Recent Psychedelic Drug Research and German Ethology

And Timothy Leary: An Idiosyncratic Mélange

Here I am again, on acid. I mean: I’m writing about acid. Psychedelic drug research and other drugs besides LSD. Here I am, writing about them again. Why? ‘Cuz it’s an exceedingly, overwhelmingly fascinating topic to me. I get a contact high just writing about it. You too?

So, a current obsession of mine is trying to keep up with what’s going on in psychedelic research. The topic is very hot and rich, like a double mocha caramel frappucino, but much more mind-manifesting.

(Dr. David Olson of UC Davis, pioneering in psychoplastogens)

David Olson of UC Davis

Dr. Olson is the head of psychedelic research at Davis; it looks like he’s getting funding from the Pentagon, but I’m not sure. (Leonard Pickard seems to think so. Go to the 47 minute mark.) Olson and his team are up to their elbows in our 5-HT2A serotonin receptors (and their cousins). These receptors regulate feeling “normal” which perhaps many of us take for granted. Why? Because when something goes organically wrong with these receptors we have depression, schizophrenia, obsessive-compulsive disorders, etc. Of course, it’s far more complicated than this. Anyway: this receptor is an agonist for LSD, psilocybin, DMT and others. Meaning: these drugs “look” so much like serotonin that they are taken up by the 5-HT2A receptors and…ehhhhh…disrupt (?) normal brain function. Ya get way high. Serotonin regulates one of our versions of “reality”; let’s see what other versions there are that dock into 5-HT2A and other serotonin receptor types.

Olson has figured out a way to tinker with these drugs enough that they can give the therapeutic results we’ve all been reading about for the past 15 years or at least since Michael Pollan’s How To Change Your Mind made the bestseller list. Here’s the catch: he’s tinkered with the drugs so you don’t trip, but still get the benefits. Or at least that’s the goal. And he’s making inroads, which is fantastic news for anyone suffering from a host of maladies that psychedelics have been shown to have therapeutic efficacy for…and for those who get the Lovecraft horrors when they even think about tripping. That’s a lot of people, as we know.

That’s the goal: you’ve been depressed? You will get one of these drugs Olson has dubbed “psychoplastogens” and take them at home, you won’t be trippin’ balls, and your depression gets markedly better than anything SSRIs could do. I surmise the Pentagon (or DARPA) wants it for PTSD, to treat soldiers, and possibly: to prevent them from being lastingly traumatized by what they saw on the battlefields.

Olson’s term - the “plastogen” aspect - plays on the neuroplasticity of our brains. It’s been found that tinkering with the serotonin system opens up more plasticity: new learning, fast learning, un-learning. With plasticity, we’ve found that our brain functions are much more like Silly Putty than we ever thought before 1980. (William James posited in his magisterial 1890 textbook Principles of Psychology, that our brains remained plastic throughout life, pretty much. That was shot down. William James turns out to be have been right.)

There seems to be a lot of promise. Very recently as I write this, Olson’s private venture company, Delix Therapeutics, announced the results of a Phase 1B study of their drug zalsupindole/DLX-001, which is their psychoplastogen based on the ultra-strong psychedelic 5-MeO-DMT, the toad venom one you’ve read about or actually tripped on yourself. Of 18 participants, 9 got the drug once a day for 7 days; the other 9 participants got it twice over 7 days. The participants had major depressive disorder. All 18 got around a 50% reduction in depression as measured by the Montgomery-Asberg Depression Rating Scale. There was no significant difference between the two groups, suggesting getting this drug only twice in one week would show improvements. No one tripped or got delusional or dissociated. Delix will report more results later. Participants were not at home, so their brain activity could be monitored. We’ll hear more about this within a year, it seems. They’re ready for a next phase: people taking DLX-001 at home. It seems like very good news for people who have major depressive disorder, but I think we need to see a lot more research and clinical trial data. Olson has another drug called Tabernathalog, which is an analog of Ibogaine without the trip. I know the Olsons are often linked to Utah and Mormonism, and “Tabernathalog” sounds like a hat-tip to all that, but I have no evidence for this. Olson hasn’t answered my email. I think he’s really really busy, honestly.

(Dr. Gül Dölen of UC Berkeley, making inroads in critical periods and psychedelics)

Gül Dölen at UC Berkeley

She does not design drugs like Olson, but she’s a very creative researcher. She also seeks to avoid using email ever again, it seems, so she hasn’t answered any of my Qs. I may have to drive to both Davis and Berkeley to see if I can talk to both of them for 15 minutes.

Dölen made news when she gave octopuses MDMA/Ecstasy/”Molly” and these normally asocial creatures became very social. She studied philosophy, then neuroscience, linguistics, and then got into psychedelic research. Dölen says it’s an open secret that a lot of neuroscientists got interested in psychedelics because so many of these drugs are molecularly isomorphic to serotonin, which implies a superhighway of insight into perennial philosophical questions about the nature of consciousness.

What was so eye-opening about the octopus experiment - which sounds like a stunt to get noticed but was not - was that there was a theory that psychedelics quiet the amygdala or prefrontal cortex, but octopuses don’t have either of those. The reigning psychedelic theory of entropic brain processes put out by two giants in the field, Dave Nutt, and Robin Carhart-Harris, seem to require the Default Mode Network in its explanatory scheme. Octopuses don’t seem to have one. Dölen thinks it all has to do with serotonin transport systems, something we share with eight-armed alien-like mollusk friends.

We branched off from them 500 million years ago, they certainly seem to have consciousness, they recognize humans and signal to them using complex body movements, they have no skeleton, so they can squeeze through very tight openings. But they’re very intelligent! Come to grips with it, older scientists: these mollusks are intelligent and conscious. I for one can’t eat them at sushi restaurants anymore. They have three hearts, blue blood, on and on. For a brainy take on them and us, see philosopher Peter Godfrey-Smith’s Other Minds: The Octopus, the Sea, and the Deep Origins of Consciousness (2016).

Dölen disagrees with Olson on the ultimate therapeutic questions around psychedelics: she thinks the trip is necessary for long-term healing, like those people who were depressed, took one trip on psilocybin, and weren’t depressed ten years later. Where she agrees with Olson is that neuroplasticity is where the action is, and that has to do with serotonin receptors. But she thinks what’s going on is that our critical periods become re-opened on these psychedelics.

Critical periods are the periods in which we are open to massive amounts of learning, and according to Takao Hensch of Harvard, who specializes in critical periods, “There are probably as many critical periods as there are basic functions.”¹ From a 2021 article in Frontiers In Neuroscience, “A critical period is a window in which environmental input is necessary for the appropriate development of the relevant brain circuit. During a critical period, the brain has a heightened plasticity in which experiences have robust effects on establishing stable neurocircuitry. During this developmental period, the brain’s malleability creates both a vulnerability to environmental insults or deprivations as well as a remarkable ability to quickly and robustly acquire skills.”² There are established critical periods for walking, seeing, hearing, language acquisition, parental bonding, developing absolute pitch, learning the local cultural norms, and, as Hensch alludes to, many more.

At first Dölen thought MDMA opened critical periods for social learning, but using prior intent, she and her team found that LSD also opened critical periods. Then psilocybin, ibogaine, and even ketamine did, too. WTF? Last I saw they linked this to 65 genes involved with critical period open states. How long do the critical periods stay open? For longer than the trip lasts, which blows me away. It’s now thought you’re open to radical new or re-learning for a day or two and up to two months. This raises a massive question about “setting.” A battered wife doing psilocybin-assisted psychotherapy cannot just go back home to where her husband is beating the crap out of her: she’ll re-imprint the trauma, probably making it worse. The implications for this seem humongous to me. ³

Are psychedelics reset buttons?

Timothy Leary and Robert Anton Wilson urged self-metaprogramming: have intent and a goal in mind before you trip. And of course Set and Setting were of paramount import. Leary had read everything on imprinting (the older term for critical periods) that he could find before the government locked him up for having a small amount of cannabis. What was he reading? The Germans who discovered imprinting.

German-Austrian-Dutch Biology

In 1973, Leary was languishing in solitary confinement, reading and writing books. That same year, Karl von Frisch, Niko Tinbergen, and Konrad Lorenz received the Nobel Prize for Medicine and Physiology for their work in Ethology, which is the science of observing animals not in a lab, but natural environments. Frisch had deeply characterized bees’ language; Tinbergen had a host of discoveries, including what’s called “supernormal signaling”: you can replace a bird’s egg in the nest with one larger, and it will invest significant energy taking care of it. This aspect of exaggerating that which is already biologically desirable has been linked to our long history as hominids of seeking out food that is sugary and fatty: very hard work for 99% of our time, but now: fast food and an obesity epidemic. It’s been linked to the world of Art, to our consumption of pornography, all kinds of things.

Lorenz contributed hugely to the ur-theory of critical periods: imprinting. As a kid I saw on PBS the greylag goose following him around. It had imprinted on him as its “mother” because Lorenz was present when its imprint vulnerability was open.

Ethology was largely a European response to American Behaviorism. In the US, ethology seems to have creeped in via what was Sociobiology in the 1970s, later Evolutionary Psychology. Behaviorism was what Chomsky and Leary had both attacked, in their own ways, in the 1950s and 1960s. In the American mind, it’s often linked to “brainwashing.” What’s kinda weird is that Jacob von Uexkuell, one of the great-grandfathers of German biology in the 20th century, who coined the term umwelt, the specific way an organism must perceive the world given the capabilities of its perceptual apparatus and sensory organs, was a major Nazi. He even helped shaped Nazi ideology. And Lorenz was a Nazi party member. A rabid member:

The immensely high reproduction rate in the moral imbecile has long been established…Socially inferior human material is enabled…to penetrate and finally to annihilate the healthy nation. The selection for toughness, heroism, social utility…must be accomplished by some human institution if mankind, in default of selective factors, is not to be ruined by domestication-induced degeneracy. The racial idea as the basis of our state has already accomplished much in this respect. We must - and should - rely on the healthy feelings of our Best and charge them…with the extermination of elements of the population loaded with dregs.⁴

So: you can’t escape them: mad scientists with inhumane intent. Nobel Prize winners you wouldn’t want living in your neighborhood. Sometimes they’re fucking brilliant with some of the stuff they come up with. How do we deal with this knowledge? Please answer in the comments. Back to Leary.

(Leary. It seems he was fascinated by instincts before he knew about imprinting. I write this just from looking at the index to his 1957 book The Interpersonal Diagnosis of Personality)

Timothy Leary

The Leary scholar James Penner thought Leary’s ideas around “de-conditioning” and “reimprinting” using psychedelic drugs were his biggest breakthroughs.⁵ In a 1965 article published in ETC: A Journal of General Semantics, “Languages: Energy Systems Sent and Received,”⁶ Leary discusses information signaling systems throughout the body, including the effects of imprinting. It’s a long, brilliant article, and at one point he speculates with his knowledge of imprinting by noting three aspects of it that didn’t seem to be covered by the literature:

1. “The first is the rather terrifying implication that early, accidental and involuntary events can blindly and tenaciously couple the instinctual machinery to entirely inappropriate stimuli. It raises the disturbing question for each individual - which orange basketballs imprinted you?”⁷ Leary here alludes to some research on imprinting in which ducklings rejected the mother in favor of an orange basketball. For me, it makes me think of billionaire tech bros who think of themselves as gods with the right to change the world, because they’re so brilliant and rich and to hell with democratic ideas. It makes me think of Astrid Sabiha Lloyd’s recent article about psychedelics expanding the Ego. Sabiha Lloyd doesn’t mention the long open critical period established by Gül Dölen and her team, but I couldn’t help thinking of these guys tripping at Burning Man and everyone around them kissing their asses for days and weeks with how great they are, etc. Do these guys need to be imprinting that shit?

2. “Another issue is the relationship of conditioning and learning to imprinting. One possibility is that imprinting sets up the basic attachment-avoidance of stimuli and that all subsequent learning is accomplished by means of association to the original imprint.” This became the basic working hypothesis throughout Leary’s subsequent work and in Robert Anton Wilson’s Prometheus Rising, which I consider the great text explaining Leary’s life-work: the Eight-Circuit Model of Consciousness. In these works, conditioning and learning are constantly malleable, but only within the parameters of earlier imprinting on the oral-biosurvival “circuit,” the anal-territorial/political “circuit,” the symbolic-semantic “circuit,” and the socio-sexual “circuit.” All four of these dimensions were imprinted, and the local culture acts as a Behaviorist-At-Large, subtly encouraging and dissuading citizens to fit into society. The 2nd circuit: anal-territorial-political, is far older than the semantic and social ones, and therefore more pronounced in all our own realities, which explains all the alpha male baboons and terror and war in our history as species. Within Leary’s and Wilson’s Philosophical Anthropology, this has led to the Nightmare of History, because, in a very strong sense to them, these processes spelled out the mechanisms for robotic behavior at the individual level all the way up to national and trans-national behavior levels. The good news is that they posited four circuits beyond these, which largely escape Behaviorism. Some other article…And:

3. “Another aspect of imprinting is its addictive quality. The human being is ‘hooked’ to the external world. Sensory deprivation experiments suggest that when the human being is cut off from his ‘supply’ of external stimuli, he shows all the symptoms of a ‘dope fiend’: restlessness, discomfort, anxiety.” Maybe in 2025 think here of your Internet fix? Your phone/laptop/compuer is external to your body. Cut off that “supply” for awhile: how do you feel? The problem here is that some of us were well past the legal drinking age when we first got a computer and an email address: could we have imprinted the Internet? I personally prefer to stay off “all that” and read codex/dead tree books, which I am clearly addicted to, and will feel anxiety, discomfort or restlessness if deprived of my supply. But to those born, say, after 1995? I think we must consider that they have imprinted Internet. What does that entail? Too rich for my blood, right here, right now!

Some Qs

I wonder how effective Olson’s psychoplastogens will be. I wonder how many critical periods will be shown to be opened by psychedelics and amenable to therapy. How many things that we assume are “hardwired” in us can actually change under psychedelics? Will Olson’s or Dölen’s work prove more influential? Can a person who’s nearing retirement age but still wants to learn a foreign language, take up a musical instrument, or become really good at mathematics benefit from a targeted psychedelic approach? Will humans eventually get so good and creative at serial re-imprinting during critical periods with psychedelics that it will become some sort of art-form? Are there certain genetic profiles that will reveal that some people can re-imprint easily, while for others it is difficult or impossible? Can we learn to discern what our own values really are, then use psychedelics to help us change our lives so we live in accord with those values in a more integrated way and not be so scattered and chasing after things we’ve been told we should want? Can we keep Authority at bay and use psychedelics according to our own wants, desires and needs? There will be unforeseen outcomes of all this: what will these be? Are psychedelics overhyped? There’s some quality data that suggests non-psychedelic approaches re-open critical periods: new technology, shock, confusion, and isolation: how will the research on these go? We have reason to believe our immune systems become imprinted: how far does this extend?⁸ Will more knowledge of critical periods change standard practices?⁹

Only time will reveal tentative answers to these and any of your questions around this fascinating subject.

(artwork courtesy of Bobby Campbell)

1. This quote gleaned from Rachel Nuwer’s I Feel Love: MDMA and the Quest For Connection In a Fractured World, p.172.

2. see Frontiers In Neuroscience, Sept 19, 2021, “Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy.” If I put a hyperlink to the article the pictures show up here in the footnotes, making it unwieldy, which is a drag, I know.

3. see the June 14, 2023 article in Nature: “Psychedelics Reopen the Social Reward Learning Period.” Incidentally, longtime underground psychedelic therapist Leo Zeff seems to have noticed a long time before Dölen’s team’s research that you’re still open for weeks after the trip: he cautioned his trippers to not quit jobs or take new ones, start or end a relationship, etc, for three weeks after. Zeff didn’t use the term “imprint,” much less “critical period” but intuited what was going on after long experience of working in the field, underground. One of his “patients,” a guy named “Andrew” thought the three-week rule was right and added, “Just be with it awhile. See what pertains to the trip itself and what is meant to be actualized in your life.” see The Secret Chief Revealed, by Myron Stolaroff, pp.88-89. The Secret Chief was Leo Zeff all along!

4. found in Behave: The Biology of Humans at Our Best and Worst, Robert Sapolsky, pp.9-10. Sapolsky - one of my favorite humans - found this quote from Lorenz in R. Learner's Final Solutions: Biology, Prejudice and Genocide, 1992. Prior to Sapolsky quoting Lorenz he had quoted founder Behaviorist John Watson, with a similar horrific quote we associate with fascism. He followed that with a quote from Egas Moniz, Portuguese neurologist who won the Nobel in 1949, who pioneered icepick lobotomies for people who were social misfits or just too weird, according to…others.

5. Timothy Leary: The Harvard Years, ed. James Penner, p.9.

6. Penner, pp. 268-301. I consider this one of the truly sparkling works from Leary’s ingenium.

7. Penner, pp.276-277, for this quote and the following two from Leary.

8. I’m thinking of Original Antigenic Sin, which has become widely accepted in medical circles: the first flu you got, the way your body attacked and defeated this flu and this flu’s characteristics, stays with you for life. In other words, the version of the flu virus you first caught as a child influences how sick you get from influenza viruses the rest of your life. I probably caught the 1968 H3N2 “Hong Kong Flu” which was a doozy. As an adult, when I get the flu there’s always a couple of days in which I think: gotta go to the hospital, feel like I’m gonna die. From first symptoms: fever, chills, etc, to feeling like I’m recovered: around five weeks for me, maybe six. When I first read about OAS it was a revelation.

9. David Jay Brown, one of the great psychonauts, thinks circumcision leaves an imprint of trauma and violence. See New Science of Psychedelics, p.43.

(art work courtesy of Bobby Campbell)