3,4-Methyl​enedioxy​methamphetamine (MDMA), is commonly known as ecstasy or molly.



It is a psychoactive drug primarily used for recreational purposes.



Its effects include:  altered sensations, increased energy, empathy, as well as pleasure.



When taken by mouth, effects begin in 30 to 45 minutes and last 3 to 6 hours.



Routes of administration: Common: by mouth



Uncommon: snorting, inhalation, injection, rectal.



P450 extensively involved in metabolism, including CYP2D6



Onset of action 30–45 minutes.



Elimination half-life -5.8 ± 2.2 hours 



Duration of action 4–6 hours.



Excretion by Kidney



Adverse effects: addiction, memory problems, paranoia, difficulty sleeping, teeth grinding, blurred vision, sweating and a rapid heartbeat



May cause death due to hyperthermia and dehydration.



Use is associated with depression and fatigue.



Acts primarily by increasing the activity of the neurotransmitters serotonin, dopamine and noradrenaline in the brain.



It is of the amphetamine class of drugs and has stimulant and hallucinogenic effects.



It is illegal in most countries.



MDMA has no approved medical uses.



In the United States, as of 2017, about 7% of people have used MDMA at some point in their lives.



Individuals experience subjective effects within 30 to 60 minutes of oral consumption and reaching peak effect at 75 to 120 minutes.



Effects plateaus about 3.5 hours.



Short-term psychoactive effects include:






Increased self-confidence, sociability, and perception of facilitated communication



Entactogenic effects, increased empathy or feelings of closeness with others and oneself.



Dilated pupils



Relaxation and reduced anxiety.



Increased emotionality.



A sense of inner peace.



Mild hallucinations.



MDMA is associated with high motor activity, reduced sense of identity, and poor awareness of surroundings. 



Use in a quiet environment is associated with increased lucidity, concentration, sensitivity to aesthetic aspects of the environment, enhanced awareness of emotions, and improved capability of communication.



Its effects have been characterized by infantile ideas, mood lability, and memories and moods connected with childhood experiences.



It has empathy-producing effects.



it is often the drug of choice within the rave culture and used at clubs, festivals, and house parties.



The sensory effects of music and lighting are often synergistic with the effects of the drug. 



The drug  is used less often than other stimulants: less than once per week.



MDMA is sometimes taken in conjunction with other psychoactive drugs such as LSD, mushrooms, and ketamine.



It has no accepted medical indications.



Widely known as ecstasy.



The purity of substances sold as molly have been found to vary widely, containing  multiple other chemicals.



Powdered MDMA ranges from being pure MDMA to crushed tablets with 30–40% purity.



MDMA tablets typically have low purity, and sometimes contain 3,4-methylenedioxyamphetamine, and other amphetamine derivatives, caffeine, opiates, or painkillers.



While MDMA is usually consumed by mouth, it is sometimes snorted.



Its adverse effects are usually the result of high or multiple doses.



A single dose toxicity can occur in susceptible individuals.



Health risks of short term MDMA are hyperthermia and dehydration.



Fatal hyponatremia has  developed in MDMA users attempting to prevent dehydration by consuming excessive amounts of water.



Its immediate adverse effects:












Increased wakefulness



Increased perspiration and sweating



Increased heart rate and blood pressure



Increased psychomotor activity



Loss of appetite



Nausea and vomiting






Erectile dysfunction



Visual and auditory hallucinations 



Adverse effects that may occur or persist for up to a week.



There is no evidence of structural or functional brain changes in MDMA users with only a moderate (<50 doses used and <100 tablets consumed) lifetime exposure. 



The long-term use of MDMA produces neurodegeneration in striatal, hippocampal, prefrontal, and occipital serotonergic axon terminals.



MDMA neurotoxic damage to serotonergic axons have been shown to persist for more than two years.



It may cause elevations in brain temperature and is are positively correlated with MDMA-induced neurotoxicity.



No serotonergic neurotoxicity is present in most casual users.



Adverse neuroplastic changes to brain microvasculature and white matter can occur using low doses of MDMA.



Use is associated with reduced gray matter density in certain brain structures.



Lon-term use associated with global reductions in gray matter volume, thinning of the parietal and orbitofrontal cortices, and decreased hippocampal activity.



Regular use associated with impaired 


cognition, attention, learning, memory, visual processing, and sleep.



These impairments is correlated with lifetime MDMA usage and are partially reversible with abstinence.



Effects for memory impairments in ecstasy users are generally small overall.



It is associated with increased impulsivity and depression.



Serotonin depletion following MDMA use can cause depression, and one of the main reasons for cessation of its use.





At high doses it  increases the permeability of the blood-brain barrier, thereby making the brain more susceptible to environmental toxins and pathogens.



MDMA is a moderately teratogenic drug: 


In utero exposure is associated with a neuro- and cardiotoxicity and impaired motor functioning. 



The severity of these developmental delays increases with heavier MDMA use.



Approximately 60% of users experience withdrawal symptoms when they stop taking MDMA: symptoms include fatigue, loss of appetite, depression, and trouble concentrating.



Estimated to have a psychological dependence and physical dependence potential roughly three-fourths to four-fifths that of cannabis.



MDMA is less addictive than other stimulants.



No medications available to treat MDMA addiction.



Acute toxicity is related to the serotonin syndrome and sympathomimetic effects.



Management of acute MDMA toxicity: treatment of hyperthermia, hyponatraemia, serotonin syndrome, and multiple organ failure.



Symptoms of MD overdose: 



Disseminated intravascular coagulation



Intracranial hemorrhage



Severe hypertension






Hypotensive bleeding









Mental confusion






Stimulant psychosis



Cognitive and memory impairment



Retrograde or anterograde amnesia












Loss of consciousness



Serotonin syndrome



Muscle rigidity






Acute respiratory distress syndrome



Acute kidney injury



Cerebral edema









Hyponatremia (Syndrome of inappropriate antidiuretic hormone)



MDMA also interacts with drugs which inhibit CYP450 enzymes.



Concurrent use with other serotonergic drug can result in a life-threatening serotonin syndrome.



Overdose resulting in death has also been reported in people who took MDMA in combination with certain monoamine oxidase inhibitors.



It  acts primarily as a presynaptic releasing agent of serotonin, norepinephrine, and dopamine.



It is also a monoamine transporter substrate, so it enters monoamine neurons via these neuronal membrane transport proteins.



MDMA produces competitive reuptake inhibition at the neuronal membrane transporters.



Inhibition of VMAT2 by MDMA results in increased concentrations of the associated neurotransmitters serotonin, norepinephrine, or dopamine in the cytosol of a monoamine neuron.



Its actions increase the synaptic concentrations of monoamine neurotransmitters.



MDMA has ten times more affinity for uptake at serotonin transporters compared to dopamine and norepinephrine transporters.



MDMA has mainly serotonergic effects.



Serotonin binds to receptors on neurons.



The MDMA concentration in the blood reaches its maximal concentration in the blood stream between 1.5 and 3 hours after ingestion.



MDMA duration of action  is usually four to six hours.



AFTER 4-6 hours serotonin levels in the brain are depleted, but return to normal within 24–48 hours.



There are a number of metabolites of MDMA.



80% of MDMA is metabolized in the liver, and about 20% is excreted unchanged in the urine.



The metabolism may be primarily by cytochrome P450 (CYP450) enzymes CYP2D6 and CYP3A4 and COMT. 



MDMA and metabolites are primarily excreted as conjugates: sulfates and glucuronides.



MDMA and MDA may be measured  in blood, plasma or urine to monitor  use, confirm a diagnosis of poisoning or assist in the forensic investigation.






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