Flow diagram of included neuroimaging studies in chronic cannabis users.

<p>Flow diagram of included neuroimaging studies in chronic cannabis users.</p

Functional neuroimaging studies in chronic cannabis users.

<p>Note: Yr.  =  years; CU  =  Cannabis users; HC  =  Healthy controls; M  =  Male; F  =  Female; SD  =  Standard deviation; FL  =  Frontal lobe; PL  =  Parietal lobe; TL  =  Temporal lobe; OL  =  Occipital lobe; I  =  Insula; BG  =  Basal ganglia; Cb  =  Cerebellum; fMRI  =  Functional magnetic resonance imaging; SPECT  =  Single photon emission tomography; PET  =  Positron emission tomopgraphy; DSC  =  Dynamic susceptibility contrast; V_T  =  Distribution volume; BP_ND  =  Non-displaceable binding potential; FDG  =  Fludeoxyglucose; L  =  Left hemisphere; R  =  Right hemisphere; ROI  =  Region of interest; MSIT  =  Multi-Source Interference Task; CBF  =  Global cerebral blood flow; rCBF  =  Regional cerebral blood flow; BOLD  =  blood oxygenation-level dependent; NE  =  Not specified; PFC  =  Prefrontal cortex; DLPFC  =  Dorsolateral prefrontal cortex; VMPFC  =  Ventromedial prefrontal cortex; OFC  =  Orbitofrontal cortex; ACC  =  Anterior cingulated cortex; NAcc  =  Nucleus accumbens; VS  =  Ventral striatum; STG  =  Superior temporal gyrus; SWM  =  Spatial working task; IGT  =  Iowa Gambling Task.</p>*<p>If not otherwise specified, results are presented in terms of chronic cannabis users.</p><p>○  =  Significant differences; ○  =  Non-significant differences;  =  Not examined.</p>**<p>Two subjects in the marijuana group met criteria for alcohol abuse.</p>***<p>Four teens in the chronic cannabis group met criteria for alcohol use disorder, two cases of abuse and two cases of dependence.</p>†<p>One control, three recent users and two abstinent users met criteria for alcohol use disorders.</p>†<p>Multiple comparison correction.</p

Influence of gender and genetics (<i>COMT, 5-HTTLPR</i>) on the temporal course of systolic blood pressure (upper-left panel), heart rate (lower-left panel), and oral temperature (right-end panel) (mean ± SEM); women n = 12 <i>vs.</i> men n = 15; COMT, <i>val/val</i> n = 8 <i>vs. met/*</i> n = 18; 5-HTTLPR, <i>l/*</i> n = 18 <i>vs. s/s</i> n = 9).

<p>*<i>p</i><0.05, **<i>p</i><0.01. Graph A corresponds to gender differences in OT, graph B corresponds to differences in OT as a function of 5-HTTLPR polymorphisms (<i>l/l</i> n = 11 <i>vs. s/s</i> n = 9). Subjects <i>l/s</i> (n = 7) are not represented for graph clarity, but data almost fully overlaps with the <i>s/s</i> trace.</p

Anthropometric data of included volunteers and MDMA doses according to gender and genotypes (mean ± SD [min, max]).

<p>MDMA, ±3,4-methylenedioxymethamphetamine; CYP2D6, cytochrome P450 2D6; FA: functional alleles COMT, catechol-O-methyltransferase; 5-HTTLPR, gene-linked polymorphic region. BMI: body mass index; <i>p.o: per os. *p</i><0.05<i>; **p</i><0.01.</p

Gender differences in physiological and subjective effects after MDMA administration (mean ± SD; women n = 12 <i>vs.</i> men n = 15) (only significant effects included).

<p>AUC: area under the effect-time curve; Emax: peak effect; Tmax: time of peak effect. VAS: visual analogue scale. ARCI: Addiction Research Center Inventory, PCAG: pentobarbital-chlorpromazine-alcohol group. VESSPA: Evaluation of the Subjective Effects of Substances with Abuse Potential.</p>*<p>p<0.05,</p>**<p>p<0.01.</p

Gender differences in pharmacokinetic parameters of MDMA and its metabolites (mean ± SD; for MDMA and HMMA: women n = 11 <i>vs.</i> men n = 15; for MDA and HMA: women n = 11 <i>vs.</i> men n = 12).

<p>MDMA, ±3,4-methylenedioxymethamphetamine; MDA, 3,4-methylenedioxyamphetamine; HMA, 3-methoxy-4-hydroxyamphetamine; HMMA, 3-methoxy-4-hydroxymethamphetamine; AUC: area under the concentration-time curve, C_max: peak plasma concentration; T_max: time with peak plasma; T_1/2: half-life of elimination; K_e: elimination constant; K_a: absorption constant; Vd: apparent volume of distribution; Cl: clearance; n.d: not determined, due to high variability (a).</p>**<p><i>p</i><0.01.</p

Genetic differences in physiological and subjective effects after MDMA administration (mean ± SD; women n = 12 vs. men n = 15) (only significant effects included).

<p>AUC: area under the effect-time curve; Emax: peak effect; COMT, catechol-O-methyltransferase; SBP: systolic blood pressure; DBP: diastolic blood pressure. 5-HTTLPR, gene-linked polymorphic region VESSPA: Evaluation of the Subjective Effects of Substances with Abuse Potential.</p>*<p>p<0.05;</p>**<p>p<0.01. N = [COMT, valval n = 8 vs. met/* n = 18; 5-HTTLPR, l/* n = 18 vs. s/s n = 9.</p

Plasma Concentrations of MDMA, HMMA, MDA, and HMA in both genders (mean ± standard error of the mean, SEM; for MDMA and HMMA: women n = 11 <i>vs.</i> men n = 15; for MDA and HMA: women n = 11 <i>vs.</i> men n = 12).

<p>Influence of <i>CYP2D6</i> genotype in plasma concentrations of HMMA (mean ± SEM; subjects with 2 FA n = 18 <i>vs.</i> with 1 FA n = 8. *<i>p</i><0.05, **<i>p</i><0.01.</p

Demographic variables, drug consumption characteristics.

a<p>Mean (SD).</p>b<p>Including students.</p>c<p>Standardized mean difference.</p

Genotype distributions of the participants.

<p>Results as the number of subjects (n) and percentage per genotype (%).</p>a<p>The first of both values corresponds to the comparison of ecstasy users, cannabis users, and controls. The second (with an *) corresponds to the comparison of heavy ecstasy users, light ecstasy users, cannabis users, and controls.</p