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MDMA, also known as ecstasy or molly, is a synthetic compound that has similarities to methamphetamine in terms of dopaminergic effects but also controls the release of serotonin. This distinction makes MDMA different from classic psychedelics and pure stimulants. The combination of increased dopamine and serotonin levels creates empathogenic effects, enhancing social connectedness and empathy for oneself and others. This distinctive property of MDMA has led to both recreational use and promising results in clinical trials, particularly for the treatment of PTSD.
MDMA was initially synthesized by a drug company but was later rediscovered and explored for its subjective effects. It is currently classified as a Schedule 1 drug, making it illegal in the United States. However, breakthrough status has been granted, allowing for research and exploration of MDMA as a potential therapeutic agent. The history of MDMA and its legal status provide important context for understanding its current use and potential for future legality.
MDMA significantly impacts brain function and connectivity, particularly in areas associated with threat detection and social engagement. Studies have shown that MDMA reduces activation in the amygdala, which is involved in threat detection, and enhances connectivity between the amygdala and the insula, a brain region associated with interoception. These changes in brain connectivity are linked to the relief of PTSD symptoms and improvements in emotional well-being, empathy, and bonding with others. Additionally, MDMA enhances dopamine release, leading to rewarding effects.
MDMA can be neurotoxic, particularly to dopamine and serotonin neurons. However, there are ways to use MDMA therapeutically that minimize potential toxicity. Studies explore dosages and spacing between sessions to mitigate adverse effects. The long-term effects and safety of MDMA, both after acute and chronic use, are still being investigated. Researchers are working to understand the potential risks and develop strategies to ensure the safe and effective use of MDMA.
MDMA activates the serotonin 1B receptor, leading to social connection being strongly rewarded and reinforced. It increases empathy and compassion, making individuals more likely to feel connected to others even after the drug wears off.
The release of serotonin by MDMA increases empathy and sociability, while the release of dopamine rewards and motivates social interaction. This combination of neurotransmitters enhances social connection and leads individuals to perceive others as kind and be kinder to themselves.
While MDMA increases oxytocin release, it does not directly contribute to the known effects of MDMA on empathy and sociability. The activation of serotonin at specific receptors, particularly the serotonin 1B receptor, in specific brain areas is responsible for enhancing sociability and empathy, along with the simultaneous increase in dopamine.
According to studies, when pure MDMA is taken in controlled clinical settings and not combined with other neurotoxic drugs, the risk of toxicity appears to be lower than what is often reported in the media. However, high doses of MDMA, frequent use, and combined use with other drugs or in settings with increased body temperature or blood pressure can still lead to neurotoxicity.
MDMA combined with talk therapy has shown significant promise in the treatment of post-traumatic stress disorder (PTSD). Clinical trials have demonstrated that MDMA therapy can help patients with PTSD approach their traumatic experiences in a safe and supportive environment, leading to cognitive and somatic reframing of the trauma and significant reduction in symptoms. Additionally, MDMA therapy has shown potential for treating depression, alcohol use disorder, and eating disorders associated with PTSD. The combination of MDMA and talk therapy allows patients to deeply engage with their trauma and emotions, leading to long-lasting relief and improved quality of life.
In this episode, I discuss Methylenedioxymethamphetamine (MDMA), which is also commonly known as “ecstasy” or “molly,” including how it works in the brain to cause short- and long- term-shifts in emotional processing and its clinical applications for the treatment of post-traumatic stress disorder (PTSD), alcohol and other substance-use addictions. I discuss the neuronal mechanisms for how MDMA elevates mood, empathy, motivation, social engagement, and reduces “threat detection” and how these effects can synergistically support talk therapy. I also explain the ongoing debate about the potential neurotoxicity of MDMA, myths about the origins and treatments for post-MDMA “crash,” the evolving legal landscape around MDMA use for clinical purposes, and I caution recreational users about the extremely dangerous additives (e.g., fentanyl) now commonly found in black market MDMA. This should be of interest to those curious about MDMA, neuropharmacology, the origins of emotional processing in the brain, empathy, PTSD, neuroplasticity, mental health and psychiatry.
For the full show notes, visit hubermanlab.com.
AG1: https://athleticgreens.com/huberman
LMNT: https://drinklmnt.com/hubermanlab
Waking Up: https://wakingup.com/huberman
Momentous: https://livemomentous.com/huberman
(00:00:00) MDMA “Ecstasy”
(00:04:54) Sponsors: LMNT & Waking Up
(00:08:18) MDMA History & Synthesis; Legality
(00:14:45) MDMA, Methamphetamine (Meth), Dopamine & Serotonin
(00:23:30) MDMA vs Psychedelics vs Ketamine
(00:26:54) MDMA & Serotonin 1B Receptor, Subjective Feelings, Trauma
(00:30:12) Sponsor: AG1
(00:34:51) Amygdala & Threat Detection, Pro-Social Behavior, MDMA Dosages
(00:45:48) Interoception, MDMA & Post-Traumatic Stress Disorder (PTSD)
(00:52:36) Long-Term Effects, Threat Detection & PTSD
(00:56:14) MDMA, Social Connection & Empathy; Meth, SSRIs
(01:07:22) Oxytocin & MDMA
(01:16:10) Safety & Neurotoxicity; Recreational Use, Caffeine & Fentanyl
(01:26:36) Is MDMA Neurotoxic?; Poly-Pharmacology, Body Temperature
(01:37:07) Post-MDMA “Crash”, Prolactin & P‑5‑P
(01:43:07) PTSD & Trauma; Talk Therapy, SSRIs
(01:54:09) PTSD Treatment: Talk Therapy + MDMA
(02:02:46) MDMA & Addiction; Dissociative PTSD & Empathy
(02:09:47) Side-Effects?, MDMA Efficacy & Legality
(02:15:22) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Social Media, Neural Network Newsletter
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