What Psilocybin Does to the Brain

Psychedelic compounds produce intense subjective experiences and have shown promise in the treatment of posttraumatic stress disorder (PTSD) and treatment-resistant depression, amongst other psychiatric conditions. But what do we actually know about what happens in the brain when we consume these substances? Down to the level of single brain cells, what produces these effects? In our new paper, we tried to answer some basic questions no one has answered before.

To do so, we looked at the effect of a 2 mg/kg dose of psilocybin, the active ingredient in magic mushrooms, on the brains of awake mice by using electrodes that enable the recording of neural activity from single brain cells (neurons), networks of neurons, and cumulative brain wave activity, known as local field potential (LFP). Whilst there are many different ways to estimate the human-equivalent dose that would produce similar effects, we can say with confidence that this is a strong, though still clinically relevant, dose of psilocybin.

By placing the electrode in a region of the brain known as the anterior cingulate cortex, we aimed to find out how psilocybin affects the neural circuits shown to be associated with emotional processing and internal awareness (interoception). This region of the brain is also part of the broader prefrontal cortex, an area known to be critical in higher functions, such as cognitive and emotional processing.

Alteration in Brain Waves

When we examined the mice during their peak experience phase, we found psilocybin had numerous effects on neural activity. One of the most pronounced was an alteration in brain waves.

In general, brain waves occur at a range of different frequencies. We found that slower oscillations (delta, theta, and alpha waves) were significantly reduced by psilocybin, whilst the power of faster gamma waves resulted in an increase. These oscillations have many functions in the brain, one of which is to enable communication between one region and another. It is thought that slow waves are more responsible for information flow between distant regions of the brain, while faster, gamma waves enable information flow within local regions of the brain. As such, the shift in the power from low to high frequencies caused by psilocybin may indicate that the anterior cingulate cortex transmits and receives less information to and from faraway brain regions and, thereby, may represent a reduction in the top-down processing function that it normally exerts.

Activity of Single Neurons

The activity of single neurons was also impacted, with approximately 40 percent increasing their activity. Neurons often fire in a way that is coordinated to brain oscillations (this is a phenomenon known as “phase-locking”). However, this locking between brain waves and single neuron activity degraded under psilocybin.

Neurons communicate with one another in two ways: via binary signals called action potentials, or spikes, and through neuron firing known as “burst firing.” Burst firing occurs when the neuron fires several spikes in quick succession. These bursts of neural activity provide a more powerful means of communication between neurons and are strongly implicated in neuroplasticity and memory formation.

We observed that, under psilocybin, burst firing was reduced overall, but that a subset of neurons actually increased their burst firing. Surprisingly, when we examined the relationship between neurons whose burst firing changed and whether they showed phase-locking behaviour, we found a consistent relationship whereby neurons that increased their burst firing reduced their degree of phase-locking. Taken altogether, psilocybin seems to increase the overall activity of the anterior cingulate cortex, but in a chaotic manner that disrupts the regularity of brain activity.

When we combine all of our findings, it would appear that psilocybin reduces intercommunication between the anterior cingulate cortex and distant brain regions and makes activity both more excitable and more irregular. These results support the idea put forward by Robin Carhart-Harris and Karl Friston in their REBUS model (Relaxed Beliefs Under Psychedelics), which posits that psychedelics disrupt the influence of top-down modulation upon sensory information coming into the brain, instead favouring incoming sensory input. This means psychedelics may enable the brain to rely less on prior beliefs and expectations, and be more receptive to incoming information.

Perhaps the disruption to neural activity we found in the anterior cingulate cortex is symptomatic of this reduced influence of top-down processing regions on brain activity. However, as is always true of science, this is merely a data point from which to perform further research to get closer to the ground truth of what psilocybin is doing to brain activity, though, hopefully it is a data point that has taken us one step farther on that path.