Scientists first observed LSD in action

The most important receptor

The key to understanding the work of any psychoactive substance is knowing which cellular receptors it binds to and how exactly this happens. In the case of LSD, the pathway to opening the receptor took decades. The structure of the molecule itself in the LSD crystal was able to be established back in 1972, but the structure of the receptor with which it binds and through which acts on the nervous system remained a mystery for a long time, and only this year scientists described it in an article published in the journal Cell.

It turned out that the name of the LSD receptor is 5-HT2B. Usually, this membrane protein acts as a serotonin receptor - a neurotransmitter that regulates hunger, mood and some other sensations. “We first observed a psychedelic substance at work, ” comments team leader Bryan Roth, a pharmacologist at the University of North Carolina.

Holds and does not let go

Observation of the binding of the LSD molecule to the receptor has helped to explain the outstanding duration of the psychedelic effect, which may not weaken up to 20 hours depending on the dose. It turned out that the LSD molecule enters the receptor cavity, and then attracts its upper part and turns out to be enclosed in it, as in a pan with a closed lid. Serotonin acts differently: it binds to the receptor for a while, and then it separates, so its effect is not so stable and does not last so long.

Music of meaning

Another group of scientists, who published their results in the journal Current Biology, studied the biochemical mechanisms of individual effects of LSD - in particular, the sense of awareness of the causes and relationships of everything that has been repeatedly described in scientific and fiction. It turned out, again, the whole thing is in the receptors of serotonin 5-HT2B and the like.

All participants in the experiment were asked to make a list of musical compositions that meant a lot to them. Then, one group of participants received LSD, the other received placebo, and the third received LSD in combination with ketanserin, which prevents the binding of LSD molecules to serotonin receptors, but does not interfere with the binding of other substances to receptors.

Some time after receiving the preparations, the experiment participants were given the opportunity to listen to music: sometimes from the list of songs very important to them, sometimes similar tracks, and sometimes jazz compositions that most of the participants did not characterize as “meaningful” music. The placebo group and the group taking LSD in combination with ketanserin did not saturate jazz with meanings even after taking the drugs. But people who received pure LSD said that they felt jazz as full of meaning, a very important and pleasant melody for them personally.

The experience of “meaningfulness” was recorded both from the words of the participants in the experiment, and with the help of fMRI, which showed increased activity of some parts of the brain in those who received a pure drug. From this, scientists concluded that it is in the 5-HT2B receptors that when bound to LSD, there is a feeling that Douglas Adams called “Unity with the Universe” in the novel “Hitchhiker's Guide to the Galaxy”.

Team Leader Katrin Preller, a psychopharmacologist at the University Psychiatric Hospital in Zurich, hopes her research will draw other scientists into the biochemical foundations of a sense of meaning. Pathologically altered, this feeling accompanies such disorders as schizophrenia and paranoia - it seems to patients that random coincidences are not accidental, that what is happening has a hidden, often hostile cause.

Studying the mechanism of binding LSD to cell receptors can help create drugs, just like LSD, which can relieve symptoms of depression, but lack hallucinogenic properties.

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