Drug Researchers Find MDMA’s Serotonin-Depleting Effects May Be Overstated

The discovery of alterations in GLX levels in the striatum suggests that MDMA use may have broader neurobiological effects than previously believed (Mustafa et al., 2020). I am writing to discuss the significant findings presented in the study titled “Chronic 3,4-Methylenedioxymethamphetamine (MDMA) Use Is Related to Glutamate and GABA Concentrations in the Striatum But Not the Anterior Cingulate Cortex” (Zimmermann et al., 2023). Besides from hyperthermia, brain edema is another severe complication of MDMA use.

Those with serious side effects or who quit Molly and are still experiencing symptoms should seek a professional to oversee the treatment of side effects. In general, ceasing the use of MDMA will eventually cause these levels to stabilize and minimize the symptoms of drug withdrawal, but this process can take time. As Molly induces feelings of love and empathy, those under its influence often display more outward positive emotions than they typically would without the drug. Molly causes behavioral and physical changes in its users. As a party drug, Molly is popular among high school and college students. However, most of the drugs used to cut Molly come from China.

Effects

The atypical antipychotic clozapine has been shown to reverse hyperthermia and cutaneous vasoconstriction induced by MDMA in rats or rabbits82 but human data to support its clinical use are lacking. The various treatments for hyperpyrexia induced by MDMA or other psychostimulants have not been systematically evaluated in the emergency room setting. Four-Methylthioamphetamine is another serotonergic compound73 that has been linked to hyperthermia.74 Other novel substances, such as 3,4-methylendioxypyrovalerene, which potently inhibits dopamine and norepinephrine uptake52 and induces marked and prolonged agitation, has also been reported to induce hyperthermia.75 Notably, hyperthermia has also been described with the dopamine and norepinephrine transporter inhibitor methylphenidate.76

The long-term impacts of MDMA on brain structure and function are a subject of ongoing research and debate. These effects are primarily due to MDMA’s impact on the norepinephrine system and its overall stimulant properties. Physical symptoms related to brain activity are also common with MDMA use. Cognitive changes are another significant aspect of MDMA’s short-term effects.

It has been linked to an increased risk of stroke, with evidence suggesting that it may cause cerebrovascular accidents, particularly in young people. As research progresses, it’s likely that our understanding of MDMA’s effects on the brain will continue to evolve. While the potential therapeutic benefits of MDMA are exciting, it’s crucial to continue studying its long-term neurological impacts to fully understand both the risks and benefits of its use.

However, β blockade without α blockade should be avoided in drug-induced sympathomimetic toxicity because of the unopposed α-adrenergic receptor stimulation that enhances vasoconstriction83 and results in further increases in blood pressure60,84 and possibly body temperature. Sedation with benzodiazepines and intravenous fluid replacement are the most important acute supportive care measures in patients with substance-induced sympathomimetic toxidromes and/or agitation.3,5,78 The management of hyperpyrexia includes cooling (fanning, water, ice packs, ice bath, cooling blankets) and mechanical ventilation.10 Dantrolene, which acts at skeletal muscles to inhibit the release of calcium, has also been used.6,10,79 However, dantrolene does not inhibit the thermogenic effects of MDMA,80 and the drug does not modulate the mechanism of MDMA-induced hyperthermia discussed above. Altogether, the mechanistic studies in humans provide support for the conclusion that MDMA mainly increases body temperature via the release of norepinephrine, which then increases metabolic heat generation and impairs heat dissipation via vasoconstriction.

Cognitive And Memory Changes

This is supported by a case report by Fortis et al. (2004), who found a strong association between MDMA abuse and cerebral infarction in a young man who presented with confusion and sweating, and was subsequently diagnosed with an ischemic infarct in the brainstem. This alteration in the 5-HT neurotransmission system may predispose MDMA users to cerebrovascular accidents. MDMA is a synthetic drug that acts as a stimulant by speeding up the central nervous system and increasing feelings of empathy and compassion. While not everyone who uses MDMA will experience a stroke, it is important to be aware of the potential risks and warning signs to reduce the likelihood of severe outcomes. The toxic effects of MDMA abuse can lead to malignant hyperthermia, acute respiratory failure, cardiac arrhythmias, and hypertension, all of which are risk factors for stroke.

Effects on the Brain

One area of concern is the potential for long-lasting changes to the serotonin system. These cognitive effects are thought to be related to MDMA’s impact on prefrontal cortex function and its modulation of various neurotransmitter systems. While users often report feeling mentally clear and focused, MDMA can actually impair certain cognitive functions. Users may experience enhanced tactile sensations, increased appreciation of music, and mild visual effects such as color enhancement. This emotional state is largely attributed to the flood of serotonin and oxytocin released by MDMA, creating a temporary state of heightened emotional sensitivity and openness. The short-term effects of MDMA on the brain are profound and multifaceted.

However, the intense serotonin release induced by MDMA can have potential long-term consequences on the serotonin system. Subjective effects of MDMA include elevated mood, increased self-confidence and sensory sensitivity, and a peaceful feeling coupled with insight, empathy, and closeness to persons.2 It has gained a deceptive reputation as a “safe” drug among its users. The study’s findings shed light on the impact of chronic MDMA use on the principal excitatory neurotransmitter system in the brain in addition to its well-known effects on the serotonin system. The MDMA-induced elevations in body temperature in humans appear to depend on the MDMA-induced release of norepinephrine and involve cutaneous vasoconstriction and likely also enhanced metabolic heat generation. MDMA induces a syndrome of inappropriate secretion of antidiuretic hormone89-91 which may lead to symptomatic hyponatremia including brain edema in particular in women.92-94 Thus, excessive water consumption but also fluid treatment can be potentially dangerous in the prevention or the treatment of MDMA-induced hyperthermia.

A small number of Ecstasy users have been seen to have liver damage. The acute effects may even lead to cardiotoxicity and heart failure. These include tachycardia, hypertension, and the indirect effects on the heart caused by the suppression of thirst, appetite, and sleep.

There have been several reported cases of young people experiencing strokes after using MDMA. This can lead to vasoconstriction and vasodilatation in specific brain regions, increasing the risk of a stroke. MDMA has been linked to cerebrovascular accidents, which are caused by alterations in the serotonin neurotransmission system. MDMA has a range daniel radcliffe fetal alcohol of effects on the cardiovascular system.

• Longitudinal PET and single-photon emission computed tomography (SPECT) studies consistently show reduced serotonin transporter (SERT) availability in individuals with a history of MDMA use.
• The risks of prolonged or heavy MDMA use extend beyond cognitive and mood effects.
• The basic mechanisms include increased heat production and/or decreased heat loss (Fig. 1).
• There are respected researchers on both sides of the spectrum – some believe that the drug isn’t dangerous while others think its use can have significant long term consequences.
• MDMA use has been linked to an increased risk of cerebrovascular accidents, which are a type of stroke.
• The present review focuses on the findings from placebo-controlled studies that assessed MDMA in humans and addresses treatment options for hyperpyrexia caused by recreational Ecstasy use.
• The serotonin 5-HT2A receptor antagonist ketanserin reduced the MDMA-induced elevation in body temperature in humans,44 consistent with studies in rats.58 However, in humans, ketanserin alone also reduced body temperature compared with placebo, and the effects with MDMA were therefore mostly additive.44 Additionally, ketanserin has α1-adrenergic receptor-blocking properties59 and may reduce peripheral vascular resistance and body temperature.

Some studies suggest an increased stress response persists even after stopping MDMA, potentially raising the risk of mood disorders. While dopamine’s role in MDMA’s long-term effects is less pronounced than serotonin’s, it may still contribute to behavioral and motivational changes. Human studies suggest long-term users may experience diminished pleasure from natural rewards, indicating disruptions in the brain’s reward system.

Effects on Sexual Health

However, there are also some common adverse effects, some severe risks, and possible long-term damage. When people buy MDMA from dealers on the street, they do not know what they are taking. As the drug is illegal, there is no government regulation over its production. As is alcoholism a mental illness a result, people may become more affectionate than usual and feel a connection with strangers.

Additionally, the study used correlation analysis to assess the relationship between metabolite concentration and frequency of MDMA use among drug users (Zimmermann et al., 2023). MDMA, commonly known as ecstasy, is a widely used recreational drug known for its empathogenic and euphoric effects. Additionally, animal studies indicate that the blood-brain barrier is disrupted during MDMA-induced hyperthermia also leading to brain edema.95 In contrast, α blockade reduced the blood pressure response to MDMA and elevations in body temperature,31 and combined α/β blockade reduced MDMA-induced increases in blood pressure, heart rate, and body temperature30,63 and blood pressure response to cocaine.85-87 Accordingly, α blockers (e.g., phentolamine) or α/β blockers (e.g., carvedilol) could be useful in situations of extreme sympathomimetic stimulation, although real-world clinical data are mostly lacking.

• A Journal of Neuroscience (2020) study found MDMA exposure in rodents reduced dopamine transporter function, potentially impairing reward processing.
• MDMA, also known as ecstasy or molly, is a synthetic drug that is widely used by young people at parties and nightclubs.
• These are the brain’s neurotransmitters, which influence mood, sleep, and appetite.
• The brain struggles to replenish serotonin levels after each surge, leading to depletion.
• Unlike SSRIs, which block SERT to gradually increase extracellular serotonin, MDMA is taken up into serotonergic neurons and reverses SERT’s function.
• The purity and dosage of street drugs can vary widely, potentially leading to unexpected and dangerous effects.

Understanding the Risks of Recreational Use

Unlike methamphetamine, which triggers substantial dopamine release, MDMA produces a moderate increase. Although MDMA primarily affects serotonin, it also influences dopamine, which regulates motivation, pleasure, and reward. These changes may contribute to emotional instability and increased susceptibility to anxiety and depression, particularly in heavy users. A Neuropsychopharmacology (2021) study found repeated MDMA exposure in animals reduced serotonin transporter density, suggesting structural changes in serotonin-releasing neurons.

One article will say that it is far more damaging to the brain than we originally thought, yet another says that there is no long-term damage as a result of taking Ecstasy. If you do a search on Google, it seems as though there is a lot of conflicting evidence as to whether Ecstasy causes brain damage. There are respected researchers on both sides of the spectrum – some believe that the drug isn’t dangerous while others think its use can have significant long term consequences.

MDMA significantly impacts serotonin, a neurotransmitter involved in mood, emotion, and cognition. Understanding these effects is crucial as MDMA continues to be explored for both recreational and therapeutic use. When the person is drug-free, a comprehensive treatment program is implemented. The drug is slowly flushed out of the person’s how to know if you got roofied system.

Additionally, the occipital cortex, which is also rich in serotonin-releasing neurons and 5-HT2A receptors, is particularly sensitive to serotonin neuronal injury. Additionally, abuse of MDMA can lead to the loss of serotonergic neurons, causing serotonin depletion and up-regulation of post-synaptic 5-HT2 receptors. MDMA has been linked to cerebrovascular accidents, which are caused by alterations in the serotonin system.