First fMRI study of mescaline reveals altered sensory filtering and brain networks

A recent study published in Neuroscience Bulletin utilized functional magnetic resonance imaging (fMRI) to investigate the effects of mescaline on the brains of awake rats. The research aimed to explore how the psychedelic compound alters sensory filtering and brain networks. Mescaline, a psychedelic found in cacti and used ceremonially by Indigenous communities, is known to activate serotonin receptors, particularly the 5-HT2A receptor, which are involved in perception, mood, and thinking.

The researchers studied 24 rats, with half receiving 50 milligrams of mescaline per kilogram of body weight and the others receiving a control solution. During brain imaging, the rats were trained to remain awake and tolerate the scanning procedure. The study focused on the cerebellum, a brain region responsible for coordinating movement, balance, attention, memory, emotional regulation, and sensory information processing.

The results demonstrated that mescaline reduced activity in the cerebellum while increasing communication between it and several other brain regions. Additionally, the psychedelic altered responses to a rewarding smell (almond) and changed the brain's ability to filter sounds, with effects varying according to sound frequency. The study found that mescaline decreased activity in 26 of 169 examined brain regions and increased activity in 33 regions, with the largest effects concentrated in the cerebellum.

Furthermore, mescaline reduced the volume of brain areas showing typical increases in activity and expanded the volume of areas with suppressed activity. Notably, prepulse inhibition – the ability to filter sensory information by reducing startle response – was affected differently depending on sound frequency. The cerebellum showed particularly strong connections with the hippocampus (memory and context), the thalamus (sensory information relay and organization), the somatosensory cortex (touch and bodily sensations), and the midbrain (alertness, motivation, and reward).

Interestingly, the rats' normal response to the almond odor was largely weakened, suggesting that mescaline affected sensory filtering in a more selective manner. At specific frequencies, sound filtering improved at 4 and 20 kilohertz but worsened at 12 kilohertz. The authors concluded that mescaline exhibits a distinctive neurobiological profile, characterized by cerebellar-selective hypoactivation (reduced activity) and global hyperconnectivity (excessive communication across brain networks).

However, some limitations should be acknowledged. The researchers did not record physiological factors such as heart rate, breathing, or blood gases, which could have influenced the fMRI results. Moreover, the study only tested a single dose of mescaline, and the findings in rats may not fully translate to humans due to physiological differences.