Scientists May Have Pinpointed How LSD Works in the Brain

One pill makes you larger
And one pill makes you small
And the ones that mother gives you
Don’t do anything at all
Go ask Alice, when she’s 10 feet tall

Despite her status as an early proponent of LSD, Alice didn’t really have an answer for why it did what it did when she was ten feet tall or just small either. And while the doormouse’s “feed your head” recommendation certainly identified the part of the body that would get the benefit, it didn’t explain why the men on the chessboard got up either. Fortunately, the loosening of the laws and taboos that have long restricted research in lysergic acid diethylamide (LSD) are being lifted and scientists are finally able to explore the drug’s effects and potential benefits using human testing. A new study has just been published in the Proceedings of the National Academy of Sciences and it appears scientists have identified which part of the head is being fed. Pay attention, Alice!

“Using cutting-edge neuroimaging methods we investigated directed connectivity between cortico–striato–thalamo-cortical (CSTC) regions after administration of LSD together with the specific role of the serotonin 2A receptor.”

Recent studies have suggested that LSD somehow affects the ability of the thalamus to act as a bouncer at the doorway to the posterior cingulate cortex – limiting the number of stimuli that can enter so brain’s capacity doesn’t become overloaded. It was theorized the LSD somehow distracts the bouncer, allowing too many dancers, drinkers and other stimuli into the brain, causing LSD’s hallucinations, feelings of bliss and ego dissolution.

“The world around us is not the world we perceive because the thalamus filters out what it considers to be irrelevant information. We don’t necessarily perceive all there is because that would be an overload of information.”

Katrin Preller, a researcher on the project at the University Hospital for Psychiatry in Zurich, led the study. Twenty-five healthy volunteers were given LSD and some were unknowingly given ketanserin, a drug that blocks serotonin receptors, thus blocking the chemical that is believed to help regulate mood and social behavior among other things and is believed to play a part in the effects of LSD. In addition to the brain scans, the volunteers were given a questionnaire specifically designed to identify when a person is tripping.

What did the brain scans and questionnaires show?

“Our results confirm major predictions proposed in the CSTC model and provide evidence that LSD alters effective connectivity within CSTC pathways that have been implicated in the gating of sensory and sensorimotor information to the cortex. In particular, LSD increased effective connectivity from the thalamus to the posterior cingulate cortex in a way that depended on serotonin 2A receptor activation, and decreased effective connectivity from the ventral striatum to the thalamus independently of serotonin 2A receptor activation.”

In doormouse terms, LSD not only incapacitates the posterior cingulate cortex doorman, but throws the door wide open and perhaps even makes it bigger, thus letting in more partying stimuli than the brain can handle. Fortunately, many of the effects are pleasant and, as Steve Jobs liked to point out, long-lasting and potentially life-changing. For the medical field, it means its original purpose – a psychiatric drug to treat a variety of mental disorders – may finally be realized, says Preller.

“We are getting nearer to understanding the complexity of what happens with LSD in the brain and that is particularly important if we are to develop new medicines.”

Thanks, Katrin! You too, Alice. And don’t forget Grace. And the dormouse.

Paul Seaburn (CLICK HERE TO READ AND SEE MORE)