Dr. Matthew Johnson: The World's Most Published Scientist on the Human Effects of Psychedelics

Dr. Matthew Johnson: The World's Most Published Scientist on the Human Effects of Psychedelics

Bryan Fields: It does seem that psychedelics, in the right context, could have a profound effect that could change someone's life. What's up guys, welcome back to another episode of The Dime. I'm Bryan Fields, and with me as always is Kellen Finney, and this week we've got a very special guest, Dr. Matthew Johnson, professor at Johns Hopkins. Dr. Johnson, thanks for taking the time, how you doing today? Guest: Oh, it's a pleasure to be with you. Thanks for having me. Doing good, excited to dive in. Kellen Finney: How are you doing? I'm doing really well, really excited to talk to Dr. Johnson, really excited to dive into psychedelics and all the fun stuff that's going on in the world right now. But more importantly, how are you doing today, Bryan? Bryan Fields: Yeah, I'm excited. There's a lot of information that we need some clarity on from Matt Johnson, and I think it's the right time, especially with psychedelics and all the compounds and information coming out. But before we dive into some of those specifics, we've got a very aggressive East Coast/West Coast battle here, and just for the record, Dr. Johnson, which side do you choose? Guest: I gotta be East Coast. I mean, I grew up mid-Atlantic, I went to college in Oregon, but I've been back on the East Coast since grad school, so 25 years or so. So I gotta go with my East Coast tribe. Bryan Fields: I love it, let the record state that. So since at least one of you is a fellow East Coaster... Guest: Like you, feel free to call me Matt. Appreciate the "Dr. Johnson" intro, but let's keep it real, call me Matt. Bryan Fields: So Matt, for our listeners, can you give a little background about yourself and how you got into psychedelics research? Guest: Yeah, so I have a PhD in experimental psychology, so I don't focus on treating disorders like a clinical psychologist, although I have very similar training. But it's more about understanding behavior, how people behave in certain situations. A big focus of my research, going back to grad school and even college, I dabbled in some cocaine research in rats. Big focus has been behavioral pharmacology, which is a fancy way of saying studying drugs — psychoactive drugs, whether legal or illegal, that affect the mind. In grad school I did work with a number of different drugs, a lot with tobacco smoking, and as a scientist, caffeine, alcohol, tobacco — these are all drugs; legal versus illegal is kind of a superficial societal thing. I did a lot of work understanding addiction to a lot of these substances, applying behavioral economics to understand the decision-making surrounding it, and how people would respond under different conditions to choose to smoke. Moving into my postdoc work, I got more involved with drug administration research beyond just tobacco in humans — cocaine, alcohol, methamphetamine, benzodiazepines, GHB, a long list. In that time I got involved with psychedelic work as well, back in 2004, and have been doing it ever since. I've had a long line of research supported by NIH studying sexual risk behavior associated with certain drugs — giving people cocaine or alcohol or methamphetamine in the lab and asking hypothetical sexual decision-making questions. It sounds crazy but it helped determine what's really driving risk behavior. And with psychedelics, since 2004 I've studied so-called "healthy normals" — non-therapeutic study of effects on personality, subjective effects like the "mystical experience," and long-term outcomes, which tend to be positive under prepared, structured conditions. Then I moved into therapeutic applications, working with distressed cancer patients, some terminal, finding long-term reductions in anxiety and depression. For about 15 years I've had a research line using psilocybin to help people quit smoking, combining my long-term interest in tobacco and nicotine with psychedelics. I've also done work with depression using psilocybin, and some work with more exotic psychedelics including salvinorin A, the primary active agent in Salvia divinorum, which is still legal in most places. I also did work comparing dextromethorphan — a ketamine relative found in cough medicine, so-called "robo-tripping" — to psilocybin. I received the first government grant since the 1960s to look at the therapeutic applications of one of the classic psychedelics, psilocybin, for tobacco addiction. That's where I spend most of my time these days, but I have a few other irons in the fire in the psychedelic world. Bryan Fields: So back in 2004, psychedelics did not have the kind of societal or cultural acceptance I'd say they have now — not fully accepted now, but definitely more mainstream. When you were first getting into that work, what was the motivation? Was there hesitancy? Walk us through those early days. Guest: It's something I wanted to research going back to college, when I uncovered the history of psychedelics — this was the 90s, at the college library, Dewey Decimal System, reading everything I could, discovering the older history of using LSD to treat alcoholism and the existential distress of terminal cancer patients. Combined with my growing interest in behavioral pharmacology broadly — how caffeine keeps you up, how alcohol makes people friendlier — psychedelics always stood out. I tell people if they're interested in the science of psychoactive drugs, they either have to be fascinated with psychedelics or they don't know much about them. There's the indigenous, cultural, sacred use across many cultures going back to prehistoric times, and the massive changes attributed to them since the 60s — artists, musicians, even Nobel Prize winner Kary Mullis said he wouldn't have been able to invent PCR, which revolutionized biology, if it weren't for psychedelic experiences. As a psychologist interested in behavior change, it's fascinating — how substances affect behavior and how we can leverage that for positive change, like helping addicted people quit. Even before modern research, there were stories of heavy drinkers taking acid once for fun and having a transformative experience that made them quit drinking. I've published research documenting these stories — people claiming mushrooms or LSD helped them quit drinking, smoking, cocaine, opioids, even cannabis, often without any therapeutic intent going in. I don't know of any other substance with that kind of single-use, decades-long transformative claim. Even cannabis, which has legitimate therapeutic uses, tends to be palliative and require continued use — not a one-time life-changing event. Kellen Finney: Was the first time you heard a story like that — a one-dose breakthrough — were you skeptical? Take us through that early skepticism and what solidified your belief this could be a game changer. Guest: My skepticism was more around the broader question of how much someone really changes — I think the changes are relatively targeted but can have a profound impact. I'd met people who quit drinking through 12-step programs and had similar "aha" experiences outside of psychedelics, so it seemed clear that people can have big life-changing experiences generally. It's become fashionable for psychedelic scientists to say they were skeptics until their first study opened their eyes — take that with a grain of salt, because it's really hard to do this human research, especially with a Schedule I substance; you put in years of work before you even dose somebody. It's okay to be a scientist and have a strong hypothesis based on observing patterns in the world, while still being open to the data. Looking at the history and the stories, it did seem psychedelics in the right context could have a profound effect. I've been blown away by the magnitude of some results — sometimes participants describe experiences after sessions that are so overwhelming and clear to them that something has changed, and you think, this has got to be good, this is going to have a lasting impact. Bryan Fields: With most drugs, the dose makes the poison. You've focused a lot on dose throughout your career — trying to figure out if there's a specific quantity that facilitates that "aha" moment. Walk us through how you choose doses and how that's shaped your studies. Guest: I've done studies using different doses — probably the biggest used four different doses of psilocybin plus a placebo in healthy normal people, looking at therapeutically meaningful outcomes like the mystical experience that relate to clinical outcomes. The results align with the older literature on "heroic doses" for classic psychedelics. A lot of people, especially with microdosing being in vogue, confuse doses — some of my study participants were seasoned psychonauts, and even they'd say "holy [expletive], you weren't kidding" about our high dose. It's not just more than a microdose, it's more than a typical recreational dose too — this is heroic dose range. Bryan Fields: Can you give us some boundaries — microdosing, recreational range, and heroic dose? Guest: Everyone's different, especially with mushrooms since potency varies like orange juice varies in vitamin C content. But high dose, in terms of psilocybin, is 30 milligrams or higher — most of my work uses 30 milligrams, historically body-weight adjusted, though we've published research suggesting that's not really necessary. That 30 milligrams is roughly equivalent to what Terence McKenna called the "heroic dose" of Psilocybe cubensis mushrooms — about five dried grams, based on average mushroom potency. To make that concrete: friends splitting an eighth-ounce of mushrooms two or three ways is not a microdose and not quite a heroic dose either — a heroic dose is closer to one person taking almost a quarter-ounce alone. A microdose is often less than half a gram, roughly one-twentieth of a full dose. At a heroic dose, if you're at Burning Man, you probably want to be zipped up in your tent for the night, not walking around. At the physiological level, psychedelics like psilocybin are remarkably safe for most healthy people — there's no known lethal overdose; you could take 100 times a high dose and it won't stop your breathing, damage your liver, or cause a fatal cardiac event, unlike most drugs. The big exception is people at severe risk of heart disease, since anything that raises blood pressure and pulse could trigger a heart attack or stroke. The real risk is behavioral — doing something dangerous while intoxicated in public, like panicking and running into traffic. It's rare, but it has happened. Kellen Finney: With microdosing continuing to rise in popularity, is there literature demonstrating real individual benefit, or is it largely a placebo effect? And if it is placebo, does that matter if people feel better? Guest: There haven't been many studies, but the more careful lab studies, including self-blinding research from Imperial College, suggest a lot of the claimed benefit, if not all, is a placebo effect — which isn't surprising, since most effective medicine is a combination of real pharmacological effect plus placebo. My best guess is there may be some real antidepressant efficacy, since we've known for 80 years that chronically augmenting the serotonin system can alleviate depressive symptoms for some people — that's different from the heroic-dose model of one-to-three sessions with lasting effects; microdosing is about regular use every few days. So far, lab studies mostly find microdosing causes mild intoxication — like impaired time perception — which is fine lying on a couch during a heroic-dose session, but not ideal if you're driving or working. On the addiction question, classic psychedelics like psilocybin and LSD don't appear to be addictive, even though they can be misused. As for whether placebo benefit is "okay" — there's a theoretical concern: most classic psychedelics activate serotonin 2B receptors in addition to 2A receptors, and chronic activation of 2B receptors has been linked to heart valve disease (this is why the diet drug fen-phen was pulled from the market). That's not a concern for occasional heroic-dose use, but taking something twice a week for five years raises the question, and nobody really knows the answer yet. There's also the real-world risk of legality — a Silicon Valley CEO was dropped from a board for bragging about microdosing a Schedule I substance, and Elon Musk faced consequences (every SpaceX employee now gets drug tested) just for smoking a joint on the Joe Rogan podcast. On creativity, I'd put higher odds on high-dose heroic experiences producing creative outcomes — think The Beatles before and after LSD — since psychedelics likely broaden the selection of ideas, some brilliant, some terrible, and society needs both the wild idea generators and the people who sift through them. Microdosing and creativity is mostly anecdotal at this point. Bryan Fields: Let's switch gears and do a quick rapid fire. True or false: cannabis is addictive. Guest: True, with a caveat — most people who try it don't become addicted, and the consequences for those who do are nowhere near those of alcohol or many other addictive substances, but yes, a subset of users do have trouble stopping. Bryan Fields: The number one thing a majority of society gets wrong about psychedelics? Guest: They don't necessarily lead you to become a more ethical, better person. Bryan Fields: True or false: all drugs have roughly the same abuse potential. Guest: False. Bryan Fields: True or false: the psychology of xenophobia hinders the public's understanding of the medicinal benefits of psychedelics. Guest: Definitely true. Bryan Fields: A compound you haven't studied but are most intrigued by? Guest: 5-MeO-DMT. Bryan Fields: If psychedelic therapies fail or never make it, what's the number one reason why? Guest: Overzealous enthusiasm. Bryan Fields: What researchers or studies are a must-read for you? Guest: The old days — the first big group that doesn't get the attention it deserves, the Saskatchewan group: Humphry Osmond, Abram Hoffer, Duncan Blewett, and others — the first to discover psychedelic therapy. Bryan Fields: If you could put anything on a billboard to reach billions of people — an image, a quote, a word — what comes to mind? Guest: "Think beyond yourself." Bryan Fields: If ethics and money were no issue, what research or study would you do? Guest: Examining whether psychedelics can, at least in some cases, lead to telepathic abilities or similar phenomena. Bryan Fields: Have you ever felt strongly one way pre-study only to be shocked after it concluded? Guest: Yes — with a study on Salvia, I was astonished by the degree and frequency to which people claimed subjective "entity contact," and that some claimed incidental therapeutic effects from it, which isn't a common anecdote with smoking Salvia divinorum otherwise. Bryan Fields: What's your current perspective on the state of psychedelic research — do you believe it's cult-like? Guest: Yeah, definitely there's a lot of cult vibes. There's a lot of hero worship and ego inflation among certain scientists. People confronting huge existential questions — does God exist, what's the meaning of life — after a psychedelic experience can be easily taken advantage of, including inappropriate relationships between clinicians and clients. That's a very real potential for abuse in this field, similar to what's happened in religious contexts, and we're going to see cases of credentialed doctors sleeping with patients and acting as would-be gurus. Bryan Fields: Prediction time — what breakthroughs do you expect, and what will the landscape look like in five years? Guest: Based on the current trajectory, depending on the FDA and the EMA in Europe, we'll likely have multiple approved uses for MDMA and psilocybin for several disorders — depression, various substance use disorders, maybe end-of-life care — plus more understanding of the underlying brain mechanisms. There'll be more research into other psychedelics and other disorders, and we'll likely find out some things don't work — it wouldn't be surprising if psychedelics don't pan out for something like anorexia, because nothing works for everything. Bryan Fields: Kids, drugs, and a developing brain — do you think we'll see studies on potential benefits for kids? Any guesses on where there could be a big opportunity? Guest: Yes, in therapeutic populations for sure. The FDA actually incentivizes this — MAPS has plans to study MDMA in adolescents, because there's real risk in not treating severe PTSD or depression in kids, including suicide risk. Once something is approved for adults, the pathway moves to older minors, typically starting around 16 to 17 years old. Parents are naturally risk-averse with kids, which is understandable, but you have to be balanced and remember untreated mental health disorders in kids and adolescents carry real risk too. You want to be cautious and principled, not let a theoretical, bumper-sticker-level concern block responsible inquiry. Kellen Finney: I agree with what Matt's saying. Think about how many kids have had traumatic experiences they carry into their psyche for a decade-plus, then hit their mid-20s or mid-30s and realize all their issues stem from something unresolved at age 12. There's an opportunity for psilocybin or MDMA therapy to address that early and extend someone's quality of life for decades. There's massive potential, but as Matt said, significant caution and work is needed before giving a child a psychoactive compound like that. Bryan Fields: I think if these compounds can help people, and there's scientific evidence they change lives, it's important we pursue that — giving kids with PTSD from early trauma a chance to reset. It'll take a lot of science to confirm those claims, but helping people is something society should do a better job of pursuing. Guest: And we should remember we routinely give kids all kinds of psychoactive substances with frankly worse profiles — Adderall is essentially amphetamine, just as addictive as cocaine. I'm not saying it should never be used, but it's overused, in my opinion, by a lot. We routinely give kids benzodiazepines and stimulants that, in the scheme of things, carry more reason for concern than, say, MDMA or psilocybin used a couple of times under professional medical supervision in a clinic for PTSD or depression. It's all about the risk-benefit ratio — helping people without harming them. Bryan Fields: Perfectly well said. Matt, for listeners who want to get in touch or read more, where can they find you? Guest: Probably the best place is to follow me on Twitter, or X as they call it these days, at Drug_Researcher. Bryan Fields: Awesome, we'll link it all in the show notes. Thanks for taking the time, this was fun. Guest: Oh, my pleasure, guys.