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Psilocybin Interactions with Glutamate

Researchers studying the loss of ego commonly experienced while tripping on psychedelics such as magic mushrooms have discovered that a key neurotransmitter may be linked to the phenomenon. A report on the research by scientists at Maastricht University in the Netherlands was published last month in the journal Neuropsychopharmacology.

Quite often, those who use psychedelic drugs such as psilocybin mushrooms and LSD experience a change in the perception of self and one’s connection to the larger world. Known as ego-dissolution, ego-disintegration, or ego-loss, the experience can result in a reduced state of self-awareness and a disruption of the boundaries of self and the world, leading to an increased feeling of unity with the environment. For some, the experience of ego-dissolution is a positive one, or a good trip, while others may have a negative, sometimes terrifying, bad trip.

Previous research has shown that ego and self-awareness may be related to levels of glutamate, the brain’s most abundant neurotransmitter. To test the theory, the team of researchers at Maastricht University designed a double-blind and placebo-controlled experiment to study the effect that psilocybin had on the glutamate levels of 60 healthy volunteers. Brain activity of the test subjects was monitored using magnetic resonance imaging (MRI).

The researchers discovered that psilocybin led to increased levels of glutamate in an area of the brain known as the prefrontal cortex, which is thought to be responsible for planning complex behavior, personality expression, decision-making, and moderating social behavior. They also recorded lower levels of glutamate in the hippocampus, an area of the brain that has been linked to the formation of memories and one’s sense of self-esteem.

The researchers also noted that the higher levels of glutamate in the prefrontal cortex caused by taking psilocybin were associated with a good trip, while the lower levels of glutamate in the hippocampus were linked to experiencing a bad trip.

“Whereas changes in [cortical] glutamate were found to be the strongest predictor of negatively experienced ego dissolution, changes in hippocampal glutamate were found to be the strongest predictor of positively experienced ego dissolution,” the researchers wrote.

More Research Needed

While it’s yet not clear if glutamate is actually related to the experience of ego-dissolution, other studies have suggested that psychedelics may decouple different regions of the brain.

“Our data add to this hypothesis, suggesting that modulations of hippocampal glutamate in particular may be a key mediator in the decoupling underlying feelings of (positive) ego dissolution,” wrote the researchers.

Although more research is needed, the discovery of psilocybin’s effect on glutamate levels could help explain how the drug can be used therapeutically for a variety of mental health conditions including depression and severe anxiety.

“Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic state, and importantly, provide a neurochemical basis for how these substances alter individuals’ sense of self, and may be giving rise to therapeutic effects witnessed in ongoing clinical trials,” the authors wrote.

Source – HighTimes