New Study Reveals Lasting Brain Oscillations Induced by Psilocybin in Rats

Recent research published in Molecular Psychiatry has shed light on how psilocybin, a psychedelic compound, influences neural activity in the rat brain, particularly in the medial prefrontal cortex. Conducted by teams from the University of Bristol, Compass Pathways, and other institutions, the study investigated how a single dose of psilocybin affects neuron behavior and network oscillations over both short and long timescales.

Using advanced neural recording technology called Neuropixels, researchers monitored electrical activity from over 2,000 neurons in the rat prefrontal cortex. They administered a synthetic form of psilocybin, known as COMP360, which is similar to doses previously used in human clinical trials for depression. Their findings indicated that psilocybin robustly induces specific oscillations at around 100Hz, particularly within the infralimbic region of the prefrontal cortex—a brain area associated with mood regulation and depression treatment in humans.

Interestingly, the team observed that these oscillations persisted for days after a single dose, suggesting that psilocybin might promote neural plasticity. The 100Hz activity was most prominent during states of quiet wakefulness and less during active cognitive tasks, aligning with clinical observations that psychedelic benefits are maximized during calm, restful periods.

Furthermore, the study identified that the infralimbic region functions as a key hub for these oscillations, which could resemble a form of localized, chemical electroconvulsive therapy. This discovery points to a potential mechanism by which psilocybin might exert its therapeutic effects, as this brain area in humans shares similarities with a critical depression treatment target—the subgenual anterior cingulate cortex.

Remarkably, enhanced oscillatory activity in this region was also observed six days following the drug administration, highlighting possible long-lasting network changes. These neural patterns reflect a state of network plasticity and heightened information processing capabilities.

However, responses among individual neurons were diverse, with some increasing activity, others decreasing, and some unaffected. This variability suggests that multiple neuron types and circuits respond differently to psilocybin, prompting further research into neuron-specific effects.

The investigators plan to extend their studies to examine other brain areas involved in depression, emotion, memory, and reward, as well as the influence of psilocybin on sleep patterns—an important factor in mental health. Their goal is to deepen understanding of how psychedelic substances modulate brain circuits and to explore their potential for treating mental health disorders.

This groundbreaking work offers valuable insights into the neural mechanisms influenced by psilocybin and underscores the importance of further research into its therapeutic potential.