Does sleep relate to next-day cannabis use during treatment? Findings from an adolescent and young adult motivational enhancement and cognitive behavioral therapy plus topiramate intervention.

BACKGROUND: Interventions for youth cannabis use have limited efficacy. Sleep is likely to affect treatment response, as sleep difficulties are cross-sectionally associated with use and common during treatment. This analysis examined how sleep duration and subjective trouble sleeping related to next-day cannabis use among youth during cannabis treatment. METHOD: Participants (N=64) received a psychosocial intervention plus topiramate versus placebo while completing a 6-week ecological momentary assessment study. Time-varying effect modeling (TVEM) examined within- and between-person associations between sleep and cannabis use and how the strength of within-person associations varied over the course of treatment. RESULTS: TVEM resvealed that, between-participants, youth with longer average sleep duration used cannabis less often controlling for baseline cannabis use, topiramate, and weekend status. Daily within-person fluctuations in sleep duration and trouble were not associated with use. CONCLUSIONS: Findings suggest regularly shorter sleep may impede treatment outcomes. Adolescents who regularly have insufficient sleep durations likely need additional intervention to improve sleep difficulties in tandem with cannabis use reduction.

N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.

Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as potential adjunctive treatments to bolster treatment outcomes. N-acetylcysteine is a promising candidate pharmacotherapy for adolescent AUD because of its tolerability and demonstrated ability to modulate glutamatergic, GABAergic, and glutathione systems. The primary objective of this double-blind, placebo-controlled, within-subjects crossover preliminary investigation was to measure potential changes within glutamate + glutamine (Glx), GABA, and glutathione levels in the dorsal anterior cingulate cortex (dACC) using proton magnetic resonance spectroscopy during 10-days of N-acetylcysteine (1200 mg twice daily) compared to 10-days of placebo in non-treatment seeking adolescents who use alcohol heavily (N = 31; 55% female). Medication adherence was confirmed via video. Effects on alcohol use were measured using Timeline Follow-Back as an exploratory aim. Linear mixed effects models controlling for baseline metabolite levels, brain tissue composition, alcohol use, cannabis use, and medication adherence found no significant differences in Glx, GABA, or glutathione levels in the dACC after N-acetylcysteine compared to placebo. There were also no measurable effects on alcohol use; however, this finding was underpowered. Findings were consistent in the subsample of participants who met criteria for AUD (n = 19). The preliminary null findings in brain metabolite levels may be due to the young age of participants, relatively low severity of alcohol use, and non-treatment seeking status of the population investigated. Future studies can use these findings to conduct larger, well-powered studies within adolescents with AUD.

Combined pharmacotherapy and evidence-based psychosocial Cannabis treatment for youth and selection of cannabis-using friends.

BACKGROUND: Theoretical models of behavior change argue that youth should decrease their time with cannabis-using friends and increase their time with non-using friends during treatment. Informed by behavior-change models of recovery and socialization and selection peer-influence models, the current study examined whether combining evidence-based psychosocial treatment with adjunctive pharmacotherapy helps youth decrease their affiliations with cannabis-using friends and increase their affiliations with non-using friends during cannabis misuse treatment. METHODS: Youth ages 15-24 years (51 % male), participated in a double-blind randomized clinical trial that tested the effects of motivational enhancement and cognitive behavioral therapy (MET-CBT) plus topiramate (N = 39) or placebo (N = 26) on cannabis craving and use. Ecological momentary assessment data, collected via smartphones throughout the six-week intervention, assessed youths' time with cannabis-using and non-using friends, cannabis use, and craving in daily life. Multiple group multilevel structural equation modeling tested study hypotheses. RESULTS: Across the topiramate (48 % completion rate) and placebo (77 % completion rate) conditions, greater time spent with cannabis-using friends promoted greater next day cannabis use and craving (socialization effect). In turn, cannabis craving, but not use, promoted continued selection of cannabis-using friends. This indirect effect was only supported in the placebo condition due to the selection piece of this cycle not being significant for youth who received topiramate. Neither cannabis craving nor use were associated with time with non-using friends the next day. CONCLUSIONS: MET-CBT and adjunctive topiramate pharmacotherapy interrupted youth selection processes. This finding suggests that changing peer affiliations could be one mechanism by which treatments can work.

Day-level shifts in social contexts during youth cannabis use treatment.

OBJECTIVE: Social context plays a critical role in youth cannabis use. Yet few studies have examined if and when social contexts shift during cannabis use treatment. This study examined daily shifts in youths' social contexts with the goal of characterizing how specific social contexts (e.g., time with cannabis-using friends or siblings) relate to cannabis craving and use during cannabis treatment. METHOD: Participants were 65 cannabis users (51% male), ages 15-24 years, who participated in a double-blind randomized clinical trial that tested the effects of motivational enhancement and cognitive behavioral therapies plus either adjunctive pharmacotherapy or placebo on cannabis craving and use. Ecological momentary assessment (EMA) data, collected from a pre-randomization period through the completion of the six-week intervention, assessed youths' social contexts, cannabis use, and craving. RESULTS: Time-varying effects models identified shifts in social contexts during treatment. Overall, time spent with cannabis-using friends and siblings decreased, where time spent with non-using friends or alone increased across the trial. Time with parents or non-using siblings was unchanged. Comparing the relative associations of social contexts with same-day craving and use, more time with cannabis-using friends and with siblings was uniquely associated with greater craving and use. CONCLUSIONS: Social context is an important factor in youth substance-use treatment. While time spent with cannabis-using friends and siblings decreased over treatment for all participants, those who continued to spend time with using individuals reported greater craving and use. This research supports increased attention to shifting youths' social contexts to enhance treatment success. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Appetitive startle modulation in the human laboratory predicts Cannabis craving in the natural environment.

RATIONALE: Drug-related cues evoke craving and stimulate motivational systems in the brain. The acoustic startle reflex captures activation of these motivational processes and affords a unique measure of reactivity to drug cues. OBJECTIVES: This study examined the effects of cannabis-related cues on subjective and eye blink startle reactivity in the human laboratory and tested whether these effects predicted youth's cue-elicited cannabis craving in the natural environment. METHODS: Participants were 55 frequent cannabis users, ages 16 to 24 years (M = 19.9, SD = 1.9; 55% male; 56% met criteria for cannabis dependence), who were recruited from a clinical trial to reduce cannabis use. Eye blink electromyographic activity was recorded in response to acoustic probes that elicited startle reactivity while participants viewed pleasant, unpleasant, neutral, and cannabis picture cues. Following the startle assessment, participants completed an ecological momentary assessment protocol that involved repeated assessments of cue-elicited craving in real time in their real-world environments. RESULTS: Multilevel models included the presence or absence of visible cannabis cues in the natural environment, startle magnitude, and the cross-level interaction of cues by startle to test whether cue-modulated startle reactivity in the laboratory was associated with cue-elicited craving in the natural environment. Analyses showed that cannabis-related stimuli evoked an appetitive startle response pattern in the laboratory, and this effect was associated with increased cue-elicited craving in the natural environment, b = - 0.15, p = .022, 95% CI [- 0.28, - 0.02]. Pleasant stimuli also evoked an appetitive response pattern, but in this case, blunted response was associated with increased cue-elicited craving in the natural environment, b = 0.27, p < .001, 95% CI [0.12, 0.43]. CONCLUSIONS: Our findings support cue-modulated startle reactivity as an index of the phenotypic expression of cue-elicited cannabis craving.

Using Ecological Momentary Assessment to Identify Mechanisms of Change: An Application From a Pharmacotherapy Trial With Adolescent Cannabis Users.

OBJECTIVE: The present study used youth's in vivo reports of subjective responses to cannabis while smoking in their natural environments to identify real-world mechanisms of topiramate treatment for cannabis misuse. METHOD: Participants were 40 cannabis users (≥ twice weekly in past 30 days), ages 15-24 years (47.5% female), with at least one cannabis use episode during the final 3 weeks of a 6-week, randomized clinical trial. Youth reported subjective "high" while smoking, stimulation, sedation, stress, craving, and grams of marijuana used in the natural environment via wireless electronic devices. Bayesian multilevel structural equation modeling (MSEM) evaluated mediation via indirect effect tests. RESULTS: Significant within (daily) and between (person) variability and distinctive within and between effects supported the MSEM approach. Subjective high while smoking was significantly reduced for youth in the topiramate condition, relative to placebo, and the indirect effect of reduced subjective high on total grams of cannabis smoked that day was significant. Indirect effects through other subjective responses were not significant. CONCLUSIONS: The results of this initial study suggest that altering subjective responses to smoking, specifically subjective high, may be a key target for developing adjunctive pharmacotherapies for cannabis misuse. More generally, this work provides an example for applying ecological momentary assessment and analytic techniques to evaluate mechanisms of behavior change in longitudinal data.

Topiramate and motivational enhancement therapy for cannabis use among youth: a randomized placebo-controlled pilot study.

Cannabis misuse accounts for nearly all of the substance abuse treatment admissions among youth in the United States. Most youth do not experience sustained benefit from existing psychosocial treatments; however, medication development research for treating adolescent cannabis misuse is almost nonexistent. We conducted a double-blind, placebo-controlled, pilot study to test the potential efficacy of topiramate plus motivational enhancement therapy (MET) for treating cannabis use among adolescents. Sixty-six heavy cannabis users, ages 15 to 24 years, were randomized to one of two 6-week treatment conditions: topiramate plus MET or placebo plus MET. Topiramate was titrated over 4 weeks then stabilized at 200 mg/day for 2 weeks. MET was delivered biweekly for a total of three sessions. Only 48 percent of youths randomized to topiramate completed the 6-week trial (n = 19), compared with 77 percent of youths in the placebo condition (n = 20). Adverse medication side effects were the most common reason for withdrawal among participants in the topiramate group. Latent growth models showed that topiramate was superior to placebo for reducing the number of grams smoked per use day, but it did not improve abstinence rates. The same pattern of results was found when values for missing outcomes were imputed. We show that topiramate combined with MET demonstrated efficacy for reducing how much cannabis adolescents smoked when they used but did not affect abstinence rates. The magnitude of this effect was modest, however, and topiramate was poorly tolerated by youths, which calls into question the clinical importance of these findings.

Arginine vasotocin induces calling behavior with a female social stimulus and interacts with gonadotropins to affect sexual behaviors in male Xenopus tropicalis.

Arginine vasotocin (AVT) and the mammalian homologue, arginine vasopressin (AVP), modulate vertebrate social behaviors, including vocalizations in male anurans. To study the impact of AVT and social stimuli on calling in male Xenopus tropicalis, we injected males with vehicle, 1 µg, or 10 µg AVT and recorded vocalizations under four social contexts (no stimulus, with male call playback, with a female, and with call playback and a female). More males called when injected with 10 µg AVT. Furthermore, calling males called only when paired with a female. We identified four call types: long fast trill; short fast trill; slow trill; or click. Next, we injected males with vehicle, 10 µg, or 20 µg AVT and recorded vocalizations with or without a female. AVT treatment did not affect calling in this experiment, but we confirmed that more males, regardless of AVT treatment, called when a female was present. Then we evaluated the effect of human chorionic gonadotropin (hCG) on male sexual behavior. 20 IU hCG elevated behavior compared to controls while the 10 IU hCG treatment group was not different from either treatment. Last, we examined the effect of AVT on hCG-induced reproductive behavior. Males were injected with 10 IU hCG or with 10 IU hCG and 20 µg AVT. Males receiving hCG and AVT clasped and called significantly more than males receiving hCG only. Our results suggest that AVT and a female stimulus induce vocalizations in a male pipid anuran, X. tropicalis, and the interaction between gonadotropins and neurohormones influences reproductive behaviors in this anuran amphibian.

Spirituality and treatment of addictive disorders.

Spirituality is generally protective against the initiation of alcohol and drug use and progression to disordered use. In addition, mutual-help organizations, such as Alcoholics Anonymous, were founded on spiritual principles, and reliance on a "higher power" is a central component of the 12 steps. Despite this, spirituality is not commonly addressed in formal treatment of addictions. The purpose of this paper is to provide a summary of the role of spirituality in the development and recovery from addictive disorders for health care professionals.

Diagnostic orphans for alcohol use disorders in a treatment-seeking psychiatric sample.

Individuals who endorse one or two of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criterion items for alcohol dependence but do not meet criteria for either alcohol abuse or dependence have been referred to in the literature as "diagnostic orphans." The goal of the present study is to compare diagnostic orphans for alcohol use disorders (AUD) to patients with lifetime DSM-IV alcohol abuse, alcohol dependence, and those with no-AUD symptoms on a series of demographic, diagnostic, and clinical measures. Participants were treatment-seeking psychiatric outpatients (n=1793; 61.5% women) who completed an in-depth, face-to-face diagnostic evaluation for DSM-IV axis I and axis II disorders. Results revealed that diagnostic orphans were younger, had a higher frequency of family history positive for alcoholism, and higher rates of cannabis dependence, as compared to the no-AUD symptoms group. Diagnostic orphans differed significantly from patients with alcohol abuse and dependence on a number of demographic, diagnostic, and clinical measures. Most notably, on a lifetime basis, diagnostic orphans were less likely to meet diagnostic criteria for various substance use disorders, as compared to individuals with alcohol abuse and dependence. Taken together, these results generally do not support combining diagnostic orphans to individuals with alcohol abuse.

Randomized Clinical Trial of Motivational Enhancement of Substance Use Treatment Among Incarcerated Adolescents: Post-Release Condom Non-Use.

Evaluated impact of motivational enhancement (ME) of substance abuse treatment compared to relaxation training (RT) on sex without condoms (overall and involving substance use) 3 months following release among incarcerated adolescents. This randomized clinical trial involved 114 incarcerated adolescents from the Northeast. Regression analyses determined if treatment condition, baseline levels of depressive symptoms, and their interaction predicted condom non-use 3 months post-release, controlling for baseline condom non-use. Among those who reported fewer baseline depressive symptoms, those in ME condition reported significantly less condom non-use, in general and involving marijuana use compared with those in RT condition. Periods of incarceration represent opportunities to help juvenile detainees reduce behaviors that impact their health and the health of those with whom they interact in the community.

Altered affective modulation of the startle reflex in alcoholics with antisocial personality disorder.

BACKGROUND: Individual differences in neural circuitry that regulate emotional reactivity may be associated with alcoholism and antisocial personality disorder (ASPD), a common comorbid condition. The emotion-modulated startle reflex was used to investigate emotional reactivity among alcohol-dependent (AD) men with and without ASPD. METHODS: Sixty-two men were tested: (1) AD (n = 24), (2) AD-ASPD (n = 17), and (3) non-AD, non-ASPD controls (n = 21). Participants completed self-report instruments and clinical interviews and had eye-blink electromyograms measured in response to acoustic startle probes while viewing color photographs rated as affectively pleasant, neutral, and unpleasant. RESULTS: Startle blink magnitudes were larger during unpleasant as compared with pleasant slides for control and AD groups, resulting in significant linear trend effects (p < 0.001) and nonsignificant quadratic trend effects. In contrast, AD-ASPD did not show a significant difference in blink magnitude during unpleasant and pleasant slides and did not show a significant linear valence trend or quadratic trend effect (p > 0.6). Subjective valence and arousal ratings of the photographs were similar across groups. CONCLUSIONS: Adult male alcoholics with ASPD have abnormal emotional responsiveness to both pleasant and unpleasant stimuli relative to alcoholics without ASPD and to controls.

Altered emotion-modulated startle in young adults with a family history of alcoholism.

BACKGROUND: Alcoholism risk may be accompanied by poor regulation of emotions, signaling altered central nervous system processes. This study used the emotion-modulated startle paradigm to test the hypothesis that young adults with a positive paternal history of alcoholism (FH+), relative to family-history-negative persons (FH-), have altered emotional reactivity to environmental cues. METHODS: We tested 30 FH+ and 30 FH-, 15 males and 15 females in each group. Participants completed self-report instruments and interviews and had eye blink electromyograms (EMG) measured to acoustic startle probes while viewing color photographs rated as affectively pleasant, neutral, and unpleasant. RESULTS: FH- had the expected linear increase in startle magnitude, with eye blink EMG gaining in strength (F = 18, p < 0.0002) from pleasant to neutral to unpleasant slides. In contrast, FH+ did not show EMG potentiation to the unpleasant slides and therefore lacked the same linear trend (F < 1, p > 0.4). Notably, FH groups rated the emotional valence and arousal of the photographs in similar ways. Self-reported negative affect partly accounted for the lack of startle potentiation in FH+, suggesting that startle modulation differences between the groups may be associated with underlying psychological characteristics. CONCLUSIONS: These findings implicate altered limbic outputs to the startle pathway in FH+ despite normal conscious evaluation of emotional arousal and pleasantness of the slides. This method may provide a useful paradigm for testing processing of emotionally relevant stimuli in relation to risk for alcohol use disorders.