question: Why using MDMA can reduce our standart serotonine level
comment: Yes, bodies are adaption machines. No matter what you put inside it the human Body will try to keep up functional levels. If you flood it with serotonin it will adapt to this high supply and will constantly demand it from the outside.
passages: Current findings regarding altered visual orientation processing from MDMA use comes from research by White, Brown and Edwards (2013). Their study sought to extend the results found in previous research, such as Maisini et al. (1990), and investigate how MDMA affects visual processing in the occipital lobe. The participants of the study were divided into three groups: Ecstasy users who were amphetamine abstinent, Ecstasy users who also used amphetamines, and drug naive control participants. Ecstasy users who additionally used amphetamine were included as results from prior studies have indicated that concurrent amphetamine use may mediate the effects of MDMA on orientation neurons.
   Section::::Original publication.
   The relationship between the effect of MDMA and serotonin's role in visual orientation processing has been investigated following a prior study conducted in the 1990s by Maisini, Antonietti and Moja (1990). Their experiment involved subjects ingesting a mixture which significantly reduced brain serotonin levels. This reduction in serotonin resulted in an increase in the magnitude of the TAE in those subjects. This study has since been used as the foundation for the idea that MDMA neurotoxicity, due to its effect on serotonin neurons, could influence the magnitude of the TAE in individuals who use MDMA.
  
  Section::::Present Research.
   The results of the study indicated that the amphetamine abstinent Ecstasy group showed a broader tuning bandwidth than the controls. This demonstrates that MDMA use produces changes to serotonergic functioning as it disrupts lateral inhibition between orientation sensitive neurons. This disruption causes the neurons to activate to a wider range of orientations other than their preferred orientation. This finding, therefore, supports the idea that serotonin plays a role in sharpening the tuning bandwidths of orientation neurons. Overall, the results support the idea that "MDMA-mediated serotonin depletion can lead to broader orientation tuning bandwidths" p. 163. The authors do, however, go on to say that although deficits in certain tasks are present, the extent of these deficits requires further investigation.
   Side effects, which can last from a few hours to several days, include impaired balance, fatigue, low mood, headache, nausea, loss of appetite, tightness and feeling cold. 
  
  Section::::Post-traumatic stress disorder.:Rationale for MDMA treatment.
   The Multidisciplinary Association for Psychedelic Studies (MAPS) is funding pilot studies and clinical trials investigating the use of MDMA in psychotherapy to treat posttraumatic stress disorder (PTSD), social anxiety in autistic adults, and anxiety in terminal illness. In November 2016, the United States Food and Drug Administration (FDA) approved large-scale phase 3 clinical trials involving the use of MDMA for the treatment of PTSD in individuals who do not respond to traditional prescription drugs or psychotherapy. MDMA has also been proposed as an adjunct to substance abuse treatment. In 2017, doctors in the UK began the first clinical study of MDMA in alcohol addiction.
   MDMA is part of the amphetamine family and elicits its positive effects by altering brain serotonin, dopamine and norepinephrine neurotransmitter levels. As the drug begins to take effect, the brain becomes flooded with serotonin which can then become depleted within 3–6 hours following consumption. It has also been shown that an enzyme required to synthesize serotonin becomes deactivated, therefore, inhibiting the brain's replenishment of used serotonin. Due to changes that the brain undergoes during and following MDMA consumption, various consequences have been noted. These have included memory impairment, anxiety, paranoia, mood swings and depression. This has raised further concerns as to what extent MDMA may damage and change the brain's chemistry and what this means for its users.
   Section::::History and Effect of MDMA.
   The family of drugs typified by MDMA produce their effects through multiple mechanisms of action in the body, and consequently produce three distinct cues which animals can be trained to respond to: a stimulant cue typified by drugs such as methamphetamine, a psychedelic cue typified by drugs such as LSD and DOM, and an "entactogen-like" cue which is produced by drugs such as MDAI and MBDB. These drugs cause drug-appropriate responses in animals trained to recognize the effects of MDMA, but do not produce responses in animals trained selectively to respond to stimulants or hallucinogens. Because these compounds selectively release serotonin in the brain but have little effect on dopamine or noradrenaline levels, they can produce empathogenic effects but without any stimulant action, instead being somewhat sedating.
   Recent research investigating MDMA has revealed the neurotoxic effect of the drug on brain serotonin neurons. Long term and potentially permanent changes to serotonergic axons have been noted in animal and primate studies where they were administered doses of MDMA similar to those taken by some human users. MDMA has subsequently been used to investigate the role that serotonin may play in visual orientation processing. Serotonin neurons are thought to reside in the occipital lobe, which is an area of the brain responsible for visual processing of line orientation, edges, motion and stereoscopic depth perception. Because MDMA is known to affect serotonin and that serotonin is thought to be involved in vision, individuals who take MDMA may exhibit differences in their visual orientation processing.
   MDMA is illegal in most countries and, as of 2018, has no approved medical uses. Limited exceptions are sometimes made for research. Researchers are investigating whether MDMA may assist in treating severe, treatment-resistant posttraumatic stress disorder (PTSD) with phase 3 clinical trials to look at effectiveness and safety expected to begin in 2018. In 2017 the FDA granted MDMA a breakthrough therapy designation for PTSD, meaning if studies show promise, a review for potential medical use could occur more quickly.
   Serotonin depletion following MDMA use can cause depression in subsequent days. In some cases depressive symptoms persist for longer. Some studies indicate repeated recreational users of ecstasy have increased rates of depression and anxiety, even after quitting the drug. Depression is one of the main factors for cessation of use.
  
  At high doses, MDMA induces a neuroimmune response which, through several mechanisms, increases the permeability of the blood-brain barrier, thereby making the brain more susceptible to environmental toxins and pathogens. In addition, MDMA has immunosuppressive effects in the peripheral nervous system and pro-inflammatory effects in the central nervous system.
   Once the effects of MDMA wear off, there is a "period of neurochemical depletion" that invokes anhedonia, lethargy, anger, depression, irritability, brooding, greater everyday stress, altered pain thresholds, changes in sleep, and bad dreams, especially in female participants. The symptoms are thought to be due to depletion of serotonin, as a result of the large release of serotonin triggered by MDMA, and have been called "neurotoxic in terms of causing serotonergic dysfunction". One extreme example is a Special Air Forces soldier who participated in an MDMA psychotherapy session and was arrested following his treatment for attacking a stranger. In court, he blamed his actions on the MDMA-assisted psychotherapy. 
   Very high doses can be fatal in rats with a 50% fatality rate for those subcutaneously injected with 28 mg/kg of MDAI. This is a result of the way serotonin release interferes with thermoregulation.
  
  Section::::Use in scientific research.
  
  MDAI and other similar drugs have been widely used in scientific research, as they are able to replicate many of the effects of MDMA, but without causing the neurotoxicity which may be associated with MDMA and some related drugs. No tests have been performed on cardiovascular toxicity.
  
  Section::::Use as a recreational drug.
   Sometimes MDMA is labelled as an "empathogenic" drug, because of its empathy-producing effects. Results of different studies show its effects of powerful empathy with others. When testing MDMA for medium and high dosage ranges it showed increase on hedonic as well as arousal continuum. The effect of MDMA increasing sociability is consistent, however effects on empathy have been more mixed.
  
  Section::::Use.
  
  Section::::Use.:Recreational.
   Studies conducted by the Multidisciplinary Association for Psychedelic Studies (MAPS) seek to understand how MDMA could be helpful in the treatment of post-traumatic stress disorder. The Phase 2 trials of these studies consisted of 107 participants who had chronic, treatment-resistant PTSD, and had suffered from PTSD for an average of 17.8 years. Out of the 107 participants, 61% no longer qualified for PTSD after three sessions of MDMA-assisted psychotherapy two months after the treatment. At the 12-month follow-up session, 68% no longer had PTSD. As of 2019 MAPS is continuing their research in Phase 3 trials.
  
  Section::::Methods.
   According to a dose-response study, "dimethyltryptamine does slightly elevate blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of beta-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rise equally in response to all doses of DMT, and melatonin levels were unaffected." Research published in "Cell Reports" states that DMT promotes neural plasticity in rats and flies, making neurons more likely to branch out and connect with one another.
  
  Section::::Effects.:Dependence liability.
   The MDMA concentration in the blood stream starts to rise after about 30 minutes, and reaches its maximal concentration in the blood stream between 1.5 and 3 hours after ingestion. It is then slowly metabolized and excreted, with levels of MDMA and its metabolites decreasing to half their peak concentration over the next several hours. The duration of action of MDMA is usually four to six hours, after which serotonin levels in the brain are depleted. Serotonin levels typically return to normal within 24–48 hours.
   , the long-term effects of MDMA on human brain structure and function have not been fully determined, however, there is consistent evidence of structural and functional deficits in MDMA users with a high lifetime exposure. Additionally, MDMA use at high doses, as distinct from high lifetime exposure, has been shown to produce brain lesions, a form of brain damage, in the serotonergic neural pathways of humans and animals. There is no evidence of structural or functional changes in MDMA users with only a moderate (<50 doses used and <100 tablets consumed) lifetime exposure, nevertheless, MDMA in moderate use may still be neurotoxic. Further, it is not clear yet whether "typical" users of MDMA (1 to 2 pills of 75 to 125 mg MDMA or analogue every 1 to 4 weeks) will develop neurotoxic brain lesions. Long-term exposure to MDMA in humans has been shown to produce marked neurodegeneration in striatal, hippocampal, prefrontal, and occipital serotonergic axon terminals. Neurotoxic damage to serotonergic axon terminals has been shown to persist for more than two years. Elevations in brain temperature from MDMA use are positively correlated with MDMA-induced neurotoxicity. However most studies on MDMA and serotonergic neurotoxicity in humans focus on the heaviest users, who consume more than 7 times the average. It is therefore likely that no serotonergic neurotoxicity is present in most casual users. Adverse neuroplastic changes to brain microvasculature and white matter also occur in humans using low doses of MDMA. Reduced gray matter density in certain brain structures has also been noted in human MDMA users. Global reductions in gray matter volume, thinning of the parietal and orbitofrontal cortices, and decreased hippocampal activity have been observed in long term users. The effects established so far for recreational use of ecstasy lie in the range of moderate to large effects for SERT reduction.
   Section::::Adverse effects.:During pregnancy.
  
  MDMA is a moderately teratogenic drug (i.e., it is toxic to the fetus). In utero exposure to MDMA is associated with a neuro- and cardiotoxicity and impaired motor functioning. Motor delays may be temporary during infancy or long-term. The severity of these developmental delays increases with heavier MDMA use.
  
  Section::::Adverse effects.:Reinforcement disorders.
   Section::::Other research.
  
  MDMA has been proposed as an adjunct for other psychiatric disorders. For example, MDMA-assisted psychotherapy has been tested in a pilot study of anxiety related to advanced stage cancer. This study was terminated due to lack of funding and insufficient patient enrollment. Recreational users have published personal testimonies recounting positive body image experiences both during and following their use of MDMA, and MDMA-assisted psychotherapy has been proposed as a potential treatment for eating disorders. 
  
  Section::::Society and culture.
  
  Section::::Society and culture.:Legality.
   Synaptic downscaling is tied to the beneficial effects of sleep: This is what ties it all together. LTD from the synaptic downscaling of the slow wave activity causes just the right amount of reduction to our neuronal firing patterns. The prolonged LTD from sleep would allow for all the non-essential LTP that took place during our day to become forfeit. It helps reduce the amount of synaptic noise that is created when so much potentiation happens during the day.
   Section::::MDMA and Visual Orientation Processing.
   MDMA was used for psychedelic therapy for a variety of indications before its criminalization in the U.S. in 1985. In response to its criminalization, the Multidisciplinary Association for Psychedelic Studies (MAPS) was founded as a nonprofit drug-development organization to develop MDMA into a legal prescription drug for use as an adjunct in psychotherapy. The drug is hypothesized to facilitate psychotherapy by reducing fear, thereby allowing people to reprocess and accept their traumatic memories without becoming emotionally overwhelmed. In this treatment, people participate in an extended psychotherapy session during the acute activity of the drug, and then spend the night at the treatment facility. In the sessions with the drug, therapists are not directive and support the patients in exploring their inner experiences. People participate in standard psychotherapy sessions before the drug-assisted sessions, as well as after the drug-assisted psychotherapy to help them integrate their experiences with the drug. The phase 2 clinical trials of the MDMA-Assisted Psychotherapy, was publicized at the end of November 2016. Preliminary results suggest MDMA-assisted psychotherapy might be effective. MAPS received FDA approval of a phase 3 trials.
   Approximately 60% of MDMA users experience withdrawal symptoms when they stop taking MDMA. Some of these symptoms include fatigue, loss of appetite, depression, and trouble concentrating. Tolerance to some of the desired and adverse effects of MDMA is expected to occur with consistent MDMA use. A 2007 analysis estimated MDMA to have a psychological dependence and physical dependence potential roughly three fourths and four fifths that of cannabis.
  