opioid-related side effects like respiratory depression.
- No assessment of abuse potential or behavioral changes expected with opioid exposure.
- While allegedly collected, no report of clinical chemistry, hematology, or urinalysis data.
- The study was not peer-reviewed nor published in a reputable scientific journal. In fact, it was still in draft format.
In Summary
The study is incomplete, shows significant public health risk with these products, and it doesn’t justify extrapolating to humans to establish the safety of 7 or Pseudo, especially when:
- The beagles had serious adverse events at very low doses in the original study design and had adverse events in the redesigned studies starting at 1/10 of the dosage of the initial study design’s first dose.
- The set dosing data for humans for products already being sold are based on a leap of faith, not robust safety data.
- Beagle-to-human extrapolation is already a cautious stretch; human sales go far beyond what the model supports. Dosages currently sold in the market have already exceeded the HED that can cause Adverse Events (AEs) and Serious Adverse Events (SAEs) based on the study.
- With reported risk addiction due to 7 being 22 times more potent opioid receptor binding affinity than morphine, many consumers will take more than the 32.4 mg limit that links to serious adverse events and expose themselves at lower doses to high risk of adverse events.
Final Thoughts
What HART is ignoring, irrespective of the science they put forward, is that 7 and Pseudo have been chemically formulated and put into the market with the intent to cure, treat and mitigate disease — namely chronic pain and opioid use disorder. They have intentionally produced a novel drug and are currently marketing it without FDA approval, which is a clear violation of federal law. They should be doing more science as a part of a robust Investigational New Drug (IND) and New Drug Application (NDA) submission that not only proves the efficacy and safety of 7 and Pseudo but also shows that they are better than the drugs they seek to replace (Oxycontin, Percocet, etc.). Until such time that they have done this and gained approval from the FDA for prescribed use of 7 and Pseudo, these products should not be on the market, and should certainly not be available for $6 a pill at your local smoke shop or convenience store.
To learn more about Stop Gas Station Heroin and its mission, navigate to stopgasstationheroin.com.
Sources
[1] Human Equivalent Dose (HED) = Animal Equivalent Dose (AED) x 0.54. This is based on conversion mentioned in study design and also standard dose conversion.