Essentials: Psychedelics for Treating Mental Disorders | Dr. Matthew Johnson

Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now, my conversation with Dr. Matthew Johnson. Well, Matthew, I've been looking forward to this for a long time. I'm a huge fan of your scientific work, and I'm eager to learn from you. So-

Likewise. Big fan and happy to do this with you.

Great. Well, thank you. My first question is a very basic one, which is, what qualifies a substance to- as a psychedelic?

Nomenclature is a real challenge in this area of psychedelics. So starting with the word psychedelic, it just- if- if you're a pharmacologist, it's- it's not very satisfying, because that term really spans different pharmacological classes. In other words, if you're really concerned about receptor effects and the basic effects of a compound, it spans several com- classes of compounds. But overall- so it's really more of a- a cultural term or a- it does have a relationship to drug effects, but it's at the- at- at a very high level. So all of the so-called psychedelics across these distinct, uh, classes that I can talk more about, um, the way I put it is, they all have the ability to profoundly alter one's sense of reality, and that can mean many things. Part of that is profoundly altering the sense of self, um, acutely, so when someone's on the psychedelic. Um, so the different classes that can be- the specific pharmacological classes that can be called a psychedelic are, one, the- what are called the classic psychedelics. So in the literature, you'll see that term. And hallucinogen and psychedelic all have traditionally been used synonymously. Um, I think there was a little of a tendency to stay away from psychedelic 'cause of the baggage, but there's been a return to that in the last several years. But the classic psychedelics or classic hallucinogens are things like LSD, um, psilocybin, which is in so-called magic mushrooms. It's in over 200 species that we know of so far of mushrooms. Uh, dimethyltryptamine, or DMT, which is in dozens and dozens of- of- of plants. Um, mescaline, which is in the peyote cacti and some other cacti like San Pedro. And even amongst these classic psychedelics, um, there are two structural- structural classes. So that's the chemistry. There's the tryptamine-based compounds like psilocybin and DMT, and then there's the phenethylamine-based compounds. So these are the basic- two of the basic, the building blocks that- that you're starting from, either a tryptamine structure or a phenethylamine structure. But that's just the chemistry. The- all of the- what's more important, or at least to- to someone like me, are the receptor effects, and then ultimately, that's going to have a relationship to the behavioral and subjective effects. So all of these classic psychedelics serve as agonist or partial agonist at the serotonin-2A receptor, so subtype of serotonin receptor. Then you have these other classes of- of- of- that you- compounds that you could call a psychedelic. Another bi- big one would be the NMDA antagonist, so this would include ketamine, PCP, and dextromethorphan, something I've done some research with, which folks might recognize from, like, robo tripping, guzzling, like, you know, uh, cough syrup. A large overlap in the types of subjective effects that you get from those compounds compared to the 2A agonist classic psychedelics. Um, but then you have another big one, MDMA, which really stands in a class by itself. So it's been called an entactogen, and- and, uh-