“David Olson’s lab (UC Davis) just published one of the most consequential papers in Science today. In a quest to understand the mechanism of brain plasticity triggered by psychedelics, they found that intracellular serotonin receptors mediate the action.”
This is the intro from Elemer Piros, Senior Biotechnology Analyst at EF Hutton. This new study shows that traditional serotonin-based SSRIs (the current treatment mode for many mental health conditions) don’t pass neural cell membranes and do not induce plasticity, explaining why SSRIs are largely ineffective for so many patients.
On the other hand, psychedelics crossed the cell membrane easily. According to Mr. Piros, this is potentially groundbreaking research. See his full note below.
David Olson’s lab (UC Davis) just published one of the most consequential papers in Science today. In a quest to understand the mechanism of brain plasticity triggered by psychedelics, they found that intracellular serotonin receptors mediate the action.
Serotonin, because of its polar chemical composition, cannot readily pass the neuronal cell membrane. Serotonin doesn’t induce plasticity. Therefore, boosting serotonin levels by selective serotonin reuptake inhibitors (SSRIs) was largely a futile effort for the meaningful treatment of depression. Only a small portion of patients respond.
Psychedelic medicines, such as DMT, psilocybin and LSD, because of their lipophilic (tend to combine or dissolve in lipids) nature cross the lipid bilayer of the cell membrane easily. As the team elegantly showed, plasticity was induced by DMT and other drugs in the class. However, when they added electric charges to these molecules, the plasticity-promoting effects disappeared. Now we better understand why a one-time or infrequent treatment with psychedelics lead to a long-lasting antidepressant benefit.
The story gets better with an intriguing hypothesis. We knew for some time that the human brain contains endogenous DMT. So far, its functional relevance was unclear. There are those who attain a psychedelic state with deep meditation or with intensive breath work. Could it be that they are able to command natural DMT in the brain to precipitate those experiences?
The phenomenon of “reactivation” or spontaneous reoccurrence of a psychedelic-like state is well known. Could DMT release be the explanation?
Dr. Olson is the Chief Innovation Officer and Co-Founder of Delix Therapeutics, a private company developing a portfolio of psychedelic-inspired drug candidates, which Dr. Olson calls “psychoplastogens”.