Houston, Texas, USA : Psychedelic drugs such as LSD have a profound impact on human consciousness, particularly perception. Researchers at Yale and the University of Zurich provide new insight into the psychedelic effects of LSD on the brain and potential therapeutic uses of the drug.
The new data indicate that LSD triggers a reduction of functional connections between regions of the brain governing cognitive processes and increases connectivity in brain networks associated with sensory functions. It does so by stimulating a particular receptor for the neurotransmitter serotonin (serotonin-2A or 5HT2A receptor). The 5HT2A receptor has been implicated in the regulation of mood and cognition.
Using gene expression maps and data-driven tools to measure brain-wide communication, the team was able to infer the patterns of brain signals in subjects who had taken LSD and identify the 5HT2A receptor as a crucial mechanism leading to changes in perception and thought.
“There is a net effect of LSD on the entire brain but the effect is not uniform,” explained Alan Anticevic, assistant professor of psychiatry and psychology and co-senior author of the paper, which appears in the journal eLife.
In recent years, scientists have become increasingly interested in the use of psychedelics to treat mental health disorders such as depression. While serotonin plays a key role in maintaining mood balance and decreased levels are associated with depression, another immediate impact of the new findings may be in the treatment of schizophrenia, Anticevic suggested.
Most schizophrenia patients are treated with atypical antipsychotic drugs, which block some of the serotonin receptors identified by the new study. However, many patients don’t respond well to such treatments.
“Clinicians may be able to identify individual patients most likely to benefit from these drugs by looking for similar patterns of brain activity identified in the study,” noted Katrin Preller, assistant professor at the University of Zurich and visiting professor at Yale, who is the lead author of the paper.
Using a technology optimized by Anticevic and Dr. John Murray, assistant professor of psychiatry at Yale and co-author on the paper, researchers pinpointed gene activity in the brain and showed how it influences neurotransmitter function.
In the 1960s, Yale researchers Daniel X. Freedman, Nicholas Giarman, and George Aghajanian first implicated the serotonin system, and the 5HT2A receptor, in the actions of LSD, noted Dr. John Krystal, professor and chair of psychiatry at Yale.
“It has taken over 50 years and technical advances in brain imaging and molecular neuroscience to enable us to build on the earlier work in mechanistic clinical research,” Krystal said. “This path, and other related research strategies will take us deeper in our search for the roots of human consciousness and the biology of mental illness.”
Citation: Katrin H Preller et al. Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor, eLife (2018). DOI: 10.7554/eLife.35082
Image : Researchers explain how LSD changes perception. LSD reduced brain-wide communication among brain areas involved in planning and decision-making, but it increased communication between areas involved in sensation and movement, which can be attributed to the 5HT2A serotonin receptor.
Image credit: Katrin Preller & Alan Anticevic
A second study found that LSD blurs boundaries between the experience of self and other
LSD blurs boundaries between the experience of self and other
LSD reduces the borders between the experience of the self and others, and thereby affects social interactions. Researchers at the University of Zurich have now found that the serotonin 2A receptor in the human brain is critically involved in these intertwined psychological mechanisms . This knowledge could contribute to new therapies for psychiatric disorders such as schizophrenia or depression.
Virtually all mental health disorders come with difficulties in interpersonal relations that in the long run negatively affect the progression of the disease. The associated health and social restrictions can only be marginally improved by current forms of therapy. One of the reasons for this is that there has been very little research into the basic neurobiological principles and in particular the neurochemical mechanisms of these kinds of disorders. A further symptom of various psychiatric disorders is distortions of self-experience. People suffering from mental disorders often show either an inflated or weakened sense of self.
Researchers at the University Hospital of Psychiatry Zurich have now investigated the links between changes in the sense of self and changes in social interaction, and the pharmacological mechanisms that play a role in these processes.
“LSD blurs the boundaries between one’s own self and others during a social interactions,” explains Katrin Preller. She led the research team of the Neuropsychology and Brain Imaging group together with Prof. Franz Vollenweider and cooperated with the Max Planck Institute of Psychiatry in Munich on the study. While lying in an MRI scanner, study participants communicated with a virtual avatar by means of eye movements after having been administered a placebo, LSD, or LSD in combination with ketanserin.
Changes in social interaction
“This allowed us to show that brain regions which are important for distinguishing between self and others were less active under the influence of LSD,” says Preller. “And this also changed social interactions.” The researchers were also able to show that the LSD-induced changes were blocked by ketanserin indicating that the serotonin 2A receptor (5-HT2A receptor) plays a critical role in this mechanism.
Approaches for new drugs
These findings demonstrate that self-experience and social interaction are closely linked. Varying impairments of these intertwined processes could be the result of an impaired transfer of information mediated by the 5-HT2A receptor system. This could be important for the development of new pharmacological therapies. For example, blocking this receptor in patients suffering from an incoherent sense of self such as schizophrenia could improve their symptoms as well as their social abilities. On the other hand, stimulating this receptor could help patients who suffer from an increased self-focus, as is the case with depression, for example.
Citation for second study: Journal of Neuroscience, DOI: 10.1523/JNEUROSCI.1939-17.2018