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This paper explores published peer-reviewed articles that discusses the relationship between cognitive dysfunction and chronic abuse of the drug ecstasy, also known as MDMA. Firstly, etiology of how ecstasy affects our brain and causes dysfunction of cognition was reviewed. Then, the discussion of the role MDMA plays on serotonin in the human brain was considered, and in return, took a look at the relationship between ecstasy and depression. Ecstasy had many adverse symptoms, both physiological, psychologically, and cognitively. The course of symptoms was dependent on dose of drug taken. After examining the articles, it was found that heavy ecstasy users do experience cognitive deficits, but not to the extent of having a debilitating disorder. Further, a research carried out to investigate MDMA and depression found that there were no significant connections between both variables (Durdle, Lundahl, Johanson, & Tancer, 2008). Treatment for any possible cognitive impairment and drug addiction was explored further.
Keywords: MDMA, ecstasy, cognitive deficits, depression, addiction, mood disorders
Cognitive Deficits and Depression Associated with Chronic Ecstasy Abuse
The psychosocial drug ecstasy is a new drug that is booming in our current generation. Ecstasy, also known as “MDMA,” “Molly,” and “e,” has the main compound methamphetamine. Scientifically known as 3,4-menthylenedioxymethamphetamine, ecstasy gained its pronounced popularity in the 1980s when dance parties were booming (Meyer, 2013). Fast forward to today, many people still use ecstasy recreationally in the same environment where the music is loud and the lights are bright. Furthermore, MDMA comes in most popularly used after marijuana and cocaine according to many surveys.
The psychological acute effects of ecstasy are its main attraction for recreational use. When under the influence of MDMA, many experience powerful feelings and emotions such as elation, intimacy, arousal, increased extroversion, and pleasure (Gouzoulis-Mayfrank & Daumann, 2009; Meyer, 2013; Parrott, 2013). Lasting between three to five hours, these acute effects may also be associated with negative feelings like anxious moods, aggressive behavior, and feelings of depression (Gouzoulis-Mayfrank & Daumann, 2009). Ecstasy also has subacute side effects once the drug wears off. This process is well known as the “comedown,” which they may experience unstable mood, irritability, lack of sleep, impaired cognitive functioning (e.g. memory and concentration), tremors, and anxious/depressive feelings (Meyer, 2013).
There are many controversies when it comes to ecstasy/MDMA and the negative effects on the human brain. Questions about long-term damage, toxicity, and potential dependence have been raised and researched throughout the past few decades. However, there has yet to be confounding results about the use of this psychosocial drug due to a variety of limitations. One of the main setbacks is caused by polydrug use. Majority of MDMA users are polydrug users in which they take one or more drugs while on MDMA, such as alcohol, cannabis, and cocaine. As such, research on chronic ecstasy use among humans poses difficulties attempting to pinpoint the exact result that is caused only by ecstasy (Meyer, 2013). On top of that, a comparison analysis found that ecstasy was rated as the drug that induced less impairment (Parrott, 2013).
Further, there is a hypothesis that ecstasy may play a role in depressive symptomology alongside acute and long-term negative effects. Due to MDMA’s attraction and relationship to serotonin, ecstasy use has been found to be associated to symptoms of both depression and anxiety (Gouzoulis-Mayfrank & Daumann, 2009). In spite of several investigations, it is still unclear if psychological symptoms precede ecstasy use or proceeds after taking the drug (Durdle, Lundahl, Johanson, & Tancer, 2008).
This literature review will discuss the findings of peer-reviewed articles to dive further into the burning questions of MDMA’s effects on the brain and understand the cognitive deficits and possible cognitive disorders, specifically major depressive disorder, in regards to chronic abuse of ecstasy/MDMA.
Though ecstasy acts on many parts of the brain, MDMA has a very special attraction to serotonin and the role it plays in our body, as mentioned above. Ecstasy is a very strong stimulant drug that mainly effects the central nervous system (Parrott, 2013). MDMA’s main action is on the amount of reuptake of serotonin when released into the synaptic cleft. Ecstasy reverses the reuptake of serotonin via the transporter (Meyer, 2013; Parrott, 2013).
Heavy MDMA users may experience a process called ‘serotonergic neurotoxicity’ where there is a significant damage to axon terminals that carry serotonin in our brains. Furthermore, it is investigated that ecstasy also causes a decrease in serotonin transporters (SERTs) (Gouzoulis-Mayfrank & Daumann, 2009; Jager et al., 2008; Meyer, 2013; Parrott, 2013). However, there has been mixed results about serotonergic neurotoxicity. According to research by Jager et al. (2008), they found that there were no significant conclusions of decrease in serotonergic axon terminals, though it must be taken into consideration that the study was focused mostly on the effects on associative memory. Contrary to that, research done on monkeys showed that the was a decreased number of axons, in terms of density, which supports the loss of serotonergic axon hypothesis (Meyer, 2013).
Due to serotonergic neurotoxicity and the fact that serotonin neurotransmitter is associated with depression, it is not a shock that depressive symptomology could be seen with MDMA users (Durdle et al., 2008; Gouzoulis-Mayfrank & Daumann, 2009). The perspective that chronic use of ecstasy could cause depression is unclear for several reasons, such as controlling for polydrug use with MDMA and depression preceding drug abuse (Gouzoulis-Mayfrank & Daumann, 2009). In a study carried out by Durdle et al., (2008), they were aiming to explore major depression with ecstasy and marijuana use. Durdle et al., (2008) found that there were no significant results that indicated that MDMA-only had a causal relationship with major depressive disorder. Nonetheless, other research has found a high prevalence of depressive symptoms, though there were insufficient number of symptoms to provide a diagnosis (Gouzoulis-Mayfrank & Daumann, 2009).
Besides that, MDMA use could possibly impair cognitive functioning such as memory and concentration. According to Gouzoulis-Mayfrank and Daumann (2009), Jager et al. (2008) and Parrott (2013), they found that the prefrontal cortex of the human brain and hippocampus had low serotonin yield, which is caused by serotonergic neurotoxicity in heavy ecstasy users, in return effecting memory as hippocampus is responsible for memory. It was also discovered that the brain during associative learning under the fMRI showed high activity in the middle occipital gyrus while on MDMA which shows “evidence of serotonergic modulation of functional brain activity in the prefrontal cortex and limbic structures during a cognitive challenge” (Jager et al., 2008, p. 253).
Once the drug ecstasy gradually leaves the body, an individual may still experience some subacute effects. During this period, serotonin undergoes momentary exhaustion due to SERT activity still being blocked by MDMA, restricting the reuptake of serotonin (Meyer, 2013). This brief serotonin depletion also has its own prompted symptoms, which will be discussed about further in this literature.
Symptoms and Course
Heavy MDMA users experience the course of acute effects, acute/subacute complications, aftereffects, and possible long-term symptoms and/or recovery.
When high on ecstasy, an individual may experience physiological symptoms such as restlessness, low central body temperature (hyperthermia), jaw clenching (trismus), dry mouth, headache, and nausea (Meyer, 2013; Parrott, 2013). MDMA is not limited to just positive effects, like most people report feeling as MDMA has the ability to intensify any feelings like depressive mood, spike in anxiety, diminution of self-control, mental confusion, aggression, and dysphoria (Gouzoulis-Mayfrank &Daumann, 2009; Meyer, 2013; Parrott, 2013).
There may also be adverse subacute consequences overdosing on ecstasy such as psychosis, induced seizures, stroke due to high blood pressure, liver intoxication, organ failure, and in some cases, death (Gouzoulis-Mayfrank & Daumann, 2009). However, it is important to note that these repercussions could be due to use of other drugs while taking MDMA, such as cannabis and alcohol (Durdle et al., 2008; Jager et al., 2008).
As mentioned previously, users of ecstasy may experience effects as the drug slowly wears off, which is also popularly known as the “comedown” among avid MDMA users. Decrease in positive mood, signs and symptoms of depression, difficulty concentrating, and sleep deprivation are some examples of the negative aftereffects of MDMA use (Meyer, 2013). The “comedown” is typically caused by the low serotonin levels in the brain as the blockage of serotonin reuptake causes the remainder of serotonin to be destroyed (Durdle et al., 2008; Gouzoulis-Mayfrank & Daumann, 2009; Meyer, 2013).
The largest amount of research done on long-term effects of ecstasy on human cognition is memory deficits. According to Gouzoulis-Mayfrank and Daumann (2009), Jager et al. (2008), and Parrott (2013), default in memory were found in abstained MDMA users. It was also founded by Meyer (2013) that there were significant losses of all types of memory skills but visual memory. Nevertheless, it is also seen that ecstasy use has a larger impact on higher cognitive functioning, such as “executive processing, logical reasoning, problem solving, and emotional intelligence” (Parrott, 2013, p. 297) compared to basic cognitive skills.
There is potential for recovery from cognitive deficits associated with chronic MDMA use. Higher density of serotonin axons and serotonin transporters over time was seen in longitudinal studies, though a lengthy recovery may be expected when high doses of MDMA was used (Meyer, 2013). Effects of ecstasy are dose-dependent, which means the higher the amount od MDMA ingested, the higher the chances of adverse effects and complications (Gouzoulis-Mayfrank & Daumann, 2009; Meyer, 2013). A study also discovered that abstinent ecstasy users showed unaffected or even improved efficiency in memory (Parrott, 2013). Hence, natural recovery from chronic abuse of ecstasy is possible, but only if the individual addicted to the drug abstains from taking it.
Recovery is foreseeable if the addicted individual stays abstinent, in which cognitive deficits may improve. However, there needs to be treatment for the addiction itself. With abuse, there is a lack of number of MDMA abusers who seek professional help. Once help has been obtained, treatment may consist of psychotherapy, both individually and/or in a group, relapse prevention methods, and cognitive behavioral therapy (Meyer, 2013). Further, on top of necessary medications, this is also applicable to individuals suffering from depressive and anxiety symptomology, regardless of if the symptoms or disorders happened before or after ecstasy use (Durdle et al., 2008). Ecstasy overdose requires treatment for drug intoxication before anything else (Meyer, 2013).
Cognitive deficits and mood disorders associated to chronic ecstasy abuse is still under-evaluated, and solid conclusions cannot be made, leaving many questions about MDMA unanswered. However, with what we know currently, heavy ecstasy users do experience certain negative cognitive effects as well as psychological symptomology. Furthermore, this literature review reiterates the necessity for more in-depth research to be done on ecstasy use to better understand the relationship it has with serotonin as well as the possible disorders and deficiency it may bring along.
- Durdle, H., Lundahl, L.H., Johanson, C.E., & Tancer, M. (2008). Major depression: the relative contribution of gender, MDMA, and cannabis use. Official Journal of the Anxiety and Depression Association of America, 25(3), 241-247.
- Gouzoulis-Mayfrank, E., & Daumann, J. (2009). Neurotoxicity of drugs of abuse – the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines. Dialogues in Clinical Neuroscience, 11(3), 305-217.
- Jager, G., Win, M. M., Tweel, I., Schilt, T., Kahn, R. S., Brink, W., … Ramsey, N. F. (2008). Assessment of cognitive brain function in ecstasy users and contributions of other drugs of abuse: results from an fMRI study. Neuropsychopharmacology, 33, 247-258.
- Meyer, J. S. (2013). 3,4-methylenedioxymethamphetamine (MDMA): current perspectives. Substance Abuse and Rehabilitation, 4, 83-99.
- Parrott, A. C. (2013). Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research. Human Psychopharmacology: Clinical and Experimental, 28, 289-307.
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