Impact of Legalization on Cannabis Use, Attitudes, and Purchasing Preferences: A Repeated Cross-Sectional Survey of Canadian Young Adults.

Objective: The Government of Canada legalized recreational cannabis use in October of 2018 with the implementation of the Cannabis Act. The act aimed to reduce the illicit cannabis market, improve consumer health outcomes, and reduce youth access to cannabis. However, little is known about the attitudes and behaviors of young adults, who have been shown to have a high prevalence of cannabis use, towards cannabis after legalization. Method: In this descriptive study, we examined cannabis use, attitudes, and purchasing preferences among Canadian university-attending young adults both before and after the legalization of cannabis. Participants were recruited from a large Canadian university from 2017 to 2021. Results: Our findings showed that there was an increase in cannabis use immediately following legalization that subsequently decreased in later years. Additionally, attitudes about the legalization of cannabis became more favorable in later years (following legalization), particularly among those who did not use cannabis. Most young adults were also keen to purchase cannabis from a government-owned store before legalization. However, with the exception of past-month consumers, this preference decreased substantially following legalization. Conclusions: The current research adds to the knowledge base about changes in cannabis-related attitudes and use after legalization and focuses on a key population - young adults.

Uncovering the metabolite complexity and variability of cultivated hemp (Cannabis sativa L.): A first phytochemical diversity mapping in Greece.

The high value of fiber-type Cannabis sativa L. (hemp) due to its phytochemicals has yet to be fully recognized and leveraged. Besides cannabidiol (CBD), which is the most prevalent non-psychoactive cannabinoid, hemp contains numerous other cannabinoids with unexplored bioactivities, in addition to various compound classes. Previous works have aimed to correlate chemical profiles of C. sativa inflorescences with important parameters, mostly based on experiments under controlled conditions. However, mapping studies that explore the phytochemical diversity of hemp in a more realistic context are crucial to guide decisions at multiple levels, especially in areas where hemp cultivation was recently re-authorized, including Mediterranean countries. In this work, a powerful strategy was followed to map the phytochemical diversity of cultivated hemp in Greece, being the first study of its kind for this environment. A panel of 98 inflorescence samples, covering two harvesting years, eleven geographical regions and seven commonly used EU varieties, were studied using a combination of targeted and untargeted approaches. Quantitative results based on UPLC-PDA revealed relatively constant CBD/THC (total) ratios, while profiling by LC-HRMS effectively probed the phytochemical variability of samples, and led to the annotation of 88 metabolites, including a multitude of minor cannabinoids. Multivariate analysis substantiated a strong effect of harvesting year in sample discrimination and related biomarkers were revealed, belonging to fatty acids and flavonoids. The effect of geographical region and, especially, variety on chemical variation patterns was more intricate to interpret. The results of this work are envisioned to enhance our understanding of the real-world phytochemical complexity of C. sativa (hemp), with a view to maximized utilization of hemp for the promotion of human well-being.

Compliance Trends in a 14-Week Ecological Momentary Assessment Study of Undergraduate Alcohol Drinkers.

High compliance is a priority for successful ecological momentary assessment (EMA) research, but meta-analyses of between-study differences show that reasons for missed prompts remain unclear. We examined compliance data from a 14-week, 182-survey EMA study of undergraduate alcohol use to test differences over time and across survey types between participants with better and worse compliance rates, and to evaluate the impact of incentives on ongoing participation. Participants were N = 196 students (65.8% female; Mage = 20.6). Overall compliance was 76.5%, declining gradually from 88.9% to 70% over 14 weeks. Declines were faster in participants with lower overall compliance, but we found no demographic, personality, mental health, or substance use differences between participants with better versus worse compliance rates. Compliance varied by survey type, and unannounced bonus incentives did not impact compliance rates. Participants completed fewer surveys the week after winning a gift card. We offer recommendations for designing future EMA studies.

Stress and Mood Associations With Smartphone Use in University Students: A 12-Week Longitudinal Study.

The current study used device-logged screen-time records to measure week-to-week within-person associations between stress and smartphone use in undergraduate students (N = 187; mean age = 20.1 years). The study was conducted during fall 2020 and focused on differences across types of app used and whether accumulated screen use each week predicted end-of-week mood states. Participants uploaded weekly screenshots from their iPhone "Screen Time" settings display and completed surveys measuring stress, mood, and COVID-19 experiences. Results of multilevel models showed no week-to-week change in smartphone hours of use or device pickups. Higher stress levels were not concurrently associated with heavier smartphone use, either overall or by type of app. Heavier smartphone use in a given week did not predict end-of-week mood states, but students who tended to spend more time on their phones in general reported slightly worse moods-a between-persons effect potentially reflecting deficits in well-being that are present in students' off-line lives as well. Our findings contribute to a growing scholarly consensus that time spent on smartphones tells us little about young people's well-being.

The daily association between affect and alcohol use: A meta-analysis of individual participant data.

Influential psychological theories hypothesize that people consume alcohol in response to the experience of both negative and positive emotions. Despite two decades of daily diary and ecological momentary assessment research, it remains unclear whether people consume more alcohol on days they experience higher negative and positive affect in everyday life. In this preregistered meta-analysis, we synthesized the evidence for these daily associations between affect and alcohol use. We included individual participant data from 69 studies (N = 12,394), which used daily and momentary surveys to assess affect and the number of alcoholic drinks consumed. Results indicate that people are not more likely to drink on days they experience high negative affect, but are more likely to drink and drink heavily on days high in positive affect. People self-reporting a motivational tendency to drink-to-cope and drink-to-enhance consumed more alcohol, but not on days they experienced higher negative and positive affect. Results were robust across different operationalizations of affect, study designs, study populations, and individual characteristics. These findings challenge the long-held belief that people drink more alcohol following increases in negative affect. Integrating these findings under different theoretical models and limitations of this field of research, we collectively propose an agenda for future research to explore open questions surrounding affect and alcohol use.

Association Between Stimulant Treatment and Substance Use Through Adolescence Into Early Adulthood.

Importance: Possible associations between stimulant treatment of attention-deficit/hyperactivity disorder (ADHD) and subsequent substance use remain debated and clinically relevant. Objective: To assess the association of stimulant treatment of ADHD with subsequent substance use using the Multimodal Treatment Study of ADHD (MTA), which provides a unique opportunity to test this association while addressing methodologic complexities (principally, multiple dynamic confounding variables). Design, Setting, and Participants: MTA was a multisite study initiated at 6 sites in the US and 1 in Canada as a 14-month randomized clinical trial of medication and behavior therapy for ADHD but transitioned to a longitudinal observational study. Participants were recruited between 1994 and 1996. Multi-informant assessments included comprehensively assessed demographic, clinical (including substance use), and treatment (including stimulant treatment) variables. Children aged 7 to 9 years with rigorously diagnosed DSM-IV combined-type ADHD were repeatedly assessed until a mean age of 25 years. Analysis took place between April 2018 and February 2023. Exposure: Stimulant treatment of ADHD was measured prospectively from baseline for 16 years (10 assessments) initially using parent report followed by young adult report. Main Outcomes and Measures: Frequency of heavy drinking, marijuana use, daily cigarette smoking, and other substance use were confidentially self-reported with a standardized substance use questionnaire. Results: A total of 579 children (mean [SD] age at baseline, 8.5 [0.8] years; 465 [80%] male) were analyzed. Generalized multilevel linear models showed no evidence that current (B [SE] range, -0.62 [0.55] to 0.34 [0.47]) or prior stimulant treatment (B [SE] range, -0.06 [0.26] to 0.70 [0.37]) or their interaction (B [SE] range, -0.49 [0.70] to 0.86 [0.68]) were associated with substance use after adjusting for developmental trends in substance use and age. Marginal structural models adjusting for dynamic confounding by demographic, clinical, and familial factors revealed no evidence that more years of stimulant treatment (B [SE] range, -0.003 [0.01] to 0.04 [0.02]) or continuous, uninterrupted stimulant treatment (B [SE] range, -0.25 [0.33] to -0.03 [0.10]) were associated with adulthood substance use. Findings were the same for substance use disorder as outcome. Conclusions and Relevance: This study found no evidence that stimulant treatment was associated with increased or decreased risk for later frequent use of alcohol, marijuana, cigarette smoking, or other substances used for adolescents and young adults with childhood ADHD. These findings do not appear to result from other factors that might drive treatment over time and findings held even after considering opposing age-related trends in stimulant treatment and substance use.

Social cognition in youth with a first-degree relative with schizophrenia: A systematic scoping review.

Social-cognitive deficits are present in individuals at familial high-risk (FHR) for schizophrenia and may play a role in the onset of the illness. No literature review has examined the social-cognitive profiles of youth at FHR who are within the peak window of risk for developing schizophrenia, which could provide insight on the endophenotypic role of social cognition. This systematic scoping review (1) summarizes the evidence on social-cognitive deficits in youth at FHR, (2) explores brain correlates, and (3) describes social-cognitive deficits and prodromal symptom associations. We searched PsycInfo and PubMed for studies investigating social cognition in FHR youth aged 35 or younger and included 19 studies (FHR=639; controls=689). Studies report that youth at FHR have difficulty recognizing negative emotions, particularly fear. Youth at FHR also have difficulty performing complex theory of mind tasks. Abnormality in corticolimbic and temporoparietal regions are observed in youth at FHR during social-cognitive tasks, but results are inconsistent. Finally, there is evidence for negative associations between prodromal symptoms and performance on emotion regulation and theory of mind tasks, but the research is scarce. This review highlights the need for studies on youth at FHR using longitudinal designs and extensive social-cognitive, brain imaging and clinical measures.

Evaluation of the anti-inflammatory effects of selected cannabinoids and terpenes from Cannabis Sativa employing human primary leukocytes.

Cannabis is well established as possessing immune modulating activity. The objective of this study was to evaluate the anti-inflammatory properties of selected cannabis-derived terpenes and cannabinoids. Based on their activity in cannabis-chemovar studies, α-pinene, trans-nerolidol, D-limonene, linalool and phytol were the selected terpenes evaluated. The cannabinoid compounds evaluated included cannabidivarin, cannabidiol, cannabinol, cannabichromene, cannabigerol and delta-9-tetrahydrocannabinol. Human PBMC were pretreated with each compound, individually, at concentrations extending from 0.001 to 10 µM and then stimulated with CpG (plasmacytoid dendritic cell), LPS (monocytes), or anti-CD3/CD28 (T cells). Proliferation, activation marker expression, cytokine production and phagocytosis, were quantified. Of the 21 responses assayed for each compound, cannabinoids showed the greatest immune modulating activity compared to their vehicle control. Delta-9-tetrahydrocannabinol possessed the greatest activity affecting 11 immune parameters followed by cannabidivarin, cannabigerol, cannabichromene, cannabinol and cannabidiol. α-Pinene showed the greatest immune modulating activity from the selected group of terpenes, followed by linalool, phytol, trans-nerolidol. Limonene had no effect on any of the parameters tested. Overall, these studies suggest that selected cannabis-derived terpenes displayed minimal immunological activity, while cannabinoids exhibited a broader range of activity. Compounds possessing anti-inflammatory effects may be useful in decreasing inflammation associated with a range of disorders, including neurodegenerative disorders.

Identification of minimum essential therapeutic mixtures from cannabis plant extracts by screening in cell and animal models of Parkinson's disease.

Medicinal cannabis has shown promise for the symptomatic treatment of Parkinson's disease (PD), but patient exposure to whole plant mixtures may be undesirable due to concerns around safety, consistency, regulatory issues, and psychoactivity. Identification of a subset of components responsible for the potential therapeutic effects within cannabis represents a direct path forward for the generation of anti-PD drugs. Using an in silico database, literature reviews, and cell based assays, GB Sciences previously identified and patented a subset of five cannabinoids and five terpenes that could potentially recapitulate the anti-PD attributes of cannabis. While this work represents a critical step towards harnessing the anti-PD capabilities of cannabis, polypharmaceutical drugs of this complexity may not be feasible as therapeutics. In this paper, we utilize a reductionist approach to identify minimal essential mixtures (MEMs) of these components that are amenable to pharmacological formulation. In the first phase, cell-based models revealed that the cannabinoids had the most significant positive effects on neuroprotection and dopamine secretion. We then evaluated the ability of combinations of these cannabinoids to ameliorate a 6-hydroxydopmamine (OHDA)-induced change in locomotion in larval zebrafish, which has become a well-established PD disease model. Equimolar mixtures that each contained three cannabinoids were able to significantly reverse the OHDA mediated changes in locomotion and other advanced metrics of behavior. Additional screening of sixty-three variations of the original cannabinoid mixtures identified five highly efficacious mixtures that outperformed the original equimolar cannabinoid MEMs and represent the most attractive candidates for therapeutic development. This work highlights the strength of the reductionist approach for the development of ratio-controlled, cannabis mixture-based therapeutics for the treatment of Parkinson's disease.

Personality and Alcohol Use across College: Examining Context-Dependent Pathways toward Alcohol Problems.

BACKGROUND: College life is characterized by marked increases in alcohol consumption. Extraversion and neuroticism are associated with alcohol use problems in college and throughout adulthood, each with alcohol use patterns consistent with an externalizing and internalizing pathway respectively. Students higher in extraversion drink more frequently and consume more alcohol, while neuroticism is paradoxically not consistently associated with elevated alcohol use. OBJECTIVE: This study examined whether students higher in neuroticism may drink the day before stressors, namely tests and assignment deadlines. METHOD: Multilevel generalized linear models were performed using data from a longitudinal study of first-time, first-year undergraduates assessing alcohol use across four years of college, with daily diary bursts each semester. RESULTS: Students higher in extraversion had heavier alcohol use and greater alcohol use problems in their fourth year of college. Neuroticism was not associated with drinking behaviors or with drinking before a test or assignment, but was associated with greater fourth year alcohol problems. Students lower in extraversion who reduced heavy drinking the day before academic events had fewer alcohol use problems at the fourth year of college relative to students higher in extraversion. CONCLUSIONS: Students higher in extraversion appear to exhibit a continuity of established alcohol use patterns from adolescence, predisposing them to a more hazardous trajectory of college alcohol use. Characteristics of low extraversion may afford some protection from alcohol-positive college culture. High neuroticism appears associated with a hazardous trajectory of college alcohol use, but continued research into situational factors of alcohol use in high neuroticism is warranted.

Paths to postsecondary education enrollment among adolescents with and without childhood attention-deficit/hyperactivity disorder (ADHD): A longitudinal analysis of symptom and academic trajectories.

We examined developmental trajectories of attention-deficit/hyperactivity disorder (ADHD) symptoms, standardized achievement, and school performance for adolescents with and without ADHD who did and did not enroll in postsecondary education (PSE; N = 749; 79% boys; 63% White, 17% non-Hispanic Black, 10% Hispanic, and 10% other ethnicities). In a multisite study (recruitment based in New York, North Carolina, Pennsylvania, California, and Quebec), participants were originally enrolled between 1994 and 1998 at ages 7 to 9.9 and followed up through 2012 (Mage = 25 at final follow-up). Adolescents who eventually enrolled in PSE had less severe symptoms, but differences were modest and trajectories were similar over time. For all adolescents, standardized achievement trajectories declined up to two thirds of a standard deviation from ages 9 to 17. By the end of high school, the average GPA of adolescents with ADHD was three quarters of a point higher for those who eventually enrolled in PSE compared to those who did not. Overall, school performance mattered more than academic achievement for understanding eventual enrollment of adolescents with ADHD.

Potential use for chronic pain: Poly(Ethylene Glycol)-Poly(Lactic-Co-Glycolic Acid) nanoparticles enhance the effects of Cannabis-Based terpenes on calcium influx in TRPV1-Expressing cells.

The objective of these in vitro studies was to investigate the impact of the encapsulation of three cannabis-based terpenes, namely ß-myrcene (MC), ß-caryophyllene (CPh), and nerolidol (NL), on their potential efficacy in pain management. Terpene-encapsulated poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) were prepared by an emulsion-solvent evaporation method. The terpene-loaded NPs were examined in HEK293 cells that express the nociceptive transient receptor potential vanilloid-1 (TRPV1), an ion channel involved in pain perception. TRPV1 activation was assessed by monitoring calcium influx kinetics over 1 h in cells pre-treated with the fluorescent indicator Fluo-4. In addition, the fluorescence intensity changes induced by the NPs in living cells were also explored by a fluorescence microscope. Furthermore, the cytotoxicity of the terpene-loaded NPs was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenyl tetrazolium bromide (MTT) proliferation assay. The terpene-loaded NPs had a diameter in the range of 250-350 nm and a zeta potential of approximately -20 mV. The encapsulation efficiency was 18.5%, 51.3%, and 60.3% for MC, NL, and CPh NPs, respectively. The nano-formulations significantly increased the fluorescence intensity in comparison with free terpenes. Furthermore, combinations of terpene-loaded NPs produced significantly higher calcium responses when compared to combinations of free terpenes. Similar findings were shown by the fluorescence images. In conclusion, the terpene-PLGA NPs can be promising therapeutics for more effective pain management.

First-Year University Students' Mental Health Trajectories Were Disrupted at the Onset of COVID-19, but Disruptions Were Not Linked to Housing and Financial Vulnerabilities: A Registered Report.

This study modeled disruptions in first-year undergraduates' trajectories of mental health associated with the COVID-19 pandemic, testing whether disruptions were worse for students who moved residences, reported low family income, or were food insecure. Participants (n = 510) at a large Canadian university reported depression, anxiety, and stress in September, November, January, and March. In March 2020, in tandem with COVID-related campus closures, students also reported for each mental health measure whether their responses were influenced by personal experiences surrounding the pandemic. As hypothesized, students who reported feeling more COVID-related disruption reported poorer mental health in March. Contrary to hypotheses, mental health disruptions were not more pronounced for students who moved, had low income, or were food insecure. Survey administration at an early stage of COVID-19 combined with supports afforded by moving in with parents and near-universal government income assistance may have mitigated the incremental distress we hypothesized for vulnerable students.

People prefer to diversify across different types of prosocial behaviour.

People have multiple opportunities to act prosocial any given day but only limited resources to do so (e.g. time, effort and money they are willing to invest). We test whether people prefer to diversify their prosocial efforts across different types of help: casual help, direct help, indirect help and emotional support. In two daily diary studies (total N = 711), we examine whether previous prosocial behaviour affects subsequent prosocial behaviour for the same or other types of prosocial behaviour. We found that day-to-day prosocial behaviours reflected a diversified helping pattern. Participants were less likely to help the same way (i.e. the same type of prosocial behaviour) on subsequent days and more likely to help in different ways (i.e. a different type of prosocial behaviour). This tendency did not extend to casual help in Study 2, implying that the next day reduction in doing the same type of prosocial behaviour is limited to prosocial behaviours that are at least somewhat effortful or time consuming.

Mental Health of Students Reporting Food Insecurity during the Transition to University.

Purpose: The present study examined differences in mental health and well-being between students with and without suspected food insecurity during their transition to university.Methods: We drew on existing data from 4 samples of first-year undergraduates enrolled at 3 large universities in 3 provinces (Alberta n = 199, Québec n = 299, and Ontario n = 461 and n = 510). Students completed online surveys assessing a wide range of health-related behaviours and indicators, and students were classified as food secure or insecure based on their responses to screening questions.Results: Mental health (depression, anxiety, low satisfaction with life) was consistently poorer in students classified as food insecure across all samples. The magnitude of mental health deficit was comparable to socioeconomic disadvantage associated with food insecurity.Conclusions: Students experiencing food insecurity are disproportionately launching their university careers with poorer mental health, revealing a critical point of intervention for these socioeconomically higher-risk students.

Balancing Prosocial Effort Across Social Categories: Mental Accounting Heuristics in Helping Decisions.

Three studies examine whether individuals might use mental accounting heuristics in helping decisions, budgeting their prosocial effort in similar ways to how money is budgeted. In a hypothetical scenario study (N = 283), participants who imagined that they previously helped someone of a specific social category (e.g., "family," "colleagues") were less willing to help someone of that category again. Similarly, when reporting actual instances of day-to-day help in a diary study (N = 443), having helped more than usual in a social category yesterday was associated with less effort and less time spent on helping in the same category today. In contrast, helping more than usual in other social categories did not reduce helping today. Finally, a scenario study (N = 489) suggested that the mental accounting effect in helping decisions may, in part, be explained by perceived utility of help (helping others in the same social category is seen as less rewarding).

Health trajectories of children with severe obesity attending a weight management program.

PURPOSE: The objective of the present study is to examine physical and mental health trajectories of change in youth with severe obesity attending a tertiary care weight management program. It was predicted that younger children would show favourable changes in body mass index (BMI), markers of cardiovascular health, quality of life, and mental health. METHODS: This 2-year longitudinal study examined health trajectories of children referred to a weight management program at a Canadian paediatric tertiary care centre from November 2010 to December 2013. Participants were 209 of 217 consecutive referred paediatric patients (families) aged 3 to 17 years who met criteria for severe obesity and consented to participate. To maximize generalizability of results, there were no exclusion criteria. Primary outcomes were children's quality of life and BMI. Secondary outcomes included anxiety, depression, and non-high-density lipoprotein cholesterol levels. RESULTS: The findings suggest an improvement in mental health, quality of life, and cardiometabolic health of children and adolescents of all ages over the 2 years of programming. These positive findings were consistent across gender, age, and distance to the program. BMI trajectory changes varied across age cohorts such that younger children showed more favourable outcomes. The retention rate over the 2 years was high at 82.9%. CONCLUSIONS: This is the first study to show improvements in both physical and mental health outcomes beyond 1 year in a tertiary care setting with a high-risk population of children and youth with severe obesity. Findings highlight the need to examine both mental and physical health outcomes beyond 1 year.

Peer Information and Substance Use Decision Making in Street-Involved Youth.

In the context of adolescent substance use, peers are a primary source of both influence and information. Substance-related peer information sharing is a relatively understudied phenomenon, particularly in street-involved youth. We recruited 84 youth from a community drop-in center to complete a survey assessing substance use and peer influence on drug use. A subset of youth completed a semi-structured interview assessing factors related to peer information sharing around drug use. Results showed that peer influence was highly relevant to drug use patterns in street-involved youth. Trust in the person supplying information, personal and peer experience, and salience of information played important roles in youths' assessments of drug-related information exchanged with peers. Implications for improving community information dissemination strategies are discussed.

Cannabis Chemovar Nomenclature Misrepresents Chemical and Genetic Diversity; Survey of Variations in Chemical Profiles and Genetic Markers in Nevada Medical Cannabis Samples.

Introduction: Medical cannabis patients receive clinical benefits from the secondary metabolites of the plant, which contain a variety of cannabinoids and terpenoids in combinations that can be used to classify the chemovars. State-regulated medical cannabis programs rely on breeder-reported "strain" names both within diversion control systems and to describe the medical cannabis products that are sold to patients in medical cannabis dispensaries. In state-regulated medical cannabis programs, there is no conventional nomenclature system that correlates the breeder-reported names with their profiles of active ingredients, and these "strain" names are invalid as they refer to chemical differences properly referred to as to chemovars. Materials and Methods: To determine the actual levels of chemical diversity represented in 2662 samples of Cannabis flower collected between January 2016 and June of 2017 in Nevada, chemical profile data were measured from these samples by a state-qualified third-party testing laboratory. Principal component analysis (PCA) was used to define clusters in data sets representing both cannabinoids and terpenoids, cannabinoids only, or terpenoids only. Results: The PCA of the terpenoid only data set revealed three well-defined clusters. All three terpenoids only data clusters had high tetrahydrocannabinolic acid synthase, but the terpene profiles listed in reverse-order of abundance best defined these chemovars. The three chemovars in Nevada were labeled with 396 breeder-reported sample names, which overestimate the diversity and do not inform patients regarding chemical properties. Representative DNA samples were taken from each chemovar to determine whether the genetic diversity was greater than the chemical diversity. The limited genotyping experiment was based on DNA sequence polymorphisms. The genetic analysis revealed twelve distinct genetic clades, which still does not account for the entirety of the 396 reported sample names. The finite genotypes did not correlate with the chemotypes determined for the samples. This suggests that either the DNA-markers used were too narrowly restricted for factual separation or that environmental factors contributed more significantly to the chemical profiles of cannabis than genetics. Conclusion: The three chemovars and twelve genotypes reflect low medical diversity on the market in Nevada during its "medical use only" phase. Furthermore, the 396 breeder-reported sample names within this set imply a false sense of diversity of products in Nevada dispensaries.

Early substance use in the pathway from childhood attention-deficit/hyperactivity disorder (ADHD) to young adult substance use: Evidence of statistical mediation and substance specificity.

This study tested whether early and developmentally atypical substance use mediates risk for adult substance use among children with attention-deficit/hyperactivity disorder (ADHD), and whether that risk is substance-specific. Participants were children with ADHD previously enrolled in a randomized controlled trial (RCT), and a demographically similar non-ADHD group, assessed at 2 through 16 years after the original RCT baseline. Self-reports of heavy drinking, marijuana use, daily smoking, and other illicit drug use were collected at follow-ups to establish atypically early and frequent use. Models estimated statistically mediated effects of childhood ADHD on adult substance use via early substance involvement, with planned comparisons to evaluate substance specificity. Results supported the mediation hypothesis, showing that childhood ADHD was associated with more frequent adult substance use via early substance involvement for marijuana, cigarettes, illicit drugs, and to a lesser extent, alcohol. Mediation was not escalated by comorbid childhood conduct disorder or oppositional defiant disorder except for early use of nonmarijuana illicit drugs. Substance-specificity in the mediational pathway was largely absent except for cigarette use, where ADHD-related early smoking most strongly predicted adult daily smoking. Findings from this study provide new evidence that atypically early substance use associated with childhood ADHD signals important cross-drug vulnerability by early adulthood, but cigarette use at a young age is especially associated with increased risk for habitual (daily) smoking specifically. Efforts to prevent, delay, or reduce substance experimentation should occur early and focus on factors relevant to multiple drugs of abuse in this at-risk population. (PsycINFO Database Record (c) 2020 APA, all rights reserved).