Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor.

The psychedelic drug LSD alters thinking and perception. Users can experience hallucinations, in which they, for example, see things that are not there. Colors, sounds and objects can appear distorted, and time can seem to speed up or slow down. These changes bear some resemblance to the changes in thinking and perception that occur in certain psychiatric disorders, such as schizophrenia. Studying how LSD affects the brain could thus offer insights into the mechanisms underlying these conditions. There is also evidence that LSD itself could help to reduce the symptoms of depression and anxiety disorders. Preller et al. have now used brain imaging to explore the effects of LSD on the brains of healthy volunteers. This revealed that LSD reduced communication among brain areas involved in planning and decision-making, but it increased communication between areas involved in sensation and movement. Volunteers whose brains showed the most communication between sensory and movement areas also reported the strongest effects of LSD on their thinking and perception. Preller et al. also found that another drug called Ketanserin prevented LSD from altering how different brain regions communicate. It also prevented LSD from inducing changes in thinking and perception. Ketanserin blocks a protein called the serotonin 2A receptor, which is activated by a brain chemical called serotonin that, amongst other roles, helps to regulate mood. By mapping the location of the gene that produces the serotonin 2A receptor, Preller et al. showed that the receptor is present in brain regions that show altered communication after LSD intake, therefore pinpointing the importance of this receptor in the effects of LSD. Psychiatric disorders that produce psychotic symptoms affect vast numbers of people worldwide. Further research into how LSD affects the brain could help us to better understand how such symptoms arise, and may also lead to the development of more effective treatments for a range of mental health conditions.