Treatment of Adolescent Cannabis Use Disorders.

This review summarizes treatments for cannabis use disorder (CUD) in adolescents. The best supported CUD treatments are cognitive behavioral psychotherapies, including family-based models that facilitate environmental changes and youth-focused models that incorporate skills training, motivational interviewing, and contingency management to promote reductions in cannabis use. Some medications show promise in reducing cannabis craving and withdrawal symptoms. Further research is needed on the efficacy and implementation of existing treatments given the changes in cannabis use trends over time and on emerging technologies that may expand access to evidence-based CUD treatments.

Program Evaluation to Aid Choice of Aripiprazole or Risperidone for Hospitalized Adolescents with Cannabis Use Disorder and Psychosis.

Introduction: Co-occurring cannabis use and psychosis is an increasing problem. No single behavioral or pharmacologic treatment has emerged as clearly superior. To address the gap, this nonrandomized, quality improvement project compares outcomes for adolescents with co-occurring cannabis use disorder and psychosis prescribed risperidone or aripiprazole. Materials and Methods: This project is a retrospective chart review of 110 adolescents (ages 13-21 years) hospitalized for psychosis and co-occurring cannabis use disorder. The primary outcomes are length of stay and length of stay index. Results: Adolescents prescribed risperidone compared with aripiprazole had a significantly greater length of stay (9.7 days vs. 5.8 days, p = 0.002) and length of stay index (1.4 vs. 0.79, p = 0.004). Conclusions: Adolescents hospitalized for co-occurring psychosis and cannabis use disorder had a significantly longer length of stay and length of stay index. These data are consistent with a more rapid reduction in acute psychotic symptoms for aripiprazole compared with risperidone in the context of co-occurring cannabis use disorder.

Cannabis self-administration in the human laboratory: a scoping review of ad libitum studies.

Cannabis self-administration studies may be helpful for identifying factors that influence cannabis consumption and subjective response to cannabis. Additionally, these paradigms could be useful for testing novel pharmacotherapies for cannabis use disorder. This scoping review aims to summarize the findings from existing ad libitum cannabis self-administration studies to determine what has been learned from these studies as well as their limitations. We examined studies that specifically examined cannabis smoking, focusing on subjective response and self-administration behavior (e.g., smoking topography). A systematic search was conducted using PubMed and Embase from inception to October 22, 2022. Our search strategy identified 26 studies (total N = 662, 79% male) that met our eligibility criteria. We found that tetrahydrocannabinol (THC) concentration significantly affected subjective response to cannabis in some but not all studies. In general, cannabis self-administration tended to be most intense at the beginning of the laboratory session and decreased in later parts of the session. There was limited data on cannabis self-administration in adults older than 55. Data on external validity and test-retest reliability were also limited. Addressing these limitations in future ad libitum cannabis self-administration studies could lead to more valid and generalizable paradigms, which in turn could be used to improve our understanding of cannabis use patterns and to help guide medication development for cannabis use disorder.

An analysis of cannabinoid hyperemesis syndrome Reddit posts and themes.

INTRODUCTION: Reddit hosts a large active community of members dedicated to the discussion of cannabinoid hyperemesis syndrome. We sought to describe common themes discussed and the most frequently mentioned triggers and therapies for cannabinoid hyperemesis syndrome exacerbations in the Reddit online community. METHODS: Data collected from six subreddits were filtered using natural language processing to curate posts referencing cannabinoid hyperemesis syndrome. Based on a manual review of posts, common themes were identified. A machine learning model was trained using the manually categorized data to automatically classify the themes for the rest of the posts so that their distributions could be quantified. RESULTS: From August 2018 to November 2022, 2683 unique posts were collected. Thematic analysis resulted in five overall themes: cannabinoid hyperemesis syndrome-related science; symptom timing; cannabinoid hyperemesis syndrome treatment and prevention; cannabinoid hyperemesis syndrome diagnosis and education; and health impacts. Additionally, 447 trigger and 664 therapy-related posts were identified. The most commonly mentioned triggers for cannabinoid hyperemesis syndrome episodes included: food and drink (n = 62), cannabinoids (n = 45), mental health (e.g., stress, anxiety) (n = 27), and alcohol (n = 22). Most commonly mentioned cannabinoid hyperemesis syndrome therapies included: hot water/bathing (n = 62), hydration (n = 60), antiemetics (n = 42), food and drink (n = 38), gastrointestinal medications (n = 38), behavioral therapies (e.g., meditation, yoga) (n = 35), and capsaicin (n = 29). DISCUSSION: Reddit posts for cannabinoid hyperemesis syndrome provide a valuable source of community discussion and individual reports of people experiencing cannabinoid hyperemesis syndrome. Mental health and alcohol were frequently reported triggers within the posts but are not often identified in the literature. While many of the therapies mentioned are well documented, behavioral responses such as meditation and yoga have not been explored by the scientific literature. CONCLUSIONS: Knowledge shared via online social media platforms contains detailed information on self-reported cannabinoid hyperemesis syndrome disease and management experiences, which could serve as valuable data for the development of treatment strategies. Further longitudinal studies in patients with cannabinoid hyperemesis syndrome are needed to corroborate these findings.

Effects of cannabidiol on anandamide levels in individuals with cannabis use disorder: findings from a randomised clinical trial for the treatment of cannabis use disorder.

Cannabidiol (CBD) has shown promise in treating psychiatric disorders, including cannabis use disorder - a major public health burden with no approved pharmacotherapies. However, the mechanisms through which CBD acts are poorly understood. One potential mechanism of CBD is increasing levels of anandamide, which has been implicated in psychiatric disorders including depression and cannabis use disorder. However, there is a lack of placebo-controlled human trials investigating this in psychiatric disorders. We therefore assessed whether CBD affects plasma anandamide levels compared to placebo, within a randomised clinical trial of CBD for the treatment of cannabis use disorder. Individuals meeting criteria for cannabis use disorder and attempting cannabis cessation were randomised to 28-day administration with placebo (n = 23), 400 mg CBD/day (n = 24) or 800 mg CBD/day (n = 23). We estimated the effects of each CBD dose compared to placebo on anandamide levels from baseline to day 28. Analyses were conducted both unadjusted and adjusted for cannabis use during the trial to account for effects of cannabis on the endocannabinoid system. We also investigated whether changes in plasma anandamide levels were associated with clinical outcomes relevant for cannabis use disorder (cannabis use, withdrawal, anxiety, depression). There was an effect of 800 mg CBD compared to placebo on anandamide levels from baseline to day 28 after adjusting for cannabis use. Pairwise comparisons indicated that anandamide levels unexpectedly reduced from baseline to day 28 in the placebo group (-0.048, 95% CI [-0.089, -0.007]), but did not change in the 800 mg CBD group (0.005, 95% CI [-0.036, 0.047]). There was no evidence for an effect of 400 mg CBD compared to placebo. Changes in anandamide levels were not associated with clinical outcomes. In conclusion, this study found preliminary evidence that 28-day treatment with CBD modulates anandamide levels in individuals with cannabis use disorder at doses of 800 mg/day but not 400 mg/day compared to placebo.

Effect of four-week cannabidiol treatment on cognitive function: secondary outcomes from a randomised clinical trial for the treatment of cannabis use disorder.

RATIONALE: Chronic cannabis use is associated with impaired cognitive function. Evidence indicates cannabidiol (CBD) might be beneficial for treating cannabis use disorder. CBD may also have pro-cognitive effects; however, its effect on cognition in people with cannabis use disorder is currently unclear. OBJECTIVES: We aimed to assess whether a 4-week CBD treatment impacted cognitive function. We hypothesised that CBD treatment would improve cognition from baseline to week 4, compared to placebo. METHODS: Cognition was assessed as a secondary outcome in a phase 2a randomised, double-blind, parallel-group and placebo-controlled clinical trial of 4-week daily 200 mg, 400 mg and 800 mg CBD for the treatment of cannabis use disorder. Participants had moderate or severe DSM-5 cannabis use disorder and intended to quit cannabis use. Our pre-registered primary cognitive outcome was delayed prose recall. Secondary cognitive outcomes were immediate prose recall, stop signal reaction time, trail-making task performance, verbal fluency and digit span. RESULTS: Seventy participants were randomly assigned to placebo (n = 23), 400 mg CBD (n = 24) and 800 mg CBD (n = 23). A 200 mg group was eliminated from the trial because it was an inefficacious dose at interim analysis (n = 12) and was not analysed here. For the primary cognitive outcome, there was no effect of CBD compared to placebo, evidenced by a lack of dose-by-time interaction at 400 mg (0.46, 95%CIs: - 1.41, 2.54) and 800 mg (0.89, 95%CIs: - 0.99, 2.81). There was no effect of CBD compared to placebo on secondary cognitive outcomes, except backwards digit span which increased following 800 mg CBD (0.30, 95%CIs: 0.02, 0.58). CONCLUSIONS: In this clinical trial for cannabis use disorder, CBD did not influence delayed verbal memory. CBD did not have broad cognitive effects but 800 mg daily treatment may improve working memory manipulation. CLINICAL TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000,361-36).

Unravelling the landscape of Cannabis craving pharmacological treatments: a PRISMA-guided review of evidence.

Currently, few treatments are available for craving in general, and none of them have received approval for cannabis craving. The objective of this review is to evaluate existing studies analysing treatments for cannabis craving and explore novel treatment possibilities for these patients. The study followed PRISMA guidelines and conducted an extensive database search. Inclusion criteria included human randomised controlled trials examining drug effects on craving symptoms. Exclusion criteria involved studies unrelated to craving, non-pharmacological treatments, duplicates, and non-English/Spanish/Portuguese articles. Our included 22 studies that investigated a wide range of compounds used for cravings related to other drugs, as well as interventions based on healthcare professionals' empirical knowledge. The current pharmacological treatments largely involve off-label drug use and the utilisation of cannabinoid-based medications, such as combinations of THC and lofexidine, oxytocin, progesterone, and N-acetylcysteine. These emerging treatments show promise and have the potential to revolutionise current clinical practices, but further investigation is needed to establish their efficacy. In this context, it is essential to consider non-pharmacological interventions, such as psychotherapy and behavioural treatments. These approaches play a crucial role in complementing pharmacological interventions and addressing the complex nature of the disorder.

Correlates of treatment engagement and client outcomes: results of a randomised controlled trial of nabiximols for the treatment of cannabis use disorder.

INTRODUCTION AND AIMS: There is increasing interest and evidence for the use of cannabinoid medications in the treatment of cannabis use disorder, but little examination of the correlates of successful treatment. This paper is a secondary analysis of a randomised placebo-controlled trial of nabiximols for the treatment of cannabis use disorder (CUD), aiming to identify which client and treatment characteristics impact treatment engagement and outcomes. METHOD: Bayesian multiple regression models were used to examine the impact of age, gender, duration of regular cannabis use, daily quantity of cannabis, cannabis use problems, self-efficacy for quitting, sleep, mental health, pain measures, and treatment group upon treatment engagement (retention, medication dose, and counselling participation) and treatment outcomes (achieving end-of-study abstinence, and a 50% or greater reduction in cannabis use days) among the 128 clients participating in the 12-week trial. RESULTS: Among the treatment factors, greater counselling attendance was associated with greater odds of abstinence and ≥ 50% reduction in cannabis use; nabiximols with greater odds of ≥ 50% reduction and attending counselling, and reduced hazard of treatment dropout; and higher dose with lower odds of ≥ 50% reduction. Among the client factors, longer duration of regular use was associated with higher odds of abstinence and 50% reduction, and lower hazard of treatment dropout; greater quantity of cannabis use with reduced hazard of dropout, greater odds of attending counselling, and higher average dose; greater pain at baseline with greater odds of ≥ 50% reduction and higher average dose; and more severe sleep issues with lower odds of ≥ 50% reduction. Males had lower odds of attending counselling. DISCUSSIONS AND CONCLUSIONS: These findings suggest that counselling combined with agonist pharmacotherapy may provide the optimal treatment for cannabis use disorder. Younger clients, male clients, and clients with sleep issues could benefit from extra support from treatment services to improve engagement and outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au.

Assessment of patient perception of treatment assignment and patient-reported outcomes in a cannabis use disorder trial.

Background: Blinding is a cornerstone of trial methodology. Prior work indicates participant-perceived assignment may be associated with trial outcomes. Less is known about how perception changes over time and if this is associated with outcomes.Objectives: To evaluate if participants change their perception of assignment over time in a blinded trial, and if perception is associated with different types of patient-reported outcomes (PROs).Methods: This was a secondary analysis of data from the Achieving Cannabis Cessation-Evaluating N-Acetylcysteine Treatment (ACCENT) trial, which evaluated the efficacy of N-acetylcysteine (NAC) relative to placebo for treating cannabis use disorder. Participants (N = 234; 164 men, 70 women) were asked at weeks 5 and 9 what treatment (placebo or NAC) they believed they were receiving. We included PROs proximal (cannabis-associated problems, craving) and distal (anxiety) to the intervention. Analysis was by multiple linear regression and mixed models.Results: Approximately 20% of participants in both arms changed their perception over time. Relative to participants who consistently perceived assignment to placebo, participants who consistently perceived assignment to NAC did not always have comparatively better average scores (coefficient -3.3 [95% CI: -7.0, 0.5]). In some analyses, participants who switched to guessing NAC from placebo had comparatively better average scores (coefficient -3.0 [95% CI: -9.3, 3.4]), but this was inconsistent across outcomes or strata defined by actual assignment or guess accuracy.Conclusion: The study suggests that the proportion of individuals who switch their perception over time is modest. However, this group may influence the estimates of intervention effects on some PROs.

Trazodone Prolonged-Release Monotherapy in Cannabis Dependent Patients during Lockdown Due to COVID-19 Pandemic: A Case Series.

(1) Background: During the SARS-CoV-2 (COVID-19) pandemic, cannabis use increased relative to pre-pandemic levels, while forced home confinement frequently caused sleep/wake cycle disruptions, psychological distress, and maladaptive coping strategies with the consequent appearance of anxiety symptoms and their potential impact on substance use problems. (2) Aim: Long-acting trazodone (150 mg or 300 mg daily) has a potential benefit as monotherapy in patients with cannabis use disorder. The present work aims to investigate the effectiveness of trazodone in optimizing the condition of people with cannabis dependence under pandemic conditions. (3) Methods: All cases with cannabis use disorder were uniformly treated with long-acting trazodone 150 mg or 300 mg/day; their craving and clinical status were monitored through appropriate psychometric scales. Side effects were recorded as they were reported by patients. We described the cases of three young patients-one man and two women-who were affected by chronic cannabis use disorder and who experienced lockdown-related psychological distress and sought psychiatric help. (4) Results: The described cases highlight that the once-a-day formulation of trazodone seems to have a therapeutic role in patients with cannabis use disorder and to guarantee tolerability and efficacy over time. No significant side effects emerged. (5) Conclusions: The use of long-acting trazodone (150 mg or 300 mg daily) has a potential benefit as monotherapy in patients with cannabis use disorder. Trazodone deserves to be studied in terms of its efficacy for cannabis use disorder.

Synaptic changes induced by cannabinoid drugs and cannabis use disorder.

The legalization of cannabis in many countries, as well as the decrease in perceived risks of cannabis, have contributed to the increase in cannabis use medicinally and recreationally. Like many drugs of abuse, cannabis and cannabis-derived drugs are prone to misuse, and long-term usage can lead to drug tolerance and the development of Cannabis Use Disorder (CUD). These drugs signal through cannabinoid receptors, which are expressed in brain regions involved in the neural processing of reward, habit formation, and cognition. Despite the widespread use of cannabis and cannabinoids as therapeutic agents, little is known about the neurobiological mechanisms associated with CUD and cannabinoid drug use. In this article, we discuss the advances in research spanning animal models to humans on cannabis and synthetic cannabinoid actions on synaptic transmission, highlighting the neurobiological mechanisms following acute and chronic drug exposure. This article also highlights the need for more research elucidating the neurobiological mechanisms associated with CUD and cannabinoid drug use.

Results from a randomized, double-blind, placebo-controlled, crossover, multimodal-MRI pilot study of gabapentin for co-occurring bipolar and cannabis use disorders.

Disrupted brain gamma-aminobutyric acid (GABA)/glutamate homeostasis is a promising target for pharmacological intervention in co-occurring bipolar disorder (BD) and cannabis use disorder (CUD). Gabapentin is a safe and well-tolerated medication, FDA-approved to treat other neurological diseases, that restores GABA/glutamate homeostasis, with treatment studies supporting efficacy in treating CUD, as well as anxiety and sleep disorders that are common to both BD and CUD. The present manuscript represents the primary report of a randomized, double-blind, placebo-controlled, crossover (1-week/condition), multimodal-MRI (proton-MR spectroscopy, functional MRI) pilot study of gabapentin (1200 mg/day) in BD + CUD (n = 22). Primary analyses revealed that (1) gabapentin was well tolerated and adherence and retention were high, (2) gabapentin increased dorsal anterior cingulate cortex (dACC) and right basal ganglia (rBG) glutamate levels and (3) gabapentin increased activation to visual cannabis cues in the posterior midcingulate cortex (pMCC, a region involved in response inhibition to rewarding stimuli). Exploratory evaluation of clinical outcomes further found that in participants taking gabapentin versus placebo, (1) elevations of dACC GABA levels were associated with lower manic/mixed and depressive symptoms and (2) elevations of rBG glutamate levels and pMCC activation to cannabis cues were associated with lower cannabis use. Though promising, the findings from this study should be interpreted with caution due to observed randomization order effects on dACC glutamate levels and identification of statistical moderators that differed by randomization order (i.e. cigarette-smoking status on rBG glutamate levels and pMCC cue activation). Nonetheless, they provide the necessary foundation for a more robustly designed (urn-randomized, parallel-group) future study of adjuvant gabapentin for BD + CUD.

Influence of pregabalin maintenance on cannabis effects and related behaviors in daily cannabis users.

No medications are approved for cannabis use disorder (CUD), though a small clinical trial demonstrated that the voltage-dependent calcium channel (VDCC) ligand gabapentin reduced cannabis use in treatment seekers. VDCCs are modulated by cannabinoid (CB) ligands, and there are shared effects between CB agonists and VDCC ligands. This overlapping neuropharmacology and the initial clinical results supported the evaluation of pregabalin, a "next-generation" VDCC ligand, as a CUD medication. Two separate placebo-controlled, double-blind, counterbalanced, within-subjects human laboratory studies tested placebo and 300 (N = 2 females, 11 males; Experiment [EXP] 1) or 450 (N = 3 females, 11 males; EXP 2) mg/day pregabalin in cannabis users who were not seeking treatment or trying to reduce/quit their cannabis use. The protocol consisted of two outpatient maintenance phases (11 days in EXP 1 and 15 days in EXP 2) that concluded with four experimental sessions within each phase. During experimental sessions, maintenance continued, and participants completed two 2-day blocks of sampling and self-administration sessions to determine the reinforcing effects of smoked cannabis (0% and 5.9% delta9-tetrahydrocannabinol [THC]), as well as subjective, attentional bias, performance, and physiological responses. In addition, naturalistic cannabis use, side effects, sleep quality, craving, and other self-reported substance use were measured during pregabalin maintenance. Cannabis was self-administered and produced prototypical effects, but pregabalin generally did not impact the effects of cannabis or alter naturalistic use. These human laboratory results in cannabis users not trying to reduce/quit their use do not support the efficacy of pregabalin as a stand-alone pharmacotherapy for CUD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cannabis hyperemesis syndrome: Incidence and treatment with topical capsaicin. / Síndrome de hiperémesis por cannabis: incidencia y tratamiento con capsaicina tópica.

There are few studies in Spain on cannabinoid hyperemesis syndrome (CHS), as well as on the use of topical capsaicin as a treatment. METHODS: Retrospective study of patients over 14 years of age seen in a hospital emergency department during 2018 and 2019 with a diagnosis of CHS based on the following criteria: compatible clinical picture, cannabis use less than 48h and positive urine cannabis test. Epidemiological and clinical variables, attendance times and treatment (including use of topical capsaicin 0.075%) were collected. RESULTS: Fifty-nine attendances were studied, from 29 patients (4.4 cases/10,000 visits, 95% CI 2.8-4.7). Fifty per cent returned for CHS, differing only in more tobacco (P=.01) and cocaine (P=.031) use. Capsaicin was used in 74.6% of visits. The mean time to resolution of vomiting after application was 17.87min. CONCLUSIONS: Although probably underdiagnosed, CHS has a low incidence in the emergency department in Spain, with high patient recurrence. The use of capsaicin ointment is efficient and safe.

Cannabinoids for the treatment of cannabis use disorder: New avenues for reaching and helping youth?

Cannabis use peaks during adolescence and emerging adulthood, and cannabis use disorder (CUD) is associated with a wide range of adverse outcomes. This is particularly pertinent in youth, because the developing brain may be more vulnerable to adverse effects of frequent cannabis use. Combining evidence-based psychosocial interventions with safe and effective pharmacotherapy is a potential avenue to improve youth outcomes, but we lack approved CUD pharmacotherapies. Here, we review new potential avenues for helping youth with CUD, with a particular focus on cannabinoid-based treatments. Evidence from placebo-controlled RCTs suggests synthetic delta-9-tetrahydrocannabinol (THC) decreases withdrawal symptoms, but not cannabis use, in adults with daily cannabis use/CUD, while findings regarding formulations containing THC combined with cannabidiol (CBD) are mixed. Preliminary evidence from two placebo-controlled RCTs in adults with CUD suggests that both Fatty Acid Amide Hydrolase inhibitors and CBD can reduce cannabis use. However, larger trials are needed to strengthen the evidence. Findings from adults point to cannabinoid-based treatments as a potential strategy that should be examined in youth with CUD.

Varenicline as a treatment for cannabis use disorder: A placebo-controlled pilot trial.

BACKGROUND: An efficacious pharmacotherapy for cannabis use disorder (CUD) has yet to be established. This study preliminarily evaluated the safety and efficacy of varenicline for CUD in a proof-of-concept clinical trial. METHODS: Participants in this 6-week randomized, placebo-controlled pilot trial received either varenicline (n = 35) or placebo (n = 37), added to a brief motivational enhancement therapy intervention. Outcomes included cannabis withdrawal, cannabis abstinence, urine cannabinoid levels, percent cannabis use days, and cannabis sessions per day. RESULTS: Both treatment groups noted significant decreases in self-reported cannabis withdrawal, percentage of days used, and use sessions per day during treatment compared to baseline. While this pilot trial was not powered to detect statistically significant between-group differences, participants randomized to varenicline evidenced numerically greater rates of self-reported abstinence at the final study visit [Week 6 intent-to-treat (ITT): Varenicline: 17.1% vs. Placebo: 5.4%; RR = 3.2 (95% CI: 0.7,14.7)]. End-of-treatment urine creatinine corrected cannabinoid levels were numerically lower in the varenicline group and higher in the placebo group compared to baseline [Change from baseline: Varenicline -1.7 ng/mg (95% CI: -4.1,0.8) vs. Placebo: 1.9 ng/mg (95% CI: -0.4,4.3); Δ = 3.5 (95% CI: 0.1,6.9)]. Adverse events related to study treatment did not reveal new safety signals. CONCLUSIONS: Findings support the feasibility of conducting clinical trials of varenicline as a candidate pharmacotherapy for CUD, and indicate that a full-scale efficacy trial, powered based on effect sizes and variability yielded in this study, is warranted.

Treatment of Cannabinoid Hyperemesis With Olanzapine: A Case Series.

The use and availability of cannabis for recreational and medical purposes has become more widespread with increased legalization. Adverse health outcomes of this increased use include cannabinoid hyperemesis syndrome (CHS), which is underrecognized in medical settings. Cessation of substance use is the recommendation of choice for the complete resolution of CHS. However, interventions that provide rapid relief may be necessary in treatment-refractory cases. Little evidence is available to guide care in these cases. Here we report 4 cases of treatment-refractory CHS, all of which remitted after treatment with olanzapine. Olanzapine is known to block multiple neurotransmitter receptors involved in nausea and vomiting in chemotherapy-induced nausea and vomiting. Outcomes of the cases reported here suggest that off-label use of olanzapine may be effective in the symptomatic treatment of refractory CHS and may be the preferred treatment in cases in which comorbid psychotic symptoms or agitation are present.

Non-abstinent treatment outcomes for cannabis use disorder.

BACKGROUND: Abstinence remains a standard outcome for potential treatment interventions for Cannabis Use Disorder (CUD). However, there needs to be validation of non-abstinent outcomes. This study explores reductions in self-reported days of use as another viable outcome measure using data from three completed randomized placebo-controlled clinical trials of pharmacological interventions for CUD. METHODS: The three trials tested the effect of quetiapine (QTP, n = 113); dronabinol (DRO, n = 156); and lofexidine + dronabinol (LFD, n = 122). Self-reported cannabis use was categorized into three use-groups/week: heavy (5-7 days/week), moderate (2-4 days/week) and light use (0-1 days/week). Multinomial logistic regressions analyzed the treatment by time effect on the likelihood of light and moderate use compared to heavy use in each study. RESULTS: Across the three trials, there was no significant overall time-by-treatment interaction (QTP: p = .06; DRO: p = .15; LFD: p = .21). However, the odds of moderate compared to heavy use were significantly higher in treatment than in placebo groups starting around the midpoint of each trial. No treatment differences were found between the odds of light compared to heavy use. CONCLUSIONS: While study-end abstinence rates have been a standard treatment outcome for CUD trials, reduction from heavy to moderate use has not been standardly assessed. During the last several weeks of each trial, those on active medication were more likely to move from heavy to moderate use, which suggests that certain medications may be more impactful than previously assessed. Future studies should determine if this pattern is associated with less CUD severity and/or improved quality of life.

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.