Author: adm1nlxg1n

Catechol-0-methyltransferase (COMT) is responsible for several methylation reactions in the metabolism of MDMA 37 and, perhaps not coincidently, this ubiquitous enzyme has also been reported to be less active in women 97. The effect of MDMA on core body temperature emerges gradually during ontogeny while a reduction in body weight is evident at all ages (Table 1). Mood swings, anxiety, depression – these are all potential long-term consequences. It’s as if the drug borrows happiness from your future self, leaving you to deal with the emotional debt. This cocktail approach can compound the risks, creating a perfect storm of neurotoxicity.

MDMA alters several physiological processes including reducing food 71 and, to a lesser extent, water intake 39,50. Elevated salivation has also been documented following MDMA 146 which, in combination with increased grooming, aids in thermoregulation. Further, rats increase their respiratory rate after MDMA which causes substantial evaporative water loss 56.

Is Ecstasy the Same as Meth? The Key Differences

Researchers have found a link between SERT density and the length of abstinence, a period where the drug is not being used. This means that, without MDMA, serotonin and 5-HT levels may be restored in the brain (Müller et al., 2019), which in turn could possibly lead to improved mood and memory. MDMA stimulates the release of neurotransmitters like dopamine and serotonin, which can produce euphoric feelings such as heightening of the five senses and increased empathy (Mustafa et al., 2018).

Similarly, the dynamic changes in postsynaptic monoamine receptor levels are also likely contributors to the differential sensitivity to the physiological and behavioral effects of MDMA. Interestingly, direct administration of MDMA, or amphetamine, to the chicken embryo five days prior to hatching induced an acute reduction in motility 13. Young rats (PD 28) also exhibit an acute elevation in motor-activity, particularly horizontal activity, following MDMA 16,17.

HUMAN STUDIES

Age-at-first ecstasy use predicted midbrain SERT binding in ecstasy users that started to use during adolescence but not in users that started during adulthood. In adolescent rats, MDMA administration resulted in a less pronounced loss of SERT binding in the frontal cortex. The differences between the effects of MDMA on the developing and matured brain most likely occur because of the differential maturational stage of the 5-HT projection fields at the time of first exposure in combination with 5-HT’s neurotrophic effects on the connective organisation of the developing brain. Darvesh et al. 151 demonstrated that the systemic administration of MDMA to rats significantly increased the formation of nitric oxide and the nitrotyrosine in the striatum. These results support the conclusion that nitrogen reactive species (formed by the reaction of NO with O2•− radicals) could also be involved in MDMA damage.

The Siren Song of Serotonin

• MDMA also inhibits serotonin reuptake by its binding to the transporter protein, thus prolonging signaling at the synapses.
• Positive events in your life (like falling in love, perhaps) cause greater serotonin release, increasing receptor binding.
• MDMA has also been shown to trigger neuroinflammation which seems to be linked with glial activation, in particular microglial activation (Costa et al. 2013, 2014; Frau et al. 2013; Lopez-Rodriguez et al. 2014).
• MDMA may also suppress nigral GABA release following 5-HT2A/2C receptor activation thus causing disinhibition of the striatal DA neurons (Gudelsky and Yamamoto 2008).
• However, MDMA dependence is still less understood, but it has been reported to be different from other drugs or alcohol (Degenhardt, Bruno, & Topp, 2010).

The picture on the right (B) is from a monkey that was injected with a very large dose of MDMA.1 As you can see, many of its serotonin axons have been lost. Neurotoxicity can manifest in many forms and severity levels and MDMA appears to be neurotoxic under certain circumstances. High doses or several doses throughout the period of ingestion, frequent use (e.g. weekly use at nightlife events), aduleration, and substance mixing all are implicated in the adverse event of MDMA neurotoxicity. Data from phase II trials of MDMA-AP do not support risks of clinically significant neurotoxicity from MDMA use as side effects were observed to be mild and limited to the week after use, while participants also saw profound improvements in clinical symptoms for PTSD. In summary, MDMA induced neurotoxicity is easy to avoid with moderate doses, adequate time between use, and pure substances without combination. The toxicity effects induced by MDMA made the researchers motivated to explore its potential treatments.

Data Analysis

The effects of single, large doses (up to 40 mg/kg) of MDMA on thermal homeostasis were compared in neonatal (PD 10), adolescent (PD 40), and young-adult (PD 70) rats by 10. It is important to note that a single 50 mg/kg dose is lethal for fifty percent of adult rats 62. MDMA treatment in a hot environment (33 °C) did not significantly alter rectal temperature in neonates but evoked an intense, prolonged, and potentially life-threatening, hyperthermia among adolescents and adults.

2. Effects of MDMA on memory and learning

This motor response has yet to be thoroughly characterized after perinatal exposure. Rat pups that received MDMA on PD 1–4 show a general increase in limb movements, but at this age, these do not result in locomotion (unpublished observations). Although the syndrome has been documented following prepubescent MDMA exposure 48,118, direct comparisons using the same treatment regimen at different ages has yet to be conducted.

• The binding in the cerebellum, which is presumed to be low in SERT, was used as a reference for background radioactivity (non-specific binding + free ligand).
• Bi-directional dose dependent 5-HT and 5-HIAA levels alterations were identified two-weeks after MDMA treatments to male pubescent rats 74.
• Because tryptophan hydroxylase is the rate-limiting enzyme for 5-HT synthesis, it is likely that decreases in this enzyme restrict the extent of 5-HT production, thus reducing the levels of this neurotransmitter regardless of whether or not axonal damage has occurred.
• Second, even if forebrain serotonergic fibers are not physically damaged, as postulated by the downregulation hypothesis, long-lasting deficits in 5-HT levels and in SERT expression would still cause severe dysfunction of the serotonergic system.

Cognitive changes in ecstasy users

Similarly, the damage in serotonergic system was also observed in non-human primates and in the human brain (Green et al. 2003; Ricuarte et al. 1988). Historical evidence showed that the mechanism of MDMA upon its administration is through its binding affinity to the serotonin receptors (Liechti, Saur, Gamma, Hell, & Vollenweider, 2000). The activation of these receptors triggers a massive release of neurotransmitters. MDMA also inhibits serotonin reuptake by its binding to the transporter protein, thus prolonging signaling at the synapses.

However, these changes went away after the ‘ecstasy’ users had stopped using drugs for a few months. Neuroadaptation (such as the brain scan research amply demonstrates the existence of) will not be considered. Ricaurte claims the drug manufacturer switched the labels on two vials (one of methamphetamine, one of MDMA) causing the error. The manufacturer (RTI) has vigorously disputed the claim that a switch occurred at their facilities (which are very tightly run under D.E.A. oversight.) The study reportedly cost the American taxpayers $1.3 million.

This was demonstrated in a study in which researchers first injected all the animals with MDMA, and, on every hour, they have some of the animals an injection of Prozac. Only those animals that got the Prozac during the first six hours exhibited no neurotoxic damage. Those that were injected with Prozac on the seventh, eighth, ninth and tenth hours, etc., sustained damage, with the ones that received Prozac injections later sustaining more damage than the others. Forebrain structures that are essential for cognitive function like the hippocampus and frontal cortex are highly sensitive to MDMA 58. The serotonin system in these regions undergoes dynamic 23,51,115 and protracted development 104.

Thus, initial studies showed that MDMA and its main metabolite 3,4-methylenedioxyamphetamine stimulate efflux of 3H5-hydroxytryptamine (5-HT) 28 (Figure 1) and 3Hdopamine from preloaded synaptosomes 29,30. Subsequent reports, using in vivo microdialysis, demonstrated that MDMA increases extracellular 5-HT, dopamine and noradrenaline levels in multiple brain regions with effects on 5-HT being greater in magnitude 31-34. MDMA also enhances the release of acetylcholine, an effect that appears to be secondary to the activation of serotonergic, dopaminergic and/or histaminergic receptors 35. The evaluation of monoamine release after MDMA intake has not been studied in humans or non-human primates, but mdma and the brain: is ecstasy neurotoxic several studies suggest that the interaction of MDMA with the 5-HT carrier and a subsequent release of 5-HT could be responsible for most of the physiological and psychological responses to MDMA in humans 5-8,36.

This is the most severe stage of alcohol withdrawal, and the one that comes with the most serious risks (called “delirium tremens”‌). Not everyone who withdraws from alcohol will experience these symptoms, but the risks are high. This is why it’s important to be under medical supervision when you are going through withdrawal. Stage two starts after 24 hours have passed from the last time you took a drink of alcohol.

Developing Healthy Coping Mechanisms

However, even mild symptoms can intensify if alcohol use continues or if medical supervision is not sought. Recognizing and responding to these symptoms early can prevent complications and ensure a smoother detox process. These are progressive phases caused by the brain’s reaction to the sudden absence of alcohol, which previously suppressed nervous system activity. Symptoms escalate as the body struggles to regain balance, ranging from mild discomfort to life-threatening complications.

Injecting Drugs: Health Risks and Social Consequences

• Most people with mild to moderate alcohol withdrawal don’t need treatment in a hospital.
• There are a few common symptoms that appear during the alcohol withdrawal process.
• Understanding the timeline of alcohol withdrawal headaches helps you anticipate and prepare for each recovery phase.
• Motivational interviewing is another effective approach that helps individuals explore and resolve ambivalence about change.
• Maybe you’ve picked up a new workout routine, daily journaling practice, or started a new podcast.

Recognizing and celebrating your progress can help maintain motivation and reinforce the positive changes you’ve made in your life. Surrounding yourself with individuals who share your interests and support your sobriety can help you build a strong, sober social network. Work with your therapist or support group to develop a comprehensive, long-term recovery plan. This plan should include strategies for maintaining sobriety, such as attending support group meetings, engaging in regular therapy sessions, and practicing self-care.

Care at Cleveland Clinic

The higher the number, the worse a person’s symptoms are and the more treatments they likely need. From there, doctors can control and stabilize these symptoms effectively. Alcohol withdrawal is a serious condition that may rapidly become life-threatening. For these reasons, immediate detox care and longer-term treatment is needed for those going through withdrawal.

The condition results from the brain’s adaptation to alcohol’s depressant effects, leading to an overactive nervous system once alcohol is removed. Symptoms range from mild anxiety and tremors to severe seizures and delirium tremens. Alcohol withdrawal treatment involves medical detoxification, medications (e.g., benzodiazepines, anticonvulsants), and supportive care. According to a report by the World Health Organization (WHO) (2023), medically supervised detoxification reduces the risk of severe complications and improves outcomes. The critical 48-hour mark represents the peak intensity of alcohol withdrawal, where you’ll face potentially life-threatening complications that require immediate medical intervention.

Mental Health Resources

• Treatment for alcohol withdrawal symptomsis best handled by medical professionals in a detox program, rehab facility or similar inpatient setting.
• These symptoms can intensify over 24 hours, especially if you’ve had a recent head injury or illness.
• According to a report by the World Health Organization (WHO) (2023), medically supervised detoxification reduces the risk of severe complications and improves outcomes.
• Treatment options for alcohol withdrawal typically involve a combination of medical detoxification, medications for symptom management, and therapy and support.

Understanding the timeline of alcohol withdrawal headaches helps you anticipate and prepare for each recovery phase. The duration variability of headaches typically follows a predictable pattern, though individual experiences may differ greatly based on drinking history and overall health status. Due to heightened security measures, accessing medical support websites may occasionally be restricted, requiring alternate reliable resources for withdrawal information. Three distinct phases characterize alcohol withdrawal tremors, beginning with hand tremors that typically emerge 6-10 hours after your last drink.

You may still feel post-acute withdrawal symptoms like anxiety and fatigue. This is totally normal as your body adjusts to its new normal without alcohol. Post acute withdrawal symptoms can persist on and off for weeks or even months. During the acute withdrawal phase, it is crucial to seek medical assistance to ensure the individual’s safety and to manage the symptoms effectively. Medical detoxification in a supervised setting is often recommended during this phase.

Day 30

We want to give recovering addicts the tools to return to the outside world completely substance-free and successful. Alcohol withdrawal happens in patients who have a physical dependence on alcohol. Wernicke encephalopathy may occur in people who have a thiamine (vitamin B12) deficiency, a condition that is common among those addicted to alcohol.

Lifestyle Quizzes

If you find it difficult to relax on your own, consider seeking guidance from a therapist or counselor who can teach you effective stress management techniques. If you recognize these signs in yourself or a loved one, it’s important to seek help as soon as possible. Early intervention and treatment can prevent complications and improve long-term outcomes.

These groups also often host sober social events, which is important if your social life has always centered around drinking alcohol. Your doctor will want to know if you have any mild itching, numbness, a pins-and-needles feeling, or burning. Some people try to avoid withdrawal symptoms by cutting back on alcohol instead of giving it up all at once.

When alcohol is suddenly removed from the system, the brain amps up and quickly becomes overstimulated. Outpatient counseling and psychotherapy is a great resource for everyone, whether or not they’re going through alcohol recovery. For people who are withdrawing and alcohol withdrawal timeline: symptoms and more recovering from serious alcohol use, it can be necessary.

Doctors may prescribe other medications to treat withdrawal-related symptoms. One example is a beta-blocker (such as propranolol) to reduce high blood pressure. Doctors at our alcohol treatment centers can ensure that these medications are administered properly, in the proper dosages, and at the right time. Get therapy and medical care—just $25 with insurance, no hidden fees— for alcohol recovery, depression, everyday illnesses, and more.