Molly: An in-depth look at the history, pharmacology, and subjective effects of MDMA, including its use in therapy to treat PTSD and potential risks.
TL;DR: “Molly” is a slang term for MDMA, a synthetic psychoactive substance that stimulates the release of neurotransmitters and has both stimulant and psychedelic-like effects. MDMA is classified as an "empathogen" or "entactogen" due to its ability to increase empathy and sociability. It has been used recreationally since the mid-1980s, but its therapeutic potential in treating PTSD has also been explored through MDMA-assisted psychotherapy. MDMA available outside clinical settings is often substandard and mixed with other substances, increasing the risk of adverse health outcomes.
“Molly" is a slang term used to refer to a crystalline or powdered form of MDMA (3,4-methylenedioxymethamphetamine), which is a synthetic psychoactive substance that falls under the phenethylamine class. Molly is structurally similar to amphetamine and possesses both stimulant and psychedelic-like effects.
Molly, also commonly referred to as “Ecstasy,” has been one of the most popular recreational psychoactive drugs since the mid-1980s. The term “Ecstasy” typically refers to MDMA in pill form. However, both “Molly” and Ecstasy” are often used interchangeably.
MDMA, initially known as ‘Methylsafrylamin’, was first synthesized by Dr. Anton Köllisch, a chemist at Merck, in 1912. Dr. Köllisch was researching pathways that could lead to hemostatic substances, although it is often falsely claimed that Merck intended to market MDMA as an ‘anorectic drug’ or ‘appetite suppressor’.
Decades after its initial synthesis under the name ‘Safryl-Methyl-Amin’, the first mechanistic studies to investigate how MDMA interacts with the body and produces its effects were conducted by Merck chemist Max Oberlin to. Although Oberlin was forced to halt his research due to rising material costs, he encouraged other researchers to continue exploring this field.
During the 1970s, MDMA was increasingly detected in both street samples and clandestine laboratories. By the 1980s, MDMA was being distributed on a large scale, and eventually, it was classified as a schedule I controlled substance in the U.S. in 1985.
MDMA is classified as an "empathogen" or "entactogen," which is a relatively new class of psychoactive drugs that differ pharmacologically and phenomenologically from classic psychedelics and amphetamines. These substances are characterized by their ability to increase empathy and sociability and enhance mood and well-being, which sets them apart from other types of drugs.
MDMA stimulates the release of the neurotransmitters or “chemical messengers”: norepinephrine, serotonin, and dopamine. MDMA also blocks the reuptake of these chemicals, resulting in increased concentration levels in the brain.
When MDMA is ingested, serotonin, which is associated with mood elevation, and norepinephrine, which has physical effects, are released in greater amounts than dopamine.
Studies have demonstrated that MDMA can decrease activity in the limbic system, a network of brain structures involved in emotions, motivation, learning, and memory. MDMA was also observed to reduce communication between the medial temporal lobe and medial prefrontal cortex, which are involved in emotional control.
Interestingly, these connectivity patterns are opposite to what is typically observed in individuals who experience anxiety.
MDMA may also increase communication between the amygdala, where we process fear, and the hippocampus, an area involved in the formation, organization, and storage of memories. These effects may be central to MDMA’s efficacy as a therapeutic aid in the treatment of post-traumatic stress disorder (PTSD), potentially enabling patients to access memories of traumatic life events with decreased fear.
A group of neuroscientists at Johns Hopkins University recently demonstrated that MDMA releases oxytocin and stimulates oxytocin-mediated plasticity. This refers to the ability of oxytocin, a hormone and neurotransmitter known for its role in social bonding, trust, and attachment, to facilitate changes in the connections between neurons, which is known as neural plasticity.
Oxytocin’s ability to promote empathy, trust, and the processing of bonding cues may play a role in the development of a solid therapeutic rapport between therapists and patients in MDMA-assisted psychotherapy.
The acute subjective effects of MDMA typically begin 30–60 minutes after consumption. After a 15-30 minute “come up” period, the drug’s peak effects set in, typically lasting for 90–150 minutes.
According to research on the acute effects of MDMA, participants report feeling more sociable, empathic, and euphoric after taking MDMA. Additionally, common emotional effects include tenderness, affection, closeness to others, increased ability to interact with or be open with others, greater self-confidence and self-acceptance, and decreased defensiveness. People also report an overall sense of well-being, although some also experience nervousness and anxiety.
MDMA also has sensory effects, including changes in visual perception, altered sound perception (such as enhanced music appreciation), altered time perception, heightened awareness, and tingling sensations.
Somatic or physical effects may include increased energy, increased body temperature, accelerated heartbeat, bruxism (teeth grinding), muscle clenching, sweating, sweaty palms, and dry mouth. Some people also experience negative physical effects such as nausea and headaches, though these are quite rare.
It is crucial to acknowledge that the MDMA available to individuals outside of clinical settings, primarily in pill form, is generally substandard and frequently mixed with substances that can raise the risks of adverse health outcomes. A recent analysis discovered that 40% of the 529 Molly samples tested did not contain any MDMA whatsoever.
The US Food and Drug Administration (FDA) approved the Multidisciplinary Association for Psychedelic Studies (MAPS) to test MDMA for PTSD treatment in 2003. After successful clinical trials, the FDA granted Breakthrough Therapy Designation in 2017 and agreed on special protocol assessment for phase III trials.
The results of MAPS' first phase III trial showed that over two thirds of participants who received MDMA-assisted psychotherapy no longer met PTSD criteria two months post-treatment. MAPS' final phase III trial is now fully enrolled and expected to lead to MDMA-assisted psychotherapy becoming a legal medicine by mid-2024.
It is not possible to predict with certainty what the experience of taking MDMA will be like, as individual responses can vary widely. However, ensuring that the drug is used in the right circumstances is likely to facilitate a positive experience.
Set and setting can play an important role in shaping the MDMA experience. “Set” refers to an individual's mindset or mental state going into the experience, while "setting" refers to the physical and social environment in which the experience takes place.
Research has shown that a supportive and comfortable environment, such as one provided by trained therapists, can lead to more positive outcomes for MDMA-assisted psychotherapy. By setting intentions and creating a safe and comfortable environment, individuals can enhance the potential therapeutic benefits of MDMA.
The effects of set and setting are rightly emphasized when discussing the use of MDMA and other mind-altering substances. However, what is often neglected but equally important is the dose. In clinical trials, participants are typically administered doses of MDMA ranging from 80 to 150mg, with a top-up dose given 90-150 minutes later.
Molly, or MDMA, is considered to be relatively safe in comparison to other commonly accepted recreational drugs such as tobacco and alcohol.
Typically, MDMA doesn't cause any life-threatening effects on its own, but there are still potential health risks associated with its use. Fortunately, these risks can be minimized through the use of harm reduction practices.
MDMA can interfere with the body's ability to regulate temperature, especially when combined with physical activity like dancing and prolonged exposure to warm environments. This can lead to hyperthermia, the main cause of MDMA-related deaths (though it's still relatively low compared to other drugs).
To reduce the risk of overheating, it's important to take regular breaks from physical activity and stay well-hydrated. However, over-hydrating can be dangerous, as MDMA can cause water retention and lead to low blood sodium levels (hyponatremia), which can be fatal.
To prevent hyponatremia, it's important to pay close attention to how much water you're drinking and avoid combining MDMA with diuretics like alcohol. By being mindful of hydration levels and avoiding excessive physical exertion, users can help ensure a safer MDMA experience.
There has been much discussion surrounding the neurotoxicity of MDMA in recent years. While it is generally agreed upon by scientists that MDMA is safe when used responsibly, continuous and high-dose usage can lead to some form of neurotoxicity. Therefore, it is highly discouraged to use MDMA at high doses for long periods of time.
It is still unclear how much of this risk applies to the typical recreational user who only uses MDMA occasionally. However, users are advised to wait for several months between each use to allow serotonin levels to return to normal and to decrease the risk of neurotoxicity.
Long-term, heavy use of MDMA can lead to valvulopathy, a condition that affects the proper functioning of one or more heart valves.
A study published in 2007 found that 28% of regular or former MDMA users had pathologic echocardiographic results, compared to 0% of the control group. It's important to note that the individuals who developed valvular heart disease were consuming three doses of MDMA per week for at least six years.
This suggests that the severity of MDMA-induced valvulopathy may be dependent on high-dose, cumulative use. More research is needed to fully understand the cardiovascular effects of MDMA.
In summary, MDMA, also known as “Molly” or “Ecstasy,” is a synthetic psychoactive substance that can have both stimulant and psychedelic-like effects. It belongs to a relatively new class of drugs called "empathogens" or "entactogens," which can enhance empathy, sociability, and mood.
While MDMA has been popular for recreational use since the 1980s, recent studies have shown that it may have therapeutic potential in the treatment of mental health disorders, such as PTSD, when used in a controlled setting.
However, it's crucial to note that the MDMA available outside of clinical settings is often of substandard quality and can pose serious health risks. Therefore, it's essential to use caution and seek professional help when considering MDMA use for any purpose.
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