June 12, 2023 • 2hr 13min

The Science of MDMA & Its Therapeutic Uses: Benefits & Risks

Huberman Lab

In this episode, Dr. Andrew Huberman discusses MDMA (3,4-Methylenedioxymethamphetamine), commonly known as ecstasy or molly. He covers the history, pharmacology, subjective effects, potential therapeutic applications, and safety considerations of this unique compound. MDMA is currently being studied as an adjunct to psychotherapy for treating post-traumatic stress disorder (PTSD) and is showing remarkable promise in clinical trials. MDMA was first synthesized by Merck in 1912 but was largely forgotten until it was rediscovered by chemist Alexander Shulgin in the 1970s. It gained popularity as a party drug in the 1980s and 1990s before being made illegal. However, research into its therapeutic potential has continued and accelerated in recent years.

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Key Takeaways

MDMA (ecstasy) is a synthetic compound that causes large increases in both dopamine and serotonin release in the brain, leading to effects of increased energy, mood elevation, empathy, and prosocial behavior.
MDMA is showing remarkable promise as an adjunct to psychotherapy for treating PTSD, with clinical trials showing 88% of patients having a clinically significant response and 67% no longer meeting criteria for PTSD after treatment.
The mechanism appears to be MDMA allowing patients to access and process traumatic memories with less fear and more self-compassion, leading to lasting changes in how those memories are stored and activated.
At therapeutic doses in controlled settings, MDMA does not appear to have significant neurotoxicity, contrary to some earlier claims. However, recreational use carries risks, especially due to contamination with other substances.
MDMA is still illegal but is likely to be approved for medical use in the near future based on the strength of clinical trial results for PTSD treatment.
The "crash" after MDMA use may be due to increases in prolactin rather than serotonin depletion. Supplements like P-5-P (active B6) to lower prolactin may help mitigate this effect.
MDMA-assisted therapy also shows promise for treating alcohol use disorder and other addictions that are often comorbid with PTSD.

Introduction

In this episode, Dr. Andrew Huberman discusses MDMA (3,4-Methylenedioxymethamphetamine), commonly known as ecstasy or molly. He covers the history, pharmacology, subjective effects, potential therapeutic applications, and safety considerations of this unique compound. MDMA is currently being studied as an adjunct to psychotherapy for treating post-traumatic stress disorder (PTSD) and is showing remarkable promise in clinical trials.

MDMA was first synthesized by Merck in 1912 but was largely forgotten until it was rediscovered by chemist Alexander Shulgin in the 1970s. It gained popularity as a party drug in the 1980s and 1990s before being made illegal. However, research into its therapeutic potential has continued and accelerated in recent years.

Topics Discussed

Pharmacology and Mechanisms of Action (14:45)

MDMA has a unique pharmacological profile:

It causes large increases in both dopamine and serotonin release in the brain
The increase in serotonin is 3-8 times greater than the increase in dopamine
It also increases oxytocin release, though this may not be directly related to its therapeutic effects
MDMA primarily acts on the serotonin 1B receptor, unlike classic psychedelics which act on the 5-HT2A receptor

"MDMA is increasing dopamine to increase motivation and to reward something. What gets rewarded? Well, what gets rewarded is the serotonin activation of particular brain networks associated with sociability."

Subjective Effects and Brain Changes (34:51)

The subjective effects of MDMA include:

Increased energy and alertness
Elevated mood and sense of wellbeing
Increased empathy and prosocial behavior
Reduced fear and anxiety
Increased openness and introspection

Brain imaging studies have shown:

Decreased activity in the amygdala, reducing threat detection
Increased activity in reward centers like the nucleus accumbens
Changes in how emotional faces are perceived, with threatening faces seen as less threatening

Therapeutic Applications for PTSD (1:43:07)

MDMA is showing remarkable promise as an adjunct to psychotherapy for treating PTSD:

Clinical trials have shown 88% of patients having a clinically significant response
67% of patients no longer met criteria for PTSD after treatment
The treatment protocol involves 3 preparatory therapy sessions, 3 MDMA-assisted therapy sessions, and 3 integration sessions
MDMA appears to allow patients to access and process traumatic memories with less fear and more self-compassion

"What's very clear is that anytime you add quality talk therapy to a drug treatment, you're going to improve the outcomes for that drug treatment."

Safety and Neurotoxicity (1:16:10)

Contrary to some earlier claims, MDMA does not appear to be significantly neurotoxic at therapeutic doses:

A key study claiming neurotoxicity in primates was retracted due to the animals being given methamphetamine instead of MDMA
Studies of moderate to heavy MDMA users have not found significant cognitive deficits
Neurotoxicity risk increases with higher doses, frequent use, and combination with other drugs
Hyperthermia (overheating) significantly increases risk of neurotoxicity

However, recreational use carries significant risks:

Street MDMA is often adulterated with other substances, including dangerous drugs like fentanyl
Combining MDMA with other drugs, including caffeine, can increase neurotoxicity risk
Using MDMA in hot environments without proper hydration increases risk

The Post-MDMA "Crash" (1:37:07)

The "crash" or low mood often experienced after MDMA use may be due to increases in prolactin rather than serotonin depletion as previously thought:

MDMA causes large increases in prolactin release
Elevated prolactin is associated with lethargy and low mood
Supplements like P-5-P (active B6) that lower prolactin may help mitigate the crash

Legal Status and Future Directions (2:09:47)

MDMA is currently a Schedule I drug in the United States, meaning it has no accepted medical use and a high potential for abuse. However:

It has been granted "breakthrough therapy" status by the FDA for PTSD treatment
Phase 3 clinical trials are ongoing
MDMA is likely to be approved for medical use in supervised settings as early as 2023 or 2024
Research is also exploring MDMA-assisted therapy for alcohol use disorder and other conditions

Conclusion

MDMA is a fascinating compound with unique effects on brain chemistry and subjective experience. While it carries risks when used recreationally, it is showing remarkable promise as an adjunct to psychotherapy for treating PTSD and potentially other mental health conditions. The ability of MDMA to increase empathy, reduce fear, and allow processing of traumatic memories appears to lead to lasting changes in how those memories are stored and activated in the brain.

As research continues and MDMA moves closer to medical approval, it has the potential to revolutionize treatment for PTSD and provide relief for many who have not responded to current therapies. However, it's crucial that any future medical use occurs in controlled settings with proper screening, preparation, and integration to maximize benefits and minimize risks.

The story of MDMA also highlights the importance of rigorous scientific research into compounds that may have been prematurely dismissed due to recreational use or cultural stigma. As our understanding of the brain and mental health evolves, we may find valuable therapeutic tools in unexpected places.