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Psilocybin Reduces Neural Activity in the Brain's Ego Center

Psilocybin alters the functional connectivity of ego-related brain networks.

The latest psilocybin research by Roland Griffiths and colleagues at Johns Hopkins University puts the functional connectivity of an ego-related brain structure called the "claustrum" in the spotlight. The recent findings (Barrett et al., 2020) from JHU on how psilocybin alters the functional connectivity and neural activity of the claustrum were published online May 23 in the journal NeuroImage.

Roland Griffiths is a world-renowned pioneer of 21st-century psilocybin research. In recent years, he played a pivotal role in psychedelic drugs receiving a "breakthrough therapy (BT) designation." Griffiths is a professor of psychiatry and neuroscience and Center Director of the Johns Hopkins Center for Psychedelic and Consciousness Research, where the latest clinical study of psilocybin and the claustrum was conducted.

Why Haven't You Heard of the Claustrum (Latin for "Hidden Away") Until Now?

Santiago Ramón y Cajal (1852-1934) and a handful of other neuroscientists have expressed interest in the claustrum throughout history. Nevertheless, the claustrum has lived up to its Old Latin name (which means "hidden away") by staying off most scientists' radar for centuries.

In a relatively obscure paper, "What Is the Function of the Claustrum?" Francis Crick and Christof Koch (Crick & Koch, 2005) describe the structure and function of this brain region:

"The claustrum is a thin, irregular, sheet-like neuronal structure hidden beneath the inner surface of the neocortex in the general region of the insula. Its function is enigmatic. Its anatomy is quite remarkable in that it receives input from almost all regions of cortex and projects back to almost all regions of cortex."

In his lifetime, Francis Crick (1916-2004), who won a Nobel Prize in 1962 "for discoveries concerning the molecular structure of nucleic acids [DNA] and its significance for information transfer in living material," speculated that the claustrum plays a role in the integrated nature of consciousness and humans' sense of self. Christof Koch (b. 1956) is a German-American neuroscientist who is best known for his research into the neural basis of consciousness.

Why Investigate Psilocybin's Influence on the Claustrum?

The claustrum contains a disproportionately large number of 5-HT2A receptors for psychedelic drugs such as LSD and psilocybin. Because of the claustrum's robust expression of 5-HT2A receptors and how it integrates input/output with almost every region of the cerebral cortex, the Johns Hopkins researchers wanted to investigate how psilocybin modulates claustrum function in humans using fMRI brain imaging.

For this study, Barrett et al. recruited fifteen participants who were familiar with both the MRI environment and had participated in a previous experiment on the subjective effects of a high dose of psilocybin (25 mg). To investigate how psilocybin affects the claustrum, participants took 10 mg of psilocybin (or a placebo) and had an fMRI brain scan 100 minutes later.

The researchers found that psilocybin reduced neural activity in the claustrum by 15-30 percent. The fMRI brain scans also showed that "psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention."

Subjective effects ratings for psilocybin vs. placebo were completed immediately after each resting-state brain scan and were rated on a 0-10 scale (0 = none; not at all to 10 = extreme; strongest imaginable). Interestingly, a bigger reduction of neural activity in the claustrum was correlated with participants self-reporting more intense mystical experiences after ingesting psilocybin. Last year, Griffiths published a paper on these so-called "God Encounter Experiences." (Griffiths et al., 2019)

In a June 4, 2020 news release, the Johns Hopkins researchers said: "This ties in with what people report as typical effects of psychedelic drugs, including feelings of being connected to everything and reduced senses of self or ego."

In previous experiments, psilocybin-evoked reductions of the functional connectivity within the default mode network have been correlated with higher subjective effects and "strongest imaginable" peak mystical or "ego-dissolving" experiences.

Over the years, I've had some lifechanging "ego-dissolutive" hallucinogenic experiences that I'd rate as a "10" on a 0-10 scale of subjective effects.

Gerd Altmann/Pixabay
Source: Gerd Altmann/Pixabay

Anecdotally, I know from first-hand experience that higher doses of magic mushrooms feel like they decrease neural activity in the brain's ego center during the complete loss of subjective self-identity known as "ego death." (See "One Mystical Psychedelic Trip Can Trigger Lifelong Benefits")

"Our findings move us one step closer to understanding mechanisms underlying how psilocybin works in the brain," first author Frederick Barrett, assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and member of the Center for Psychedelic and Consciousness Research, said in the news release.

He added: "This will hopefully enable us to better understand why [psilocybin] is an effective therapy for certain psychiatric disorders, which might help us tailor therapies to help people more."

In future research, Barrett and his JHU colleagues will explore how other psychedelics such as Salvinorin A—which is a psychotropic molecule and dissociative hallucinogen derived from a Mexican plant—affect the claustrum.

Regarding the general direction of future research in this field, the authors note: "As a future direction that may apply broadly to the psychedelic field, comparison of the effects of psychedelic drugs in participants with and without previous exposure to psychedelics will be important to understanding interactions between the acute and enduring effects of these compounds."


Frederick S. Barrett, Samuel R. Krimmel, Roland Griffiths, David A. Seminowicz, Brian N. Mathure. "Psilocybin Acutely Alters the Functional Connectivity of the Claustrum With Brain Networks That Support Perception, Memory, and Attention." NeuroImage (First published online: May 23, 2020) DOI: 10.1016/j.neuroimage.2020.116980

Roland R. Griffiths, Ethan S. Hurwitz, Alan K. Davis, Matthew W. Johnson, Robert Jesse. "Survey of Subjective 'God Encounter Experiences': Comparisons among Naturally Occurring Experiences and Those Occasioned by the Classic Psychedelics Psilocybin, LSD, Ayahuasca, or DMT." PLOS ONE (First published: April 23, 2019) DOI: 10.1371/journal.pone.0214377

Francis C. Crick and Christof Koch. "What Is the Function of the Claustrum?" Philosophical Transactions of the Royal Society B: Biological Sciences (First published online: June 29, 2005) DOI: 10.1098/rstb.2005.1661