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What Is MDMA: Party Drug Or Therapeutic Agent?

Discussion in 'Pharmacology' started by Mahmoud Abudeif, May 7, 2021.

  1. Mahmoud Abudeif

    Mahmoud Abudeif Golden Member

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    MDMA, short for 3,4 methylenedioxymethamphetamine, is a psychoactive drug whose effects can resemble those of both stimulants and psychedelics. The drug is known to produce distortions in time and perception, enhance the enjoyment of sensory experiences, and make people feel more energized. Its defining feature is that it increases self-awareness and empathy, which together enable a feeling of connectedness that many users report.

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    In its tablet or capsule form, MDMA is known as Ecstasy, whereas Molly — slang for ‘molecule’ or ‘molecular’ — refers to the crystalline powder form of MDMA. However, both versions may contain a number of other drugs that can be harmful and even life-threatening. In fact, sometimes drugs sold as Ecstasy or Molly do not even contain MDMA, which is replaced by other stimulants such as methylone or ethylone. Ecstasy tablets purchased on the street are often adulterated with methamphetamine, ketamine, caffeine, ephedrine, cocaine, phencyclidine (PCP), or over-the-counter cough suppressants such as dextromethorphan.

    MDMA is one of the most popular recreational drugs in the world. The drug is often associated with raves and the party scene, although recently many people in their late 30s and 40s have started using MDMA at home due to its anxiety-relieving effects. In fact, the role of MDMA in clinical practice is going through a revival thanks to recent research showing it can treat post-traumatic stress disorder (PTSD), anxiety, and addiction. In 2017, the Food and Drug Administration (FDA) granted breakthrough therapy status to MDMA-assisted psychotherapy.

    MDMA was first developed by the German pharmaceutical giant Merck in 1912. Initially, MDMA was known as “Methylsafrylaminc,” a precursor compound that the company used to synthesize medications designed to control bleeding.

    For decades the drug was little known until it started gaining a small following among psychiatrists in the 1970s and early 1980s who recognized its therapeutic value by making patients more communicative and open about their problems. It’s worth noting that Alexander Shulgin, an American chemist and pharmacologist affiliated with the University of San Francisco, was the linchpin of MDMA research during these early days.

    Shulgin was first introduced to MDMA in 1976 by one of his students at a course he was teaching at the time at San Francisco State University. The American chemist went on to develop a new synthesis method that made it much easier to make MDMA. He then went on to introduce the chemical to psychologists in California, which then spread to hundreds of psychologists and lay therapists around the nation who found small doses of MDMA greatly aided talk therapy. Some therapists called the drug ‘Adam’ since they believed MDMA helped patients return to a more innocent, primordial state.

    The CIA took note as well and experimented with MDMA, along with other hallucinogenic drugs like LSD, as part of its MK-Ultra project that sought to assess whether psychedelics could be used for ‘mind control’. Although this secret project is notorious for testing psychedelic drugs on unwitting subjects, classified reports suggest that the CIA only used MDMA on non-human subjects. These experiments produced the first known toxicology studies on MDMA — given the codename EA-1475.

    It was also around this time that MDMA started becoming widely available on the street. Eventually, the DEA banned MDMA in 1985 under its ‘War on Drugs’ policy, placing it on the list of Schedule I substances — along with LSD, heroin, and marijuana — that supposedly have no currently accepted medical use and a high potential for abuse. To this day, MDMA is still classed as a Schedule I drug. Most of the MDMA in the U.S. is synthesized in clandestine labs in Canada and the Netherlands.

    What are the effects of MDMA

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    It takes around 15 minutes for MDMA to circulate through the bloodstream and reach the brain, where it leads to psychoactive effects similar to both a stimulant and hallucinogen. These effects typically last three to six hours.

    MDMA is classed as an empathogen, meaning it increases a user’s feeling of empathy and compassion towards others. The main action of MDMA in the brain is that it increases serotonin, the neurotransmitter that, among other things, is responsible for regulating prosocial behavior, empathy, and optimism.

    However, too much serotonin in the brain can trigger “serotonin syndrome”, which especially happens when MDMA is taken together with other drugs such as alcohol, amphetamines, or cocaine.

    Some of the most common side effects of MDMA include euphoria, feeling energetic, dilated pupils, jaw clenching and teeth grinding, excessive sweating and skin tingles, muscle aches and pains, reduced appetite, accelerated heartbeat, high blood pressure, dehydration, and heatstroke.

    Overdosing on MDMA or simply taking repeated doses of the drug over a long time can cause visual and auditory hallucinations, irrational behavior, anxiety, irritability, paranoia, vomiting, high body temperature, racing heartbeat, convulsions.

    After the MDMA high wears off, most users will experience a 24- to 48-hour period during which they may feel lethargic, have a low appetite, or experience a state of unease or generalized dissatisfaction with life (dysphoria, or the opposite of euphoria). Colloquially, this unpleasant period is known as “suicide Tuesday”, a reference to the fact that the crash happens after a heavy weekend of partying.

    Tolerance of MDMA sets in rapidly, making users chase the euphoric effects with repeated doses. But rather than reaping the desirable effects, users who abuse MDMA and have high tolerance typically wind up experiencing more of the sympathomimetic effects, placing them at risk for cardiovascular instability, arrhythmias, and hyperthermia. Long-term abuse of MDMA can result in depression, memory and concentration problems, and liver problems.

    Long-term use of MDMA can also cause dependence, although it is exceedingly rare compared with other highly addictive drugs such as cocaine or alcohol. Less than 1% of patients seeking drug treatment at clinics in Australia are for ongoing problems related to MDMA. MDMA is described as a “self-limiting” drug as the intensity of the positive effects decreases with increased use, while negative effects increase.

    The spikes in blood pressure and heart rate can be dangerous for people with underlying cardiovascular problems. But perhaps the greatest risk of MDMA is that it raises body temperature, especially since its use is often accompanied by strenuous physical activity (such as dancing) in a hot environment such as a crowded venue or in the summer heat. This combination exacerbates fluid loss, which further interferes with the body’s ability to cool itself properly.

    In the early 2000s, some public officials went on a crusade against ecstasy, which they nicknamed “agony”. Some warnings included that MDMA use can lead to Parkinson’s disease, a lifetime of depression, and even “holes in your brain”. Dr. John Halpern, a psychiatrist at Harvard University, thoroughly debunked these claims finding no evidence that ecstasy users have decreased cognitive performance.

    The effects of MDMA can also vary because ecstasy and molly are often tainted with other substances, which have their own psychoactive effects when used alone or in combination with MDMA. Purchasing illegal substances off the street or in nightclubs is always a gamble because you can never be sure what’s inside. In 2018, a pill testing trial at a major music festival in Australia found that nearly half the pills tested were of low purity. Some 84% of people who had their pills tested thought they had bought MDMA but only 51% actually contained any MDMA. On the other end of the spectrum, pill tests in the UK and New Zealand have sometimes found up to three doses of MDMA in a single pill.

    People have died as a result of taking MDMA, although the number of deaths is relatively low compared to other drugs such as heroin, alcohol, and pharmaceuticals. Most of the deaths are not directly from the drug itself but as a result of other complications or contaminants. There were 92 MDMA-related deaths in England and Wales in 2018, up from 56 the year before, and 10,000 hospitalizations for MDMA-related illness/injury in 2011 in the US.

    Water intoxication and MDMA

    People taking on MDMA should drink around 500ml of water an hour if they’re active and half of this amount if inactive in order to combat the dehydration effects of the drug. However, it’s easy to go overboard especially due to overheating from the venue and the effects of MDMA itself.

    Unlike alcohol, MDMA is an antidiuretic, meaning it makes you retain water. When you have too much water in your body, the ratio of salts and water can be thrown off balance. Cells can start swelling with water, and the body can suffer from water intoxication, a condition called hyponatremia. Symptoms include headache, vomiting, and confusion or seizures. In some cases, water intoxication can lead to death.

    MDMA-assisted therapy

    Ecstasy has long been associated with rave culture, particularly electronic dance music (EDM) events. Raves refer to all-night dance parties characterized by loud music and a psychedelic atmosphere.

    But more recently, MDMA is seeing a resurgence as a therapeutic drug, particularly for PTSD. There hasn’t been a new, effective drug meant to treat PTSD in nearly 20 years, but promising clinical trials performed since the previous decade have shown that MDMA might greatly enhance therapy.

    The treatment protocol involves pure MDMA ingested in pill form that is not adulterated with any other substances. Moreover, the drug is always taken under the supervision of a specially-trained therapist over the course of a 12-week program. During this time, the patient will experience 2-3 daylong sessions, each lasting roughly 8 hours.

    Therapists say that MDMA heightens feelings of safety and social connections, allowing patients to revisit traumatic memories and process all the terrible things they went through without triggering the same panic.

    Speaking to NPR, Saj Razvi, a Colorado-based psychotherapist who was a clinical investigator in the Phase 2 trials of an MDMA study for PTSD, said that these sessions can look almost like a “bad trip”. But although they may seem nerve-wracking, MDMA-assisted therapies lead to emotional breakthroughs that otherwise “may take months or years to accomplish”.

    After this phase 2 trial of MDMA-assisted therapy concluded in 2017, researchers found that 54% of the patients who took the drug improved their symptoms to the point that they no longer fit the diagnosis for PTSD, compared to 23% for the control group. What was particularly staggering was that the positive effects appeared to increase, rather than wane, over time. One year after their therapy, 68% of the participants who took MDMA no longer had PTSD.

    Although MDMA is still a schedule I substance in the United States, researchers are able to perform clinical trials with the drug thanks to private sponsors such as the Multidisciplinary Association for Psychedelic Studies (MAPS). The non-profit is now working to get the FDA on board in order to include MDMA in its expanded access program, which will allow patients to use MDMA.

    Besides PTSD, research has found MDMA-assisted psychotherapy considerably reduces anxiety in autistic adults and terminally-ill cancer patients, as well as prevents alcoholism relapse.

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