Social Anxiety and Cannabis-Related Problems: The Serial Roles of Distress Tolerance and Cannabis Use Motives.

Background: Individuals with elevated social anxiety are vulnerable to experiencing negative consequences related to cannabis use. One transdiagnostic vulnerability factor that has received little attention in the social anxiety-cannabis problem relation is distress tolerance, which is associated with more cannabis use to manage negative affect broadly (i.e., coping motives) and cannabis-related problems. However, it is unknown whether distress tolerance is related to greater cannabis use to manage social anxiety specifically (i.e., social anxiety motives). Objectives: This study tested whether the relation between social anxiety and cannabis problems occurred via perceived distress tolerance among 309 (77.3% female) undergraduates who endorsed current (past three-month) cannabis use. Results: Social anxiety was negatively associated with distress tolerance and positively associated with cannabis problems, coping, and social anxiety motives. Social anxiety was indirectly (via distress tolerance) related to more cannabis problems and motives to cope with negative affect generally and to cope with social anxiety specifically. Social anxiety was indirectly related to more cannabis problems via the serial effects of distress tolerance and coping and social anxiety motives. Conclusions: Findings suggest that individuals with elevated social anxiety may be vulnerable to using cannabis to manage negative affect (generally and social anxiety specifically) due to low perceived ability to tolerate psychological distress, which may lead to more cannabis problems. Keywords: cannabis; marijuana; distress tolerance; social anxiety; motives; coping motives.

Indirect Associations Between PTSD Symptoms and Cannabis Problems in Young Adults: The Unique Roles of Cannabis Coping Motives and Medicinal Use Orientation.

Background: Cannabis use in young adulthood has been associated with exposure to traumatic events and posttraumatic stress disorder (PTSD). Coping motives for cannabis use represent one mechanism linking PTSD with cannabis problems, yet some individuals with PTSD consider their cannabis use to be medicinal in nature. While a medicinal orientation to cannabis overlaps conceptually with coping motives, it could be associated with unique cannabis outcomes. Objectives: This study examined trauma-related coping motives and medicinal cannabis orientation as mediators of the association between PTSD symptoms and cannabis outcomes in young adults. Method: Data came from an online survey of 212 university students (M age = 19.41; 70.3% Women; 43.4% White) who used cannabis in the past month and endorsed a traumatic life event. Path analyses examined associations of PTSD symptoms with past month cannabis frequency and problems through medicinal cannabis orientation (i.e., number of mental health symptoms that cannabis is used to manage) and trauma-related coping motives. Results: PTSD symptoms were associated with trauma-related coping motives but not with medicinal cannabis orientation. Both trauma-related coping motives and medicinal cannabis orientation were uniquely associated with greater cannabis use frequency, but only trauma-related coping motives were associated with greater cannabis problems. There were significant indirect relationships from PTSD symptoms to cannabis use frequency and problems through trauma-related coping motives but not through medicinal cannabis orientation. Conclusions: Results support unique contributions of trauma-related coping motives and medicinal cannabis orientation to cannabis outcomes and suggest that trauma-related coping motives are specifically implicated in the link between PTSD and cannabis problems.

Cannabis Use Characteristics Associated with Self-Reported Cognitive Function in a Nationally Representative U.S. sample.

BACKGROUND: With increases in cannabis use and potency, there is a need to improve our understanding of the impact of use on cognitive function. Previous research indicates long-term cannabis use may have a negative effect on executive function. Few studies have examined persistence of it in protracted abstinence, and there is limited evidence of predictors of worse cognitive function in current and former users. In this study, we aim to evaluate the associations between cannabis use status (current, former, and never use) and self-report cognition. Further, we investigate if cannabis use characteristics predict self-report cognitive function. METHODS: Cross-sectional cannabis use data from the National Epidemiological Survey on Alcohol and Related Conditions-III (NESARC-III), a national survey (N = 36,309) conducted in the USA between 2012 and 2013 were used alongside the Executive Function Index scales. The data were analyzed by using Ordinary Least Squares regression. RESULTS: Current (N = 3,681, Female = 37.7%) and former users (N = 7,448, Female = 45.4%) reported poorer cognition than never users (N = 24,956, Female = 56.6%). Self-reported cognition of former users was in-between that of current and never users. Several cannabis use characteristics were associated with self-reported cognition in current and former users. CONCLUSION: While prospective studies are required to confirm, findings suggest cannabis use is linked to worse cognition. There may be some limited recovery of cognition in former users and some cannabis use characteristics predict impairment. These findings add to our understanding of the cognitive impact of cannabis use. As worse cognitive function may impact relapse, findings have implications for personalization of cannabis use disorder treatment.

Does tobacco dependence worsen cannabis withdrawal in people with and without schizophrenia-spectrum disorders?

BACKGROUND AND OBJECTIVES: Rates of cannabis use disorder (CUD) are higher in people with schizophrenia than in the general population. Irrespective of psychiatric diagnosis, tobacco co-use is prevalent in those with CUD and leads to poor cannabis cessation outcomes. The cannabis withdrawal syndrome is well-established and increases cannabis relapse risk. We investigated whether cannabis withdrawal severity differed as a function of high versus no/low tobacco dependence and psychiatric diagnosis in individuals with CUD. METHOD: Men with CUD (N = 55) were parsed into four groups according to schizophrenia diagnosis and tobacco dependence severity using the Fagerstrom Test for Nicotine Dependence (FTND): men with schizophrenia with high tobacco dependence (SCT+, n = 13; FTND ≥ 5) and no/low tobacco dependence (SCT-, n = 22; FTND ≤ 4), and nonpsychiatric controls with high (CCT+, n = 7; FTND ≥ 5) and no/low (CCT-, n = 13; FTND ≤ 4) tobacco dependence. Participants completed the Marijuana Withdrawal Checklist following 12-h of cannabis abstinence. RESULTS: There was a significant main effect of tobacco dependence on cannabis withdrawal severity (p < .001). Individuals with high tobacco dependence had significantly greater cannabis withdrawal severity (M = 13.85 [6.8]) compared to individuals with no/low tobacco dependence (M = 6.49, [4.9]). Psychiatric diagnosis and the interaction effects were not significant. Lastly, cannabis withdrawal severity positively correlated with FTND (r = .41, p = .002). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Among individuals with CUD and high tobacco dependence, cannabis withdrawal severity was elevated twofold, irrespective of diagnosis, relative to individuals with CUD and no/low tobacco dependence. Findings from this study emphasize the importance of addressing tobacco co-use when treating CUD.

Scoping Review of Cannabis-Reduction Psychosocial Interventions and Reasons for Use among Young Adults with Psychosis.

Objective: No evidence-based intervention effectively reduces cannabis use in young adults with psychosis (YAP). To generate hypotheses about why, a scoping review was conducted to synthesize evidence about motivations for cannabis use and reduction/cessation for YAP and the psychosocial interventions trialed to identify possible gaps between motivations and interventive strategies. Methods: A systematic literature search was conducted in December, 2022. Reviews of titles and abstracts (N = 3,216) and full-texts (n = 136) resulted in 46 articles. Results: YAP use cannabis for pleasure, to reduce dysphoria, and for social and recreational reasons; motivations for cessation include insight about cannabis-psychosis interactions, incompatibility with goals and social roles, and support from social networks. Interventions with at least minimal evidence of efficacy include motivational interviewing, cognitive-behavioral strategies, and family skills training. Conclusions: Authors recommend additional research on mechanisms of change and motivational enhancement therapy, behavioral activation, and family-based skills interventions matched to YAP motivations for use/cessation.

Electrophysiological and behavioral correlates of cannabis use disorder.

Current research indicates deficits in cognitive function together with widespread changes in brain activity following long-term cannabis use. In particular, cannabis use has been associated with excessive spectral power of the alpha rhythm (8-12 Hz), which is also known to be modulated during attentional states. Recent neuroimaging studies have linked heavy cannabis use with structural and metabolic changes in the brain; however, the functional consequences of these changes are still not fully characterized. This study investigated the electrophysiological and behavioral correlates of cannabis dependence by comparing patients with a cannabis use disorder (CUD; N = 24) with cannabis nonuser controls (N = 24), using resting state electroencephalogram (EEG) source-imaging. In addition to evaluating mean differences between groups, we also explored whether particular EEG patterns were associated with individual cognitive-behavioral measures. First, we replicated historical findings of elevated levels of (relative) alpha rhythm in CUD patients compared with controls and located these abnormalities to mainly prefrontal cortical regions. Importantly, we observed a significant negative correlation between alpha spectral power in several cortical regions and individual attentional performance in the Go/NoGo task. Because such relationship was absent in the nonuser control group, our results suggest that reduced prefrontal cortical activation (indexed by increased relative alpha power) could be partly responsible for the reported cognitive impairments in CUD. Our findings support the use of electroencephalography as a noninvasive and cost-effective tool for biomarker discovery in substance abuse and have the potential of directly informing future intervention strategies.

Impact of cyclooxygenase-2 inhibition on cannabis withdrawal and circulating endocannabinoids in daily cannabis smokers.

Attenuating enzymatic degradation of endocannabinoids (eCBs) by fatty acid amide hydrolase (FAAH) reduces cannabis withdrawal symptoms in preclinical and clinical studies. In mice, blocking cyclooxygenase-2 (COX-2) activity increases central eCB levels by inhibiting fatty acid degradation. This placebo-controlled study examined the effects of the FDA-approved COX-2 selective inhibitor, celecoxib, on cannabis withdrawal, 'relapse', and circulating eCBs in a human laboratory model of cannabis use disorder. Daily, nontreatment-seeking cannabis smokers (12M, 3F) completed a crossover study comprising two 11-day study phases (separated by >14 days for medication clearance). In each phase, the effects of daily BID placebo (0 mg) or celecoxib (200 mg) on cannabis (5.3% THC) intoxication, withdrawal symptoms (4 days of inactive cannabis self-administration) and 'relapse' (3 days of active cannabis self-administration following abstinence) were assessed. Outcome measures included mood, cannabis self-administration, sleep, food intake, cognitive performance, tobacco cigarette use and circulating eCBs and related lipids. Under placebo maintenance, cannabis abstinence produced characteristic withdrawal symptoms (negative mood, anorexia and dreaming) relative to cannabis administration and was associated with increased OEA (a substrate of FAAH) and oleic acid (metabolite of OEA), with no change in eCB levels. Compared to placebo, celecoxib improved subjective (but not objective) measures of sleep and did not affect mood or plasma levels of eCBs or associated lipids and increased cannabis craving. The overall absence of effects on cannabis withdrawal symptoms, self-administration or circulating eCBs relative to placebo, combined with an increase in cannabis craving, suggests celecoxib does not show promise as a potential pharmacotherapy for CUD.

Cannabis use, abuse, and withdrawal: Cannabinergic mechanisms, clinical, and preclinical findings.

Cannabis sativa is the most widely used illicit drug in the world. Its main psychoactive component is delta-9-tetrahydrocannabinol (THC), one of over 100 phytocannabinoid compounds produced by the cannabis plant. THC is the primary compound that drives cannabis abuse potential and is also used and prescribed medically for therapeutic qualities. Despite its therapeutic potential, a significant subpopulation of frequent cannabis or THC users will develop a drug use syndrome termed cannabis use disorder. Individuals suffering from cannabis use disorder exhibit many of the hallmarks of classical addictions including cravings, tolerance, and withdrawal symptoms. Currently, there are no efficacious treatments for cannabis use disorder or withdrawal symptoms. This makes both clinical and preclinical research on the neurobiological mechanisms of these syndromes ever more pertinent. Indeed, basic research using animal models has provided valuable evidence of the neural molecular and cellular actions of cannabis that mediate its behavioral effects. One of the main components being central action on the cannabinoid type-one receptor and downstream intracellular signaling related to the endogenous cannabinoid system. Back-translational studies have provided insight linking preclinical basic and behavioral biology research to better understand symptoms observed at the clinical level. This narrative review aims to summarize major research elucidating the molecular, cellular, and behavioral manifestations of cannabis/THC use that play a role in cannabis use disorder and withdrawal.

Apathy and Anhedonia in Adult and Adolescent Cannabis Users and Controls Before and During the COVID-19 Pandemic Lockdown.

BACKGROUND: COVID-19 lockdown measures have caused severe disruptions to work and education and prevented people from engaging in many rewarding activities. Cannabis users may be especially vulnerable, having been previously shown to have higher levels of apathy and anhedonia than non-users. METHODS: In this survey study, we measured apathy and anhedonia, before and after lockdown measures were implemented, in n = 256 adult and n = 200 adolescent cannabis users and n = 170 adult and n = 172 adolescent controls. Scores on the Apathy Evaluation Scale (AES) and Snaith-Hamilton Pleasure Scale (SHAPS) were investigated with mixed-measures ANCOVA, with factors user group, age group, and time, controlling for depression, anxiety, and other drug use. RESULTS: Adolescent cannabis users had significantly higher SHAPS scores before lockdown, indicative of greater anhedonia, compared with adolescent controls (P = .03, η p2 = .013). Contrastingly, adult users had significantly lower scores on both the SHAPS (P < .001, η p2 = .030) and AES (P < .001, η p2 = .048) after lockdown compared with adult controls. Scores on both scales increased during lockdown across groups, and this increase was significantly smaller for cannabis users (AES: P = .001, η p2 = .014; SHAPS: P = .01, η p2 = .008). Exploratory analyses revealed that dependent cannabis users had significantly higher scores overall (AES: P < .001, η p2 = .037; SHAPS: P < .001, η p2 = .029) and a larger increase in scores (AES: P = .04, η p2 =.010; SHAPS: P = .04, η p2 = .010), compared with non-dependent users. CONCLUSIONS: Our results suggest that adolescents and adults have differential associations between cannabis use as well as apathy and anhedonia. Within users, dependence may be associated with higher levels of apathy and anhedonia regardless of age and a greater increase in levels during the COVID-19 lockdown.

Reduced Segregation Between Cognitive and Emotional Processes in Cannabis Dependence.

Addiction is characterized by an erosion of cognitive control toward drug taking that is accentuated by negative emotional states. Here we tested the hypothesis that enhanced interference on cognitive control reflects a loss of segregation between cognition and emotion in addiction. We analyzed Human Connectome Project data from 1206 young adults, including 89 with cannabis dependence (CD). Two composite factors, one for cognition and one for emotion, were derived using principal component (PC) analyses. Component scores for these PCs were significantly associated in the CD group, such that negative emotionality correlated with poor cognition. However, the corresponding component scores were uncorrelated in matched controls and nondependent recreational cannabis users (n = 87). In CD, but not controls or recreational users, functional magnetic resonance imaging activations to emotional stimuli (angry/fearful faces > shapes) correlated with activations to cognitive demand (working memory; 2-back > 0-back). Canonical correlation analyses linked individual differences in cognitive and emotional component scores with brain activations. In CD, there was substantial overlap between cognitive and emotional brain-behavior associations, but in controls, associations were more restricted to the cognitive domain. These findings support our hypothesis of impaired segregation between cognitive and emotional processes in CD that might contribute to poor cognitive control under conditions of increased emotional demand.

Characterizing psychosis-relevant phenomena and cognitive function in a unique population with isolated, chronic and very heavy cannabis exposure.

BACKGROUND: The literature on psychosis-relevant outcomes in cannabis users does not adequately address the confounding effects of other substance use/misuse and psychiatric disorders. METHODS: We studied a unique population for whom cannabis use is central and necessary to their way of life. They are forbidden from using other substances, including tobacco and alcohol. Their use of cannabis is heavy, chronic, and begins early. The cases were compared with matched controls who did not use cannabis, alcohol, or drugs. The controls were from the same location and shared similar beliefs and lifestyle, except for cannabis use. Attenuated psychosis-relevant phenomena were assessed with the Schizotypal Personality Questionnaire (SPQ) and cognitive functioning with a culture-neutral computerized cognitive battery. RESULTS: Fifteen cases and 12 matched controls were studied. The cases averaged >30 000 lifetime cannabis exposures. Relative to controls, the cases had significantly higher mean (s.d.) SPQ scores 24 (14.32) v. 13 (8.92), p = 0.031; and poorer cognitive performance, reflected by a lower mean (s.d.) composite cognitive score -0.23 (0.32) v. +0.28 (0.52), p = 0.03. Moderate to large effect sizes were noted for differences in tests of attention, psychomotor speed, working memory, cognitive flexibility, visuo-spatial processing, and verbal memory. A subsample of cases had higher SPQ scores and worse cognitive performance than their siblings not using cannabis. CONCLUSION: Heavy, chronic, and early cannabis use that is not confounded by other drug use is associated with psychosis-relevant phenomena and cognitive deficits. The findings are relevant to the evolving attitudes and laws about cannabis.

Impaired cognitive performance under psychosocial stress in cannabis-dependent men is associated with attenuated precuneus activity

Background: Deficient regulation of stress plays an important role in the escalation of substance use, addiction and relapse. Accumulating evidence suggests dysregulations in cognitive and reward-related processes and the underlying neural circuitry in cannabis dependence. However, despite the important regulatory role of the endocannabinoid system in the stress response, associations between chronic cannabis use and altered stress processing at the neural level have not been systematically examined. Methods: Against this background, the present functional MRI study examined psychosocial stress processing in cannabis-dependent men (n = 28) and matched controls (n = 23) using an established stress-induction paradigm (Montreal Imaging Stress Task) that combines computerized (adaptive) mental arithmetic challenges with social evaluative threat. Results: During psychosocial stress exposure, but not the no-stress condition, cannabis users demonstrated impaired performance relative to controls. In contrast, levels of experienced stress and cardiovascular stress responsivity did not differ from controls. Functional MRI data revealed that stress-induced performance deteriorations in cannabis users was accompanied by decreased precuneus activity and increased connectivity of this region with the superior frontal gyrus. Limitations: Only male cannabis-dependent users were examined; the generalizability in female users remains to be determined. Conclusion: Together, the present findings provide first evidence for exaggerated stress-induced cognitive performance deteriorations in cannabis users. The neural data suggest that deficient stress-related recruitment of the precuneus may be associated with the deterioration of performance at the behavioural level.

Risk for Substance Use Disorders in young adulthood: Associations with developmental experiences of homelessness, foster care, and adverse childhood experiences.

BACKGROUND: Multiple developmental risk factors for Substance Use Disorders (SUDs) during young adulthood have been identified. In this investigation, we examined the impact of homelessness, foster care, and adverse childhood experiences (ACEs) prior to 12th grade on the development of three common SUDs during young adulthood-Alcohol Use Disorder (AUD), Tobacco Use Disorder (TUD) and Cannabis Use Disorder (CUD). Our hypothesis was that while both homelessness and ACEs are significant risk factors for young adult SUDs, foster care involvement might convey protection. METHODS: Using nationally representative data from the National Longitudinal Study of Adolescent to Adult Health, measures of ACEs were derived from the CDC-Kaiser ACE study, and DSM-V SUD diagnoses were derived from items originally based on DSM-IV. SUD diagnoses were binned into "mild", "moderate", and "severe" groupings. Survey-based logistic models were used to estimate risks of SUDs while controlling for demographics. RESULTS: The results suggest that the experience of homelessness prior to 12th grade in addition to ACEs were significantly associated with the development in young adulthood of the most severe forms of AUD and TUD and all severity levels of CUD. Foster care was not associated with either risk or protection from SUDs. CONCLUSIONS: The experience of homelessness during development may be viewed as another detrimental ACE that is a risk factor for the most common SUDs in young adulthood. Given the magnitude of the current epidemic of homelessness in the U.S., these results should raise substantial concern.

A multimodal investigation of cerebellar integrity associated with high-risk cannabis use.

With legalization efforts across the United States, cannabis use is becoming increasingly mainstream. Various studies have documented the effects of acute and chronic cannabis use on brain structure and cognitive performance, including within the frontal executive control network, but little attention has been given to the effects on the cerebellum. Recent evidence increasingly points to the role of the cerebellum in various nonmotor networks, and the cerebellum's expression of cannabinoid receptors may pose particular vulnerabilities to the consequences of cannabis use. Using a combined approach of resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), the present study aims to assess how cannabis use relates to the cerebellum's intrinsic functional connectivity and underlying white matter structure and whether these properties are associated with craving or severity of cannabis use. Resting-state fMRI and DTI data, as well as self-reports of substance use history, were analyzed from a sample of 26 adults at risk for cannabis use disorder (CUD) and an age- and sex-matched comparison group of 25 cannabis-naïve adults (control). Results demonstrated that individuals at risk for a CUD showed key differences in cerebellar functional connectivity, with specific impacts on the dorsal attention and default mode networks. In addition, group differences in white matter were localized to the middle cerebellar peduncle (MCP), with a relationship between lower MCP diffusivity and higher levels of self-reported craving. These findings lend further support to the cerebellum's role in key cognitive networks and potential consequences for substance use disorders.

Stress-induced cortical dopamine response is altered in subjects at clinical high risk for psychosis using cannabis.

Stress and cannabis use are risk factors for the development of psychosis. We have previously shown that subjects at clinical high risk for psychosis (CHR) exhibit a higher striatal dopamine response to stress compared with healthy volunteers (HV), with chronic cannabis use blunting this response. However, it is unknown if this abnormal dopamine response extends to the prefrontal cortex (PFC). Here, we investigated dorsolateral PFC (dlPFC) and medial PFC (mPFC) dopamine release using [11 C]FLB457 positron emission tomography (PET) and a validated stress task. Thirty-three participants completed two PET scans (14 CHR without cannabis use, eight CHR regular cannabis users [CHR-CUs] and 11 HV) while performing a Sensory Motor Control Task (control scan) and the Montreal Imaging Stress Task (stress scan). Stress-induced dopamine release (ΔBPND ) was defined as percent change in D2/3 receptor binding potential between both scans using a novel correction for injected mass of [11 C]FLB457. ΔBPND was significantly different between groups in mPFC (F(2,30) = 5.40, .010), with CHR-CUs exhibiting lower ΔBPND compared with CHR (.008). Similarly, salivary cortisol response (ΔAUCI ) was significantly lower in CHR-CU compared with CHR (F(2,29) = 5.08, .013; post hoc .018) and positively associated with ΔBPND . Furthermore, CHR-CUs had higher attenuated psychotic symptoms than CHR following the stress task, which were negatively associated with ΔBPND . Length of cannabis use was negatively associated with ΔBPND in mPFC when controlling for current cannabis use. Given the global trend to legalize cannabis, this study is important as it highlights the effects of regular cannabis use on cortical dopamine function in high-risk youth.

Does Cannabis Dependence Add on to the Neurocognitive Impairment Among Patients With Opioid Dependence? A Cross-Sectional Comparative Study.

BACKGROUND AND OBJECTIVES: Chronic opioid exposure has been linked with neurocognitive impairments. Evidence of residual impairment with cannabis use is less consistent. We investigated whether patients with opioid and cannabis dependence perform poorly compared with those with opioid dependence alone. METHODS: We recruited three groups of participants aged 18 to 55 years: opioid and cannabis dependence (OCaD; n = 21), only opioid dependence (OD; n = 19), and a control group (HC; n = 20). Subjects with other substance use, human immunodeficiency virus, head injury, epilepsy, and severe mental illness were excluded. Cognitive tests, performed after at least 1 week of abstinence, consisted of the Wisconsin card sorting test (WCST), Iowa gambling task (IGT), trail making tests A and B (TMT-A and B), verbal and visual N-back test (NBT), and standard progressive matrices for intelligence quotient (IQ). The general linear model was used to compare the groups with age and years of education as covariates. RESULTS: IQ and severity of opioid dependence were comparable in the three groups. The mean duration of cannabis use was 76.2 (±39.4) months. Compared with the HC, both OD and OCaD had significant impairment on the IGT, WCST, TMTs, and NBT. No significant group difference was observed between the OD and OCaD groups. DISCUSSION AND CONCLUSIONS: Opioid dependence is associated with impairments in decision making, executive function, working memory, and attention. Co-morbid cannabis dependence had similar profiles of cognitive impairments. SCIENTIFIC SIGNIFICANCE: Co-morbid cannabis dependence might not add on to the existing cognitive dysfunction in opioid dependence. Further studies should be done with a larger sample. (Am J Addict 2020;29:120-128).

Measuring individual benefits of psychiatric treatment using longitudinal binary outcomes: Application to antipsychotic benefits in non-cannabis and cannabis users.

We present and evaluate a method for predicting individual treatment benefits based on random effects logistic regression models of binary outcomes that change over time. The method uses empirical Bayes predictors based on patients' characteristics and responses to treatment. It is applicable to both 1-dimentional and 2-dimentional personalized medicine models. Comparisons between predicted and true benefits for simulated new patients using correlations, relative biases and mean-squared errors were used to evaluate prediction performance. The predicted benefits had relatively small biases and relatively high correlations with the true benefits in the simulated new patients. The predictors also captured estimated overall population trends in the evolution of individual benefits. The proposed approach can be used to retrospectively evaluate patients' responses in a clinical trial, or to retrospectively or prospectively predict individual benefits of different treatments for new patients using patients' characteristics and previous responses. The method is used to examine changes in the disorganized dimension of antipsychotic-naïve patients from an antipsychotic randomized clinical trial. Retrospective prediction of individual benefits revealed that more cannabis users had slower and lower responses to antipsychotic treatment as compared to non-cannabis users, revealing cannabis use as a negative prognostic factor for psychotic disorders in the disorganized dimension.

Different Effects of Cannabis Abuse on Adolescent and Adult Brain.

Cannabis abuse is a common phenomenon among adolescents. The dominant psychoactive substance in Cannabis sativa is tetrahydrocannabinol (THC). However, in the past 40 years the content of the psychoactive ingredient THC in most of the preparations is not constant but has increased due to other breeding and culturing conditions. THC acts as the endocannabinoids at CB1 and CB2 receptors but pharmacologically can be described as a partial (not a pure) agonist. Recent evidence shows that activation of the CB1 receptor by THC can diminish the production of neuronal growth factor in neurons and affect other signalling cascades involved in synapsis formation. Since these factors play an important role in the brain development and in the neuronal conversion processes during puberty, it seems reasonable that THC can affect the adolescent brain in another manner than the adult brain. Accordingly, in adolescent cannabis users structural changes were observed with loss of grey matter in certain brain areas. Moreover, recent studies show different effects of THC on adolescent and adult brains and on behaviour. These studies indicate that early THC abuse can result in neuropsychological deficits. This review gives an overview over the present knowledge in this field.

Parent-adolescent relationship characteristics and adolescent cannabis use: A growth curve analysis.

Background: Adolescent cannabis misuse may be associated with serious academic, conduct, and health problems. Identifying factors associated with adolescent cannabis misuse over time may provide insight to address these factors in interventions. Parent-adolescent relationship characteristics (i.e., attachment, discipline) have been linked to adolescent cannabis misuse and may be important factors to study. Objectives: We investigated time-varying associations between parent-adolescent relationship domains and weekly adolescent-reported cannabis misuse. We hypothesized that during times when parents reported less positive aspects of their relationship with their adolescents, adolescents would report higher levels of cannabis misuse. Methods: Data were drawn from a community clinic treatment study for adolescents with substance use and co-occurring psychiatric disorders (n=110; average age=15.71; 57.3% male). Latent growth modeling with time-varying predictors (parent-adolescent relationship characteristics) was used to examine if the associations between adolescent cannabis misuse and relational frustration, discipline, and attachment varied across the study period (baseline, 3-, 6-, and 12-months). Results: Weekly cannabis misuse significantly increased over time, even after accounting for parental relationship characteristics. When parents rated higher levels of relational frustration relative to their average level of frustration, adolescents reported higher cannabis misuse at all study periods except 12-month follow-up. Conclusion: Results support the importance of considering how specific aspects of the parentadolescent relationship, in this case elevated parental frustration, are associated with adolescent cannabis misuse during treatment and after its completion. Findings suggest parental relationship frustration is a key factor to assess and address within individually tailored interventions for co-occurring cannabis misuse and psychiatric disorders.

Parental protective and risk factors regarding cannabis use in adolescence: A national sample from the Chilean school population.

Background: Research has increased our understanding of the parental factors associated with the initiation and development of cannabis use disorder in adolescents, but few studies about this have been performed in middle- or low-income countries.Objective: First, to examine whether perceived past parental drug use, parental monitoring, and attitude toward adolescent cannabis use are associated with general and problematic cannabis use in Chilean adolescents. Second, to explore whether perceived past parental drug use weakens the associations of protective factors with general and problematic adolescent cannabis use.Methods: Regression analyses were performed on cross-sectional data from a multistage probabilistic sample stratified by clusters (municipalities, school and grade) of 43,060 students (47% male, mean age 15.5 years) from grades 8 to 12, which was collected from the Chilean National School Survey on Drug Use (2013).Results: Perceived past parental drug use increased the likelihood of adolescent cannabis use in general, but not its problematic use. Parental monitoring of adolescents' whereabouts and parental opposition to adolescent cannabis use decreased the likelihood of adolescent cannabis use in general, as well as problematic use. Perceived past parental drug use only interacted with parental monitoring of school activities.Conclusions: In line with research from the United States, the Netherlands and Spain, parental monitoring of adolescents' whereabouts and a strong parental opposition to cannabis use appear to be protective factors, irrespective of past parental use. However, the effectiveness of monitoring adolescents' school activities seems to decrease when parents are perceived as having used drugs in the past.