Day 1: DMT Psychoeducation

Today’s preparation involves the following tasks:

  1. Task 1: Complete a short ‘pre-preparation’ survey (5 minutes)

  2. Task 2: Read the psychoeducational material (20 minutes).

  3. Task 3: Download and read the ‘Strategies for Reducing Alcohol Consumption’ manual (30 minutes)

  4. Task 4: Complete a few short reflections in your journal (5 minutes)

TASK 1: PRE-PREPARATION SURVEY 

Please complete the pre-preparation survey. This should only take about 5 minutes to complete and will ask you about how you are feeling today, specifically in relation to how prepared you feel for your upcoming DMT experience.

You can find the pre-preparation survey here. 

TASK 2: PSYCHOEDUCATION

Please read the following psychoeducational material about DMT and the upcoming UNITy trial. If any questions or concerns arise when reading this material, make a note and bring these ideas to your preparation interview. 

  • N,N-Dimethyltryptamine (DMT) is a powerful psychedelic drug. The molecule is structurally quite similar to other psychedelics (including psilocybin or ‘magic mushrooms’), and together they form a group of molecules called ‘tryptamines’. These molecules bind to serotonin receptors in the brain to induce psychedelic effects. However, their effects and the ‘trip’ they produce can be profoundly different. DMT produces a very short, very intense trip.

  • DMT is a naturally-occurring molecule that is found in a wide variety of plants and animals. However, the form that we are using in the study has been synthesised in a lab. It is structurally identical to naturally-occurring DMT, in a formulation that makes it safe and stable for injection. This synthetic form is preferable because it is more sustainable, accurate to dose and guaranteed to be free from contaminants.

  • The nature of a DMT-induced experience is extremely variable, with the intensity and quality of the experience depending largely on the dosage and individual sensitivity.

    In its typical manifestation, a DMT 'trip' is characterized by striking visual hallucinations that can be imbued with a profound sense of significance or deeper understanding. These experiences often transcend ordinary aesthetic perceptions, leading to encounters with intricate geometric patterns, shifting landscapes, and even entities that seem separate from oneself.

    DMT has the potential to invoke a vast spectrum of emotional responses. These can range from overwhelming euphoria to deep introspection, and at times, even encounters with what appear to be external consciousnesses or beings. Such experiences, while profoundly subjective, are often reported to carry a sense of objective reality.

    One of the more remarkable effects of DMT is its capacity to alter the perception of time and space. Moments can feel like eternity, and spatial relations can become impossible to comprehend, thus ushering users into seemingly new dimensions.

    DMT can also induce substantial shifts in the perception of self and personal identity, sometimes leading to experiences of ego dissolution or unity with the universe. This can result in deeply introspective insights and transformative experiences, often imbued with a spiritual or mystical quality that can linger long after the effects of the drug have worn off.

    In addition to these intense visual alterations, DMT can also produce auditory hallucinations. These can range from subtle alterations in the perception of sound to hearing complex auditory phenomena, like music or voices, that aren't present in the physical environment.

  • Like most other psychedelics, DMT primarily affects the serotonin receptors in the brain. Activation of serotonin 5-HT2A receptors is thought to underlie the profound visual and/or auditory distortions experienced under DMT.
 It's not fully understood why action at the 5-HT2A receptor causes psychedelic effects, but it could have something to do with where they are found in the brain. 5-HT2A receptors are mostly found on neurons responsible for integrating information across layers of the cortex. DMT binding on these receptors alters their usual firing pattern, which may, in turn, have effects on cognition and perception.

    Current leading theories claim that psychedelics make the brain more ‘chaotic’ compared to idle, resting consciousness. However, this could also be a result of psychedelics changing the internal tasks that people are attending to, such as visual or emotional processing.

    We also know that like other psychedelics, DMT reduces alpha waves, which occur in sober states when we pay attention to visual information. More uniquely among psychedelic compounds, DMT also induces fast gamma spikes in the brain’s electrical activity, which we also see when people are in REM sleep. It has been speculated that these electrophysiological changes may underlie the immersive, visionary character of DMT experiences.

    
DMT is also unique among psychedelics because of its action at the sigma-1 receptor. However, the contributions of this receptor to the DMT experience are not well understood, as action at the sigma-1 receptor alone doesn't produce psychoactive effects.

    
Finally, unlike other psychedelics, DMT is cleared from the brain extremely quickly resulting in an extremely short trip.
 As our brains may naturally produce DMT in extremely small quantities, it's been suggested that our bodies have evolved to become extremely efficient at breaking down DMT in order to prevent our naturally occurring levels of DMT to rise to levels that could affect consciousness. This, however, is entirely speculative.

    In the longer term, DMT, like other psychedelics, is thought to have long-lasting positive effects on the brain. DMT has been shown to increase neuroplasticity, and reduce inflammation. While the implications of this have yet to be fully uncovered DMT may improve cognitive processes such as memory, attention and mood by increasing the brain’s ability to adapt to change and facilitating the maintenance of healthy neurons.

  • No. Although DMT is one of the main psychoactive ingredients in ayahuasca, ayahuasca is a brew created from a combination of plants that contains many other ‘ingredients’ and impurities. DMT is the ‘pure’ form of the drug, meaning its effects are much more intense.

    Ayahuasca is traditionally extracted from the plant Psychotria viridis, which contains DMT. However, the body naturally (and very rapidly) breaks down DMT with enzymes in the stomach and liver, which prevent its ‘psychoactive’ effects. Therefore, ayahuasca is also brewed with an extract called Banisteriopsis caapi, which contains proteins that block these enzymes in your body from breaking down DMT.

    In contrast, the drug we are using in the study is pure, synthesised DMT, which we will dose intravenously. This allows the DMT to bypass the problems associated with those enzymes that break down the DMT.

    It is therefore very different to ayahuasca and its effects will be more intense and short-lasting.

  • Synthetic ‘street’ DMT usually comes in the form of a white, crystal power, which can be smoked, vaporized, injected, or snorted. Its purity is often unknown.

    For the UNITy Project, we will use a pharmaceutical-grade DMT, which participants will be administered via an intravenous tube at a highly controlled infusion rate. This allows us to standardise the drug dose and timing of effects far better than the alternative methods of consumption.

  • Synthetic DMT (like we will be using in the study) kicks in almost immediately after infusion, with effects felt within a minute or two.

    The intensity and duration of a DMT trip depend on several things, including dosage, method of dosing and, person-to-person differences.

    For the UNITy trial, we will be using the IV infusion method. We will infuse the drug for 10 minutes. After the infusion stops, the effects will take a few minutes to wear off, meaning the effects of the drug will generally be felt for around 30 minutes, but with the most intense ‘peak’ for around 10-15 minutes during the infusion.

  • Previous research has demonstrated the profound effects that psychedelics can have on mental wellbeing. However, these have typically focused on psilocybin (magic mushrooms) and lysergic acid (LSD), which last a long time and are typically combined with a form of psychological therapy. The brain effects and therapeutic effects of DMT are still an under-researched topic. In fact, our study will be the first (and largest) fMRI study to examine how DMT induced-brain changes might change heavy drinking behaviour and general mental health.

    DMT is unusual compared to other psychedelics in that it is very short-acting. This is one of its key strengths from a research and medical perspective. Its rapid and brief effects mean we can directly examine brain changes before, on and after the drug in a single session (less than 1 hour, vs. a day or more). We will learn how the drug changes conscious experience at the brain-level and see if we can predict longer-term outcomes from these brain effects. If similar, or even greater changes in outcomes of interest can be achieved with a 20-minute DMT trip vs. an 8-12 hour LSD trip, this would be very useful from a clinical standpoint, as people could have a therapy session within a much shorter time-window.

  • This is an experimental study and there are no immediate guaranteed benefits, other than the knowledge that you are contributing to progress in science and mental health. By participating in the UNITy study, you will be helping science which will push forward our understanding of the brain and behaviour and potentially allow us to maximise the benefit of psychedelic drugs for therapy and general wellbeing in the future. If you would like, we can send you a picture of your brain scans to keep.

    There are some possible, but non-guaranteed benefits. In animal studies, psychedelics like DMT have been shown to promote neuroplasticity - the capacity of the brain to change and adapt. This effect is thought to underlie its potential for substantial and non-specific improvements in the lives of both mentally healthy and unhealthy people. This may have implications for improving general wellbeing, as well as facilitating treatment for people suffering from addiction and mental illnesses such as depression and anxiety. Psychedelics have even been used to alleviate the existential distress that some patients with terminal illnesses experience. However, the extent to which DMT does these things in humans remains unknown. We are not assessing the efficacy of a treatment, but are looking at the brain and behavioural effects of DMT to understand how future treatments might look and work.

    In previous studies, psychedelic substances have been suggested to enhance our feelings of social connectedness and well-being. In a study from Johns Hopkins University, participants who had a ‘mystical or ‘spiritual’ experience during a psychedelic trip described it as one of their most meaningful and spiritually significant life experiences. Following this experience, there were sustained positive changes in life satisfaction, purpose, and meaning.

    Please note: there is no guarantee that you will receive these (or any other) long-term benefits from DMT in our study. Also, remember you will only have a 25% chance of getting DMT.

    What is also currently unknown is whether the changes in perspective and mental wellbeing people report after taking DMT are because of the direct effects of the drug on brain receptors, or due to the subjective experience itself and circumstances in which it is taken. We hope to answer some of these unknown questions in our study.

  • As with any psychological study, our first and foremost priority is to ensure the entire process is as safe as possible.

    Various studies have demonstrated the safety and efficacy of drugs such as DMT. Compared to other drugs (e.g. alcohol, cocaine, heroin, cannabis, tobacco) DMT is very non-toxic. This is partly because the amount of drug that is required for a trip is very small. We have a rigorous screening process to ensure that only suitable candidates receive the drug. Because there may be unintended side effects for people with different physical or mental health problems or taking other medications, it is vitally important that you disclose all of these to the study team.

    We are using only medical-grade DMT that has been rigorously safety-tested by our licensed supplier. The intravenous administration of drugs will be done by an experienced professional and you will have the support and care of an experienced team of researchers, clinical psychologists and medical professionals to ensure that the entire process is as safe as possible. There is no evidence to suggest that DMT is toxic or addictive.

    Since 1994, DMT has been administered to ~100 people (~330 doses) within the research setting. A clinical trial by Small Pharma (the drug supplier) and Imperial College London is currently investigating the effects of the exact form of DMT that we will be using in depressed individuals. A regulatory approved Phase 1 trial by Small Pharma showed that this drug did not cause serious side effects in healthy volunteers who had never taken a psychedelic before.

    The same group has recently shown that the drug is safe and did not cause any serious side effects. However, better-controlled, large-scale research with DMT is needed, particularly with a focus on how it works, and why individuals have different responses to it. This is one reason why we are carrying out the UNITy project.

    Remember, a controlled laboratory setting is one of the safest environments to explore psychedelics and you are among a supportive team of qualified professionals to ensure your safety and comfort throughout the entirety of the experience.

  • DMT is one of the most powerful hallucinogenic drugs we know of. It’s very short-lived but very intense. Most people will never experience such a radical and sudden shift in perception and state of mind as on DMT. This experience can lead to important new insights about yourself and the world and some people describe it as being the most personally meaningful and profound experience of their life. However, such a sudden change in perception can be challenging for people who are not used to or expecting it. In the psychedelics world, we call this ‘ontological shock’. Being cast into a completely altered psychological space can feel like the rug has been pulled out from underneath you.

    By knowing what to expect, being open to whatever the experience brings and knowing how to deal with negative emotions and thoughts that may arise, you will be able to better navigate any challenges during your trip:

     When the drug is starting to take effect, people can feel an intense buzzing or ‘rushing’ sensation. Some people describe this like being blasted off in a rocket. Some like this feeling, for others, it can cause anxiety. If so, remind yourself that it is to be expected and will only last for a short while.

    When the drug is reaching its peak, you will likely see, hear, and feel things that are not really happening, but can seem very real. You might have thoughts that you have never had before, see and feel things you can’t describe, or feel like you’re in another world.

    You may feel completely disconnected from your body, or feel like your body has ceased to exist and become one with its surroundings. These feelings of ‘loss of the self’ can cause some people to worry that they have died or ‘gone too far’ and irreversibly altered their brains. Do not worry, this will not be the case. Nobody has ever died due to DMT and there is no chance of ‘overdose’ here. Equally, although your thoughts may seem completely different to normal, everything is only temporary and you will return to normal once the drug wears off.

    If you find yourself worried about this, or experiencing these thoughts, just notice the thoughts, do not judge or attach undue weight to them and remind yourself that it is just the drug and it will pass.

    People often experience time dilation or loss of a sense of time. It might therefore feel like you have been in the trip for much shorter or much longer than 15 minutes, or that you are unable to keep track of time at all. Again, this is very normal and you will only receive drug for 15 minutes before we stop the infusion and the effects start to wear off.

    Some people report interacting with other ‘beings’ that may be animals, aliens or other entities. You may find such beings scary at first. If so, remind yourself that they are a product of your mind and the drug and it is likely that represents something important to learn from. If you encounter such entities, be curious. Ask them questions. A good question to ask them is ‘What can you show me?’

    Some people might re-experience past events or find that past emotions or thoughts arise on DMT. There are some anecdotal reports of past emotional trauma resurfacing on the drug, although not in scientific studies. It is for this reason that we asked you to tell us about any past experience of trauma or mental health problems before taking part.

  • Research indicates that DMT has a wide range of effects, but it is generally considered safe and well-tolerated in healthy individuals (Timmerman et al., 2019; DeSouza et al., 2022). Studies also confirm reports from recreational users of profound and immersive hallucinations at high doses (see 'What does DMT feel like', above).

    There is some research showing that DMT alters the frequency and organisation of brain waves, as measured with EEG. We are primarily interested in how it alters the connectivity between different brain regions using fMRI.

    There is some evidence that DMT is associated with therapeutic improvements in depression and alcoholism, although these studies have used ayahuasca rather than pure DMT (see Więckiewicz et al., 2022 for a review). This is why it is so important to do studies with pure, synthesised DMT. It is also being investigated for potential uses in epilepsy, Parkinson’s disease, Alzheimer’s and multiple sclerosis.

  • To take part in the study, first, you must complete a thorough screening with a member of the team to check you are eligible. You will also have a chat with a qualified clinical psychologist to check your suitability to participate. We will then ask you about your mood, momentary thoughts and wellbeing using an App we will ask you to download onto your phone. You will use this app on your smartphone to provide responses as soon as you receive a notification to complete them. This will be several times a day, taking 1-2 minutes each time.

    This study will consist of 3 separate visits to our UCL lab across a period of 2 weeks, each of which will last approximately 4.5 hours.

    During Sessions 1 and 3, you will undergo questionnaires, psychometric tests, and brain scans (fMRI) while watching a film. We will also address any questions or concerns you may have, ensure your comfort, and inquire about your expectations before your next visit.

    Session 2 will be the ‘dosing day’. It will include similar biometric and psychometric tests, but this time you will receive DMT, D-cycloserine, lisuride, or placebo. Before we begin your infusion, we will ask you some questions to check you are psychologically and physically ready for the infusion. You will need to fast for 4 hours prior to attending this session. In addition, an ‘integration interview’ will take place in which we discuss your experiences during your infusion with you. At the end of the day, we will book you a taxi home.

    After the final session, you will continue to log your mood and thoughts and answer some questions daily for 2-weeks via the app.

    Once the follow-up period is over, you will be sent questionnaires about your dosing experience and current well-being at 1, 3, 6 and 9 months.

    More detail on what each session will involve can be found in the information sheet, and we are happy to answer any other questions you may have about the procedure should you decide to volunteer.

  • After your DMT experience, you will have the opportunity to describe your experience (in full) with a member of our participant care team, who will be able to offer support for various aspects of your experience.

    The next day, you will have a ‘check-in’ telephone call with a member of our participant care team to see how things are going.

    You will also receive a 7-day integration course that can be completed at your own pace. This course will allow you to reflect on your experiences and initiate your integration process.

    If you would like additional support following these integration calls, our team will be able to refer you to suitable integration groups.

TASK 3: ‘STRATEGIES FOR REDUCING ALCOHOL CONSUMPTION’

Please download and read our ‘Strategies for Reducing Alcohol Consumption’ manual.

TASK 4: REFLECTIONS 

In your journal, spend a few minutes reflecting on the following prompts:

  1. Write down a list of words to describe how you are feeling about your upcoming DMT experience.

  2. What would you like to build, create or nurture in your life?

  3. Start to think about your intention for this experience. In other words, why do you want to have a DMT experience? What do you hope to learn from this experience? What do you hope to explore? 

    • Having a clear intention can serve as a guiding idea during your DMT trip, providing a safe thought to return to if needed