Single Psilocybin Dose Reverses Pain And Depression In Mice Within 24 Hours 1/2
StudyFinds Analysislong article 1st part
In A Nutshell
One dose, weeks of relief: A single psilocybin injection reversed both chronic pain and depression-like symptoms in mice within 24 hours, with effects lasting at least 12 days.
Brain circuits, not injuries: The pain relief came from calming overactive neurons in a mood-and-pain processing region of the brain, not from healing the actual injuries, which remained visible at the study’s end.
Location matters: Psilocybin worked when it reached the brain’s anterior cingulate cortex but had no effect when injected near the spinal cord, showing pain relief happens in the brain.
Gentle balance beats brute force: Psilocybin’s partial activation of two serotonin receptors simultaneously proved more effective than fully activating either one alone or blocking pain signals entirely.
Pain and depression are intertwined: Mice with worse pain consistently showed worse anxiety and depression, and psilocybin relieved both simultaneously by rebalancing the same brain circuits.
PHILADELPHIA — Researchers at the University of Pennsylvania found that a single treatment with psilocybin, the active compound in magic mushrooms, rapidly reversed both chronic pain and depression-like symptoms in mice. The relief lasted for at least 12 days, the duration of observation after treatment.
The study, published in Nature Neuroscience, confirms what doctors have long observed but struggled to treat: chronic pain doesn’t just hurt the body. It rewires the brain, creating psychological suffering that worsens the original pain.
Chronic Pain Breaks the Brain’s Thermostat
The research team created two types of lasting pain in mice during the four-week study. Some had nerve damage. Others had severe inflammation in their paws.Both groups became hypersensitive to touch and developed what looked like mouse versions of profound anxietyand depression. They avoided open spaces, gave up faster in swimming tests, and showed impaired movement coordination.
Brain imaging revealed the culprit. A region called the anterior cingulate cortex, which processes both the emotional experience of pain and regulates mood, had essentially broken. Think of it like a smoke detector that won’t stop blaring even after the fire’s out. Nerve cells in this area were firing 40% more than they should have been, and they wouldn’t calm down.
Hitting the Reset Switch
On day 27, researchers gave mice a single injection of psilocybin. Within 24 hours, sensitivity to pain dropped to normal levels in both groups. The mice also returned to typical behavior in tests measuring anxiety and depression.
The improvements lasted. Even 12 days after the single treatment (when the experiment ended), pain relief continued and moodremained stable.
The location of psilocybin’s action mattered enormously. When researchers injected psilocin(what psilocybin becomes in the body) directly into the anterior cingulate cortex, they saw dramatic improvements. When they injected it into the spinal cord near the injury site, nothing changed. The activity levels that had been 40% above normal dropped back to baseline within minutes.
Why It Worked
Psilocybin affects two types of serotonin receptors in the brain: 5-HT2A and 5-HT1A. The researchers found it needs both to work its magic.
When researchers blocked either one before giving psilocybin, all benefits vanished. Pain returned, anxiety stayed high, depression-like behaviors persisted.
But overstimulating those same receptors individually didn’t help either. Maxing out 5-HT2A receptors alone actually increased activity in already overactive circuits. Maxing out 5-HT1A receptors alone decreased activity but provided only modest pain relief and no mood benefits.
Only psilocybin’s partial activation of both receptors simultaneously restored normal brain activity. Rather than blocking pain signals or dampening all brain activity, psilocybin recalibrates specific circuits that chronic pain has knocked out of balance.
https://studyfinds.org/single-psilocybin-dose-reverses-pain-depression/