Single-dose psilocybin rapidly and sustainably relieves allodynia and anxiodepressive-like behaviors in mouse models of chronic pain

Summary & key facts

Researchers gave a single dose of psilocybin to adult male and female mice with long-term pain. The drug quickly and lastingly reduced both increased touch pain and mouse behaviors that look like anxiety and low mood. The team traced these effects to changes in the front part of the brain and to psilocybin’s active form, psilocin, acting on two serotonin receptors. These results are in mice, so they do not prove the same will happen in people, but they show a single treatment can, in animals, act on the same brain circuits to ease both pain and mood problems.

Key facts:

• The study used two different mouse models of chronic pain and tested a single dose of psilocybin in adult male and female mice.
• After one dose, mice showed a rapid and sustained reduction in mechanical allodynia, which means less pain from light touch.
• The same single dose also reduced behaviors in mice that researchers interpret as anxiety-like and depression-like.
• Direct injections of psilocin, the active chemical made from psilocybin, into the front part of the brain showed that that brain region is important for relieving both pain and mood symptoms.
• Live imaging of brain cells showed that psilocin quickly lowered abnormally high activity in specific neurons in the anterior cingulate cortex, a region linked to pain and emotion.
• Giving drugs that strongly activate two serotonin receptors known as 5-HT2A and 5-HT1A copied some, but not all, of psilocin’s effects, which suggests psilocin works by partially activating those receptors together in shared brain circuits.
• These findings are from mice and do not prove that a single dose of psilocybin would have the same rapid and lasting effects in humans.
• The results support the idea that chronic pain and mood problems can come from overlapping brain circuits, and that acting on those circuits can affect both kinds of symptoms at once.

Abstract

Chronic pain and mood disorders co-occur, exacerbate one another and share neurobiological mechanisms, but whether a single intervention could promptly alleviate both conditions remains unclear. Here, in two chronic pain models, we show that a single dose of psilocybin induces a rapid and sustained reversal of both mechanical allodynia and anxiodepression-like states in adult male and female mice. Using local psilocin injections, the key active metabolite of psilocybin, we show that the engagement of prefrontal cortical circuits is critical for the concurrent alleviation of both conditions. Two-photon calcium imaging reveals that psilocin rapidly normalizes chronic pain-associated hyperactivity in anterior cingulate cortex layer 2/3 pyramidal neurons. Pharmacologic manipulations with full agonists of 5-HT2A and 5-HT1A receptors replicated some, but not all, of psilocin’s cellular and behavioral effects, suggesting that psilocin’s actions arise from partial agonism at these receptors within shared circuits governing pain and mood processing. Hammo et al. show that a single dose of psilocybin rapidly and sustainably relieves both chronic pain and anxiodepressive-like behaviors in mice by restoring prefrontal activity through partial agonism at 5-HT2A and 5-HT1A receptors.

Topics

Neurotransmitter Receptor Influence on Behavior Pain Mechanisms and Treatments Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Allodynia Anesthesia Anhedonia Anterior cingulate cortex Antidepressant Chronic pain Cingulate cortex Cortex (anatomy) Default mode network Dopamine Glutamate receptor Hallucinogen Hyperalgesia Mediator Medicine Mood Mood disorders Neurochemical Neurology Neuroscience Neurotransmitter NMDA receptor Nociception Pharmacology Prefrontal cortex Psilocybin Psychology Psychopharmacology Receptor Serotonin

Substances

Psilocybin

Conditions & symptoms

Anxiety Chronic Pain Depression Anxiety or worry Chronic pain Sadness or low mood