[Epistemic status: very speculative, asserted with only ~30% confidence. On the other hand, even though psychiatrists don’t really talk about this it’s possible other groups know this all already]

A few weeks ago I gave a presentation on the history of early psychedelic research. Since I had a tough crowd, I focused on the fascinating biographies of some of the early psychedelicists.

Timothy Leary was a Harvard professor and former NIMH researcher who made well-regarded contributions to psychotherapy and psychometrics. He started the Harvard Psilocybin Project and several other Harvard-based experiments to test the effects of psychedelics on normal and mentally ill subjects. He was later fired from Harvard and arrested; later he accomplished a spectacular break out of prison and fled to Algeria. During his later life, he wrote books about how the human brain had hidden circuits of consciousness that would allow us to live in space, including a quantum overmind which could control reality and break the speed of light. He eventually fell so deep into madness that he started hanging out with Robert Anton Wilson and participating in Ron Paul fundraisers.

Richard Alpert was Leary’s co-investigator at the Harvard Psilocybin Project. He, too, had all the signs of a promising career, including a psychology PhD from Stanford, a visiting professorship at Berkeley, and a combination academic/clinical position at Stanford. After his work with Leary, he moved to India, changed his name to Baba Ram Dass, and became one of the world’s most prominent advocates for bhakti yoga.

John Lilly was a doctor, a neuroanatomy researcher, and an inventor who helped develop the principle behind many modern neuroprosthetics. He was always very strange, and did a lot of work in human-dolphin communication and SETI even before starting his work with LSD. But in the 1960s, he ran across Richard Alpert, joined in his LSD experiments, and became even stranger. He started writing books with names like “Programming And Metaprogramming The Human Biocomputer”, and arguing that benevolent and malevolent aliens were locked in a battle to manipulate Earth’s coincidences and with them the future of the human species. He became an expert yogi and claimed to have achieved samadhi, the highest state of union with God.

Kary Mullis is kind of cheating since he was not technically a psychedelicist. He was a biochemist in the completely unrelated field of bacterial iron transport molecules. But he did try LSD in 1966 back when it was still a legal research chemical. In fact he tried 1000 micrograms of it, one of the biggest doses I’ve ever heard of someone taking. Like the others, Mullis was a brilliant scientist – he won the Nobel Prize in Chemistry for inventing the polymerase chain reaction. Like the others, Mullis got really weird fast. He is a global warming denialist, HIV/AIDS denialist, and ozone hole denialist; on the other hand, he does believe in the efficacy of astrology. He also believes he has contacted extraterrestrials in the form of a fluorescent green raccoon, and “founded a business with the intent to sell pieces of jewelry containing the amplified DNA of deceased famous people like Elvis Presley”.

I wondered if there might be a selection bias in which psychedelicists I heard about, or that I might be cherry-picking the most unusual examples, so I looked for leading early psychedelics researchers I’d never heard of before and checked how weird they were. My sources told me that the two most important early psychedelicists were Humphry Osmond (who invented the word ‘psychedelic’ and may have been the first person to experiment with LSD rigorously) and his colleague John Smythies.

Osmond has an impressive early resume: started off as a surgeon, became a psychiatrist, did some well-regarded research into the structure of the human metabolite adrenochrome. And although he did not become fluorescent-alien-raccoon level weird, he can’t quite be called normal either. He became one of the founders of orthomolecular psychiatry, a discipline arguing that schizophrenia and other psychiatric diseases can be cured by massive amounts of vitamins – this is currently considered pseudoscience. His publications include the article “Selection of twins for ESP experimentation” in International Journal of Parapsychology, and a history of psychedelics records that “after his mescaline experiment in 1951, Dr. Osmond claimed to have successfully transmitted telepathic information to a fellow researcher, Duncan Blewett, who was also under the influence of mescaline, leading an independent observer to panic at the uncanny event.” He seems to have maintained a lifetime interest in parapsychology, Jungian typological analysis, and a field of his own invention called “socio-architecture”.

Smythies was a neuropsychiatrist, neuroanatomist, biochemist, EEG researcher, editor of the International Review of Neurobiology, etc, etc, etc (also, a cousin of Richard Dawkins). He is 94 but apparently still alive and going strong and making new neuroanatomical discoveries. He was one of the first people to investigate the pharmacology of psychedelics and helped with Osmond’s experiments in the early 1950s. He has also written The Walls Of Plato’s Cave, a book presenting a new theory of consciousness which “extends our concepts of consciousness and analyses possible geometrical and topological relations between phenomenal space and physical space linked to brane theory in physics” (I kind of wish I was a fly on the wall at his and Dawkins’ family reunions).

My point is that the field of early psychedelic research seemed to pretty consistently absorb brilliant scientists, then spit out people who, while still brilliant scientists, also had styles of thought that could be described as extremely original at best and downright crazy at worst.

I think it’s important to try to understand why.

First possibility: you had to be kind of weird to begin with in order to be interested in researching psychedelics. On the one hand, this is surely true; on the other, the early psychedelicists ended up really weird. At least in the early days I’m not sure psychedelics had the reputation for weirdness they now enjoy, and I’m also not sure that we’re living in a world where a high enough percent of psychiatrists go off to become gurus in India, that we can just dismiss LSD research as happening to attract that type of person.

Second possibility: I know that almost all of these researchers (I’m not sure about Smythies) used psychedelics themselves. Psychedelic use is a sufficiently interesting experience that I can see why it might expand one’s interest in the study of consciousness and the universe. Perhaps this is especially true if you’re one of the first people to use it, and you don’t have the social setting of “Oh, yeah, this is that drug that makes you have really weird experiences about consciousness for a while”. If you’re not aware that psychedelic hallucinations are a thing that happens, you might have to interpret your experience in more traditional terms like divine revelation. Under this theory, these pioneers had to become kind of weird to learn enough for the rest of us to use these substances safely. But why would that make John Lilly obsessed with aliens? Why would it turn Timothy Leary into a space colonization advocate and Ron Paul supporter?

The third possibility is the one that really intrigues me. A 2011 study found that a single dose of psilocybin could permanently increase the personality dimension of Openness To Experience. I’m emphasizing that because personality is otherwise pretty stable after adulthood; nothing should be able to do this. But magic mushrooms apparently have this effect, and not subtly either; participants who had a mystical experience on psilocybin had Openness increase up to half a standard deviation compared to placebo, and the change was stable sixteen months later. This is really scary. I mean, I like Openness To Experience, but something that can produce large, permanent personality changes is so far beyond anything else we have in psychiatry that it’s kind of terrifying.

(related: 1972 study finds LSD may cause permanent increase in hypnotic susceptibility, which other sources have linked to being “fantasy prone” and “creative”)

And that’s one dose. These researchers were taking psychedelics pretty constantly for years, and probably experimented with the sort of doses you couldn’t get away with giving research subjects. What would you expect to happen to their Openness To Experience? How many standard deviations do you think it went up?

It seems possible to me that psychedelics have a direct pharmacological effect on personality that causes people to be more open to unusual ideas. I know this is going against most of the latest research, which says psychedelics have no long-term negative mental health effects and do not cause psychosis. But there’s a difference between being schizophrenic, and being the sort of guy who is still a leading neuroanatomist but also writes books about the geometric relationships between consciousness and the space-time continuum.

I’m not sure anyone has ever done studies to rule out the theory that psychedelics just plain make people weird. Indeed, such studies would be very difficult, given that weird people with very high Openness To Experience are more likely to use psychedelics. This problem would even prevent common sense detection of the phenomenon – even if we noticed that frequent psychedelic users were really weird, we would attribute it to selection effects and forget about it.

In this situation, the early psychedelicists could be a natural experiment giving us data we can’t get any other way. Here are relatively sober scientists who took psychedelics for reasons other than being weird hippies already. Their fate provides signal through the noise which is the general psychedelic-using population.

I think this is only medium-risk; the explanation that weird people gravitate toward psychedelics, even in the sciences, is a strong one. But it’s sufficient that I am hesitant to repeat the common view that psychedelics are not at all dangerous, or that they have no permanent side effects. There seems to me at least a moderate chance that they will make you more interesting without your consent – whether that is a good or a bad thing depends on exactly how interesting you want to be.