Mechanisms of action of LSD-like substances

The mechanisms of action by which LSD and similar substances are capable of producing such impressive effects as visual hallucinations and changes in consciousness in such small doses remain mysterious, but more and more scientists agree that an important role in this process is played by changes in the activity of brain systems associated with serotonin. The first part of this evidence arose from the analysis of the chemical structure of the main hallucinogens. LSD, psilocybin, harmalin are classified according to their chemical structure as indolalkylamines. The same chemical structure has a natural substance serotonin.

The proximity of the chemical structure prompted the assumption that LSD and others like it can imitate serotonin and therefore activate the serotonin receptors of the brain. Currently, this hypothesis has received significant support. For example, it has been proven that LSD and other hallucinogens envelop serotonin receptors and that the force with which this occurs is strictly dependent on the power of the hallucinogen.

One of the problems associated with the above hypothesis is mescaline. The chemical structure of mescaline is very different from all other hallucinogens. By chemical nature, it is more like amphetamines than LSD. For this reason, it was thought that its mechanism of action was different from LSD. However, unlike amphetamines (as well as methyl amphetamines such as MDA), mescaline has a pronounced hallucinogenic effect, virtually identical to LSD. Another evidence in favor of a common mechanism of action for LSD and mescalin appeared in the study of tolerance. Tolerance to all effects of LSD develops very quickly. The same applies to mescaline. In addition, there is cross-tolerance between LSD, mescaline, and other drugs of this group. And, finally, recent data suggest that mescaline (or perhaps one of the mescaline metabolites) also envelop serotonin receptors.

As noted in Chapter 3, serotonin is everywhere in the brain. That is why the effects of LSD-like hallucinogens are so diverse. Serotonin is believed to play an important role in changing mood, which is the reason for the powerful emotional impact of these drugs. However, it is not known which parts of the brain are responsible for the hallucinogenic effect of these drugs.