The scientists hope their long-awaited study on LSD in humans will open the floodgates to further research into psychedelics.
Researcher, drug policy reformer, and Countess of Wemyss Amanda Feilding made a promise to Albert Hofmann, the "father of LSD," after meeting him in the 90s: She would carry out scientific research with his "problem child" on human subjects by his 100th birthday in 2006.
The study, published in PNAS, is the result of years of work conducted by researchers at Imperial College London and supported by the Beckley Foundation, which Feilding founded in 1998. It reveals some of the effects LSD (lysergic acid diethylamide) has on the brain, and offers insight into how psychedelic drugs could both shed light on the fundamental nature of consciousness and be used as a therapeutic tool to treat psychological disorders such as depression and addiction.
"It's a very proud day for us and for British science really; we are the first to do this and it's very much a dream come true," said lead investigator Robin Carhart-Harris as he introduced the findings alongside Feilding and research co-director David Nutt at an event at the Royal Society.
In this study, the researchers gave 20 volunteers an injection of 75 micrograms of LSD—an amount Carhart-Harris described as "a moderate dose"—and imaged their brain while they were under the influence using two types of fMRI and a MEG scan. They also asked them questions about their experience on the drug, allowing them to draw correlations between the subjects' reports and their observed brain activity. The participants underwent the same experience with a placebo of saline.
The volunteers all had some prior experience with psychedelics and were screened for mental and physical health to check they would tolerate being in the potentially anxiety-inducing position of having to lie still in an fMRI machine while on acid.
"[Psychedelics] are very powerful tools to understand this major problem of 'what is the nature of consciousness?'"
The researchers ended up with 15 clear datasets, the rest discarded due to movement-related noise, and what they found offers insight into the brain mechanisms behind two definitive aspects of the psychedelic experience: visual hallucinations and effects on consciousness, and particularly what's known as "ego dissolution" or a breakdown of the sense of self as it's usually understood.
Carhart-Harris highlighted the effects on consciousness as particularly interesting. "Really, I think this is why psychedelics in general, but also LSD, are special," he said. "They really alter consciousness in this very fundamental and unusual, novel way, and therefore they're very powerful tools to understand this major problem of 'what is the nature of consciousness?'"
The study revealed several interesting leads. In fMRI scans of subjects' brains on LSD, researchers found reduced communication between the parahippocampus and regions related to the sense of self such as the retrosplenial cortex. "There's a kind of dislocation, if you want, in this circuit, and a disintegration in the system which underlies these functions," explained Carhart-Harris. Most importantly, the magnitude of this observed pattern correlated with subjects' ratings of the ego-dissolution effect.
In their paper, the researchers compare their overview of results with studies on other psychedelics, such as psilocybin. "It seems increasingly evident that psychedelics reduce the stability and integrity of well-established brain networks and simultaneously reduce the degree of separateness or segregation between them; that is, they induce network disintegration and desegregation," they write. Carhart-Harris explained this as the brain being less "compartmentalized" and more "unified" under psychedelics, functioning in a "simpler" or "freer" way. In the paper, he and his coauthors characterizes this phenomenon as brain activity becoming more "entropic."
As for psychedelic visuals, the researchers observed an increase in blood flow in the visual cortex and increased communication between the visual cortex and other areas of the brain when on LSD. "We also saw that the magnitude of this effect correlated with our volunteers' ratings of complex visual imagery," Carhart-Harris said.
These findings may seem niche, but they add to a fundamental understanding of how the brain and consciousness works. By showing how LSD acts on the brain, they also bolster research into the therapeutic potential of psychedelic drugs, which has lately seen something of a revival. In their conclusion, the researchers speculate that the "entropic" effects observed under LSD could help to disrupt psychiatric disorders in which the brain has "become entrenched in pathology, such that core behaviors become automated and rigid."
Perhaps as remarkable as the study's results, however, is the fact that it was done at all. Since LSD became illegal in 1966, it's been very difficult to use the drug in scientific research. As a Schedule 1 drug in the UK, LSD is officially considered to have no therapeutic applications, which makes getting the required licences and ethics approvals to run trials with it particularly hard. (Fielding in particular is campaigning for it to be moved to Schedule 2.)
The taboo around research with illegal drugs can also put off research institutions and make it hard to get funding. It even makes getting hold of the drugs difficult—they need to be specially made to a sufficient standard for a scientific trial, which is a costly process with its own set of regulations. Indeed, this imaging study was partly funded through a crowdfunding campaign.
David Nutt, who is well-known for his criticism of UK drug policy, said the study was "easily the most significant thing I've ever done." He noted jovially that his much-publicised dismissal as a government drugs adviser in 2009 allowed him to help follow the vision of psychedelics research Feilding had previously presented.
"I will say to you that this, for human neuroscience, is the same as the discovery of the Higgs boson"
For her part, Feilding characterised the groundbreaking study as a "coming-of-age" of Hoffman's discovery. "But for the taboo surrounding this field, he would, surely, have won the Nobel Prize," she said.
She spoke of her own use of LSD after being introduced to it in the 60s, and her enduring aim "to re-integrate these valuable compounds into the fabric of society, and to make their benefits available where appropriate."
There are of course many unanswered questions remaining, and the researchers are working on other studies with psychedelics, the most imminent being a clinical trial looking at the effects of psilocybin (magic mushrooms) in depressed patients.
It's worth noting this was a small trial, and only involved participants who had previously used psychedelics, which could impact the results. Carhart-Harris also pointed out that it's difficult to measure things like ego dissolution, which is highly subjective.
However, the team hopes that publishing this study will help open the floodgates for further research. Having published their findings in a highly-regarded journal and presented them in the eminent surroundings of the Royal Society, they want to push the impression that psychedelics research is not a fringe interest but a mainstream concern.
"I think we've now achieved something that, hopefully, is transformational," said Nutt. "If you want to quote this, I will say to you that this, for human neuroscience, is the same as the discovery of the Higgs boson, because we have known for almost as long as we knew there was a Higgs boson that we needed to study the effects of LSD on the brain, but no one did it because the reputational risk was too oppressive."
"We've done it, we've discovered remarkable insights, and now there is no reason for others not to do it."