Article

One Month of Cannabis Abstinence in Adolescents and Young Adults Is Associated With Improved Memory

Authors:
  • Massachusetts General Hospital/ Harvard Medical School
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Abstract

Objective: Associations between adolescent cannabis use and poor neurocognitive functioning have been reported from cross-sectional studies that cannot determine causality. Prospective designs can assess whether extended cannabis abstinence has a beneficial effect on cognition. Methods: Eighty-eight adolescents and young adults (aged 16-25 years) who used cannabis regularly were recruited from the community and a local high school between July 2015 and December 2016. Participants were randomly assigned to 4 weeks of cannabis abstinence, verified by decreasing 11-nor-9-carboxy-∆⁹-tetrahydrocannabinol urine concentration (MJ-Abst; n = 62), or a monitoring control condition with no abstinence requirement (MJ-Mon; n = 26). Attention and memory were assessed at baseline and weekly for 4 weeks with the Cambridge Neuropsychological Test Automated Battery. Results: Among MJ-Abst participants, 55 (88.7%) met a priori criteria for biochemically confirmed 30-day continuous abstinence. There was an effect of abstinence on verbal memory (P = .002) that was consistent across 4 weeks of abstinence, with no time-by-abstinence interaction, and was driven by improved verbal learning in the first week of abstinence. MJ-Abst participants had better memory overall and at weeks 1, 2, 3 than MJ-Mon participants, and only MJ-Abst participants improved in memory from baseline to week 1. There was no effect of abstinence on attention: both groups improved similarly, consistent with a practice effect. Conclusions: This study suggests that cannabis abstinence is associated with improvements in verbal learning that appear to occur largely in the first week following last use. Future studies are needed to determine whether the improvement in cognition with abstinence is associated with improvement in academic and other functional outcomes. Trial registration: ClinicalTrials.gov identifier: NCT03276221.

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... Roten and colleagues (2015) examined cannabis cessation in treatment seeking adolescents in a placebo controlled trial comparing cognitive performance of abstinent and non-abstinent adolescents at four and eight weeks. Findings across these three studies suggest that abstinence from cannabis results in verbal learning and memory recovery after one-to-two weeks of abstinence and psychomotor speed after a month of abstinence, while deficits in sustained and selective attention and inhibition endured for at least three to four weeks (Hanson et al., 2010;Roten, Baker, & Gray, 2015;Schuster et al., 2018). It is worth noting that the effects of continuously monitored cannabis cessation within young adult cannabis users compared to controls has not yet been investigated, as the only study that included young adults (Schuster et al., 2018) compared abstinent users to still using cannabis users without a healthy control group. ...
... Findings across these three studies suggest that abstinence from cannabis results in verbal learning and memory recovery after one-to-two weeks of abstinence and psychomotor speed after a month of abstinence, while deficits in sustained and selective attention and inhibition endured for at least three to four weeks (Hanson et al., 2010;Roten, Baker, & Gray, 2015;Schuster et al., 2018). It is worth noting that the effects of continuously monitored cannabis cessation within young adult cannabis users compared to controls has not yet been investigated, as the only study that included young adults (Schuster et al., 2018) compared abstinent users to still using cannabis users without a healthy control group. Taken together, findings suggest that some cognitive deficits from cannabis use may be from acute intoxication or resolve with abstinence. ...
... Taken together, findings suggest that some cognitive deficits from cannabis use may be from acute intoxication or resolve with abstinence. However, deficits in attention may represent a long-term chronic effect of cannabis use (Hanson et al., 2010;Pope & Yurgelun-Todd, 1996;Schuster et al., 2018). Notably, these studies often neglect to account for length of abstinence leading up to their enrollment in the study, despite the fact that this initial abstinence period may play an important role in the return of cognitive functioning (Ganzer et al., 2016). ...
Article
Objectives Previous research suggests recovery from cannabis-related deficits in verbal learning and memory functioning after periods of cannabis abstinence in adolescents. Here, we examine how cannabis cessation affects cognitive performance over 2 weeks of monitored abstinence compared to controls in adolescents and young adults. Methods Seventy-four participants (35 cannabis users) aged 16–26 ceased all cannabis, alcohol, and other illicit substance consumption for a 2-week period; abstinence was monitored via weekly urinalysis, breath, and sweat patch testing. Starting at baseline, participants completed weekly abbreviated neuropsychological batteries. Measures included tests of attention, inhibition, verbal working memory, and learning. Repeated measures assessed within and between subject effects for time and group status, while controlling for past year alcohol and nicotine use. Results Cannabis users showed increased performance compared to controls on sustained attention tasks after 2 weeks of cannabis use. Conclusions Deficits in attention, but not verbal learning and memory, recovered after 2 weeks of monitored abstinence. This differs from previous literature, suggesting that other cognitive domains may show signs of recovery after periods of cannabis cessation in adolescents and young adults.
... In a study by Hanson et al. (2011) [47], verbal learning deficits of cannabis users improved after three weeks of abstinence. Similarly, Schuster et al. (2018) [66] found improved verbal memory after one month of cannabis abstinence in a group of frequent adolescent cannabis users. At the time point of testing, the clinical group had been abstinent for at least 6 weeks-the verbal comprehension capacities in our inpatient group might therefore already have recovered at the time point of testing. ...
... In a study by Hanson et al. (2011) [47], verbal learning deficits of cannabis users improved after three weeks of abstinence. Similarly, Schuster et al. (2018) [66] found improved verbal memory after one month of cannabis abstinence in a group of frequent adolescent cannabis users. At the time point of testing, the clinical group had been abstinent for at least 6 weeks-the verbal comprehension capacities in our inpatient group might therefore already have recovered at the time point of testing. ...
Article
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The prevalence of substance abuse is high during adolescence, and several studies have linked the use of alcohol and cannabis in adolescence to different cognitive impairments. To investigate whether specific cognitive deficits can be observed in adolescents with substance use disorder (SUD), we compared the cognitive profiles of inpatient adolescents diagnosed with SUD to a control group matched for sex, age and educational status. The inpatient adolescents received diagnoses of cannabis use disorder, alcohol use disorder or both. We compared the WISC-V profiles of 22 inpatients (45.5% female, Mage: 14.5; SD: 0.8) and the WAIS-IV profiles of 27 inpatients (44.4% female, Mage: 17.1; SD: 0.9) to 49 matched control participants with no diagnosed SUD. At the time of testing, participants were hospitalized for treatment of their SUD and were abstinent for a period of at least 6 weeks. To gain greater power, we jointly analyzed the Verbal Comprehension Index, Working Memory Index, Processing Speed Index and Full Scale IQ as assessed by WISC-V and WAIS-IV. The clinical group performed significantly worse than the control group on all the above indices. When only the group of inpatients was observed, in a model with the factors sex, educational status, presence of a comorbid diagnosis of depression and the number of comorbid diagnoses, only the factor educational status was significantly associated with the Full Scale IQ, whereas the factors sex and a comorbid diagnosis of depression in this group were associated with the Processing Speed Index. The results show that adolescents diagnosed with SUD (cannabis and/or alcohol) display broad cognitive impairments after 6 weeks of abstinence. Future research is required to further explore the role of comorbid diagnoses.
... This indicates that each condition was independently associated with worse memory performance, but the combination of both was not notably larger or smaller than expected by summing the simple main effects. Though we cannot determine whether MJ was exacerbating memory weaknesses in the MDD participants, or whether poor memory preceded MJ use, it is possible that memory weaknesses could improve if MDD patients abstained from using MJ, as other studies in non-depressed samples show that MJ abstinence is associated with improved memory performance (Hanson et al., 2010;Medina et al., 2007;Schuster, Gilman, Schoenfeld, Evenden, Hareli, Ulysse, Nip, Hanly, Zhang, & Evins, 2018). Future studies should examine this effect in MDD patients with co-morbid MJ use. ...
... Second, because this study was cross-sectional, we cannot determine whether MJ use worsened verbal memory performance in the MJ-using groups, or whether memory decrements preceded MJ use. Future investigations of the MJ-MDD interaction in young adults should include longitudinal designs or incentivize abstinence to investigate change in memory performance (Schuster et al., 2018). Third, the confounding effects of heavier alcohol use (confounded with MJ use) and anxiety disorders (confounded with MDD) may limit our interpretation of results. ...
Article
Marijuana (MJ) use and major depressive disorder (MDD) have both been associated with deficits in verbal learning and memory as well as structural brain abnormalities. It is not known if MJ use by those with MDD confers additional impairment. The goal of this study was to examine unique and combined effects of MDD and MJ use on verbal memory and brain structure. Young adults (n=141) aged 18–25 years with MJ use and no lifetime MDD (MJ, n=46), MDD and no MJ use (MDD, n=23), MJ use and lifetime MDD (MDD+MJ, n=24), and healthy controls without MDD or MJ use (CON, n=48) were enrolled. Participants completed the California Verbal Learning Test, Second Edition (CVLT-II), a measure of verbal learning and memory. A sub-sample of 82 participants also underwent a structural magnetic resonance imaging (MRI) scan. Group differences in CVLT-II performance, cortical thickness, and hippocampal volume were assessed. We found an additive effect of MDD and MJ on memory recall. Only MDD, but not MJ, was associated with poorer initial learning, fewer words recalled, more intrusion errors, and lower percent retention. There was also an additive effect of MDD and MJ use on reduced cortical thickness in the middle temporal gyrus. Findings indicate that MJ use and MDD have additive adverse associations with verbal recall and cortical thickness in the middle temporal gyrus, suggesting that MJ use among those with MDD may be contraindicated. Prospective studies are warranted to determine whether this association may be causal.
... This might be due to the fact that we partially included patients that were abstinent from cannabis during the previous weeks which might have ameliorated the effects of cannabis use on cognitive task performance at the time of testing and were not detectable in our small sample. A previous study indicated that 4 weeks of abstinence might already ameliorate cannabis associated impairments in cognitive task performance [42]. The two groups only differed in cannabis, tobacco and alcohol use and the fact that we only saw an association with CCU-extent and no group differences seems to underline the impact on CCU-extent and not presence of regular cannabis in general on cognitive performance. ...
Article
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The association between extent of chronic cannabis use (CCU-extent) and cognitive impairment among adolescents has been the subject of controversial debate. Linking DNA methylation to CCU-extent could help to understand cannabis associated changes in cognitive performance. We analyzed cognitive task performances, CpG methylation in peripheral whole-blood samples and self-reported past-year CCU-extent of n = 18 adolescents ( n = 9 psychiatric outpatients with chronic cannabis use (CCU), n = 9 without) who were matched for age, gender and psychiatric disorders. Patients with CCU were at least 24 h abstinent when cognitive tasks were performed. A Principal Component Analysis (PCA) was carried out to identify group differences in whole genome DNA methylation. Mediation analyses were performed between CCU-extent associated CpG sites and CCU-extent associated variables of cognitive tasks. PCA results indicated large differences in whole genome DNA methylation levels between the groups that did not reach statistical significance. Six CpG sites revealed reduced methylation associated with CCU-extent. Furthermore, CCU-extent was associated with lower scores in verbal learning. All six CpG sites mediated the effects between CCU-extent and verbal learning free recall. Our results indicate that CCU is associated with certain patterns in the methylome. Furthermore, CCU-extent associated impairments in memory function are mediated via differential methylation of the six CCU-associated CpG sits. Six identified CpG are located in genes previously described in the context of neurodegeneration, hippocampus-dependent learning and neurogenesis. However, these results have to be carefully interpreted due to a small sample size. Replication studies are warranted.
... Apart from acute effects (Ranganathan et al., 2017;Schuster et al., 2018), the causal link between cannabis use and educational attainment (Defoe, Khurana, Betancourt, Hurt, & Romer, 2018;Lynskey & Hall, 2000), or cognition is unclear (Morin et al., 2019;Scott, Slomiak, et al., 2018). A study on a cannabinoid receptor 1 (CB1) antagonist suggests that altered CB1-signaling is involved in acute THC-induced verbal memory impairment (Englund et al., 2016). ...
Article
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Although previous studies have highlighted associations of cannabis use with cognition and brain morphometry, critical questions remain with regard to the association between cannabis use and brain structural and functional connectivity. In a cross‐sectional community sample of 205 African Americans (age 18–70) we tested for associations of cannabis use disorder (CUD, n = 57) with multi‐domain cognitive measures and structural, diffusion, and resting state brain‐imaging phenotypes. Post hoc model evidence was computed with Bayes factors (BF) and posterior probabilities of association (PPA) to account for multiple testing. General cognitive functioning, verbal intelligence, verbal memory, working memory, and motor speed were lower in the CUD group compared with non‐users (p < .011; 1.9 < BF < 3,217). CUD was associated with altered functional connectivity in a network comprising the motor‐hand region in the superior parietal gyri and the anterior insula (p < .04). These differences were not explained by alcohol, other drug use, or education. No associations with CUD were observed in cortical thickness, cortical surface area, subcortical or cerebellar volumes (0.12 < BF < 1.5), or graph‐theoretical metrics of resting state connectivity (PPA < 0.01). In a large sample collected irrespective of cannabis used to minimize recruitment bias, we confirm the literature on poorer cognitive functioning in CUD, and an absence of volumetric brain differences between CUD and non‐CUD. We did not find evidence for or against a disruption of structural connectivity, whereas we did find localized resting state functional dysconnectivity in CUD. There was sufficient proof, however, that organization of functional connectivity as determined via graph metrics does not differ between CUD and non‐user group.
... The degree of recovery of function with abstinence is a topic of great interest. In a study of adolescents and emergent adults (16-25 years of age), whose abstinence was monitored over 1 month following regular use, improvements were seen in verbal memory, primarily due to improved verbal learning in the first week of abstinence (162). However, cross-sectional studies indicate that effects on attention, verbal and working memory, and psychomotor speed, but not on other cognitive domains, persist in adolescents abstinent for 28 (163) and 35 days (164). ...
Article
Background: Cannabis is the most widely used illicit substance worldwide, and legalization for recreational and medical purposes has substantially increased its availability and use in the United States.Objectives: Decades of research have suggested that recreational cannabis use confers risk for cognitive impairment across various domains, and structural and functional differences in the brain have been linked to early and heavy cannabis use.Methods: With substantial evidence for the role of the endocannabinoid system in neural development and understanding that brain development continues into early adulthood, the rising use of cannabis in adolescents and young adults raises major concerns. Yet some formulations of cannabinoid compounds are FDA-approved for medical uses, including applications in children.Results: Potential effects on the trajectory of brain morphology and cognition, therefore, should be considered. The goal of this review is to update and consolidate relevant findings in order to inform attitudes and public policy regarding the recreational and medical use of cannabis and cannabinoid compounds.Conclusions: The findings point to considerations for age limits and guidelines for use.
... Urine cannabinoid concentrations were determined from non-treatment seeking adolescents and young adults between the ages of 15 and 25 years in an outpatient setting, drawn from a larger Boston-based study on cognition during cannabis abstinence (Schuster et al., 2018;Schuster et al., 2016). Participants were recruited via peer referral, community advertisements, and via advertising at a public high school in a northwest Boston suburb. ...
Article
Background Despite adolescents and young adults being the most frequent users of cannabis, all information on cannabis drug testing interpretation is based on data from adults. Aims This study aimed to define the time course of urinary 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH) excretion among 70 adolescent and young adult cannabis users during 1 month of biochemically-verified cannabis abstinence. Methods Urine specimens were collected at non-abstinent baseline and after 2, 3, 8, 15, 21 and 28 days of abstinence. Specimens were tested for THCCOOH with a ‘rapid’ immunoassay drug test and a confirmatory assay using liquid chromatography-tandem mass spectrometry, with a 5 ng/mL limit of quantitation. Elimination rate was tested using a population pharmacokinetics model. Results/outcomes Participants had an average of 26 days of abstinence (SD = 6). Initial creatinine-adjusted THCCOOH concentration (CN-THCCOOH) was 148 ng/mg (SD = 157). Half-life was 2 days (SD = 5), with a 10-day window of detection (estimated range: 4–80 days). At the final timepoint and among those with > 25 days of abstinence ( n = 62), 40% ( n = 25) had THCCOOH concentrations > 5 ng/mL (i.e. detectable on confirmatory assay) and 19% ( n = 12) were ‘positive’ per federal drug testing guidelines (i.e. values greater than 50 ng/mL on the screening immunoassay and 15 ng/mL on the confirmatory assay). More frequent past month cannabis use was associated with higher baseline CN-THCCOOH concentrations, but not with rate of elimination. Nested five-fold cross-validation suggested high model reliability and predictive validity. Conclusions/interpretation Findings underscore that, as with adults, detectable cannabinoid metabolites do not necessarily indicate recent use in adolescents and young adults. Algorithms that account for THCCOOH levels, assessed longitudinally and time between specimen collections are best equipped to confirm abstinence. Clinical Trial Registration NCT03276221; https://clinicaltrials.gov/ct2/show/NCT03276221?term=Randi+Schuster&rank=1
... 100 Schuster and colleagues 101 showed that 90% of youth in such a program achieved biochemically validated sobriety from cannabis for 30 days. A later study supported the effectiveness of contingency management for achieving abstinence and showed improvements in memory with abstinence 102 ; however, 94% of individuals who stopped using cannabis resumed regular cannabis use within 2 weeks. 101 Abstaining from using cannabis for a prolonged time can be difficult for youth who have become accustomed to using and may use cannabis for several reasons, including facilitation of social activities, pleasure, stress reduction, sleep, or as a way of feeling more independent. ...
Article
The rapidly changing landscape of cannabis in terms of availability, potency, and routes of administration, as well as the decrease in risk perception and changing norms, have contributed to an increase in the popularity of cannabis. Cannabis use is associated with a poorer recovery from a psychotic disorder, increasing the risk of relapse, rehospitalization, and lower social functioning. Data are mixed regarding cannabis use as a component cause of psychosis in people at risk for psychotic disorder. Care providers, parents, and schools must educate youth and adolescents about the risks of cannabis use.
... However, these effects may not be durable over extended periods of time, particularly after the individual has been abstinent from use. Some research has indicated that cognitive deficits in memory function improve within one week of abstinence [23]. A recent meta-analysis about the effects of cannabis use on adolescents and young adults identified two major issues across the research literature: 1) many studies have found statistically significant results, but the magnitude of the effects may not lead to clinically relevant deficits, and 2) these effects may not persist after cessation of use [24]. ...
Article
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Background Using a nationally representative longitudinal cohort, we examine how cognitive aptitude in early adolescence is associated with heterogeneous pathways of marijuana use from age sixteen through young adulthood. We also examine whether this relationship can be explained by the role of cognitive aptitude in the social organization of peer group deviance. Methods Using the National Longitudinal Survey of Youth 1997, we identified 5 latent trajectories of frequency of marijuana use between ages 16 and 26: abstainers, dabblers, early heavy quitters, consistent users, and persistent heavy users. Multinomial regression assessed the relationship of cognitive aptitude in early adolescence with these latent trajectories, including the role of peer group substance use in this relationship. Results A one decile increase in cognitive aptitude in early adolescence is associated with greater relative risk of the dabbler trajectory (RR = 1.048; p < .001) and consistent user trajectory (RR = 1.126; p < .001), but lower relative risk of the early heavy quitter trajectory (RR = 0.917; p < .05) in comparison with the abstainer trajectory. There was no effect for the persistent heavy user trajectory. The inclusion of peer group substance use–either via illegal drugs or smoking–had no effect on these relationships. Conclusions Adolescents who rate higher in cognitive aptitude during early adolescence may be more likely to enter into consistent but not extreme trajectories of marijuana use as they age into young adulthood. Cognition may not influence patterns of marijuana use over time via the organization of peer groups.
... In the short term, research led by neuropsychologist Randi Schuster at Massachusetts General Hospital in Boston has found that certain cannabis-related cognitive losses may be reversible. Among regular users aged 16 to 25, those who cut out cannabis for four weeks saw improvements in verbal memoryespecially during the first week (20). "We don't know how long it would take for them to reach-or if they would reach-the level of a nonuser," says Gilman, one of the study's authors. ...
... There is evidence that heavy cannabis use during adolescence may lead to developmental disadvantages in the domains of attention and memory (Jacobus & Tapert, 2014;Volkow et al., 2016). There are studies that report that these domains recover after periods of abstinence (Schuster et al., 2018;Scott et al., 2018), but Meier et al. (2012) found neurocognitive problems persist even after cannabis use is stopped. There is also evidence of an association between cannabis use and schizophrenia, with a stronger correlation in individuals who began cannabis use during adolescence (Volkow et al., 2016). ...
... Due to the requirement for cannabis users to remain abstinent for a minimum of 14 days leading up to MRI scan and participants last reported cannabis use on average occurred 31 days prior to scanning, these findings suggest that abnormal activation to inhibitory control task is observable beyond the acute withdrawal stage. Indeed, this length of abstinence is linked with resolution of withdrawal symptoms, and past work has shown recovery of cognitive deficits in cannabis users following sustained abstinence (Hanson et al. 2010;Medina et al. 2007;Schuster et al. 2018). However, no studies to date have examined the impact of monitored, sustained abstinence that is longer than 30 days on BOLD response. ...
Article
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RationalePrevious studies have suggested that chronic cannabis use has been associated with increased blood oxygen level–dependent (BOLD) response during a response inhibition task; however, these studies primarily included males.Objectives We investigated whether gender moderated the effects of cannabis use on BOLD response and behavioral performance during a Go-NoGo task in adolescents and young adults following 2 weeks of monitored abstinence.Methods Participants included 77 16–26-year olds (MJ = 36, controls = 41). An emotion-based Go-NoGo task required participants to inhibit their response during a calm face. A whole-brain analysis looked at differences between cannabis group, gender, and their interaction.ResultsSignificant greater BOLD responses were observed in cannabis users compared with that in controls in the left frontal cortex, left cingulate cortex, and the left thalamus during correct response inhibitions; gender did not moderate these effects.Conclusion Supporting previous research, cannabis users showed greater BOLD responses in core areas associated with response inhibition during a Go-NoGo task, even after a minimum of 2 weeks of abstinence.
... In another good-quality experimental study, Schuster et al. (2018) recruited 88 adolescent participants aged 16 to 25 years. Controlling for variables such as age, gender, and drug use (see Table 2), the sample was divided into a group who continued using cannabis, and a group who had to sustain cannabis abstinence for 4 weeks. ...
Article
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Using cannabis (e.g., smoking marijuana) is becoming popular, partly due to a legalization trend across different countries. This tendency has resulted in cannabis consumption being accepted by society as if it were harmless. However, evidence shows that the use of this drug has detrimental effects on cognitive, academic, and professional performance, which tend to be larger in younger users (e.g., high school students). In this review article, we focus on the decline of visuospatial processing associated with cannabis consumption in nondependent or nonclinical high school students. We start by providing evidence of the pivotal role of visuospatial processing for learning. Next, we review experimental and correlational evidence of declines in visuospatial processing related to cannabis use. Three types of correlational studies are considered: (a) comparisons of declines between visuospatial processing and other cognitive tasks, (b) studies comparing declines between high school students and adult participants, and (c) stringent correlational studies (e.g., large samples, longitudinal data, twin studies). We also include evidence in abstinent cannabis conditions. We conclude that using cannabis may moderately impair visuospatial processing and learning in nondependent high school students, although the effects could disappear under abstinence and tend to be lower than on other cognitive functions. Instructional implications for educators and future research directions are discussed.
... Although cannabis use waslinked with poorer verbal memory, this did not survive correction for multiple comparisons. Agrowing body of evidence suggests that, following 1w eek to amonth of abstinence, cognitive functioning in substance users (and particularlyincannabis users) is no different than in healthy controls (Hanson et al., 2010;Roten et al., 2015;Schuster et al., 2018;Wallace et al., 2020). Although the domains of recovery have differed (e.g., some showr ecovery in verbal memory, whereas others showr ecovery in attention) and there are differences in the age group sampled,r esults are hopeful for teens and young adults whos eek to abstain or reduce substance use for extended periods. ...
Article
Objective: Despite preliminary evidence of unique acute cognitive and psychopharmacological changes attributable to combined alcohol and cannabis use, few studies have investigated more chronic effects of same-day co-use, particularly during neurodevelopmentally sensitive periods. Therefore, relationships between past-month binge alcohol and cannabis co-use and cognitive functioning were examined in adolescents and young adults. Method: Data from the Imaging Data in Emerging Adults with Addiction (IDEAA) Consortium were used to assess cognitive functioning in emerging adults with a large range of substance use (n = 232; 15-26 years old) who were abstinent for at least 3 weeks. Multiple regressions assessed cognitive functioning by past-month binge episodes, cannabis use episodes, and same-day co-use, controlling for covariates (e.g., study site, sex, age). Results: After correcting for multiple comparisons, more past-month co-use episodes were related to decreased Ruff 2&7 selective attention accuracy (p = .036). Sex significantly covaried with California Verbal Learning Test-Second Edition initial learning. Conclusions: Although few significant relationships were found and effect sizes are modest, the persistence of an effect on attention despite a period of sustained abstinence highlights the need to carefully investigate patterns of substance use and potential independent and interactive effects on the developing brain.
... Future studies should carefully consider whether the mild increase in the frequency and quantity of alcohol consumption in youth outweighs the known health, psychiatric, and cognitive benefits of full cannabis abstinence. (Schuster et al., 2018;Wallace et al., 2020) The substantial variability between participants in drinking behavior during the cannabis abstinence period should also be noted. While, on average, the CB-Abst group showed an increase in the frequency and amount of drinks consumed during the 30-day abstinence period, 17% had no change and 23% showed a decrease. ...
Article
Objective Cannabis and alcohol use are correlated behaviors among youth. It is not known whether discontinuation of cannabis use is associated with changes in alcohol use. This study assessed alcohol use in youth before, during, and after four weeks of paid cannabis abstinence. Methods Healthy, non-treatment seeking, cannabis users (n = 160), aged 14–25 years, 84% of whom used alcohol in the last month, were enrolled for a 4-week study with a 2–4 week follow-up. Participants were randomly assigned to four weeks of either biochemically-verified cannabis abstinence achieved through a contingency management framework (CB-Abst) or monitoring with no abstinence requirement (CB-Mon). Participants were assessed at baseline and approximately 4, 6, 10, 17, 24, and 31 days after enrollment. A follow-up visit with no cannabis abstinence requirement for CB-Abst was conducted after 2–4 weeks. Results Sixty percent of individuals assigned to the CB-Abst condition increased in frequency and quantity of alcohol consumption during the 4-week period of incentivized cannabis abstinence. As a whole, CB-Abst increased by a mean of 0.6 drinking days and 0.2 drinks per day in the initial week of abstinence (p's < 0.006). There was no evidence for further increases in drinking frequency or quantity during the 30-day abstinence period (p's > 0.53). There was no change in drinking frequency or quantity during the 4-week monitoring or follow-up periods among CB-Mon. Conclusions On average, four weeks of incentivized (i.e., paid) cannabis abstinence among non-treatment seeking youth was associated with increased frequency and amount of alcohol use in week 1 that was sustained over 4 weeks and resolved with resumption of cannabis use. However, there was notable variability in individual-level response, with 60% increasing in alcohol use and 23% actually decreasing in alcohol use during cannabis abstinence. Findings suggest that increased alcohol use during cannabis abstinence among youth merits further study to determine whether this behavior occurs among treatment seeking youth and its clinical significance.
... A recent review of systematic and metaanalytic reviews concluded that although heavy cannabis use was consistently associated with impairments in learning and memory, these impacts disappear relatively quickly with abstinence, and potential moderators include heaviness/ chronicity of use and THC content of product consumed (Kroon et al. 2020). A recent study of adolescents and young adults found that verbal learning improvements due to cannabis abstinence largely occur within the first week after stopping use, indicating a rapid recovery of cognitive functions (Schuster et al. 2018). Given the ample evidence for acutely impairing effects of cannabis (Broyd et al. 2016), and for the link between these effects and biologically-detectable THC Petker et al. 2019), it is entirely possible that daily cannabis users in the present study still had sufficient heterogeneity in cannabis use patterns to obscure cannabis-related cognitive deficits. ...
Article
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Rationale There is increasing interest in and evidence for the negative impacts of cannabis use in cognitive performance and symptoms of attention-deficit/hyperactivity disorder (ADHD), with age of first cannabis use as a potential amplifier of these associations. However, the existing literature is inconsistent, which may be due to methodological limitations, including small sample sizes. Objective To examine current cannabis use and age of first cannabis use in relation to neurocognitive task performance and ADHD symptoms in a large sample of binge-drinking young adults. Methods Participants were young adults (N=730, M age=21.44, 52.6% female) assessed for current cannabis use, neurocognitive task performance, and ADHD symptoms. Three-group ANCOVAs compared individuals reporting frequent (daily/multiple times daily), occasional (weekly/monthly), or no cannabis use. Results Covarying alcohol use, tobacco use, age, sex, income, and education, daily cannabis users exhibited significantly more impulsive delay discounting and hyperactive-impulsive ADHD symptoms compared to both other groups. However, cannabis use was not associated with inattentive ADHD symptoms, verbal intelligence, working memory, probability discounting, short-term verbal memory, or behavioral inhibition. Age of initiation of cannabis use exhibited neither main effects nor interactions in relation to any domains of cognitive performance or ADHD symptomatology. Conclusions The current findings provide support for a link between cannabis use in relation to immediate reward preference and symptoms of hyperactive-impulsive ADHD in young adults, but only among frequent users. No other neurocognitive domains exhibited associations with cannabis and age of first use was neither independently nor interactively associated with cognitive outcomes.
... The model by Schwilke et al. is acknowledged as a major advancement in the understanding of urinary excretion of cannabinoids in chronic users, and the publication has been cited in >40 peer-reviewed articles. Thus, it has been applied in research and clinical trials where use of the mathematical model has been the best tool to verify abstinence in study participants (10,11). However, the model has not yet been implemented as warranted in routine UDT practice at the institutional level, where clinicians in charge of patient care and management act on the results. ...
... This is further supported by recent work showing a differential response of the pre-attentive, automatic mismatch negativity (MMN) waveform between short-term and long-term tobacco-naïve cannabis users, where deficits were only observed in long-term users (Impey et al. 2015). This is consistent with previous findings that cannabisinduced changes in cognition are associated with higher levels of circulating THC (Hunault et al. 2009), but reverse with abstinence (Rabin et al. 2017;Melissa et al. 2018). Furthermore, users in our sample are moderate cannabis users when compared to other studies, which may be why no significant gating differences were observed (Patrick and Struve 2000;Edwards et al. 2009;Broyd et al. 2013). ...
Article
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Objectives: Long-term cannabis use has been associated with the appearance of psychotic symptoms and schizophrenia-like cognitive impairments; however these studies may be confounded by concomitant use of tobacco by cannabis users. We aimed to determine if previously observed cannabis-associated deficits in sensory gating would be seen in cannabis users with no history of tobacco use, as evidenced by changes in the P50, N100, and P200 event-related potentials. A secondary objective of this study was to examine the effects of acute nicotine administration on cannabis users with no tobacco use history. Methods: Three components (P50, N100, P200) of the mid-latency auditory-evoked response (MLAER) were elicited by a paired-stimulus paradigm in 43 healthy, non-tobacco smoking male volunteers between the ages of 18-30. Cannabis users (CU, n = 20) were administered nicotine (6 mg) and placebo gum within a randomized, double-blind design. Non-cannabis users (NU, n = 23) did not receive nicotine. Results: Between-group sensory gating effects were only observed for the N100, with CUs exhibiting a smaller N100 to S1 of the paired stimulus paradigm, in addition to reduced dN100 (indicating poorer gating). Results revealed no significant sensory gating differences with acute administration of nicotine compared to placebo cannabis conditions. Conclusions: These findings suggest a relationship between gating impairment and cannabis use; however, acute nicotine administration nicotine does not appear to impact sensory gating function.
... Controversial side effects have been observed after marijuana and synthetic cannabinoids exposition [9,10]. Learning and memory impairment has been reported in several studies, especially in young individuals [11,12]. Since brain development is completed only around the age of 25, cannabis use in adolescence may be associated with increased adverse effects on brain formation and function, particularly in areas sensitive to the pharmacological effects of cannabis. ...
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Alzheimer’s disease (AD) is a detrimental brain disorder characterized by a gradual cognitive decline and neuronal deterioration. To date, the treatments available are effective only in the early stage of the disease. The AD etiology has not been completely revealed, and investigating new pathological mechanisms is essential for developing effective and safe drugs. The recreational and pharmacological properties of marijuana are known for centuries, but only recently the scientific community started to investigate the potential use of cannabinoids in AD therapy—sometimes with contradictory outcomes. Since the endocannabinoid system (ECS) is highly expressed in the hippocampus and cortex, cannabis use/abuse has often been associated with memory and learning dysfunction in vulnerable individuals. However, the latest findings in AD rodent models have shown promising effects of cannabinoids in reducing amyloid plaque deposition and stimulating hippocampal neurogenesis. Beneficial effects on several dementia-related symptoms have also been reported in clinical trials after cannabinoid treatments. Accordingly, future studies should address identifying the correct therapeutic dosage and timing of treatment from the perspective of using cannabinoids in AD therapy. The present paper aims to summarize the potential and limitations of cannabinoids as therapeutics for AD, focusing on recent pre-clinical and clinical evidence.
... All study procedures were approved by the Partners Healthcare Human Subjects Committee. A detailed description of study procedures has been documented elsewhere (40)(41)(42)(43). Briefly, at the baseline visit participants were randomized to 4 weeks of cannabis abstinence using an escalating financial incentive structure (contingency management; CB-Abst) or 4 weeks of monitoring with no abstinence requirement (CB-Mon). ...
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Background: Cannabis use is prevalent among adolescents, and many report using in attempts to alleviate negative mood and anxiety. Abstinence from substances such as alcohol and tobacco has been reported to improve symptoms of anxiety and depression. Few studies have examined the effect of cannabis abstinence on symptoms of anxiety and depression. Objective: To test the effect of 4 weeks of continuous cannabis abstinence on depressive and anxious symptoms. Methods: Healthy, non-treatment seeking adolescents who used cannabis at least weekly ( n = 179) were randomized to either 4 weeks of cannabis abstinence achieved through a contingency management paradigm (CB-Abst) or cannabis use monitoring without an abstinence requirement (CB-Mon). Abstinence was assessed by self-report verified with quantitative assay of urine for cannabinoids. Anxiety and depressive symptoms were assessed weekly with the Mood and Anxiety Symptom Questionnaire (MASQ). Results: Symptoms of depression and anxiety decreased throughout the study for all participants (MASQ-AA: stnd beta = −0.08, p = 0.01, MASQ-GDA: stnd beta = −0.11, p = 0.003, MASQ-GDD: stnd beta = −0.08, p = 0.02) and did not differ significantly between randomization groups ( p 's > 0.46). Exploratory analyses revealed a trend that abstinence may be associated with greater improvement in symptoms of anxiety and depression among those using cannabis to cope with negative affect and those with potentially hazardous levels of cannabis use. Conclusions: Among adolescents who use cannabis at least weekly, 4 weeks of cannabis abstinence was not associated with a significant change in anxiety or depressive symptoms compared to continued use. For recreational cannabis users who may be concerned about reducing their use for fear of increased symptoms of anxiety and depression, findings suggest that significant symptom worsening may not occur within the first 4 weeks of abstinence. Further studies are needed in clinical populations where anxiety and depression symptoms are measured more frequently and for a longer period of abstinence. Future studies are also needed to determine whether there are subgroups of adolescents who are uniquely impacted by sustained cannabis abstinence.
... It will be important for future longitudinal research to address the directional relationships between working memory, ADHD symptoms, and delay discounting in relation to cannabis use more definitively. These cognitive vulnerabilities could serve as risk factors for higher frequency and severity of cannabis use, but one longitudinal study nonetheless found that positive recovery effects on verbal memory can occur within one month of abstinence (Schuster et al., 2018). This is also supported by meta-analytic findings that an abstinence period of longer than 72 hr is associated with improved cognition (Scott et al., 2018). ...
Article
Objective To evaluate the associations between cannabis use and neurocognitive functioning, including self-reported attention deficit hyperactivity disorder (ADHD) symptoms, in a large sample of emerging adults (ages 21–25) using a cross-sectional design. A secondary objective was to examine age of cannabis initiation as a moderator. Methods Participants were high-risk drinking emerging adults ( n = 598) reporting past-month cannabis use in the following categories: 1) non-users (i.e., never or not in the past month; n = 276), 2) occasional users (i.e., monthly or weekly users; n = 201), and 3) daily users ( n = 121). Categorical comparisons were conducted on working memory, attention, behavioral inhibition, delay and probability discounting, verbal intelligence, and ADHD symptoms. Complementary dimensional analyses examined cannabis severity in relation to neurocognition using regressions. Covariates were age, race, sex, income, years of education, tobacco use, and alcohol use. Results Frequency of cannabis use was significantly associated with poorer working memory performance, more impulsive delay discounting, and greater endorsement of ADHD symptoms, but not other domains. Effect sizes were small and poorer performance was selectively present among daily, not occasional, cannabis users. Earlier age of initiation was not independently or interactively associated with neurocognitive performance. Conclusions Daily cannabis use was selectively adversely associated with aspects of memory, impulsivity, and subjective attentional functioning, but most cognitive indicators were not implicated, and evidence of amplification by earlier age of initiation was not observed. Ascertaining causal versus consequential roles of cannabis in neurocognitive functioning is an important priority.
... Previous research has focused on the effects of heavy cannabis use on neuropsychological functioning in adolescents and young adults, with studies showing small overall effect sizes (Scott et al., 2018). Nonetheless, cognitive difficulties have been shown to improve with abstinence (Schuster et al., 2018;Wallace, Wade, & Lisdahl, 2020), supporting their association with continued use. In young adults, sex has been reported to moderate the association between cognitive dysfunction and the frequency (Lisdahl & Price, 2012) and amount of cannabis use, as well as the age of initiated use (Crane, Schuster, Mermelstein, & Gonzalez, 2015). ...
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Objective Adolescence into young adulthood represents a sensitive period in which brain development significantly diverges by sex. Regular cannabis use by young people is associated with neuropsychological vulnerabilities, but the potential impact of sex on these relationships is unclear. Method In a cross-sectional study, we examined sex differences in multi-domain neuropsychological functioning using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and tested whether sex moderated the relationship between cognitive performance and age of initiation, frequency of cannabis use, amount of cannabis use, and withdrawal symptoms in at least weekly adolescent and young adult cannabis users ( n = 171; aged 13–25 years; 46.2% female). Results Male cannabis users had poorer visual recognition memory and female cannabis users showed worse attention and executive functions, with medium to large effect sizes. These sex effects persisted, when controlling for age, IQ, amount of alcohol and nicotine use, mood and anxiety symptoms, emotional stability and impulsive behavior. Earlier age of initiated use and more use were associated with worse attentional functions in females, but not males. More use was more strongly associated with worse episodic memory in males than in females. More use was associated with poorer learning in males only. Conclusions Domain-specific patterns of neuropsychological performance were found by sex, such that males showed poorer visual memory and females showed worse performance on measures of attention (sustained visual, multitasking) and executive functioning (spatial planning/working memory subdomains). Larger studies including healthy controls are needed to determine if the observed sex differences are more exaggerated relative to non-users.
... Preliminary longitudinal studies also suggested that cannabis onset is related to poorer verbal memory performance over time (Hanson, Medina, Padula, Tapert, & Brown, 2011;Jacobus et al., 2015;Nguyen-Louie et al., 2015). Yet deficits may not be permanent; some studies find improved memory in those who remain abstinent from cannabis for up to a month (Hanson et al., 2010;Schuster et al., 2018), while others do not (Wallace, Wade, & Lisdahl, In Press). A meta-analysis found cannabis to have a small effect on learning and delayed memory performance (d = −.33 and d = −.26, ...
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Objective Verbal memory deficits are linked to cannabis use. However, self-reported episodic use does not allow for assessment of variance from other factors (e.g., cannabis potency, route of consumption) that are important for assessing brain-behavior relationships. Further, co-occurring nicotine use may moderate the influence of cannabis on cognition. Here we utilized objective urinary measurements to assess the relationship between metabolites of cannabis, 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THCCOOH), and nicotine (cotinine) on verbal memory in young adults. Method Adolescents and young adults ( n = 103) aged 16–22 completed urinary drug testing and verbal memory assessment (RAVLT). Linear regressions examined the influence of THCCOOH and cotinine quantitative concentrations, and their interaction, on RAVLT scores, controlling for demographics and alcohol. Cannabis intake frequency was also investigated. Secondary analyses examined whether past month or recency of use related to performance, while controlling for THCCOOH and cotinine concentrations. Results THCCOOH concentration related to both poorer total learning and long delay recall. Cotinine concentration related to poorer short delay recall. Higher frequency cannabis use status was associated with poorer initial learning and poorer short delay. When comparing to self-report, THCCOOH and cotinine concentrations were negatively related to learning and memory performance, while self-report was not. Conclusions Results confirm the negative relationship between verbal memory and cannabis use, extending findings with objective urinary THCCOOH, and cotinine concentration measurements. No moderating relationship with nicotine was found, though cotinine concentration independently associated with negative short delay performance. Findings support the use of both urinary and self-report metrics as complementary methods in substance use research.
... Furthermore, testing of verbal memory in regular adolescent and young adult consumers (16-25 years old) showed that after abstinence for 1-3 weeks, their general memory was better than that of healthy volunteers; they also showed improvements in memory during the fi rst week of abstinence over the initial level. No infl uence on attention was seen: this increased identically as experience increased independently of marijuana consumption [Schuster et al., 2018]. Studies using a computerized neurocognitive test battery [Scott et al., 2017] showed that "light" cannabis consumers (1-2 times per week or less) aged 14-17 experienced no effect on memory or other cognitive capacities. ...
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Cannabinoids are natural compounds found in the hemp (Cannabis sativa). Scientific interest in cannabinoids arose after the discovery of the major psychoactive component in hemp, Δ9-tetrahydrocannabinol. Subsequent studies detected receptors in the brain subject to the actions of this compound, along with ligands for these receptors, i.e., endogenous cannabinoids (EC), which make up, along with the enzymes synthesizing, transporting, and degrading them, the endocannabinoid system (ECS). Interest in EC has consistently increased in recent years, especially after their important role in cognitive functions was discovered. They are regulators of synaptic transmission in the brain, mediate numerous forms of plasticity, and control neuron energy metabolism. EC exert influences using a series of mechanisms and interactions with neuromediators, neurotrophic factors, and neuropeptides. The main functions of EC in the brain are retrograde synaptic signaling and neuromodulation, which maintain cellular homeostasis. Information on the influences of cannabinoid drugs on cognitive functions is very contradictory. The cause of this may be that there are still inadequate strictly scientific data from clinical and sociological studies, while in animal experiments different authors use different methods and approaches for actions on the ECS. Thus, effects can differ depending on the substances used, their doses, and routes of administration, and the tasks and experimental conditions selected for testing. There is an extensive literature on the protective effect of ECS activation in neurodegenerative diseases in humans and models of cognitive deficit in animals. This review addresses data providing evidence of the influences of cannabinoid drugs and activation of the EC system on cognitive functions in the normal brain and in neurodegenerative diseases, Alzheimer’s disease, and temporal epilepsy. The possible causes of contradictions in existing data are also discussed.
... This is further supported by recent work showing a differential response of the pre-attentive, automatic mismatch negativity (MMN) waveform between short-term and long-term tobacco-naïve cannabis users, where deficits were only observed in long-term users (Impey et al. 2015). This is consistent with previous findings that cannabisinduced changes in cognition are associated with higher levels of circulating THC (Hunault et al. 2009), but reverse with abstinence (Rabin et al. 2017;Melissa et al. 2018). Furthermore, users in our sample are moderate cannabis users when compared to other studies, which may be why no significant gating differences were observed (Patrick and Struve 2000;Edwards et al. 2009;Broyd et al. 2013). ...
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Background and objectives: Cannabis is a widely used substance that may impair select cognitive domains, including attention and memory. Problematic cannabis use is a common clinical problem among patients with major depressive disorder (MDD). Few studies have investigated the effects of cannabis abstinence on cognition in MDD. Thus, our study aimed to determine whether a 28-day period of cannabis abstinence is associated with improvements in cognition in patients with MDD and comorbid cannabis use disorder (CUD). Methods: We evaluated the effects of 28 days of cannabis abstinence on cognition in MDD patients with comorbid CUD facilitated by contingency management, motivational interviewing, psychoeducation, and coping-skills training (N = 11). Primary outcomes included Baseline to Day 28 changes in verbal memory and learning, while secondary outcomes included Baseline to Day 28 changes in working memory, visuospatial working memory (VSWM), visual search speed, mental flexibility, response inhibition, attention, manual dexterity, and fine motor movement. Results: Eight participants (72.7%) met the pre-specified criteria for cannabis abstinence and three participants significantly reduced their cannabis use (≥90%). Visual search speed, selective attention, and VSWM improved over the study period. These improvements were not associated with changes in cannabis metabolite levels from baseline to endpoint. Discussion and conclusions: Our findings suggest that 28 days of cannabis abstinence may improve select cognitive domains in patients with MDD and comorbid CUD. Scientific significance: This was the first study to longitudinally examine the effects of cannabis on cognition in MDD. Clinical trial: Effects of Cannabis Abstinence on Symptoms and Cognition in Depression (NCT03624933; https://www. Clinicaltrials: gov).
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Background: Fetal alcohol spectrum disorder (FASD) has been recently estimated to afflict up to 5% of American children. Most of these children exhibit different degrees of symptomatology of disruptive behaviors. Yet, there has been very little research on the efficacy and safety of pharmacological modalities, limited mostly to stimulants for attention deficit hyperactive disorder or second generation atypical antipsychotics for aggression. Recently, the use of cannabinoids has been described for symptoms related to autistic spectrum disorder with apparent favorable effects, as well as for other disruptive behaviors. The objective of our study was to follow up in a retrospective case series the effect of cannabis in children and young adults diagnosed with FASD. Methods: In two children and three FASD young adults with severe disruptive behavior, changes in behavior after cannabis use were measured by the parent version of the Nisonger Child Behavior Rating Form. Results: In all five cases, there was a highly statistical decrease in the disruptive behavior score from 18±1.0 before cannabis use to 6±2.1 after introduction of cannabis (p=0.0002). Discussion: In children and young adults with FASD, cannabis, mostly cannabidiol (CBD), has been associated with a marked and statistically significant improvement in serious disruptive behavior. These cases suggest that the efficacy and safety of CBD should be tested in well-controlled studies.
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Introduction: Among adolescents and young adults, cannabis use is prevalent. Prior studies characterizing withdrawal effects in this age range have primarily included treatment seeking or comorbid psychiatric samples ; these studies have identified several affected domains, especially sleep, mood, and anxiety. The present study compared a community (i.e., nontreatment seeking) sample of cannabis-using and control participants on mood, anxiety, sleep, and withdrawal inventories during the course of a monitored 3-week cannabis abstinence period. Materials and Methods: Seventy-nine adolescent and young adult participants (cannabis-using group = 37 and control group = 42) were recruited from the community to undergo 3 weeks of confirmed abstinence (i.e., urine and sweat patch toxicology) and completion of Cannabis Withdrawal Symptom Criteria, State-Trait Anxiety Inventory, Beck's Depression Inventory, and Pittsburgh Sleep Quality Index across the study period. Repeated measures and cross-sectional regressions were used to examine main effects of group and interactions with time (where appropriate), while accounting for recent alcohol use and cotinine levels. Results: Cannabis-using participants reported higher mood (p = 0.006), overall withdrawal (p = 0.009), and sleep-related withdrawal (p < 0.001) symptoms across abstinence compared to controls. Overall withdrawal severity (p = 0.04) and sleep-related withdrawal symptoms (p = 0.02) demonstrated a quadratic trajectory across the monitored abstinence periods, with an increase from baseline and subsequent decreases in symptom severity. No differences of anxiety scores (p = 0.07) or trajectories (p = 0.18) were observed. By study completion, groups did not differ among sleep quality components (all p's > .05). Conclusions: These findings revealed that nontreatment-seeking cannabis-using adolescents and young adults reported heightened total withdrawal symptoms during a 3-week sustained abstinence period relative to controls. Cannabis-using participants demonstrated an increase in withdrawal symptom trajectory during the first week followed by decreased symptoms from weeks 2 to 3, which contrasts with prior linear decreases observed in cannabis-using adolescent and young adults. More mood symptoms were observed in the cannabis-using group even while excluding for comorbid psychopathologies-along with significantly more sleep problems during the abstinence period. Implications include the necessity to provide psychoedu-cation for recreational, nontreatment-seeking cannabis-using individuals about cannabis withdrawal, mood symptoms, and sleep quality difficulties when cannabis cessation is attempted, to improve likelihood of long-term sustained abstinence.
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Teenagers' use of cannabis is a significant problem due to the known detrimental effects it has on the developing brain. Cannabis use in the teenage years is associated with a disruption to the brain's reward system, impaired memory and cognition, and the potential for structural brain changes. Smoking cannabis can have a negative impact on the pulmonary system because it is a respiratory irritant. Teenagers are increasingly using electronic cigarettes, or vaping, to administer cannabis, which delivers a higher concentration of its psychoactive properties. Teenagers are not recognizing the health or other risks of using cannabis, such as motor vehicle accidents. All teenagers should be screened for cannabis use, and education about cannabis use should be age-specific and start in elementary education and continue through high school. Nurses are in a prime position to provide up-to-date, evidence-based education to teenagers, parents, and other health care professionals about teenagers' use of cannabis. Additional measures that can affect cannabis use in teenagers are screening for other underlying mental health disorders; improving quality of life, self-efficacy, and spirituality; and providing teenagers with opportunities to naturally stimulate the brain's reward center. [Journal of Psychosocial Nursing and Mental Health Services, 57(3), 11-15.].
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Cannabis use in the United States is growing at an unprecedented pace. Most states in the United States have legalized medical cannabis use, and many have legalized nonmedical cannabis use. In this setting, health care professionals will increasingly see more patients who have questions about cannabis use, its utility for medical conditions, and the risks of its use. This narrative review provides an overview of the background, pharmacology, therapeutic use, and potential complications of cannabis.
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Although many studies have examined the acute behavioural effects of cannabinoids in rodents, few have examined the lasting effects of cannabinoids at different developmental ages. This study compared lasting effects of cannabinoid exposure occurring in adolescence to that occurring in early adulthood. Forty, 30-day old (adolescent) and 18, 56-day old (adult) female albino Wistar rats were injected with vehicle or incremental doses of the cannabinoid receptor agonist (–)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP 55,940) once per day for 21 consecutive days (150, 200 and 300 μg/kg i.p. for 3, 8 and 10 days, respectively). Following a 21-day drug-free period, working memory was assessed using an object recognition task. Locomotor activity was also measured in the object recognition apparatus via a ceiling-mounted passive infrared sensor. Three days later, anxiety was assessed using a social interaction test. In the object recognition task, significantly poorer working memory was observed in the adolescent but not adult CP 55,940-treated rats. Adolescent, but not adult CP 55,940-treated rats, also exhibited a significant decrease in social interaction with a novel conspecific. These results suggest that chronic exposure to a cannabinoid receptor agonist well after the immediate postnatal period, but before reaching sexual maturity, can lead to increased anxiety and a lasting impairment of working memory.
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Earlier initiation of cannabis use is associated with poorer neuropsychological functioning across several domains. Given well-documented sex differences in neuromaturation during adolescence, initiation of cannabis use during this time may affect neuropsychological functioning differently for males and females. In the current study, we examined sex differences in the relationship between age of initiated cannabis use and neuropsychological performance after controlling for amount of lifetime cannabis use in 44 male and 25 female young adult cannabis users. We found that an earlier age of initiated use was related to poorer episodic memory, especially immediate recall, in females, but not in males. On the other hand, we found that, surprisingly, an earlier age of initiated use was associated with better decision making overall. However, exploratory analyses found sex-specific factors associated with decision making and age of initiated use, specifically that attention-deficit/hyperactivity disorder (ADHD) symptoms in females may drive the relationship between an earlier age of initiated use and better decision making. Further, an earlier age of initiated use was associated with less education, a lower IQ, and fewer years of mother's education for females, but more lifetime cannabis use for males. Taken together, our findings suggest there are sex differences in the associations between age of initiated cannabis use and neuropsychological functioning. The current study provides preliminary evidence that males and females may have different neuropsychological vulnerabilities that place them at risk for initiating cannabis use and continued cannabis use, highlighting the importance of examining the impact of cannabis on neuropsychological functioning separately for males and females.
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The Timeline Followback (TLFB), a retrospective calendar-based measure of daily substance use, was initially developed to obtain self-reports of alcohol use. Since its inception it has undergone extensive evaluation across diverse populations and is considered the most psychometrically sound self-report measure of drinking. Although the TLFB has been extended to other behaviors, its psychometric evaluation with other addictive behaviors has not been as extensive as for alcohol use. The present study evaluated the test-retest reliability of the TLFB for cocaine, cannabis, and cigarette use for participants recruited from outpatient alcohol and drug treatment programs and the general community across intervals ranging from 30 to 360 days prior to the interview. The dependent measure for cigarette smokers and cannabis users was daily use of cigarettes and joints, respectively, and for cocaine users it was a "Yes" or "No" regarding cocaine use for each day. The TLFB was administered in different formats for different drug types. Different interviewers conducted the two interviews. The TLFB collected highly reliable information about participants' daily use of cocaine, cannabis, and cigarettes from 30, 90, to 360 days prior to the interview. Findings from this study not only suggest that shorter time intervals (e.g., 90 days) can be used with little loss of accuracy, but also add to the growing literature that the TLFB can be used with confidence to collect psychometrically sound information about substance use (i.e., cocaine, cannabis, cigarettes) other than alcohol in treatment- and nontreatment-seeking populations for intervals from ranging up to 12 months prior to the interview. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
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Decades of research have examined the effects of cannabis on neurocognition. Recent advances in this field provide us with a better understanding of how cannabis use influences neurocognition both acutely (during intoxication) and non-acutely (after acute effects subside). Evidence of problems with episodic memory is one of the most consistent findings reported; however, several other neurocognitive domains appear to be adversely affected by cannabis use under various conditions. There is significant variability in findings across studies, thus a discussion of potential moderators is increasingly relevant. The purpose of this review was to 1) provide an update on research of cannabis' acute and non-acute effects on neurocognition, with a focus on findings since 2007 and 2) suggest and discuss how neurodevelopmental issues and sex differences may influence cannabis effects on neurocognition. Finally we discuss how future investigations may lead to better understanding of the complex interplay among cannabis, stages of neurodevelopment, and sex on neurocognitive functioning.
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Pediatric neuroimaging studies1, 2, 3, 4, 5, up to now exclusively cross sectional, identify linear decreases in cortical gray matter and increases in white matter across ages 4 to 20. In this large-scale longitudinal pediatric neuroimaging study, we confirmed linear increases in white matter, but demonstrated nonlinear changes in cortical gray matter, with a preadolescent increase followed by a postadolescent decrease. These changes in cortical gray matter were regionally specific, with developmental curves for the frontal and parietal lobe peaking at about age 12 and for the temporal lobe at about age 16, whereas cortical gray matter continued to increase in the occipital lobe through age 20.
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The possible medicinal use of cannabinoids for chronic diseases emphasizes the need to understand the long-term effects of these compounds on the central nervous system. We provide a quantitative synthesis of empirical research pertaining to the non-acute (residual) effects of cannabis on the neurocognitive performance of adult human subjects. Out of 1,014 studies retrieved using a thorough search strategy, only 11 studies met essential a priori inclusion criteria, providing data for a total of 623 cannabis users and 409 non- or minimal users. Neuropsychological results were grouped into 8 ability domains, and effect sizes were calculated by domain for each study individually, and combined for the full set of studies. Using slightly liberalized criteria, an additional four studies were included in a second analysis, bringing the total number of subjects to 1,188 (i.e., 704 cannabis users and 484 non-users). With the exception of both the learning and forgetting domains, effect size confidence intervals for the remaining 6 domains included zero, suggesting a lack of effect. Few studies on the non-acute neurocognitive effects of cannabis meet current research standards; nevertheless, our results indicate that there might be decrements in the ability to learn and remember new information in chronic users, whereas other cognitive abilities are unaffected. However, from a neurocognitive standpoint, the small magnitude of these effect sizes suggests that if cannabis compounds are found to have therapeutic value, they may have an acceptable margin of safety under the more limited conditions of exposure that would likely obtain in a medical setting.
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We report the dynamic anatomical sequence of human cortical gray matter development between the age of 4-21 years using quantitative four-dimensional maps and time-lapse sequences. Thirteen healthy children for whom anatomic brain MRI scans were obtained every 2 years, for 8-10 years, were studied. By using models of the cortical surface and sulcal landmarks and a statistical model for gray matter density, human cortical development could be visualized across the age range in a spatiotemporally detailed time-lapse sequence. The resulting time-lapse "movies" reveal that (i) higher-order association cortices mature only after lower-order somatosensory and visual cortices, the functions of which they integrate, are developed, and (ii) phylogenetically older brain areas mature earlier than newer ones. Direct comparison with normal cortical development may help understanding of some neurodevelopmental disorders such as childhood-onset schizophrenia or autism.
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Although many studies have examined the acute behavioural effects of cannabinoids in rodents, few have examined the lasting effects of cannabinoids at different developmental ages. This study compared lasting effects of cannabinoid exposure occurring in adolescence to that occurring in early adulthood. Forty, 30-day old (adolescent) and 18, 56-day old (adult) female albino Wistar rats were injected with vehicle or incremental doses of the cannabinoid receptor agonist (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP 55,940) once per day for 21 consecutive days (150, 200 and 300 microg/kg i.p. for 3, 8 and 10 days, respectively). Following a 21-day drug-free period, working memory was assessed using an object recognition task. Locomotor activity was also measured in the object recognition apparatus via a ceiling-mounted passive infrared sensor. Three days later, anxiety was assessed using a social interaction test. In the object recognition task, significantly poorer working memory was observed in the adolescent but not adult CP 55,940-treated rats. Adolescent, but not adult CP 55,940-treated rats, also exhibited a significant decrease in social interaction with a novel conspecific. These results suggest that chronic exposure to a cannabinoid receptor agonist well after the immediate postnatal period, but before reaching sexual maturity, can lead to increased anxiety and a lasting impairment of working memory.
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The current study examined whether adolescent rats are more vulnerable than adult rats to the lasting adverse effects of cannabinoid exposure on brain and behavior. Male Wistar rats were repeatedly exposed to Delta-9-tetrahydrocannabinol (Delta(9)-THC, 5 mg/kg i.p.) in a place-conditioning paradigm during either the adolescent (post-natal day 28+) or adult (post-natal day 60+) developmental stages. Adult rats avoided a Delta(9)-THC-paired environment after either four or eight pairings and this avoidance persisted for at least 16 days following the final Delta(9)-THC injection. In contrast, adolescent rats showed no significant place aversion. Adult Delta(9)-THC-treated rats produced more vocalizations than adolescent rats when handled during the intoxicated state, also suggesting greater drug-induced aversion. After a 10-15 day washout, both adult and adolescent Delta(9)-THC pretreated rats showed decreased social interaction, while only Delta(9)-THC pretreated adolescent rats showed significantly impaired object recognition memory. Seventeen days following their last Delta(9)-THC injection, rats were euthanased and hippocampal tissue processed using two-dimensional gel electrophoresis proteomics. There was no evidence of residual Delta(9)-THC being present in blood at this time. Proteomic analysis uncovered 27 proteins, many involved in regulating oxidative stress/mitochondrial functioning and cytoarchitecture, which were differentially expressed in adolescent Delta(9)-THC pretreated rats relative to adolescent controls. In adults, only 10 hippocampal proteins were differentially expressed in Delta(9)-THC compared to vehicle-pretreated controls. Overall these findings suggest that adolescent rats find repeated Delta(9)-THC exposure less aversive than adults, but that cannabinoid exposure causes greater lasting memory deficits and hippocampal alterations in adolescent than adult rats.
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In adults, studies examining the long-lasting cognitive effects of marijuana use demonstrate subtle deficits in attention, executive function, and memory. Because neuromaturation continues through adolescence, these results cannot necessarily generalize to adolescent marijuana users. The goal of this study was to examine neuropsychological functioning in abstinent marijuana using and demographically similar control adolescents. Data were collected from 65 adolescent marijuana users (n=31, 26% females) and controls (n=34, 26% females) 16-18 years of age. Extensive exclusionary criteria included independent psychiatric, medical, and neurologic disorders. Neuropsychological assessments were conducted after>23 days of monitored abstinence. After controlling for lifetime alcohol use and depressive symptoms, adolescent marijuana users demonstrated slower psychomotor speed (p<.05), and poorer complex attention (p<.04), story memory (p<.04), and planning and sequencing ability (p<.001) compared with controls. Post hoc analysis revealed that the number of lifetime marijuana use episodes was associated with poorer cognitive function, even after controlling for lifetime alcohol use. The general pattern of results suggested that, even after a month of monitored abstinence, adolescent marijuana users demonstrate subtle neuropsychological deficits compared with nonusers. It is possible that frequent marijuana use during adolescence may negatively influence neuromaturation and cognitive development.
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Background: Rates of young adult cannabis use are rising, perceived harm is at its historical nadir, and most users do not want to quit. Most studies evaluating effects of cannabis use in young adults are cross-sectional, limiting causal inference. A method to reliably induce abstinence periods in cannabis users would allow assessment of the effects of abstinence and resumption of use on a variety of outcomes in a within-subjects, repeated measures design. Methods: We examined the efficacy and feasibility of a voucher-based contingency management procedure for incentivizing one month of continuous cannabis abstinence among young adults who reported at least weekly cannabis use, volunteered to participate in a laboratory study, and did not express a desire to discontinue cannabis use long-term. Continuous cannabis abstinence was reinforced with an escalating incentive schedule, and self-report of abstinence was confirmed by frequent quantitative assays of urine cannabis metabolite (THCCOOH) concentration. New cannabis use during the abstinence period was determined using an established algorithm of change in creatinine-adjusted cannabis metabolite concentrations between study visits. Results: Thirty-eight young adults, aged 18-25 years, enrolled and 34 (89.5%) attained biochemically confirmed 30-day abstinence. Among those who attained abstinence, 93.9% resumed regular use within two-weeks of incentive discontinuation. Conclusion: Findings support the feasibility and efficacy of contingency management to elicit short-term, continuous cannabis abstinence among young adult, non-treatment seeking, regular cannabis users. Further work should test the effectiveness of this contingency management procedure for cannabis abstinence in periods longer than one month, which may be required to evaluate some effects of abstinence.
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Background: Adolescent marijuana use is associated with neurocognitive impairment, but further work is needed to assess the relationship between treatment-associated abstinence and cognitive performance. Methods: This secondary analysis, conducted in the context of a marijuana cessation pharmacotherapy trial in adolescents, examined cognitive performance at baseline and at two time points during treatment using the CNS Vital Signs assessment battery. Results: Abstinence from marijuana, relative to continued use, as assessed via urine cannabinoid testing, was associated with significant improvement in composite memory (p<0.001), verbal memory (the most impacted component of composite memory) (p<0.001), and psychomotor performance (p=0.045) scores. Conclusions: These findings suggest that some domains of cognitive performance improve significantly even in the early stages of treatment-associated abstinence.
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[Correction Notice: An Erratum for this article was reported in Vol 26(3) of Psychology of Addictive Behaviors (see record 2011-29227-001). Figure 1 should have been presented in color. All versions of this article have been corrected.] Marijuana (MJ) remains the most widely abused illicit substance in the United States, and in recent years, a decline in perceived risk of MJ use has been accompanied by a simultaneous increase in rates of use among adolescents. In this study, the authors hypothesized that chronic MJ smokers would perform cognitive tasks, specifically those that require executive function, more poorly than control subjects and that individuals who started smoking MJ regularly prior to age 16 (early onset) would have more difficulty than those who started after age 16 (late onset). Thirty-four chronic, heavy MJ smokers separated into early and late onset groups, and 28 non-MJ smoking controls completed a battery of neurocognitive measures. As hypothesized, MJ smokers performed more poorly than controls on several measures of executive function. Age of onset analyses revealed that these between-group differences were largely attributed to the early onset group, who were also shown to smoke twice as often and nearly 3 times as much MJ per week relative to the late onset smokers. Age of onset, frequency, and magnitude of MJ use were all shown to impact cognitive performance. Findings suggest that earlier MJ onset is related to poorer cognitive function and increased frequency and magnitude of MJ use relative to later MJ onset. Exposure to MJ during a period of neurodevelopmental vulnerability, such as adolescence, may result in altered brain development and enduring neuropsychological changes. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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Converging lines of evidence suggest an adverse effect of heavy cannabis use on adolescent brain development, particularly on the hippocampus. In this preliminary study, we compared hippocampal morphology in 14 "treatment-seeking" adolescents (aged 18-20) with a history of prior heavy cannabis use (5.8 joints/day) after an average of 6.7 months of drug abstinence, and 14 demographically matched normal controls. Participants underwent a high-resolution 3D MRI as well as cognitive testing including the California Verbal Learning Test (CVLT). Heavy-cannabis users showed significantly smaller volumes of the right (p < 0.04) and left (p < 0.02) hippocampus, but no significant differences in the amygdala region compared to controls. In controls, larger hippocampus volumes were observed to be significantly correlated with higher CVLT verbal learning and memory scores, but these relationships were not observed in cannabis users. In cannabis users, a smaller right hippocampus volume was correlated with a higher amount of cannabis use (r = -0.57, p < 0.03). These data support a hypothesis that heavy cannabis use may have an adverse effect on hippocampus development. These findings, after an average 6.7 month of supervised abstinence, lend support to a theory that cannabis use may impart long-term structural and functional damage. Alternatively, the observed hippocampal volumetric abnormalities may represent a risk factor for cannabis dependence. These data have potential significance for understanding the observed relationship between early cannabis exposure during adolescence and subsequent development of adult psychopathology reported in the literature for schizophrenia and related psychotic disorders.
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To develop and validate empirically a mathematical model for identifying new cannabis use in chronic, daily cannabis smokers. Models were based on urinary creatinine-normalized (CN) cannabinoid excretion in chronic cannabis smokers. For model development, participants resided on a secure research unit for 30 days. For model validation, participants were abstinent with daily observed urine specimens for 28 days. A total of 48 (model development) and 67 (model validation) daily cannabis smokers were recruited. All voided urine was collected and analyzed for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) by gas chromatography-mass spectrometry (GCMS; limit of quantification 2.5 ng/ml) and creatinine (mg/ml). Urine THCCOOH was normalized to creatinine, yielding ng/mg CN-THCCOOH concentrations. Urine concentration ratios were determined from 123,513 specimen pairs collected 2-30 days apart. A mono-exponential model (with two parameters, initial urine specimen CN-THCCOOH concentration and time between specimens), based on the Marquardt-Levenberg algorithm, provided a reasonable data fit. Prediction intervals with varying probability levels (80, 90, 95, 99%) provide upper ratio limits for each urine specimen pair. Ratios above these limits suggest cannabis re-use. Disproportionate numbers of ratios were higher than expected for some participants, prompting development of two additional rules that avoid misidentification of re-use in participants with unusual CN-THCCOOH excretion patterns. For the first time, a validated model is available to aid in the differentiation of new cannabis use from residual creatinine-normalized 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (CN-THCCOOH) excretion in chronic, daily cannabis users. These models are valuable for clinicians, toxicologists and drug treatment staff and work-place, military and criminal justice drug-testing programs.
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Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs.
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Cognitive deficits that persist up to a month have been detected among adult marijuana users, but decrements and their pattern of recovery are less known in adolescent users. Previously, we reported cognitive deficits among adolescent marijuana users after one month of abstinence (Medina, Hanson, Schweinsburg, Cohen-Zion, Nagel, & Tapert, 2007). In this longitudinal study, we characterized neurocognitive changes among marijuana-using adolescents across the first three weeks of abstinence. Participants were adolescent marijuana users with limited alcohol and other drug use (n=19) and demographically similar non-using controls (n=21) ages 15-19. Participants completed a brief neuropsychological battery on three occasions, after 3days, 2weeks, and 3weeks of stopping substance use. Abstinence was ascertained by decreasing tetrahydrocannabinol metabolite values on serial urine drug screens. Verbal learning, verbal working memory, attention and vigilance, and time estimation were evaluated. Marijuana users demonstrated poorer verbal learning (p<.01), verbal working memory (p<.05), and attention accuracy (p<.01) compared to controls. Improvements in users were seen on word list learning after 2weeks of abstinence and on verbal working memory after 3weeks. While attention processing speed was similar between groups, attention accuracy remained deficient in users throughout the 3-week abstinence period. This preliminary study detected poorer verbal learning and verbal working memory among adolescent marijuana users that improved during three weeks of abstinence, while attention deficits persisted. These results implicate possible hippocampal, subcortical, and prefrontal cortex abnormalities.
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Research suggests that use and abuse of marijuana can be especially harmful if it occurs during adolescence, a period of vast developmental changes throughout the brain. We examined the effects of 2mg/kg (9)-tetrahydrocannabinol (THC) administered daily via intra-peritoneal injections during juvenile/early adolescence (postnatal day 22-40) or late adolescence (postnatal day 41-60) on locomotor activity, development of tolerance, and acquisition/retention of spatial avoidance in adulthood. THC caused locomotor depression in both male and female animals dosed during early adolescence but only in female animals dosed during late adolescence. Evidence of reverse tolerance to THC was seen in early adolescent animals only. In the active place avoidance test (APA), male and female animals administered THC during early adolescence made more errors on the reversal trial requiring flexibility in learning, but in animals dosed during late adolescence there were no significant sex or treatment differences. The results of the locomotor activity study indicate that females may be more sensitive to the effects of THC than males, while results of both locomotor activity and APA studies suggest that early adolescents appear to be more vulnerable to these effects than late adolescents/young adults.
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Functional neuroimaging data from adults have, in general, revealed frontocerebellar dysfunction associated with acute and chronic marijuana (MJ) use. The goal of this study was to characterize cerebellar volume in adolescent chronic MJ users following 1 month of monitored abstinence. Participants were MJ users (n=16) and controls (n=16) aged 16-18 years. Extensive exclusionary criteria included history of psychiatric or neurologic disorders. Drug use history, neuropsychological data, and structural brain scans were collected after 28 days of monitored abstinence. Trained research staff defined cerebellar volumes (including three cerebellar vermis lobes and both cerebellar hemispheres) on high-resolution T1-weighted magnetic resonance images. Adolescent MJ users demonstrated significantly larger inferior posterior (lobules VIII-X) vermis volume than controls, above and beyond effects of lifetime alcohol and other drug use, gender, and intracranial volume. Larger vermis volumes were associated with poorer executive functioning. Following 1 month of abstinence, adolescent MJ users had significantly larger posterior cerebellar vermis volumes than non-using controls. These greater volumes are suggested to be pathological based on linkage to poorer executive functioning. Longitudinal studies are needed to examine typical cerebellar development during adolescence and the influence of marijuana use.
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Marijuana and hashish are the illicit drugs most frequently used by human adolescents. Given the continued neurodevelopment throughout adolescence, adolescents may be more vulnerable than adults to certain neural consequences of heavy marijuana use. This study aimed to assess whether an experimental model of adolescent chronic exposure to Delta9-tetrahydrocannabinol (THC), may induce lasting effects on learning and memory. Adolescent rats have been treated with THC or its vehicle from 35 to 45 postnatal days (PND) and left undisturbed until their adulthood (75 PND) when aversive and spatial memory was assessed using the passive avoidance and radial maze tasks. No alteration was found in aversive memory, but in the radial maze THC pretreated animals exhibited a worse performance than vehicles, suggesting a deficit in spatial working memory. To correlate memory impairment to altered neuroplasticity, level of marker proteins was investigated in the hippocampus, the most relevant area mediating spatial memory. A significant decrease in the astroglial marker glial fibrillar acid protein was found as well as in pre- and postsynaptic protein expression (VAMP2, PSD95) and NMDA receptor levels in pretreated rats. To parallel these changes to alteration in dendritic morphology, Golgi-Cox staining was performed in the hippocampal dentate gyrus. Pretreated rats had a significantly lower total dendritic length and number than vehicles, as well as reduced spine density. Our data suggest that THC pretreated rats may establish less synaptic contacts and/or less efficient synaptic connections throughout the hippocampus and this could represent the molecular underpinning of the cognitive deficit induced by adolescent THC treatment.
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The Alcohol Use Disorders Identification Test (AUDIT) has been developed from a six-country WHO collaborative project as a screening instrument for hazardous and harmful alcohol consumption. It is a 10-item questionnaire which covers the domains of alcohol consumption, drinking behaviour, and alcohol-related problems. Questions were selected from a 150-item assessment schedule (which was administered to 1888 persons attending representative primary health care facilities) on the basis of their representativeness for these conceptual domains and their perceived usefulness for intervention. Responses to each question are scored from 0 to 4, giving a maximum possible score of 40. Among those diagnosed as having hazardous or harmful alcohol use, 92% had an AUDIT score of 8 or more, and 94% of those with non-hazardous consumption had a score of less than 8. AUDIT provides a simple method of early detection of hazardous and harmful alcohol use in primary health care settings and is the first instrument of its type to be derived on the basis of a cross-national study.
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Volumetric studies have consistently shown reductions in cerebral gray matter volume between childhood and adolescence, with the most dramatic changes occurring in the more dorsal cortices of the frontal and parietal lobes. The purpose of this study was to examine the spatial location of these changes employing methods typical of functional imaging studies. T1-weighted structural MRI data (1.2 mm) were analyzed for nine normally developing children and nine normal adolescents. Validity and reliability of the tissue segmentation protocol were assessed as part of several preprocessing analyses prior to statistical parametric mapping (SPM). Using SPM96, a simple contrast of average gray matter differences between the two age groups revealed 57 significant clusters (SPM[Z] height threshold, P<0.001, extent threshold 50, uncorrected). The pattern and distribution of differences were consistent with earlier findings from the volumetric assessment of the same subjects. Specifically, more differences were observed in dorsal frontal and parietal regions with relatively few differences observed in cortices of the temporal and occipital lobes. Permutation tests were conducted to assess the overall significance of the gray matter differences and validity of the parametric maps. Twenty SPMs were created with subjects randomly assigned to groups. None of the random SPMs approached the number of significant clusters observed in the age difference SPM (mean number of significant clusters = 5.8). The age effects observed appear to result from regions that consistently segment as gray matter in the younger group and consistently segment as white matter in the older group. The utility of these methods for localizing relatively subtle structural changes that occur between childhood and adolescence has not previously been examined.
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Controlled clinical research has demonstrated the efficacy of contingency management procedures in treating substance use disorders. Now is the time to begin introducing these procedures into standard clinical practice. This article reviews the rationale of contingency management interventions and provides a review of representative scientific work in the area. It also discusses behaviors that can be modified, reinforcers that can be used, and behavioral principles that can be adapted to improve outcomes. This paper provides practical advice and a guideline for clinicians and researchers to use when designing and administering contingency management interventions. The recommendations are based on empirically validated manipulations. Areas in which more research is needed are suggested as well.
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To critically review and integrate the existing literature on magnetic resonance imaging (MRI) studies of the normally developing brain in childhood and adolescence and discuss the implications for clinical MRI studies. Changes in regional brain volume with age and differences between the sexes are summarized from reports in refereed journal articles pertaining to MRI of the developing human brain. White matter volume increases with age. Gray matter volumes increase during childhood and then decrease before adulthood. On average, boys have larger brains than girls; after correction for overall brain volume the caudate is relatively larger in girls, and the amygdala is relatively larger in boys. Differences are of clinical interest given gender-related differences in the age of onset, symptomatology, and prevalence noted for nearly all childhood-onset psychiatric disorders. Attention-deficit/hyperactivity disorder is frequently used as an example to demonstrate these points. Understanding the developmental trajectories of normal brain development and differences between the sexes is important for the interpretation of clinical imaging studies.
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Magnetic resonance imaging (MRI) provides accurate anatomical brain images without the use of ionizing radiation, allowing longitudinal studies of brain morphometry during adolescent development. Results from an ongoing brain imaging project being conducted at the Child Psychiatry Branch of the National Institute of Mental Health indicate dynamic changes in brain anatomy throughout adolescence. White matter increases in a roughly linear pattern, with minor differences in slope in the four major lobes (frontal, parietal, temporal, occipital). Cortical gray matter follows an inverted U-shape developmental course with greater regional variation than white matter. For instance, frontal gray matter volume peaks at about age 11.0 years in girls and 12.1 years in boys, whereas temporal gray matter volume peaks at about age at 16.7 years in girls and 16.2 years in boys. The dorsal lateral prefrontal cortex, important for controlling impulses, is among the latest brain regions to mature without reaching adult dimensions until the early 20s. The details of the relationships between anatomical changes and behavioral changes, and the forces that influence brain development, have not been well established and remain a prominent goal of ongoing investigations.
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The Cannabis Use Disorders Identification Test (CUDIT) was used for the first time as part of a randomized controlled trial for brief interventions in mild to moderate alcohol-dependent out-patients. This sample may be seen as a population at increased risk of cannabis use disorder. The CUDIT was developed by modifying the Alcohol Use Disorders Identification Test (AUDIT). The ability of the CUDIT to accurately screen for cannabis abuse or dependence was examined in the portion of the sample who reported some cannabis use over the preceding 6 months (n=53), as was self-reported frequency of cannabis use in the preceding 6 months. The CUDIT was superior to the frequency measure, achieving positive predictive power of 84.6% and sensitivity of 73.3% at a cut-off of 8, compared to positive predictive power of 81.8% and sensitivity of 60.0% for 80 or more cannabis use-days. These results indicate the viability of a screening measure for identifying cannabis use disorder in at risk populations.
A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood
  • A Pfefferbaum
  • D H Mathalon
  • E V Sullivan
  • J M Rawles
  • R B Zipursky
  • K O Lim
Pfefferbaum A, Mathalon DH, Sullivan EV, Rawles JM, Zipursky RB, Lim KO: A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol 1994;51:874-887. [PubMed: 8080387]