Ayahuasca is a potent hallucinogen that has been used throughout the Amazon basin for centuries, and is popular among visitors on spirit quests. Researchers have long wondered whether controlled doses of hallucinogens might be used to treat depression and other forms of mental illness. But until fairly recently, nobody really had a clear idea exactly how hallucinogens work. Now the substance is under serious study as a possible treatment for depression and alcoholism.

Because the study of hallucinogens has been hampered by legal and ethical concerns, few studies have been conducted until recently. The conventional belief was that psilocybin created its effects by increasing neurotransmitter activity, thereby increasing nervous activity. However, neuropsychopharmacologist Robin Carhart-Davis and colleagues drew a different conclusion from their 2012 study on the hallucinogen psilocybin, the active ingredient in “magic” mushrooms. Psilocybin did not seem to increase neuroactivity. Rather, the researchers found that activity in key regions of the brain actually decreased under psilocybin’s influence.

During the 2012 study, researchers gave experienced hallucinogen users a standardized dose of psilocybin and examined them via MRI. A control group received a placebo instead. The MRI revealed that blood flow decreased in the brains of the study group and remained normal in the control group. Blood flow decreased most in the anterior and posterior cingulate cortex and the medial prefrontal cortex. These areas of the brain under normal conditions are exceptionally active, with increased blood flow compared to the rest of the brain. Furthermore, connectivity between these areas of the brain decreased under the influence of psilocybin.

According to Carhart-Harris et al., these portions of the brain are associated with fundamental aspects of human experience, including consciousness, fundamental thought processes, and the sense of self. These are crucial regions geographically as well, described as “hubs” where information is shared and transmitted across multiple sectors of the brain. When these connection hubs are limited, information sharing in the brain is either reduced or has to find another way around. Inhibition is reduced. The overall result is what Carhart-Davis calls “unconstrained cognition,” or mind-altering effects.

This mechanism might lend itself to possible therapeutic applications. The medial prefrontal cortex in particular is known to be especially active and connected in cases of depression; an overactive medial prefrontal cortex is also associated with unhealthy brooding and pessimism. The studies continue, but psilocybin and other hallucinogens may prove helpful in their ability to quiet this crucial portion of the brain. Some hallucinogen users report the effect of intense experiences reverberating for months or years afterwards, so treatments based on these substances have the potential to be more durable than conventional treatments. Researchers pursuing this line of inquiry will have to keep their minds open.



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Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 6 (February 7, 2012), pp. 2138-2143
National Academy of Sciences