Alcohol substitution during one month of cannabis abstinence among non-treatment seeking youth.

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 4 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 4 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, 4 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.

Urinary 11-nor-9-carboxy-tetrahydrocannabinol elimination in adolescent and young adult cannabis users during one month of sustained and biochemically-verified abstinence.

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.

Cross-domain correlates of cannabis use disorder severity among young adults.

BACKGROUND: Correlates of cannabis use and dependence among young adults have been widely studied. However, it is not known which factors are most strongly associated with severity of cannabis use dependence (CUD) severity. Identification of the salient correlates of CUD severity will be of increasing clinical significance as use becomes more socially normative. METHODS: This study used a data-driven, hypothesis-free approach to examine the most robust correlates of CUD severity among a sample of 76 young adults (ages 18 to 25 years) who used cannabis at least weekly. Seventy-one candidate variables were examined for association with CUD severity. These included demographic variables, self-reported and psychodiagnostic assessments of mood and anxiety, self-reported measures of personality, cannabis and other substance use characteristics, and objective and subjective measures of cognition. RESULTS: Of the 71 candidate variables considered, 27 were associated with CUD severity on a univariate level at a p-value ≤.20. Correlates of CUD severity in the multivariable model using stepwise selection were: more frequent cannabis use in the past 90 days, greater expectancies that cannabis causes cognitive and behavioral impairment, greater self-reported metacognitive deficits, greater anxiety, and lower reaction time variability on a test of sustained attention. Internal validation tests support high prediction accuracy of all variables in the multivariable model, except for lower reaction time variability. CONCLUSIONS: Cannabis use frequency, beliefs about use, perceived cognitive abilities, and anxiety are robustly associated with CUD severity in young adult, regular cannabis users, and may be important in guiding prevention and treatment efforts.

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

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.

Phase IIb Trial of an α7 Nicotinic Receptor Partial Agonist With and Without Nicotine Patch for Withdrawal-Associated Cognitive Deficits and Tobacco Abstinence.

PURPOSE/BACKGROUND: The objective of this study was to determine whether a novel α7 nicotinic acetylcholine receptor partial agonist improves cognition during nicotine withdrawal and improves abstinence rates. To do so, the effect of the α7 nicotinic acetylcholine receptor partial agonist, encenicline, on cognition and abstinence was evaluated when given as monotherapy and when combined with transdermal nicotine patch (nicotine replacement therapy [NRT]). METHODS: Adult daily smokers, n = 160, who were motivated to quit smoking completed cognitive testing at satiated baseline and after overnight abstinence and then were randomized to receive a 12-week trial of encenicline 1 mg twice daily or identical placebo the day of the overnight abstinent cognitive testing. In the first 6 weeks of the 12-week encenicline administration, participants were also randomized to 6 weeks of NRT patch or placebo patch. Primary outcomes were cognition during abstinence and 7-day point-prevalence abstinence at week 12. RESULTS: No beneficial effects of encenicline were observed on cognition or abstinence when compared with placebo or when combined with NRT compared with placebo capsule + NRT. Of the 4 conditions, abstinence rates were lowest among those assigned to encenicline alone. CONCLUSIONS: Beneficial effects of NRT were observed on cognitive and abstinence outcomes when combined with encenicline compared with encenicline plus placebo patch. Addition of NRT to encenicline improved odds of abstinence approximately 3-fold compared with encenicline plus placebo patch. We conclude that encenicline, 1 mg/d, did not improve abstinence-associated cognitive impairment or abstinence rates as monotherapy or adjunctive therapy to NRT patch.

Prolonged cannabis withdrawal in young adults with lifetime psychiatric illness.

Young adults with psychiatric illnesses are more likely to use cannabis and experience problems from use. It is not known whether those with a lifetime psychiatric illness experience a prolonged cannabis withdrawal syndrome with abstinence. Participants were fifty young adults, aged 18-25, recruited from the Boston-area in 2015-2016, who used cannabis at least weekly, completed the Structured Clinical Interview for DSM-IV to identify Axis I psychiatric diagnoses (PD+ vs PD-), and attained cannabis abstinence with a four-week contingency management protocol. Withdrawal symptom severity was assessed at baseline and at four weekly abstinent visits using the Cannabis Withdrawal Scale. Cannabis dependence, age of initiation, and rate of abstinence were similar in PD+ and PD- groups. There was a diagnostic group by abstinent week interaction, suggesting a difference in time course for resolution of withdrawal symptoms by group, F(4,46)=3.8, p=0.009, controlling for sex, baseline depressive and anxiety symptoms, and frequency of cannabis use in the prior 90days. In post hoc analyses, there was a difference in time-course of cannabis withdrawal. PD- had significantly reduced withdrawal symptom severity in abstinent week one [t(46)=-2.2, p=0.03], while PD+ did not report improved withdrawal symptoms until the second abstinent week [t(46)=-4.1, p=0.0002]. Cannabis withdrawal symptoms improved over four weeks in young people with and without a lifetime psychiatric diagnosis. However, those with a psychiatric illness reported one week delayed improvement in withdrawal symptom severity. Longer duration of cannabis withdrawal may be a risk factor for cannabis dependence and difficulty quitting.

A contingency management method for 30-days abstinence in non-treatment seeking young adult cannabis users.

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.

Early onset marijuana use is associated with learning inefficiencies.

OBJECTIVE: Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. METHOD: Forty-eight young adults, aged 18-25, who used marijuana at least once per week and 48 matched nonusing controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: early onset users (EMJ), who started using marijuana at or before age 16 (n = 27), and late onset marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. RESULTS: Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. CONCLUSIONS: Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. (PsycINFO Database Record

Ecological momentary assessment of working memory under conditions of simultaneous marijuana and tobacco use.

BACKGROUND AND AIMS: The neuropsychological correlates of simultaneous marijuana and tobacco use are largely unknown, which is surprising as both substances have similar neural substrates and have opposing influences on working memory (WM). This study examined the effects of marijuana alone, tobacco alone and simultaneous marijuana and tobacco use on WM. DESIGN: Primary aims were tested using a within-subject design, controlling for multiple subject- and momentary-level confounds via ecological momentary assessment (EMA). SETTING: Data collection occurred in the Chicago, USA area in participants' natural environments. PARTICIPANTS: Participants were 287 community young adults from a larger natural history study, oversampled for ever smoking, all of whom event-recorded at least one substance use occasion during the study week. MEASUREMENTS: Momentary tobacco, marijuana and alcohol use were recorded during multiple EMA across 1 week of data capture. WM was assessed at the end of each EMA assessment. Contextual variables that may influence WM were recorded via EMA. FINDINGS: There were main effects for marijuana and tobacco: WM was poorer with marijuana [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.84-0.99] and better with tobacco (OR = 1.11, 95% CI = 1.04-1.18). These effects were not qualified by an interaction (OR = 1.03, 95% CI = 0.84-1.26). Alcohol also reduced WM (OR = 0.87, 95% CI = 0.79-0.95), and the tobacco × alcohol interaction was significant (OR = 0.81, 95% CI = 0.66-0.99), indicating that the facilitative effect of tobacco disappeared with concurrent alcohol use. CONCLUSIONS: Relative to when individuals did not use these substances, working memory decreased with acute marijuana and alcohol use and increased with acute tobacco use. However, the putative effect of marijuana on working memory and the facilitative effect of tobacco on working memory were no longer present when used simultaneously with tobacco and alcohol, respectively. Data suggest that tobacco use may compensate for working memory decrements from marijuana among young adults and highlight the importance of investigating further the negative impact of alcohol use on cognition.

Neuropsychological sex differences associated with age of initiated use among young adult cannabis users.

INTRODUCTION: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Acceptability and feasibility of a visual working memory task in an ecological momentary assessment paradigm.

Neuropsychological performance has historically been measured in laboratory settings using standardized assessments. However, these methods may be inherently limited in generalizability. This concern may be mitigated with paradigms such as ecological momentary assessment (EMA). We evaluated the initial feasibility and acceptability of administering a visual working memory (VWM) task on handheld computers across 1 EMA study week among adolescents/young adults (N = 39). Participants also completed standardized laboratory neurocognitive measures to determine the extent to which EMA VWM performance mapped onto scores obtained in traditional testing environments. Compliance with the EMA protocol was high as participants responded to 87% of random prompts across the study week. As expected, EMA VWM performance was positively associated with laboratory measures of auditory and VWM, and these relationships persisted after adjusting for predicted intelligence. Further, discriminant validity tests showed that EMA VWM was not linked with laboratory scores of verbal abilities and processing speed. These data provide initial evidence on the convergent and discriminant validity of interpretations from this novel, ecologically valid neurocognitive approach. Future studies will aim to further establish the psychometric properties of this (and similar) tasks and investigate how momentary fluctuations in VWM correspond with contextual influences (e.g., substance use, mood) and clinical outcomes.

Preliminary evidence for a sex-specific relationship between amount of cannabis use and neurocognitive performance in young adult cannabis users.

Accumulating evidence suggests neuropsychological deficits from cannabis use, with a burgeoning area of preclinical research indicating possible sex-differences. However, few studies have examined how cannabis use may differentially impact neurocognition in male and female cannabis users. As such, we examined potential sex-differences in associations between amount of cannabis use (across several time frames) and neurocognitive performance among young adult regular cannabis users. Consistent with previous studies, more cannabis use was generally associated with poorer episodic memory and decision-making, but not other measures of inhibitory control. However, patterns of results suggested sex-specific dissociations. In particular, more cannabis use was more consistently associated with poorer episodic memory performance in females than males. Conversely, more cannabis use was associated with poorer decision-making performance for males, but not females. These results provide further evidence for residual cannabis-associated neurocognitive deficits and suggest the importance of examining the impact of cannabis on neurocognition separately for males and females.

Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences.

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.

Gender-specific relationships between depressive symptoms, marijuana use, parental communication and risky sexual behavior in adolescence.

A large body of research has identified correlates of risky sexual behavior, with depressive symptoms and marijuana use among the most consistent psychosocial predictors of sexual risk. However, substantially less research has examined the relationship between these risk variables and adolescent risky sexual behavior over time as well as the interaction of these individual-level predictors with family-level variables such as parenting factors. Additionally, most studies have been restricted to one index of risky sexual behavior, have not taken into account the complex role of gender, and have not controlled for several of the factors that independently confer risk for risky sexual behavior. Therefore, the current study investigated the association between depressive symptoms and parameters of parenting on marijuana use, number of sexual partners and condom usage measured 9 months later for both boys and girls. Participants were 9th and 10th grade adolescents (N = 1,145; 57.7% female). We found that depressive symptoms may be a gender-specific risk factor for certain indices of risky sexual behavior. For boys only, marijuana use at Time 2 accounted for the variance in the relationship between depressive symptoms at Time 1 and number of partners at Time 2. Additionally, strictness of family rules at Time 1 was associated with the number of partners with whom girls engaged in sex at Time 2, but only among those with lower levels of depressive symptoms at Time 1. Results from the current investigation speak to the utility of examining the complex, gender-specific pathways to sexual risk in adolescents. Findings suggest that treatment of mental health and substance use problems may have important implications in rates of risky sexual behavior and, conceivably, controlling the high rates of serious individual and public health repercussions.

Performance of young adult cannabis users on neurocognitive measures of impulsive behavior and their relationship to symptoms of cannabis use disorders.

Recent studies suggest that abstinent cannabis users show deficits on neurocognitive laboratory tasks of impulsive behavior. But results are mixed, and less is known on the performance of non-treatment-seeking, young adult cannabis users. Importantly, relationships between performance on measures of impulsive behavior and symptoms of cannabis addiction remain relatively unexplored. We compared young adult current cannabis users (CU, n = 65) and nonusing controls (NU, n = 65) on several laboratory measures of impulsive behavior, as well as on a measure of episodic memory commonly impacted by cannabis use. The CU group performed more poorly than the NU group on the Hopkins Verbal Learning Test-Revised Total Immediate Recall and Delayed Recall. No significant differences were observed on the measures of impulsive behavior (i.e., Iowa Gambling Task, IGT; Go-Stop Task; Monetary Choice Questionnaire; Balloon Analogue Risk Task). We examined relationships between neurocognitive performance and symptoms of cannabis use disorder symptoms (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, DSM-IV CUD) among the CU group, which revealed that poorer IGT performance was associated with more symptoms of DSM-IV CUD. Our results show poorer memory performance among young adult cannabis users than among healthy controls, but no differences on measures of impulsive behavior. However, performance on a specific type of impulsive behavior (i.e., poorer decision making) was associated with more cannabis use disorder symptoms. These results provide preliminary evidence to suggest that decision-making deficits may be more strongly associated with problems experienced from cannabis use, rather than solely being a consequence of cannabis use, per se.

The influence of inhibitory control and episodic memory on the risky sexual behavior of young adult cannabis users.

Cannabis use is associated with risky sexual behavior (RSB) and sex-related negative health consequences. This investigation examined the role of inhibitory control and episodic memory in predicting RSB and sex-related negative consequences among current cannabis users. Findings indicated that the relationships among cannabis, neurocognition, and sexual-risk varied according to the dimension of neurocognition and the parameter of RSB in question. Specifically, more risk-taking was associated with more RSB. Furthermore, amount of recent cannabis use was associated with more RSB and sex-related negative consequences, but only among those with worse performances on a measure of decision-making and of risk-taking. Contrary to hypotheses, worse episodic memory also significantly predicted higher overall sexual-risk and decreased safe-sex practices. Results indicate that worse neurocognitive performance in the areas of risk-taking, decision-making, and episodic memory may influence the degree to which cannabis users engage in RSB and experience negative health consequences as a result. (JINS, 2012, 18, 1-7).

Substance Abuse, Hepatitis C, and Aging in HIV: Common Cofactors that Contribute to Neurobehavioral Disturbances.

Although the prevalence of neurocognitive disturbances among individuals with HIV has decreased in recent years, rates of impairment still remain high. This review presents findings from comorbid conditions that may contribute to further neurocognitive impairments in this already vulnerable population. We will focus on three co-factors that have received substantial attention in the neuroAIDS literature: drug use, hepatitis C co-infection (HCV), and aging. All three conditions commonly co-occur with HIV and likely interact with HIV in complex ways. Collectively, the extant literature suggests that drug use, HCV, and aging serve to worsen the neurocognitive profile of HIV through several overlapping mechanisms. A better understanding of how specific comorbidities interact with HIV may reveal specific phenotypes of HIV-associated neurocognitive disorder that may aid in the development of more targeted behavioral and pharmacological treatment efforts.