Ask a healthy person who's tripped on psychedelics what it felt like, and they'll probably tell you they saw sounds or heard colors: The crash-bang of a dropped box took on an aggressive, dark shape. A bright green light seemed to emit a piercing, high-pitched screech.
In actuality, this "cross-wiring" — synaesthesia, as it's known scientifically — may be one example of the drug "freeing" the brain from its typical connection patterns. And this fundamental change in how the brain sends and receives information also might be the reason the drugs are so promising as a treatment for people with mental illnesses like depression, anxiety, or addiction.
"I'm absolutely sure that, within ten years, psilocybin will be an accepted treatment for depression," David Nutt, the director of the neuropsychopharmacology unit in the division of brain sciences at Imperial College London told me last month.
To understand why he might believe this so strongly, it helps to take a look first at how a healthy brain works — and then at how a psychedelic trip appears to modify the way a depressed brain does.
Normally, information is exchanged in the brain across various circuits, or what Paul Expert, who coauthored one of the first studies to map the activity in the human brain on psilocybin, described to me as "informational highways." On some highways, there's a steady stream of traffic. On others, however, there are rarely more than a few cars on the road. Psychedelics appear to drive traffic to these underused highways, opening up dozens of different routes and freeing up some space along the more heavily used ones.
Robin Carhart-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 last year in New York at a conference on the therapeutic potential of psychedelics. With psilocybin, "there was a definite sense of lubrication, of freedom, of the cogs being loosened and firing in all sorts of unexpected directions," Carhart-Harris said.
This might be just the kick-start that a depressed brain needs.
Here's a visualization that Expert created to show the brain connections in a person on psilocybin (shrooms) — the chart on the right — compared to the connections in the brain of someone not on the drug (left):
(Journal of the Royal Society Interface)
One key characteristic of depression is overly strengthened connections in brain circuits in certain regions of the brain — particularly those involved in concentration, mood, conscious thought, and the sense of self. This may be part of the reason that electroconvulsive therapy, which involves placing electrodes on the temples and delivering a small electrical current, can help some severely depressed people — it tamps down on some of this traffic.
"In the depressed brain, in the addicted brain, in the obsessed brain, it gets locked into a pattern of thinking or processing that's driven by the frontal, the control center, and they cannot un-depress themselves," Nutt told me.
Nutt is 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 to free someone with depression from those types of thoughts, traffic would need to be diverted from some of these congested ruts and, even better, redirected to emptier highways.
That's precisely what psychedelics appear to do.
"Psychedelics disrupt that process so people can escape," Nutt said. "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."
Last year, a team of Brazilian researchers published a review of all the clinical trials on psychedelics published between 1990 and 2015. After looking at 151 studies, the researchers found only six that met their analysis criteria. The rest were either too small, too poorly controlled, or problematic for another reason.
(Boxes containing magic mushrooms sit on a counter at a coffee and smart shop in Rotterdam November 28, 2008.)
Nevertheless, based on the six studies, the researchers concluded that ayahuasca, 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," they wrote.
Because the existing research is so limited, scientists still can't say exactly what is happening in the brain of someone who has tripped on psychedelics.
What we do know, though, is that things like practicing a musical instrument or learning a skill change the brain, and 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" in the way the brain processes information, said Expert.
And something about the experience appears to be much more powerful for some people than even years of taking antidepressants.
A small recent trial of psilocybin 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, co-directed by Amanda Feilding, who founded the Beckley Foundation, was designed to determine only if the drug was safe, all of the study participants said at a one-week follow-up that they saw a significant decrease in symptoms. The majority said at a follow-up three months later that they continued to see a decrease in symptoms.
"We treated people who'd been suffering for 30 years, and they're getting better with a single dose," said Nutt, who was one of the authors of the study. "So that tells us this drug is doing something profound."
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