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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, PTDS, neuroplasticity, mental health and psychiatry. Thank you to our sponsors AG1: https://drinkag1.com/huberman Helix Sleep: https://go.helixsleep.com/audio-partner/ ROKA: https://roka.com/huberman HVMN: https://hvmn.com/huberman LMNT: https://partners.drinklmnt.com/free-gift-with-purchase?rfsn=6327528.ecaabe8&rfsn_cn=EXCLUSIVE+GIFT+FOR+THE+HUBERMAN+LAB+COMMUNITY Momentous: https://livemomentous.com/huberman Social & Website Instagram - https://www.facebook.com/unsupportedbrowser Twitter - https://twitter.com/hubermanlab Facebook - https://www.facebook.com/unsupportedbrowser TikTok - https://www.tiktok.com/@hubermanlab Website - https://www.hubermanlab.com/ Newsletter - https://www.hubermanlab.com/newsletter Articles A Conserved Role for Serotonergic Neurotransmission in Mediating Social Behavior in Octopus: https://www.cell.com/current-biology/fulltext/S0960-9822(18)30991-6?_returnURL=https://linkinghub.elsevier.com/retrieve/pii/S0960982218309916%3Fshowall%3Dtrue Effects of MDMA on sociability and neural response to social threat and social reward: https://link.springer.com/article/10.1007/s00213-009-1635-z?error=cookies_not_supported&code=3bf700ea-0b46-492b-80b1-505b050e6902 The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity: https://www.biologicalpsychiatryjournal.com/article/S0006-3223(14)00005-5/fulltext Distinct neural mechanisms for the prosocial and rewarding properties of MDMA: https://www.science.org/doi/10.1126/scitranslmed.aaw6435?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans: https://www.sciencedirect.com/science/article/abs/pii/S0306453014001255?via%3Dihub RETRACTED: Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA ("Ecstasy"): https://www.science.org/doi/10.1126/science.1074501 Science forced to retract article on “ecstasy”: https://www.bmj.com/content/327/7415/579.2 Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs: https://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2010.03252.x MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study: https://www.nature.com/articles/s41591-021-01336-3?error=cookies_not_supported&code=c094435d-797e-4e2d-a2cd-51c424bda44f The effects of MDMA-assisted therapy on alcohol and substance use in a phase 3 trial for treatment of severe PTSD: https://www.sciencedirect.com/science/article/pii/S037687162200093X Books PIHKAL: A Chemical Love Story: https://www.amazon.com/Pihkal-Chemical-Story-Alexander-Shulgin/dp/0963009605?_encoding=UTF8 Trauma: The Invisible Epidemic: https://www.amazon.com/Trauma-Invisible-Epidemic-Works-Heal/dp/1683647351?_encoding=UTF8 The Body Keeps the Score: https://www.amazon.com/Body-Keeps-Score-Healing-Trauma/dp/0143127748?_encoding=UTF8 Other Resources Multidisciplinary Association for Psychedelic Studies (MAPS): https://maps.org/ Participate in a MAPS trial: https://maps.org/take-action/participate-in-trial Huberman Lab episode on psilocybin: https://www.hubermanlab.com/episode/how-psilocybin-can-rewire-our-brain-its-therapeutic-benefits-and-its-risks Huberman Lab episode on psychedelics for mental health: https://www.hubermanlab.com/episode/dr-robin-carhart-harris-the-science-of-psychedelics-for-mental-health Huberman Lab episode on dopamine, mindset & drive: https://www.hubermanlab.com/episode/controlling-your-dopamine-for-motivation-focus-and-satisfaction Huberman Lab episode on leveraging dopamine: https://www.hubermanlab.com/episode/leverage-dopamine-to-overcome-procrastination-and-optimize-effort Timestamps 00:00:00 MDMA “Ecstasy” 00:04:37 Sponsors: Helix Sleep, ROKA, HVMN 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 00:33:36 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 01:06:10 Sponsor: LMNT 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 Title Card Photo Credit: Mike Blabac - https://www.blabacphoto.com/ Disclaimer: https://www.hubermanlab.com/disclaimer