“Pop a Molly, smoke a blunt, that mean I’m a high roller” — Lil Wayne rapping on the Niki Minaj song “Roman Reloaded”

“Let’s take it back to the first party/ When you tried your first molly and came out of your body” — Kayne West, “Blood on the Leaves”

“Popped a molly and you know, you know you’ll never stop, you think I’m turnt up, wait until my album drops” — Miley Cyrus, “Ain’t Worried About Nothin’ ” (Remix)

A new generation of young adults is embracing the party drug ecstasy (MDMA) – now hyped under the street name “Molly” as a purer, safer high.

Hip hop artists rap about Molly’s euphoric effects, and the drug is widely popular with fans of electronic dance music (EDM) and all-night “rave” parties. In recent years, Molly has spread beyond nightclubs and techno music festivals to a broader range of ethnicities and age groups, according to the National Institute on Drug Abuse.

But how safe is today’s Molly/MDMA?  Does the implied purity of this illicit drug give users a false sense of security?

MDMA has been linked to four deaths at U.S. music venues in 2013.  And there have been a handful of fatalities in the United Kingdom, where some users unknowingly ingested MDMA that was altered with more harmful chemicals – a growing concern worldwide.

In America, MDMA use is relatively small (only 1 percent of the U.S. population used MDMA in 2012; see sidebar article, “Emerging Trends.”).  However, the drug being rebranded as “Molly” is a recent phenomenon, gaining popularity in the U.S. and abroad.

MDMA is still involved in only a tiny fraction of hospital emergency room visits related to illicit drug use.  But those are on the rise; ER visits prompted by MDMA – or MDMA combined with other drugs – increased 128 percent in the United States from 2005 to 2011 (from 4,460 visits in 2005 to 10,176 visits in 2011), according to the Substance Abuse and Mental Health Services Administration (SAMHSA).

MDMA’s Appeal

Molly, which is slang for “molecular,” is the crystal or powder form of MDMA.  It’s typically sold as a capsule (a 100 mg pill costs around $30) and acts as both a stimulant and a psychedelic.  MDMA floods the body with mood-boosting chemicals as it stimulates three of the brain’s neurotransmitters – serotonin, dopamine and norepinephrine.

Within an hour after ingesting the drug, users report feeling increased energy and well-being, a heightened sensory awareness, and a profound connection with others.

Can MDMA Help PTSD, Terminal Patients?

Although MDMA was developed in 1912 by Merck Pharmaceuticals, the drug did not gain popularity until the 1970s when psychiatrists used MDMA to help patients open up about emotionally-upsetting memories.  As a party drug, MDMA arrived in nightclubs in the late 1980s under the street name “ecstasy” (now marketed as “Molly”).  It was classified as an illegal drug in 1985 under the Controlled Substances Act.

Today, pure MDMA is being studied in carefully monitored environments for its mood-boosting therapeutic value.  Clinical trials are underway to determine if MDMA can ease anxieties for patients with post-traumatic stress disorder, terminal cancer and other conditions.

“Recent studies suggest that MDMA-assisted psychotherapy can have long-lasting beneficial effects on PTSD symptoms,” says Dr. John H. Halpern, a psychiatrist at Harvard Medical School who has conducted multiple MDMA studies and directs the Laboratory for Integrative Psychiatry at McLean Hospital in Belmont, Mass.

Halpern notes that MDMA can reduce activity in the brain’s left amygdala (the region that perceives fear), making that part of the brain less sensitive to angry faces.

“Studies also find that people given MDMA exhibit increased interpersonal closeness when describing other people. MDMA elevates the hormone oxytocin, and this seems to explain some, but not all, of the beneficial effects of MDMA upon anxiety,” Halpern says.  He notes that these effects are based on a combination of MDMA with talk therapy.

MDMA may also have potential to treat social anxiety in people with autism, and relieve the angst of those facing a life-threatening illness, Halpern says.

Greatest Health Risk:  Tainted MDMA

People who take Molly as a recreational drug want their capsule to contain only the pure ingredient MDMA (3,4-methylenedioxy-N-methylamphetamine).  But since MDMA is illegal and not regulated, its purity is not guaranteed – and the drug is no safer in powdered form, experts say.

A dose of Molly may be cut with other synthetics that mimic MDMA’s euphoric effects but are harmful alone or when mixed with MDMA.

In 2012, pills sold as “ecstasy” in the United States were found to contain illicit or unregulated drugs such as methamphetamine, ketamine, dimethyltryptamine, benzylpiperazine, TFMPP and PMA — as well as prescription drugs such as procaine, lidocaine, phenacetin and methorphan, according to the United Nations Office on Drugs and Crime (UNODC).

Experts say it’s also possible that a batch of Molly may contain no pure MDMA at all.

In its 2014 report, “The Changing Nature of Ecstasy,” the UNODC makes this assertion:

“Users can no longer be certain of the content of pills sold as “ecstasy” and are thereby exposed to increased health risks and potentially dangerous effects.”

One especially risky substance occasionally mixed with MDMA is the drug PMA, or para-methoxyamphetamine.  PMA is toxic at lower doses than MDMA and can rapidly elevate body temperature.  In the United Kingdom, PMA sold as MDMA or ecstasy was linked to several unintentional overdose deaths in 2013.

“MDMA, like all substances, has health risks,” Halpern says.  “Health risks also arise from the illicit status of ecstasy (material represented as MDMA) when other drugs, such as PMA, are sold as MDMA or when doses are not standardized so that people cannot gauge what dose they “should” take.”

“Without a product insert explaining the safe parameters for dosing and risks and side-effects,” Halpern says, “the user has an extra risk that would not otherwise be there if there were a legal way to procure the substance.”

Adverse Effects of MDMA

Even in its pure form, MDMA is not a benign drug, according to the National Institute on Drug Abuse, which notes:  “Research thus far on MDMA’s addictive properties has shown varying results, but we do know that some users report symptoms of dependence, including continued use despite knowledge of physical or psychological harm, tolerance (or diminished response), and withdrawal effects.”

“I don’t think MDMA is “addictive” in the same way heroin or cocaine or alcohol is addictive,” says Dr. Una D. McCann, a psychiatry professor at Johns Hopkins School of Medicine.  “There can be “psychological” addiction (people who become extremely involved in the “rave culture”), but this is not typical.”  She adds that “MDMA is definitely a health risk” and says animal studies demonstrate that MDMA leads to dose-related neurotoxicity toward the brain’s serotonin (5-HT) neurons.

Heat Stroke & Hydration Dangers

Two of the most serious health risks involving MDMA are heat stroke (hyperthermia) and dehydration.  MDMA can elevate thirst, heart rate and body temperature — especially when the user is dancing vigorously for hours in a hot, crowded nightclub.  While high on MDMA, the person may not perceive exertion due to the drug’s euphoric effects and sensory/time distortions.  In rare cases, dehydration can lead to heat stroke and multiple organ failure.

Drinking water can reduce the risk of heat stroke, and many EDM clubs sell electrolyte-balancing drinks such as “Mollywatr” to encourage hydration.  However, there is a rare but documented risk of obsessively drinking too much water while high on MDMA.  This can lead to over-hydration and an electrolyte disorder known as hyponatremia (low blood sodium).  In rare cases, the condition can result in fatal swelling of the brain.

Other Concerns

Additional symptoms related to MDMA use can include:

• Nausea, chills sweating
• Teeth clenching and grinding
• Muscle tension/cramping
• Blurred vision
• High blood pressure
• Cardiac abnormalities (MDMA can reduce the heart’s pumping efficiency)
• Withdrawal symptoms after the drug wears off, including:
  • Insomnia
  • Loss of appetite
  • Anxiety
  • Depression (caused by depleted serotonin after MDMA use).  Depression may be severe; users nickname the crash “Suicide Tuesdays.”

Increasing the dose of MDMA over a long period of time, or mixing MDMA with alcohol or drugs such as LSD (a practice known as “candy flipping”) or ketamine (“kitty flipping”) can lead to more serious health effects. Overdose from pure MDMA is rare and may involve panic attacks, loss of consciousness or seizures.

Long-Term Risks

Reports of brain lesions or long-term damage to brain function caused by MDMA have been discounted, Halpern says.  He points to design flaws in previous research studies, related to poor matching of the “ecstasy using” group with the control group.

“These issues leave open the contributions made by use of other drugs, or conditions or predispositions that lead people toward repeated substance use,” Halpern says.

“When using well-matched controls, I did not find impaired cognitive function,” with long-term MDMA use, Halpern says.  “A single prospective study (performed by others) looking at people before and after using ecstasy an average of ten times found problems with a type of verbal memory and failed to find any changes on amount of serotonin transporter. Generally if studies are not careful with matching controls with drug use, they will report finding problems.”

Halpern says that independent studies in the Netherlands and the United Kingdom do not rate MDMA high for relative harm, in comparison with other drugs.  “That isn’t to say there are no health risks associated with MDMA,” Halpern says.  “The media has reported on a number of these, including overheating and the extremely rare but often fatal case of hyponatremia (low blood sodium).  But looking at the big picture, MDMA can’t compete with alcohol, tobacco or opioids as a health risk.”

Emerging Trends:  MDMA

It’s the drug of choice in dance clubs and rave culture, but how widespread is MDMA? Overall, use of the drug known by the street names Molly and Ecstasy has declined in the past decade – perhaps due to reduced availability.

“What we do know is that popularity waxes and wanes. The largest numbers of users and new users were around year 2000 and not at the present,” says Dr. John H. Halpern, an MDMA researcher and psychiatrist at Harvard Medical School.  “In the last few years, there has been some uptick in usage, which appears to follow the trending resurgence in popularity of electronic dance music. Yet the early predictions of ever expanding numbers of users failed to materialize.”

The “typical” MDMA user reports one to three uses, according to representative North American or European samples.  “Most users will try MDMA on a handful of occasions in their life and then stop,” Halpern says.

These are emerging trends for MDMA (Ecstasy/Molly):

• Worldwide, an estimated 18.8 million people use Ecstasy at least once annually (2.8 million people in North America), according to the United Nations Office on Drugs and Crime (UNODC).

• In the year 2000, about half (51.4%) of 12th graders surveyed in the United States said ecstasy was “fairly easy” or “very easy” to obtain, vs. only 35.1 percent in 2013 (Monitoring the Future National Survey Results on Drug Use).

• MDMA use by Americans fell from a peak of 2.4 percent of the adult population in year 2001, to 1% of the population in 2012, according to the World Drug Report 2014 from the UNODC.

• An estimated 800,000 Americans tried Ecstasy in 2013 – slightly more than those who tried cocaine (600,000 people) but far less than those who tried marijuana (2.4 million) or abused painkillers (1.5 million).

• The average age for trying Ecstasy in the United States in 20.5 years, according to the 2014 National Survey on Drug Use and Health from the Substance Abuse and Mental Health Services Administration (SAMHSA).