There’s been an explosion of interest in the use of psychedelics in psychiatry. Like everyone else, I hope this works out. But recent discussion has been so overwhelmingly positive that it’s worth reviewing whether there’s a case for skepticism. I think it would look something like this:

1. Psychedelics have mostly been investigated in small studies run by true believers. These are the conditions that produce a field made of unreplicable results, like the effects of 5-HTTLPR. Some of the most exciting psychedelic findings have already failed to replicate; for example, a study two years ago found that psilocybin did not permanently increase the Openness personality trait. This was one of the most exciting studies and had shaped a lot of my thinking around the issue. Now it’s gone.

2. Some of the most impressive stories involve psychedelic-assisted psychotherapy, where people who talk with a therapist, while on a substance, obtain true insight and get real closure. But every psychotherapy has amazing success stories floating out there. Back when psychoanalysis was new, the whole world was full of people telling their amazing success stories about how Dr. Freud helped them obtain true insight and get real closure. I think of psychotherapy as a domain where people can get as many amazing success stories as they want whether or not they’re really doing anything right, for unclear reasons.

3. Ketamine is the best comparison for psychedelics. Like psychedelics, it’s often used as a recreational drug, and produces profound experiences. Like psychedelics, it got hyped as an exciting new innovation that was going to revolutionize everything in psychiatry (in this case, depression treatment). But it’s been in pretty common (albeit non-formulary) use for five years now, and nothing has been revolutionized; my (very anecdotal) impression is that most patients who seek ketamine treatment find it only about as helpful as anything else. The gold-standard FDA studies are abysmal, worse than most other antidepressant medications. I’m sure ketamine works great for some people, just as SSRIs, therapy, and diet/exercise work well for some people. But at least so far it hasn’t been revolutionary.

4. Another good comparison is NSI-189. Again, a totally revolutionary new drug with a totally revolutionary new mechanism, with so many anecdotes of amazing success that depressed people started getting it on the black market before the FDA trials were even underway. People were posting testimonials that NSI-189 changed their life and that it was going to destroy the market for every other antidepressant. When the FDA trials finally finished, it was discovered to be ineffective. Seriously, the graveyards are littered with revolutionary new treatments for treatment-resistant depression that have great success in anecdotes and preliminary studies.

5. Between 10% and 50% of Americans have tried psychedelics. If psychedelics did something shocking, we would already know about it. I occasionally hear stories like “I did LSD and my depression went away”, but I also occasionally hear stories like “I did LSD and then my depression got worse”, so whatever. I know plenty of people who use heroic amounts of LSD all the time, and are still nervous wrecks. It’s possible there’s some set and setting that will improve this, but see part 7 below.

(one exception to this might be microdosing, which is a pretty new idea and might work differently from regular trips.)

6. In my model of psychedelics, they artificially stimulate your insight system the same way heroin artificially stimulates your happiness system. This leads to all those stories where people feel like they discovered the secret of the universe, but when they recover their faculties, they find it was only some inane triviality. This sounds very likely to produce people who think their psychedelic experience has changed everything and solved all their problems, which means we should discount these impressions as evidence that psychedelics really do change everything and solve all your problems. Granted, feeling like you truly understand the universe may itself help with depression, but I worry this is not a very lasting effect. See my posts on PIHKal and Universal Love, Said The Cactus Person.

7. Even if all of the above are wrong and psychedelics work very well, the FDA could kill them with a thousand paper cuts. Again, look at ketamine: the new FDA approval ensures people will be getting the slightly different esketamine, through a weird route of administration, while paying $600 a pop, in specialized clinics that will probably be hard to find. Given the price and inconvenience, insurance companies will probably restrict it to the most treatment-resistant patients, and it probably won’t help them (treatment-resistant patients tend to stay that way). Given the panic around psychedelics, I expect it to be similarly difficult to get them even if they are legal and technically FDA-approved. Depressed people will never be able to walk into a psychiatrist’s office and get LSD. They’ll walk into a psychiatrist’s office, try Prozac for three months, try Wellbutrin for three months, argue with their insurance for a while, eventually get permission to drive to a city an hour away that has a government-licensed LSD clinic, and get some weird form of LSD that might or might not work, using a procedure optimized to minimize hallucinations. I don’t know what the optimal set and setting for LSD is, but if it’s anything other than “the inside of a government-licensed LSD clinic, having a government-licensed LSD therapist ask you standard questions”, you won’t get it.

I hope I am wrong about this, I really do. And I think there’s a good chance that I might be. I really want psychedelic research to succeed and I support it wholeheartedly. But there’s been so much hype around so many things before that I want to avoid getting burned again, so I ‘ll stay skeptical for now.