Molecules: MDMA

August 01, 2023

Molecules: MDMA

MDMA

MDMA (3,4-methylenedioxymethamphetamine) is a synthetic drug that produces stimulating and psychoactive effects. Here are some key facts about MDMA:

MDMA is classified as an entactogen or empathogen due to its ability to produce feelings of empathy, emotional openness, and connection.
It acts as a serotonin-norepinephrine-dopamine releasing agent, increasing levels of these neurotransmitters in the brain.
Desired effects include euphoria, sensory enhancement, energy, emotional warmth, empathy, and self-acceptance.
MDMA was originally synthesized by Merck pharmaceutical company in 1912. It was used in the 1970s psychotherapy practices before becoming a banned recreational drug.
Street names for MDMA include "Molly" and "Ecstasy." Tablet forms often include other substances.
Typical doses range from around 80-150 mg. Effects last 3-6 hours.

In summary, MDMA is a synthetic empathogen popular recreationally but also displaying promise when used carefully in therapeutic settings to increase emotional openness.

MDMA (3,4-methylenedioxymethamphetamine) is a synthetic drug that belongs to the phenethylamine class of psychoactive compounds. Here's an explanation of how MDMA relates to phenethylamines:

Phenethylamines are a broad class of organic compounds that contain a phenethylamine core structure made up of a benzene ring bound to an ethylamine group.
Many phenethylamines act as central nervous system stimulants and hallucinogens due to their ability to modulate monoamine neurotransmitter activity.
MDMA is structurally similar to the stimulant amphetamine, but contains an additional methylenedioxy ring attached to the phenethylamine backbone.
This gives MDMA unique psychoactive properties compared to other phenethylamines. While stimulating like amphetamine, it also enhances serotonin activity, producing empathic and prosocial effects.
Other well-known phenethylamines include mescaline and the 2C-x family of psychedelics which are substituted phenethylamines.
Many phenethylamines are found naturally in plants and animals, while others like MDMA are synthetic compounds developed in the lab.
In general, phenethylamines stimulate the nervous system via interactions with dopamine, norepinephrine and serotonin receptors and transporters.

So in summary, MDMA is a unique synthetic phenethylamine that combines stimulant properties with serotonin releasing action to produce a distinctive empathogenic experience. Exploring phenethylamine structure-activity relationships continues to yield therapeutic insights.

MDA (3,4-methylenedioxyamphetamine) and MDMA (3,4-methylenedioxymethamphetamine) are two closely related synthetic psychoactive drugs with some key differences:

Chemical structure - MDA has an amphetamine backbone while MDMA has a methamphetamine backbone. MDA lacks the N-methyl group of MDMA.
Potency - MDA is typically described as more potent than MDMA, with effective doses around 50-100mg versus 80-150mg.
Duration - MDA has a slightly longer duration, lasting 4-6 hours versus 3-5 hours for MDMA.
Effects - MDA is more stimulating and hallucinogenic, with greater psychedelic visual and audio effects compared to the empathogenic effects of MDMA.
Neurochemistry - While both increase serotonin, dopamine and norepinephrine, MDA has greater affinity for serotonin receptors resulting in more psychedelic activity.
Toxicity - MDA is typically considered more neurotoxic than MDMA due to increased free radical production and oxidative stress.
Legality - MDA is a Schedule I controlled substance while MDMA is Schedule I but can be used in FDA trials.
Origins - MDA was first synthesized and patented in 1910 by the German pharmaceutical company Merck. MDMA was later patented by Merck in 1912.

In summary, MDA and MDMA have similar chemical origins but produce somewhat different effects, with MDA known for being more potent and hallucinogenic compared to the more prosocial MDMA.

Here is a brief overview of how MDMA works at serotonin synapses in the brain:

MDMA enters the presynaptic neuron via the serotonin transporter (SERT) in place of serotonin.
Inside the neuron, MDMA reverses the direction of the SERT and causes serotonin to flow out of the cell into the synaptic cleft rather than being reabsorbed.
This serotonin flooding activates postsynaptic serotonin receptors, especially 5-HT1 and 5-HT2 subtypes, leading to the mood and perceptual changes.
MDMA also interacts with the vesicular monoamine transporter-2 (VMAT2), further promoting serotonin release from vesicular storage into the cytosol and out of the cell.
In addition, MDMA inhibits the enzyme tryptophan hydroxylase, which is the rate-limiting step in serotonin synthesis. This can temporarily decrease serotonin production.
The massive serotonin release produces the empathogenic and prosocial effects typical of MDMA. However, it depletes serotonin levels for a period of time until synthesis can catch up.
MDMA also elevates dopamine and norepinephrine activity, contributing to its stimulant properties.

In summary, MDMA profoundly alters neurotransmission at serotonin synapses mainly by promoting serotonin release via transporter reversal and membrane transport inhibition. This results in the subjective mood and social effects.

Serotonin syndrome, also known as serotonin toxicity or serotonin poisoning, is a potentially life-threatening condition caused by too much serotonin activity in the brain. Some key facts:

It is most often caused by taking medications that boost serotonin to dangerous levels, such as antidepressants SSRIs and MAOIs.
Illicit drugs like MDMA and LSD can also trigger serotonin toxicity when combined with medications.
Symptoms include high fever, agitation, increased heart rate and blood pressure, muscle rigidity, confusion and sometimes seizures.
It results from excessive stimulation of postsynaptic serotonin receptors which leads to a cascade of neuromuscular and autonomic effects.
Diagnosis is based on symptoms and medication history. There are no definitive diagnostic tests.
Treatment involves stopping any serotonin-influencing medications and drugs, plus supportive care with fluids, cooling, medications to control blood pressure, sedation, etc.
Most cases are mild. However, in severe cases it can lead to organ failure, seizures, coma, and potentially death if not addressed quickly.
Preventing drug interactions and overdose and monitoring medication doses can help avoid toxicity episodes.

In summary, serotonin syndrome is an excess of serotonergic activity in the central nervous system that requires prompt medical treatment to stabilize the person and reverse the symptoms.

Several studies are currently underway investigating the potential therapeutic use of MDMA for certain mental health conditions:

PTSD - MDMA-assisted psychotherapy has shown promise in treating post-traumatic stress disorder in multiple trials, leading to breakthrough therapy designation by the FDA. Larger phase 3 trials are underway.
Anxiety associated with life-threatening illness - Small studies found MDMA reduced anxiety and improved quality of life in patients with terminal cancer. More research is planned.
Alcohol use disorder - A pilot study suggests MDMA-assisted therapy can help reduce alcohol misuse. Further trials are in progress.
Eating disorders - A small safety study in bulimia nervosa patients showed reduced symptoms after MDMA-assisted therapy. Researchers are working to confirm the results.
Autism spectrum disorder - Early studies found MDMA increased emotional engagement and improved social skills for adults with autism during therapy sessions.
Depression and anxiety - Researchers are investigating if MDMA could help treat anxiety, depression, and other mood disorders when combined with psychotherapy.
Mechanisms of action - Neuroimaging studies and animal research is examining how MDMA impacts brain activity and connectivity to produce its therapeutic effects.

While still in early phases, ongoing clinical trials continue to demonstrate the promising role MDMA-assisted therapy could play in treating psychological and behavioral health conditions that are often treatment-resistant.

The state of Utah has sponsored some early research into using MDMA-assisted psychotherapy for PTSD treatment:

In 2017, the Utah legislature approved the use of MDMA and psilocybin in FDA-approved medical trials at the University of Utah.
This enabled a Phase 2 clinical trial led by Dr. Craig Blinderman to study using MDMA-assisted therapy on 20 patients with treatment-resistant PTSD.
Participants underwent preparatory psychotherapy sessions before undergoing 2-3 day-long psychotherapy sessions assisted by measured doses of MDMA provided by a pharmaceutical company.
Follow-up sessions focused on integrating the experiences. Participants reported dramatically decreased PTSD symptoms after treatment.
In 2021, based on the encouraging preliminary results, Utah approved expanding the program to include 50 more PTSD patients in Phase 3 trials.
Utah's political leaders were persuaded by the potential of MDMA-assisted therapy to help sufferers of PTSD, including many veterans and first responders in the state.
Utah is one of a few conservative states pioneering access to psychedelic medicine through controlled clinical trials. Early results are informing FDA's review of MDMA-assisted therapy for PTSD.

Nevada is another state where MDMA-assisted therapy research has been pioneered:

In 2017, the Multidisciplinary Association for Psychedelic Studies (MAPS) sponsored an FDA-approved Phase 2 clinical trial at a private psychotherapy clinic in Las Vegas.
The trial studied MDMA-assisted therapy for 28 patients with severe PTSD, mostly from sexual trauma or combat.
Participants underwent preparation, MDMA-assisted therapy sessions, and integration afterwards with mental health professionals.
Two months after treatment, over 68% no longer qualified for a PTSD diagnosis, with further improvements seen a year later.
Based on the successful Phase 2 trial, in 2021 the FDA granted Breakthrough Therapy Designation for MDMA-assisted therapy for PTSD.
MAPS is now sponsoring Phase 3 trials at 15 sites nationally including Las Vegas, involving 200 PTSD patients and placebo controls.
If Phase 3 confirms the results, FDA approval for the treatment is expected by 2023, making MDMA a legal medication for PTSD under federal and Nevada law.
Nevada sites are also participating in MDMA trials for anxiety in terminally ill patients and alcohol use disorder.
The early Nevada research was key in demonstrating MDMA's promise as an adjunct to psychotherapy when used responsibly in controlled settings.