How magic mushroom ingredient psilocybin helps patients with depression or PTSD change how they feel, by rewiring the brain with more connections

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The use of psychedelic drugs such as LSD and psilocybin was a legitimate field of medical research in the 1940s and 1950s, and LSD was even employed as a psychiatric medicine. But such research stopped in the mid-1960s when they were declared Schedule 1 illegal drugs in the United States.

Over the past decade, however, researchers have returned to studying the therapeutic uses of psychedelics to treat depression and post-traumatic stress disorder (PTSD) and as part of palliative care for those suffering from terminal cancer.

Fresh research suggests that psilocybin, the active ingredient in “magic mushrooms”, can be a treatment for depression.

“Humans have been using magic mushrooms for thousands of years, and indigenous societies have long used them in rituals,” says Bruna Giribaldi, clinical trial manager at the Centres for Psychedelic Research and Neuropsychopharmacology at Imperial College London.

Psychedelics or hallucinogens cause visual hallucinations

 which change the way you see the world. But the most important part of their effects for those of us who are looking at their therapeutic uses is that they also heighten people’s emotions.”

Speaking at an online conference organised by New Scientist Live, an offshoot of the UK’s New Scientist magazine, Giribaldi noted that psilocybin has the power to help patients relive traumatic experiences that have been repressed. It can also make depressed users feel better about themselves.


“It’s important to highlight that psychedelics don’t just make people see things, they make people feel things in a different way. They allow people to have profound feelings of love and compassion for themselves and others, which can be incredible.

“Such feelings can also help them to feel deeply connected to themselves and others. People can feel pleasure and have spiritual experiences,” she said.

Once ingested, psilocybin is rapidly metabolised to psilocin, which acts on serotonin receptors in the brain. Serotonin is a neurotransmitter, one of the chemicals that the brain uses to communicate with itself. (One of the many things serotonin does is improve mood.)

Serotonin binds to many kinds of receptors to send messages around the brain, and psilocybin affects its relationship with a specific receptor known as 5-HT2A. The more psilocybin you give a patient, the more 5-HT2A receptors serotonin binds to.

What happens next is the interesting part. Such bindings do happen naturally, but with psilocybin, many, many more connections are made. The brain effectively rewires itself by adding a lot more “wires”, and these new connections enable the different areas of the brain to work together in a different way.

Those who have read about LSD experiences will have heard of the idea of colours having a sound attached to them, for instance. When psychedelic drug users talk about the fridge singing to them, this is what is going on in their brains.


“Psilocybin makes areas of the brain that don’t usually connect with each other start connecting, and that means, for instance, your visual field can connect with your emotions,” said Giribaldi.

Many parts of the brain start communicating with many other parts, so our view of the outside world – which is formed by the way the brain interprets the perceptions it receives from our senses – changes as a result.

So how do these changes help depressed people?

“The theory is that psychedelics relax the strong beliefs that people have about the world,” Giribaldi said. “By relaxing your beliefs, you are able to see things in a different way….”

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