For the first time ever, researchers have peered into the brains of people tripping out on LSD. The groundbreaking scans reveal the dramatic extent to which the psychedelic drug affects normal brain function, while pointing towards therapies for similar psychological disorders. In a new paper published in Proceedings of the National Academy of Sciences, a research team led by Robin Carhart-Harris from Imperial College London has demonstrated the sweeping ways in which LSD affects normal brain function -- accentuating the power of certain brain regions, while diminishing the function of others. In addition to assisting with consciousness studies, these fresh insights are poised to increase interest in the use of psychedelic drugs for therapeutic purposes and for disease modelling. It could also further inspire other researchers to study LSD and its effects on the human brain.
The LSD molecule. Lysergic acid diethylamide, more commonly known as LSD or acid, was first synthesised by Swiss scientist Albert Hofmann in 1938. Since that time, very little scientific work has been done to study this psychedelic drug and its effect on the brain. Research stalled during the late 1960s when the drug was criminalised in the US, but there has also been a strong social stigma associated with such a potent "hard drug".
Consequently, it's been difficult for researchers to get past regulatory hurdles and to convince ethical boards of the need to study the effects of LSD on the human brain. This taboo is beginning to wane, sparking a new era in neuroscientific research.
"People are starting to realise that it's not impossible to do this sort of research, it's just very difficult," explained Carhart-Harris to Gizmodo. "I think once a few people have done it, then they can tell others how to do it. It's simply a momentum effect."
The researchers recruited 20 volunteers. Carhart-Harris told Gizmodo that the recruitment phase was "the easiest part of the project" as volunteers jumped at the opportunity. All participants were healthy, and they all had prior experience with LSD, which was an important safety concern. Putting someone in a brain scanner -- which can be claustrophobic and noisy -- who has never done LSD before sounds like a recipe for disaster.
The researchers used several different imaging techniques, including fMRI and magnetoencephalography (MEG). Each participant was injected with either 75 micrograms of LSD (a standard "hit") or a placebo consisting of a saline solution (the control group). As the volunteers tripped out in the brain scanners with their eyes closed, the machines recorded the inner workings of their acid-addled brains. Afterwards, each participant rated their visual hallucinations and altered states of consciousness.
These brain scans were done back in 2014. Since that time, Carhart-Harris and his colleagues have been pouring over this unprecedented trove of data.
Primary visual cortex communication under placebo (top), LSD (2nd row) and difference (bottom row). Image: Imperial College London
The researchers were particularly struck by the way LSD affected the primary visual cortex, the part of the brain that helps us process our environment and helps us perform such basic tasks as identifying colour, seeing contrasts and lines, and helping with spatial orientation.
Ordinarily, most neural communication within the visual cortex is confined and restricted to this web-shaped network. But when a person is on LSD, this area expands its power and scope, producing vivid hallucinations. Users typically describe seeing such things as crawling geometric shapes, radiant colours and objects that appear to ripple or "breathe".
"Under the influence of LSD, the network within the visual cortex experiences a striking expansion of communication," said Carhart-Harris. "It becomes much less restricted and confined to the visual system, resulting in more of the brain contributing to visual processing and the visual experience."
Another major finding had to do with the phenomenon of ego dissolution, or what some LSD users refer to as "ego death". Most of us take it for granted that we have a constant and immutable sense of self. It provides us with purpose and drive, while allowing us to see ourselves as being distinct from others. But on acid, these associations are weakened; the normal sense of self is broken down. For some, this translates to feelings of universal connectedness, which is why some users describe their acid trips as being transcendent or religious-like.
"Psychedelics are a stark reminder that the sense of self that we have is kind of precarious," said Carhart-Harris. "Under LSD, consciousness is still intact -- but what's missing is this sense of self, a sense of having an ego."
The reason for this, he said, has to do with a particular network in the brain that's responsible for self-awareness, namely the parahippocampus and retrosplenial cortex. When on LSD, this network experiences decreased connectivity, resulting in a disintegrated sense of self. "The greater this effect, the greater our participants described the experience of ego dissolution," said Carhart-Harris. Once the effects of LSD subsided, the sense of self -- and normal brain function -- was restored.
So LSD does quite a number on the brain. Carhart-Harris said its sweeping effects has something to do with the way that LSD affects synaptic transmissions within the brain. LSD mimics serotonin (a neurotransmitter that influences mood), and it hijacks the serotonin system in some interesting ways. When the drug binds or sticks to one particular serotonin receptor (the serotonin 2A receptor to be exact), it changes the shape of the receptor, and that leads to a number of downstream effects, such as hallucinations and altered states of consciousness. The flexibility of consciousness is being modulated by LSD, which is done through the receptor.
"What this tells us is there is something special and something important about these serotonin 2A receptors and how they modulate consciousness," explained Carhart-Harris. It's not the quantity of consciousness that's being altered, he explained, but rather its quality.
People on LSD also experience emotional and behavioural shifts. When high on acid, some users tend to think in hyper-associative ways (that is, linking things or concepts that don't necessarily have a connection), they mix stimuli together and they become more open to influence. The transition from an ecstatic mood to utter panic can happen in a snap.
Carhart-Harris says many of these characteristics are reminiscent of psychological disorders. "This study tells us not just about what LSD does, but also the nature of normal brain function," he said. "You need these systems to be intact in order to have [the senses] we rely on."
Acid trips bear a striking resemblance to certain psychological disorders, including early stage psychosis, schizophrenia and depression. In all these cases, a certain inflexibility exists in the brain. Carhart-Harris hopes that certain drugs -- including psychedelics -- can be used to "reboot" the brain as a way to remove this inflexibility. But he admits this could take time; it's still very early days.
"Consciousness research is a relatively young science," he told Gizmodo. "In terms of psychedelic research, brain imaging of psychedelics is still pretty embryonic. So in order for us to really understand these findings, we need to slot it in a network of understanding, and we don't really have that network yet. We've got a treasure trove of data, and we've got the beginnings of an understanding of what all this means, but we're still really only scratching the surface."
Image showing the difference between primary visual cortex communication under placebo (left) and LSD (right). Image: R. Carhart-Harris/Imperial College London