There has been a recent increase in public awareness of the drug 3,4-methylenedioxymethamphetamine (MDMA), commonly known as Ecstasy. A purified version of this drug, known as “Molly”, is perceived by users to be safer than other illicit drugs, as it is expected to be free of toxic adulterants. This article reviews the clinical effects and toxicity associated with MDMA, as well as data on the purity of Molly and Ecstasy.

A number of highly publicized deaths and recent references in popular music have increased the public's awareness of the drug “Molly,” a purified version of 3,4-methylenedioxymethamphetamine (MDMA) which is commonly known as Ecstasy.1,2 Despite its definition as “pure” or “molecular” MDMA, the purity and content of substances sold under the name of Molly on the street is questionable, as dealers often cut the powder with other ingredients, most commonly methamphetamine and caffeine.3,4 

In recent years, clinicians have seen a doubling in the number of MDMA-related cases in emergency departments from 10,200 visits in 2004 to 22,000 visits in 2011, according to the Drug Abuse Warning Network.5 Given the recent media interest, this review focuses specifically on studies centering on Molly and examining their findings and contribution to existing MDMA literature.

A September 15, 2013, search of PubMed with the terms “molly mdma” (3 results), “molly ecstasy” (3 results), “mdma reviews” (430 results), “mdma toxicity,” (827 results) and “mdma purity.” (18 results) resulted in numerous publications that reflect different themes in MDMA and illicit drug research including clinical effects, toxicity, purity, and the potential for the development and use of synthetic or alternative versions of the drug.

The three articles specifically referring to Molly were chosen, then supporting articles providing background for those three articles were selected from search results based on a review of titles and abstracts to ascertain the depth and focus of each article on clinical effects, toxicity, and purity, both relating to and expanding on the scope of the three Molly articles. Two newspaper articles on recent Molly-related deaths at electronic music festivals were also selected from 33 results of a September 15, 2013, search of LexisNexis Academic “All News (English)” database newspapers using the search term “molly drug.”

MDMA has both stimulant and psychedelic (entactogen) effects.6 The popularity of MDMA or Molly stems from its reputation for positive effects of mental stimulation, emotional warmth, empathy toward others, general sense of well-being and decreased anxiety.6 Some users have also reported enhanced sensory perception as a key result of the MDMA experience.7,8 

These positive effects are thought to be primarily due to MDMA's effect on serotonin. MDMA also affects the release of dopamine and norepinephrine but to a lesser extent than serotonin. MDMA is thought to cause the mood elevating effects by excess release of serotonin. 9 Studies have hypothesized that MDMA-induced release of serotonin is due to reversal of the 5-HT uptake transporter. Mild hallucinogenic-type perceptual effects are thought to be due to stimulation of the postsynaptic 5-HT2 receptor. 10 The negative behavioral effects experienced by users for several days afterwards may be attributed to depletion of serotonin.10,11 Pretreatment of patients administered MDMA with the selective serotonin reuptake inhibitor (SSRI) citalopram markedly attenuated the overall MDMA experience including subjective, cardiovascular, and acute adverse responses. Positive mood effects have also been linked to dopaminergic D2 receptor stimulation. Haloperidol pretreatment altered the subjective MDMA effects from a pleasurable state of well-being and euphoria to one of dysphoria with slightly increased anxiety.10 MDMA- induced release of norepinephrine is likely the cause of increase in heart rate and blood pressure that is often seen with MDMA use.

Adverse effects of MDMA include nausea, chills, sweating, involuntary jaw/teeth clenching and teeth grinding (users may commonly be seen with pacifiers), muscle cramping, blurred vision, hyperthermia, dehydration, increase in blood pressure, arrhythmias, heart failure and kidney failure. The following adverse effects have a reported duration of up to one week or longer (in regular users) post-MDMA use: anxiety, restlessness, irritability, sadness, impulsiveness, aggression, sleep disturbances, decreased or lack of appetite, thirst, decreased interest in and pleasure from sex and significant reductions or changes in mental abilities. Signs and symptoms of MDMA overdose have included high blood pressure, faintness, panic attacks, loss of consciousness and seizures.7 

Molly is perceived by users as safer than other illicit drugs as it is expected to be pure and free of adulterants which are commonly associated with toxicity.12 A study from the University of Miami attempts to address this assumption through the presentation of three case studies of patients who had taken unknown quantities of allegedly pure Molly alone or in combination with marijuana or alcohol. The three patients developed intracranial hemorrhaging despite a lack of pre-existing cerebrovascular disease.12 This study concluded that “purified MDMA”, or Molly is no safer than traditional MDMA due to its potential to cause potentially life threatening intracranial hemorrhage in previously healthy patients.12 

The toxicities associated with MDMA have been extensively demonstrated in the literature including nephrotoxicity (e.g., urinary retention, acute renal failure),13,14 hepatotoxicity (e.g., jaundice, hepatomegaly, hepatitis, fibrosis),15,16 cardiovascular toxicity (e.g., myocardial infarction, cerebrovascular accident),1719  intracranial hemorrhage,20 drug interactions,21,22 hyperthermia,23,24 effects on male fertility (e.g., decreased serum testosterone and testicular changes in animal studies),25 immunosuppression,26 and neurotoxicity (e.g., serotonin syndrome and memory deficits).6,2739  Fatalities in which the cause of death was determined to be MDMA-related (i.e., MDMA or methylenedioxyamphetamine (MDA) directly contributed to death), have also received attention in research.40,41 

A review of the literature suggests that the major toxicity associated with MDMA use is neurotoxicity in the form of deficits in cognitive function, specifically short and long term memory,42 higher cognition (e.g., logical reasoning, executive processing), impaired problem solving abilities, and decreased emotional intelligence.43 Users are affected by neurocognitive impairment through a reduction in serotonin transporter levels in the cerebral cortex as well as vision, sleep disturbance, and psychiatric status changes and a risk, if used during pregnancy, for psychomotor impairments in children.43 MDMA use causes acute toxicities, but rarely death as an isolated substance.42 This appears to be consistent with the perception of Molly users that a pure version is slightly safer in that it is less likely to result in death, but as purchased on the street, the drug has no guarantees of purity.

MDMA may interfere with its own metabolism by MDMA metabolites interfering with the body's ability to break down the drug. If users ingest additional doses of MDMA to extend the euphoric effects of the drug, unexpectedly high blood levels could result from this interference with metabolism that could worsen the cardiovascular and other toxic effects of the drug. MDMA may also interfere with the metabolism of other drugs, including some that are commonly used in combination (e.g., ethanol) or as adulterants.21 MDMA is frequently used in combination with other substances of abuse including ethanol, amphetamines, hallucinogens and cannabis, which increases the potential for toxicity.21 A study of MDMA related deaths in Australia revealed that of 82 reported deaths from 2000 to 2005, in nearly 60% of the cases, Molly was used with at least one other drug, the most common drugs implicated being methamphetamine, opioids, benzodiazepines, and ethanol.40 Regular cannabis and MDMA use may cause toxicities including psychological (e.g., anxiety, obsessive compulsive behavior, psychosis, depression, and paranoia) and immune system alterations resulting in increased susceptibility to infection (e.g., uncomplicated urinary tract infections, colds, sinusitis and pharyngitis).21 Regular concurrent use of methamphetamine and MDMA has reportedly resulted in severe neurotoxicity.21 

Purity is a major concern with regards to Molly. A recent study looking at brands of Ecstasy including Molly, examines the psychosocial attitudes of sellers and users towards the drug and how it is marketed.3 Data were obtained on purity and perception of illicit substances based on brand name through information gathered from sellers of Ecstasy and their clientele. Ecstasy brand names such as Molly follow a similar trend as early LSD brand marketing with innocent or nostalgic sounding brand names (“Mickey Mouse in Fantasia,” “Alice in Wonderland,” “Snoopy”).3 Ecstasy brands intentionally market the drug as fun and harmless with kid friendly logos, attempting to build customer recognition and trust in purity of the product.3 A drawback to the logos is the potential for counterfeit versions of the drug where the logo is used, but the product may not be the same, leading to ingestion of questionable substances of unknown toxicity.3 Due to this difficulty, it was felt that the reputation and trustworthiness of the seller was more important than the logos on the tablets,3 although there is still danger in this reliance on dealer reputation as dealers have variable levels of knowledge on the manufacturing and content of the drugs. There were different perceptions regarding powder versus pills as powder is more easily adulterated, but the powder has the reputation as the highest purity form.3 

Several studies of the purity of Ecstasy have been performed, which show that Ecstasy tablets have a wide range of purity. During the 6 years of monitoring conducted by Tanner-Smith on average only 39% of the tablets analyzed were comprised solely of MDMA while 49% included MDMA and other substances and 15% contained no MDMA and only other substances.44 During the 15 years of monitoring conducted by Vogels, et. al., on average 78% of tablets analyzed were comprised of only ecstasy like substances, while the remainder were found to include numerous substances including benzylpiperazine, ketamine, lidocaine, procaine, ephedrine, caffeine and methamphetamine.45 Of these 78%, the MDMA concentration varied significantly ranging from 1 mg to 225 mg MDMA per tablet.45 

Adding to concerns on the purity of Molly, some substances sold under the name of Molly on the street may actually be an alternative version which mimics the effects of MDMA and evades legal restrictions. The drug TFMPP is sold under the names of “Molly,” “Legal X,” and “Legal E.” 47 It is referred to as “legal” because it is not a prohibited substance under the Controlled Substances Act. 46 The Drug Enforcement Administration (DEA) placed TFMPP under emergency Schedule I status in 2002, however this designation was removed in 2004 following an FDA evaluation recommending removal to non-controlled status. 46 The DEA reports recent escalation in abuse of this substance. 46 TFMPP is commonly abused together with the schedule I controlled substance benzylpiperazine (BZP). 46 

A recent study reviews the neurochemical effects of this alternative Molly TFMPP and BZP, administered alone or in combination on rat brains.47 It was determined that BZP administration resulted in an elevation of extracellular DA and 5-HT in vivo that was similar to MDMA. TFMPP on the other hand showed an elevation of extracellular 5-HT in vivo, but was at least 3-fold less potent than MDMA. Co-administration at low doses showed extracellular increases in DA and 5-HT consistent with neurochemical responses seen in low dose MDMA administration. Based on these pharmacological results it is possible that the combination of BZP and TFMPP in humans may produce MDMA like psychoactive effects, but the potential for adverse effects (i.e., seizures) remains.47 

A review of recent literature concerning the recreational drug Molly has revealed consistencies with existing literature. Molly is a pure form of the drug MDMA and may cause similar toxicities including neurotoxicities such as intracranial hemorrhage. Although users associate powdered Molly with safety due to its reputation for higher purity, substances sold by the name of Molly on the street commonly contain adulterants or may not contain MDMA at all. Drugs such as TFMPP combined with BZP mimic some of the mechanistic activities of MDMA and may cause the same psychoactive and adverse effects.

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