Scientists Identify Key Neural Mechanisms Behind an LSD Trip

LSD appears to cause information to disintegrate as it is passed through a neural circuit that determines how we process internal and external stimuli.
Brain regions in the CTSC targeted by LSD
Image: PNAS

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New research has identified a key neural mechanism that leads to altered states of consciousness in humans after taking LSD. The research lends strong support to a decade-old theory that attributes the trippy effects of many psychedelics to a breakdown of information processing in a region of the brain that regulates how we respond to internal and external stimuli.


As detailed in a paper published Monday in the Proceedings of the National Academy of Sciences, researchers at the University of Zurich dosed 25 people with LSD and used an MRI machine to study a neural pathway called the cortico-striato-thalamo-cortical (CSTC) loop. The CSTC loop is part of the broader salience network in our brains, which is a collection of neural regions responsible for determining which external and internal stimuli get our attention.

In 2008, two psychiatrists theorized that disruptions in the normal functioning of the CSTC loop was largely responsible for the altered states of consciousness experienced by people who take LSD, psilocybin, and other classical psychedelics. In particular, this CSTC model focused on the thalamus, a region of the brain that processes sensory information, regulates the information that gets passed to the cortex, which is responsible for consciousness, attention, memory, and other major brain functions.

According to the CSTC model, disruptions to the thalamus can take many different forms. It could involve blocking NMDA receptors, which are important for memory; increasing dopamine neurotransmitters, which are heavily involved with regulating movement; or flooding serotonin 2A receptors, which are deeply involved with cognition. Normally, the thalamus acts like a gate that determines what sensory information gets passed to the cortex, but these types of neurotransmitter imbalances throw that gate wide open. This decreased sensory filter is why psychedelics result in a strange visuals and body sensations—at least in theory.


Read More: The Long, Hard Road to a Science of Bad Drug Trips

This new research is the first time that the CSTC model was tested in humans and the results of the study lend strong evidence to the CSTC theory of why we trip. LSD targets many of the receptors that regulate the CSTC loop, so by imaging the brains of their subjects when they were on LSD and when they were sober, the researchers could see how LSD affects the normal functioning of the CSTC loop.

As the researchers discovered, LSD did in fact increase the amount of connectivity between the thalamus and certain regions of the cortex. While this is largely in line with the CSTC modeled proposed a decade ago, there is one key difference. In this research, the LSD only resulted in increased connectivity with certain regions of the cortex, particularly those associated with changes in what the researchers described as “self-experience.”

“This might explain the seemingly paradoxical subjective effects often reported in psychedelic-induced altered states of consciousness that are characterized by increased arousal as well as a dreamlike experience, impaired cognition but at the same time reported perceived mental clarity, and psychosis-like effects combined with blissful experiences,” the researchers concluded.

In the future, the researchers hope to show how their model of psychedelic altered states of consciousness can be combined with other explanations of why we trip. For example, evidence suggests that psychedelic experiences are also related to increased entropy in the brain, which results in “disorganization of brain activity and more flexible cognition.”

Given the significant role that the salience network plays in mental disorders such as schizophrenia, OCD, and depression, studying the influence of LSD on the CSTC loop in the salience network may also help development treatments for these diseases.

Correction: A previous version of this article said the researchers were affiliated with Johns Hopkins University when they were in fact affiliated with the University of Zurich. Motherboard regrets the error.