MDMA

Overall Health Benefits of MDMA

• Treats post-traumatic stress disorder (PTSD) [1-26]
• Improves mood [27-34]
• Treats alcohol addiction [35-39]

What is MDMA?

3,4-Methyl​enedioxy​methamphetamine (MDMA) is a potent empathogen–entactogen, which means that it belongs to a class of drugs that produce experiences of empathy, emotional openness, oneness, and interrelatedness. MDMA is commonly seen in tablet form known as ecstasy. In crystal form, MDMA is colloquially referred to as molly or mandy. This drug is primarily used for recreational purposes to achieve feelings of pleasure, empathy, and increased energy. When taken by mouth, the individual can start to experience the effects in 30-45 minutes and they last for 3-6 hours. Aside from recreational purposes, MDMA can also be used for medical purposes. In 2017, the United States Food and Drug Administration (FDA) approved MDMA-assisted psychotherapy for the treatment of mental health conditions such as post-traumatic stress disorder (PTSD).

How MDMA Works

In the serotonergic neurons (unique resource of the neurotransmitter/brain chemical serotonin), extracellular MDMA significantly increases the amount of serotonin in the synaptic clefts which are junctions through which signals from the neurons/nerve cells can be sent to each other. It does this by binding to serotonin transporters (SERT). Intracellular MDMA also boosts serotonin release by inhibiting vesicular monoamine transporter 2 (VMAT2) and monoamine oxidase A (MAO-A). Since the neurotransmitter serotonin regulates mood and is known as the body’s natural “feel good” chemical, increasing serotonin levels may help treat mood disorders such as anxiety, depression, and PTSD.

Chemical Structure of MDMA

Research on MDMA

A. Treats Post-Traumatic Stress Disorder (PTSD)

PTSD is a disorder that develops in individuals who have experienced a terrifying or dangerous event. Symptoms may include flashbacks, severe anxiety, nightmares, and uncontrollable thoughts about the stressful event. MDMA causes the release of oxytocin (also known as the “love hormone”) in the brain, which creates feelings of trust, bonding closeness, desire, and social recognition. When combined with psychotherapy or talk therapy, MDMA can help reduce symptoms of PTSD and improve the quality of life of affected individuals.

Studies show that MDMA administration in addition to psychotherapy may produce beneficial effects in the treatment of PTSD:

1. A systematic review of multiple clinical trials found promising evidence for the potential therapeutic use of MDMA alongside psychotherapy in the treatment of PTSD. [1]
2. In military veterans, firefighters, and police officers with chronic PTSD duration of 6 months or more, active doses (75 mg and 125 mg) of MDMA with adjunctive psychotherapy significantly reduced PTSD symptom severity after 12 months. [2]
3. In twenty-eight people with PTSD, the administration of two active doses (100 and 125 mg) with a low dose (40 mg) of MDMA during eight-hour psychotherapy sessions for 12 months resulted in significant reductions in Clinician-Administered PTSD Scale total scores. [3]
4. In individuals with treatment-resistant PTSD, MDMA-assisted psychotherapy was associated with significant symptom reduction and enhanced quality of life. [4-7]
5. In patients with severe PTSD and comorbidities such as dissociation, depression, alcohol and substance use disorders, and childhood trauma, MDMA-assisted psychotherapy was found to induce significant and robust attenuation in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), a measure of PTSD symptoms. [8]
6. An analysis of six phase 2 trials found that the majority of participants who had undergone MDMA-assisted psychotherapy reported improved relationships and well-being and symptom improvement that continued at least 12 months post-treatment. [9]
7. In victims of sexual abuse with severe PTSD, oral administration of MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart, resulted in significant reductions in the symptoms of depression and PTSD. [10]
8. In healthy male volunteers, MDMA in conjunction with psychotherapy enhanced explicit and implicit emotional empathy. [11]
9. In patients with a history of severe trauma, MDMA-assisted psychotherapy resulted in significant reductions in PTSD symptoms and improvements in relationship satisfaction. [12]
10. Several analyses of clinical trials assessing the beneficial effects of MDMA on PTSD reported that it can be an effective pharmacologic therapy when combined with psychotherapy. [13-24]
11. In a small sample of women with chronic PTSD, low doses of MDMA (between 50 and 75 mg) reduced symptoms without any adverse side effects. [25]
12. In individuals with PTSD, MDMA treatment resulted in improved self-reported sleep quality compared with placebo. [26]

B. Improves Mood

MDMA binds to serotonin transporters (SERT) and boosts serotonin release by inhibiting vesicular monoamine transporter 2 (VMAT2) and monoamine oxidase A (MAO-A). With increased serotonin levels, the overall mood can be improved since this neurotransmitter regulates mood and is known as the body’s natural “feel good” chemical.

Studies found that MDMA can help improve mood through its antidepressant and anti-anxiety effects:

1. In a rat model of depression, MDMA at 5 and 10 mg/kg following single and repeated administration produced antidepressant-like effects. [27]
2. In human subjects with depression, oral MDMA consumption resulted in a significant decrease in depressive symptoms. [28]
3. In a large nationally representative sample of US adults, MDMA/ecstasy use is associated with a lower risk of depression. [29]
4. In female polydrug ecstasy users, MDMA treatment at a dose of 75 mg induced a reduction in self-rated depressive feelings. [30]
5. In adults with autism, MDMA treatment resulted in statistically significant improvements in social anxiety compared to placebo. [31]
6. In a group of participants who received MDMA at 125 mg, a significant reduction in anxiety was observed compared to the placebo group. [32]
7. In patients with social anxiety disorder, MDMA enhanced memory reconsolidation, self-transcendence, and therapeutic relationships. [33-34]

C. Treats Alcohol Addiction

Narrative reports and data from early investigations found that MDMA may indirectly activate 5-HT2A receptors, which are known to control the neurochemical and behavioral effects of addictive substances including alcohol. [35] In addition, MDMA has anti-anxiety and antidepressant effects – both of which can help treat alcohol addiction since the disorder is associated with traumatic experiences and depression.

Evidence suggests that MDMA administration can help address the symptoms of alcohol addiction:

1. In a phase 3 trial assessing the safety and efficacy of MDMA-assisted therapy for the treatment of patients with severe PTSD, subclinical improvements in alcohol use without an increased risk of illicit drug use were observed. [36]
2. A study reported that MDMA may allow patients with alcohol use disorder to explore and address painful memories without being overwhelmed by negative effects. [37]
3. In patients with alcohol use disorder, MDMA-assisted psychotherapy improved psychosocial functioning and reduced alcohol consumption to 18.7 units per week compared to 130.6 units per week before the detox. [38]
4. In alcoholic patients, a full 8-week MDMA-assisted psychotherapy course reduced alcohol cravings and improved the participants’ outlook in life. [39]

Associated Side Effects of MDMA

MDMA side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on MDMA. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of MDMA. Despite this, it was listed as a side effect associated with MDMA even though these associated side effects are very uncommon.

Side effects associated with MDMA may include the following:

• Fatigue
• Headache
• Irritability
• Jaw-clenching
• Restlessness
• Transient increases in blood pressure

References

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