New research shows psychedelics activate receptors inside brain cells that other compounds, like serotonin, cannot.
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March 2, 2023 The clinical evidence for using psychedelics to treat major depressive disorder, PTSD, addiction, and other mental health conditions is building.
But despite the growing pile of data, we do not know just how psychedelics might be helping. (This isn’t unusual, by the way — we still don’t really know why most antidepressants work, just that they do.) One theory behind conditions like depression is that they’re caused by the breakdown of connections between brain cells.
Researchers have found, in multiple studies, that psychedelics can increase connections between cortical neurons — specifically, they spark growth of the tendril-y antennae on neurons, called dendrites, that catch signals from other brain cells. In theory, this may mean new connections being formed and strengthened, helping the brain to rewire itself.
Now, surprising new research out of UC Davis may have finally explained why psychedelics spark dendrite growth when other drugs, which activate the same targets in your neurons, do not — and it may be the key to their therapeutic value. It’s a discovery that could be “potentially paradigm changing,” Bryan Roth, a distinguished professor of pharmacology at UNC-Chapel Hill who was not involved with the research, tells Freethink.
Many psychedelics and the neurotransmitter serotonin both activate the same receptor in brain cells: 5-HT2A.
Rewiring the brain: The first clues about how psychedelics may be physically altering neurons came from ketamine, which researcher Ron Duman’s lab at Yale showed could promote dendritic growth in mice. Subsequent research tied this growth to ketamine’s antidepressant effects.
In 2018, David E. Olson’s lab at UC Davis published a paper in Cell Reports showing that a variety of psychedelics (“like pretty much all the major ones you’ve heard of,” he says) were effective at promoting the growth of the cortical neuron dendrites. Those findings have since been backed up and expanded upon by multiple labs and in multiple models, including neurons in a dish, in fruit flies, in mice, and, in 2021, in pigs. Here’s the thing, though: all the research led to a very odd realization. If psychedelics spur neuronal growth, why is that the many other drugs that interact with the same receptor — including serotonin itself — do not?
“The goal of this study,” Olson says, “was to solve an enigma.”
Serotonin and psychedelics: Despite the many mysteries of how psychedelics do what they do, there has long been a consensus among scientists that one particular receptor on brain cells, called “5-HT2A,” is key.