03/12/2025
The Remarkable Story of 18MC, A Drug that Can Cure Any Addiction
Professor Martin Kuehne, a brilliant natural products chemistry researcher at the University of Vermont, had spent the 1980’s and the 1990’s studying the natural products in a variety of chemical classes, including the iboga and coronaridine families of compounds. Even a non-chemist can spot the similarities between these two classes just by looking at the structures （See below)
Although the compounds could be isolated, the instrumental technology of this time period was not yet sufficiently sophisticated to determine exactly what the structures were. The standard practice for natural product chemists was to systematically synthesize the molecules in a logical manner step by step. If the end result of the synthesis exactly matched what they thought the structure was proposed to be, they had a structure proof. If it did not, the proposed structure had to be revised. This is Scientific Method in practice. Martin and his group not only devised a synthesis to prove the various structures, but went on to mimic the way the plants make them naturally. They then went on to make variations of the natural products, which Chemists call “derivatives”. These had to be prepared from scratch, with long, many-step syntheses. Among the compounds made was one where a tiny modification had been installed: a methoxy on the end of the ethyl on the far end of the molecule. Although this should have had no more effect than a wart on the ass of the elephant, it had a dramatic impact on its neurological activity.
A collection of the compounds made by Martin Kuehne’s group was brought to Stan Glick, a pharmacologist at the Albany School of Pharmacy, for testing. When tested on rats, 18MC stood out as stopping the craving of addicted animals, whether the addiction was from alcohol, ni****ne, or opiates. A joint patent came out in 1998, followed by a couple of allied patents a couple of years later.
Imagine a toggle switch in the brain, and that toggle switch gets pushed over to addiction when exposed to addicting substances. Thereafter the owner of that brain is a slave to the addiction so long as that toggle switch has been pushed over. Ibogaine is the first compound known to push that toggle switch back to the day before the addiction started, but there is a high price to pay for users of ibogaine. Those who take it get quite sick, physically, and frequently there is heart damage. Moreover, it distorts the function of the brain, and elicits a “waking dream”, where long term memories come flooding back to the user. Although this is technically not a psychedelic effect, it was enough for the DEA to classify it as Schedule 1 not long after its appearance. There is also the added problem that Ibogaine originates from a rare shrub in Africa, and the high demand has all but wiped out the original source. Although synthetic Ibogaine is coming on the scene, there is still a serious health trade-off with its use.
Because of what 18MC has, and has not in its structure, it is fine-tuned to just one activity: pushing back that toggle switch in the brain. It does not have any of the adverse health effects of Ibogaine, but still stops the craving. In the animal testing, it was capable of doing this with a single dose. 18MC is not as scheduled material because there is no “fun” component in its activity.
To tell the rest of the story, I have to switch to the first person, because I am part of it.
In the 1990’s Stan Glick approached AMRI, a company where I was a minority owner and senior research chemist, with the request that they scale up the preparation so that they could do clinical trials. At that time, although I was aware of the project, I was not part of it. The 21-step synthesis proved insurmountable for AMRI, and they were never able to produce more than 35 g, not the many kilos required for clinical trials. After AMRI went public, I retired, moved to Champaign, Illinois, and started my company Obiter Research. It was not long before we were approached to make kilos of 18MC. At the time, I had to decline because the existing prep was simply not scalable. Among the many other challenges, one of the steps required an equal weight of palladium. While one can get away with this on a 100 g scale, it is simply not realistic to contemplate using hundreds or thousands of kilos of palladium to manufacture.Nonetheless, I realized the potential for 18MC, and for the next two years tried to find a practical alternative way to make it on our own. Everything we tried proved to be a dead end. About this time, two people I had consulted for previously approached me with a proposal to start a final enterprise before they retired. I suggested 18MC, hoping to get some funding. They liked the idea, and Savant was formed The first meeting was in Manhattan, with some very significant players present, but the group was skeptical that enough 18MC could be produced for testing, and wanted to use a seriously poorer alternative. Full of naïve bravado, I bragged that by June I could have 200 g for testing. This was the end of January. We delivered, thanks to the star performance of my two lead chemists, Matt Burge and Sean Kerrigan. However, it cost me half a million dollars to do. (Quite a few others subsequently joined the project, and thanks go out to all of them, too.)
It turns out that 18MC has more than one activity: it is also effective as a treatment for Leishmaniasis, so this first material was largely used for Phase 1 trials in Brazil treating this horrible parasitic disease. Armed with some grant money, Savant was able to contract Obiter to produce GMP material, about half a kilo for further clinical testing. Some Phase 2 testing was done with Savant, but Savant sold itself to MindMed, and in 2021, MindMed used the last of the GMP batch on Phase 2 clinical testing. Along the way, Obiter had vastly improved the process, so that now scale was not a limitation, and now holds five patents, the key one around a composition of matter claim. By 2018, the original patent on 18MC expired, making it generically available for use, but still protected by the only way to make it, held by Obiter. MindMed shelved 18MC in 2021 to focus on their other priorities. (MindMed Shelves 18-MC for Opioid Use Disorder and Further Cuts Pipeline | Psychedelic Spotlight). As an insider and significant shareholder, I can say that there is a lot more to this choice than meets the eye. I have liquidated my holdings in this company.
So here I am, at 72 years old, and I have in my hands the ability to help a lot of suffering people in the form of patents that are aging every day. Recently I thought that if I can find philanthropic money to complete the FDA trials, I could just donate the patents or provide 18MC at cost, we could at least get it out to the public. No such luck. We are unable to find anyone willing to help philanthropically, and now, with the Federal government in turmoil, it will be next to impossible to get a drug through the FDA. There is one other avenue that can be exploited to introduce 18MC to the people who need it. Since 18MC can be thought of as the next-generation version of ibogaine, improved due to the lack of bad side effects, it would be logical to offer it as an experimental drug to ibogaine clinics. Obiter will be producing GMP batches of 18MC in 2025, and offering it to ibogaine clinics to assess its performance first hand. Since these clinics already have experience with ibogaine, these are the logical places to start, anyway. GMP on the small scale is rather expensive, and necessarily, the early batches are costly. However, with increased demand, we can get efficiency of scale, and the price can drop considerably. Obiter has sent out invitations to a number of ibogaine clinics around the world, but due to the limited supply, we can only respond on a first-come-first serve basis. Already, at the time of this writing, much of our first lot has been claimed, even though it is not yet complete. Do you want to be the clinic that has only ibogaine to offer?
