Scientists this week published a study that reveals what the human brain looks like under the influence of psilocybin, the hallucinogenic chemical found in magic mushrooms.


The study has turned a few heads, and raised some interesting questions. What does the human brain look like during a mushroom trip? Come to think of it, what sort of activity do scientists see in the brains of people after they smoke a joint, or once they've downed a few beers? Let's take a peek at what your brain really looks like on drugs — illicit and otherwise — and what scientists stand to learn from collecting this kind of information.

The results of the mushroom study were published in this week's Proceedings of the National Academy of Sciences, by neuropsychopharmacologist David Nutt and his team. The researchers recruited thirty people to participate in the investigation, all of whom were experienced with the use of hallucinogenic drugs. The study was designed to monitor the changes in brain activity that emerge during the transition from a normal, sober state of consciousness to one influenced by the effects of the psychedelic compound psilocybin. This was accomplished by recording subjects' brain, both before and after the intravenous administration of 2 milligrams of psilocybin (i.e. the psilocybin was injected directly into the subject's blood stream via a vein). Two mg of psilocybin delivered intravenously is comparable to 15mg delivered orally — what the researchers describe as "a moderate dose."


Your Brain on Shrooms

Shown here are the effects of psilocybin that the researchers observed. Regions labeled in blue indicate a decrease in brain activity. This activity was measured via two variations of a common neuroimaging method called functional magnetic resonance imaging (or fMRI for short), which works by monitoring blood flow in the brain. (It bears mentioning that while the rest of the images of brain activation in this post were also detected via fMRI, other neuroimaging techniques do exist, including CT scanning, magnetoencephalography, and positron emission tomography, to name a few.)

Many people have either had or heard of mind-bending experiences attributable to psilocybin — so if you or someone you know has experimented with mushrooms, the fact that the researchers' observations reflected a decrease in brain activity during a trip will probably strike you as odd. What's going on here, man?


"Psychedelics are thought of as ‘mind-expanding' drugs, so it has commonly been assumed that they work by increasing brain activity," explained Nutt in an interview with Nature's Mo Costandi. "Surprisingly, we found that psilocybin actually caused activity to decrease in areas that have the densest connections with other areas."

Did you catch that? The most important thing to take away from this study isn't the fact that brain activity decreased, it's where the activity decreased. The greatest dips in activity were observed in regions of the brain known as the medial prefrontal cortex (mPFC) and the anterior and posterior cingulate cortices (ACC and PCC, respectively). And as if that wasn't enough, the researchers' findings also suggest that psilocybin takes its disabling effects one step further by disrupting connections between the mPFC and PCC.


You can think of your mPFC, PCC, and a third region of your brain called the thalamus, as transportation hubs that coordinate the flow of information throughout your brain. Decreased activity within and between the brain's hubs, conclude Nutt and his colleagues, allows for "an unconstrained style of cognition."


What the hell does that mean? Costandi fleshes things out for us, with a little help from Aldous Huxley [Photo via]:

In his 1954 book The Doors of Perception, novelist Aldous Huxley, who famously experimented with psychedelics, suggested that the drugs produce a sensory deluge by opening a "reducing valve" in the brain that normally acts to limit our perceptions. The new findings are consistent with this idea, and with the free-energy principle of brain function developed by Karl Friston of University College London that states that the brain works by constraining our perceptual experiences so that its predictions of the world are as accurate as possible.


The observations by Nutt and his colleagues come together quite nicely with a model of "unconstrained cognition." There is, however, one small snag: the team's findings directly contradict those observed in previous studies.

"We have completed a number of similar studies," explains Franz Vollenweider, a neuropsychopharmacologist at the University of Zurich in Switzerland, "and we always saw an activation of these same areas" [emphasis added].


So why don't the researchers' findings match up? The short answer is: don't know; needs more research. But that doesn't mean we can't hypothesize. For example, in Vollenweider's study, test subjects were administered psilocybin orally, and their brains were imaged an hour later. In Nutt's study, however, the psychedelic compound was administered intravenously, and the brain scans were performed immediately.

According to Keith Laws, a neuropsychologist at the University of Hertfordshire, previous studies have shown that the decreases in brain activity observed by Nutt and his colleagues are also linked to the anticipation of unpleasant experiences. Being dosed with psilocybin intravenously, muses Laws, was probably a pretty stressful experience, even for experienced drug users. "I suspect," Laws explains, "that [Nutt and his colleagues] measured something to do with anxiety."


Your Brain on Booze

The human brain is a tangled mess of somewhere between 80 and 120-billion neurons, and these neurons are continuously creating and breaking trillions of connections with one another. What the incongruous results of Nutt and Vollenweider call attention to is the fact that neuroimaging studies have to approach the complexity of the brain from as many angles as possible. More specifically, it reveals that the answer to the question "what does my brain look like when I smoke/snort/shoot/drink/eat _________" cannot be answered by any one study.


Think about all the factors you'd have to consider when conducting such an investigation; it would be impossible to incorporate them all. We've already mentioned one (the potentially disparate effects of intravenous versus oral administration of a drug) but there are many, many more.


For example, after you've decided how to dose your patient, you must decide whether you want them to perform a task, or just sit there while you observe their brain activity. This image, for instance, is taken from a study — published in Neuropsychopharmacology in 2005 — that examined the brain activity of drunk test participants who were subjected to a realistic, simulated driving challenge.

This figure is brimming with information (those interested can click through to familiarize themselves with the nitty-gritty details), but here's the gist: Various regions of the brain scans in the figure are labeled with different colors. These colors correspond to activity observed at specific points of interest within the brain. We're interested in the ones labeled in pink and red. These hues correspond to the orbitofrontal and motor regions of the brain, respectively. The former is involved in decision-making, the latter in the planning, control, and execution of voluntary motor functions.


When the researchers upped the blood alcohol level of their test subjects — first from 0.0% to 0.04%, and later from 0.04% to 0.08% — it was within these two brain circuits that they observed the greatest disruption in activation. Translation: these cerebellar snapshots help reveal why, on a neurophysiological level, drinking nerfs your motor skills and decision making in a simulated (and, presumably, real-life) driving situation.


Your Brain on Weed

Other researchers examine what the human brain looks like not while under the influence, but following years of long-term exposure to drugs. These images, for example, are from a 2005 study that compared the brain activity of 24 chronic marijuana users with that of 19 non-smokers during a series of visual attention tasks. [Click here for the full figure with description]


In the alcohol study mentioned above, test subjects were put behind the wheel of a simulated car; in this study, participants were asked to to mentally track the movement of a ball on a screen as it drifted about, intermingling with other randomly moving balls — sort of like a computerized version of cups and balls, only without any deliberate attempts at misdirection.

The areas labeled in red correspond to regions of the brain that were less active in the chronic marijuana users than in non-drug users during the motion-tracking task. Interestingly, the majority of these areas correspond to parts of the brain associated with what is called the "visual-attention network," which, as its name implies, is involved in various attention-requiring tasks.


Could the attention and memory deficits that are commonly reported in heavy marijuana users be related to this decreased activation? Potentially — but it's more complicated than that. See the areas labeled in blue and green? Those are regions outside the brain's normal attention network where activity was actually higher in pot smokers than in non-drug users. According to the researchers, these altered patterns of brain activation "suggest neuroadaptation in the attention network due to chronic marijuana exposure." In other words, they show that heavy pot-smoking is actually associated with a reorganization in the way your brain handles tasks demanding of your attention.

But again: snapshots like these can only tell you so much. In order to flesh out the innermost workings of the human mind, more experiments examining different angles must be performed. What might the authors of the marijuana study have observed, for example, had they actually gotten their chronic marijuana-smokers high prior to the ball-tracking test? Would these results vary depending on whether they administered THC (the principle psychoactive ingredient in marijuana) intravenously or via inhalation? What would happen inside the brain of a person who had never smoked pot before?


The attention to detail required by this kind of research may lead some people to question why anybody would attempt to make sense of this stuff in the first place, to which I reply: Are you kidding? Why wouldn't' you want to know this stuff? Unlocking how substances affect the human brain is one step removed from understanding how we experience everything that surrounds us. That drive — to understand how we perceive the world — is so fundamental to our being it predates the modern conception of science itself.


Brain imaging studies are the kind of research that will help make an alcohol surrogate — like Synthehol in Star Trek — a reality (which, by the way, is something that scientists are seriously looking into; in fact, Nutt — the lead author of the psilocybin study we talked about earlier — has published research on it). It's also the kind of research that can aid in the development of therapies capable of treating disorders ranging from depression to addiction.

Take cigarette addiction, for example. Nicotine-dependence is the most common substance abuse disorder in the United States. Why? Because that shit is habit-forming.


Your Brain on Cigarettes

People who smoke consistently report that cigarettes enhance their mood, attention, working memory, and motivation (to name just a handful of the cognitive states augmented by nicotine), and that abstaining from or withdrawing from cigarettes completely compromises said states. Scientists have long recognized that regions of your brain known as the frontal lobe and the cingulate cortex are involved in cognitive processes related to the same cognitive effects enhanced by smoking (mood, attention, motivation, and so on). It stands to reason that the better scientists understand the interplay between nicotine, the frontal lobe, the cingular cortex, and other areas of the brain, the better they'll understand the mechanisms of addiction and how to overcome it.


Check out this figure — it's from the first study to examine regional patterns of brain activity following exposure to nicotine using fMRI.


Regions in red and yellow depict regions of activity. This data was the first to visualize the regions of the brain acted upon by nicotine-administration in humans, and supported the hypothesis that activation of the frontal and cingulate regions of the brain is responsible for cigarettes' behavioral and mood-altering qualities.

Over a decade after this study was published, the first author — researcher Elliott Stein — used neuroimaging to show that nicotinic action and nicotine addiction are actually associated with entirely separate pathways in the brain, revealing yet again not only the complex nature of the human mind, but how brain-imaging studies — especially when combined with behavioral, molecular, and genetic investigations — can improve our understanding of how it operates.


Additional Resources


Top image via; all other images via their respective publications, unless otherwise indicated