LSD: when the bottom of the brain “turns the top of the brain into a great big TV screen”

In this series 'Psychedelics and Mental Health' The Lovepost interviews experts in psilocybin, LSD (lysergic acid diethylamide), Ayahuasca and cannabis, to explore the resurgence of psychedelics in research. We consider how they have been used across the ages to treat mental health conditions, address trauma, enhance people’s enjoyment of life, and their connection to Self and nature. We discuss the impact the 'war on drugs' had on psychedelic research, usage and public perception while also paying particular attention to its racial and political motivations. As the world wakes up to the potential of hallucinogens, we consider a future where these drugs are better understood and positively integrated into mental health care.

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Dr Michael Winkelman a scholar that works around shamanism, medical anthropology and psychedelic medicine.

Dr Michael Winkelman is an accomplished scholar whose work spans a broad range of topics including shamanism, medical anthropology and psychedelic medicine. His research has made significant contributions to the growing body of literature which explores the effects of psychedelics on health and their potential as a new avenue for treating mental health disorders such as addictions. He has also examined the cultural and historical contexts of psychedelic use, including their role in shamanic healing traditions and contemporary Western society.

Despite the promise of psychedelics for medical and therapeutic use, current regulations have hindered research. The American Food and Drug Administration (FDA) has classified these substances as Schedule I, meaning that they are considered to have a high potential for abuse and have no currently accepted medical use. Winkelman has been a vocal advocate for reclassifying psychedelics to facilitate further research into their therapeutic potential. In discussion with The Lovepost, Dr Winkelman shared his insights on LSD’s history, cultural significance and potential as a tool for healing and personal growth.

Let’s start simply. What is LSD?

LSD is a chemical, found in natural substances and produced synthetically. It was first discovered by Western science in the context of Albert Hoffman's research on a fungus called ergot which grows on ryes and other grains. A chemical that he took from that ergot, based upon certain processes, is LSD. It's one of the many alkaloids found in ergot moulds. Another version of it is also found, for instance, in morning glory seeds. It's a substance that is very similar to a lot of other psychedelics and serotonin as well.

So it's found naturally throughout the environment?

Not ‘throughout’. It's found in two very specific plants. Not even really [in the plants]—in the ergot fungus and in the morning glory seeds . . . and other related species.

It’s hard to believe that something this controversial can be found in seeds. Let’s start with the science: how does LSD interact with the mind? Is it through ingestion?

Well, I suppose you could get high on LSD just thinking about it, but it works better if you get it into your brain. Once in the brain, it affects the way that we perceive and experience the world.

But that all begins in the serotonergic system and, in particular, the 5-HT2A serotonin receptors which are principally located in the cortex, colostrum and basal ganglia; but are also found in other areas of the brain. This receptor system is stimulated by LSD. The 5-HT2A psychedelics are classic psychedelics. One of the immediate effects is, as I said, on the serotonergic system, which modulates lots of different kinds of processes including the activities of other neurotransmitter systems.

However, one of the differences of LSD and these other 5-HT2A psychedelics with serotonin is that when they stimulate a serotonin receptor, they're not easily removed from the receptor to allow the receptor to function again. So the receptor keeps firing with the same message until it habituates and quits functioning. This has a couple of different effects that we perceive as ‘mind effects’, as the specific aspects of the serotonergic system get taken offline. One such effect is the release of another neurotransmitter system called the dopaminergic system. This dopaminergic system liberates the basal part of the brain, the bottom of the brain, with the emotional brain—with the frontal brain.

Through the process of destabilising serotonin and releasing dopamine, we get some major changes in the operation of the brain system. One of those changes has to do with the deactivation of the prefrontal cortex—the control system that mediates [between] the frontal part of the brain and instructions for the lower parts of the brain. And so the habitual top-down control exercised by our frontal brain is deactivated with these classic psychedelics.

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Synthetically produced by natural substances that holds similar characteristics to psychedelics and serotonin.

Another effect is a deactivation of aspects of the default mode network. This is a key integration system found just below the prefrontal cortex. The prefrontal cortex is like the top end of the system. This default mode network has a number of functions, including linking us to our habitual sense of self, our habitual memories . . . and our traditional notions of who we are as a person. The top-down control and this personal system get deactivated eventually by the psychedelics, replaced by an ascending pattern that loops out of the basal brain up to the frontal cortex, and then back down to the basal brain.

And so they begin to activate the serotonergic ascending linkages . . . and they come to dominate the entire brain with information coming out of the lower brain. Part of these effects—in destabilising the normal control, and then allowing for the lower brain’s information to come up—is a heightened stimulation of the visual centres of the brain, and the connectivity of the visual centres with other regions of the brain that they don't normally communicate with. Indeed, the whole brain has this pattern: under the classic psychedelics, a condition of global connectivity replaces the normal top-down control of the brain.

One of the overall long-term effects throughout the experience is, ultimately, an enhanced connectivity between regions of the brain that normally don't communicate with one another—particularly lower brain regions that don't have to do with language and our habitual way of thinking about ourselves. So that's why we have dramatically different experiences in our minds and our perceptual apparatus.

Wow, that was an amazing explanation. It’s very complex but the directions of communications really help to visualise it. Thank you so much.

Well, you'll find this idea in detail with citations in my articles and, in some of the books I've done on psychedelics.

You’re at the frontier of research. Can you take some steps back, so that we arrive at this frontier with a better understanding? Maybe you could start with some history of LSD’s cultural use.

Well, this will be a bit of a historical perspective going all the way back to the Greeks, thousands of years ago. There's good evidence that they used ergot alkaloids as a sacrament, part of the Eleusinian mysteries—these sacred initiations of these cults in Greece. [They] probably had even deeper roots in the Greek cults of Demeter and Persephone, which were probably psilocybin mushroom cults. That's the deep history.

What happened between then and 1938, when LSD was discovered or, we might say, rediscovered by Albert Hoffman . . . well, there’s a lot of speculation. We don't know for certain, as far as I know.

In the 1950s, we started to see the modern era of LSD research. It began in a few psychiatric labs. Then the CIA found out about it and decided it was a good mind-control experiment to engage in. They began to dose people in the military, and dose other countries, and dose CIA agents—dos[ing] unsuspecting people in the United States. As a result, some people say the whole 1960s psychedelic revolution was a big CIA experiment that got out of hand.

By the time the CIA realised what they had unleashed, it was too late to undo it—in part because the word was getting out, not just about LSD but other kinds of psychedelics were [also] coming into the consciousness and awareness of our culture. Carlos Castaneda, a writer and anthropologist, popularised the notion of other realities [being made] accessible through drugs. This took us to connections with other kinds of classic psychedelics and similar ones, like the peyote and San Pedro cactus, and eventually Ayahuasca.

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Serotonin receptors stimulated by LSD modulates different processes and activities.

Then with Nixon, the whole thing shutdown. We went into a psychedelic Dark Ages in which it was really just anthropology keeping this alive. [During this time] we had a few new compounds discovered that the FDA would quickly ban.

We started to see a renaissance in the 1990s. Certainly, the continued cultural use during this period of prohibition contributed ultimately to the renaissance. It was scientific research from people like Rick Strassman and research at Johns Hopkins like Roland Griffith's, which began to bring about a medical renaissance in the study of these substances that were, to a certain extent, studied during the 1950s and 1960s—but [they] didn't get enough [of the] good kind of attention.

I just want to pick up here about the LSD boom in the 1950s or 1970s. Back then, there were no restrictions on the use of LSD. Therapists could order hundreds of thousands of doses and give them to people to try. People were doing experiments and finding that there were lots of good effects from the controlled use of the substances, {and] even sometimes good effects with poorly controlled use. Unfortunately, some bad effects ensued with unsupervised use. But during this time medical science discovered that this could be useful for treating addictions, for treating character disorders, for treating a variety of different forms of mental illness—although they didn't get the kinds of good controlled double-blind studies that they needed to determine whether the effects are strictly pharmacological or whether it was sort of a placebo effect, an expectancy effect.

I'm glad you picked up on that point as it helps to build the cultural picture. Thank you for that. And where was your own passion within this evolution? What was it that drew you to psychedelic research?

Well, I guess it was doing psychedelics, reading Carlos Castaneda, taking comparative religion and learning about shamanism. From there, I figured there had to be a connection between psychedelic effects and the origins of shamanism and human spirituality. I was basically trying to track down the evidence for those perspectives that most of my career has been about.

What an intersection! Keep going, please: how did you go from the origins of shamanism to this cutting-edge medical research?

Most of my research is summarising other people's research. I'm an anthropologist, trained in psychology and public health. So what I tried to do is, on the one hand, look at what people and other cultures have done. And then on the other hand, look at what medical science is telling us about the effects of LSD and psilocybin—and then try to bring the two together. How does modern scientific research on this substance illuminate the way in which it has been used in other cultures? And ultimately, what kind of role this may have played in the human past?

Some of my recent work has been on psychedelic sociality and human evolution. We have a whole special issue in Frontiers in Pharmacology on Psychedelic Sociality. How did the ingestion of psilocybin millions of years ago—and over hundreds of thousands, or millions of years—affect our evolution as a species? What were the ways in which this exogenous environmental source of important neural chemicals—the serotonin precursors—[affected] human behaviour, human relations and human thought? And what we see in the evidence [is that] there is good reason to believe that it was an important part of human cultural evolution [and] human social evolution. [It may have played a role in] enhancing sociability, enhancing extroversion, creating new models of the world, giving us new ways of thinking about things, and giving us a set of spiritual experiences that we, in turn, responded to and began to exploit as part of our human evolution.

What I see in psilocybin in particular (which is basically a sister molecule to LSD) is a set of chemicals that stimulated how humans were able to conceptualise cultural models of the world, relate better to one another, develop empathy for others, develop altruistic tendencies, and unleash a variety of different kinds of healing potentials. [We can see] their implications by looking at what these kinds of substances do in clinical studies today.

That sounds hopeful.

The downside is that LSD is still scheduled by the FDA. The FDA considers LSD to be as debilitating and dangerous as heroin, even more dangerous than cocaine and morphine. Can you believe it? Our [US] government says it's safer to use cocaine and morphine than it is to take psilocybin or LSD.

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Demeter, enthroned and extending her hand in a benediction toward the kneeling Metaneira, who offers the triune wheat that is a recurring symbol of the mysteries (Varrese Painter, red-figure hydria, c. 340 BC, from Apulia)

Honestly, the more people I talk to about psychedelics, the reasoning behind the classifications makes less and less sense. Why does the FDA think that?

Well, there was a very biased set of administrative decisions made. It's not based on science. Administrators [like] the head of the FDA get to decide how to classify substances. There was a political decision made to consider marijuana and LSD the most dangerous drugs on the planet when they're not. There's no scientific evidence to show that, [and] much to the contrary.

So any forward motion is going to take a lot of unlearning.

Yeah, and political changes. Hopefully, we see something promising on the horizon here. They say that [US President] Biden has developed some task force on reclassifying psychedelics. If he does that, and the task force persuades the FDA to change its classification, it could really open the doors for a lot of new kinds of studies.

What is involved in these kinds of studies? Trips or microdosing? Can we start by talking about the difference between a trip and microdosing, both in the experience and the effects?

Okay. Microdoses are typically considered to be such low-level doses that there are no perceptible effects or differences. Indeed, the very little citizen science research with the general public that has been done with controls up to now suggests that at what are considered to be microdosing levels, there may not be any effect. However, many people will attest that even if you cannot perceive the effects, by giving your body the serotonin precursors you're doing better. You're feeling better and you're doing things better. The idea is [that] it's a very subtle enhancement of the serotonergic system.

A trip is normally considered to be a high dose. In between, they have psycholytic doses that are often thought to be more amenable to a person engaging in a normal conversation, in normal therapy, with enhanced access to memories and emotional material. A trip? Normally we're talking 250, 300, 400, or 500 micrograms of LSD, in which the person can be on the verge of completely losing any contact with what we would consider [to be] consensual reality—ordinary reality. They go into a visual imaginary world. They see, in the case of [N-Dimethyltryptamine or] DMT . . . they enter into DMT universes. Under Ayahuasca, people say they go to totally fabulous worlds they've never seen before. They enter into an alternative universe through their own experiences. That's the big trip.

So that's from connecting the top of the brain to the bottom of the brain and all the places in between?

More likely, [it’s caused by] stimulating the messages from the bottom of the brain and the visual centres of the brain to take over the rest of the brain. It turns the top of the brain into a great big television screen.

How do we apply this great big television screen? What mental illnesses could LSD treat and how?

What I'll first say is that we have a variety of different forms of evidence of how LSD can treat a variety of illnesses. It begins with the effects on the serotonergic system. [In] most of the major drugs used in psychiatry today, the so-called serotonin reuptake inhibitors [or SSRIs] basically affect the serotonin system. They're not much different in a basic structure from the psychedelics. So psychedelics go to enhance serotonin, which modulates a lot of regulatory processes and normally makes us feel good and more connected.

What kinds of illnesses could [psychedelics] treat? Well, in the two volumes of  psychedelic medicine, we look at much of the history of the use of LSD to treat things  from obsessive compulsive disorder [OCD] to depression and post-traumatic stress disorder [PTSD]. We could [also] talk about cluster headaches or suicide headaches and a variety of different kinds of addictions, dependencies on alcohol, etc. When we expand this to look at what's being done recently with things such as psilocybin, we see a broader range of effects when dealing with, for instance, treatment-resistant depression. People take one dose of psilocybin, and they're better than the baseline the next day. They're still better the next week. They're normally better the next month and three months out. The effect may begin to wane after three to six months.

We see a similar thing in treating cluster headaches and suicide headaches. The effects are immediate and [they] alleviate this extreme pain. Most people have an effect that lasts more than six months. But it appears that by nine months to a year, yeah, you need another dose. If we look at other things rather than just LSD — like 3,4-Methylenedioxymethamphetamine [MDMA] —we see that you may need a number of treatments. But one of the remarkable things about psilocybin and LSD [is that] it appears that one major breakthrough experience of full-blown mystical experience is enough to have an immediate, long-term impact on wellbeing and behaviour.

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Relief of a painting depicting dancing figures with a mushroom as a head and a mushroom-like object in the right hand (from Samorini 1992). Estimated to be between 7000 and 9000 years old. (Image courtesy of Giorgio Samorini)

Can you elaborate on the immediate versus long-term effects?

Once again, the 5-HT2A psychedelics (these classic psychedelics: psilocybin, LSD, Ayahuasca) . . . can rehabilitate deteriorated or lost nerve networks. They can create new nerve networks. Basically LSD is a nerve-network builder on steroids, if you take the metaphor . . . [W]hat they're able to do with these large-dose breakthrough experiences is produce long-term impacts through effects that allow the brain to rewire itself.

‘Nerve-network builder on steroids’ is a good metaphor. Can we discuss the effects that make some people fearful of LSD—particularly the idea of a bad trip that ruins your life forever. What causes bad trips, and how do these impact a person in the long term?

I think the first thing that we ought to recognise about bad trips is that what they typically involve is the person coming to realise something—[becoming] aware of something that they didn't like. They had some trauma. So one of the mechanisms by which bad trips occur—and therapy occurs—is that people recover memories or become aware of aspects of themselves or their relationship that aren't good. And so if the bad experience is dealt with appropriately, then it can provide the basis for long-term improvements.

This points to two important issues about people using LSD and other psychedelics. First, there needs to be some screening. Someone that has a long history, or a previous history of psychosis or schizophrenia; who has severe mental illness apart from depression; character disorders, [they] probably aren't good candidates. They certainly should be started off on very small doses and well monitored.

On the other hand, if you're going to give someone a big dose, then we go back to the fundamentals of psychedelic therapy. It's called set and setting. What this means is that the nature of the experience is produced by factors that have to do with the person's mental set, their mental framework and what's going on with them. Even having a mental framework about problems and depression is okay as long as you're set on figuring out what you need to do to resolve the problems.

But the mental framework makes a big difference in the experience. People in religious cultures take these things and have religious experiences. People in secular cultures may only have a neat social event, but nothing spectacular.

So then the setting. Where is this substance being consumed? Trying to sit on a tram in downtown New York at rush hour is probably a recipe for a bad experience. Being out in nature, in a safe setting with your friends, is probably a setting for [a] good experience. The setting extends to the whole system of therapeutic support. Who's going to be around you? Who's going to help take care of you if you feel really bad? Who's going to [keep] track of you and make sure you don't wander off into the highway, if you're so screwed up you don't know where you are? So the idea of having a sitter certainly is essential for initial experiences and high-dose experiences. You need someone sober who you trust is going to be there to take care of you. And so there's a whole movement now, training people to be psychedelic sitters, recognising that this therapeutic support is essential for making sure that a bad trip doesn't happen—or if it does happen, [that it] is guided with therapeutic intent and integrated into some ways that make it a positive experience for the person.

If we know this, what’s stopping us? What are the barriers to scientific research? We've touched on the class schedule. Is that the big obstacle?

I think the biggest problems with scientific research are [related to the FDA’s] schedule 1 [status]. I mean, this is prohibited for scientific research, so it's not getting done in the US. Some [studies] are getting done in other countries which don't have such restrictive laws.

But there are other problems. For instance, a big psychedelic experience is something that . . . has to be closely monitored for 24 hours. And the principle of psychedelic therapy is that there needs to be a male and a female sitter. Suddenly, it becomes very expensive to do any of this research even if it were legal because you have to have two people employed in a controlled setting for a 24-hour period. How these are being overcome is still to be seen. I mean, the barriers to scientific research are being overcome by doing research in places like Jamaica and Mexico and [by using] other psychedelics, not LSD.

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LSD produces long-term effects allowing the brain to rewire itself.

There are also new ideas being developed. I'm developing a concept for psychedelic research that's already been established: citizen science. It has to do with scientists recruiting citizens to be part of their scientific study. For instance, people who can count the number of birds in their neighbourhood, or the number of butterflies. Are [there] people who are willing to participate in scientific research while they're taking a drug, to help figure out what the side effects are and what might be optimal dosages? Or it can be someone who says, “Okay, yep, my grandfather's got Alzheimer's. We have to have him under care 24 hours a day. But you know, I'll participate in this little study. I'll start giving my grandfather microdoses of LSD and see if he gets any better. And maybe on some of the weekends, when the whole family's around to help take care of him, we're gonna give him some big doses of LSD. See if his brain rewires, and he comes back.” So these are some of the experimental idea areas that I'm moving into. I want to develop a multi-country, multi-site research study on the effects of psychedelics and treating Alzheimer's patients. So, going around the government is my plan now.

That means a lot to me because I've lost three grandparents to Alzheimer's. I hope that goes well. Alzheimer's is a terrible thing. How about beyond your work? What do you see in the future of LSD treatment?

Well, I think the future can be bright. If it can get rescheduled, then [I foresee that] we'll use it to treat addictions such as cigarette addiction or alcohol addiction. It'll be used for treatment-resistant depression, maybe even early-stage depression. It will be used for cluster headaches [and] the suicide headaches. It'll be used for obsessive-compulsive disorders. It'll be used in trauma therapy. It'll be used for Alzheimer's, maybe Parkinson's. And maybe, ultimately, it'll be a cognitive enhancer. So instead of waiting for things to turn south, you'll say, “I want to do LSD sessions every other month and see how this improves my life. [How] can this help enhance my overall understanding of [my] life trajectory and how to get there?”

Wonderful. And is there anything else you'd like to add?

Well, a lot of these things that are now the future of LSD treatment are starting to be the present. My recent book with Ben Sessa, called Advances in Psychedelic Medicine, looks at a number of areas in which we already have substantial clinical research from around the world that allows us to conclude that there is no reason not to begin using LSD, psilocybin [or] Ayahuasca for a variety of mental illnesses. We already have the effective stage one and stage two, or phase one and phase two, evaluations of the substances. We're already into phase three, which is treating patient populations. We just need to find the right legal classifications and the right jurisdictions—for instance, using things like Ibogaine in Mexico, using psilocybin in Jamaica, and using Ayahuasca in Brazil. These can be used as medicines now. There's no reason to wait. Let's do it.