People who use psychedelic drugs — psychoactive substances that produce profoundly altered states of consciousness — often report a loss of sense of self and dissolution of their ego, also called ‘ego-death.’ They report their sense of “I,” usually distinct from the rest of the world, disintegrating when they trip on psychedelic drugs, such as magic mushrooms or LSD. For the longest time, scientists have attempted to trace the process of this ego dissolution in the brain, often having ended up with anecdotal or observational evidence. Now, a new first-of-its-kind study evaluating the effect of psilocybin (magic mushrooms) on the human brain reveals a possible neurotransmitter pathway that could hold the answer.

Previous theories suggest people who are tripping on psychedelics have elevated levels of neurotransmitter glutamate in the part of the brain that is believed to be linked to self-awareness. This hypothesis, however, had not been tested in humans until now. Scientists from the Maastricht University in the Netherlands conducted a double-blind, controlled trial with 60 participants using magnetic resonance imaging (MRI), to monitor their glutamate levels while they tripped on magic mushrooms.

The study, published in the journal Neuropsychopharmacology, shows people who had negative experiences of their ego death had higher levels of glutamate in their pre-frontal cortex, which is responsible for personality expression, social behavior, and decision-making. People who had positive experiences with the disintegration of their ego had lower levels of glutamate in the hippocampus, the part of the brain that’s involved in the formation of memories, and is associated with emotions and self-esteem. This fluctuation in glutamate — considered one of the most common neurotransmitters in the brain — could explain the loss of autobiographical information (and loss of personal identity) that previous research has established accompanies the use of psychedelics.

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While these findings have taken scientists one step closer to establishing a proven connection between glutamate and ego-death, they don’t yet show exactly how this process of ego death comes about. While further investigation into the phenomenon of psychedelics-induced ego death is needed, scientists stress that the findings chart a way forward into researching the therapeutic effects of psychedelics. Charting the effects of reality-altering psychedelics could help better understand mental health issues that are characterized by distortions of self-perception, such as depression.

Drugs like ketamine and MDMA have already been tapped to treat drug-resistant depression and post-traumatic stress disorder, respectively. With further research into how the brain perceives altered realities caused by drugs, scientists believe they can better understand, and therefore treat, altered realities caused by mental health issues.