What psychedelics do to your brain

David Nutt is the head of Imperial College London’s Centre for Psychedelic Research. When the Centre opened in 2019 it was the world’s first dedicated institute for this kind of work - looking at how these drugs actually work in the brain, and whether the effects might be useful to treat problems with mental health. Sally Le Page asked David the former question: do we know what these drugs do to your brain?

David - We do know, because we have brain imaging techniques which have shown very clearly that these drugs have a very profound, disruptive effect on ongoing brain activity. We also know that this effect is mediated through targeting serotonin receptors. These are the proteins that serotonin works on in the brain, and there are 15 different serotonin receptors, but these hallucinogens all work on a very special one called the 5-HT2A receptor which is peculiarly dense in the human brain.

Sally - It's got a very snappy name that one. What does it do?

David - Well, there are people that think it's responsible for the evolution, the vast expansion of the human brain in recent evolution. My own view is it's latent in parts of the brain where we do our very high level thinking, looking backwards, looking forwards, where we have our dreams and our imaginations. I think it coordinates essentially the laying down of new ideas and new ways of thinking, new ways of dealing with problems, which is why in the end I think these drugs have turned out to be useful in conditions like mental illness and depression.

Sally - So when we take these drugs, what does it do to our overall brain if it's affecting these single little receptors?

David - The high level parts of your cortex, the thinking parts, the parts which integrate your hearing, your sight, your touch, etcetera - they get disrupted by psychedelics. Psychedelics, in a very simple way, put you back to what your brain was like when you were a child, when all kinds of connections were possible. The process of neur development is not a growing of the brain; it's a shrinking of the brain, getting rid of connections which you don't want. Over the decades from childhood, the brain becomes more and more constricted in what it does and more and more rigid, and psychedelics disrupt that and put you back transiently into that state of childhood wonder.

Sally - So growing up is like doing topiary on your brain, and then taking these psychedelics is letting the brain - the plant - just grow wild again, so you can kind of start from scratch.

David - Yeah, that's right. It's a kind of reset. A lot of our patients describe the influence of psilocybin treatment as being like a defrag of a hard drive, or a reformatting. It allows people to break out of ways of thinking. Often depressed people, for instance, get locked into thinking the same thought time and time again. "I made a mistake, I shouldn't have done this, I was a bad person." They can't escape that thinking because our brains are extraordinarily efficient at learning to do things, but if they learn to do the wrong thing and have the wrong thought, they're very hard to disrupt. And psychedelics are probably the most powerful way of disrupting that kind of unwanted thinking.

Sally - Does this disruption explain the other side effects we see - like the hallucinations, and feeling at one with the universe?

David - Absolutely. Now that's what we discovered first. The reason we started treating depressed people with psilocybin was because we saw that the ability of psilocybin to disrupt the networks of the brain which contained thinking is the same as its ability to disrupt the networks which control vision, and sense of self, and position and place in the universe. So visual hallucinations, they're really remarkable, because under psychedelics your visual cortex temporarily is unable to properly reconstruct the signals in the eye into images, and those simple hallucinations - we know from sophisticated electrophysiological experiments - those are the very early ways in which you reconstruct what you see. So under psychedelics, you actually see the primary workings of your visual cortex, which is actually, I think, extraordinarily interesting and something which you haven't experienced since you were a child.