Psychedelic drugs are often used for recreational purposes. However, there has recently been some indication that they may be effective against PTSD and treatment-resistant depression. If it is easy to know who belongs to the treatment group, it can be difficult because it is difficult to conduct controlled experiments. Still, some progress has been made in understanding what’s going on in psychedelics on a molecular level.
Many hallucinogens appear to bind to and activate specific receptors for the nerve signaling molecule serotonin. SSRIs and selective serotonin reuptake inhibitors), it seems logical for antidepressant effects. , the situation remains a bit confusing.
New data suggest that hallucinogens activate serotonin signaling in a very different way than serotonin itself, and may reach receptors located in parts of the cell that serotonin cannot reach.
good reception
Serotonin signaling is complex. Humans have seven classes of receptors. Some activate signaling pathways, others inhibit. Her one group of receptors responds to serotonin by taking ions into cells and triggering nerve impulses. The rest interact with proteins within the cell, causing a long-lasting response to serotonin.Psychotropins such as LSD and mescaline bind to members of this latter group and activate them.
This behavior results in some pretty dramatic changes in how people perceive their surroundings. There is also some evidence that this occurs through the growth and branching of structures that receive input from other neurons, called dendrites, and may allow for additional or modified inputs. One hypothesis is that this change in connectivity allows cells to escape whatever network configuration is associated with a medical disorder.
The researchers confirmed these results using DMT, a psychedelic found in ayahuasca, and psilocin, the active form of the drug psilocybin, usually obtained from mushrooms. Twenty-four hours after the mouse was administered one of these drugs, neurons in the mouse’s brain had increased density of extensions from dendrites. This growth was accompanied by an increase in the activity frequency of individual neurons. Performing the same tests in mice lacking genes for the specific serotonin receptors these drugs target blocked both of these effects, confirming that serotonin signaling is central to the alterations.
Researchers then began testing the drug’s chemical relatives and saw a clear pattern. Making the drug less likely to interact with water enhanced its effects on neurons. This suggests that the ability to cross highly water-repellent membranes may be required to facilitate dendritic changes. To confirm this, the researchers pierced the membrane and enhanced the activity of a water-friendly drug variant that does not readily pass through the membrane.
This is a little confusing because the serotonin receptors are inside the membrane and interact with the outside of the cell. They have to—that’s where the serotonin is. Why should anything that interacts with a cell pass through the membrane to the interior of the cell?
keep inside
Cell surface receptors are key to the cell’s response to serotonin. But receptors don’t just magically appear on the cell’s surface, they’re made elsewhere in the cell, processed, and transported to the surface. Researchers have found a cluster of serotonin receptors inside a structure called the Golgi apparatus. It is not clear whether this population is simply directed to the cell surface, or whether it is retained there by a specific biological activity.
Normally, these receptors do not contact serotonin, so they do not signal from this location. But researchers have modified the protein to pump out serotonin inside cells, showing it has the same effect as psychedelics, and may activate the receptor, which in turn alters neural connections. I suggested that it is the key to
Does this have anything to do with the medical effects of hallucinogens? Tests using mice in which this internal serotonin signaling is active in the brain have shown that the mice can exhibit behaviors thought to mimic depression. It was shown to be of low
Although suggestive, this study does not clearly show that this inner population of serotonin receptors is required for therapeutic response to hallucinogens. It does not address whether it is involved in actual psychedelic responses to should be regarded as a hint for
Another big question: if serotonin doesn’t reach these internal receptors, do they have normal function? One interesting possibility is what the DMT tested here activates them. It means that This drug is also produced in humans, albeit at much lower levels than found in some plants. .
chemistry, 2023. DOI: 10.1126/science.adf0435 (About DOI).
