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Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole‐brain, voxel‐based, multi‐tissue mega‐analytic approach, thereby extending our recent surface‐based region of interest findings on a nearly matching sample using a complementary methodological approach. T1‐weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel‐based morphometry. The effects of group, sex, group‐by‐sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group‐by‐sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group‐by‐sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo‐occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD. [ABSTRACT FROM AUTHOR]

Background: The most important two medicinal cannabinoids are Δ9‐tetrahydrocannabinol (THC) and cannabidiol (CBD). Vaporised administration is superior due to its higher systemic availability, lower individual variability and faster drug delivery. Although it is common THC is co‐administered with CBD, the influence of CBD on the pharmacokinetics, especially the systemic availability of THC after vaporised administration, is unknown. Aims: To investigate the influence of different doses of co‐administered CBD on the systemic availability of THC, and to compare the availability of THC and CBD in a sample of frequent and infrequent cannabis users. Methods: The study used a randomised, double‐blind, crossover placebo‐controlled design. THC and/or CBD in ethanol was vaporised and inhaled. Plasma concentrations of THC and CBD were analysed. The THC data created in this study were pooled together with published THC pharmacokinetic data in order to cover all the phases of THC disposition. Population pharmacokinetic model of THC was developed based on the pooled data. The model of CBD was developed based on the data created in this study. Results: Population pharmacokinetic models of THC and CBD were developed. With concomitant inhalation of high‐dose CBD, the systemic availability of THC decreased significantly. Frequent cannabis users appeared to have higher systemic availability of THC and CBD when high‐dose CBD was administered. Conclusions: The results observed in this study are useful for guiding future pharmacokinetic studies of medicinal cannabinoids, and for development of dosing guidelines for medical use of cannabis in the 'real‐world' setting. [ABSTRACT FROM AUTHOR]

Cannabis use is highly prevalent and often considered to be relatively harmless. Nonetheless, a subset of regular cannabis users may develop dependence, experiencing poorer quality of life and greater mental health problems relative to non-dependent users. The neuroanatomy characterizing cannabis use versus dependence is poorly understood. We aimed to delineate the contributing role of cannabis use and dependence on morphology of the hippocampus, one of the most consistently altered brain regions in cannabis users, in a large multi-site dataset aggregated across four research sites. We compared hippocampal volume and vertex-level hippocampal shape differences (1) between 121 non-using controls and 140 cannabis users; (2) between 106 controls, 50 non-dependent users and 70 dependent users; and (3) between a subset of 41 controls, 41 non-dependent users and 41 dependent users, matched on sample characteristics and cannabis use pattern (onset age and dosage). Cannabis users did not differ from controls in hippocampal volume or shape. However, cannabis-dependent users had significantly smaller right and left hippocampi relative to controls and non-dependent users, irrespective of cannabis dosage. Shape analysis indicated localized deflations in the superior-medial body of the hippocampus. Our findings support neuroscientific theories postulating dependence-specific neuroadaptations in cannabis users. Future efforts should uncover the neurobiological risk and liabilities separating dependent and non-dependent use of cannabis. [ABSTRACT FROM AUTHOR]

Cannabis is the most commonly used illicit substance worldwide and the prevalence of users continues to increase. Over the last 2 decades, the world has seen significant changes regarding cannabis for recreational use as well as application in its use as a therapeutic medicine. This is likely to have influenced the decreasing perception of risks associated with the use of cannabis. Cannabis, however, is not benign and, depending on the pattern of its use, can incur a range of harmful effects, which have implications when prescribing medicinal cannabinoids for individuals. Based on research evidence from recreational use of cannabis as well as the emerging data from trials of medicinal cannabis, we propose some clinical domains that will need specific considerations when prescribing medicinal cannabis. [ABSTRACT FROM AUTHOR]

Editorial. Investigates whether the adverse consequences of cannabis use is age-dependent. Effect of regular cannabis use on psychosocial outcomes of adolescents; Factors causing greater risk of developing adverse consequences; Public health consequences.

'Ecstasy' (3,4-methylenedioxymethamphetamine or MDMA) is a recreational drug that is gaining popularity world wide. There is a paucity of research regarding the ways in which Ecstasy is used and the nature of its effects. A 'snowball' peer network technique was used to recruit 100 users who completed anonymous questionnaires. The research revealed that Ecstasy is primarily used by infrequent recreational drug users for 'fun' at dance parties and social gatherings. The primary reported effects of Ecstasy were a 'positive mood state' and feelings of intimacy and closeness to others. The secondary effects of Ecstasy were the stimulant effects of energy and activation, and the psychedelic effects of insight and perceptual and sensual enhancement. Ecstasy was reported to share the properties of both amphetamines and hallucinogens in the nature of its side effects and residual effects which were no more severe than those of the latter two classes of drug. It appeared Ecstasy was not conducive to regular and frequent use, because tolerance was reported to develop to the positive effects of Ecstasy, while negative effects increased with use. Although few problems associated with the recreational use of Ecstasy have surfaced to date, animal research has shown it to be neurotoxic to serotonergic nerve terminals. Caution must be observed until further research can determine the level of hazard in humans. [ABSTRACT FROM AUTHOR]

Event-related potentials (ERPs) for tone pips from attended and unattended sources, which varied on discriminability, were compared with ERPs for the same stimuli recorded during performance of a visual task. This comparison revealed that Nd, the negative shift of attended relative to unattended ERPs, consisted of three components: a negativity in the attended ERP from 100 to 270 ms, a positivity in the unattended ERP from 170 ms to the end of the epoch, and a second negativity in the attended ERP from 270 to 700 ms. In general, the later onset of early Nd with more difficult between-source discriminations could be attributed to the later onset of the positivity in unattended ERPs. A number of hypotheses were advanced for the origin of the unattended positivity: the suppression of the later of two negative components in the 100-220-ms range, an enhanced P2 component, an endogenous positivity, or the resolution of a protracted negativity elicited by preceding attended stimuli. [ABSTRACT FROM AUTHOR]

Opinion. Presents the authors' arguments in defense of their monograph entitled `The Health and Psychological Consequences of Cannabis Use.' Comparison with other works; Cultural context of cannabis use.

In this article the author comments on the study of J. Macleod and M. Hickman on the causality of the relation of cannabis use to schizophrenia. The author notes that while the strength in causality evidence between cannabis and schizophrenia is hard to deny, some arguments in the study are pushed by own belief that the cause of cannabis use is related to tobacco use. Meanwhile, the author suggests that the study should have used an approach in order to examine the ways to prevent cannabis use.

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence., (© 2021 Society for the Study of Addiction.)

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures., (© 2019 Society for the Study of Addiction.)

Background: The US National Institutes of Mental Health Research Domain Criteria (RDoC) seek to stimulate research into biologically validated neuropsychological dimensions across mental illness symptoms and diagnoses. The RDoC framework comprises 39 functional constructs designed to be revised and refined, with the overall goal of improving diagnostic validity and treatments. This study aimed to reach a consensus among experts in the addiction field on the 'primary' RDoC constructs most relevant to substance and behavioural addictions., Methods: Forty-four addiction experts were recruited from Australia, Asia, Europe and the Americas. The Delphi technique was used to determine a consensus as to the degree of importance of each construct in understanding the essential dimensions underpinning addictive behaviours. Expert opinions were canvassed online over three rounds (97% completion rate), with each consecutive round offering feedback for experts to review their opinions., Results: Seven constructs were endorsed by ≥ 80% of experts as 'primary' to the understanding of addictive behaviour: five from the Positive Valence System (reward valuation, expectancy, action selection, reward learning, habit); one from the Cognitive Control System (response selection/inhibition); and one expert-initiated construct (compulsivity). These constructs were rated to be related differentially to stages of the addiction cycle, with some linked more closely to addiction onset and others more to chronicity. Experts agreed that these neuropsychological dimensions apply across a range of addictions., Conclusions: The study offers a novel and neuropsychologically informed theoretical framework, as well as a cogent step forward to test transdiagnostic concepts in addiction research, with direct implications for assessment, diagnosis, staging of disorder, and treatment., (© 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)