Brain Network Connectivity - Placebo and Psilocybin

The Science of Psychedelics and Exceptional Human Experience

“I don’t take reality for granted.”

Weird stuff happens. People really do experience telepathy, alien abduction and pre-cognition.

In the UK, we usually push such stories to one side and either forget about them, or (worse) medicate them. David Luke, Senior Lecturer for Psychology at the University of Greenwich tries to understand them.

I’m in the back room at Cafe 1001, in the heart of hipsterville on Brick Lane in London. It’s crammed with mostly young professionals and students, but there are pockets of older people.

Many have experience of psychedelics – my white-haired neighbour generously shared his story of being injected with the venom of a psychedelic toad in Mexico – but many don’t, here to add substance to their friends’ Gap Year stories of Peruvian shamen.

What This Is / What This Is Not

I’m going to use David Luke’s talk as a jumping off point to introduce you to the fascinating scientific renaissance in psychedelic research. By doing this, I’m actually limiting us to only the first half of his talk.

If you want to hear more about his investigative psychology into exceptional human experience – including how he managed to use mescaline to stimulate pre-cognition of future events (whaaaaat?!) – then I sincerely urge you to hunt down one of his highly stimulating and entertaining lectures. Or buy his book, Otherworlds: Psychedelics and Exceptional Human Experience.

On with the programme…

What Are Psychedelics?

Psychedelics are the most direct way we have of altering our state of consciousness and having moments of exceptional human experience.

“LSD is like a helicopter ride to the top of the mountain.”
– Alan Watts (apparently)

Psychedelics compounds used to be neatly divided into two categories: tryptamines that act on our serotonin receptors and phenethylamines that act on our dopamine receptors.

Tryptamines Phenethylamines
LSD Mescaline
Mushrooms (psilocybin) MDMA

Then Salvia was discovered. Salvia isn’t even an alkaloid – it’s a structurally unique diterpenoid. How many more psychoactive structures and compounds are to be discovered, explored – and legislated against!

Sasha Shulgin, “the godfather of psychedelics”, proposed that the number of known psychedelic substances would increase by a factor of 10 every 50 years. He was bang on.

In 1900, Western medicine knew of just 2 psychedelics, rising to 20 in 1950 and 200 in the year 2000. According to David Luke’s research, in 2012 there were 350 psychedelic drugs known to science (many of them created by Shulgin himself, a self-fulfilling prophet).

The 1971 UN Convention on Psychotropic Substances might have stopped almost all legitimate scientific research for 40 years, but discoveries and use have continued unabated.

What Happens During a Psychedelic Trip?

Remarkable developments in neuroscience since 1971 mean that clever people can now see what happens in the brain during a psychedelic trip.

This has led to two major discoveries: one exactly as you’d expect and one a complete surprise, to layman and expert alike.

Brain network connectivity under a placebo (left) and psilocybin (right). From Petri et al. (2014). Far out.

When you take a psychedelic, crazy things happen. You’d expect the brain to be making many more disparate connections than in daily life. Exactly as you can see in the image above.

What you might not expect is that the brain, while tripping, is less active than normal.

Contrary to popular (and until recently scientific) belief, the psychedelic imagery of an acid trip is not stimulated by the drug. Rather, it seems that Aldous Huxley was accurate in describing the mind as a “reducing valve” of reality.

Psychedelics reduce activity in parts of the brain that make up something called the Default Mode Network. This network has been likened to our sense of ego or “self”.

By reducing brain activity in the Default Mode Network, psychedelics allow “reality” to flow unchecked, and without engaging the filters and biases of our ego.

There would seem to be a contradiction between these two neurological discoveries: that psychedelics encourage more disparate connections, while simultaneously making the brain less active. But there is no contradiction.

David Luke asks us to imagine London rush hour traffic. The city’s network of roads are both very active and the flow of cars highly congested. Now imagine you asked half of the commuters to stay in bed that morning, and sent the other half to far flung places – Bognor Regis, St Agnes, Kirkstall.

That’s your brain on acid: less active, but making more disparate connections.

The Dangers of Psychedelics (Or: What Rarely or Never Happens on a Psychedlic Trip)

Hopefully one day scientists talking about psychedelics won’t have to waste time telling us that LSD and mushrooms are non-toxic, non-psychotic and non-addictive. But we are not yet at that day.

Bad Trips

According to the 2014 LSD, Psilocybin, and DMT User Survey, more than 50% of recreational users of both LSD and psilocybin had never had a “bad trip”. Only 10-15% of users had bad trips a quarter of the time or more often.

Important Side Note: The research did not take into account the user’s set (their state of mind) and setting (their surroundings) when they took the drug. Set and setting make up the context for your psychedelic experience and are critical in determining how your trip will unfold. Many people take psychedelics in contexts that they can’t control and with strangers, at an acid rave for example. Not always a great idea.

By contrast, around 85% of LSD and psilocybin users reported “personally meaningful, mystical and/or spiritual insights” at least a quarter of the time they tripped. More than 50% reported these experiences at least three quarters of the time.

The figures for DMT, smoked, vaporised or orally consumed, were skewed even further in the direction of “successful” trips.

I think this is an important starting point when considering the dangers of psychedelics. Most people, most of the time have profoundly positive experiences.

Nevertheless, bad things do happen.


“What do you do for recreation?”
“Oh, the usual. Bowl. Drive around. The occasional acid flashback.”
The Big Lebowski (Coen Brothers 1998)

Hallucinogen Persisting Perception Disorder – AKA flashbacks – are a thing. David Luke is currently working with three such cases (one of whom was in the audience at Cafe 1001), but he describes the phenomenon as rare. He has only come across these three cases in his entire academic career.

David Luke also suggests that people who experience these unnerving persistent hallucinations can still learn to live a normal life with them. Indeed, in response to an audience question about mental health, he argues that, in other cultures, “sufferers” of HPPD might be accommodated and their visionary power valued.

Mental Health Problems

Using a data set of over 130,000 randomly selected US adults, including almost 20,000 psychedelic users, Pål-Ørjan Johansen and Teri Suzanne Krebs found no connection between lifetime psychedelic use and increased likelihood of mental health problems.

In fact, their results show that psychedelic drugs use is associated with a reduced likelihood of having been a mental health inpatient, or planning or attempting suicide in the past year.

The association between psychedelic use and mental health. From Johansen & Krebs (2005). There isn’t one.


The lethal dose of LSD in humans has never been found. Extrapolating from experiments with rats, it would be approximately equivalent to taking 10,000 trips all at once.

Even then, David Luke tells an anecdote of a drug smuggler who accidentally took his entire supply during a transatlantic flight – and survived. Meanwhile, you can buy a lethal dose of paracetamol (10-15g) in your local Tesco.

Other Bad Stuff

In 2010, David Nutt, former UK government drugs advisor, published a study that attempted to measure the relative harm of a whole array of drugs, from legal alcohol and tobacco to highly illegal LSD and magic mushrooms.

David Nutt and his team at the Independent Scientific Committee on Drugs looked at mortality, health damage, dependence, mental impairment, injury and a whole host of other personal and social adversities, inclucing crime, environmental damage, loss of relationships and economic cost.

I recommend reading the original study, but this graph gives you an idea of how misplaced our fears and energies are with regard to drug use.

Drugs ordered by their overall harm scores – the taller the column, the greater the harm. Blue is harm to the user; red is harm to others. From Nutt et al. (2010). Yes that’s alcohol on the far left and mushrooms on the far right.

Psychedelics like LSD and mushrooms are the least harmful recreational drugs we have in the UK, roughly 4 times less harmful than tobacco and 10 times less harmful than alcohol.

Therapeutic Uses of Psychedelics

The popular myth that psychedelic drug use will only “blow your mind” is unfortunately supported by the classification of LSD and others as Schedule 1 substances: those with high risk of addiction and no known therapeutic use.

In truth, as well as being highly unlikely to foster dependence, psychedelics are potentially of great therapeutic use.

Promising clinical trials suggest that they may be significantly more effective than other pharmaceuticals at tackling severe depression, addiction and anxiety in a variety of different contexts.

Here’s an incomplete list of recent studies using psychedelics in a therapeutic context. A great summary and bibliography of these studies (aside from the autism study, linked separately below) is found in Nichols, Johnson and Nichols Psychedelics as Medicines: An Emerging New Paradigm (2016).



Sample Study

Addiction: alcohol


Krebs & Johansen (2012)

Addiction: alcohol


Krupitsky & Grinenko (1997)

Addiction: alcohol


Bogenschutz et al. (2015)

Addiction: general


Fabregas et al. (2010)

Addiction: tobacco


Johnson et al. (2014), Garcia-Romeu et al. (2014)

Anxiety, social: autism


Danforth et al. (2015)

Anxiety: advanced stage cancer


Grob et al. (2010)

Depression, recurrent


Osorio et al. (2015)

Depression, treatment resistant


Carhart-Harris et al. (2016)

Obsessive Compulsive Disorder


Moreno et al. (2006)

Post-Traumatic Stress Disorder


Mithoefer (2013)

David Luke is quick to point out the irony of psychiatrists beginning to use prohibited Schedule 1 psychedelics to cure people of addiction to legal and lethal drugs like alcohol and tobacco. That is the very odd world we live in.

Side Note: There is also a growing literature around the potential therapeutic use of psychedelics for inflammatory diseases. These are a major component in leading causes of death, disability and reduced quality of life – coronary heart disease, diabetes, Alzheimer’s, Parkinson’s, arthritis and asthma to name but half a dozen. See Nichols et al. for more on this new avenue of exploration.

Psychedelic Citizen Science

David Luke repeatedly stresses that more research needs to be done on psychedelic use. This is an important point and deserves its own paragraph:

More research needs to be done on psychedelic use.

Having said that, thanks to the curse of government prohibition and the blessing of the internet, more and more power and legitimacy is in the hands of citizen scientists.

Psychedelic drugs are natural and widely available. They even grow in our fields. You can buy growing kits for psilocybe mushrooms, download field guides, or join picking meetups all over the country.

You can order psychedelic truffles from pefectly legal head shops in Amsterdam (delivery isn’t legal), or go to the “Dark Net” for anonymised transactions for a bewildering array of drugs bought with digital, untraceable Bitcoin. (Here’s a step-by-step guide to the darknet from the Psychedelic Society.)

You can download thousands of open access academic papers from top psychologists and neuroscientists, attend conferences and talks (like this one), or join forums with thousands of other psychonauts, pooling decades of experience.

You can even join more formal citizen science studies like Jim Fadiman’s microdosing experiment.

Knowledge is out there.

The Future of Psychedelic Regulation

David Luke stresses the need for us to make “some good choices” with regard to future psychedelic regulation. I’m optimistic.

No matter what the law says, legal enforcement is the responsibility of the police and your local police commissioner decides the policing priorities for your region.

Recognising studies like David Nutt’s on the relative harm of drug use, both Durham and Bristol and Avon police forces have deprioritised first time and possession drug offences. We could yet reach de facto decriminalisation.

What we need is more research. At the moment, psychdelic research is funded in the main by philanthropy. Sometimes, remarkably, through crowdfunding.

Pharmaceutical companies are not interested in funding psychedelic research because  the “one hit and you’re fixed” results aren’t profitable. The current UK government aren’t interested in funding research either because that’d really pee off their Daily Mail fanbase.

But keeping government and big pharma out of the research could be a great thing. Independently funded scientists can do independent work that is focussed on the good of the general population, not of governments or pharmaceutical companies.

A Final Word

David Luke stays behind long after his talk, answering questions, sharing insights and generally being a good person. I suppose this is what draws me to the subject. Without having a monopoly on such traits, I am yet to meet a psychonaut who isn’t really nice.

I was invited to this talk as the guest of Funzing, an online hosting platform for an eclectic variety of events in London. Basically what would happen if Uber did disco yoga, offender profiling or hummus workshops. So thanks to them.

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David Charles is co-writer of BBC radio sitcom Foiled. He also writes for The Bike Project, Thighs of Steel, and the Elevate Festival. He blogs at

4 thoughts on “The Science of Psychedelics and Exceptional Human Experience”

  1. Lot’s of interesting stuff here. But, and I say this as someone who did his share of psychedelics and have no bone to pick with drugs, I have to cast a critical eye on some of these statistics. For example…

    “Using a data set of over 130,000 randomly selected US adults, including almost 20,000 psychedelic users, Pål-Ørjan Johansen and Teri Suzanne Krebs found no connection between lifetime psychedelic use and increased likelihood of mental health problems.”

    I’m curious what “lifetime psychedelic use” means. If a person does psychedelics for 5 years, then has a freak out, ends up in the psyche ward and swears off drugs, would that remove them from the “lifetime user” category? My point being that the category sort of self edits itself to weed out people who might have mental heath problems. (Since few people would develop problems and keep using psychedelics.)

    Regard the David Nutt study, it seems reasonable that it’s basically correct. But I’m curious about how he factored all this stuff together. Illegal drugs are made illegal because they are presumed to cause harm. Thus it shouldn’t be surprising that they do less overall harm than legal drugs. The real question would be how much harm would they do if they were legal. (My suspicion is that the answer in regards to psychedelics would be, “not much.” That may not be the case with cocaine etc.)

    Additionally, how does one really compare one drug to another? You can’t say, “5 ounces of cocaine does more damage than an a 5 ounce glass of wine” because that doesn’t really reflect how much people use. (If I recall correctly from my drugging days, 5 ounces of coke is pretty much a heart attack. 😉 )

    It’s possible Nutt accounts for this somehow but I’d need more details to put my faith in these statistics.

    Anyway, very interesting blog. I was just reading some of Huxley’s writing on mescaline the other day. That reducing valve comment caught my eye.

    1. What a great comment – thanks! You’re quite right to have a critical eye on these statistics. There is a lot of dodgy science out there!

      Going back to the original Johansen and Krebs study, I can see that I have made a mistake, or at least aided a misunderstanding. The authors use “lifetime use” to mean any lifetime use. Both you and I assumed that it meant long-term use, but that is not the case.

      Their data analysis looked at mental health outcomes for people who have:

      • ever used any psychedelic
      • ever used a specific psychedelic: LSD, psilocybin, mescaline, peyote
      • used LSD in the past year

      The results were significant in eleven areas. People who had ever used any psychedelic were less likely to have been mental health inpatients in the past year (p=0.01). This is true across the board for any lifetime use of LSD, psilocybin, mescaline, peyote and also past year use of LSD.

      The remaining six significant results were that any psilocybin use is associated with lower likelihood of serious psychological distress in the past year (p=0.007), prescription of psychiatric medication (p=0.0004) and diagnosis of depression (p=0.002).

      Mescaline/Peyote is associated with greater symptoms of a major depressive episode (p=0.02), but not associated with diagnosis of depression (p=0.59).

      Finally, past year use of LSD is associated with reduced likelihood of serious psychological distress in the past year (p=0.04) and outpatient (p=0.01) mental health treatment in the past year.

      Thank you for asking this question and making me go back to the original data – it is much more conclusive than I remembered! The full reference is: Johansen, Pal-Ørjan, and Teri Suzanne Krebs. “Psychedelics Not Linked to Mental Health Problems or Suicidal Behavior: A Population Study.” Journal of Psychopharmacology 29, no. 3 (2015): 270–279.

      Moving on to your comments about David Nutt’s study, again you’re right to be critical. I’d really recommend you read the original study if you’re interested. Judging relative harm is an inexact science, as you point out, and it is fascinating how it was put together. A combination of clever statistical modelling, scientific and social evidence and expert judgement.

      Of course, certain drugs if made illegal might increase harm – think prohibition in the US – and perhaps certain drugs if made legal would reduce overall harm. Both tobacco and to a much lesser extent alcohol seem to be declining in use and becoming less socially acceptable (if not illegal), so perhaps in ten years, David Nutt’s graph will look very different.

      Nutt, David J., Leslie A. King, Lawrence D. Phillips, and others. “Drug Harms in the UK: A Multicriteria Decision Analysis.” The Lancet 376, no. 9752 (2010): 1558–1565.

      Anyway, thanks for your thoughtful comment and I hope that answers some of your questions.


      1. Ah, so that’s what lifetime use is – interesting…

        To some degree, I suspect a drug’s “ease of use” ties in with its potential for damage. For instance, you can easily drink a couple drinks a night for decades, or smoke dozens of cigarettes a day without really disrupting your life. But most psychedelics simply are so disruptive that you can’t “make a habit” of them (unless you’re independently wealthy and don’t have to work.)

        That said, I do think there’s something additionally addictive about tobacco/alcohol/cocaine etc. vs. psychedelics.

        1. You’re absolutely right. There also don’t seem to be any cravings associated with psychedelics, whereas I quite often hear friends announce they really wanna get wrecked. Not that they’re addicted to alcohol, but that craving is there. Even when people take microscopic amounts of a psychedelic (i.e. microdosing) on a regular basis, it is very easy to cycle off the drug. Indeed it’s easy to forget to take it even when you intend to! I don’t think any alcoholic or smoker ever forgets their first drink or smoke of the day.

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