This story was originally published on Sapiensoup.

For someone who has never taken a psychedelic drug it can be difficult to imagine what it’s like. You’ve probably heard of melting walls, tasting colors or kaleidoscopic vision.¹ Such pronounced hallucinations are typically the outcome of high doses of LSD or psilocybin. In moderate doses, however, the effects are more subtle. Colors appear more vivid and patterns may morph slightly, but users usually don’t see things that aren’t actually there.

It’s still grass, but the colors are amplified and the individual blades of grass seem to compose geometric shapes, maybe you can even detect objects or faces.

The higher the dose, the more intense the hallucinations. The following image demonstrates a visual experience one may get from a slightly higher dose of LSD:

In any case, visual effects are just one aspect of the psychedelic experience. Psychedelic drugs create an altered state of consciousness that I like to describe as interpreting reality in a different way. Others have described it as seeing the world through the unbiased eyes of a child. But if you ask ten other people, you’ll get ten other answers. So, let’s hold the subjective descriptions aside for a moment and look at a quantified model of altered states of consciousness.

Measuring altered states of consciousness

In order to measure psychedelic experiences, researchers use a model called the five-dimensional altered states of consciousness rating scale (5D-ASC). ³ Each psychedelic drug creates a unique signature on that scale. In the chart below I’ve combined data from several 5D-ASC studies ⁴ in order to compare the psychedelic experience of MDMA, LSD, psilocybin and ketamine.

The psychedelic experience according to the 5D-ASC scale

Just three of the five ⁵ dimensions are displayed above. Let’s take a closer look at what they mean:

1.Perception

Imagery & sound

The degree of hallucinations is dependent on (1) the type of drug and (2) the amount taken. Of the four drugs charted above, MDMA has little potential for producing audiovisual hallucinations, while LSD is the most reliable for creating some sort of changed imagery. The imagery can be elementary: seeing patterns or lights behind closed eyes, or complex: seeing entire scenes behind closed eyes or having an extremely vivid imagination. A different study, using psilocybin, showed that a high dose is twice as likely to produce visual hallucinations than a low dose. ⁶

Changed Meaning

The things you hear and see might change their meaning under the influence of a psychedelic drug. Think of a glass of water: under normal circumstances you might think ‘I drink water when I’m thirsty’. But when consuming a psychedelic substance you might think ’water is the essence of life’. In a recreational drug use context, this change of meaning could make for a few fun stories. In a therapeutic context, however, changing meaning is an important step in order to change thinking and eventually, changing behavior. Think of something that would usually scare you to death, say: spiders. Imagine you took a psychedelic substance and then a spider crawled up next to you. Instead of writhing with disgust, you might think ‘What a peculiar yet fascinating creature’ and pursue its movements with childlike wonder.

Disrupting negative thought patterns is a key element of psychotherapy and can be a lengthy process. Though psychedelic substances present themselves as powerful tools to profoundly and instantaneously change an individual’s perspective, more research has to be done in order to prove their safety.

2. Self-disintegration

Disembodiment & losing control

Who isn’t worried about losing control over their body? This fear is what makes the dimension of self-disintegration so frightening for many of us. It includes feelings of floating, detaching the mind from the body, no longer having a body or one’s own will, having difficulties distinguishing the important from the unimportant or making decisions. Some of that sounds scary, agreed. At the same time, certain practices such as meditation and sensory deprivation tanks aim for creating some of the exact same experiences.

Ketamine scores particularly high in this dimension. LSD, psilocybin and MDMA produce fewer disembodiment experiences.

Anxiety

Note how all four psychedelic drugs score very low on anxiety. That means that even in combination with a possibly daunting out-of-body experience or visual hallucination, users don’t feel anxious about their experience. So-called bad trips more often than not result from a bad choice regarding set and setting, which we’ll discuss in just a moment.

3. Oceanic boundlessness

If the previous section was about the negative side of self-disintegration, this section is about the positive side of it. ‘What’s positive about the disintegration of the self’ you ask? Well, let me ask you in return: do you ever struggle with your self? Most of us experience feelings of anxiety, perfectionism, compulsion, stress, inferiority or guilt. Putting one’s self on hold at times can offer a great deal of relief.

Oceanic boundlessness is a blissful state of contentedness. People experience a deep connection with the world around them. Some describe it as connecting to something “larger” than the self, others talk about having spiritual experiences. LSD and psilocybin score higher than ketamine and MDMA in this dimension. The exception is the blissful state category, where MDMA is ahead by comparison. That makes sense, if you recall how MDMA floods the brain with serotonin, the happiness inducing neurotransmitter.

Different drugs, different experiences

Why do MDMA, LSD, psilocybin and ketamine produce distinctly different experiences? They are all called ‘psychedelics’ because they induce an altered state of consciousness. ⁷ But biochemically, they create their effects by interacting with different elements within the central nervous system.

Mechanistic classification of drugs ⁸

Within that model, you can further categorize psychedelic drugs according to their subgroups, medical use cases and effects in the brain. MDMA is an empathogen or entactogen, LSD and psilocybin are hallucinogens and ketamine is a dissociative anesthetic.

If you struggle to understand the drug’s effects in the brain, read the explanatory primer on the Serotonergic System. With plenty of illustrations and infographics it’ll take you step by step from knowing nothing about neurotransmitters and synaptic receptors to knowing more than most people.

User stories

How does the theory translate into real experiences of real individuals? What follows are some colorfully described user stories.

MDMA

“When ecstasy is coming on it feels fantastically exhilarating. Users report feeling blissed out, energetic, and emotionally opened and loving.” How MDMA works in the brain. ⁹

LSD

“Ecstatic feelings of love and happiness, affinity for other people, feeling of being at home with one’s self and the universe, flowing visions with more intricacy, beauty, and color than anything found in nature, sound which one can taste and feel with heart and soul, a sense of suspension in time and feeling akin with eternity and infinity, a brilliantly lucid mind able to see itself from vast and novel perspectives, an overwhelming tide of emotions…” ¹⁰

Psilocybin

Mushrooms produce effects similar to those of LSD but with a different signature. Users frequently describe their experience to be unpredictable and more mysterious. With magic mushrooms “I’ve often felt that I’m in the presence of an ancient teacher, whereas with LSD, it can feel like I’m simply traversing my own mental pathways.” ¹¹

Ketamine

Ketamine functions very differently than the other drugs discussed in this series. While most psychedelics interact with the serotonergic system, ketamine interacts with the glutamatergic system. Glutamate is the most abundant neurotransmitter in the brain and plays a vital role in controlling synaptic plasticity, learning and memory. ¹²

Ketamine’s psychoactive effects derive from blocking a certain type of glutamate receptor, ¹³ specifically the NMDA receptor. Being a dissociative anesthetic, the ketamine-induced psychedelic experience has pronounced out-of-body elements including at times even loss of bodily control. At low doses, ketamine puts users in a dreamy, mildly psychedelic state. At high doses, some find it terrifying and some call it “the most intense, bizarre, and enjoyable psychedelic”. ¹⁴ One experienced user described it like this: “As the high is coming on there is a break in the continuity of consciousness. […] Frequently there is no recollection of ever having been myself, been born, had a personality or body, or even known of planet earth. The experience is one of being in total orgasm with the universe. I feel like I’m in hyperspace, simultaneously connected to all things.” ¹⁵

Bad trips

What about bad trips? Do they exist? Yes, they do. The research team around Roland Griffiths at Johns Hopkins University performed an online survey in which they asked psilocybin users to share details about their worst “bad trip”.

62 percent of respondents rated their worst bad trip to be amongst the ten most psychologically difficult or challenging experiences of their lives. What’s surprising is that about the same percentage of users also considered it amongst the ten most meaningful experiences of their lives. “A difficult experience, sometimes described as catharsis, often results in positive personal meaning or spiritual significance.” says Griffths.

How 2,000 psilocybin users rated their worst bad trip ¹⁶

Challenges may eventually lead to personal growth. 76 percent of participants reported that their difficult experience led to increases in current well-being and life satisfaction. ¹⁷ This suggests that a “bad trip” might not be so bad after all.

And what triggered these difficult experiences in the first place? Dosage, set and setting were significantly related to the degree of difficulty and duration of the unpleasant experience.

The importance of ‘Set and Setting’

The individual psychedelic experience depends on a number of things. Obviously, it depends on the dose and type of drug the user is consuming. But it also depends on the user’s body composition, gender, genes, their sensitivity to certain drugs or drug interactions with other pharmaceuticals the user is taking, such as contraception or psychiatric meds. And as if all that wasn’t enough variability already, the experience depends greatly on what is called set and setting. Set refers to the individual’s mindset and experience, whereas setting refers to the surrounding and atmosphere.

Taking MDMA during a couples therapy session has entirely different effects than taking MDMA at an electronic dance festival. The psychedelic experience is a function of the mindset as well as the physical and social environment.

The influence of set and setting may explain the staggering variance within early psychedelic research. When LSD was first distributed in the 1950s, it was marketed as a psychosis-inducing drug and was used in clinical psychiatry. Experiments usually took place in highly impersonal surroundings—think stark hospital rooms—and the subjects were often psychiatric in-patients or from socially disadvantaged populations, such as prisoners or drug addicts. In some cases, they had little choice but to participate in these experiments. Now imagine such a subject being tied down to a hospital bed, harsh lighting, rude staff and doctors looking for signs that the administered substance has made the subject become psychotic. Anyone would have a difficult time in such a setting—with or without the drug.

Less than a decade later, LSD became popular amongst college students as a substance that would expand consciousness and enhance creative thinking. Participants joined the studies voluntarily because they were anticipating a meaningful experience. The experiments were often carried out in lovingly furnished rooms with interesting art, flowers and music for the volunteers to enjoy while they waited for the drug to kick in. The researchers would respond to the participant’s personal needs and treat them with kindness and respect. ¹⁹

This all goes to show that set and setting profoundly influence actual psychedelic experiences. Through continued research, however, we’ve been able to pin down a few common denominators of all psychedelic experiences, such as timelessness, selflessness and effortlessness. ²⁰

Also by Marlene Rupp

Your Brain on Psychedelic Drugs
Psychedelics and Mental Health

This article was originally published on Sapiensoup. Photo credit Greg A. Dunn

During my LSD sessions, I would learn a great deal” said Cary Grant about the 100 acid trips he dropped in the search of his true self. “And the result was a rebirth. I finally got where I wanted to go”. ¹⁰ Steve Jobs described taking LSD as “a profound experience, one of the most important things in my life”. ¹¹ How is it that we never hear such grand endorsements about heroin, alcohol or cigarettes? What is it about psychedelics that has the power to change lives for the better? The answer might lie in the unique ways that psychedelics interact with the brain. In this post we’ll go deep on the molecular level—in a fun way.

The experiences of Cary Grant and Steve Jobs are in no way isolated cases. In a recent experiment at Johns Hopkins University School of Medicine, 36 healthy volunteers were given a high dose of the hallucinogen psilocybin (the active ingredient in so-called ‘magic mushrooms’). Two thirds of participants rated it amongst “the five most meaningful and spiritually significant events of my life”. They reported increased well-being and positive behavior changes even 14 months after the psychedelic experience with no additional uses of the substance.¹⁴

‘Higher’ state of consciousness?

In this post, when I say ‘psychedelic drugs’ I’m referring to the classic psychedelics namely LSD, psilocybin, DMT, ayahuasca and peyote. Users of these drugs often report experiencing a ‘higher state of consciousness’ in which their perception seems enriched.

When researchers first scanned a human brain under the influence of these drugs, they expected to measure an increase in brain activity. To their surprise, most of the brain remained at the same level of activity except for a few areas. In those few areas the activity didn’t increase as expected, but rather decreased. What’s more, the participants experiencing the most intense psychedelic effects also showed the strongest decreases of activity in those particular areas. In other words, the lesser the activity, the stronger the trip.

Now, how does that make sense? Psychedelic drugs leave your brain’s executive functions intact: you can move, think, speak, know when to use the bathroom and other useful things. What they shut down however are certain connector hubs in the brain.

To understand the role of these connector hubs, think of traffic in a big city. When you shut down a major highway, drivers have to deviate from their normal routes and often find themselves in unfamiliar territory. Because a big city has an abundance of streets, drivers can still get to their destination, but only after a more lengthy and perhaps interesting ‘trip’.

Something similar happens when psychedelics shut down certain connector hubs in the brain. All of a sudden, there is a lot more cross-talk between areas which usually wouldn’t communicate.

The visualization below compares the brain’s communication pathways during (a) a regular state, with all the connector hubs intact. And (b) the psychedelic state, with the connector hubs shut down, leading to an abundance of novel communication pathways between brain areas.

By this time, you may be asking yourself ‘What are these mysterious connector hubs and what do they do in the first place?’ The following section is all about these hubs and how they make up the so-called default mode network in your brain. This network is a relatively new discovery and turns out to play a key role in understanding the effects of psychedelics.

The Default Mode Network

Whenever your mind is not engaged in a specific task, it switches into a kind of “autopilot” mode referred to as the default mode network or DMN for short. One way to think about the DMN is as an integration center, where information is collected and organized in ways that makes it coherent with regard to the rest of your cognition.¹⁵ The DMN is like a librarian who—when not handling immediate customer requests—indexes and categorizes books to keep the library neatly organized.

Another way to think about the DMN is as the center of the self. It’s engaged in self-reflection and metacognition, i.e. thinking about thinking. It allows you to mentally travel back and forth in time, pondering autobiographical events or future problems.^{17 21 22 23}

These important functions make the DMN a vital connector hub in the human brain and part of what distinguishes us from other species. However, an overactive DMN is associated with people being neurotic, depressed or anxious.

The brain’s default mode network (DMN) consists of the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) and the angular gyrus (AG) ²⁴

Disrupting the default mode network

When psychedelic drugs shut off certain connector hubs, they also reduce the stability of the networks that exist on top of these hubs, in our case: the default mode network.²⁵ So, if you were to disrupt your DMN—for example through the use of psychedelic drugs—how would it change the way you think and act?

When the usual DMN connectivity is not available and signals therefore travel on different routes, you experience reality in a different way. This is why the psychedelic state is often called an altered state of consciousness. ‘Seeing with your eyes shut’ and a disintegration of the self as you know it are two typical characteristics of such a state.²⁶ To learn more, check out The Psychedelic Experience post with a side-by-side comparison of how different drugs change your perception.

Particularly in people suffering from mood disorders, psychedelics frequently show another interesting effect: their condition improves. Mental disorders such as depression, anxiety and obsessive compulsive disorders (OCD) are often associated with a hyperactive DMN.²⁷ If you disrupt the DMN, you often see substantial and long-lasting reductions in symptoms. We’ll talk more about concrete study results in a follow-up article next week.

Psychedelics are unique in how they can modulate the DMN. How they work in the brain is endlessly fascinating—and unfortunately—pretty complicated. And yet, I’ll have a try in explaining it in simple terms:

Your brain on psychedelic drugs

Right. Let’s break that down into normal language:

Receptor binding

Psychedelics interact with the serotonergic system in the brain, meaning they can bind to serotonin receptors. Why? Because serotonin, LSD and psilocin—the psychoactive metabolite of psilocybin—look very similar on a molecular basis.

But whereas serotonin binds to about a dozen different subtypes of serotonin receptors, psychedelic drugs bind to a very specific subtype, the so-called serotonin 2A receptor. LSD additionally binds to a few other subtypes of serotonin and dopamine receptors, but to a lesser degree. Most relevant for the psychedelic experience is the serotonin 2A receptor.

Long axons

Serotonin 2A receptors sit on specific types of neurons which have long axons that span across the brain, as opposed to neurons with short axons that only connect to other cells in their close vicinity. These large neurons have axons that leave the cortex and run down into areas below the prefrontal cortex.²⁸ Doing so, they have top-down control over the regions they connect to, and in this case it’s areas associated with emotions and stress responses. ²⁹

Excitatory neurons

Neurons can be either excitatory or inhibitory. Think of training a dog.

Both, “speak” and “quiet” are signals that produce a certain reaction. An excitatory signal tells the neuron to “fire”, whereas an inhibitory signal says “don’t fire”. Remember, psychedelics stimulate serotonin 2A receptors, and those are located on excitatory neurons, meaning causing the neuron to fire. Logically, one would think that taking a psychedelic drug would lead to more firing in the brain. Paradoxically, the opposite is the case. How does that make sense?

When activation leads to inaction

LSD binds to the serotonin 2A receptor and causes the neuron to fire off an excitatory signal. When these neurons fire, they also stimulate nearby, inhibitory neurons called fast spiking interneurons, which have serotonin 2A receptors as well. So what happens is a massive firing and an even greater inhibition at the same time. Eventually, the inhibitory signaling is stronger than the excitatory and you’re left with a net decrease in activity.³⁰

Unique signaling

Just because serotonin and psychedelic drugs bind to the same serotonin 2A receptor doesn’t mean that they produce the same signal. For a long time, scientists believed that receptors worked like light switches, meaning that they are either on or off. According to this theory, psychedelics and serotonin must have had the exact same effect: either binding to the receptor and activating it, or clearing the receptor and deactivating it. But today we know that each molecule interacts with a receptor in its own unique way, causing a unique signal within the cell. How does that work? When a molecule binds to a receptor, the receptor has to physically accommodate the molecule’s unique shape. And by doing so it activates certain signaling pathways within the neuron.³¹ The jargon for this principle is functional selectivity, in case you wish to go deeper.

Ok, so an LSD molecule doesn’t actually look like a rainbow. Rather, it’s a big, rigid molecule which takes up a lot more space within the receptor than the smaller, more flexible serotonin molecule.³²

And receptors don’t look like sticks but more like funny party streamers being tied together at the ends with a thin thread. So, when LSD binds to a receptor, it looks a little something like this:³³

You can see how the party streamers give way to the big LSD molecule and thereby trigger a distinct signaling pathway within the cell. Tip: if you ever talk to a biochemist about this, don’t call it a party streamer—call it a helix.

As of today, it remains unknown which signaling pathway is most relevant for the psychedelic experience.³⁴ What we do know is that it’s a different pathway than the one activated by serotonin.

Why an acid trip lasts so long

Serotonin molecules clear receptors a split second after binding to them. In contrast, when LSD binds to a receptor, the receptor collapses over the molecule and forms a lid, preventing the LSD from clearing.³⁵

 

As long as the LSD molecule is trapped within the receptor, it causes the receptor to send off signals—for a few hours and sometimes longer. That’s why mere micrograms of LSD can make users ‘trip’ for 6-15 hours.³⁶

Drugs as tools

You can probably see now that psychedelics work like no other molecule in the brain. Fossil evidence supports that humans have made use of psychoactive plants for as much as 10,000 years during ritual ceremonies.³⁷ Ancient societies regarded psychedelic drugs as tools; will modern society adopt this perspective once again? Personally, I see a number of persuasive reasons why we should:

First, psychedelic drugs are remarkably safe. There is not one single documented case of an overdose from LSD or psilocybin in humans. What makes them unsafe is acquiring them from strangers on the street with no transparency regarding additives and purity.

Second, they don’t cause addiction. If a user were to take psychedelics with high frequency, they lose their effects. The body quickly builds up a tolerance which can’t be overcome by stronger doses. It takes a refractory period of at least a few days until the desired effect can be reproduced. In that way, it’s really a drug for ‘special occasions’.

Third, there is a ton of anecdotal evidence that psychedelics are useful tools for personal growth. And a growing body of scientific evidence supports that psychedelics may be extraordinarily effective in treating mood disorders and addiction.

WWhen you take psilocybin, it’s like taking onboard your own psychotherapist.” said a study participant about his psychedelic experience.²⁶ A widespread belief about psychedelic drugs is that they can turn users mentally ill; what the data shows, however, is that psychedelics can achieve quite the opposite effect: they afford patients a relief of symptoms. Indeed, a growing body of evidence supports that psychedelic drugs may be extraordinarily effective in treating mood disorder and addiction.

Depression. Anxiety. Addiction. Most everyone of us knows somebody who is battling such a condition. Talk therapies may help, but sometimes they don’t. Antidepressants may help, but sometimes they don’t. Some patients are of the opinion that antidepressants are like “Band-Aids” in the way that they never really tackle the underlying issues of their problems.²⁷

I haven’t yet heard psychedelics getting described as “Band-Aids”. What I have heard from users is that psychedelics do something like the opposite: they confront you with your greatest vulnerabilities and help you come to peace with them.

“We’re looking at a new paradigm for the way these [mental disorders] can be treated”³⁴ says pharmacologist Dr. David Nichols, president and co-founder of the Heffter Research Institute. In this post we’ll look at the latest results from psychedelic research and how they may revolutionize our approach to mental health.

Treating mental disorders

Recent studies have found psychedelics to reduce symptoms of anxiety,^{35 38} depression,^{39 40 41} and obsessive-compulsive disorder⁴² as well as addiction.^{43 44} The effects often lasted for several months after just one or two exposures to the drug.⁴⁵

The results of these recent studies are frankly mind-blowing. I’d like to present to you three of them, all carried out by reputable research teams across the U.S. and Europe.

Treatment-resistant depression

The World Health Organization estimates that more than 300 million people suffer from depression.⁴⁶ Antidepressants and psychotherapy can offer some relief, but 20 percent of patients are treatment-resistant, meaning they don’t respond to any intervention whatsoever.⁴⁷

In a recent pilot study performed in the U.K., Dr. Carhart-Harris and his team studied the effects of psilocybin in exactly these kinds of treatment-resistant patients.⁴⁸ The participants had suffered from moderate to severe depression for, on average, 18 years of their lives. All of them had previously tried psychiatric drugs and therapy or counseling, but with no success.

The chart below shows the individual depression assessments of the twelve participants. One week after the dose, 67 percent were free from depression. And three months after the dose, 42 percent remained in remission.

And the long-term effects? Six months after the experiment, 30 percent of the initially treatment-resistant patients remained entirely free from depression. For 75 percent, the psychedelic experience brought some degree of reduction in depressive symptoms.⁴⁹

Note that this was an open-label study with a small number of participants and no control group. A lack of controls is usually a red flag and tells you that the study shouldn’t be taken at face value. In this case however, the study at hand was a pilot for larger randomized controlled trials. Research is expensive and just like engineers build a prototype before they roll out large-scale production, researchers do pilot studies before they run full-blown trials. With dramatic results like these, it’s reasonable to expect fully randomized, double-blind, placebo-controlled studies in the near future. And speaking of placebo-controlled studies…

How do you fake a trip?

Controlling for the placebo effect poses a real challenge in psychedelic research. With a psychoactive substance, it’s easy for participants to know whether they have received the placebo or the active substance, and this can render the controls ineffective.

 

 

So what can be done? Some researchers use active placebos. Instead of giving the participant a do-nothing pill, they’re given either a very mild dose of the tested drug or an entirely different psychoactive substance. This approach obviously comes with its own challenges, but given the limited options it might be the better bet.

End-of-life anxiety

How would you feel if you were diagnosed with life-threatening cancer? Not surprisingly, facing one’s own mortality can unleash strong emotions. Up to 40 percent of cancer patients develop a mood disorder which in turn interferes with their chances of recovery.⁵⁰ Psychedelic drugs certainly can’t heal cancer, but it appears they can mitigate the accompanying psychological distress.

Lead researcher Roland Griffiths and his team at Johns Hopkins University School of Medicine tested this hypothesis with 51 cancer patients. One group received a high dose of psilocybin, whereas the control group received an active placebo, which in this case was a very low dose of psilocybin that had no detectable behavioral effects. In this way, all participants were told they were taking psilocybin and this controlled for expectancy.

Five weeks after the treatment with high-dose psilocybin, 92 percent of depressed patients and 76 percent of anxious patients showed significant improvements in symptoms. These positive results were not only immediate, but also long-lasting. Six months after their psychedelic experience, the patients suffering from depression were still going strong with improvement rates of 79 percent. Regarding end-of-life anxiety, the improvement rate further increased from 76 percent five weeks after the treatment to 83 percent six months after the treatment. What’s more, half a year after the psilocybin session, over 80 percent of all participants stated that the experience had increased their well-being and/or life satisfaction.⁵¹

“Such a substantial and enduring effect after one dose is unprecedented in the field of psychiatry.” says Roland Griffiths, professor of neuroscience and psychiatry at Johns Hopkins.⁵²

Nicotine addiction

Smoking causes almost half a million deaths in the U.S. every year and is related to annual health care expenditures of $170 billion.⁵³ Overcoming nicotine addiction poses a real challenge to smokers. Smoking cessation programs such as the popular Quit for Life program achieve abstinence rates of only 17.2 percent at six months. If supported with medication and weekly counseling meetings, the success rate can rise to 35 percent, dependent on the medication used.⁵⁴ The highest success rates were seen in programs containing extensive cognitive-behavioral therapy, plus pharmaceuticals, plus nicotine replacements. Such comprehensive programs show abstinence rates of 45 to 59 percent at six months.^{55 56}

Matthew Johnson, expert in drug dependence at Johns Hopkins, wanted to see if psilocybin could help smokers to quit their addiction. In an open-label pilot study, 15 nicotine-dependent smokers were guided through a 15-week smoking cessation protocol which provided high levels of psychological support, but no pharmaceuticals or nicotine replacements. The participants had smoked on average 19 cigarettes per day for 31 years and had attempted to quit smoking six times before. After the program, which included up to three psilocybin sessions, 80 percent of the participants were smoke free at the six-month mark.⁵⁷

At 12 months after the quitting date, 67 percent of participants were smoke free, and 87 percent rated their psilocybin sessions amongst the five most personally meaningful and spiritually significant experiences of their lives. Even at around 2.5 years after the quitting date, a solid 60 percent of study participants remained smoke-free.⁵⁸

The numbers produced by these three studies are impressive to say the least. Equally impressive is hearing what the participants have to say about these treatment experiences.

Real people, real experiences

Recall the treatment-resistant depression study from above. Six months after the single psilocybin session, the research team followed up with the participants and interviewed them about their session experience and their life ever since.⁵⁹

Almost half of participants reported major lifestyle changes during the months following the psilocybin session. Frequent changes involved improvements to diet, exercise, and cutting down on drinking alcohol. “I lost a lot of weight just purely because I didn’t want to eat badly and that went on for some months. I couldn’t eat what I knew wasn’t good for me.” Some changed their social circles, went out more, got new jobs, learned to drive, built a new kitchen, volunteered with refugees, travelled or picked up acting, comedy or dance classes.

Across all the stories, researchers identified two major themes of inner change. First, a change from disconnection to connection and second, a change from emotional avoidance to acceptance.

Disconnection to connection

Depression can feel as if you’re in a “mental prison” where you’ve gotten stuck in your thoughts. It “robs you of your confidence in yourself” and makes you increasingly less able to engage with your environment. The result is isolation, and whether it’s a perceived or actual isolation, depression is a lonely condition.

About the time following the psilocybin session, participants reported how they “had the mental agility to overcome problems”. They noticed a boost in self-worth, how they were able to adopt fresh perspectives and how they rekindled previous interests. “[My wife and I] went for dinner for the first time in 6 years: we were like a couple of teenagers.” told one participant. Another shared “I went past a bike shop and went in off the street and said ‘can I hang out and help out?’ I went there for 6 months and helped renovate his shop.”

Some described it as reconnecting to “who they had been” before the depression had developed. Their self-perception changed. Nearly half of the group described realizations of “being a good person” and feelings of self-compassion and self-worth. They felt not only more connected to their surrounding but also more connected to themselves.

Avoidance to acceptance

Boys don’t cry. A common root of depression is the inability or unwillingness to deal with certain emotions. “My whole life I’ve self-medicated to try to make emotions more bearable, sometimes with food, cigarettes, painkillers.”

One participant saw “emotions as weakness” because he had been raised in an environment where he learned to “put his feelings in a box because you can’t be upset, you’re a man”. Others had gone through traumatic events in their past. Regardless the origin, when participants came face-to-face with their emotions during the psilocybin sessions—which happened regularly—it triggered intense yet cathartic experiences. Powerful bouts of sobbing were observed throughout the sessions, which participants later described as “purification”.

After the session, participants noticed a fresh openness to experiencing emotions, a change that was often long-lasting. One participant described it as “a rebooting of the mind”, another noting that “it reconfigures you somehow.”

All participants said they preferred psilocybin over conventional treatments. To many of them, antidepressants and talk therapies seemed as if they were reinforcing disconnection and emotional avoidance. Some participants explained that their past therapists were trying to motivate them from the ‘outside’. Psilocybin, however, helped them to access an ‘inner voice’ which they said felt immensely powerful and highly motivating. “It’s almost as if when you take the capsules it’s like taking onboard your own psychotherapist.” With psilocybin, they had an empowered experience of self-reflection, which previous therapy attempts did not provide.

Rosalind Watts, the lead researcher of this study, proposes that with psilocybin “patients and clinicians may be granted a broader palette of treatment options in the future, affording them an opportunity to select a treatment that best suits the specific needs and/or desires of a given patient.”

A new approach to mental health

Why are psychedelics so fundamentally different from regular antidepressants? Antidepressants work by increasing the overall levels of serotonin in the synapse, which in turn, leads to more frequent activation of serotonin receptors. Psychedelics activate serotonin receptors too, but in a more targeted way than antidepressants. They activate only certain subtypes of serotonin receptors which are understood to increase cognitive flexibility.⁶⁰ Like one of the study participants stated above, psilocybin gave him “the mental agility to overcome problems” and that is precisely what’s required to achieve long-lasting results.

In a nutshell: do psychedelics alone cure mental disorders? No. Rather, psychedelics may serve as a catalyst for patients adopting new perspectives and making important lifestyle changes. Hence, kicking off a treatment protocol with strategically planned dosing session may substantially increase the overall effectiveness of the treatment.⁶¹

Given the growing body of evidence supporting the safety and efficacy of psychedelic drugs, I believe it’s a matter of time until jurisdictions around the globe will approve psychedelics for medical use. Organizations like MAPS, Beckley Foundation and Heffter Research Institute play a key role in advancing psychedelic research and driving drug-policy reforms in a peaceful and sensible manner.

This piece was originally published on Sapiensoup