Applying machine learning to international drug monitoring: classifying cannabis resin collected in Europe using cannabinoid concentrations.

In Europe, concentrations of ∆9-tetrahydrocannabinol (THC) in cannabis resin (also known as hash) have risen markedly in the past decade, potentially increasing risks of mental health disorders. Current approaches to international drug monitoring cannot distinguish between different types of cannabis resin which may have contrasting health effects due to THC and cannabidiol (CBD) content. Here, we compared concentrations of THC and CBD in different types of cannabis resin collected in Europe (either Moroccan-type, or Dutch-type). We then tested the ability of machine learning algorithms to classify the type of cannabis resin (either Moroccan-type, or Dutch-type) using routinely collected monitoring data on THC and CBD. Finally, we applied the optimal algorithm to new samples collected in countries where the type of cannabis resin was unknown, the UK and Denmark. Results showed that overall, Dutch-type samples had higher THC (Hedges' g = 2.39) and lower CBD (Hedges' g = 0.81) than Moroccan-type samples. A Support Vector Machine algorithm achieved classification accuracy exceeding 95%, with little variation in this estimate, good interpretability, and plausibility. It made contrasting predictions about the type of cannabis resin collected in the UK (94% Moroccan-type; 6% Dutch-type) and Denmark (36% Moroccan-type; 64% Dutch-type). In conclusion, we provide proof-of-concept evidence for the potential of machine learning to inform international drug monitoring. Our findings should not be interpreted as objective confirmatory evidence but suggest that Dutch-type cannabis resin has higher THC concentrations than Moroccan-type cannabis resin, which may contribute to variation in drug markets and health outcomes for people who use cannabis in Europe.

Psychological factors predicting patients' risk of relapse after enrollment in drug use treatment: A systematic review.

BACKGROUND AND AIMS: Despite high rates of relapse after treatment for drug use, to our knowledge there is no systematic literature identifying psychological factors that predict risk of relapse to drug use (excluding alcohol or tobacco). Our aim was to identify psychological factors that predict risk of relapse to drug use after enrollment in drug use treatment. The identification of such factors can support treatment planning and relapse prevention. METHODS: We searched for peer-reviewed articles published between 2000 and 2023 in PsycINFO, PsycArticles, Web of Science, and PubMed. The inclusion criteria were: peer-reviewed publications, quantitative studies, in English, adult samples, with a prospective design, and analyses of minimum one psychological factor as predictor of relapse to drug use. All authors were involved in abstract and full-text screening, and in assessing risk of bias. The findings are presented in a narrative synthesis and tables are organized by type of drug. RESULTS: Of 2226 publications initially identified, 45 were eligible. Twenty-three focused on predicting relapse to stimulants, 15 to opioids, and 7 to unspecified drugs. Substance use at baseline was an important factor predicting risk of relapse to opioids, and possibly stimulants. There was an indication that craving and attention problems potentially predict relapse to use of some drugs. Mental health factors (e.g., psychiatric diagnosis) did not predict relapse. Several psychological factors (e.g., cognition, emotion, personality, motivation) were scarcely examined. Over half of the studies had moderate to high risk of bias. CONCLUSIONS: Based on the 45 studies, few psychological factors predicted risk of relapse to drug use. Higher comparability between studies and more rigorous methodology are necessary in order to derive more precise recommendations that inform and improve clinical practice. PRE-REGISTRATION: PROSPERO, CRD42020182839.

Preliminary evaluation of a novel group-based motivational interviewing intervention with adolescents: a feasibility study.

Drinking is closely intertwined with social life among many adolescents, particularly in Europe. Group-based interventions, such as group-based motivational interviewing (group MI), have shown the capacity to prevent and reduce hazardous drinking and related problems among adolescents, but few examinations have been conducted in a European high school setting. This study examines the preliminary outcomes of a pilot group MI intervention among Danish adolescents. High school students (ages 15-18 years) were randomly allocated to two 1-h group MI sessions delivered in a school setting (N = 65) or an assessment only control condition (N = 67). Data were collected in August and November 2020 using online self-administrated questionnaires regarding the acceptability of the intervention and past month alcohol use. The pilot group MI intervention showed high feasibility and acceptability in this setting and with this age group. Group MI adolescents significantly reduced peak drinks per drinking day compared to assessment only adolescents (-2.7 drinks, p < 0.05). Results are discussed in relation to the metrics being evaluated during COVID-19 lockdown, including increased social restrictions at follow-up compared to baseline. Group MI shows promise for reducing hazardous alcohol use among Danish adolescents. In addition, the findings indicate the importance of building on and extending this work in future larger, better-powered randomized controlled trials.

Validity of an online, self-administered Timeline Followback for alcohol use with adolescents.

Objective: The Timeline Followback (TLFB) is a widely used and well-validated interview-based tool for assessing patterns of recent health risk behavior. There is some evidence of the validity of the TLFB as a self-administered online tool for assessing alcohol use, but further research is needed to establish its validity in younger populations and populations outside the United States. Further, it is unknown how self-administered online TLFB formats compare to more timesaving and commonly used single-item alcohol questions. The primary aim of the current study was to validate a new online, self-administered TLFB for alcohol use against the TLFB interview in a sample of European (Danish) adolescents aged 16-18 years (N = 30). Methods: Participants completed a TLFB telephone interview, a self-administered online version of the TLFB, and single-item alcohol questions. Assessments were administered using a within-subject, counter-balanced design. Estimates of number of drinking days, binge-drinking days, maximum drinks consumed on one occasion, total drinks, and drinks per drinking day were compared across metrics. Results: All correlations between the drinking outcomes assessed via the TLFB interview and the TLFB online were positive, and statistically significant (rss = 0.86-0.94, p < 0.01). Wilcoxon signed-rank tests showed no significant differences between the TLFB interview and the TLFB online on drinking days, binge drinking days, max drinks, and total drinks. Participants reported drinking significantly more drinks per drinking day on the TLFB online (M = 4.66) compared to on the TLFB interview (M = 4.12; p = 0.009). Conclusion: Overall, the results support the validity of the online, self-administered TLFB in a sample of European (Danish) adolescents.

Prevention of hazardous use of alcohol among high school students: a study protocol for the randomized controlled trial 'Our choice'.

BACKGROUND: Adolescent hazardous alcohol use is prevalent and has serious short- and long-term consequences. The trial 'Our Choice' examines efficacy, feasibility and acceptability of prevention interventions targeting school, parent, and student levels at Danish high schools. We hypothesize that students in a structural intervention (school and parent levels) reduce hazardous alcohol use and related health behaviors compared to students in an assessment only control group 12 months post baseline; and that adding group-based Motivational Interviewing (group MI) yields further improvements. The study examines the efficacy of interventions targeting multiple levels with the aim of providing novel insights into prevention of adolescent hazardous alcohol use and related health outcomes. METHOD: The study employs a parallel group cluster randomized controlled trial design with three conditions: (1) structural condition targeting school and parent levels, (2) structural condition combined with group MI which also targets the student level, and (3) assessment-only control condition. A participatory approach is used to adapt and develop interventions. Sixteen high schools in Denmark and about N = 3100 first-year students (15-18 years) enrolled in high school in August 2023 will be recruited. Data will be collected via online questionnaires pre-interventions (baseline), 2, 6, 9 and 12 month post baseline and analyzed with generalized linear mixed models. The primary outcome is past month high intensity drinking; secondary outcomes are alcohol use, alcohol-related consequences, well-being, tobacco, and illegal substance use. Feasibility and acceptability will be assessed via surveys (students) and interviews (high school staff) to inform future implementation. DISCUSSION: 'Our Choice' is the first trial to compare the efficacy of a structural intervention targeting school- and parent levels to an intervention targeting these levels and the student level via group MI - on hazardous drinking and related health outcomes among students. Preventing and reducing hazardous alcohol use during adolescence is crucial due to the short- and long-term negative consequences. The tested interventions can be implemented at low cost. The study has significant implications for adolescent health and well-being and has potential to inform evidence-based decisions on alcohol prevention policy, education, and health professions. TRIAL REGISTRATION NUMBER: The trial was retrospectively registered at ClinicalTrials.gov on August 24th, 2023. TRIAL REGISTRATION NUMBER: ID NCT06018389.

Hazardous alcohol use among Danish adolescents during the second wave of COVID-19: Link between alcohol use and social life.

Background: Adolescent drinking has historically been closely linked to social events, and across many countries, students typically increase drinking rates when they transition to upper secondary school. COVID-19-related restrictions offered a unique possibility to examine how changes in social life impact adolescent drinking in the transition to upper secondary school. Aim: The current study investigated changes in hazardous alcohol use, social life and well-being among Danish first-year students (mean age = 16.8 years) during the second wave of the COVID-19 pandemic when restrictions gradually became more intensified. Methods: Data were collected at two time points among 352 Danish students in the first months of upper secondary school (August and November 2020). Multilevel regression models tested changes across time on past 30 days hazardous alcohol use (dependent variables). Separate models tested whether changes in alcohol use were related to gender, social interaction, loneliness and mental health. Results: During increased COVID-19-related restrictions in the second wave, students decreased the frequency and quantity of drinking (number of drinking days and binge drinking), which was associated with attending fewer parties. Students also reported less high-intensity drinking and fewer alcohol-related consequences. Students reported better mental health, but more students were affected by loneliness. Changes in mental health or loneliness were not related to reduced hazardous alcohol use. Conclusion: Our results provide evidence that alcohol use decreased among Danish students transitioning to upper secondary school during the COVID-19 pandemic when restrictions increased, thereby providing support for a close link between adolescent alcohol use and social life; this is an important frame that is relevant when designing interventions to promote healthier and less risky choices throughout the next phase(s) of the pandemic and in general.

Patient and public involvement to inform the protocol of a clinical trial comparing total hip arthroplasty with exercise: an exploratory qualitative case study.

OBJECTIVE: To explore patient, clinician and decision-maker perceptions on a clinical trial evaluating the effectiveness of total hip arthroplasty (THA) compared with exercise to inform the trial protocol. DESIGN: This is an exploratory qualitative case study using a constructivist paradigm. SETTING AND PARTICIPANTS: Participants were enrolled into three key stakeholder groups: patients eligible for THA, clinicians, and decision makers. Focus group interviews were conducted in undisturbed conference rooms at two hospitals in Denmark, according to group status using semi-structured interview guides. ANALYSIS: Interviews were recorded, transcribed verbatim and thematic analysed using an inductive approach. RESULTS: We conducted 4 focus group interviews with 14 patients, 1 focus group interview with 4 clinicians (2 orthopaedic surgeons and 2 physiotherapists) and 1 focus group interview with 4 decision-makers. Two main themes were generated. 'Treatment expectations and beliefs impact management choices' covered three supporting codes: Treatment without surgery is unlikely to lead to recovery; Clinician authority impacts the management narrative; The 'surgery vs exercise' debate. 'Factors influencing clinical trial integrity and feasibility' highlighted three supporting codes: Who is considered eligible for surgery?; Facilitators and barriers for surgery and exercise in a clinical trial context; Improvements in hip pain and hip function are the most important outcomes. CONCLUSIONS: Based on key stakeholder treatment expectations and beliefs, we implemented three main strategies to improve the methodological rigorousness of our trial protocol. First, we added an observational study investigating the generalisability to address a potential low enrolment rate. Second, we developed an enrolment procedure using generic guidance and balanced narrative conveyed by an independent clinician to facilitate communication of clinical equipoise. Third, we adopted change in hip pain and function as the primary outcome. These findings highlight the value of patient and public involvement in the development of trial protocols to reduce bias in comparative clinical trials evaluating surgical and non-surgical management. TRIAL REGISTRATION NUMBER: NCT04070027 (pre-results).

The prediction of resilience to alcohol consumption in youths: insular and subcallosal cingulate myeloarchitecture.

BACKGROUND: The prediction of alcohol consumption in youths and particularly biomarkers of resilience, is critical for early intervention to reduce the risk of subsequent harmful alcohol use. METHODS: At baseline, the longitudinal relaxation rate (R1), indexing grey matter myelination (i.e. myeloarchitecture), was assessed in 86 adolescents/young adults (mean age = 21.76, range: 15.75-26.67 years). The Alcohol Use Disorder Identification Test (AUDIT) was assessed at baseline, 1- and 2-year follow-ups (12- and 24-months post-baseline). We used a whole brain data-driven approach controlled for age, gender, impulsivity and other substance and behavioural addiction measures, such as problematic cannabis use, drug use-related problems, internet gaming, pornography use, binge eating, and levels of externalization, to predict the change in AUDIT scores from R1. RESULTS: Greater baseline bilateral anterior insular and subcallosal cingulate R1 (cluster-corrected family-wise error p < 0.05) predict a lower risk for harmful alcohol use (measured as a reduction in AUDIT scores) at 2-year follow-up. Control analyses show that other grey matter measures (local volume or fractional anisotropy) did not reveal such an association. An atlas-based machine learning approach further confirms the findings. CONCLUSIONS: The insula is critically involved in predictive coding of autonomic function relevant to subjective alcohol cue/craving states and risky decision-making processes. The subcallosal cingulate is an essential node underlying emotion regulation and involved in negative emotionality addiction theories. Our findings highlight insular and cingulate myeloarchitecture as a potential protective biomarker that predicts resilience to alcohol misuse in youths, providing novel identifiers for early intervention.

Cannabinoids for the treatment of cannabis use disorder: New avenues for reaching and helping youth?

Cannabis use peaks during adolescence and emerging adulthood, and cannabis use disorder (CUD) is associated with a wide range of adverse outcomes. This is particularly pertinent in youth, because the developing brain may be more vulnerable to adverse effects of frequent cannabis use. Combining evidence-based psychosocial interventions with safe and effective pharmacotherapy is a potential avenue to improve youth outcomes, but we lack approved CUD pharmacotherapies. Here, we review new potential avenues for helping youth with CUD, with a particular focus on cannabinoid-based treatments. Evidence from placebo-controlled RCTs suggests synthetic delta-9-tetrahydrocannabinol (THC) decreases withdrawal symptoms, but not cannabis use, in adults with daily cannabis use/CUD, while findings regarding formulations containing THC combined with cannabidiol (CBD) are mixed. Preliminary evidence from two placebo-controlled RCTs in adults with CUD suggests that both Fatty Acid Amide Hydrolase inhibitors and CBD can reduce cannabis use. However, larger trials are needed to strengthen the evidence. Findings from adults point to cannabinoid-based treatments as a potential strategy that should be examined in youth with CUD.

A Randomized Controlled Trial of Attentional Control Training for Treating Alcohol Use Disorder.

Background: There is consistent evidence that community and clinical samples of individuals with an alcohol use disorder (AUD) have attentional biases toward alcohol cues. The alcohol attentional control training program (AACTP) has shown promise for retraining these biases and decreasing alcohol consumption in community samples of excessive drinkers. However, there is a lack of evidence regarding the effectiveness of ACTP in clinical AUD samples. The main aim of the present study is to investigate whether primary pharmacological and psychological, evidence-based alcohol treatment can be enhanced by the addition of a gamified AACTP smartphone application for patients with an AUD. Design and Methods: The study will be implemented as a randomized controlled trial. A total of 317 consecutively enrolled patients with AUD will be recruited from alcohol outpatient clinics in Denmark. Patients will be randomized to one of three groups upon initiation of primary alcohol treatment: Group A: a gamified AACTP smartphone application + treatment as usual (TAU); Group B: a gamified AACTP sham-control application + TAU; or Group C: only TAU. Treatment outcomes will be assessed at baseline, post-treatment, and at 3- and 6-month follow-ups. Repeated measures MANOVA will be used to compare the trajectories of the groups over time on alcohol attentional bias, alcohol craving, and drinking reductions. It is hypothesized that Group A will achieve better treatment outcomes than either Group B or Group C. Perspectives: Because attentional bias for alcohol cues is proportional to the amount of alcohol consumed, and these biases are not addressed within current evidence-based treatment programs, this study is expected to provide new evidence regarding the effectiveness of the gamified AACTP in a clinical population. Furthermore, due to promising results found using AACTP in community samples of excessive drinkers, there is a high probability that the AACTP treatment in this study will also be effective, thereby allowing AACTP to be readily implemented in clinical settings. Finally, we expect that this study will increase the effectiveness of evidence-based AUD treatment and introduce a new, low-cost gamified treatment targeting patients with an AUD. Overall, this study is likely to have an impact at the scientific, clinical, and societal levels. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05102942?term=NCT05102942&draw=2&rank=1, identifier: NCT05102942.

Purity of street-level cocaine across Denmark from 2006 to 2019: Analysis of seized cocaine.

Cocaine-related emergency department admissions are increasing, and cocaine seizures are at an all-time high in Europe. Our aim was to investigate the trends in purity and adulterants over time in cocaine available to cocaine users at street level in Denmark. We used a representative sample of cocaine seized at street level and analyzed by the national departments of forensic medicine between 2006 and 2019 (n = 1460). Latent profile analysis was used to classify the samples based on cocaine, levamisole, and phenacetin content. Low purity cocaine comprised most of the cocaine seizures in early years, but its share began to decline in 2013, and from 2016 to 2019, the high purity profile was dominant. While the total number of samples containing adulterants decreased, levamisole remained a common and dangerous adulterant. The findings underline the need to inform the public, medical doctors, and service providers for people with drug use disorders about the higher potency of street cocaine.

Exploring the use of cannabis as a substitute for prescription drugs in a convenience sample.

BACKGROUND: The use of cannabis as medicine (CaM) both prescribed and non-prescribed has increased markedly in the last decade, mirrored in a global shift in cannabis policy towards a more permissive stance. There is some evidence that cannabis functions as a substitute for prescription drugs, particularly opioids; however, more knowledge is needed on the motives of substitution users, their patterns of use, and perceived effects of substitution use. AIMS: To explore who substitutes prescription drugs with cannabis, the type of prescription drugs substituted and the type of cannabis used, and the impact that substitution with cannabis has on prescription drug use as well as the motives for substitution in terms of experienced effects and side effects. METHODS: A self-selected convenience sample was recruited through social media, public media, and patient organizations to take part in an anonymous online survey. Inclusion criteria were 18 years or older and use of cannabis (prescribed or non-prescribed) with a medical purpose. RESULTS: The final sample included 2.841 respondents of which the majority (91%) used non-prescribed cannabis, and more than half (54.6%) had used CaM with the purpose of replacing a prescribed drug. Compared to non-substitution users, substitution users were more likely to be women and to use CaM in the treatment of chronic pain and other somatic conditions. Pain medication (67.2%), antidepressants (24.5%), and arthritis medication (20.7%) were the most common types of drugs replaced with CaM. Among substitution users, 38.1% reported termination of prescription drug use, and 45.9% a substantial decrease in prescription drug use. The most frequent type of cannabis used as a substitute was CBD-oil (65.2%), followed by 'hash, pot or skunk' (36.6%). More than half (65.8%) found CaM much more effective compared to prescription drugs, and 85.5% that the side effects associated with prescription drug use were much worse compared to use of CaM. CONCLUSION: CaM is frequently used as a substitute for prescription drugs, particularly opioids. More research is needed on the long-term consequences of use of CaM, including the impact from low and high THC cannabis products on specific somatic and mental health conditions.

The Molecular Organization of Self-awareness: Paralimbic Dopamine-GABA Interaction.

The electrophysiology of the paralimbic network ("default mode") for self-awareness has drawn much attention in the past couple of decades. In contrast, knowledge of the molecular organization of conscious experience has only lately come into focus. We here review newer data on dopaminergic control of awareness in humans, particularly in self-awareness. These results implicate mainly dopaminergic neurotransmission and the control of GABAergic function directly in the paralimbic network. The findings are important for understanding addiction, developmental disorders, and dysfunctional consciousness.

Patients with osteoarthritis are least likely to receive lifestyle advice compared with patients with diabetes and hypertension: A national health survey study from Denmark.

Objectives: To investigate the association between having osteoarthritis (OA), hypertension, or diabetes, either alone or in combination, and receiving guideline-recommended exercise or weight-reduction advice. Design: Cross-sectional study. Methods: We applied logistic regression to analyse self-reported data from the 2017 Danish National Health survey (DNHS). We calculated the proportions and odds ratios of receiving exercise advice and weight-reduction advice (if BMI>30) from the general practitioner (GP) in seven patient groups: those with OA or hypertension or diabetes or any combination of these diseases. Results: From the 183,372 DNHS responders, we included 71,717 patients (≥45 years) who reported consulting a GP during the previous year. Among patients with only one disease, those with OA were least likely to receive exercise advice (13%, 1441/11,024) and weight-reduction advice (27%, 504/1877), while those with diabetes were most likely to receive these advice (32%, 387/1200 and 55%, 160/289, respectively).For OA-only patients, the adjusted odds ratios of receiving exercise advice and weight-reduction advice were 1.4 (95% CI 1.3 to 1.5) and 1.6 (95% CI 1.4 to 1.8), respectively, compared with patients with none of the three diseases. For diabetes-only patients, the adjusted odds ratios were 4.2 (95% CI 3.7 to 4.7) and 5.4 (95% CI 4.2 to 7.0), respectively. Conclusion: Few patients with OA self-reported having received guideline-recommended exercise advice, or weight-reduction advice if obese, from their GP. Furthermore, patients with OA were less likely to report having received these advice compared with patients with other chronic diseases.

Pilot study: Improving attention bias modification of alcohol cues through concealed gaze-contingent feedback in alcohol dependence.

In an attempt to improve attention bias modification (ABM), we tested whether an attentional training protocol which featured monetary operant conditioning of eye-gaze to avoid alcohol stimuli in alcohol-dependent patients could reduce attention, craving and relapse to alcohol. We employed a pilot randomized control trial (RCT) with 21 detoxified alcohol dependent patients (48.9 ±â€¯10 years of age, 9 male) from an inpatient and outpatient treatment centre. The novel concealed operant conditioning paradigm provided monetary reinforcements or punishments respective to eye-gaze patterns towards neutral or towards alcohol stimuli along with an 80% probability of a to-be-detected probe appearing following neutral stimuli (ET-ABM group). Patients in the control-group received random monetary feedback and a 50/50 ABM contingency. We compared AB on trained and untrained stimuli and addiction severity measures of obsessive thoughts and desires to alcohol following training. We further assessed addiction severity and relapse outcome at a 3-month follow-up. Results indicate that this attentional retraining only worked for the trained stimuli and did not generalize to untrained stimuli or to addiction severity measures or relapse outcome. Potential explanations for lack of generalization include the low sample size and imbalances on important prognostic variables between the active-group and control-group. We discuss progress and challenges for further research on cognitive training using gaze-contingent feedback.

Changes in the composition of cannabis from 2000-2017 in Denmark: Analysis of confiscated samples of cannabis resin.

Globally, recent studies report increases in Δ-9-tetrahydrocannabinol (THC) concentration in seized samples of cannabis for human consumption. This is important, because use of cannabis with a high concentration of THC has been linked to a number of adverse health outcomes. The objective of this study was to assess recent changes in the composition of seized cannabis resin in Denmark by (a) examining THC concentration in samples from Danish forensic laboratories from 2000 to 2017 (N = 430) and (b) examining cannabidiol (CBD) concentration and the THC:CBD concentration ratio in samples from the forensic laboratory in Western Denmark from 2008 to 2017 (N = 147). Cannabis resin samples were analyzed using a gas chromatographic analysis with flame ionization detection quantifying the total THC and CBD concentration. Results showed that the THC concentration increased 3-fold from 2000 (mean: 8.3%) to 2017 (mean: 25.3%). Significant increases occurred in all areas of Denmark. After 2011, we found a dramatic increase in cannabis resin samples with high THC concentration and the near disappearance of cannabis resin samples with medium- and low THC concentration. Furthermore, the THC:CBD concentration ratio increased significantly from 1.4 in 2008 to 4.4 in 2017. Whereas THC concentration increased, CBD concentration remained stable at ∼6%. In conclusion, the THC concentration of cannabis resin, and THC:CBD concentration ratio, have increased dramatically in Denmark, potentially leading to higher risk of harm to users. Policymakers, treatment professionals, and educators should be aware of this change. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Hunting for What Works: Adolescents in Addiction Treatment.

Although adolescents are developmentally distinct from adults, they often receive addiction treatment based on adult models. This is problematic because adolescents face significantly different conditions in addiction treatment, including distinct basic biological and neurodevelopmental stages, unique sociodevelopmental concerns, distinctive addiction trajectories, and, in turn, disparate treatment goals and outcomes. In sum, it can be difficult for even savvy clinicians to know how to approach addiction treatment with this important age group. In an effort to help clinicians and researchers consider substance use via a neurodevelopmental lens, we approached this review with 4 goals: (i) characterize the prevalence, and related health and safety implications of substance use within this age group; (ii) identify the nature of the adolescent brain, including characteristic features of this phase of neurodevelopment relevant to adolescent substance use treatment; (iii) provide an overview of current adolescent addiction interventions and avenues to improve clinical treatment and clinical research efforts for adolescents; and (iv) examine the intersection between the nature of the developing brain and adolescent substance use, and utilize that information to inform alternative routes and directions for substance use treatment in this critical age group. This review concludes by offering a novel neurodevelopmental model and framework to examine substance use interventions, along with a series of recommendations to optimize adolescent substance use treatment and clinical research.

The myeloarchitecture of impulsivity: premature responding in youth is associated with decreased myelination of ventral putamen.

Impulsivity has been suggested as a neurocognitive endophenotype conferring risk across a number of neuropsychiatric conditions, including substance and behavioural addictions, eating disorders, and attention deficit/hyperactivity disorder. We used a paradigm with interspecies translation validity (the four-choice serial reaction time task, 4CSRTT) to assess 'waiting' impulsivity in a youth sample (N = 99, aged 16-26 years). We collected magnetization prepared two rapid acquisition gradient echo (MP2RAGE) scans, which enabled us to measure R1, the longitudinal relaxation rate, a parameter closely related to tissue myelin content, as well as quantify grey matter volume. We also assessed inhibitory control (commission errors) on a Go/NoGo task and measured decisional impulsivity (delay discounting) using the Monetary Choice Questionnaire (MCQ). We found R1 of the bilateral ventral putamen was negatively correlated with premature responding, the index of waiting impulsivity on the 4CSRTT. Heightened impulsivity in youth was significantly and specifically associated with lower levels of myelination in the ventral putamen. Impulsivity was not associated with grey matter volume. The association with myelination was specific to waiting impulsivity: R1 was not associated with decisional impulsivity on the MCQ or inhibitory control on the Go/NoGo task. We report that heightened waiting impulsivity, measured as premature responding on the 4CSRTT, is specifically associated with lower levels of ventral putaminal myelination, measured using R1. This may represent a neural signature of vulnerability to diseases associated with excessive impulsivity and demonstrates the added explanatory power of quantifying the mesoscopic organization of the human brain, over and above macroscopic volumetric measurements.