One Psilocybin Dose May Help Regrow Neuronal Connections Lost In Depression

Many people with depression experience a loss of neural connections. Image: Andrii Vodolazhskyi/Shutterstock.com

Among the hallmarks of depression is a loss of neural connections – otherwise known as synapses – in key parts of the brain like the frontal cortex. Fortunately, however, new research indicates that a single dose of a psychedelic substance called psilocybin triggers the proliferation of synapses in these same cortical regions, providing a potential treatment for those with the condition.

The active compound in magic mushrooms, psilocybin has shown efficacy in treating depression in human trials – although scientists are still trying to figure out the mechanism behind this therapeutic effect. Appearing in the journal Neuron, the new study sought to determine whether or not the drug sparks an increase in the number and density of dendritic spines, which are a type of connecting arm via which neurons are able to communicate.

Within 24 hours of administering the compound to mice, the researchers noted a significant increase in dendritic spines within the rodents’ frontal cortices.  "We not only saw a 10 percent increase in the number of neuronal connections, but also they were on average about 10 percent larger, so the connections were stronger as well," explained study author Alex Kwan, associate professor of psychiatry and neuroscience at Yale, in a statement.

Crucially, these improvements were still apparent one month later, indicating that a single dose of psilocybin generates a lasting increase in synapses within key regions of the brain.

According to the study authors, this structural remodeling of the brain may help to correct certain neurological deficits associated with depression while at the same time allowing for new insights to be encoded. As such, they speculate that “psilocybin-induced neural plasticity could prime the brain for integrating new psychological experiences,” thereby allowing for a change in mindset.

In addition to this increase in dendritic spines, the researchers also observed elevated excitatory neurotransmission, suggesting that certain depression-associated deficits in brain activity may be reversed by psilocybin. Furthermore, mice that had received the drug displayed better coping behaviors when faced with stress, indicating that the neural changes elicited by the compound could lead to greater resilience.

"It was a real surprise to see such enduring changes from just one dose of psilocybin," said Kwan. "These new connections may be the structural changes the brain uses to store new experiences."

While these findings add to the evidence that psilocybin may help those with severe depression to overcome the condition, the psychedelic nature of the compound makes it unsuitable for many patients, as the hallucinations it generates can be difficult for certain people to handle. The study authors, therefore, attempted to discern whether the improvements in dendritic spine density could be maintained when the psychoactive effects of psilocybin are blocked.

To investigate, they used a compound called ketanserin, which inhibits the serotonin receptors to which psilocybin binds in order to produce alterations of consciousness. This caused the mice to cease twitching their heads when under the effects of the drug, indicating that they were not tripping.

The fact that this did not prevent the formation of new synapses within the frontal cortex suggests that the anti-depressive efficacy of psilocybin may not be dependent upon its psychedelic effects. However, as the authors point out, the psychological impact of psilocybin on humans can’t really be determined by observing the behavior of mice, which is why more research is needed in order to clarify the mechanisms behind the drug’s therapeutic properties.

 


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