LSD was criminalised across the world in the late 1960s, following a moral panic about the effect recreational use was having on young people. After a 40 year hiatus on medical use, LSD is being studied once more. Helen Glenny explains.

Mel Elwin, 36, swallowed five large pills and washed them down with water. She put on headphones, dark eye shades, and lay back in a bed. After a while, she started to relax. “I just felt really peaceful,” Mel says. “And that’s probably when I left my body.”

She had been referred to Imperial College London in 2015 by her GP after eight years with severe depression, spanning a relationship breakdown, a job loss, and the birth of her son. She’d tried three different types of antidepressants; two made her worse, the other made her numb. The pills she took contained psilocybin, the active ingredient in magic mushrooms.

Mel’s trial was the first in 40 years where psychedelic drugs were given to patients with severe, treatment-resistant depression, and it was remarkably effective. Psychedelics studies are now underway across Europe and North America, and the University of Auckland is about to start an LSD microdosing trial, bringing the psychedelic revolution here.

The acid test

In the 1950s and 60s, more than 40,000 patients were treated with LSD for depression and alcoholism. LSD was criminalised around the world in the late 1960s at the height of beat poetry, counterculture and America’s war on drugs, and as a result, psychedelics vanished from the psychiatrist’s toolbox. But over the last 10 years, a resurgence has begun.

Professor David Nutt, who heads the Imperial College lab where Mel’s trial took place, campaigns for the reclassification of drugs based on an objective ranking at how harmful they are. Psychedelics, he points out, are neither addictive nor harmful, especially when administered by doctors. For Mel’s trial, he’d wangled permission to treat 12 volunteers all suffering from treatment-resistant depression with psilocybin.

(This modern wave of psychedelics trials all use either LSD or psilocybin. They have similar, but not identical, effects. The choice often comes down to which drug is easier to get permission to use. If both are available, psilocybin is preferable because the trip only lasts six hours, allowing everyone to get home for dinner.)

Trial trips are very different to taking LSD recreationally. Mel spent hours getting to know her two “guides”; and on her dosing days she lay under blankets in a dimly-lit room, with soft table runners and ornaments giving the lab a yoga-studio vibe. She took 25mg of psilocybin, and the experience, she says, was “soul-bending”.

“I just became a ball of light, and I was literally everywhere at once,” she says. “I was the sun, I was the stars, I was the moon, I was everything. There were lots of other lights around me. They were all souls, and I was a soul.”

During the trip, her guides would check in with her every 15 minutes. If she encountered something scary, her guides would reassure her she was safe.

As part of the trial, Mel had psychotherapy sessions that helped her make sense of her experience, and she started feeling better straight away. “I booked myself into the gym and started working again,” she says. It was the first break from an eight-year depressive period. She still has hard times, but four years later, she no longer considers herself depressed.

This was just a small-scale feasibility study, but the results were fascinating. Every participant in the trial was less depressed a week after their trip. Mel was one of seven (out of 12) who was considered depression-free. After three months, five were still free from depression; a mammoth result for people for whom nothing else had worked.

Your brain on psychedelics

A team at Imperial College went one step further; giving healthy patients LSD and sliding them into an MRI scanner to image their brain activity as they trip.

They expected to see fireworks, but in most areas of the brain, activity actually decreased under LSD. Instead, a low level of activity hummed all over the brain. One region that went particularly quiet was a hub of brain structures called the “default mode network”. This is the network responsible for self-reflection, self-criticism, and thinking about the future or the past. It’s thought to be the seat of our ego, and in depressed people, it’s often in overdrive.

“Overactivity of the default mode locks people into negative, internalising thinking,” says Professor David Nutt. “Psychedelics disrupt the default mode and allow people to think differently. You’ve got this double whammy: you’ve escaped through the trip, and afterwards, your brain is more receptive to new ways of thinking.”

Mel’s experience, feeling at one with nature, and physically part of every bit of the universe, is a classic example of ego-dissolution, the result of a default mode network gone quiet.

In fact, every condition that’s been treated successfully with psychedelics involves a component of critical self-thought: I can’t get through the day without a drink, in alcoholism; I’m responsible for something that happened to me as a child, in trauma. Depression, OCD, anorexia, smoking; all involve inescapable negative loops of thought that gradually shade out reality, and psychedelics ease these loops open.

A tab a day keeps the doctor away

Most psychedelics studies use “macrodoses” – a high enough dose to induce a trip. But a team at the University of Auckland, led by associate professor Suresh Muthukumaraswamy, is investigating LSD microdosing: taking just a little, not enough to elicit any kind of psychedelic experience, frequently.

Volunteers will take a small dose every fourth morning at home; a quirk in our drug laws allows Class A drugs to be prescribed for a month or less, with “mountains of paperwork,” according to Dr Rachael Sumner, a postdoc working on the trial. “The crux of the trial is the ability for people to go home and live their normal lives.”

Microdosing on LSD isn’t expected to open up ego-dissolving experiences. Instead it may boost plasticity; the ability of the brain to change.

A lack of brain plasticity is a hallmark of depression. A less plastic brain is subject to getting stuck in rigid loops of negative thinking, the kind that goes on in the default mode network. Traditional antidepressants are believed to increase brain plasticity, but it can take six to eight weeks. “Drugs like LSD, psilocybin and ketamine all increase plasticity within hours,” says Sumner.

At this early stage, the trial is looking at microdosing in healthy male volunteers with no added therapy, but in the future, it could be combined with psychotherapy or CBT to help create enduring change. Six-hour guided explorations of an ego-free universe aren’t for everyone, so microdosing could be a solution for those who aren’t keen on a trip.

In the UK, Professor David Nutt continues to campaign for psychedelics to be legalised, at least for medical use. Attitudes are slowly changing; in the past year, Denver, Oakland and Santa Cruz, all in the USA, voted to decriminalise magic mushrooms. Johns Hopkins is running a new trial for psilocybin use in those suffering from Alzheimer’s. Mel hasn’t taken psychedelics again, saying that what she learned from her one experience is enough to keep her well. “It hasn’t all been easy, life happens. But this trial reset my brain.”