MDMA use is associated with lower gray matter volume in widespread cortical regions

s / Drug and Alcohol Dependence 140 (2014) e2–e85 e51 and onset cannabis-use was defined as usage at least once during lifetime. Results: Approximately 43% of the sample reported lifetime cannabis use, with mean onset age of 16.61 years (SD=2.62). Approximately 36% had smoked regularly (mean age=18.11, SD=2.38). Age at initiation of cannabis use and regular smoking was correlated (r=0.39). The magnitude of heritable versus nonshared environmental variation in tobacco smoking age of onset approximated38%and65%, respectively,whereas themagnitudeof heritable variation in cannabis use age of onset approximated 38%, with the remaining variance attributable to shared (24%) and nonshared (38%) environmental factors. Whereas the genetic overlap in age of onset for tobacco and cannabis-use was substantial (78%), overlap in non-shared environmental variance was negligible (6%). Thus, 60% of the covariation between initiation of cannabis use and regular tobacco use was due to additive genetic factors. Conclusions: Overlapping genetic influences linking cannabis and tobacco use play a role as early as initiation of use. Future analyses will explore whether after accounting for this genetic overlap, age at onset of marijuana and nicotine dependence are also influenced by common genetic factors. Financial support: NIDA T32DA007313-12, DA23668, AA017915, AA11998. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.158 MDMA use is associated with lower gray matter volume in widespread cortical regions Andrew J. Dornan, T.J. Watkins, M.S. Dietrich, Margaret M. Benningfield, J.U. Blackford, R.M. Salomon, Ronald L. Cowan Vanderbilt University, Nashville, TN, United States Aims: MDMA has been a popular recreational drug for 25 years and is now in trials as an adjunct to psychotherapy. Animal models show serotonergic neurotoxicity at high doses, while human studies suggest that recreational exposure is associatedwith lower serotonin signalingand long-termcognitive changes. Studies investigating the association of MDMA use with brain gray matter volume have been equivocal, with evidence for lower brain gray matter in MDMA users as well as with evidence for no difference in gray matter volume in MDMA users. Methods: We recruited 41 MDMA users (mean 31.3 lifetime MDMA episodes) and 30 non-users aged 18–34 and abstinent from recreational drugs (excluding nicotine and caffeine) for at least two weeks. Gray matter, white matter and CSF volume were measured using structural cranial MRI scans pre-processed with DARTEL and analyzed using the voxel based morphometry (VBM) method in SPM8, controlling for total intracranial volume. Results: Lifetime MDMA use was negatively associated with gray matter volume in bilateral regions of the frontal, temporal, parietal, occipital and limbic lobes (correlation coefficients ranged from −0.6 to −0.8), with no regions featuring a positive association. Although MDMA users had greater polydrug use than the control group, the association between MDMA use and lower gray matter volume remained after controlling for lifetime use of other drugs. In the between-group analysis, MDMA users had lower gray matter volume throughout the cerebrum. Regional white matter volume was also negatively associated with lifetime MDMA use and was lower in the MDMA group. Over the entire brain, the ratio of gray and white matter volume to total intracranial volume was 3.5% lower in MDMA users. Conclusions: Recreational use of MDMA is associated with lower cortical gray matter volume. Further research is needed to determine the functional consequences of lower gray matter volume and whether these differences in brain structure pre-exist MDMA use or result from MDMA exposure. Financial support: R01DA01537, R21 DA020149, K01MH083052, UL1RR024975. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.159 External validation of the potential concern index model based on individual prescribing patterns P. DuBose1, P.J. Burns1, James D. Haddox2 1 Principled Strategies, Inc., Encinitas, CA, United States 2 Health Policy, Purdue Pharma L.P., Stamford, CT,