3,4-methylenedioxy-methamphetamine (MDMA), also commonly known as ecstasy, was synthesised in 1912 as a research chemical. The stimulant and euphoric effects of MDMA lent itself to becoming hugely popular in the late 1980s rave scene. During this time, pills containing MDMA, or ecstasy tablets, became available, often containing a combination of other stimulants.

MDMA is an empathogen, producing experiences of emotional communication and connectedness, as well as stimulant. The empathogenic and fear-inhibiting effects of MDMA have been long-recognised by researchers and therapists, and MDMA therapy to treat post-traumatic stress disorder (PTSD) has recently become fully legalised in Australia.

In non pill form, MDMA appears as white/grey crystals or powder, which is ingested by wrapping the powder in papers and swallowed as “bombs” or snorted nasally.

Effects

Potential positive effects include euphoria, increased energy, sexual arousal, feelings of intimacy, sense of unity with others and the world, overall sense of well-being, feeling calm and relaxed, sense of peace and increased appreciation of music. (https://pubmed.ncbi.nlm.nih.gov/16771886/)
Positive neutral effects include mild hallucinations, the desire to dance, spontaneous body sensations, increased experience of time, tactile enhancement, tight jaw and the desire to grind teeth. (Psychonaut Wiki)
Potential negative effects include agitation, restlessness, paranoia, confusion, compulsive redosing, difficulty focusing, inability to fall asleep when tired, amnesia, difficulty urinating and feeling dehydrated. (Psychonaut Wiki)
A person may experience physical effects that include dry mouth, increased sweating, accelerated heart rate, increased body temperature, increased blood pressure, nausea, vomiting, erectile dysfunction, muscle contractions, pupil dilation and appetite suppression. (Psychonaut Wiki) (https://psychonautwiki.org/wiki/MDMA)

Dosage

Crystal form of MDMA(4)

30mg: Threshold
40-75mg: Light
60-90mg: Common sensitive/ low body mass individual
75-175mg: Common average body mass individual
110-150mg: Common less sensitive/ larger body mass individual
150-200mg: Strong
200mg+: Heavy

Weighing up and dosing MDMA is strongly recommended. If weighing scales are unavailable, harm-reduction information by The Loop guides users to “crush, dab, wait.” Guidance for this method can be found here.

When in pill form, data for different pills including MDMA content can be found here. Pills can be unexpectedly strong so taking a quarter of the pill to begin with and waiting for the effects to kick-in is recommended.(Roll Safe)

Duration

Onset: 20-70 minutes (depending on how MDMA is being ingested and how much food has been eaten)
Duration: 3-6 hours
After effects: Up to 12 hours

NB: MDMA can sometimes take an unexpectedly long-time (up to 3 hours) to have a come-up which can lead to users redosing before their first dose has taken effect, increasing the risk of overdose.

Dangers

What not to mix with:

Amphetamines: As both MDMA and amphetamines increase body temperature, blood pressure and heart and rate, taking these drugs in combination can increase the risk of these effects increasing the risk consequences including heat stroke, heart-attack and death. Taking MDMA with amphetamines may also increase the risk of toxic effects on the nervous system. (6)
Caffeine: Evidence in rodents has demonstrated that caffeine can increase the toxic effects of MDMA, such as increased body temperature, increased heart rate, and even death. Caffeine may also increase the long-term toxic effects of MDMA on the nervous system.
LSD and psilocybin: Taking LSD or psilocybin with MDMA is also known as “candyflipping” and is a popular combination because of certain desired effects. However, the combination can increase the intensity of the effects of either drug, which can be unpleasant and cause anxiety, especially when unexpected.
Alcohol: MDMA is often taken in a party setting meaning it is often combined with alcohol. Whereas alcohol is a depressant, meaning it has inhibitory effects on the nervous system, MDMA is a stimulant, meaning it has excitatory effects on the nervous system. Therefore, the effects of MDMA and alcohol can cancel each other out which can encourage users to take more of either drug, increasing the risk of overdose.
Furthermore, both MDMA and alcohol can cause toxic effects on the liver so taking alcohol and MDMA together increases this risk.
Antidepressants: As SSRI antidepressants and MDMA both increase the amount of serotonin in the nervous system, taking these in combination increases risk of serotonin syndrome which can lead to seizures and death.

What are the dangers?

Short-term risks

Hyperthermia: Hyperthermia is a dangerously high increase in body temperature which can lead to organ failure and death. MDMA increases the core body temperature and when taken in a nightclub, the combination of this effect with sweating from lots of physical exertion and a hot, crowded environment can have dangerous outcomes.
Hyponatremia (drinking too much water): MDMA is an anti-diuretic meaning it makes the body retain more water than usual. As people often feel thirsty on MDMA due to increase in body temperature, they may drink excessive amounts of water. In several cases, this has led to water toxicity and death. (8)
Contaminated pills: Ecstasy may be sold in pill forms that contain very little or no MDMA. Pills may have MDMA-like chemicals added which are toxic at low doses, such as NBOMes and PMA. In rare cases, pills contaminated with these substances have caused death.
Serotonin syndrome: Consuming stimulants or serotonergic acting drugs alongside MDMA increases the risk of serotonin syndrome. Read more under general psychedelic risks and harm-reduction advice.
Experiencing a “comedown”: Excess physical exertion with lack of sleep and nutrition combined with MDMA’s acute neurotoxic effects means users can feel in a low mood with low energy following the experiences for a couple of days to weeks after. This article gives some tips and advice to help avoid a comedown.
Risky behaviours and impulsive decision-making: As mental coordination whilst under the influence of drugs is impaired, this can lead to somebody doing something dangerous or deadly. Impaired judgement and false-senses of certainty may also mean people under the influence make decisions that wouldn’t otherwise if they were sober which can lead to negative outcomes.

Long-term risks

Neurotoxicity: Studies have implied that MDMA can cause the death of nerve cells that produce serotonin. Serotonin is an important chemical for the brain involved in many psychological functions, including mood and hunger. Destruction of serotonin-producing cells could therefore interfere with these functions.
Problems in memory and learning: Neurotoxicity caused by MDMA could lead to problems with memory and learning.
In one study, researchers found that long-term recreational use of MDMA increased the risk of memory problems and cognitive impairment in users. However, the findings in this study could be influenced by several other environmental factors.
Another study found that in rats, MDMA caused a decrease in the number of vitamin D receptors in an area of the brain called the hippocampus. As the hippocampus is crucial for cognition, depleted vitamin D in this area may be linked to impaired cognitive function.

How can the risks be minimised?

It is important to have regular dancing breaks when taking MDMA in a nightclub setting and ensure you consume water and/or electrolyte-replenishing drinks. However, fluids must be drunk in careful moderate doses, and it’s recommended not to drink more than 500mL fluid per hour to prevent risk of hyponatremia. Drinking alcohol dehydrates the body and increases risk of hyperthermia so avoiding combining alcohol and MDMA will help avoid this risk.
Often urinating can be more difficult under the influence of MDMA and the psychological need to urinate is reduced, therefore, when taking MDMA remember and attempt to make regular toilet breaks to reduce water being stored in the system. Symptoms of water intoxication include nausea with vomiting, confusion, severe fatigue, muscle weakness and cramps. If these symptoms become apparent in oneself or in friends who have taken MDMA, medical attention must be sought. (12)
MDMA in crystal form is likely to be safer for consumption than in pill-form. If testing services are available, or there is access to a testing kit, check the purity of pills.
Taking MDMA infrequently and at lower doses decreases likelihood risk of long-term risks, including neurotoxicity.
Taking vitamin D supplements may prevent damage linked to vitamin D receptor reduction in the hippocampus.

What are the potential benefits?

To date, MDMA has been clinically trialled for:

Weblinks

Rollsafe is an education website with lots of guidance, facts and safety information on MDMA from best supplements to take to avoid MDMA neurotoxicity, to which specific drugs to avoid in combination with MDMA: https://rollsafe.org/
Psychonaut wiki for MDMA: https://psychonautwiki.org/wiki/MDMA#Subjective_effects
A guide to taking MDMA for the first time written by author of the Global Drugs Survey: https://www.globaldrugsurvey.com/gds-2018/thinking-of-using-mdma-for-the-first-time-heres-our-checklist-to-help-you-stay-safe/

Videos:

What happens to your brain on MDMA: https://www.youtube.com/watch?v=jEAr7ThsYew
Dr. Ben Sessa explaining the usefulness of MDMA in treating psychiatric disorders: https://www.youtube.com/watch?v=jEAr7ThsYew

References

Credit to Dr Andrew Gibson for contributing his medical expertise and background in harm-reduction to the process of making this content.