[ad_1]
- Chronic stress and depression are known to reduce the number of nerve connections in the prefrontal cortex of the brain.
- Drugs with rapid antidepressant effects, including ketamine and classic psychedelics such as psilocybin, may work by promoting the growth of new nerve connections.
- A new study in live mice has found that a single dose of psilocybin increased the density and size of nerve protrusions called dendritic spines in the prefrontal cortex of rodents.
- The changes occurred within 24 hours and lasted for at least 1 month.
Classic psychedelics such as psilocybin, the psychoactive component of ‘magic mushrooms’, produce a temporary altered state of consciousness that affects perception, thinking and mood.
Researchers explored their potential to treat a wide range of psychiatric disorders, including substance abuse, post-traumatic stress disorder, and depression.
Small preliminary trials of psilocybin for treatment-resistant depression showed enough promise for the Food and Drug Administration (FDA) to give the drug a “breakthrough therapy” designation in 2019, allowing the launch of multi-site clinical trials.
Psychedelics can improve the brain’s ability to change, or “plasticity,” in response to adversity. This, in turn, can open a window of opportunity for healing through psychotherapy.
However, how drugs modify nerve cells, or neurons, in the brain to make possible increased psychological and behavioral plasticity.
In animal models, chronic stress reduces the number of cellular structures called synapses, which carry signals between nerves in the frontal cortex.
Drugs with rapid antidepressant effects, such as ketamine and classic psychedelics, can help reverse these changes.
For the first time in living animals, scientists have now tracked the growth of dendritic spines, which are neuronal protuberances that end in synapses, in response to psilocybin.
The researchers used a laser imaging technique called two-photon microscopy to monitor potential changes in the mice’s medial frontal cortex.
They found that in just 24 hours, a single dose of the drug increased the number of spines and their size in that part of the brain. The changes lasted at least 1 month.
The research, conducted by scientists at Yale University School of Medicine, in New Haven, CT, was published in the journal Neuron.
“We not only saw a 10% increase in the number of neural connections, but they were on average around 10% larger, so the connections were also stronger,” says lead author Alex Kwan, Ph.D. ., an associate professor of psychiatry and neuroscience.
In addition, the drug increased excitatory nerve signaling in the brains of animals 24 hours after treatment. It also improved their performance on a standard stress behavior test.
“It was a real surprise to see such lasting changes with just one dose of psilocybin,” says Professor Kwan. “These new connections can be the structural changes that the brain uses to store new experiences.”
The authors speculate that other drugs with rapid antidepressant effects can cause an equally rapid and persistent “synaptic rewiring” in the brain.
They note that the timing of the changes seen with psilocybin matches that of ketamine, which also causes a rapid increase in the number of dendritic spines in the frontal cortex.
Their research raises the intriguing possibility that scientists could create drugs that promote synaptic rewiring without causing consciousness-altering effects, such as hallucinations.
In one experiment, researchers gave mice a drug called ketanserin, which blocks some of the 5-HT2A subtypes of serotonin receptors that psilocybin binds to.
The 5-HT2A receptors are responsible for the profound changes in consciousness caused by classic psychedelics, such as LSD, DMT, and psilocybin.
Ketanserin prevented head contractions in these mice, a behavioral tic that psychedelic researchers use as an indication of consciousness-impairing effects in animals.
But psilocybin still appeared to increase synaptic plasticity in mice, even though their 5-HT2A receptors were partially blocked. However, the results were not statistically significant.
“What the ketanserin experience suggests is that the psychedelic and plasticity-promoting effects may be dissociable. That is, at least in mice, we can block the receptors responsible for it. psychedelic experience, and yet see the effects of plasticity, ”said Professor Kwan. Medical News Today.
“If this finding translates into humans, it points to the possibility of new psychedelic analogues. [structurally similar drugs] which are not hallucinogenic but can still be effective in treating depression, ”he added.
Other researchers are working on the development of non-hallucinogenic versions of psychedelics such as ibogaine to treat psychiatric disorders.
Professor Kwan noted that psilocin, the breakdown product of psilocybin that binds to 5-HT2A receptors, also binds to other serotonin receptors in the brain.
“It is therefore possible that other serotonin receptor subtypes are involved in the observed plasticity,” he said. MNT.
“We need more lab work to identify receptor subtypes,” Prof Kwan explained. “That’s what we want to do next.
[ad_2]
Source link