Psychedelics for Treating Mental Disorders | Dr. Matthew Johnson
Dr. Matthew Johnson, Ph.D., from Johns Hopkins, discusses medical research on psychedelics like psilocybin and MDMA for treating depression, addiction, and trauma. He details clinical trial protocols, potential dangers, and future legal landscape.
Deep Dive Analysis
18 Topic Outline
Defining Psychedelics and Pharmacological Classes
Hallucinations, Synesthesia, and Altered Perception
Serotonin and Dopamine Systems in Psychedelic Effects
Ketamine as an NMDA Antagonist Psychedelic
A Typical Psychedelic Experiment in a Clinical Setting
The Concept of 'Letting Go' During Psychedelic Sessions
The Mind's Eye and Perceptual Bubbles
Redefining the Sense of Self and Identity
Exporting Psychedelic Learnings to Daily Life
Understanding Flashbacks and Hallucinogen Persisting Perceptual Disorder
Ayahuasca, MDMA, and DMT: Distinct Psychedelic Experiences
Dangers of Psychedelics: Bad Trips and Long-Lasting Psychosis
Microdosing: Claims, Evidence, and Potential Risks
Risks for Kids, Adolescents, and Teenagers; Future Clinical Trials
Legal Status: Decriminalization vs. Legalization vs. Regulation
Psychedelics for Treating Concussion and Traumatic Brain Injury
Shifting Trends in Psychedelic Research and Academic Culture
Participating in Clinical Trials and Online Survey Studies
7 Key Concepts
Classic Psychedelics
These compounds, including LSD, psilocybin, DMT, and mescaline, primarily act as agonists or partial agonists at the serotonin-2A receptor. They are known for profoundly altering one's sense of reality and self, often leading to experiences like synesthesia or altered space-time perception.
NMDA Antagonists
This class of compounds, such as ketamine, PCP, and dextromethorphan, produces psychedelic-like effects, often more dissociative in nature. They are believed to increase glutamate transmission downstream, contributing to their reality-altering properties.
MDMA (Intactogen/Empathogen)
MDMA is a unique compound that primarily works by causing serotonin release, and to a lesser extent, other monoamines like dopamine. It's called an 'intactogen' because it helps individuals connect with their emotions, or an 'empathogen' for its ability to foster empathy.
Dishabituation
This refers to the psychedelic effect of breaking down the brain's normal habituation process, where familiar stimuli are filtered out. Psychedelics can make everyday objects or sensations appear novel, profound, and breathtaking, as if experienced for the first time.
Self-Representation
A core concept in psychedelic therapy, referring to how a person fundamentally perceives and defines themselves in the world. Psychedelics are thought to profoundly alter these models of self, potentially leading to lasting changes in identity and agency, even without supernatural beliefs.
Hallucinogen Persisting Perceptual Disorder (HPPD)
A rare, real phenomenon where individuals experience persisting perceptual disturbances (e.g., halos, tracers, color distortions) after psychedelic use. It is clinically distressing and must last for several months, but has not been observed in controlled clinical trials and can also be triggered by other substances or even occur spontaneously.
State-Dependent Learning
This is a common experience often mistaken for a flashback, where returning to a similar context (e.g., smoking cannabis, relaxing in a warm bath) after a psychedelic experience can bring back similar thoughts and emotions. It is typically not distressing or perceptual in nature.
12 Questions Answered
Psychedelics are broadly defined as compounds that profoundly alter one's sense of reality and self. This includes classic psychedelics (serotonin-2A agonists), NMDA antagonists like ketamine, kappa opioid agonists like salvinorin A, and MDMA, which causes serotonin release.
Classic psychedelics primarily act as agonists or partial agonists at the serotonin-2A receptor. This activation leads to downstream effects, including increased glutamate transmission, and is thought to 'dissolve' or alter the brain's predictive models of reality and self-representation.
A 'K-hole' is a state of profound dissociation induced by high doses of ketamine, where a person becomes less behaviorally active and can feel completely disconnected from their body. People claim these NMDA antagonist psychedelics offer profound insights, similar to classic psychedelics, despite their dissociative nature.
Participants undergo extensive screening for psychiatric and cardiovascular health, followed by 4-8 hours of preparation to build rapport with guides and understand potential experiences. On session day, they ingest pure psilocybin in a capsule, wear eyeshades, and are encouraged to 'let go' of control, with guides present for support and physiological monitoring.
Letting go allows individuals to fully immerse themselves in the expanded perceptual bubble of the experience without resistance. This surrender is believed to be crucial for processing deep emotional responses, confronting fears, and ultimately facilitating lasting changes in self-representation and agency.
True flashbacks, known as Hallucinogen Persisting Perceptual Disorder (HPPD), are very rare and have not been observed in controlled clinical trials. More common are 'state-dependent learning' phenomena, where similar contexts or thoughts can briefly bring back aspects of the experience, which are typically not distressing.
MDMA primarily works by flooding the synapse with serotonin and dopamine, rather than directly mimicking neurotransmitters at receptors like classic psychedelics. This mechanism is thought to reduce amygdala reactivity, potentially aiding in the reprocessing and reconsolidation of traumatic memories with a lower chance of extremely challenging experiences.
The two main dangers are destabilization for individuals with severe psychiatric illnesses (like schizophrenia or bipolar disorder) and 'bad trips' (experiences of strong anxiety, fear, or losing one's mind). While rare, bad trips can lead to accidental injury or death if not in a safe, controlled environment.
Microdosing involves taking about a tenth of an entry-level psychedelic dose, with claims of improved focus, creativity, and mood. Current peer-reviewed, double-blind studies have generally shown no benefit, and sometimes even slight cognitive impairment, suggesting that reported benefits may largely be due to placebo effects.
There is no formal research on psychedelic use in individuals under 18, but the FDA has signaled interest in such studies due to the prevalence of depression in adolescents. While the developing brain is a special concern, it is also highly plastic, and future research will likely explore therapeutic potential with extreme caution for treatment-resistant conditions.
Federally, psychedelics remain Schedule I illegal compounds. Decriminalization at local or state levels means law enforcement may prioritize these offenses lower, but possession can still lead to federal charges. Full legalization or prescription-based regulation is being explored, with MDMA potentially approved for PTSD within three years.
This is an exploratory area, but anecdotes suggest psychedelics may improve cognitive function and mood after head impacts. Rodent research shows various forms of neuroplasticity (e.g., dendrite growth) post-administration. Future human trials aim to assess if psychedelics can directly repair brain injuries and improve cognitive function in retired athletes with repetitive head impacts.
16 Actionable Insights
1. Prioritize Experience for Brain Change
Recognize that deep changes in neural circuitry, emotionality, and self-perception primarily occur through real, impactful somatic and perceptual experiences, not merely through language or affirmations. This understanding helps avoid the “treacherous” trap of believing one can simply talk oneself out of deeply ingrained psychological states.
2. Screen for Psychiatric Predisposition
Before considering psychedelics, undergo extensive screening for severe psychiatric illnesses like psychotic disorders (schizophrenia) or mania (bipolar disorder), including family history. This is critical to mitigate the risk of profound destabilization.
3. Ensure Safe Psychedelic Environment
If considering psychedelics, ensure they are taken in a safe, controlled environment, ideally with sober, supportive individuals. Avoid navigating complex or unfamiliar environments to enhance safety and manage potential challenges.
4. Practice Letting Go During Psychedelics
During a psychedelic experience, actively practice letting go of control and surrendering to the experience. This approach can be a gateway to transcendental experiences and positive long-term outcomes, whereas resisting the experience can lead to a “bad trip.”
5. Post-Psychedelic Major Decision Delay
After a psychedelic experience, wait at least two weeks before making any major life decisions, such as ending relationships, quitting jobs, starting new relationships, or getting pets. This allows your sober mind to process insights and make well-considered choices.
6. Allow All Emotional Responses
In a therapeutic psychedelic session, allow any emotional response, including intense crying, to manifest freely. This is encouraged to facilitate the experience and is part of the therapeutic process.
7. Utilize Eye Shades for Internal Focus
During a psychedelic experience, use eye shades to enhance the “mind’s eye” and deepen internal perceptual experiences. This can help focus on the internal journey.
8. Process Experience Through Writing & Integration
Following a psychedelic session, write down your experience without self-criticism and participate in a subsequent integration session with guides. This helps process the experience and discuss its meaning for lasting benefit.
9. Understand Psychedelic Variability
Be aware that psychedelic experiences are highly variable and can range from profoundly beautiful to terrifying. Managing expectations by understanding this variability is crucial to avoid surprises.
10. Skepticism on Microdosing Claims
Be skeptical of claims that microdosing significantly increases creativity, enhances cognition, or provides sustained mood improvement, as current peer-reviewed, double-blind studies have not shown consistent benefits and sometimes indicate impairment.
11. Caution with Chronic Microdosing
Exercise caution with long-term, frequent microdosing (e.g., twice a week for years) due to theoretical concerns about serotonin 2B agonist effects, which have been linked to heart valve problems. While infrequent therapeutic use may not pose a risk, chronic use could.
12. Ensure Proper Hydration & Electrolytes
Prioritize proper hydration and adequate electrolyte intake (sodium, magnesium, potassium) daily. This is critical for optimal brain and body function, preventing diminished cognitive and physical performance, and supporting cell/neuron function.
13. Hydration Routine with Element
Dissolve one packet of Element in 16-32 ounces of water and drink it first thing in the morning, and also during any physical exercise. This routine helps ensure proper hydration and electrolyte balance.
14. Practice Yoga Nidra or NSDR
Incorporate yoga nidra or non-sleep deep rest (NSDR) into your routine, even for short 10-minute sessions. This practice can greatly restore cognitive and physical energy.
15. Verify Drug Information Scientifically
Do not attribute bizarre behaviors or negative effects to unfamiliar drugs without scientific evidence. Misinformation and xenophobia can lead to incorrect and harmful conclusions.
16. Find Clinical Trials for Psychedelics
To explore participation in Dr. Matthew Johnson’s clinical trials, visit hopkinspyschedelic.org. For broader psychedelic clinical trials in the US and Europe, search clinicaltrials.gov. Apply through official portals for specific, FDA-approved protocols.
6 Key Quotes
All of the so-called psychedelics across these distinct classes that I can talk more about, the way I put it is they all had the ability to profoundly alter one's sense of reality.
Dr. Matthew Johnson
I call them uppers, downers, and all-arounders and the psychedelics are all-arounders. It's like, yeah, you could be, you could have the most beautiful experience of your life or the most terrifying experience of your life.
Dr. Matthew Johnson
I think the most common denominator are persisting changes in self-representation. That's the way one holds the sense of self, the relate, the fundamental relationship of a person in the world.
Dr. Matthew Johnson
I know this sounds like bullshit and this sounds like, but my God, I could just decide. Like they're feeling this gravity of agency, which I think is interesting because regardless of the debates on the reality of free will, I think the philosophy of that, whether it's ultimately free will, like pure agency, if that exists, which I'm skeptical of, or just the idea that clearly we have a sense of agency, there's something there, whether it's the sense of agency even, that is, the human being has and that seems to be at times fundamentally like supercharged from a psychedelic experience.
Dr. Matthew Johnson
The neural networks of the brain put language last. We tell stories, you know, and stories are very powerful, but I think one of the most cruel aspects of the whole self-help literature and popular psychology is this idea that everything you say, your brain and body hear it.
Dr. Andrew Huberman
I think the most interesting thing about psychedelics are the heroic doses. I mean the idea you can give something one, two, three times and you see improvements in depression months later and in addiction over a year later and with these people dealing with potentially terminal illness.
Dr. Matthew Johnson
1 Protocols
Clinical Psychedelic Session (Psilocybin)
Dr. Matthew Johnson- **Screening:** Undergo psychiatric interviews (DSM-based) and cardiovascular screening to rule out psychotic disorders, bipolar disorder, or severe heart risk.
- **Preparation (4-8 hours):** Develop therapeutic rapport with guides and receive didactic explanation of potential psychedelic experiences, emphasizing that all emotional responses are welcome.
- **Session Day (Ingestion):** Ingest pure psilocybin in a small capsule (20-30mg range, adjusted for body weight in some studies), which takes 15 minutes to an hour to kick in.
- **During Session:** Wear eyeshades to facilitate internal focus, lie on a couch, and listen to music. Guides are present to monitor physiological responses (blood pressure, pulse every 30 minutes) and provide support, encouraging the participant to 'let go' of control.
- **Coming Down/Initial Integration:** As the effects subside (5-6 hours in), engage in initial discussion about the experience, but avoid total unpacking.
- **Homework:** Write something (e.g., bullet points, essay) about the experience that night, without self-criticism, as a processing tool.
- **Integration Session (Next Day):** Attend a 1-2 hour session to discuss the experience, its meaning for their specific condition (e.g., cancer, smoking cessation), and how to apply learnings to daily life. Advice is given to defer major life decisions (e.g., relationship changes, quitting jobs) for a week or two.