Opinion – Psychedelic turn: China enters the race for non-hallucinogenic psychedelics

2022 has barely begun and a small bombshell in the field of reborn psychedelic science comes out in this Friday’s edition (28) of the journal Science: Chinese researchers announce LSD-like compounds that would have an effect against depression without triggering the altered state of consciousness known as “trip” ( hallucinations, mystical experiences, ego dissolution and so on).

It’s the pharmaceutical industry’s dream.

Multiple studies have demonstrated the potential of psychedelics –DMT, LSD, psilocybin, etc.– in treating mood disorders such as depression, post-traumatic stress disorder, and anxiety. They carry the disadvantage of causing mental distortions that last several hours, which require constant supervision and would make possible substance-based treatments already somewhat stigmatized by the failed War on Drugs of the 1970s enormously expensive.

A current of psychedelic research favors, therefore, the search for compounds that maintain the therapeutic action and discard the psychedelic effect, which some consider unnecessary (controversial position, as will be seen below). The group led by Cao Dongmei and Wang Sheng, from the Shanghai Institute of Biochemistry and Cell Biology, has taken a step in that direction, albeit for the time being using only mice.

Nobody knows what goes on inside the skull of rodents, but it is possible to observe what they do with it. Researchers turn to a well-established model of behaviors correlated with human depression (“freezing” or “freezing”) and hallucinations (“head twitch”) for clues about the neurological effect of these drugs.

The Shanghai team embarked on a thorough study of the molecular structures formed by LSD and psilocin (from “magic” mushrooms) when they fit into the 5HT2 receptor._A. This structure on the surface of neural cells is the lock into which the key of serotonin fits, a neurotransmitter important in the regulation of functions such as mood and libido and the target of several antidepressants on the market (which, however, do not work for 30-40 years). % of depressed).

Chinese scientists did the same molecular mapping of serotonin itself embedded in 5HT2_A, and also with lisuride, a substance similar to LSD and known not to be hallucinogenic, used in the treatment of Parkinson’s and migraines. Careful examination of the contact points on each lock and key set gave the group clues as to what changes they could make to LSD and psilocin so as not to trigger the psychedelic effect, while preserving the antidepressant action.

With the help of the mice, they arrived at two compounds, IHCH-7079 and IHCH-7806, which seem to have antidepressant action without initiating the journey, that is, head tics in rodents. The next step, of course, will be to find out if the same thing happens to humans.

“We predict that the frameworks reported here will accelerate the search for new psychedelics and non-hallucinogenic psychedelic analogues for the treatment of neuropsychiatric disorders,” the study authors conclude in Science.

The China team is not the first to take this more sober path, so to speak, towards the new psychedelic, or quasi-psychedelic, pharmacology. It is at the heart of the strategy designed by David E. Olson of the University of California at Davis, as already discussed here about an ibogaine analogue he created, which aims to test against chemical dependence, but without detonating the African root journey that can last tens of hours.

Olson founded the company Delix Therapeutics to explore this non-psychedelic vein of psychedelics. Its corporate motto is “Rewiring the brain to heal the mind”, and the first part of the sentence makes it clear that it is about seeking physico-chemical changes to treat depression etc., and not about substances that provide self-knowledge, borderline experiences or pregnant visions. of meaning — as the traditional psychedelic therapists advocate.

For the pharmaceutical industry, it would be interesting to come up with antidepressant drugs that dispense with prolonged psychotherapeutic treatments, preferably for continuous use. Other clinical research strategies privilege psychedelics as adjuncts to psychotherapy, with protocols in which they are used only occasionally.

All the reborn psychedelic field doesn’t need, at the moment, is to be polarized by the false dilemma between pharmacology and self-knowledge. We’ve already seen this movie, in the 1980s, with the advent of the supposedly miraculous “happy pills” (selective serotonin reuptake inhibitors like Prozac), and it doesn’t have a happy ending: never have there been so many depressed, addicted and traumatized people in the world as this millennium, which started so sick.

PS: The main illustration of this text, composed with the molecular images generated by Cao Dongmei’s group, forms the image of a cyclist, and readers unfamiliar with the rich pre-prohibition psychedelic history will wonder why. It is a reference to the so-called Bicycle Day, April 19, 1943, when Swiss chemist Albert Hofmann started the first intentional lysergic trip and ran home from his laboratory on a skinny.

PS2: To learn more about the history and new developments of science in this area, including in Brazil, look for my book “Psiconautas – Travels with Brazilian Psychedelic Science”