Published June 2023 on YouTube

The Science of MDMA & Its Therapeutic Uses: Benefits & Risks | Huberman Lab Podcast

1. MDMA “Ecstasy”

Andrew discusses the differences between recreational and therapeutic use of MDMA, and its potential as a treatment for PTSD. He explains how MDMA works at the level of neurons, the brain circuits it activates and deactivates, and the success of clinical trials using MDMA. He also addresses concerns about its toxicity and long-term effects.

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3. MDMA History & Synthesis; Legality

The History of MDMA:Andrew Huberman discusses the fascinating history of MDMA, from its synthesis by Merck to its rediscovery by Alexander Schulgen and its use in an underground group of therapists and physicians. He also explains why MDMA is a unique and exciting compound from a clinical treatment perspective.
MDMA's Legal Status:Andrew discusses the history of MDMA, its effects, and its potential for clinical treatment. He also talks about the ongoing debate regarding its legality and the race between two groups to establish its toxicity or lack thereof.

4. Understanding MDMA

Understanding MDMA:Andrew explains the properties of MDMA and how it affects the release and reuptake of neurotransmitters, specifically dopamine. He simplifies the process of how neurons communicate and the role of neuromodulators in this process.
MDMA's Effects:Andrew explains how MDMA affects dopamine and serotonin levels in the brain, leading to huge increases in both neurotransmitters. MDMA prevents the reuptake of dopamine and serotonin, causing more to hang out in the synapse and bind to receptors. This leads to increases in dopaminergic tone and dopaminergic drive.
MDMA's Unique Effects:Andrew explains how MDMA causes big increases in dopamine and serotonin, leading to mood elevation, stimulation, and a prosocial effect. The combination of these effects creates an empathogen, which can be beneficial for the treatment of PTSD.

5. MDMA vs Psychedelics vs Ketamine

Andrew Huberman explains the difference between MDMA and other psychedelics such as psilocybin and LSD. He also discusses the use of ketamine in treating depression. MDMA is an empathogen that creates affiliative effects, while ketamine is dissociative.

6. MDMA & Serotonin 1B Receptor, Subjective Feelings, Trauma

Understanding MDMA:Andrew explains how MDMA affects the brain, specifically the big increases in serotonin that create a situation where people have more energy, feel pleasure, and increase trust. He emphasizes that MDMA does not cure PTSD but rather makes talk therapy for PTSD more effective by engaging specific neural circuits. The increases in serotonin that MDMA produces seem to act on different receptors than LSD and psilocybin.
MDMA's Impact:Andrew Huberman explains how MDMA affects the brain by activating the serotonin one B receptor, which creates a desire to bond and trust, and increasing dopamine, which motivates people to take action. This combination makes people more willing to engage in conversations with themselves and others, which is crucial in MDMA therapy for PTSD treatment.

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8. Understanding MDMA Effects

Understanding MDMA Effects:Andrew explains the different experiments that can be done to understand the effects of MDMA on the brain, including brain imaging to analyze the Default Mode Network and changes in brain networks after taking the drug.
MDMA and the Brain:Andrew discusses the effects of MDMA on the brain and shares an interesting study on the effects of MDMA on octopuses. He highlights the work of Harriet De Witt and her research on how MDMA impacts people's perceptions of others' emotional expressions on their face.
MDMA and Emotional Perception:Andrew discusses a study that found MDMA has a bi-directional effect on emotional perception, reducing the response to threatening stimuli and increasing the response to positive stimuli. The study also looked at the dosages used in neuroimaging and clinical studies, ranging from 0.75mg to 1.5mg per kilogram of body weight.
MDMA Dosages:Andrew discusses the importance of understanding MDMA dosages in relation to toxicity and the range of dosages explored in studies. The toxicity of MDMA scales with the dosage applied, not just the frequency of use, so it's crucial to consider specific dosages taken in any one session.

9. Interoception and PTSD

Interoception and PTSD:Andrew explains the role of interoception in PTSD and how MDMA can reduce the heightened connectivity between the amygdala and insula, a brain area critical for interoception.
PTSD and MDMA:Andrew explains the relationship between the amygdala and the insula in people with PTSD, and how MDMA therapy weakens the connections between the two, leading to relief of symptoms. Functional imaging machines are used to observe the brain network and the relief of symptoms from PTSD.

10. Understanding MDMA Effects

Andrew explains how MDMA impacts the brain, specifically in reducing threat detection and increasing positivity. He also compares the effects of MDMA to classic psychedelics like psilocybin and LSD, highlighting the differences in their impact on lateral connectivity in the brain.

11. MDMA's Brain Effects

MDMA's Effects on Brain Networks:Andrew discusses a study on MDMA's effects on brain networks and the role of serotonin, dopamine, and oxytocin. The study, done on mice, found distinct neural mechanisms for the prosocial and rewarding properties of MDMA. The results translate well to humans and provide insights into the effects of MDMA on specific circuits in the brain.
MDMA's Pro Social Effect:Andrew explains how MDMA increases dopamine to establish the rewarding effects of an experience, and how the activation of the serotonin one B receptor in the nucleus accumbens by MDMA leads to its pro social effect.
MDMA and Social Connection:Andrew explains how MDMA affects the brain by activating the serotonin one B receptor, which increases social connection and empathy. The release of dopamine also reinforces motivation to be kinder to oneself and others.
MDMA's Polypharmacology:Andrew explains how MDMA's effects on the brain are not just due to the increase in serotonin, but also the activation of serotonin at particular receptors in specific brain areas. He compares the effects of MDMA to SSRIs and discusses the impact of methamphetamine on social interactions.

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13. Oxytocin & MDMA

MDMA and Oxytocin:Andrew discusses how MDMA increases levels of oxytocin release in the brain, which is associated with neural networks related to pair bonding between parent and child, friends, and lovers. He also talks about a study that shows how MDMA powerfully increases oxytocin release and the effects of different doses.
MDMA and Oxytocin:Andrew explains that while MDMA does increase levels of oxytocin, it does not appear to be the source of the pro-social effects of the drug. Instead, MDMA increases dopamine to reward serotonin activation of brain networks associated with sociability.
Oxytocin and MDMA:Andrew discusses the role of oxytocin in the effects of MDMA and how it may not be directly related to the drug's sociability and empathy effects. The data suggests that the increases in oxytocin produced by MDMA may not be very relevant, but there could be other effects of oxytocin that we are not aware of.

14. MDMA Safety and Toxicity

MDMA Safety:Andrew discusses the importance of understanding the safety risks associated with MDMA use, both recreationally and in laboratory or clinical studies. He highlights the dangers of contamination with fentanyl and the potential neurotoxicity of MDMA due to its effects on dopamine and serotonin levels in the brain.
MDMA Toxicity:Andrew explains the complex literature on the neurotoxicity of MDMA, including animal studies that show reductions in serotonin tone and proteins related to the synthesis or release of serotonin. He also notes that short-term depletion of neuromodulators is not the same as long-term depletion or loss of neurons that release dopamine and serotonin.
MDMA and Primate Studies:Andrew discusses the results of primate studies on MDMA and how they differ from rodent studies. He highlights a study published in Science that suggested even recreational doses of MDMA can be neurotoxic to serotonin and/or dopaminergic neurons, but also notes that this study came under scrutiny for potential biases.
MDMA Neurotoxicity Retraction:Andrew explains the retraction of the study on MDMA neurotoxicity in primates due to issues of mislabeling and concludes that there are no data in either non-human primates or humans showing toxicity of MDMA at clinically relevant doses, provided it is pure MDMA.

15. MDMA and Neuroplasticity

MDMA and Neuroplasticity:Andrew discusses a controversial study that explores the neurocognitive and behavioral effects of taking MDMA. The study confirms that people were taking pure MDMA and not taking any other drugs, making it of immense value. Andrew also talks about the potential neurotoxicity of methamphetamine and the importance of understanding polypharmacology.
Ecstasy and Cognitive Performance:Andrew discusses a study on the effects of ecstasy on cognitive performance in moderate and heavy users of MDMA who self-identify as Latter Day Saints. The study found little evidence of decreased cognitive performance, but more impulsivity in heavy users. However, the direction of the effect is not known.
MDMA Neurotoxicity:Andrew discusses the potential neurotoxicity of MDMA and the importance of environmental and behavioral conditions when taking the drug. He also mentions a unique population within the LDS community who have taken MDMA multiple times, but it is unclear if it is sanctioned by the community.

16. Post-MDMA “Crash”, Prolactin & P 5 P

MDMA Crash:Andrew debunks the myths surrounding the post-MDMA crash and provides insights on how to offset neurotoxicity. He explains that the crash is a common phenomenon experienced after ingestion of any type of stimulant and that there is no evidence to support the use of serotonin or dopamine precursors to buffer the crash.
MDMA and Prolactin:Andrew discusses how MDMA ingestion can increase prolactin levels and lead to a feeling of lethargy and lack of motivation. He explores the use of P five P, a metabolite of vitamin B six, as a way to suppress prolactin and alleviate the post-MDMA crash. The use of P five P is an area that is starting to receive attention from clinicians using MDMA for the treatment of PTSD and other conditions.

17. PTSD & Trauma; Talk Therapy, SSRIs

Understanding PTSD:Andrew Huberman explains what post traumatic stress disorder (PTSD) is and how it can be caused by a variety of traumatic experiences, including single events and multiple event traumas. He recommends the book Trauma by Dr. Paul Conti as an excellent resource for those interested in understanding trauma and its treatment.
Talk Therapy and PTSD:Andrew Huberman discusses the components of effective talk therapy for trauma, the limitations of talk therapy alone for PTSD, and the potential benefits and drawbacks of combining SSRIs with talk therapy. He also explores the use of MDMA as a treatment option for those who do not achieve significant or long-lasting relief from PTSD with traditional therapies.
Understanding PTSD:Andrew discusses the vast symptoms of PTSD and how it affects people at different levels. He emphasizes the importance of finding lasting relief for PTSD as it can lead to comorbidities such as addiction, depression, and anxiety. Andrew also explains how PTSD is caused by changes in brain circuitry and neural communication between the brain and body.

18. MDMA for PTSD

MDMA for PTSD:Andrew discusses the potential of MDMA as a therapeutic for PTSD, citing studies by the Maps group that have shown remarkable results in the treatment of PTSD symptoms and associated addictive behaviors. Legalization of MDMA for clinical use may be on the horizon.
MDMA and PTSD:Andrew explains the effectiveness of MDMA-assisted therapy in treating PTSD. Trials have shown an 88% clinically effective response rate for patients who underwent talk therapy with MDMA compared to 60% for those who only had talk therapy. Patients undergo talk therapy sessions with two therapists before taking MDMA and then continue therapy sessions with the same therapists while on MDMA.
MDMA-Assisted Therapy:Andrew discusses the success rates of MDMA-assisted therapy for PTSD and how it compares to traditional talk therapy with a placebo. He highlights the significant difference in success rates and the potential for MDMA to become a legal treatment option for PTSD in the near future.

19. MDMA for PTSD

Exciting PTSD Treatment Results:Andrew discusses the exciting results of clinical trials on MDMA plus talk therapy for treating PTSD and how it can also resolve addiction to alcohol and other substances. He also talks about how dissociative PTSD has traditionally been hard to treat and why successful treatment involves patients getting close to their traumatic experiences.
Healing Trauma:Andrew discusses how MDMA combined with talk therapy can help individuals with PTSD reframe their traumatic experiences in a way that allows them to see themselves in the role of agency. The emotional load of these experiences becomes diminished, no longer burdening them, and allowing them to function normally.
MDMA for PTSD:Andrew discusses the potential of MDMA as a treatment for PTSD and other disorders. He explains how the compound produces a neurochemical milieu in the brain that allows therapy to be more potent in a limited number of sessions, and how it can help people reframe traumatic events to lead productive lives.

20. MDMA Therapy Prospects

MDMA Therapy:Andrew discusses the positive outcomes of combining MDMA with quality talk therapy in reducing PTSD symptoms, as shown in clinical trials. He also touches on the absence of adverse effects associated with the therapy and the efforts to keep it within the realm of legal and medical use.
MDMA's Prospective Use:Andrew discusses the potential use of MDMA in psychiatry and how it can create relief for people suffering from PTSD and addiction. He also emphasizes the importance of caution when using sympathomimetics and the dangers of fentanyl contamination in MDMA sold on the street. Andrew highlights the significance of accessing neuroplasticity to modify the nervous system in adaptive ways.

21. Support and Supplements

Andrew shares ways to support the podcast, including subscribing and leaving reviews. He also discusses the benefits of supplements for sleep, hormone support, and focus, and promotes Momentous supplements. He invites listeners to check out the Neural Network newsletter for free toolkits on improving various aspects of health.