- Does MDMA Cause Memory Loss?
- MDMA’s Effects on the Brain
- Does Ecstasy Cause Memory Loss?
- Serotonin Levels
- Brain Damage
- Molly Treatment Options
- Whether it's ecstasy, alcohol, or any other drug, Banyan Treatment Centers Stuart can help free you from a life of addiction. Call us today at 888-280-4763 to learn more about our Florida drug and alcohol treatment options.
- Repeated exposure to MDMA triggers long-term plasticity of noradrenergic and serotonergic neurons
- Repeated treatment
- Monitoring of cortical extracellular monoamines levels
- Locomotor activity
- Dexmedetomidine-induced sedation
- F13640-induced hypothermia
- Mice were killed by decapitation
Does MDMA Cause Memory Loss?
Ecstasy, or 3,4-methylenedioxymethamphetamine (MDMA), is a synthetic drug that affects perception and mood, producing euphoria, increased energy, and increased sociability.
A recent study on ecstasy and memory loss found that this drug can have long-term effects on memory, even in people who use it short term.
Our substance abuse treatment center in Stuart, FL, couldn’t help but look into this ourselves.
MDMA’s Effects on the Brain
Otherwise known as Molly, ecstasy or MDMA is chemically similar to stimulants and hallucinogens, meaning it can not only produce euphoria and alertness, but it can also produce hallucinations and other distortions in perception. Due to its side effects, Molly gained its popularity in the club scene, at music festivals, and raves. However, the practice of doing Molly has since expanded to other groups and social settings.
The MDMA memory loss claims have a lot to do with how this drug affects the brain and users’ curiosity regarding other drugs of abuse.
People usually take ecstasy as a capsule or tablet, although it sometimes comes in liquids that can be swallowed or as a powder that can be snorted.
“Molly” is the popular nickname for the supposedly “pure” crystalline powder version of MDMA, which usually comes in capsules.
Ecstasy affects three chemicals in the brain: dopamine, norepinephrine, and serotonin.
When someone takes Molly, they may experience side effects euphoria, increased energy and activity, increased heart rate, elevated blood pressure, sexual arousal, and impaired judgment. other drugs of abuse that affect dopamine.
Molly can also act in the brain’s reward system to reinforce drug-taking behaviors, making a person who takes Molly more ly to use this drug or other ones.
Does Ecstasy Cause Memory Loss?
Yes, MDMA (ecstasy) can cause memory loss. One study found that MDMA caused memory loss in ecstasy users, aged 17 to 31, who used the drug an average of 2.4 times a month. All study subjects stopped taking the drug for two weeks (which was confirmed by blood tests), so measurements of mental function would be accurate.
In the end, results showed that ecstasy users’ memories had declined over the years, particularly the areas of memory associated with recalling new memories. Users’ vocabulary, their ability to remember names, and their ability to remember how to get from one place to another were also affected.1
In another study on Molly drug abuse and memory loss, 23 new users were compared to 43 people who didn’t use any illicit drugs aside from cannabis. The study ran for 3 years, with 12-month check-ups.
On average, the participants of the study who used ecstasy took 33 pills in one year.
The results concluded that new ecstasy users who took 10 or more Molly tablets in their first year showed a decline in their immediate and long-term memory.2
Well, one of the lasting effects of Molly abuse is low serotonin levels. Serotonin is a key hormone in stabilizing mood, feelings of well-being, and happiness. It impacts the entire body, enabling brain cells and various areas of the central nervous system to communicate with each other. It’s also been found to play a huge role in memory.
Low serotonin levels are associated with memory loss and depressed mood, and even mental illnesses depression. MDMA affects serotonin levels in the brain by stimulating its constant release, depleting the brain of this important neurotransmitter. As a result, long-term ecstasy abuse can lead to psychological aftereffects, including memory loss.
Studies on MDMA and memory loss also show that impairment in memory can occur as a result of Molly’s impact on the amygdala, cingulate cortex, and hippocampus. These are three brain regions that are heavily involved in learning, memory, and processing emotions.
PET imaging has also shown that even a low dose of MDMA decreased cerebral blood flow in the motor and somatosensory cortex, amygdala, cingulate cortex, insula, and thalamus, each of which is involved with processing and forming emotions, behavioral learning, and motor and sensory function.3
Molly Treatment Options
Although many people believe that MDMA is harmless, this isn’t the case. It’s just one of the many illegal drugs that cause memory loss.
You should also keep in mind that ecstasy long-term brain damage can lead to other side effects mental illness, liver disease, and drug use of other kinds.
There’s also been a rise in counterfeit ecstasy that contains harmful chemicals that can impact the brain and organs.
Any drug that impacts dopamine and the reward system in the brain has the potential for abuse and addiction. Additionally, anything that you find yourself unable to stop using can also be considered addictive.
The best way to recover from Molly is with the help of addiction treatment specialists.
Due to its various ingredients and side effects, ecstasy comedown effects can be difficult to manage without the help of a medically monitored detox.
Our Florida drug detox center offers medical withdrawal treatment that can help you safely withdraw from Molly or other drugs and improve your chances of recovery.
Whether it's ecstasy, alcohol, or any other drug, Banyan Treatment Centers Stuart can help free you from a life of addiction. Call us today at 888-280-4763 to learn more about our Florida drug and alcohol treatment options.
Repeated exposure to MDMA triggers long-term plasticity of noradrenergic and serotonergic neurons
Repeated exposure to MDMA triggers long-term plasticity of noradrenergic and serotonergic neurons
- Synaptic transmission
3,4-Methylenedioxymethamphetamine (MDMA or ‘ecstasy’) is a psychostimulant drug, widely used recreationally among young people in Europe and North America.
Although its neurotoxicity has been extensively described, little is known about its ability to strengthen neural circuits when administered in a manner that reproduces human abuse (i.e. repeated exposure to a low dose). C57BL/6J mice were repeatedly injected with MDMA (10 mg kg−1, intraperitoneally) and studied after a 4-day or a 1-month withdrawal.
We show, using in vivo microdialysis and locomotor activity monitoring, that repeated injections of MDMA induce a long-term sensitization of noradrenergic and serotonergic neurons, which correlates with behavioral sensitization.
The development of this phenomenon, which lasts for at least 1 month after withdrawal, requires repeated stimulation of α1B-adrenergic and 5-hydroxytryptamine (5-HT)2A receptors.
Moreover, behavioral and neuroendocrine assays indicate that hyper-reactivity of noradrenergic and serotonergic networks is associated with a persistent desensitization of somatodendritic α2A-adrenergic and 5-HT1A autoreceptor function.
Finally, molecular analysis including radiolabeling, western blot and quantitative reverse transcription-polymerase chain reaction reveals that mice repeatedly treated with MDMA exhibit normal α2A-adrenergic and 5-HT1A receptor binding, but a long-lasting downregulation of Gαi proteins expression in both locus coeruleus and dorsal raphe nucleus. Altogether, our results show that repeated MDMA exposure causes strong neural and behavioral adaptations and that inhibitory feedback mediated by α2A-adrenergic and 5-HT1A autoreceptors has an important role in the physiopathology of addictive behaviors.
3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ‘ecstasy’, is a substituted amphetamine with psychostimulant and hallucinogenic properties.
This illicit drug is extensively consumed by teenagers and young people in clubs and rave parties, despite the increasing evidence of its putative neurotoxicity1, 2, 3 and its adverse effects on mental health.
Indeed, chronic use of MDMA has been associated with many psychiatric disorders including anxiety, depression or psychosis,4, 5, 6 and may lead to addiction in vulnerable individuals.7
In rodents, MDMA induces locomotor hyperactivity and repeated injections result in behavioral sensitization.8, 9, 10 This long-lasting phenomenon is thought to have a critical role in the development of compulsive drug seeking and drug taking, as well as in cue-induced relapse.11, 12
Studies of the brain circuits underlying addictive behaviors have focused on the mesolimbic dopaminergic system,13, 14 as it was shown that all drugs of abuse, including MDMA, increase extracellular dopamine levels in the nucleus accumbens of rodents.15, 16, 17, 18 However, several in vitro studies indicate that MDMA shows higher affinity for both norepinephrine and serotonin transporters than for dopamine transporter.19, 20, 21
Moreover, growing evidence suggests that the involvement of both noradrenergic and serotonergic systems in MDMA-induced addictive behaviors may have been seriously underestimated.
The pharmacological blockade of either α1-adrenergic or 5-hydroxytryptamine (5-HT)2A receptors reduces the hyperlocomotor effects of MDMA and prevents the development of behavioral sensitization.
22, 23 Also, self-administration of MDMA is abolished in mice lacking the serotonin transporter (serotonin transporter KO mice),24 whereas mice lacking 5-HT2A receptors (5-HT2A KO mice) are insensitive to MDMA-induced reinforcement and cue-induced reinstatement of MDMA-seeking behaviors.25
Recently, we identified a new kind of neural plasticity that may be involved in the long-term behavioral effects of drugs of abuse.
Indeed, we showed that repeated administration of amphetamine, cocaine, morphine, ethanol or nicotine+monoamine oxidase inhibitor induces long-lasting sensitization of noradrenergic and serotonergic neurons in C57BL/6J mice.
26, 27, 28, 29 Molecular mechanisms underlying this phenomenon remain however unknown.
The main purpose of this study was to investigate the long-term effects of a repeated MDMA exposure on noradrenergic and serotonergic transmissions.
The reactivity of noradrenergic and serotonergic neurons was investigated by in vivo microdialysis in the prefrontal cortex (PFC) and behavioral effects were recorded in parallel.
The mechanisms underlying MDMA-induced changes were then investigated at the molecular, physiological and behavioral levels.
Animals were 2–3 months old (26–32 g) C57BL/6J male mice (Charles River, L'Arbresle, France). They were housed eight per cage and maintained on a 12 h light/dark cycle with food and water available ad libitum.
Seven hundred mice were used in this study (300 mice for the microdialysis experiments, 256 mice for the behavioral experiments, 80 mice for the neuroendocrine experiments and 64 mice for the molecular experiments). Each mouse was naive at the beginning of each experiment and was not used repeatedly for the different tests.
Animal experimentation was conducted in accordance with the guidelines for care and use of experimental animals of the European Economic Community (86/809).
3,4-Methylenedioxymethamphetamine (MDMA) hydrochloride, D-amphetamine sulfate, p-chloroamphetamine (PCA) hydrochloride, prazosin hydrochloride, WAY-100635 (N-[2-[4-(2-[O-methyl-3H]methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl) cyclohexane carboxamide trihydrochloride) hydrochloride and efaroxan hydrochloride were purchased from Sigma-Aldrich (L’Isle d’Abeau-Chesne, France). Dexmedetomidine hydrochloride was purchased from Tocris Bioscience (Bristol, UK). SR46349B hemifumarate was a generous gift from Sanofi-Aventis (Paris, France) and F13640 was kindly supplied by Pierre Fabre Laboratories (Castres, France). All drugs were dissolved in saline (0.9% NaCl) except prazosin, which was dissolved and sonicated in water (50% of final volume), and then completed with saline and SR46349B, which was dissolved and sonicated in saline plus lactic acid (0.1%), and then finally neutralized with 10 M NaOH. Doses are expressed as salts. MDMA was given at 10 mg kg−1.10 D-amphetamine was given at 2 mg kg−1 and PCA at 7 mg kg−1.26 Doses of prazosin (1 mg kg−1) and SR46349B (1 mg kg−1) were identical to those used in previously reported experiments.26 Efaroxan was given at 2.5 mg kg−1 and WAY-100635 was given at 1 mg kg−1. The dose of F13640 given was between 0.1 and 0.6 mg kg−1 (ref. 30) and of dexmedetomidine was between 0.1 and 0.5 mg kg−1.31 In systemic experiments, drugs were injected intraperitoneally (0.1 ml per mouse). In local experiments, drugs were dissolved in artificial cerebrospinal fluid (see below) at a concentration of 1–1000 μM and infused incrementally in the PFC, the LC or the dorsal raphe nucleus (DRN) through the dialysis probe.
Mice were given four consecutive daily injections of saline or MDMA in the cylindrical compartment used for microdialysis or in that used to monitor locomotor activity. After a 4-day or a 1-month withdrawal period, all experiments were performed as described below (Supplementary Figure 1a).
To test the effects of prazosin and SR46349B on the development of neurochemical and behavioral sensitization to MDMA, as well as on the MDMA-induced desensitization of α2A-adrenergic and 5-HT1A autoreceptors function, mice were given a pretreatment (saline or prazosin plus SR46349B) every day 30 min before the injection of MDMA.
Mice were anesthetized with sodium pentobarbital (60 mg kg−1; Sanofi Santé Animale, Libourne, France) and placed in a stereotaxic frame (Kopf Instruments, Tujunga, CA, USA).
An unilateral permanent cannula (CMA/7; CMA Microdialysis, Solna, Sweden) was placed at the edge of the PFC, the LC or the DRN and secured on the skull with screws and dental cement. The coordinates for the guide cannula tip were as follows: PFC—anteroposterior, +2.
6 relative to bregma, mediolateral, +0.5 and dorsoventral, 0 mm from dura; LC—anteroposterior, −5.4 relative to bregma, mediolateral, +0.75 and dorsoventral, −2.4 mm from dura; and DRN—anteroposterior, −4.36 relative to bregma, mediolateral, 0, and dorsoventral, −1.
5 mm from dura, according to the atlas of Paxinos and Franklin32 (Supplementary Figure 1b). After surgery, mice were allowed to recover for at least 4 days.
Monitoring of cortical extracellular monoamines levels
On the day of the experiment, the microdialysis probe was inserted into the PFC (membrane length, 2 mm; diameter, 0.24 mm; cutoff, 6000 Da; CMA/7; CMA Microdialysis), the LC or the DRN (membrane length, 1 mm). Artificial cerebrospinal fluid (in mM: 147 NaCl, 3.5 KCl, 1 CaCl2, 1.2 MgCl2, 1 NaH2PO4, 25 NaHCO3, pH 7.
6) was perfused through the probe at a rate of 1 μl min−1 by a CMA/100 microinjection pump and samples from the PFC were collected in a refrigerated computer-controlled fraction collector (CMA/170). Adequate steady-state monoamines levels in perfusate samples were reached 140 min after probe insertion.
Cortical samples (20 μl every 20 min) were collected for 100 min, to determine basal extracellular values. Then, MDMA, amphetamine, PCA, dexmedetomidine or F13640 were injected either intraperitoneally or infused locally into the PFC, the LC or the DRN through the dialysis probe and cortical samples were collected for 200 min.
In local experiments, the concentration of dexmedetomidine and F13640 was gradually increased every 40 min (i.e. every two samples).
Dialysate samples (20 μl) were injected every 30 min through a rheodyne valve in the mobile phase circuit with a refrigerated automatic injector (Triathlon; Spark Holland, Emmen, The Netherlands). High-performance liquid chromatography was performed with a reverse-phase column (80 × 4.6 mm; 3 μm particle size; HR-80; ESA, Chelmsford, MA, USA).
The mobile phase (for NE analysis: 0.1 M NaH2PO4, 0.1 mM EDTA, 2.75 mM octane sulfonic acid, 0.25 mM triethylamine, 3% methanol, pH 2.9; for 5-HT analysis: 0.1 M NaH2PO4, 0.1 mM EDTA, 2.75 mM octane sulfonic acid, 0.25 mM triethylamine, 15% methanol, 5% acetonitrile, pH 2.9; and for DA analysis: 0.1 M NaH2PO4, 0.1 mM EDTA, 2.
75 mM octane sulfonic acid, 0.25 mM triethylamine, 6% methanol, pH 2.9) was delivered at 0.7 ml min−1 by an ESA-580 pump. An ESA coulometric detector (Coulochem II 5100A, with a 5014B analytical cell; Eurosep Instruments, Cergy, France) was used for electrochemical detection. The conditioning electrode was set at –0.
175 mV and the detecting electrode was set at +0.175 mV.
At the end of the experiment, a blue dye was infused through the microdialysis probe. Then, the brain was quickly removed and immediately frozen at −30 °C using isopentane cooled by dry ice and serial coronal slices were cut on a microtome to ensure the accurate probe implantation.
Mice were introduced into a circular corridor (4.5 cm width, 17 cm external diameter) crossed by four infrared beams (1.5 cm above the base) placed at every 90° (Imetronic, Pessac, France).
Locomotor activity was scored when animals interrupted two successive beams and thus had traveled one-quarter of the circular corridor.
Spontaneous activity was recorded for 120 min (habituation to the experimental procedure), and then mice were injected with amphetamine or PCA, and locomotor responses were recorded for an additional 200 min.
Mice were injected with dexmedetomidine (0.1–0.5 mg kg−1, intraperitoenally) and gently rolled onto their backs 30 min later.
The hypnotic response to dexmedetomidine was defined as the loss of the mouse’s righting reflex (LORR).
The sleep time was measured as the time from the mouse’s inability to right itself when placed on its back until the time when it spontaneously and completely reverted to the prone position.
Body temperature was measured by inserting a 2-cm-long 2-mm-diameter thermistor probe into the rectum of mice that had been gently handled for 20 s. Measurements were made every 10 min for 30 min (basal temperature). Then, the response to a systemic injection of F13640 (0.1–0.
6 mg kg−1, intraperitoneally) was assessed every 10 min until the temperature had returned to the basal value.
For each animal, the hypothermic response to F13640 was calculated as the difference between basal body temperature (calculated as the average temperature during the period before injection) and the minimal body temperature after injection.
Mice were killed by decapitation
The brain was quickly removed and immediately frozen at −30 °C using isopentane cooled by dry ice. Sections (16 μm thick) were cut at −20 °C in a cryostat (Leica CM3050 S, Leica Microsystems, Wetzlar, Germany), and stored at −80 °C for