Why psychedelics are returning to psychiatry
Jon Kostakopoulos was desperate and running out of options.
A heavy drinker for more than a decade, he had made countless attempts at recovery, having attended his first AA meeting when he was just 16.
Inpatient rehabilitation, outpatient programs and medication followed. But nothing seemed to work for the New Yorker.
“I didn’t drink all the time but when I did I would have 22 standard drinks a night or I would drink a full handle by myself through the day,” he says.
“The doctors said I’d be dead by 30.”
In 2015, his mother learned from her new doctor that a clinical trial was about to begin investigating whether psilocybin-assisted therapy could treat alcohol dependence. She relayed the information to her son.
The study was being run by a team of researchers from New York University (NYU) and involved three psilocybin “sessions” alongside motivational enhancement therapy.
“I had always been afraid of psychedelics,” Mr Kostakopoulos says.
“I always believed the horror stories that something bad would happen like getting stuck in a trip, if that’s even possible, or falling out of a window or losing my mind. But I just thought, ‘This is my last hope’.”
Mr Kostakopoulos arrived at Bellevue Hospital in New York for the first treatment dressed in a t-shirt and trackpants.
“They had told me to wear something comfortable. The treatment room had been set up to look like a living room. It had a couch, chairs and a vase of flowers on the table."
His pill was presented in a wooden chalice, a nod to psilocybin's historical use in religious and healing rituals.
In fact Mr Kostakopoulos didn’t know whether it was a psychedelic or the trial’s placebo, diphenhydramine. This was after all a double-blind study.
But he says 20 minutes later he began to hallucinate.
“It was like looking through a kaleidoscope and seeing the geometric shapes. At the time it felt normal. It took a while to realise this was it.”
“I had expected the experience hitting me like a bag of bricks,” Mr Kostakopoulos says. “But it crept in, slowly.”
Nixon and the war on drugs
The use of psychedelics in psychiatry, a bit like flared trousers, seems to be coming back into fashion.
In part it has been fuelled by the rapid development of neuroimaging over the last decade. It seems researchers can take a more rigorous scientific approach in tracking the effect of the drugs on the brain.
The first modern clinical trial of a psychedelic was very small scale. It was conducted at the University of Arizona in 2006 where nine subjects with treatment-resistant OCD were given up to three different doses of psilocybin in an open-label design.1
Significant reductions in OCD symptoms were seen but no clear dose effect was observed.
Today, worldwide, there are now about 100 active psychedelic trials, including for alcohol and drug-use disorders, dementia, anorexia and chronic pain.
In Melbourne, Australia’s first psychedelic clinical trial is under way at St Vincent’s Hospital where 40 terminally ill patients are being administered psilocybin alongside psychotherapy for anxiety and depression.
But it is in Europe, the UK and US where the research has advanced most.
Institutions like John Hopkins in Maryland, Imperial College in England, Yale in Connecticut and NYU have already established psychedelic research hubs and their investigations into MDMA and psilocybin are now entering phase 3 clinical trials.
Both drugs have also been given by the FDA ‘breakthrough therapy’ status, a designation designed to expedite the development of drugs to treat serious conditions.
Read more: The push for psychedelic psychotherapy
Dr James Rucker has been involved in psilocybin trials for the treatment of difficult-to-treat depression.
The UK psychiatrist says he was drawn to psychedelics for two reasons: his fascination with the drugs themselves and his sense of powerless to help patients who had already tried treatments like antidepressants with very little benefit.
“I’m not a psychedelic evangelist — there are plenty of those and, sadly, they run the risk of re-enforcing stigma. I am, however, curious,” he says.
“Psychedelics used to be used as medicines in psychiatry. A lot of people have forgotten that.
“But then they were caught up in the US President Richard Nixon’s ‘War on Drugs’ and the moral panic that arose out of the recreational drug use of the 1960s.
“A legal ‘guillotine’ came down after that, effectively banning medical use.
“This was a knee-jerk political reaction that wasn’t informed by science, wasn’t scrutinised properly in parliament and wasn’t actually necessary.
“Now, 50 years later, we are tentatively picking up the baton of history and re-evaluating these drugs.”
He says that psilocybin — a serotonergic compound found in more than 180 species of mushrooms — works by stimulating the serotonin system in the brain in a way different from anti-depressants and psychedelics like MDMA.
“Certain frequencies of brain waves disappear under psilocybin and the part of the brain that co-ordinate verbal patterns of thought become less active,” he says.
“This is interesting because these same areas are over-active in depression, particularly in people who ruminate and think obsessively about past or future events they can’t control.”
A pharmacological treatment?
But to what extent is the drug’s therapeutic role about changing chemicals in the brain? Isn’t the drug being used for patients to explore their memories and emotions during what would more accurately be described as drug-assisted psychotherapy?
Mr Kostakopoulos says during his sessions his therapists gave him an eye mask and headphones so he could listen to a playlist of tribal and classical music.
Song transitions, he says, often resulted in his emotions shifting.
“One of my biggest concerns was that I didn’t want anything popping out at me like a 3D movie and shocking me but the therapists told me that it was best to confront anything scary and see it through fully,” he says.
“For me this happened mainly with emotions.
“They were uncomfortable emotions of just shame and guilt and embarrassment of what I had put my family and friends through and how I had been so selfish.
“That was the hardest part of the process. Those realisations.”
For most of the sessions these emotions — which he describes as exaggerated and intense — consumed him.
He experienced them mostly in darkness.
But at other times he felt like he was in a lucid dream.
“There was stuff I hadn’t really thought about before that came up,” he says.
“Stuff like my dad showing me how to ride my new bike for the first time when I was probably about four and I was seeing that like you would in a dream.”
Two particular experiences he said were heavily symbolic to him.
The first was when he saw an empty bottle appear in the middle of the desert, only for it to suddenly disintegrate into sand.
At another point, he was looking down on his dead body in what he describes as an Aztec type ceremony when a sword came down through his neck.
“This death experience was the most peaceful part of the session,” he says.
“I saw that as my addiction leaving me and that I was killing a small and bad part of myself off — the part of me that loved going out and not caring about anything other than the next drink.”
“I didn’t really talk that night. I just sat in silence, trying to grasp what I had just witnessed. I was almost shell-shocked from the whole thing,” he says.
On psilocybin’s drug-or-psychotherapy question, Dr Rucker says this: “Obviously, it is a chemical and therefore interacting with brain chemistry, but as a result, they change the nature and degree of your mental experience.
“You are likely to form a narrative around that experience as you would do with any conscious experience.
“But I would say that was a separate and distinct process from the drug experience itself. Therefore, no, the drug is not offering some form of psychotherapy to patients, per se.
“Psychotherapy is provided by human beings, generally speaking. And we do give our trial participants access to psychotherapy to help mold the narrative into one that is beneficial.
“To me it’s no more or less complicated than that. The therapeutic efficacy — if it is there — is probably contained within the milieu above.”
He said his patients have described how psilocybin introduces a form of mental ‘space’ into an otherwise crowded head. Others, like Mr Kostakopoulos, refer to lucid dreams.
“Their experiences are often profound, deeply personally meaningful but otherwise ineffable … But there seems to be a reorientation of perspective on the behaviour and thinking habits that can underpin their mental illness.”
Read more: Caution advised over psychedelic therapies
Beyond its effect on the serotonin system, researchers don’t really know ‘how’ psilocybin invokes these brain changes, he says.
“I think this is a window into the workings of the mind and represents a form of scientific enquiry that society really should embrace much more than it does.”
He says the changes can be unpredictable.
“I have had depressed patients who smoke cigarettes take psilocybin for their depression and the effect was their desire to smoke evaporated,” he says.
“So, it is not as simple as thinking of psilocybin being ‘just another antidepressant’… as far as I can see they are the catalysts of change.”
Dr Rucker, who is currently leading two phase 2 clinical trials at King’s College London, says he is "fairly convinced” by the safety of psilocybin when taken under controlled circumstances and with professional guidance.
“Psychologically, I would describe it as gently challenging for the most part,” he says.
“The odd person has a particularly strong experience but the vast majority of these we manage with simple reassurance.
“On one occasion I gave a participant a small dose of oromucosal midazolam to settle them down, they weren’t distressed, more disinhibited.”
Drinking no longer appeals
Mr Kostakopoulos is now 30 years old.
He says he hasn’t had a drink since his treatment or substituted his alcohol use for any other type of drug. He no longer has the desire.
He also hasn’t attended any follow-up therapy or support groups.
While Mr Kostakopoulos can’t explain why psilocybin worked so well for him, he says, unlike other therapies, the sessions had a profound impact.
“I’ve never felt this confident before. It’s not like I’m managing my sobriety, I’m not counting days … drinking simply doesn’t appeal to me,” he says.
“Those realisations during the sessions that everyone was affected by my drinking, it wasn’t just me, really had an impact and this time it actually stuck.
“A lot of close friends of mine have died since I left psychedelic treatment five years ago. This worked so well for me and I’m not special."
“If it saved my life, it has a good chance of saving a lot more lives out there,” he claims.
Writing in Dialogues in Clinical Neuroscience two years ago, Professor David Nutt, professor of neuropsychopharmacology at Imperial College London, stressed the "resurrection of psilocybin research" was still in its infancy.2
There have been very few double-blinded studies, he said, and patient numbers remain very low — fewer than 200 in all.
"This means we must be very cautious in making claims about the value of psychedelic therapy in psychiatry. Much more needs to be done".
He added: "The question of safety is also important.
"Although the banning of psychedelics and MDMA was made on the basis of largely fictitious claims of harm, there is no doubt that the psychedelics in particular are powerful mind-altering drugs, that can leave deep negative as well as positive memories."
In Australia, psychedelic-assisted therapy is currently illegal outside of an authorised trial, but there are moves to allow greater access to the drugs.
The lobby group Mind Medicine Australia is leading the charge, having submitted an application to the TGA to reschedule psilocybin and MDMA from being classed as prohibited substances (S9) to controlled drugs (S8).
But the Royal Australian and New Zealand College of Psychiatrists has urged caution. The evidence to date is still insufficient to inform clinical practice, it stressed in a clinical memorandum released last year.
An interim decision is expected to be published by the TGA next month.
|Mind, brain or the default mode network?|
Psychedelic medicines in psychiatry also include alcoholism, smoking cessation and other substance-use disorders, as well as OCD and possibly eating disorders.
So what is happening under the influence of these drugs to produce these effects?
Dr Nigel Strauss, a Melbourne psychiatrist and enthusiastic advocate for the potential benefits of psychedelics, in an interview with Medical Observer in 2019 referred to the concept of the so-called ‘default mode network’.
“This area, which includes the prefrontal cortex, cingulate cortex and part of the parietal lobe, is believed to be the home of what Freud called the ego, or the part of the brain responsible for judgement, tolerance, reality testing and a sense of self,” he said..
“It acts like the conductor of an orchestra controlling and preventing too many signals reaching our consciousness.”
If this process becomes excessive, our minds can be closed off from potential outcomes and possibilities, which in turn may limit creativity resulting in a narrow-minded worldview, he said. This may lead to negative psychological consequences such as depression or addiction.
“When a person is given a psychedelic drug, blood flow to the default mode network decreases, and so its influence also decreases allowing more stimuli to reach consciousness.
"This can lead to a state of so-called ‘ego dissolution’, such that the usual boundaries we all experience between self and world, subject and object fade away.
“When this happens, people may begin to see things in a profound way, the so-called peak or transformative experience, which can be achieved by other means as well, such as fasting and meditation.”
Following the psychedelic peak experience, many research subjects report a lasting positive change in their worldview, he claimed.
Any element of subjectivity surrounding the experience is likely to be met with scepticism in a naturally sceptical community.
“We are limited by language,” Dr Strauss says. “You are jumping from a currently accepted physical model to experiences of profound subjectivity.
“Science and contemporary psychiatry have real difficulty understanding and explaining all of this in a concise or clear way.”