Researchers at the University of California, Santa Cruz have shown in mice that the neuroplasticity-boosting effects of psilocybin, the psychedelic compound in magic mushrooms, can be separated from its hallucinogenic properties, bringing researchers closer to drugs that target one pathway and ignore the other.
The study, published in Nature Neuroscience, identifies two distinct neural pathways for psilocybin's actions. By genetically reconfiguring the cellular receptors psilocybin interacts with, the team was able to engineer increases in brain connectivity in mice without causing the head-twitch responses that serve as a proxy for the drug's psychedelic effects in animals.
Psilocybin is being studied as a potential treatment for depression and PTSD. Past research has established that it can increase neuroplasticity: the brain's capacity to adapt and rewire itself. This plasticity is linked to the growth of dendritic spines, the connection points between nerve cells.
The researchers found that psilocybin could boost the volume of dendritic spines and accelerate their development in less than 24 hours. In mice subjected to stress, designed to mimic depression, new spine formation increased to a greater extent and the loss of existing connections was stopped.
“I consider this work a major advance, particularly in our understanding of how psilocybin reshapes neural circuits and its potential implications for treating mental disorders,” said molecular biologist Yi Zuo. Neuroscientist Jacob Baker noted that “psychedelics are fascinating compounds because they have the potential to profoundly transform who we are by reshaping the neural circuits in our brains.” Zuo added that the findings challenge the prevailing view that psilocybin simply increases neural connectivity, and suggest its effects depend on the brain's underlying condition.
The study strongly suggests the neuroplasticity benefits of psilocybin do not rely on the psychedelic aspects of the compound. Zuo said such therapeutics could deliver the fast and lasting antidepressant benefits of psychedelics while eliminating hallucinogenic side effects, making neuroplasticity treatments safer and more accessible.
Analysis
Why This Matters
- Could lead to new depression and PTSD treatments that are safer and more accessible without the intense hallucinogenic experience.
- Challenges the assumption that the psychedelic trip is necessary for therapeutic benefits.
- Provides a concrete biological mechanism (separate pathways) for developing targeted drugs.
Background
Psilocybin is the active compound in "magic mushrooms". Past research has established that psilocybin can increase neuroplasticity in the brain. Until now, it was unclear if the neuroplasticity benefits of psilocybin relied on the psychedelic aspects of the compound.
What to Watch
- Translation of these findings from mice to humans in clinical trials.
- Isolation of the specific brain cells responsible for the hallucination responses in further studies.
- Charting spine production against changes in mood in animals to better understand the precise mood-related effects.
Checked
12 claims in this story checked against 1 source: 12 supported.
Show each claim
- SupportedIn mice, psilocybin’s brain benefits can be separated from its hallucinogenic effects.ScienceAlert: “the researchers were able to isolate the dendritic spine improvements from trip-like responses (assessed via the proxy of head twitches in the animals).”
- SupportedThe UC Santa Cruz study identifies separate pathways for plasticity and hallucinations.ScienceAlert: “What really stands out from the research are the two different pathways – one for plasticity and one for hallucinations.”
- SupportedThe study authors from UC Santa Cruz showed in mice that psilocybin’s neuroplasticity effects can be separated from its hallucinogenic properties.ScienceAlert: “The study authors, from the University of California, Santa Cruz, gave doses of psilocybin to groups of mice and were able to engineer boosts in brain connectivity without also causing trip-like sensations in the animals.”
- SupportedThe findings bring researchers closer to drugs that target one pathway and ignore the other.ScienceAlert: “we're a little closer to drugs that can target one pathway and ignore the other.”
- SupportedYi Zuo said, “I consider this work a major advance, particularly in our understanding of how psilocybin reshapes neural circuits and its potential implications for treating mental disorders.”ScienceAlert: “"I consider this work a major advance, particularly in our understanding of how psilocybin reshapes neural circuits and its potential implications for treating mental disorders," says molecular biologist Yi Zuo.”
- SupportedJacob Baker said psychedelics have the potential to profoundly transform who we are by reshaping neural circuits in our brains.ScienceAlert: “"Psychedelics are fascinating compounds because they have the potential to profoundly transform who we are by reshaping the neural circuits in our brains," says neuroscientist Jacob Baker.”
- SupportedThe study was published in Nature Neuroscience.ScienceAlert: “A new study published in Nature Neuroscience shows how that might be possible.”
- SupportedResearchers genetically reconfigured cellular receptors to increase brain connectivity in mice without causing head-twitch responses, a proxy for psychedelic effects.ScienceAlert: “by manipulating the brain cells receptive to psilocybin, the researchers were able to isolate the dendritic spine improvements from trip-like responses (assessed via the proxy of head twitches in the animals).”
- SupportedPsilocybin can increase dendritic spine volume and speed spine development in less than 24 hours.ScienceAlert: “the team found that psilocybin could boost spine volumes and speed up spine development in less than 24 hours.”
- SupportedIn stressed mice, new spine formation increased more, and the loss of existing connections stopped.ScienceAlert: “In the mice that had been put under stress before receiving the doses of psilocybin, which is a rough approximation of depression in people, the compound had a different effect. New spine formation increased to a greater extent, and the loss of existing connections was stopped.”
- SupportedZuo said the findings challenge the view that psilocybin simply increases neural connectivity and suggest its effects depend on the brain’s underlying condition.ScienceAlert: “"These findings challenge the prevailing view that psilocybin simply increases neural connectivity and suggest that its effects depend on the brain's underlying condition," says Zuo.”
- SupportedZuo said such therapeutics could deliver fast and lasting antidepressant benefits while eliminating hallucinogenic side effects, making neuroplasticity treatments safer and more accessible.ScienceAlert: “"Such therapeutics could deliver the fast and lasting antidepressant benefits of psychedelics while eliminating hallucinogenic side effects – making neuroplasticity treatments safer, more scalable, and accessible to a broader patient population," says Zuo.”
