Scans have been used to compare brain activity between people who took psilocybin
Therapists test psychedelic chaos to cure depression and addiction.

Psychiatrists have since turned to antidepressants, mood stabilisers and antipsychotics that aren’t curative.

In the first part of this series, psychotherapist Friederike Meckel Fischer was arrested by the Swiss police after she treated her patients with LSD and ecstasy (MDMA). The two drugs began life as medicines for therapy, but were then listed as scheduled drugs only for research under tight conditions. Meckel Fischer is part of a band of psychiatrists and therapists who want to reclaim these drugs for mental health treatment. This week, experimental psychiatrists talk about the effect of the drugs on depression, addiction and anxiety. But some remain sceptical about the drugs’ ability to change peoples’ behaviour. We also find out what happened to Meckel Fischer.

People on psychedelic highs often speak of having profound spiritual experiences. Back in the 1960s, Walter Pahnke, a student of Timothy Leary, the American psychologist and writer who advocated psychedelic drugs, conducted a notorious experiment at Boston University’s Marsh Chapel to show that psychedelics could induce these.

Pahnke gave 10 volunteers a large dose of psilocybin – the active ingredient in “magic” mushrooms – and 10 an active placebo, nicotinic acid, which caused a tingling sensation but no mental effects. Eight of the psilocybin group had spiritual experiences, compared with one of the placebo group.

In later studies, researchers identified core characteristics of such experiences, including ineffability (the inability to express in words the intensity of the experience); paradoxicality (the belief that contradictory things are true at the same time); and feeling more connected to other people or things.

“When the experience can be really useful is when they feel a connection even with someone who has caused them hurt, and an understanding of what may have caused them to behave in the way they did,” says Robin Carhart-Harris, a psychedelics researcher at Imperial College London. “I think the power to achieve those kinds of realisations really speaks to the incredible value of psychedelics and captures why they can be so effective and valuable in therapy. I think that can only really happen when defences dissolve away. Defences get in the way of those realisations.”

He compares the feeling of connection with things beyond oneself to the “overview effect” felt by astronauts when they look back on the Earth. “All of a sudden they think, ‘How silly of me and people in general to have conflict and silly little hang-ups that we think are massive and important.’ When you’re up in space looking down on the entirety of the Earth, it puts it into perspective. I think a similar kind of overview is engendered by psychedelics.”

Scientific study
Carhart-Harris is conducting the first clinical trial to study psilocybin as a treatment for depression. He is one of a few researchers in the world pushing ahead with research on psychedelic therapy. Twelve people have taken part in his study so far.

They begin with a brain scan, and a long preparation session with the psychiatrists. On the therapy day, they arrive at 9am, complete a questionnaire and have tests to make sure they haven’t taken other drugs. The therapy room has been decorated with drapes, ornaments, coloured glowing lights, electric candles and an aromatiser. A PhD student, who is also a musician, has prepared a playlist, which the patient can listen to either through headphones or from high-quality speakers in the room. They spend most of the session lying on a bed, exploring their thoughts. Two psychiatrists sit with them and interact when the patient wants to talk. The patients have two therapy sessions: one with a low dose, then one with a high dose. Afterwards, they have a follow-up session to help them integrate their experiences and cultivate healthier ways of thinking.

I meet Kirk, one of the participants, two months after his high-dose session. Kirk had been depressed, particularly since his mother’s death three years ago. He experienced entrenched thought patterns, such as going round and round on a racetrack of negative thoughts, he says. “I wasn’t as motivated, I wasn’t doing as much, I wasn’t exercising any more, I wasn’t as social, I was having anxiety quite a bit. It just deteriorated. I got to the point where I felt pretty hopeless. It didn’t match really what was going on in my life. I had a lot of good things going on in my life. I’m employed, I’ve got a job, I’ve got family, but, really, it was like a quagmire that you sink into.”

At the peak of the drug experience, Kirk was deeply affected by the music. He surrendered himself to it and felt overcome with awe. When the music was sad, he would think of his mother, who had been ill for many years before her death. “I used to go to the hospital and see her, and a lot of the time she’d be asleep, so I wouldn’t wake her up; I’d just sit on the bed. And she’d be aware I was there and wake up. It was a very loving feeling. Quite intensely I went through that moment. I think that was quite good in a way. I think it helped to let go.”

During the therapy sessions, there were moments of anxiety as the drug’s effects started to take hold, when Kirk felt cold and became preoccupied with his breathing. But he was reassured by the therapists, and the discomfort passed. He saw bright colours, “like being at the funfair”, and felt vibrations permeate his body. At one point, he saw the Hindu elephant god Ganesh look in at him, as if checking on a child.

Although the experience had affected him, he noticed little improvement in his mood in the first 10 days after the treatment. Then, on a Sunday morning, he felt an upheaval. “I feel like there’s space around me. It felt like when my mum was still alive, when I first met my partner, and everything was kind of okay, and it was so noticeable because I hadn’t had it in a while.”

There have been ups and downs since, but overall, he feels much more optimistic. “I haven’t got that negativity any more. I’m being more social; I’m doing stuff. That kind of heaviness that suppressed feeling has gone, which is amazing, really. It’s lifted a heavy cloak off me.”

Another participant, Michael, had been battling depression for 30 years, and tried almost every treatment available. Before taking part in the trial, he had practically given up hope. Since the day of his first dose of psilocybin, he has felt completely different. “I couldn’t believe how much had changed so quickly,” he says. “My approach to life, my attitude, my way of looking at the world, just everything, within a day.”

One of the most valuable parts of the experience helped him to overcome a deep-rooted fear of death. “I felt like I was being shown what happens after that, like an afterlife,” he says. “I’m not a religious person and I’d be hard pushed to say I was anything near spiritual either, but I felt like I’d experienced some of that, and experienced the feeling of an afterlife, like a preview almost, and I felt totally calm, totally relaxed, totally at peace. So that when that time comes for me, I will have no fear of it at all.”

Friederike Meckel Fischer trained with Samuel Widmer, a Swiss physician, psychiatrist and psychotherapist and also worked in an addiction clinic. The insights from her drug experiences gave her new empathy. “All of a sudden I could understand my clients in the clinic with their alcohol addiction,” she says. “They were coping differently than I did. They had almost the same problems or symptoms I had, only I hadn’t started drinking.” But only a few were able to say

how those experiences made them feel. She wondered: Could an MDMA experience help them release those emotions?

MDMA (3,4-methylenedioxy-methamphetamine), also known as ecstasy, is a tamer relative of the classic psychedelics – psilocybin, LSD, mescaline and DMT (psychedelic compound of the tryptamine family). They have effects that can be disturbing – sensory distortions, the dissolution of one’s sense of self and the vivid reliving of frightening memories. MDMA’s effects are shorter-lasting, making it easier to handle in a psychotherapy session.

Meckel Fischer opened a private psychedelic therapy practice in Zürich in 1997. During the next few years, she began hosting weekend group therapy sessions with psychedelics in her home, inviting clients who had failed to make progress in conventional talking therapy.

Important context
Since the 1950s, psychiatrists have recognised the importance of context in determining what sort of experience the LSD taker would have. They have emphasised the importance of “set” – the user’s mindset, their beliefs, expectations and experience – and “setting” – the physical milieu where the drug is taken, the sounds and features of the environment and the other people present.

A supportive setting and an experienced therapist can lower the risk of a bad trip, but frightening experiences still happen. According to Meckel Fischer, they are part of the therapeutic experience. “If a client is able to go through, or lets himself be led through and work through, the bad trip turns into the most important step on the way to himself. But without a correct setting, without a therapist who knows what he’s doing and without the commitment of the client, we end up in a bad trip.”

Her clients would come to her house on a Friday evening, talk about their recent issues and discuss what they wanted to achieve in the session. On Saturday morning, they would sit in a circle on mats, make the promise of secrecy, and each take a personal dose of MDMA agreed with Meckel Fischer in advance. She would start with silence, then play music and speak to the clients individually or as a group to work through their issues. Sometimes she would ask other members of the group to assume the role of a client’s family members and have them discuss problems in their relationship. In the afternoon they would do the same with LSD, which would often let the participants feel as though they were reliving traumatic memories. Meckel Fischer would guide them through the experience and help them understand it in a new way. On Sunday, they would discuss the experiences of the previous day and how to integrate them into their lives.

Meckel Fischer’s practice, however, was illegal. Therapeutic licences to use the drugs had been withdrawn by the Swiss government around 1993, following the death of a patient in France under the effect of ibogaine, another psychotropic drug. It was later determined that she died from an undiagnosed heart condition.

The early LSD researchers had no way to look at what it was doing inside the brain. Now we have brain scans. Carhart-Harris has carried out such studies with psilocybin, LSD and MDMA. He says there are two basic principles of how the classic psychedelics work.

The first is disintegration: the parts that make up different networks in the brain become less cohesive. The second is desegregation: the systems that specialise for particular functions as the brain develops become, in his words, “less different” from each other.

These effects go some way towards explaining how psychedelics could be therapeutically useful. Certain disorders, such as depression and addiction, are associated with characteristic patterns of brain activity that are difficult to break out of. “The brain kind of enters these patterns, pathological patterns, and the patterns can become entrenched. The brain easily gravitates into these patterns and gets stuck in them. They are like whirlpools, and the mind gets sucked into these whirlpools and gets stuck.”

Chaos as therapy
Psychedelics dissolve patterns and organisation, introducing “a kind of chaos”, says Carhart-Harris. On the one hand, chaos can be seen as a bad thing, linked with things like psychosis, a kind of “storm in the mind”. But there is a view that chaos has a therapeutic value. “The storm could come and wash away some of the pathological patterns and entrenched patterns that have formed and underlie the disorder. Psychedelics seem to have the potential through this effect on the brain to dissolve or disintegrate pathologically entrenched patterns of brain activity.”

The therapeutic potential suggested by Carhart-Harris’s brain scan studies persuaded the United Kingdom’s Medical Research Council to fund the psilocybin trial for depression. It’s too early to evaluate its success, but the results so far have been encouraging. “Some patients are in remission now months after having had their treatment,” Carhart-Harris says. “Previously their depressions were very severe, so I think those cases can be considered transformations. I’m not sure if there are any other treatments out there that really have that potential to transform a patient’s situation after just two treatment sessions.”

In the wake of MDMA’s prohibition, American psychologist Rick Doblin founded the Multidisciplinary Association for Psychedelic Studies (Maps) to support research aiming to re-establish psychedelics’ place in medicine. When Swiss psychiatrist Peter Oehen heard they were funding a study on using MDMA to help people with post-traumatic stress disorder (PTSD), he jumped on a plane to meet Doblin in Boston.

Friederika Meckel Fisher was prosecuted for treating her psychiatric patients with psychedelics. 

Like Meckel Fischer, Oehen trained in psychedelic therapy while it was legal in Switzerland in the early 1990s. Doblin agreed to support a study with 12 patients at Oehen’s private practice in Biberist, about half an hour by train from the Swiss capital, Bern.

Oehen thinks that MDMA’s mood-elevating, fear-reducing and pro-social effects make it a promising tool to facilitate psychotherapy for PTSD. “Many of these traumatised people have been traumatised by some kind of interpersonal violence and have lost their ability to connect, are distrustful, are aloof,” says Oehen. “This helps them regain trust. It helps build a sound and trustful therapeutic relationship.” It also puts the patient in a state of mind in which they can face their traumatic memories without becoming distressed, he says, helping to reprocess the trauma in a different way.

When Maps’s first PTSD study in the United States was published in 2011, the results were eye-opening. After two psychotherapy sessions with MDMA, 10 out of 12 participants no longer met the criteria for PTSD. The benefits were still apparent three to four years after the therapy.

Oehen’s results were less dramatic, but all the patients who had MDMA-assisted therapy felt some improvement. “I’m still in touch with almost half of the people,” he says. “I can still see people getting better after years going on in the process and resolving their problems. We saw this at long-term follow-up, that symptoms get better after time, because the experiences enable them to get better in a different way to normal psychotherapy. These effects – being more open, being more calm, more willing to face difficult issues – this goes on.”

In people with PTSD, the amygdala, a primitive part of the brain that orchestrates fear responses, is overactive. The prefrontal cortex, a more sophisticated part of the brain that allows rational thoughts to override fear, is underactive. Brain-imaging studies with healthy volunteers have shown that MDMA has the opposite effects – boosting the prefrontal cortex response and shrinking the amygdala response.

More research
Ben Sessa, a psychiatrist working around Bristol in the UK, is preparing to carry out a study at Cardiff University to test whether people with PTSD respond to MDMA in the same way. He believes that early negative experiences lie at the root not just of PTSD but of many other psychiatric disorders too, and that psychedelics give patients the ability to reprocess those memories.

“I’ve been doing psychiatry for almost 20 years now and every single one of my patients has a history of trauma,” he says. “Maltreatment of children is the cause of mental illness, in my opinion. Once a person’s personality has been formed in childhood and adolescence and into early adulthood, it’s very difficult to encourage a patient to think otherwise.” What psychedelics do, more than any other treatment is offer an opportunity to “press the reset button” and give the patient a new experience of a personal narrative.

Sessa is planning a separate study to test MDMA as a treatment, for alcohol dependency syndrome, picking up the trail of British psychiatrist Humphrey Osmond’s research 60 years ago when he experimented with using LSD to help alcoholics stop drinking.

Sessa believes psychiatry would look very different today if research with psychedelics had proceeded unencumbered since the 1950s. Psychiatrists have since turned to antidepressants, mood stabilisers and antipsychotics. These drugs, he says, help to manage a patient’s condition, but aren’t curative and also carry dangerous side effects.

“We’ve become so used to psychiatry being a palliative care field of medicine,” Sessa says. “That we’re with you for life. You come to us in your early 20s with severe anxiety disorder; I’ll still be looking after you in your 70s. We’ve become used to that. And I think we’re selling our patients short.”

Will psychedelic drugs ever be ruled legal medicines again? Maps is supporting trials of MDMA-assisted psychotherapy for PTSD in the US, Australia, Canada and Israel, and it hopes it will have enough evidence to convince regulators to approve the drug by 2021. Meanwhile, trials using psilocybin to treat anxiety in people with cancer have been taking place at Johns Hopkins University and New York University since 2007.

Few psychiatrists would give their opinions about the legal use of psychedelics in therapy. One who did, Falk Kiefer, director at the department of addictive behaviour and addiction medicine at the Central Institute of Mental Health in Mannheim, Germany, says he is sceptical about the drugs’ ability to change patients’ behaviour. “Psychedelic treatment might result in gaining new insights, ‘seeing the world in a different way’. That’s fine, but if it does not result in learning new strategies to deal with your real world, the clinical outcome will be limited.”

Value in good science
Carhart-Harris says the only way to change people’s minds is for the science to be so good that funders and regulators can’t ignore it. “The idea is that we can present data that really becomes irrefutable, so that those authorities that have reservations, we can start changing their perspective and bring them around to taking this seriously.”

After 13 days under arrest, Meckel Fischer was released. She appeared in court in July 2010, accused of violating the narcotics law and endangering her clients, the latter of which could mean up to 20 years’ imprisonment. A number of neuroscientists and psychotherapists testified in her defence, arguing that one portion of LSD is not a dangerous substance and has no significant harmful effects when taken in a controlled setting. MDMA was not included in the prosecution’s case.

The judge accepted that Meckel Fischer had given her clients drugs as part of a therapeutic framework, with consideration for their health and welfare, and ruled her guilty of handing out LSD but not guilty of endangering people. For the narcotics offence, she was fined 2 000 Swiss francs and given a 16-month suspended sentence with two years’ probation.

“I have been blessed by a very understanding lawyer and an intelligent judge,” she says. She considers the woman who reported her to the police a blessing because the case has allowed her to talk openly about her work with psychedelics.

This story was originally published by the UK-based science journalism website Mosaic. Visit mosaicscience.com/story/psychedelic-therapy