Psychedelic experiences can be unpredictable, with the same substances often producing wildly differing effects in different people. Explaining and controlling these hallucinogenic happenings has yet to be whittled down to an exact science, although a new study in the journal Biomedicines indicates that a particular brain region may hold the key to shaping each person’s unique reaction to psychedelics.
Since the first scientific studies on substances like LSD, mescaline, and magic mushrooms were conducted back in the 1950s, researchers have generally attributed the nature of psychedelic experiences to a combination of “set and setting”. In this context, set refers to the emotional and mental condition of the user while setting relates to the actual environment in which a drug is ingested.
Working on this basis, psychedelic therapists often try to nudge patients in the direction of certain experiences by manipulating various elements of set and setting, whether through counseling prior to administering any substances or the use of music and other aesthetic factors during the psychedelic experience itself.
While these measures can be effective, the authors of this latest study wanted to know if underlying neurological attributes also play a role in determining how different people respond to psychedelics. Using magnetic resonance imaging, they scanned the brains of 55 people while they tripped on psilocybin, the active compound in magic mushrooms. Once the effects of the drug had subsided, participants were asked to complete the Five-Dimensional Altered State of Consciousness (5D-ASC) questionnaire, which measures the intensity of psychedelic experiences.
Because psilocybin is known to interact primarily with serotonin 2A receptors, the study authors paid particular attention to a part of the brain called the cingulate cortex, which contains a high concentration of these receptors.
After comparing the brain scans with participants’ questionnaire responses, they found that the thickness of an area called the rostral anterior cingulate cortex strongly predicted the intensity of certain key aspects of the psychedelic experience, including Unity, Spiritual Experience, Blissful State and Insightfulness. More specifically, the thicker the rostral anterior cingulate cortex, the more extreme these experiences.
Other parts of the cingulate cortex, such as the caudal and posterior cingulate, showed no such correlation with the intensity of these effects. This led the researchers to conclude that the rostral anterior cingulate cortex alone seems to be responsible for determining how a person is affected by psilocybin.
Such findings would appear to make sense based on what we know about the structure and function of this part of the brain. For instance, it has previously been shown that the anterior region of the cingulate cortex connects the amygdala – which is strongly associated with emotions – with the prefrontal cortex, thereby creating the capacity for emotional regulation. That the thickness of the anterior cortex should mediate the emotional intensity of psychedelic trips therefore fits with our understanding of brain anatomy.
Summing up, the study authors explain that their findings “extend the traditional set and setting hypothesis of the psychedelic experience to include brain structure metrics.”