Psychedelics 2019-10-31T20:45:44+00:00

The ultimate Psychedelics research review

A comprehensive review of research literature on Psychedelics, for the lay person (2019)

In this post you are going to learn everything researchers have discovered to date, on both Psychedelics as well as Non-psychedelic hallucinogens.

We’ll share findings in research on psychedelics such as Psilocybin, LSD, Mescaline, and Ayahuasca as well as non-psychedelic hallucinogens like Ketamine and MDMA on disorders like anxiety, depression, addiction, PTSD, OCD and much more.

We’ll deep dive into findings on whether Psychedelics improve well-being, whether microdosing works and explain what “transformative experiences” are about.

You will learn how Psychedelics work in the brain, and see why we’re at the beginning of a scientific revolution, that has already started in research of Psychedelics.

By Dr. Elizabeth Gilbert

Dr. Elizabeth Gilbert is a psychologist with expertise in well-being, sense-making, and cognition. After obtaining her PhD at the University of Virginia in social psychology, she completed a post-doctoral fellowship at the Medical University of South Carolina in the department of Addiction Sciences. She also holds a law degree from Duke University and keeps an eye towards how legal policy intersects with psychology and neuroscience. She is currently head of researcher at PsychologyCompass.com – a fully-automated coach that helps knowledge-workers reach their peak mental performance.

Psychedelics are a class of drugs that produce changes in thoughts, emotions, and perceptions–including hallucinations, dream-like states, and intense spiritual-like experiences. After a 50-year hiatus, the last decade has seen a resurgence of ‘legitimate’ scientific research into psychedelics. Scientists are investigating how professionals might harness the therapeutic, creative, and well-being applications of psychedelics such as LSD and psilocybin, as well as non-psychedelic hallucinogens like Ketamine and MDMA. And the results—while limited thus far—are promising

Even a single, supervised dose of psychedelics may: 

  • decrease anxiety, depression, and substance abuse, 
  • improve well-being by 50% or more for weeks or longer, and 
  • unlike many drug treatments, have minimal long-term side effects and virtually no addiction risks.

In this review, we’ll cover the key psychedelic substances that are being studied, their potential applications, and what really occurs inside our brains when we’re ‘tripping out’. We will look at what we know, how we know it, and what ongoing research has yet to uncover. 

As new research is released, this comprehensive cover of the key findings on psychedelics will continue to be updated. So go ahead and bookmark this page now. And if you know of major new findings, I’d love to hear about them at info [at] PsychologyCompass.com.


Introduction

Around the close of the 1960s, psychedelic drug studies began to taper off. Well-known psychologists like Timothy Leary were becoming better known for recreational, rather than research-based drug use, and the US Food and Drug Administration introduced strict regulations which essentially halted any scientific progress into the latter. When psychedelics are mentioned in day-to-day conversation, most will understandably assume it’s in a non-clinical context.

However, the past 15 years have seen a comeback in government-authorized research, and more than a dozen privately-funded studies are picking up where the initial research left off. We now have findings from hundreds of subjects, from research funded by institutions such as MAPS and the Beckeley Foundation, and which is carried out in clinical settings like NYU, London’s Imperial College, and John Hopkins.

What do we know? The field is still growing, but as it emerges, classic psychedelics such as Psilocybin, LSD, mescaline, and ayahuasca as well as non-psychedelic hallucinogens like Ketamine and MDMA may have genuine therapeutic applications for the treatment of many familiar psychological conditions. These include depression, PTSD, substance abuse, and anxiety disorders, to name a few; typically difficult to treat, psychedelic research is now exploring new possibilities into how some of these symptoms can be reduced or controlled.


In this article:

  1. What Is Psychedelic Research?: Lab Findings From Human Participants
  2. Can Psychedelics Be Used To Treat Disorders?/What The Research Shows
  3. Evidence from Psychedelic Research
  4. How do Psychedelics Improve Well-being?
  5. Warnings and Weaknesses: What We Don’t Know
  6. The New Frontier: Microdosing
  7. What’s next for psychedelic research

1. What is Psychedelic Research?

There are more than 100 psychedelics in existence, and over 15% (roughly 30 million) of Americans report having used at least one of these at some point in time. All have an effect by acting on the brain’s serotonin receptors, resulting in a dream-like, hallucinogenic state of altered perception, emotion, and cognition. Other experiential effects include feelings of transcendence (sometimes described as rising above or stepping outside one’s ‘self’), and a sense of stronger connections with others and with the world.

The vast bulk of psychedelics are synthesized under laboratory conditions, however, making it hard to get a clearer figure of the scope and prevalence of psychedelic usage in the population. 

What we do know is that, very broadly, the psychedelics currently being most studied include:

  • Psilocybin – this occurs naturally in ‘magic mushrooms’, and along with LSD, is the most commonly used ‘classic’ psychedelic; Lysergic acid diethylamide – a synthetic drug, much better known as LSD, or ‘acid’;
  • Ayahuasca – best known as a psychoactive ‘tea’ which features in indigenous Amazonian spiritual rituals; and
  • Mescaline – another naturally-occurring hallucinogen which comes from peyote cacti. Compared to the previous three drugs, there is slightly less available research on the treatment effects of mescaline to date.
Source - Unsplash.com

Another fast-growing research direction is focused on the potential uses for Ketamine and MDMA – two hallucinogenic substances which elicit similar subjective experiences, but which act on different neurotransmitter pathways in the brain. While they don’t technically classify as psychedelics, over 25 studies have been carried out on over 700 participants, and they merit consideration given that more follow-up research exists on their long-term effects.

In a nutshell, psychedelic research is still very much in its (second) infancy. But we now have more fresh, empirical evidence than we have had in over half a century, and with new funding, we are starting to make more headway. We are starting to get more understanding into the physical side-effects, safe limits, and risks of psychedelic treatment for mood and substance disorders.

2. Can Psychedelics Be Used To Treat Disorders?/What The Research Shows

Most psychedelic studies to date have looked at their impact on neural cells, fruit flies, and mice. The bulk of research involving human participants builds on these. 

As yet, there is no ‘standard’ methodology for such drug studies, but most involve a few key steps:

  • Participants are recruited and informed they may be given a psychedelic drug. Due to the specific nature of the research questions (e.g. “Does psilocybin significantly reduce existential anxiety in life-threatening cancer patients”), these participants are generally patients with preexisting medical/psychological conditions.
  • The psychedelic (or placebo) is administered to participants under carefully controlled conditions. Participants may listen to “evocative music,” be instructed to “stay introspective” (Griffiths et al., 2006), or may be encouraged to lie down and relax while wearing eye masks (Grob, 2011).
  • Trained, specialist mental health professionals then continue giving supervision, reassurance and support to these participants as the drug takes effect (Johnson et al., 2008); this, of course, depends on the exact nature of the study. As a frame of reference, a psilocybin experience may last between 4 and 6 hours, and participants may be ‘monitored’ using equipment that measures heart rate or blood pressure.

Depending on the focus of the study, participants may also be assigned to different experimental conditions. For example, some studies administer some patients placebos (e.g., fake pills, or other non-psychedelic drugs), in order to compare patients who received the psychedelic to those who did not.  Other studies provide different levels of the psychedelic over multiple sessions separated by days or weeks to examine effects for different doses.

source - Photographee.eu

During or immediately after the dosing–again, depending on the study design–participants may complete psychometric assessments (measuring anxiety levels, depression, etc.), take part in clinically structured interviews, or report any variety of physical and psychological changes that are relevant to the study. The majority of research also follows a longitudinal design, with regular scheduled follow-ups for up to 6 months after the original study.

So, which psychedelics are linked with specific disorders or conditions? And what have studies revealed, to date? In the following sections, we’ll take a more in-depth look at the findings on psilocybin, LSD, and ayahuasca, before highlighting some other evidence around the use of lesser-known ‘classic’ psychedelics. 

Among other things, we’ll consider evidence that links:

  • Psilocybin with improved life satisfaction and well-being, and decreased depression and anxiety;
  • Psilocybin with enhanced smoking cessation and improved alcohol-dependence therapy;
  • LSD with addiction treatment and recovery; and
  • Ayahuasca with reduced depression, anxiety, and psychological disorders.

3. Evidence from Psychedelic Research

Psilocybin research

Evidence from Psilocybin Studies

Psilocybin is a hallucinogenic naturally-occurring psychedelic that can be found in over 200 types of fungi. Colloquially referred to as ‘shrooms’, these long, light-colored ‘magic mushrooms’ grow in tropical and subtropical areas across Mexico, South America, and the US. Research suggests that more than 20 million Americans have dabbled recreationally with psilocybin at some point. 

They are typically eaten raw, cooked, or brewed for recreational drinking in contemporary culture, though ancient Angerian rock carvings suggest humans have been experiencing their psychoactive effects since prehistoric times. Evidence of their role in Native American religious rituals also precedes the modern scientific study of their effects by several thousand years. 

source - Pixabay.com

Psilocybin and Increased Well-being

In 2006, researchers completed what is perhaps the most influential modern study of psilocybin’s therapeutic potential since the 1970s. At John’s Hopkins University (Griffiths et al., 2006), healthy participants were administered an initial, high, oral dose of psilocybin in order to examine its possible impact on well-being. 

As the psychological effects were followed up over a 14-month period, findings showed a positive upward trend in their moods, behaviors, and attitudes. Of the 36 participants- who had never previously tried psilocybin – 67% rated the experience among the top 5 most meaningful experiences of their lives, and 64% reported it as having improved their life satisfaction and well-being (Griffiths et al., 2008). 

Perhaps most interestingly, the study showed that having a more mystical experience on the day of dosing predicted more ‘meaningful’ and ‘spiritually significant’ experiences at later dates.

Impact on Interpersonal Behavior

These encouraging results were extended  several years later by Griffiths and colleagues once more, this time stepping a little further from the individual experience and looking at psilocybin’s potential impact on social behavior. 

Specifically, the researchers found empirical evidence connecting psilocybin with increased prosocial attitude changes and behaviors – such as altruistic thoughts and feelings (Griffiths et al., 2018). They also revealed significantly higher integration of spiritual values into daily life among subjects who received a high dose, and engaged in practices such as meditation. These changes persisted up to six months after the initial study, suggesting that trait-level changes may be partly responsible. 

So, what underpins these behavioral changes? In light of the very new nature of this research, it is hard to point specifically at an underpinning mechanism – but looking at Griffith and colleagues’ findings alongside prior studies (e.g., MacLean et al., 2011), it may be partly due to deeper-level changes in the Big Five personality trait of Openness. 

Earlier studies, that is, provide some evidence demonstrating that a one-off dose of psilocybin can lead to lasting increases Openness (akin to open-mindedness), which commonly typifies people with active imaginations, creative or artistic tendencies, and curious mindsets. 

Evidence on Psilocybin, Anxiety, and Depression

Given that serotonin plays a well-known role in human happiness, and given that psilocybin acts on serotonin pathways, it is hardly surprising that the psychedelic’s potential role in treating depression is a strong point of research interest. And in fact, there are multiple studies which point to promising evidence in support of this. 

The beginning of this decade heralded one of the earliest legal pilot studies on psilocybin, depression, and anxiety. As with numerous other psychedelic research designs, it involved participants with pre-existing medical conditions – in this case, 12 volunteers with late-stage cancer and a related anxiety disorder. In comparing the impact of psilocybin on these participants’ mood disorder symptoms, Grob and colleagues’ (2011) found a noticeable downward trend in the severity of the treatment group’s anxiety and depression. 

In other words, participants who had taken a moderate psilocybin dose had less serious symptoms at the 2-week mark than those in the control group – who were given a placebo. Though the difference only reached statistical significance at the 6-month mark–as can be expected with a very small number of participants–every month thereafter for half a year this trend continued. Most promisingly, there was no report of major adverse side effects – an interesting point when considered alongside the potential risks of benzodiazepines and other conventional antidepressants.

Grob and colleagues’ research findings received further support from the findings of more recent cancer patient studies. For example, with a larger sample size of 51 participants, Griffiths et al. (2016) expanded the research design to encompass two separate dosing sessions, each time with a different sized dose. In this set of studies:

  • Participants took both a high oral dose of psilocybin (22 or 30 mg grams per kilogram of body weight) and a very low dose (1 or 3 grams per kg) at a different date. The second served as a point of comparison, as with only trace amounts of psilocybin, no real effect was possible. It also acted as a control, to manage any potential effects from participants’ expectations.
  • When assessed up to five weeks after taking a high dose, patients showed significant improvements on multiple medical depression and anxiety scales, such as the Beck Depression Inventory, Hamilton Depression Rating Scale, and Hamilton Anxiety Scale
  • Measured again at the six month mark, and perhaps most astonishingly, these improvements remained statistically significant. Around 60% of patients were no longer clinically depressed or anxious, and 80% continued to display reduced anxiety- and depression-related symptoms.

Similar results are continuing to emerge as increasing scientific interest and funding come to move the field forward. Examples include:

  • A 29-patient, 2016 study by Ross and colleagues, which compared psilocybin’s effects to niacin placebos, and followed psilocybin’s effects for over 6 months. This study of life-threatening cancer patients with related anxiety diagnoses supported Griffith et al.’s (2016) results. More than 60% of patients showed substantially reduced anxiety and depression symptoms up to 6 months after taking psilocybin. They also reported no serious adverse side-effects; and
  • Another slightly different pilot study by Carhart-Harris et al. (2016a) which examined 12 patients with treatment-resistant major depression. Unlike the prior two experiments, both patients and researchers were aware of what psilocybin doses were being administered (i.e., it was an “open label” design)- but similarly, they underwent two separate dosing sessions with different sized doses. As with the previous examples, participants’ depression and anxiety symptoms significantly improved by an average of 20 to 50%, and no major adverse side effects were noted. These results held three months after the psilocybin dosing. 

Psilocybin and Substance Abuse

Substance use and misuse are frequently related to mood disorders. A large proportion of the time, abuse is a maladaptive coping strategy which can be hard to treat, often leading to dependence. Given that addict populations are commonly found to have lower serotonin levels, the potential use of psychedelics as a part of recovery has also been explored as restrictions have begun to ease. Some of the scientific results are indeed encouraging for those interested in new nicotine and alcohol dependence treatments, in particular. 

Findings On Psilocybin and Smoking Cessation

First, there is some evidence that psilocybin, alongside Cognitive Behavioral Therapy (CBT), may be effective in helping people quit smoking. One study by Johnson and colleagues (2014) involved administering the psychedelic to 15 treatment-resistant smokers (informed volunteers) on the day they quit smoking. Results showed that:

  • 80% of psilocybin-treated participants were biologically confirmed to be abstinent from smoking six months after their first dose;
  • This is substantially higher than traditional medication or behavioral studies, which typically result in a ~35% abstinence rate after six months; and
  • On top of this, follow-up studies 2.5 years later revealed that 60% of the participants were still non-smokers (Johnson et al., 2017).

For interested readers, Johnson and colleagues’ participants took the drug a total of three times; a fortnight after the initial dosing – the ‘target quit date’ – and then again at the eight-week mark. These second and third sessions involved higher psilocybin doses (30mg/70kg). Alongside these sessions, participants had 10 weeks of CBT, which has been shown to promote longer-term abstinence in smoking cessation programs (Killen et al., 2008). 

How did participants describe their experience? And what were their thoughts about the psilocybin use and the impact on quitting? The answers are varied, according to interviews conducted by Noorani and colleagues (2018) – but interestingly, most described how the drug gave them “vivid insights into [their] self-identity and reasons for smoking.

 They also mentioned: 

  • Feeling awe, interconnectedness, and curiosity which overshadowed their short-term nicotine withdrawal symptoms;
  • That these feelings lasted long after psilocybin’s immediate effects had passed;
  • That preparatory counselling and good support staff relationships helped them remain abstinent; and
  • That the study itself gave them momentum to remain abstinent over time.

Can Psilocybin Help with Alcohol Dependence?

There is also evidence suggesting psilocybin treatment may help to substantially reduce the frequency of binge-drinking behavior in alcohol-dependent individual. Bogenschutz and colleagues (2015) recruited a sample of alcohol-dependent participants to receive one or two psilocybin doses along with traditional 12-week Motivational Enhancement Therapy (a type of counseling designed to motivate patients to engage with treatment over time). ,

Ten participants were given an initial dose of psilocybin (0.3mg/kg) after 4 weeks of Motivational Enhancement Therapy and 24 hours after their last drink. Results showed that:

  • In the 4 weeks after the very first psilocybin session, participants reported a significant decrease in the number of days they were drinking (from approximately 33% of days to less than 15%), as well as the number of days they drank heavily (from approximately 25% of days to less than 10%),; and
  • 21 to 36 weeks later, participants continued to report substantial decreases in the frequency of their regular drinking days (below 20%) and their binge drinking (below 15%).
source - Pixabay.com

At this point, therefore, the research is very much still in its infancy. But we can draw a few conclusions, including:

  • Psilocybin research into substance dependence treatment has only looked at small participant samples so far, 
  • S some very promising outcomes, however,suggest it may help smokers quit and remain abstinent;
  • There is also evidence that psilocybin may contribute to helping alcohol-dependent people drink – and binge-drink – less frequently; and
  • Much like many existing approaches that target dependence, psilocybin has only been examined as part of an integrated treatment plan, alongside traditional talk therapy approaches like CBT or counselling.

Other Psilocybin Research

Psilocybin and OCD

A few pioneering studies have also explored psilocybin’s potential benefits for those with Obsessive Compulsive Disorder (OCD). OCD is an anxiety-related psychiatric condition where recurring, problematic thoughts or feelings underpin compulsive behaviors in sufferers, sometimes colloquially dubbed ‘rituals’. 

Often, OCD’s intrusive thoughts and behaviors can be hard to treat, but drugs which have had the most positive effects thus far are antidepressants acting on the brain’s serotonin pathways – Serotonin Reuptake Inhibitors (SRIs). Psilocybin studies have stemmed out of a growing interest in the fact that many OCD patients don’t respond positively to SRI treatments, and in 2006 The University of Arizona had approved psilocybin trials with human participants. 

Conducted over four sessions, 9 subjects  took psilocybin four times with a different dose that ranged between very low and very high. Perhaps surprisingly, OCD patients reported a similarly substantial degrees of symptom reduction after 24 hours (ranging from 23-100%) when given low and high doses of psilocybin – in other words, the size of the dose had no effect. This led researchers to suggest that the  results may have been a result of the participants’ expectations, or as the researchers described:

“…the mere artifact of mindset and setting…the contextual expectation of improvement…just by the  distracting psychedelic effects…or a ‘pleasurable experience.’” (2006: 1738)


Psilocybin, Spirituality, and The Meaning of Life

As we look back on the – perhaps unwarranted – stigma around psychedelic use over time, psilocybin’s ‘spiritual’ and mind-altering effects are impossible to ignore. Essentially, the ‘trip’ is a key experiential element distinguishing psychedelics from conventional pharmaceuticals, and part of the reason why research into psilocybin, LSD, and other hallucinogens has been effectively banned. 

So how do participants describe their positive psilocybin experiences? What do we know about the feelings of ‘interconnectedness’, of ‘meaning’ that have only been fleetingly mentioned so far? And how long-lasting an impact does psilocybin have when it comes to well-being?

A fascinating study by Griffiths et al. (2018) has very recently looked at this in greater depth. One of the largest psychedelic studies to date, it focused on 75 participants who took high doses of psilocybin as part of a program that involved meditation and spiritual practices. 

Interested in the positive, enduring trait-level changes that the program might bring about, the researchers administered some volunteers with a low psilocybin dose, and some with a high dose. All participants finished their meditation training, but the effects were most notable in the high-dose participants. 

These subjects described increased feelings of positive emotions such as gratitude, forgiveness, and interpersonal closeness for as long as six months later, suggesting that these healthy psychological changes were indeed enduring. They also reported several other personal, emotional transformations – quantum changes, as researchers describe them (Miller, 2004) – which the low-dose group did not. These included heightened feelings related to:

  • Life purpose and meaning;
  • Death transcendence – overcoming feelings of fear about dying;
  • Religious faith;
  • Coping; and
  • Interpersonal closeness – feelings of being connected to others.
source - Pixabay.com

We will look more closely at these mystical-type experiences a little further on. In particular, we’ll look at what might be linked to psychedelic ‘quantum change experiences’ at the brain-level, and what occurs when we ingest much smaller amounts of psychedelics – a practice known as microdosing


Is Psilocybin Dangerous?

Medical, human studies of psilocybin,like other psychiatric or psychological trials, must meet stringent ethical criteria before they can be conducted. And while we cannot draw definitive conclusions about psilocybin’s very long-term effects at this early stage in the research, it appears – very broadly – to be generally safe.

There are no reports of any major adverse, long-term side-effects in clinical trial settings. And though anecdotal case reports of bad outcomes in recreational users exist (e.g., reports of flashbacks or suicidality), large-scale population studies find no increased risks except possibly in pregnant women or people with a history of psychosis (e.g., Elsey, 2017).  

What the literature does suggest is that psilocybin can occasion some transient physiological and psychological effects in humans, and during dosing sessions, including,

  • Increased heart rate and blood pressure;
  • Headaches;
  • Nausea; and
  • Anxiety during the session itself.

Another common transient side-effect of psilocybin dosing is a general decrease in patient’s cognitive capabilities, including their executive control, memory, and balance. Thus, people using psychedelics could make poor choices or and harm themselves or others if in an unsafe environment.

source - Unsplash.com

What about ‘bad trips’? Subjective psychedelic experiences can vary from ‘life-alteringly positive’ to ‘nightmarish’, depending on the individual in question. Research suggests that this variation may at least partially be related to personality factors, with some Big Five traits being more closely linked to ‘bad trip’ experiences. Individuals high in Neuroticism, most notably, have been shown as more susceptible to experiencing anxiety during psilocybin dosing, more frequently finding them challenging compared to those with low Neuroticism (Barrett et al., 2017). Guidelines for psychedelic research suggest that safe environments and trusted companions may decrease the risk of negative experiences (Johnson et al., 2008).

Evidence from LSD Studies

LSD research

Lysergic Acid Diethlamide (LSD) – acid – stimulates our serotonin pathways in a similar way to psilocybin. Unlike psilocybin, however, it is a lab-synthesized drug. First extracted in 1938 from the ergot fungus, its popularity as a recreational hallucinogen peaked during the 70s when it was more widely distributed as ‘tabs’ which go under the tongue or swallowed. Currently, figures on recreational usage estimate that around 1 in 10 Americans have used the drug at some point. 


LSD May Decrease Depression and Anxiety

The research into LSD’s use as a treatment for mood disorders has centered around its potential role as an alternative to selective serotonin reuptake inhibitors (SSRIs) such as Sertraline (e.g. Zoloft), Fluoxetine (e.g. Prozac), and Paroxetine (e.g. Paxil). SSRIs in turn typically trigger fewer adverse side effects than tricyclic antidepressants – and are considered less addictive over the long term – but they do not help all patients and many people find their side-effects intolerable (Cipriano et al., 2018).

The new research primarily aims to examine the safety and efficacy of LSD as an alternative treatment for patients with anxiety and depressive disorders, and in particular what their therapeutic benefits might be in comparison to existing FDA-approved medication.

The only completed study to days looked at 12 patients with anxiety that was related to a life-threatening disease; diagnostically distinct from Generalized Anxiety Disorder, it aimed to investigate whether LSD-assisted psychotherapy programs would show a significant decrease in their anxiety symptoms. Carried out by Gasser and colleagues (2014), these participants were given two identically-sized oral doses of LSD, 2-3 weeks apart. Most (8 participants) received a 200 microgram dose, and three received an ‘active placebo’ dose of 20 micrograms. Researchers expected this active placebo would have mild effects on the participants, but without any of the hypothesized therapeutic benefits of the larger dose. 

Two months after the psychedelic-assisted therapy, the large-dose (LSD) group showed significant decreases in their anxiety. This same reduced anxiety, of a similar magnitude, was measured up to a year later. But perhaps most interesting is the comparison that researchers made with the 20 microgram (low-dose) group of participants, who actually showed an increase in anxiety-related symptoms at the two-month mark. None of the participants showed any long-term adverse side-effects from taking the LSD. 

For those interested in the finer details of the study, here is an overview:

  • After the 2-month mark, the low-dose group was switched up to 200 micrograms of LSD;
  • When their state anxiety levels were measured at the 12-month mark, alongside the original high-dose group, they showed similar anxiety-level decreases to the group which had been on 200 micrograms the whole time.
  • During interviews after 12 months, the majority of patients reported that the psychedelic experience helped them understand and confront their anxieties better and identify resources to help (Gasser, 2015). 

Last, but not least, both groups were also measured for trait-level anxiety: “the stable tendency to attend to, experience, and report negative emotions such as fears, worries, and anxiety across many situations” (Gidron, 2013). While some trends were observed (trait anxiety decreased in the 200 microgram experimental group and increased in the 20 microgram group after 2 months), these were not statistically significant.


Can LSD Help with Substance Abuse?

At this early stage in contemporary psychedelic research, we have not yet seen any new primary studies on LSD’s usefulness for treating substance abuse. During the 50’s, 60’s, and 70’s, however, numerous trials were conducted into the size of LSD’s impact on alcohol-dependent individuals who were trying to quit. And in 2012, these older studies were compiled and quantitatively analyzed by researchers Krebs and Johansen in a meta-analysis. 

Of the six studies they analyzed, they found robust support for LSD’s efficacy as a treatment for alcoholism – demonstrating, among other things, that the psychedelic roughly doubled participants’ chances of showing improved outcomes compared to those who weren’t dosed.

Other than this peer-reviewed meta-analysis, the LSD research is relatively limited compared to the modern literature on psilocybin. One other intriguing study that shows how LSD enhances our emotional response to music (Kaelen, 2015), nonetheless, is a good example of how new research directions are opening up.

Evidence from Ayahuasca Studies

Ayahuasca research

Traditionally brewed by Amazonian religious and tribal healers as a plant-based tea, ayahuasca is sometimes known as yage, hoasca, or aya. The active ingredient in ayahuasca, DMT, works on the brain’s serotonergic receptors, and the red-brown tea itself has a distinctive, strong taste. For centuries, Amazonian tribes have also brewed ayahuasca tea from vines that prevent the body’s natural DMT breakdown processes.


Ayahuasca in Depression Therapy

At least four major studies support ayahuasca’s possible benefits for patients with depressive disorders. The earliest lab study, conducted in 2015, was carried out on a very small scale with only 6 participants – each of whom had recurrent Major Depressive Disorder (MDD). Each was a diagnosed psychiatric inpatient, currently going through an episode of depression, and each was given a 2.2 mL dose of the drug per kilogram of their body weight (0.3 mg/mL DMT content). Results showed a significant, substantial decrease in the patient’s depression and anxiety symptoms measured at 1 day, 1 week, and 3 weeks after administration (Osorio et al., 2015). 

Building on these trials a year later – in a similarly designed, albeit slightly larger study – Sanches and colleagues (2016) obtained the same results with 17 MDD patients.  Participants averaged over a 50% reduction in symptoms at 3 weeks.

source - Pixabay.com

Another study by Palhano-Fontes and colleagues (2018) examined ayahuasca’s effects on outpatients with treatment-resistant MDD. Using both the Hamilton Depression Rating and Montgomery Åsberg Depression Rating Scales, researchers revealed that ayahuasca-dosed participants showed significant and substantially reduced depressive symptoms compared to a control group (who did not receive any ayahuasca) 7 days after treatment. To date, this particular experiment represents the only randomized controlled study into the impact of a classic psychedelics on patients with treatment-resistant depression. 

These promising results are not limited to clinical, psychiatric patients in a lab, either. As psychedelic studies slowly but surely make headway in the scientific field, we can look at results from larger, real-world volunteer samples too. 

While not as scientifically “controlled”, some ayahuasca research has also used observational techniques to study much larger samples of participants dosed at ayahuasca ceremonies. Uthaug and colleagues (2018), for instance studied 57 volunteers who were attending a ceremony. They used established Depression, Anxiety, and Stress inventories, and attempted to control the timing of the self-report measures.  They found that ayahuasca use predicted significantly decreased depression and stress ratings both over the short term (the next day) and over the longer term (4 weeks later). 

What About Other Classic Psychedelics?

Psychedelic studies are not limited by any means to the three main drugs just discussed. Other classic psychedelics, while less commonly known, have also fascinated researchers and prompted pioneering studies in promising new directions. 

In this section, therefore, we will briefly consider what very early-stage research – some published as recently as this year – has hinted at regarding drugs like:

  • 5-MeO-DMT; 
  • Ibogain; and
  • Mescaline.

5-MeO-DMT

5-Methoxy-N,N-Dimethyltryptamine (5-mEo-dmt) is a DMT derivative – its molecular structure is very similar to the latter, with additional MeO molecules. Found in numerous plant species and the Colorado River Toad, South American shamans have used it for hundreds of years to bring about spiritual experiences. 

To date, there have been no controlled clinical studies on 5-MeO-DMT, so our knowledge is predominantly based on epidemiologic – real world – observations on populations (e.g., Davis et al., 2018a), and structured (but not clinically controlled in a lab) group procedures (e.g., Davis et al., 2018b). 

Primarily, these suggest that:

  • 5-MeO-DMT fosters a similar subjective experience to psilocybin);
  • It may have similar, improving effects on depression and anxiety conditions – 79% and 80% of participants with anxiety and depression (respectively) reported improved symptoms after being dosed (Davis et al., 2018b);
  • As with psilocybin, these were associated with greater mystical experience intensity, spiritual significance, and personal meaning; and
  • Mystical effects may be induced by a fairly light dose of 5-MeO-DMT, comparable to a high dose of psilocybin (Barsuglia et al., 2018). 

Ibogaine

Used in traditional rituals and medicines since the 1800’s, Ibogaine is named for the African Iboga tree and is obtained from its roots. For several decades, it has played a role in opioid addiction therapy within Mexico and South America, with a 2008 study finding more than 3,000 patients had received Ibogaine treatment for opioid dependency or addiction (Alper et al., 2008).

A limited number of clinical studies have investigated Ibogaine’s efficacy – those that do exist are focused primarily on patients’ responses to Ibogaine treatment and centered, as one would expect, in the aforementioned world regions. A general overview suggests that:

  • Ibogaine is an effective treatment for dependence on opioids, especially heroin (Alper et al., 1999; Mash et al., 2001); 
  • It may work by reducing opioid withdrawal symptoms by as much as 50% (Brown and Alper, 2018);
  • It may even be associated with longer-term opioid abstinence – half of the patients studied were abstinent 1 month after therapy, and 20% remained so a year later (Brown and Alper, 2018); and

The psychedelic may potentially be an effective treatment for dependency on non-opiates, such as stimulants and cocaine (Schenberg et al., 2014).

What makes Ibogaine slightly different from most of the psychedelics we’ve looked at thus far is its side-effects: interestingly, it may have quite strong, unpleasant physical impacts on the user. In addition to nausea, dizziness, and tiredness, patients report fewer pleasant experiences when taking Ibogaine than classic psychedelic participants do. Instead, they often report negative emotions, memories, and “feeling[s] of death” (Schenberg et al., 2017).


Mescaline

Naturally-occurring Mescaline, an alkaloid, is sometimes incorrectly referred to as ‘peyote’ – after the cactus from which it is extracted. It is less potent than other common psychedelics; up to 200-400 mg is required for an active dose. It occurs in the small, button-shaped cactus nodes on top of the peyote, which can either be eaten or brewed as a drink – both of these methods have been employed in Native American, Mexican, and South American rituals for millennia. 

The very sparse research into mescaline’s clinical potential suggests that it may help decrease human dependence on alcohol. This limited look at mescaline dates back to the late 50’s and early 60’s, however, from studies which used the drug interchangeably or in combination with LSD (e.g., Smith, 1958; Sherwood et al., 1962). Thus, no trials have focused specifically on mescaline and its possible link with reduced substance abuse or increased well-being.


Non-Psychedelic Hallucinogens

The terms ‘psychedelic’ and ‘hallucinogen’ are often (incorrectly) used synonymously, but the two have different impacts on the brain. Differing impacts entail distinct benefits and risks;hallucinogens that are not classic psychedelics may have more severe withdrawal symptoms and other side effects.

While this guide is focused primarily on psychedelics, there are two non-psychedelic hallucinogens with potentially therapeutic effects that warrant a mention:

Ketamine

Ketamine research

A dissociative anesthetic, ketamine acts on NMDA- rather than serotonin pathways – and reduces sensations of pain. It can trigger ego dissolution, rather like the classic psychedelics already considered. 

  • According to evidence from more than 20 lab studies and 550 participants (which also involved psychotherapy), ketamine seems to have some beneficial impact on participants with psychological disorders. In particular, it may be linked with reductions in depression, cocaine abuse, suicide, OCD, and PTSD.
  • Most studies of Ketamine show results lasting 1 to 7 days, rather than months or years like some classic psychedelics.

Ketamine has been approved in the United States as a prescription anesthetic for decades, and a version of Ketamine called Esketamine received Food and Drug approval for treating treatment-resistant depression in 2019.

MDMA

MDMA research

Methylenedioxymethamphetamine (MDMA) stimulates serotonin release and falls into the ‘entactogen’ class of drugs – it induces feelings of connectedness, empathy, sympathy, and a willingness to open up to and trust others. Unlike most classic psychedelics, and rather like Ibogaine, MDMA is associated with negative (albeit short-term, less intense) side-effects including anxiety and depression.

More than half a dozen experiments have linked MDMA with significant improvements in PTSD, and it is believed this is partially due to the interpersonal effects described above.

General Surveys and Observational Studies on Psychedelics

Until now, we’ve focused primarily on controlled laboratory studies. In this next section, however, we will zoom out to consider research on psychedelics outside of the lab.  After all, these comprise a large bulk of existing ‘real-world’ findings, where dosages, participant populations, and settings can vary drastically.

Controlled psychedelic dosing in a laboratory setting is one thing, and observing their use in day-to-day life is completely different. Observational studies and surveys may not be as methodologically strict as experiments, but they can demonstrate impressively similar results. 

To illustrate, a mix of survey and observational data have indicated that: 

  • People who report using psychedelics also tend to report less psychological distress and fewer suicidal thoughts (Hendricks et al., 2015);
  • Fewer negative psychological symptoms (depression, anxiety, and disordered eating) may be related to heightened spirituality and emotional coping after psychedelic use (Bouso et al., 2012; Lafrance et al., 2017);
  • Psychedelics may help treat tobacco dependence (Johnson et al., 2017; Garcia-Romeu et al., 2017), alcohol and drug abstinence (Hendricks et al., 2014), problematic substance use, and stress (Thomas et al., 2013); and

Psychedelics may be linked with reduced likelihood of violence in relationships – this latter study circles back to the suggested role of psychedelics in aiding emotional regulation (Thiessen et al., 2018).

4. How do Psychedelics Improve Well-being?

How Psychedelics work in the brain

So, how do transformative, quantum change experiences impact the brain? How does serotonin – which we can boost through exercise, certain snacks, and even massage – lead to lasting improvements in our psychological well-being? 

The short answer is that we’re still not 100% certain. However, research indicates that psychedelics work at numerous levels in the brain, starting with lone neurons and moving up to the connections between distinct brain levels (Carhart-Harris et al., 2019). 

Perhaps an easier way to understand these dynamics is to look at what happens when psychological disorders take their toll. 

Broadly: 

  • Well-established psychiatric studies show that many mood disorders – depression, anxiety, OCD, and so forth – are linked to neural degeneration or damage in particular brain regions; 
  • This negatively impact the ability of neurons to interact with one another, which they do by releasing neurotransmitters such as serotonin;
  • Sometimes, the performance of these connective (serotonergic) pathways is precisely what psychedelics seem to enhance; and
  • Often, they appear to do this by changing the makeup of neurons themselves, or working on the pathways at a higher level.

While the research is by no means definitive on this point yet, one of the primary links between psychedelics, well-being, and cognition is that psychedelics may in fact enhance communication between our brain’s cerebral ‘thinking’ and more emotional ‘well-being’ regions. 


A Closer Look at Serotonin

What, then, occurs at the cellular level when someone takes a psychedelic? To look at this in more detail, we need to ‘zoom in’ to the synapses – or connections – between neurons.

Short-Term Psychedelic Impacts

Very succinctly and in very simplistic terms, certain neural cells release serotonin (5-HT) where they end. The ‘start’ of the next neural cell – which it aims to communicate with – is dotted with serotonin receptors (specifically, these are 5-HT2A receptors). As their name suggests, these receptors are where serotonin binds, and when it does so, the electric and magnetic signals are activated in this subsequent neuron. In other words, the neuron ‘fires’.

Classic psychedelics such as psilocybin, LSD, or ayahuasca, are also capable of binding with 5-HT2A  receptors – they are serotonin receptor agonists. Rather than triggering the normal, steady pattern of firing in this (second, connecting) neuron as serotonin would do, studies have revealed that a unique pattern of desynchronized firing may occur instead (Riba et al., 2002; Muthukumaraswamy et al., 2013). Rather than the more usual happiness that exercise or a sugary snack might bring about, the result is a hallucinogenic experience (Gonzalez-Maeso et al., 2007).

‘Non-classic’ psychedelics such as MDMA and Ketamine also impact neural communication, but do so in a slightly different way:

  • MDMA, for instance, stimulates serotonin release and increases its overall prevalence; and
  • Ketamine works on NMDA rather than serotonin receptors.


Potential Long-Term Psychedelic Impacts

It is important to re-emphasize that psychedelic research is still very much in its infancy. However, there is evidence suggesting that classic psychedelics may also have enduring changes on neural interactions – changing the very structure of the neurons themselves to enhance their connectivity long after the experience is over. 

This has been observed in rats and fruit flies, for example, whose neural connections (and receptors) increased within 24 hours of being dosed once with various hallucinogens (Ly et al., 2018). 


Larger-Scale Impacts

Given that billions of cells make up the human brain, we can zoom out once more to observe much larger-scale changes in our neural activity when we take psychedelics. 

So, what underpins the transcendental experience – the feeling of being ‘outside oneself’? We can break this down into a few different changes that occur: 

  1. Decreased ‘resting state’ activity: Interestingly, the ‘stimulated connectivity’ between individual neurons just described can also be accompanied by decreased activity in larger ‘resting state’ brain regions – one of which is the ‘default mode network’. Aptly named, the default mode network is related to ‘resting, default’ thoughts: about oneself, other people, the past, and the future. What we ate for breakfast, thinking about how we feel, and so on. 
  2. Increased connectivity: Simultaneously, psychedelics may enhance communication among these ‘resting state regions’ (the default mode network included) and other areas of the brain, above and beyond what we normally experience in day-to-day life (Carhart-Harris et al., 2016; Palhano-Fontes et al., 2015; Muller et al., 2018).
  3. Ego Dissolution: These “marked changes in brain blood flow, electrical activity, and network communication patterns” (Carhart-Harris et al., 2016: 4853) have been linked with feelings of ‘being outside themselves’ and ‘feeling interconnected with the world’.
source - Greg Dunn, Will Drinker, and Brian Edwards at mymodernmet.com

Psychedelics and Emotions

Ego dissolution, feelings of self-transcendence, and interconnectedness are quite clearly not the only subjective elements of a psychedelic trip. Indeed, research on the ‘spiritual’, ‘mystical’ effects of classic psychedelics has tried to understand what else might make the quantum change experience so profound – to the point where it can engender long-term psychological improvement.

In a nutshell, and thus far, we have at least two other research-based examples of how classic psychedelic experience are so unique and potentially transformative:

  • First, fMRI studies show psilocybin may heighten our brain’s (amygdala-based) response to other people’s emotions – this increased activity is actually the reverse of what happens when depressed patients are treated with SSRIs (Roseman et al., 2017); and
  • Second, SPECT imaging studies have shown that more blood flows to our brain’s mood regulatory regions when humans ingest ayahuasca. As a note, this latter study by Sanches and colleagues (2016) is the same one described above on patients with major depressive disorder. 

In the next section, we consider more about the transformative experience itself – what is mystical, spiritual, and potentially life-changing about it? What substances bring about lasting, quantum change?

What is the ‘Transformative Experience’?

We don’t commonly see ‘medical’ and ‘mystical’ mentioned in the same sentence – especially not in clinical settings. The two seem like strange bedfellows, and yet, the mystical or spiritual elements may be exactly what is so ‘transformational’ about psychedelic experience. At least, those who report mystical experiences are also more likely to demonstrate increased well-being and decreased depression (Ross et al., 2016; Barrett and Griffiths, 2017). 

Quantum change experiences have been described numerous ways throughout the literature, by theologians, psychologists, and Greek philosophers – arguably, the literature is extensive and spans millennia (James, 1902/2012; Stace, 1960a). A more modern description, however, details the mystical experience as:

A sense of the unity of all people and things, accompanied by a sense of reverence, and the authoritative truth value of the experience (e.g., Stace, 1960a in Johnson et al., 2019).

This overlaps significantly with participants’ descriptions of quantum change, a much newer concept. Compared to mystical experiences, though, quantum changes have a key distinctive element – they also encompass substantial behavioral change, which is abrupt. While it is almost instantaneous, this behavior change perseveres in a distinct way from incremental, ‘regular’ change (James, 1902). 

So, according to researchers, we can summarize quantum change as:

Sudden, distinctive, benevolent, and often profoundly meaningful. Said to result in personal transformations that affect a broad range of personal emotions, cognitions, and behaviors (Miller and C’de Baca, 2001; Miller, 2004

Two types of quantum change experience have even been proposed – a good example of how fascinating the phenomena are to researchers, these are (James, 1902; Stace, 1960; Maslow, 1968; Miller and C’de Baca, 2001):

  • Mystical-type quantum changes – sometimes called conversion, religious, peak, or transcendental experience; and
  • Insightful-type quantum changes – which emphasize the importance of sudden, compelling personal insights into life problems or circumstances.


Psychedelics Trigger Transformational Experiences…

It may seem obvious – psychedelics such as psilocybin, LSD, and ayahuasca stimulate transformational experiences. Since the famous first ‘Good Friday’ experiment, however, researchers have refined the scientific study of mystical experiences and now use much more rigorous, empirical approaches than before. 

To illustrate, Pahnke’s (1962) Good Friday experiment is well-known for being the first study of psilocybin’s mystical effects. It is possibly just as well-known for its flawed methodological approach, but nonetheless, represents a good first start in this area of research, revealing that 60% of psilocybin-dosed participants reported a mystical experience.

Moving forward, we now see much more rigorous studies taking place in the field, but the findings still point to the same thing: psychedelics trigger transformational experiences.

source - Unsplash.com

Specifically, we know that:

  • When dosed with psilocybin, 78% of participants reported mystical experiences. More precisely, they scored the maximum possible score on the scientifically-validated Mystical Experience Questionnaire (MEB), and this remained unchanged for 76% of participants 2 months later (Griffiths et al., 2006). Over a year later, 67% of these participants considered the psilocybin experience among the five most spiritually significant experiences of their lives.
  • A higher psilocybin dose may increase the likelihood of a mystical experience (Barrett and Griffiths, 2017; Carbanaro et al., 2018). For example,Griffiths et al., (2011) gave participants placebos as well as higher doses of psilocybin on different weeks (up to 30mg/70kg). When given placebos, 23% of participants scored the maximum possible Mystical Experience Questionnaire 30 (MEQ30) score – by the highest dose, this figure rose to 77%.
  • LSD may have a similar, but smaller, ‘mystical experience’ impact. High LSD-dosed participants scored much higher (55%) on the MEQ30 than low-dose participants, who scored less than 5% on average. Fewer than 20% of these high-dose LSD participants described having a ‘complete mystical experience’, however, suggesting that the mystical experience was less pronounced than it was for participants in psilocybin studies (Liechti et al., 2017).
  • Finally, from Griffiths et al.’s (2018) study above, we have preliminary evidence that mystical experiences may be more likely when psychedelic experiences are combined with spiritual practices such as meditation.


Transformational Experiences May Be Linked With Positive Outcomes

It is always worth re-emphasizing that the studies described are recent and small. Nonetheless, as noted, there are some early indications that the mystical experience is linked to the well-being effects that we see in various psychedelic treatments. 

Decreased depression and stress symptoms in ayahuasca study participants, for example, are predicted by the extent of ‘ego dissolution’ they experienced during the ceremony (Uthaug et al., 2018). Bogenschutz and colleagues (2015) have found a similar relationship between higher mystical-type experiences and decreased alcohol use, while Johnson and colleagues (2014) have revealed significant correlations between participants MEQ scores and their (lower) smoking cravings. And lastly, Garcia-Romeu et al. (2015) found participants with stronger mystical experiences were more likely to successfully quit smoking.

5. Warnings and Weaknesses: What We Don’t Know

When talking about psychedelics, then, what don’t we know? What can we expect next, as the psychedelic research renaissance gains momentum? This section considers some uncharted territory in the field, as well as some of the red flags that have popped up. 


Study Weaknesses

Before looking at more general study weaknesses, there is one critical shortcoming shared by all the studies in this review – almost certainly none of them have implemented completely effective double-blinding. We have mentioned:

  • Open-label studies – where both participants and researchers know what is being taken (e.g. Carhart-Harris et al., 2016a);
  • Single-blind studies – in which researchers alone have this information (e.g. Grob et al., 2011); and
  • A range of observational studies, which use a variety of methods but generally record what people are doing or experiencing in the real world.

Double-blind research methodologies, in contrast, are unique because neither researchers nor participants know which group the latter are in. Designed to minimize placebo effects and various other influences, they are considered the gold standard when it comes to reducing bias.  

Several studies have implemented double-blinding procedures–that is they have withheld information from both the experimenter and the participant about whether a placebo or an active dose of psychedelic is being administered. However, even when this information is “kept secret”, the nature of psychedelics generates some unique complications. Namely:

  • Psychedelics have rapid, obvious psychological effects – it can be hard not to tell that a participant has been dosed, even with a rigorous double-blind procedure; and
  • Convincing placebos or control conditions are still, thus, incredibly elusive.
source - Unsplash.com

For those interested in research methodology, scientists such as Griffiths and colleagues (2016) are attempting to overcome or mitigate these hurdles through study design. In the psilocybin study covered earlier (on anxiety and depression in cancer patients), the researchers tried to reduce expectancy biases by telling participants they might get a range of doses of the drug. In reality, one was a very low-dose session.


Other Weaknesses

Two more shortcomings of psychedelic research stem from the fact that thus far most studies have only looked at small groups of unique participants:

  • Unbiased Sampling – As mentioned, most psychedelic studies so far have looked at existing clinical samples – patients with diagnosed cancer, anxiety, depression, and so forth. Even for the few studies involving informed, healthy participants, we can assume only those with a certain level of openness are willing to volunteer.  The same may apply for surveys of the general population – some of us are simply less interested in new, spiritual experiences than others.
  • Limited Sample Size The single biggest lab sample used in modern psychedelic research thus far had only 75 people, which poses a clear limitation on our ability to generalize the results. Looking at more participants in a controlled lab setting will allow us to gain more insight into the impacts of different dosages, effects on individuals, and more – in short we can try more study designs and use more randomized groups of participants (dos Santos et al., 2016; Mahapatra & Gupta, 2017; Patra, 2016).”


Warnings

Some of the psychedelic research findings are promising indeed – but invariably, they are precisely that:  modern, scientific research findings. They adhere to stringent safety, ethical, and professional standards that are designed to mitigate danger, injury, or psychological damage to participants. 

Here are some well-established dangers of psychedelics, and some lesser-known risks.


Bad Trips

‘Bad trips’ – as they are colloquially termed – describe unpleasant, stressful, scary, or dangerous experiences that can occur while individuals are under the influence of psychedelics. They are not always limited to an unpleasant subjective experience, but can sometimes exacerbate existing mental conditions – even possibly triggering psychosis or the need for long-term therapy according to some case reports (Carbonaro et al., 2016; Nielen et al., 2004). 

Bad trips are more likely if an individual takes psychedelics alone or in an unsafe environment – for this reason, all recent experiments have involved professional therapists who build a trusting relationship with participants and guide them through the experience. Interestingly, individuals with high Neuroticism may also be more prone to bad trips (Barret et al.,, 2017).


Physical and Cognitive Side Effects

Many of the described studies mention an absence of ‘adverse, long-term side effects’. However, lesser and more transient side effects can and do occur which must be safeguarded against, including (Johnson et al., 2008):

  • Elevated heart rate and blood pressure;
  • Acute anxiety or dysphoria (e.g. depression, unease, agitation) after dosing;
  • Nausea or headaches; and
  • Temporary cognitive and perceptual impairment (e.g. altered vision, poor coordination).

Rising to the challenge, scientists at John’s Hopkins have made some first steps toward measuring these side effects. The Challenging Experiences Questionnaire  (2016) is the first purpose-designed psychometric assessment for measuring psychologically difficult experiences from psychedelics, and includes items such as:

  • “I was afraid that the state I was in would last forever”;
  • “I experienced a decreased sense of sanity”; and
  • “Experience of antagonism toward people around me.”

In summary, we know what we don’t know – and we can sum it up quite nicely. 

  1. Several surveys do suggest that psychedelics alone – without therapy or guidance – can improve mental disorders, and the chances are higher if a safe supportive environment is provided. But, because there are no experiments on this, it is something we do not know for sure. (It could be, for example, that the kind of people who try psychedelics just tend to be more open-minded or easy-going, or for some other reason tend to report better outcomes than others.)
  2. We do know that without supervision, certain hallucinogens (including psychedelics) can be harmful. MDMA, for example, can have a rebound effect that causes worse moods for several days.
  3. We do not know what kind of people are more or less able to benefit from psychedelics; and
  4. We do not know for sure whether some people are more vulnerable to their negative impacts, though people high in neuroticism may be more likely to have a difficult trip.

In the last part of this resource, we take a look at one of the newest, pioneering areas in psychedelic research – microdosing.

6. The New Frontier: Microdosing

Could we potentially reap psychedelic benefits without the trip? Enjoy greater creativity without the ‘vision quest’, or reduced anxiety without a quantum change? While very crudely put, these are the kind of informal questions that underpin the search for a ‘happy medium’ with psychedelics. 


What is Microdosing?

Microdosing involves administering a subtherapeutic dose of a psychedelic, one that is so small that no psychedelic effects can be felt. It is a growing area of interest for both commercial and academic lab researchers, including the Imperial College of London and Leiden University. 

At this point, findings are unclear. On one hand, remember that early lab findings suggest that very low subtherapeutic doses of psychedelics do not lead to positive, enduring outcomes (Garcia-Romeu, 2016; Willemsen, 2019).

However, a handful of first-hand reports, minimally-controlled studies, and surveys find that many people believe microdosing helps them. For example:

  • A systematic survey of 98 participants by Polito and Stevenson (2019) revealed self-reported psychological functioning was improved on the days they microdosed. Of these, 63 participants also reported their mood, attention, well-being, personality, creativity, interconnectedness, and mystical experiences for the survey, which was carried out over 6 weeks. These participants felt less depression, distractibility, and stress, as well as higher absorption and neuroticism. Interestingly, participants beliefs about what they thought would change differed from what they later reported as actually changing, suggesting that improvements were not solely due to expectations.

A 2018 study of 38 volunteers from a microdosing event  provided some evidence that people performed better at creative tasks after microdosing than they did before (Prochazkova et al., 2018). This study, however, did not include any placebo condition that would allow comparison between groups, and all participants knew they received the microdose.

source - Unsplash.com

So why might microdosing not have therapeutic benefits? While we don’t know for certain, the answer may come back to the quantum change effect – the transformative experience itself may be what leads to persistent change. 

On the other hand, it may be that we simply don’t understand microdosing yet. First, these suggestions (that microdosing has no real beneficial impact) are primarily drawn from studies which only used very few microdoses – one or two at the most (Garcia-Romeu, 2016). The only study to have used several (10) microdoses over several weeks looked only at memory and attention, and did not examine well-being, depression, substance use, or other variables often linked to microdosing reports (Willemsen, 2019). 

This is linked to the second point, which is that microdosing may work over the longer-term, by slowly changing serotonin pathways in the brain and having a more delayed overall impact on the integration between brain regions. (Traditional SSRI treatments for anxiety and depression, for example, often take daily dosing over weeks to show effects.) In the absence of longitudinal study data, therefore, it is impossible to draw any conclusions about how effective microdosing is at this point.

7. What’s Next for Psychedelic Research?

In this comprehensive guide to psychedelic research, we have seen more than a few promising new findings. There is indeed evidence that suggests psychedelics such as psilocybin, LSD, and ayahuasca can play a role in therapy by:

  • Treating alcohol dependence;
  • Supporting smoking cessation;
  • Reducing symptoms from depression-related psychological disorders; and
  • Lessening anxiety disorder-related symptoms.

More evidence also points toward positive potential impacts of psychedelics on:

  • Enduring positive affect;
  • Prosocial behavior and interconnectedness;
  • Feelings of spirituality; and
  • Various enduring changes in personality traits.

Perhaps most intriguingly, we’ve looked at evidence that suggests psychedelics may have their impact in a particularly singular way – through instantaneous, transformative quantum change effects that approved pharmaceuticals simply don’t evoke. And looking forward to the future, we can expect a lot more fascinating research to come.

The following figure–outlining the 4 parts of the Mystical Experience Questionnaire (MEQ30)–is a nice overview of how these are measured in modern empirical research: