The researchers believe they are on the cusp of nothing less than a breakthrough: A single dose of psychedelic drugs appears to alleviate the symptoms of some of the most common illnesses of the brain. With depression the leading cause of disability worldwide, the timing seems ideal.
In people like Walcoff, whose depression and anxiety struck them like a powerful blow following a cancer diagnosis, one dose of psilocybin seemed to quiet her existential dread, to remind her of her connectedness with the world around her, and perhaps most importantly, to reassure her of her place in it.
And these results don’t seem to be limited to people with cancer or another life-threatening illness. Participants in a handful of other psychedelic studies consistently ranked their trip as one of their most meaningful experiences of life — not only because of the trip itself, but because of the changes they appear to produce in their lives in the months and years afterward.
Still, the existing research is limited — which is why, scientists say, they so badly need permission from the government to do more.
1990 was a year of life and death for Clark Martin. It was the year his daughter was born and the year he was diagnosed with cancer.
Over the next twenty years, as his daughter took her first steps, experienced her first day of school, and eventually began growing into a smart, fiercely independent teenager, doctors waged a blitzkrieg on Martin’s body. Six surgeries. Two experimental treatments. Thousands of doctor’s visits. The cancer never went into remission, but Martin and his doctors managed to keep it in check by staying vigilant, always catching the disease just as it was on the brink of spreading.
Still, the cancer took its toll. Martin was riddled with anxiety and depression. He’d become so focused on saving his body from the cancer that he hadn’t made time for the people and things in his life that really mattered. His relationships were in shambles; he and his daughter barely spoke.
So in 2010, after reading an article in a magazine about a medical trial that involved giving people with cancer and anxiety the drug psilocybin, he contacted the people running the experiment and asked to be enrolled.
After weeks of lengthy questionnaires and interviews, he was selected. On a chilly December morning, Martin walked into the facility at Johns Hopkins, where he was greeted by two researchers including Johns Hopkins psychologist Bill Richards. The three of them sat and talked in the room for half an hour, going over the details of the study and what might happen.
Martin then received a pill and swallowed it with a glass of water. For study purposes, he couldn’t know whether it was a placebo or psilocybin, the drug the researchers aimed to study.
Next, he lay back on the couch, covered his eyes with the soft shades he’d been given, and waited.
Within a few minutes, Martin began to feel a sense of intense panic.
“It was quite anxiety provoking. I tried to relax and meditate but that seemed to make it worse and I just wanted everything to snap back into place. There was no sense of time and I realized the drug was in me and there was no stopping it.”
Martin, an avid sailor, told me it reminded him of a frightening experience he’d had once when, after being knocked off his boat by a wave, he’d become suddenly disoriented and lost track of the boat, which was floating behind him.
“It was like falling off the boat in the open ocean, looking back, and the boat is gone. And then the water disappears. Then you disappear.”
Martin was terrified, and felt on the verge of a “full-blown panic attack.” Thanks to the comfort and guidance of his doctors, however, he was eventually able to calm down. Over the next few hours, the terror vanished. It was replaced with a sense of tranquility that Martin still has trouble putting into words.
“With the psilocybin you get an appreciation — it’s out of time — of well-being, of simply being alive and a witness to life and to everything and to the mystery itself,” said Martin.
Lots of things happened to Martin over the course of his four-hour trip. For a few hours, he remembers feeling a sense of ease; he was simultaneously comfortable, curious, and alert. At one point, he recalls a vision of being in a sort of cathedral where he asked God to speak to him. More than anything else, though, he no longer felt alone.
“The whole ‘you’ thing just kinda drops out into a more timeless, more formless presence,” Martin said.
Over the next few hours, as his trip slowly began to draw to a close and he began to return to reality, Martin recalls a moment where the two worlds — the one in which he was hallucinating and the reality he could call up willingly from memory — seemed to merge. He turned his attention to his relationships. He thought of his daughter. His friends. His co-workers.
“In my relationships I had always approached it from a, ‘How do I manage this?’, How do I present myself?,’ ‘Am I a good listener?’, type of standpoint. But it dawned on me as I was coming out of [the trip] that relationships are pretty much spontaneous if you’re just present and connecting,” said Martin.
That shift, which Martin stresses has continued to deepen since he took the psilocybin in 2010, has had enduring implications for his relationships.
“Now if I’m meeting people, the default is to be just present, not just physically, but mentally present to the conversation. That switch has been profound.”
While he felt himself undergo a shift during his 4-hour trip on psilocybin, Martin says the most enduring changes in his personality and his approach to those around him have continued to unfold in the months and years after he took the drug. For him, the drug was merely a catalyst; a “kick-start,” he likes to call it. By temporarily redirecting his perspective within the span of few hours, Martin believes it unleashed a chain reaction in the way he sees and approaches the world.
This squares with what researchers have found by looking at the brain on psilocybin.
Ask a healthy person who’s “tripped” on psychedelics what it felt like, and they’ll probably tell you they saw sounds.
The crash-bang of a dropped box took on an aggressive, dark shape. Or they might say they heard colors. A bright green light seems to emit a piercing, high-pitched screech.
In actuality, this “cross-wiring” — or synaesthesia, as it’s known scientifically — may be one example of the drug “freeing” the brain from its typical connection patterns.
This fundamental change in how the brain sends and receives information also might be the reason they’re so promising as a treatment for people with mental illnesses like depression, anxiety, or addiction. In order to understand why, it helps to take a look at how a healthy brain works.
Normally, information gets exchanged in the brain using various circuits, or what one researcher described to me as “informational highways.” On some highways, there’s a steady stream of traffic. On others, however, there’s rarely more than a few cars on the road. Psychedelics appear to drive traffic to these unused avenues, opening up dozens of different routes to new traffic and freeing up some space along the more heavily-used ones.
Dr Robin Cahart Harris who leads the psychedelic research arm of the Center for Neuropsychopharmacology at Imperial College London, captured these changes in one of the first neuroimaging studies of the brain on a psychedelic trip. He presented his findings at a conference on the therapeutic potential of psychedelics in New York City last year. “[With the psilocybin] there was a definite sense of lubrication, of freedom, of the cogs being loosened and firing in all sorts of unexpected directions,” said Cahart-Harris.
This might be just the kick-start that a depressed brain needs.
Nutt has been one of the pioneering researchers in the field of studying how psychedelics might be used to treat mental illness. He said that in depressed people, these overly-trafficked circuits (think West Los Angeles at rush-hour) can lead to persistent negative thoughts. Feelings of self-criticism can get obsessive and overwhelming. So in order to free someone with depression from those types of thoughts, one would need to divert traffic from some of these congested ruts and, even better, redirect it to emptier highways.
Which is precisely what psychedelics appear to do.
“Psychedelics disrupt that process so people can escape. At least for the duration of the trip they can escape about the ruminations about depression or alcohol or obsessions. And then they do not necessarily go back,” said Nutt.
A 4-hour trip, a long-lasting change
“Medically what you’re doing [with psychedelics is] you’re perturbing the system,” Paul Expert, who co-authored one of the first studies to map the activity in the human brain on psilocybin, told me over tea on a recent afternoon in London’s bustling Whitechapel neighborhood.
Expert, a physicist at the King’s College London Center for Neuroimaging Sciences, doesn’t exactly have the background you’d expect from someone studying magic mushrooms.
But it was by drawing on his background as a physicist, Expert told me, that he and his team were able to come up with a systematic diagram of what the brain looks like on a psilocybin trip. Their study, published in 2014, also helps explain how altering the brain temporarily with psilocybin can produce changes that appear to continue to develop over time.
When you alter how the brain functions (or “perturb the system,” in physicist parlance) with psychedelics, “that might reinforce some connections that already exist, or they might be more stimulated,” Expert told me.
But those changes aren’t as temporary as one might expect for a 4-hour shroom trip. Instead, they appear to catalyze dozens of other changes that deepen in the for months and years after taking the drug.
“So people who take magic mushrooms report for a long time after the actual experience that they feel better, they’re happier with life,” said Expert. “But understanding exactly why this is the case is quite tricky, because the actual trip is very short, and it’s not within that short span of time that you could actually have sort of new connections that are made. That takes much more time.”
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The clinical trials that Walcoff and Martin took part in, which took place at NYU and Johns Hopkins over the course of five years, are the longest and most comprehensive studies of people with depression on psychedelics that we have to-date. Last year, a team of Brazilian researchers published a review on clinical trials of psychedelics between 1990and 2016. After looking at 151 studies, the researchers were only able to find six which met their analysis criteria. The rest were either too small, too poorly-controlled, or problematic for another reason. Nevertheless, based on the six studies they were able to review, the researchers concluded that ayahasca psilocybin, and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents.”
Because the existing research is so limited, scientists still can’t say exactly what is happening in the brain of someone who’s tripped on psychedelics that appears to unleash such a cascade of life changes like the kind Martin described.
What we do know, though, is that things like training for a musical instrument or learning a skill change the brain. It’s possible that psychedelics do something similar over the long-term, even if the actual trip — the phase of drug use that many people focus on — is pretty brief.
In other words, a trip “might trigger a sort of snowball effect,” said Expert, in the way the brain processes information.
And something about the experience appears to be much more powerful, for some people, than even years of antidepressants. A small recent trial of psilocybin that Nutt co-authored in people whose chronic depression had not responded to repeated attempts at treatment with medication suggested that this may be the case. While the trial was only designed to determine if the drug was safe, all of the study participants saw a significant decrease in symptoms at a one-week follow-up; the majority said they continued to see a decrease in symptoms at another follow-up done three months later.
“We treated people who’d been suffering for 30 years. And they’re getting better with a single dose,” said Nutt. “So that tells us this drug is doing something profound.”