Neurobiology of Ecstasy (MDMA) Abuse | Article Analysis

• Deborah Crim

A. Neurobiology of Ecstasy (MDMA) Abuse

B. Article 1 Analysis:

1. Article Title

Behavioral sensitization to 3,4-methylenedioxymethamphetamine (MDMA ecstasy) is long lasting and modulated by the context of drug administration (Ball, Klein, Plocinski, & Slack, 2012)

2. The research method used in this article.

The research method used consisted of 64 adult Sprague-Dawley rats which each rats weighing between 300 to 400 grams. A Coulbourn photo beam was used to monitor the location of the rats when they were running around. The measurements had a plus or minus of 0.999 beams per space on the floor of the ventilated cubicle (Ball, Klein, Plocinski, & Slack, 2012). Each rats was given one to four treatments of two daily injections of MDMA or a saline solution, two hours apart for five consecutive days in their home cages for the unpaired group, and the rats were monitored and tested for sensitization (paired groups) with a 30 minute injections (Ball & et. al, 2012). During the challenged injections, the rats in each treatment groups were assigned random challenge injections of 2.5 milligrams per kg weight between 15 to 100 days after their last injection of the drug treatment phase (Ball & et. al, 2012).

3. Key variables or phenomena of the hypotheses.

Those who are use to a wide range of drugs have shown to produce a change of behavior called sensitization or behavioral sensitization; which is considered an augmentation of the psychomotor effects of the drugs due to repeated exposure and represents a striking form of behavioral plasticity induced by drugs of abuse (Ball & et. al, 2012); i.e. the drug 3,4-methylenedioxymethamphetamine (MDMA; ecstasy).

4. Description of how the hypothesis was supported or not supported.

The goal of this study was to determine whether the expression of behavioral sensitization to MDMA is apparent following a very long withdrawal period of 100 days; in this research the withdrawal period was limited to 15 to 100 days for the rats (Ball & et. al, 2012).

The results showed the locomotor sensitization in the response to a challenge injection of the MDMA was evident after 15 days of withdrawal of repeated administration, but only in rats (paired animals) received the previous injections in the activity monitors and during the 100 days of withdrawal in both paired and unpaired MDMA-treated rats the sensitization differed; resulting in neural changes that underlined the behavioral sensitization to MDMA that lasted longer and involved an interaction of withdrawal time and the context of the drug administered (Ball & et. al, 2012).

5. Determination and explanation of whether the study was (or was not) conducted safely and ethically by the authors.

The test was conducted safety and according to guidelines provided for this research approved by the Guidelines for the Care and Use of Mammals in Neuroscience through the University Institutional Animal Care and Use Committee (Ball & et.al, 2012). Harlan Sprague-Dawley in Indianapolis, IN, provided the 64 rats. Each of those rats were housed in their individual hanging wire cages of a 12 hour light cycle from 7 a.m. to 7 p.m., had access to free food and water except during the testing period, and the drugs (MDMA) was provided by the National Institute on Drug Abuse (NIDA at the Research Triangle Park, NC) (Ball & et. al, 2012).

C. Article 2 Analysis:

1. Article Title

Evidence for chronically altered cortical serotonin function in human female recreational ecstasy (MDMA) polydrug users (Di lorio & et.al, 2012).

2. The research method used in this article.

The researchers utilized 25 females split into two groups; 15 MDMA users and 10 non-MDMA, their ages range from 18-25, and was required to complete the [¹⁸F]setoperone PET scans in order to assay their cortical 5-HT_2A receptor status (Di lorio & et. al, 2012).

There was two different analysis conducted, a Between Group Analysis and Within Group Analysis. During the Between Group Analysis, the females were tested with a general linear modeling analysis of MDMA users and non-MDMA users. The testing was used to see what other medicines or any other substances are currently being used. The MATLAB script extracts a mean of 5-HT_2ABP_ND in clusters, a two step approach to identify areas that was different between groups in 5-HT_2A binding within SPM and then to extract that data with the association of MDMA use greater 5-HT_2A binding potential (Di lorio & et.al, 2012). During the Within Group Analysis, researchers wanted to see if a dose-dependent effect of MDMA on the 5-HT axon loss and human functional magnetic resonance imaging (fMRI) studies revealed dose-dependent effects of MDMA on brain activation which resulted in the prediction that increased MDMA exposure would be associated higher levels of 5-HT_2ABP_ND if the 5-HT_2A receptor reflects the same processes associated with MDMA toxicity in animals (Di lorio & et. al, 2012).

3. Key variables or phenomena of the hypotheses.

Hypotheses of the research is to determine the MDMA use that is associated with chronic reductions in serotonin signaling in female human cerebral cortex as reflected by an increase in the 5-HT_2A receptors (Di lorio & et. al, 2012).

Between groups analysis showed MDMA users had an increase of the 5-HT_2ABP_ND in five cortical clusters located in the occipital-parietal, temporal, occipito-temporal-parietal, frontal, and fronto-parietal regions including the limbic system (Di lorio & et. al, 2012).

Within group analysis of MDMA/ecstasy dose effects: lifetime users showed the receptor binding in four cortical clusters located in the fronto-parietal, occipito-temporal, fronto-limbic, and frontal regions suggest that the increase of of 5-HT_2ABP_ND did not weaken with extended abstinence of MDMA(Di lorio & et. al, 2012).

4. Description of how the hypothesis was supported or not supported.

The hypothesis suggested that MDMA (ecstasy) is a popular recreational drug that produces loss of serotonin (5-HT) axons in animal models; suggestive chronic reductions of the 5-HT signaling in humans (Di lorio & et. al, 2012). A cross-sectional case-control study comparing 5-HT_2A receptors levels in abstinent female MDMA polydrug users to MDMA-naïve females; within a group design assessing the association of lifetime MDMA use and 5-HT_2A receptors, subjects had at least 90 days abstinence from MDMA use by hair sampling, cortical 5-HT_2A receptors was assessed by the 5-HT_2A-specific Positron Emission Tomography (PET) radioligand [¹⁸F]setoperone (Di lorio & et. al, 2012).

The results of the research and testing suggested that human recreational MDMA use is associated with long-lasting increases in 5-HT_2A receptor density and the levels correlate positively with lifetime MDMA use and did not decrease abstinence; MDMA produces chronic 5-HT neurotoxicity in humans (Di lorio & et. al, 2012).

5. Determination and explanation of whether the study was (or was not) conducted safely and ethically by the authors.

The study was conducted professionally, ethically, and safely. Recruiting of participants was conducted using advertisements in local media, flyers, and by word of mouth and each participant had to meet a certain criteria’s of exposure: ecstasy use, marijuana, or other recreational drugs, the participants were screened by phone for inclusion/exclusion. Those making it to the next meeting was screened in person and compensated for their participation. This study was approved by Vanderbilt University Institutional Review Board and conformed to the World Medical Association’s Declaration of Helsinki (Di lorio & et. al, 2012)

Criteria of the participants before the study:

Females were not allowed to use the drugs 2 weeks prior of enrollment and have a regular menstrual cycle or hormone regulated by oral contraceptives, those who are users had to report their MDMA use within 90 days before enrollment (Di lorio & et. al, 2012). Those who did not make the criteria due to general medical conditions such as PET or MRI scans for endocrine abnormalities, have a history of Axis-1 psychiatric diagnosis (except drug induced mood disorders), current or past substance dependence (except nicotine/caffeine), test positive in a drug screen 2 weeks prior of the PET scan, use of alcohol 72 hours of the PET scan, have used a psychoactive/vasoactive medication prior of 6 weeks of enrollment, and having a head injury with loss of consciousness greater than 20 minutes (Di lorio & et.al, 2012).

Participants was screened using the Mini-International Neuropsychiatric Interview (M.I.N.I), a North American Adult Reading Test (NAART) in order to assess the participants verbal intelligence, a urine test through the Triage Drugs of Abuse Panel by Biosite Diagnostics, a urine pregnancy test through the Sure-Vue Urine hCG by Fisher Health Care, testing of drug use, any types of cotinine, and a pregnancy test twice a week until the PET scan (Di lorio & et.al, 2012).

All research, interviews, and screening of PET was conducted at the Academic Medical Center Research Laboratory in Nashville, Tennessee by trained qualified doctors (Di lorio & et.al, 2012)..

D. Article 3 Analysis:

1. Article Title

Individual Differences in Acute Responses to MDMA in Humans: Effects of Sex and Past Ecstasy Use (Bedi & de Wit, 2011)

2. The research method used in this article.

Data from two within-subjects, a placebo-controlled, double-blind, and randomize studies conducted from 2007-09.

Participants were 21 males and 14 females who were 24 year old with a lifetime use of ecstasy on 27 occasions; i.e. dose-dependently increased ratings of feeling any drug effect, feeling high, wanting more drug, stimulation, anxiety, increased sociability, friendliness, elation, positive mood, vigor, nausea, increase in confusion (Bedi & de Wit, 2011). Each participant was observed for any increase of systolic and diastolic blood pressure and heart rates.

3. Key variables or phenomena of the hypotheses.

Study one consisted of 10 subjects with an fMRI investigation of MDMA (0.75 mg/kg) effects on social processing, second study of 25 subjects examined the effects of MDMA (0.75 mg/kg) and methamphetamine on social cognition. The data included placebo (PBO) sessions; sex differences change scores using the ANCOVAs with a peak change in PBO session, relationships between lifetime use of ecstasy and a peak change in response to MDMA using the Pearson’s correlations/partial correlations of PBO use. A questionnaire, visual analog scale measures mood and profile of the moods, and cardiovascular measure of the heart rate and blood pressure (Bedi & de Wit, 2011).

4. Description of how the hypothesis was supported or not supported.

Hypotheses to study the effects of cumulative lifetime ecstasy use on acute MDMA effects; since other studies indicate prior MDMA exposure produces lasting reductions in behavioral responses to the drug (Bedi & de Wit, 2011).

The findings showed MDMA use in females was greater than males in the symptoms of stimulation and anxiety, heart rate, diastolic blood pressure and they showed a decrease of self-rated elation and positive mood after MDMA than males.

Analysis supports the reports that women was vulnerable to acute negative subjective effects of MDMA and the behavioral effects of MDMA was greater in females; in conclusion suggested that females were more vulnerable to acute negative mood and cardiovascular effects of MDMA than males that includes recreational and therapeutic MDMA use (Bedi & de Wit, 2011).

5. Determination and explanation of whether the study was (or was not) conducted safely and ethically by the authors.

Research conducted with a medical team to respond to the effects of irregular heartbeats or an increase of blood pressure. No other explanation from the authors.

E. Take the role of the researcher. With the topic you selected, decide which of the research methods you believe is the most appropriate to study the problem. Explain Why.

The article, “Evidence for chronically altered cortical serotonin function in human female recreational ecstasy (MDMA) polydrug users” (Di lorio & et.al, 2012), would be most appropriate for the MDMA/ecstasy use because it utilizes non-users and users of MDMA/ecstasy use. Since those subjects (MDMA/ecstasy) users are currently using some form of the drug or any other drugs, it made the research possible to test how the drug affects the cortical serotonin function when observed with the PET scans. The test subjects (both users and non-users) had to conduct various mental evaluations, blood work, urinalysis, and questionnaires to make sure the subjects was physically and mentally capable to handle the research. This research will give us (researchers) a better understanding of the brains function during the different levels of performance of the drug as well as the after effects of those withdrawing from it; basically the who, what, when, where, and how questions.

References

Ball, K.T., Klein, J.E., Plocinski, J.A, and Slack, R. (December 2012). Behavioral sensitization to 3,4-methylenedioxymethamphetamine (MDMA ecstasy) is long lasting and modulated by the context of drug administration. Behav Pharmaco Vol. 22(8): 847-850. doi:10.1097/FBP.0b013e32834d13b4. Retrieved online February 2, 2014 http://europepmc.org/articles/PMC3212638/reload=0;jsessionid=66pDFXzwZ3nHklIleBHn.0

Bedi, G. & de Wit, H. (2011). Individual differences in acute responses to MDMA in humans: Effects of sex and past ecstasy use. From The Open Addiction Journal Vol. 4: 6-7. Retrieved online February 4, 2014 http://benthamscience.com/open/toaddj/articles/V004/SI001TOADDJ/6TOADDJ.pdf

Di lorio, C.R. (Ed.M), Watkins, T.J. (B.A.), Dietrich, M.S. (Ph.D.), Cao, A (Ph.D), Blackford, J.U. (Ph.D), Rogers, B (Ph.D), Ansari, M.S. (Ph.D), Baldwin, R.M. (Ph.D), Li, R. (M.Sc), Kessler, R.M. (M.D.), Salomon, R.M. (M.D.), Benningfield, M. (M.D.), & Cowan, R.L. (M.D. & Ph.D). (April 2012). Evidence for chronically altered cortical serotonin function in human female recreational ecstasy (MDMA) polydrug users. From Arch Gen Psychiatry Vol. 69(4): 399-409. Retrieved online February 4, 2014 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538835/