Ari D. Kalechstein, Ph.D., Thomas Newton, M.D., Richard De La Garza, Ph.D., James Mahoney, B.A.

1. A Meta-analytic Review of the Association between Neuropsychological Functioning and Recreational MDMA Use Ari D. Kalechstein, Ph.D., Thomas Newton, M.D., Richard De La Garza, Ph.D., James Mahoney, B.A.

2. Translation of Preclinical Findings to Human Function Preclinical Findings (e.g., Neurotransmitter Abnormalities) Clinical Findings (e.g., Neuropsychological Abnormalities)

3. Neuropsychological Consequences of Recreational MDMA Use • Mixed results: • Association MDMA use observed in some studies • Other studies did not find an association • Not surprising, controversy has ensued • Treatment approaches • Policy decisions

4. Rationale for Meta-analytic Review • Integrate findings from different studies that used different statistical methods. • Quantitative determination of trends across studies (e.g., Pearson r, Cohen’s d). • Objective analysis of data • Possibly guide future research.

5. Method – Identification of Studies • Literature search • National Library of Medicine, Medline, PsycInfo • Search Indices • Neuropsychology, cognition, neurocognition, MDMA, and ecstasy • Initial sample = 61 studies

6. Method – Inclusion Criteria Criteria for inclusion: • Administered an NP test. • Included matched controls • Age • Education and/or • premorbid IQ • MDMA users were abstinent • Employed a statistic that could converted to r or d

7. Method – Study Sample • 9 studies met inclusion criteria • 61 statistical tests examining association between NP and MDMA use

8. Method – Coding Scheme • NP domains • Attention/concentration • Visuospatial skills • Memory (verbal and nonverbal) • Motor/Psychomotor Speed • Executive Systems Function

9. Method – Effect Sizes • Operationally defined as Cohen’s d, a measure of differences in SD between group means, and Pearson’s r. • Calculated using formulae from Rosenthal (1991). • Interpretation of effect sizes using d • Small effect : .2 • Medium effect: .5 • Large effect : .8

10. Method – Analysis of Effect Sizes • Convert Cohen’s d to Z-score (Zma) using formulae described by Rosenthal (1991). • Calculate mean Zma for each NP domain. • Zma> 1.96 as cutoff for significance (p < .05).

11. Method – Stability of Findings • Failsafe N (Nfs) • If Zma> 1.96, then Nfs used to determine how many studies with null findings would be needed for Zma to become nonsignificant • “file drawer effect”

12. Results - Effect Size for Each Domain # of Mean Domain tests d (sd) r (sd) Zma Nfs Attention 9 .42 (.30) .20 (.13) 3.73 23 Visuospatial Skills 2 .32 (n/a) .16 (n/a) 1.13 n/a Motor/ Psychomotor Speed 9 .53 (.20) .25 (.10) 5.11 52

13. Results - Effect Size for Each Domain # of Mean Domain tests d (sd) r (sd) Zma Nfs Verbal Memory 9 .43 (.35) .20 (.15) 6.19 80 Nonverbal Memory 10 .42 (.30) .20 (.13) 4.08 34 Executive Function 22 .43 (.20) .20 (.15) 6.28 203

14. Implications – General Findings • Recreational MDMA use was associated with deficits on measures sensitive to: • Attention • Memory • Verbal • Nonverbal • Motor/Psychomotor Speed • Executive Systems Function

15. Implications – Future Studies • Identify factors that mediate/moderate performance on NP tests: • Demographic factors • MDMA use patterns • Environmental variables • temperature

16. Implications – Memory Deficits and Functional Outcomes • Types of memory • Verbal and Visuospatial • Immediate and Delayed • Recall of: • Medication regimen. • Appointments. • Strategies to maintain abstinence • Completion of activities of daily living

17. Implications – Executive Deficits and Functional Outcomes • a.k.a. frontal lobe functioning. • Deficits on executive tasks assoc. w/: • Poor judgment. • Lack of insight. • Poor strategy formation. • Impulsivity. • Reduced capacity to determine consequences of actions.