Breakthrough psilocybin study uncovers neurochemical origins of human ego

Impressive new research, led by scientists from Maastricht University in the Netherlands, has uncovered a new neurochemical mechanism by which psilocybin generates its hallucinogenic effects.

The death of the ego

Psilocybin, the primary psychoactive compound found in magic mushrooms, has been demonstrating such profound efficacy in early trials for treating major depression the FDA has twice granted it a Breakthrough Status designation over the past year. Exactly how psilocybin generates its beneficial therapeutic effects is still unclear, both physiologically and psychologically. Anecdotally, perhaps the most commonly reported subjective effect of a psychedelic drug is a disruption to one’s sense of ego. Timothy Leary called it «ego-loss» back in the 1960s, while more modern scientists variously use terms including ego-death, ego-disintegration and ego-dissolution.

Considering ego-dissolution is a seemingly fundamental part of many psychedelic experiences, researchers are beginning to explore how this deeply subjective phenomenological sensation could be mediating the therapeutic benefits of these drugs.

It’s not just serotonin

«As you may know, there is a growing interest in the therapeutic utility of serotonergic 5-HT2A agonists like psilocybin, for disorders like treatment-resistant depression, anxiety, addiction, and PTSD,» explains Natasha Mason, from the Department of Neuropsychology and Psychopharmacology at Maastricht University. A great deal of recent research has focused on how compounds such as LSD and psilocybin generate their psychedelic effects by stimulating 5-HT2A serotonin receptors in the brain. Using a double-blind study design with placebo control, the researchers recruited 60 volunteers, administering each either psilocybin or an inactive placebo. Alongside evaluating subjective states using well-established surveys measuring ego dissolution, resting state functional magnetic resonance imaging focused expressly on glutamate levels in the medial prefrontal cortex and the hippocampus.

«Our first main finding was that psilocybin changed levels of glutamate, a powerful and abundant excitatory neurotransmitter, in key areas of the brain,» Mason explains. As Mason notes, this is the first research to demonstrate psilocybin directly mediating alterations to glutamate levels in a human brain. The second part of the team’s study involved investigating the correlations between these psilocybin-induced glutamate changes in the brain and the subjects’ self-reported sense of ego.