“This could save lives, cure depression, help alcoholism, get people off opioids—why wouldn’t I want to be invested?”
Shark Tank host Kevin O’Leary is sitting across from me in a restaurant talking about a recent investment. He was part of a $6 million round in MindMed, a company that’s taking psychedelic drugs and turning them into medicine. Its first drug has the potential to turn a person’s addictions—to cocaine, methamphetamine, morphine, sugar, alcohol—off like a light switch. It has a clear opportunity to help lower the nearly 70,000 annual drug overdose deaths that take place in the U.S. But the compound, 18-MC, has yet to undergo human efficacy trials, leaving open a big question: Will it even work?
Scientists have been aware of the potential of LSD and psilocybin (the psychoactive component in mushrooms) as addiction killers for decades. Outside of the lab, too, people have been experimenting with various psychedelics to cure drug addiction since the 1960s. In recent years, the U.S. government has opened up to the use of psychedelics to quell intractable health problems like depression and opioid addiction. Initial research seems to indicate that altering a person’s reality leaves them with indelible experiences that can lead to sobriety.
This could save lives, cure depression, help alcoholism, get people off opioids—why wouldn’t I want to be invested?”
That is consistent with the rhetoric of so-called “psychonauts,” people who take psychedelics as a transformational exercise. Psychedelics “change one’s mind in enduring ways,” writes Michael Pollan in his 2018 book How To Change Your Mind. MindMed’s early research suggests that it’s the drugs themselves that are resetting the brain and freeing people from their cravings. The company is engineering variants as well as tiny doses of psychedelic drugs, both of which aim to treat patients without getting them high.
The company, which is not even a year old, was inspired by a Silicon Valley trend that has been simultaneously lauded and ridiculed: micro-dosing. While living in San Francisco, MindMed founder JR Rahn came into contact with hoards of tech workers who take minuscule doses of psychedelic drugs as way to wean themselves off of stimulants like Adderall, while maintaining a focused edge. But psychedelics get you high and can leave you in a mind-melded state for hours, which for a lot of people is a nonstarter. For both the micro-dosers and the people looking for help in recovering from an addiction—not to mention the Food and Drug Administration, the Drug Enforcement Agency, and the pharmaceutical companies that have the money and reach to bring a drug to market—that makes psychedelics risky business. Rahn’s first drug aimed at treating addiction has engineered out the psychedelic experience. But can it still be effective without the trip?
Meet the wonder drug
“As I lay there, I could feel the medicine take over my entire body, as if an extraterrestrial had entered my bloodstream and was taking over. I could feel it doing its work on my brain, repairing the virus known as addiction,” writes a Reddit user detailing their experience with ibogaine, a hallucinogenic substance with a reputation for wiping out the pull of addiction. It’s also the basis for 18-MC, MindMed’s first compound.
I could feel it doing it’s work on my brain, repairing the virus known as addiction.”
Ibogaine is found in a woody West African shrub that sprouts orange fruits like upside-down tear drops. In Gabon and Cameroon, members of the Bwiti religion eat rootbark from the Iboga Tabernanthe bush as part of a ceremonial confirmation of their faith. Americans have sought out this rite of passage for decades in hopes of enlightenment. In blog posts and on Reddit threads, ibogaine enthusiasts detail how the rootbark renders intense visions, hallucinations, and deep vortexes of memory followed by introspection. It can take days to go through.
This kind of self-reported experimentation constitutes a chunk of the available data on the effects of psychedelics. Personal experience has also served as a catalyst for scientific research. When Howard Lotsof, a bearded young man with soft sloping blue eyes, took ibogaine sometime in the 1960s, he was addicted to heroin. So were the six friends with whom he took the drug. As the story goes, they tripped for two days straight. In the twilight of the come down, five of them realized they had lost their compulsion for heroin. Lotsof believed he had a curative on his hands, but took his time figuring out what to do about it.
In 1983, he created a foundation and started reaching out to politicians and scientific researchers about ibogaine, asking them to test it. That same year, he filed a patent for the use of ibogaine as an addiction interrupter (and started a company called NDA International).
“I was the first one, for better or worse, whose curiosity was piqued enough,” says Stan Glick, a researcher at Albany Medical Center and retired professor of the adjacent medical school. “I thought we’d give it to a few rats, they’d do something weird, I’d satisfy my curiosity, and that would be the end of the story.”
I thought we’d give it to a few rats, they’d do something weird, and that would be the end of the story.”
Glick got ahold of pure ibogaine and tested it on morphine-addicted rats. Hours in, the rats were convulsing in whole body tremors, which Glick believes were signs of hallucination. But a day later, he found the rats were slowing if not stopping their intake of morphine.
Soon, other researchers and academic institutions, egged on by Lotsof’s advocacy, were studying ibogaine. New work revealed the substance had some other side effects including vomiting and a slowed heart rate that in some cases is lethal. Those effects coupled with the hallucinations indicated to Glick that ibogaine was not really an ideal candidate for medical use. He teamed up with Martin E. Kuehne, a medicinal chemist from the University of Vermont, to engineer a version that eliminated some of these side effects. He and Kuehne tested around 60 compounds, and discovered 18-MC. When he published his first paper on the substance in 1996, he thought there would be immediate interest. This was a substance that could potentially get someone to look at drugs they had once been desperate for and shrug.
But big pharmaceutical companies weren’t interested in the addiction space 20 years ago, Glick says. While smaller pharmaceutical companies were more eager, they lacked the necessary funds to push the compound through clinical trials.
Eventually, Glick cofounded his own drug company, Savant Health and Wellness Partners. Through this organization, 18-MC was able to land a National Institute on Drug Abuse grant in 2012 for just over $6.5 million that would take the compound through human safety trials.
As far as Glick can tell from the initial results, 18-MC does not have hallucinatory or heart effects. It is also unique in how it regulates the part of the brain involved in addictive behavior. Addictive drugs like alcohol or cocaine cause the brain to release a surge of the feel-good chemical dopamine. Rather than attacking the dopamine system itself, 18-MC leverages a different set of neural pathways to indirectly modulate dopamine release. “That’s why I think it works on multiple drugs, because it’s not focused on a specific action in the dopamine pathway,” Glick says.
If this drug works in 60% to 70% of people, which I think it might, that’s a big step forward.”
There are already a series of drugs aimed at helping addicts decouple themselves from drug dependence. They largely come in two forms: a less addictive replacement that allows a person to wean off the addictive drug, or a drug that dulls the high. Naltrexone, which dampens the dopamine release associated with drinking, has proven fairly effective at helping people dissociate the feel-good sensation from the act of drinking. However, people tend to stop using it, because there’s no real incentive—Naltrexone doesn’t kill cravings. 18-MC, on the other hand, has the potential to extinguish that nagging desire for a high altogether.
“If this drug works in 60% to 70% of people, which I think it might, that’s a big step forward,” Glick says.
The downsides of the trip, and the rise of micro-dosing
After working on the 18-MC for nine years, Savant ran out of money and was not able to move the program to the next phase. In June 2019, MindMed bought 18-MC as well as the team working on it in an all-stock deal. The plan is to run safety trials in the second half of 2020 and proceed to efficacy trials by the fourth quarter. The drug’s properties align with Rahn’s belief that hallucinogenics may work for some, but more people could be helped if the psychedelic experience was engineered out.
That goes against prevailing wisdom, which says that the trip is the thing that cures. People who have used ibogaine and other psychedelics to rid themselves of their addiction say it’s the mystical transcendence of the high that triggers them to kick their habit. Carine McLaughlin, who participated in a study at Johns Hopkins testing the effects of psilocybin on addiction, says it was the phantasmagoria of looming clouds that made her feel the weight of her nicotine addiction. “The ceiling of this room were clouds, like heavy rain clouds and gradually they were lowering and I felt like I was suffocating,” McLaughlin explained in an interview on 60 Minutes.
Roland Griffiths, who lead the study and is the founding director of the Johns Hopkins Center on Psychedelic and Consciousness Research, supports the idea that hallucinations play a significant role in patient recovery. “They come to a profound shift of worldview, essentially a shift in a sense of self,” Griffiths said on the same segment. “Their worldview changes and they are less identified with this self narrative—people might use the term ego—and that creates a sense of freedom.”
I turned to him and I said, ‘Because some of us actually have to go to work.’”
But to Rahn’s point, this nirvana comes at a cost: intoxication. Rahn recounts a conversation he had with Dennis McKenna, who is known, along with his brother, for writing the how-to book on growing magic mushrooms. “[McKenna] was saying, ‘Why would you want to micro-dose?’ And I was like, ‘What do you mean?’ He’s like, ‘There’s just such a great other world waiting for you on the other side of a macro-dose.’ And I turned to him and I said, ‘Because some of us actually have to go to work.'”
This attitude is reflective of that infamous persona in Silicon Valley: the micro-doser. While the original American psychonauts danced in Golden Gate Park’s tall grasses with flowers in their hair, today’s psychonauts sit in corner offices of buildings that scrape against marmalade skies. The micro-doser doesn’t have time for an eight-hour-long trip. They have businesses to scale.
Rather than swallowing small tabs of 50 to 150 micrograms of LSD, micro-dosers take 5 to 10 microgram doses every three to four days, per the instruction of James Fadiman, widely considered the father of micro-dosing. Instead of making the contours of objects melt or conjuring colors that don’t exist, these minuscule amounts render the world in a more saturated tones. “Basically the world looks the way it normally does, maybe a little clearer, as if when you first get a new prescription of glasses and everything looks a little brighter and the edges are a little crisper and you function better,” Fadiman explained on a podcast in 2016.
While there is a certain comedy to the idea that tech executives are downing psychedelics as some kind of ultimate brain performance hack, this trend may also be helping to wipe away the grungy sheen that has obscured psychedelics for decades. In addition to helping them focus, micro-dosing has helped this moneyed group wean themselves off of stimulants like Adderall and Ritalin, which may also bring more funding to the table.
The micro-doser doesn’t have time for an eight-hour-long trip. They have businesses to scale.
There is also a need to create a more standard form of taking these drugs. What evangelists will not tell you is that micro-dosing is not an exact science and hardly yields even results. Though there are underground sellers that cut up and sell micro-doses, many people cut their own tabs. If for whatever reason the dose is wrong, a person could be sent unintentionally floating into another world for several hours. There are also anecdotal reports that micro-dosing doesn’t reliably yield the slightly elated focus it promises and instead puts people in a scattered state.
As a pharmaceutical company, MindMed is hoping to put science behind micro-dosing, yield a more precise method of dosing, and prove once and for all that there is legitimacy to these anecdotal uses. “We will be looking at micro-dosing all types of psychedelics in the future,” Rahn says. “There’s a lot of anecdotal evidence that it works, and so I think that helps de-risk the proposition of doing an expensive phase-two trial.”
The legal limits of psychedelics
In the past, regulation has thwarted this kind of development. But the Food and Drug Administration has recently signaled its enthusiasm for psychedelics research. In the last several years, it’s awarded psilocybin (from mushrooms) and MDMA (known on club dance floors as molly) with “breakthrough” designations. The changed stance could help expedite new treatments for pervasive health problems like drug-resistant depression and PTSD (a diagnosis that affects approximately 12% of veterans).
But there’s a problem. Though the FDA has cleared a path for psychedelic drug development, the laws around these drugs haven’t changed. Psilocybin, MDMA, LSD, ibogaine, and marijuana are among the most controlled substances in the United States and are illegal to possess. They’re classified as Schedule I drugs under the Controlled Substances Act, which means they are considered to have no known medical use and a high potential for abuse.
All of the current programs involving psychedelics must be taken at a medical office and not at home. This is done in part so a physician can monitor the patient in the two hours post-treatment while they grow dizzy or enter a dreamlike state. It’s also to curb potential abuse. Such conditions could ultimately limit who has access to these drugs.
It’s unlikely that any of these drugs will ever be legalized, but they could be re-scheduled with less restrictive classifications once they are approved by the FDA. But that could be a daunting process. Changing the status of a Schedule I drug is at least partially up to the Drug Enforcement Administration, which is more concerned with containing the misuse of drugs than ensuring an effective medication is widely available.
We will be looking at micro-dosing all types of psychedelics in the future.”
However, MindMed’s current non-hallucinogenic compound, 18-MC, isn’t yet classified and may not face the same lag in getting to the market (a good sign for O’Leary, MindMed’s investor). However, the DEA could just as easily label it similarly to ibogaine. The micro-doses that MindMed plans on developing may also get caught in this legal quagmire. Rahn thinks that if his company can prove the efficacy of these drugs, the laws will bend to allow them to proliferate.
It’s worth noting that the FDA and DEA have still not removed marijuana from the Schedule I list, even though several states have legalized it and it is sold as a therapeutic. There is the possibility that if the DEA and FDA are slow to make the status change, Congress could force it. But this Congress in particular is having its own struggles moving legislative agenda along.
This strange legal conundrum may create a complicated regulatory space for doctors prescribing this medication. The DEA doesn’t specify what constitutes appropriate or legitimate use of a psychedelic (or what qualifies as abuse). That might scare off the medical community from getting involved. MindMed’s psychedelic variants could evade this legal snare all together since it’s an entirely new substance, but that decision is as much the FDA’s as the DEA’s.
Even still, there is incredible opportunity to treat addiction, particularly prescription opioid, which is estimated to cost the United States $78.5 billion annually.
“This is one of these binary investments,” O’Leary says. “Extraordinary returns, or zero.”