Treatment Of Cannabis Use Disorder Research Articles

Sex- and Gender-Based Analysis in Cannabis Treatment Outcomes: A Systematic Review

There is evidence that sex- and gender-related factors are involved in cannabis patterns of use, health effects and biological mechanisms. Women and men report different cannabis use disorder (CUD) symptoms, with women reporting worse withdrawal symptoms than men. The objective of this systematic review was to examine the effectiveness of cannabis pharmacological interventions for women and men and the uptake of sex- and gender-based analysis in the included studies. Two reviewers performed the full-paper screening, and data was extracted by one researcher. The search yielded 6098 unique records—of which, 68 were full-paper screened. Four articles met the eligibility criteria for inclusion. From the randomized clinical studies of pharmacological interventions, few studies report sex-disaggregated outcomes for women and men. Despite emergent evidence showing the influence of sex and gender factors in cannabis research, sex-disaggregated outcomes in pharmacological interventions is lacking. Sex- and gender-based analysis is incipient in the included articles. Future research should explore more comprehensive inclusion of sex- and gender-related aspects in pharmacological treatments for CUD.

Depressive symptoms and cannabis use in a placebo-controlled trial of N-Acetylcysteine for adult cannabis use disorder.

Depression is common among individuals with cannabis use disorder (CUD), particularly individuals who present to CUD treatment. Treatments that consider this comorbidity are essential. The goal of this secondary analysis was to examine whether N-acetylcysteine (NAC) reduced depressive symptoms among adults (age 18-50) with CUD (N = 302) and whether the effect of NAC on cannabis cessation varied as a result of baseline levels of depression. Bidirectional associations between cannabis use amount and depression were also examined. Data for this secondary analysis were from a National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) multi-site clinical trial for CUD. Adults with CUD (N = 302) were randomized to receive 2400mg of NAC daily or matched placebo for 12weeks. All participants received abstinence-based contingency management. Cannabis quantity was measured by self-report, and weekly urinary cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) confirmed abstinence. Depressive symptoms were measured by the Hospital Anxiety and Depression Scale. Depressive symptoms did not differ between the NAC and placebo groups during treatment. There was no significant interaction between treatment and baseline depression predicting cannabis abstinence during treatment. Higher baseline depression was associated with decreased abstinence throughout treatment and a significant gender interaction suggested that this may be particularly true for females. Cross-lagged panel models suggested that depressive symptoms preceded increased cannabis use amounts (in grams) during the subsequent month. The reverse pathway was not significant (i.e., greater cannabis use preceding depressive symptoms). Results from this study suggest that depression may be a risk factor for poor CUD treatment outcome and therefore should be addressed in the context of treatment. However, results do not support the use of NAC to concurrently treat co-occurring depressive symptoms and CUD in adults. Clinicaltrials.gov: NCT01675661.

Guanfacine extended-release for cannabis use disorder: a pilot feasibility trial

ABSTRACT Background: Currently, there are no established pharmacotherapies for cannabis use disorders (CUDs). As a long-acting alpha-2-adrenergic receptor agonist, guanfacine extended-release (G-XR) could be useful in the treatment of CUDs by mitigating withdrawal and improving behavioral control. Objectives: To evaluate the feasibility and tolerability of G-XR as a treatment for CUDs. Methods: In an eight-week open-label outpatient pilot trial, we evaluated the safety and tolerability of G-XR in 22 cannabis dependent individuals. Using 2 different titration schedules, G-XR was gradually titrated to a dose of 4 mg or the highest dose tolerated. All participants received standard medication management. Results: Retention at week eight was 41%. Average daily amount of cannabis use (in grams: F1,86 = 8.74, p = .004; in dollars: F1,86 = 16.67, p < .0001) and cannabis using days (F1,86 = 7.67, p = .007) significantly reduced over the course of study participation. There were no significant differences between the titration schedules on emergence of side effects (Fisher exact test, p = .378) or retention (Log-Rank Test X2 1 = 0.021, p = .886). A total of 3 participants achieved 3 weeks or greater of total abstinence. Conclusions: G-XR is a feasible treatment for CUDs, and should be evaluated further in an efficacy trial.

Decreased drinking in adults with co-occurring cannabis and alcohol use disorders in a treatment trial for marijuana dependence: Evidence of a secondary benefit?

The purpose of the present study was to investigate whether cannabis dependent users who met criteria for a secondary diagnosis of alcohol use disorder (AUD) would increase their use of alcohol in response to decreasing their use of marijuana in a behavioral treatment trial for cannabis use disorder (CUD). This phenomenon is commonly known as “substance substitution.” Participants were randomly assigned to one of four 9-session treatment conditions with cannabis and alcohol use measured at baseline, posttreatment, and at 4 follow-ups through 14 months. Of those enrolled (n = 198), 27 (13.6%) also met criteria for AUD. Linear mixed models were used to analyze alcohol use over time with cannabis use and time as predictors. Findings demonstrated that there were no associations between declines in cannabis use and changes in alcohol consumption in the full sample. However, among those with CUD who also had AUD, declines in cannabis use significantly predicted concurrent declines in alcohol use (p < .05). This study did not find evidence of substance substitution among individuals receiving treatment for CUD. Contrary to expectations, the results indicated that individuals with AUD were more likely to decrease, rather than increase, their alcohol use when they reduced their marijuana use. Treatment for CUD in this study appeared to result in improvements in substance use generally, at least for those with comorbid AUD.

Psychosocial and Pharmacological Interventions for the Treatment of Cannabis Use Disorder.

(Reprinted with permission from Sabioni P and Le Foll B. Psychosocial and pharmacological interventions for the treatment of cannabis use disorder [version 1; referees: 3 approved]. F1000Research 2018, 7(F1000 Faculty Rev):173 (https://doi.org/10.12688/f1000research.11191.1)).

Cannabis and the Current State of Treatment for Cannabis Use Disorder.

Although the opioid epidemic may command more national headlines, the past two decades have seen a revolution in cannabis policy driven largely by the public and by business interests. As a result, the population of cannabis users nationwide-especially of heavy users-has grown yearly. Although less visible than patients admitted to the emergency department for opioid-related overdose or to treatment for opioid use disorder, an estimated 4.5-7 million individuals in the United States are thought to meet criteria for cannabis use disorder in a given year. This article focuses on the developmental pathways of cannabis use disorder, the epidemiology of cannabis use among adolescents and adults in the context of rapidly changing state laws, and evidence-based treatment for the general psychiatrist. The authors provide an overview of pharmacological and psychosocial behavioral treatments for patients with the disorder while emphasizing aspects of clinical management unique to this patient population.

Phase 2 trial shows encouraging target for treatment of cannabis use disorder

Adult men with cannabis dependence showed reduced symptoms of cannabis withdrawal and reported less cannabis use relative to placebo in a four‐week trial of the fatty acid amide hydrolase (FAAH) inhibitor PF‐04457845. The promising results of this Phase 2A trial suggest a potential new mechanism of action for the treatment of cannabis use disorder, the researchers stated. Study results were published online Dec. 6, 2018, in Lancet Psychiatry.

Exogenous progesterone for cannabis withdrawal in women: Feasibility trial of a novel multimodal methodology

BackgroundSex differences in cannabis use disorder (CUD) and its treatment have been identified. Women report more severe withdrawal and have shown worse treatment outcomes. Ovarian hormones are implicated in these differences and research suggests that exogenous progesterone may be an effective pharmacotherapy. MethodsThe current randomized, placebo-controlled, feasibility trial tested a novel multimodal methodology for administering exogenous progesterone during acute cannabis withdrawal. Eight heavy cannabis using women received micronized progesterone (200 mg bid) (n = 3) or matching placebo (n = 5) during the early follicular phase of their menstrual cycle over a 5-day study period while abstaining from cannabis. Laboratory visits (days 1 and 5) included biological and self-report assessments, while home-based procedures (days 2–4) included ambulatory assessments, video data capture and tele-drug testing, and biological assessments. Primary outcomes were medication adherence and salivary hormone levels, and the exploratory outcome was cannabis withdrawal severity. ResultsMedication adherence rates were high as assessed via self-report (100.0%) and video data capture (98.0%). Salivary progesterone levels differed between groups over time (p < 0.027) and the progesterone group achieved levels within the normal range during the luteal phase in healthy adults. All tele-drug tests were negative confirming cannabis abstinence and there was an indication (p = 0.07) of reduced cannabis craving among participants receiving progesterone. ConclusionMore effective and sex-based treatments for cannabis use disorder are needed. The current study provides a novel multimodal methodology with low participant burden for investigating new medications for cannabis withdrawal. Clinical trials of progesterone for cannabis withdrawal may be warranted.

A case series exploring the effect of twenty sessions of repetitive transcranial magnetic stimulation (rTMS) on cannabis use and craving

Background: Several studies have suggested that repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) may exert an anti-craving effect in substance use disorders. To date, no previous studies have explored the utility of rTMS in the treatment of cannabis use disorder (CUD). We subsequently delivered a course of rTMS to three treatment seeking participants with CUD.

F137A FEASIBILITY STUDY ON KHAT ABUSE FOR FURTHER POPULATION-BASED GENETICO- EPIDEMIOLOGICAL STUDIES ON VARIOUS GENE-ENVIRONMENT INTERACTIONS

Cannabis use disorder (CUD) is prevalent and demand for treatment is increasing, yet few individuals engage in formal treatment and the efficacy of established interventions for CUD is modest. Existing clinical trials evaluating psychosocial and pharmacological treatments for CUD have incorporated a wide variety of measures for assessing cannabis use outcomes, including abstinence, self-reported frequency and quantity used, withdrawal, use/dependence severity, and other psychosocial outcomes. The heterogeneity of measures and outcomes has limited quantitative analyses of the comparative effectiveness of existing interventions. The purpose of this systematic review is to: 1) identify and characterize approaches for measuring cannabis use in existing CUD intervention trials, including abstinence, frequency and quantity of use, and 2) summarize measures used to assess treatment efficacy in other outcome domains (e.g., cannabis use severity, psychosocial functioning, cannabis withdrawal), and provide a platform for future research to evaluate which outcome measures are most likely to reflect treatment efficacy and clinically significant improvement in other outcome domains.

Sequential and simultaneous treatment approaches to cannabis use disorder and tobacco use

Tobacco smoking among those seeking treatment for cannabis use disorder (CUD) is common and is a negative predictor of cannabis outcomes. Quitting tobacco may be beneficial for those seeking to quit cannabis use. This initial proof of concept, controlled trial was designed to compare a simultaneous versus sequential tobacco intervention among those seeking treatment for CUD. Sixty-seven adults received either a simultaneous (SIM) or sequential (SEQ) approach to tobacco cessation in the context of outpatient treatment for CUD. A tobacco intervention (TI) that combined web-based counseling with nicotine replacement therapy (NRT) was provided during weeks 1–12 for SIM and was delayed until weeks 13–24 for SEQ. During weeks 1–12, no between-condition significant differences were observed on treatment participation or cannabis use outcomes. The majority of SIM participants initiated TI counseling (62%), 50% made at least one quit attempt and 41% initiated NRT. Interestingly, 39% in SEQ made tobacco quit attempts and 18% initiated NRT on their own before the TI was offered to them. However, only 30% of those in SEQ continued treatment during weeks 13–24, which compromised between-condition comparisons following the TI, but illustrated a potential clinical concern with delaying the TI. Tobacco cessation outcomes generally were poor and did not differ between conditions. This initial controlled trial suggests that addressing tobacco use during CUD treatment is acceptable and generates action towards tobacco cessation. Additional trials testing more intensive TI models may be necessary to identify more efficacious interventions for co-use of cannabis and tobacco.

Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial

Cannabis is one of the most widely used drugs worldwide. Cannabis use disorder is characterised by recurrent use of cannabis that causes significant clinical and functional impairment. There are no approved pharmacological treatments for cannabis use disorder. One approach is to potentiate endocannabinoid signalling by inhibiting fatty acid amide hydrolase (FAAH), the enzyme that degrades the endocannabinoid anandamide. We aimed to test the efficacy and safety of the FAAH-inhibitor PF-04457845 in reduction of cannabis withdrawal and cannabis use in men who were daily cannabis users. We did a double-blind, placebo-controlled, parallel group phase 2a trial at one site in men aged 18-55 years with cannabis dependence according to DSM-IV criteria (equivalent to cannabis use disorder in DSM-5). After baseline assessments, participants were randomly assigned (2:1) to receive PF-04457845 (4 mg per day) or placebo using a fixed block size of six participants, stratified by severity of cannabis use and desire to quit. Participants were admitted to hospital for 5 days (maximum 8 days) to achieve abstinence and precipitate cannabis withdrawal, after which they were discharged to continue the remaining 3 weeks of treatment as outpatients. The primary endpoints were treatment-related differences in cannabis withdrawal symptoms during hospital admission, and week 4 (end of treatment) self-reported cannabis use and urine THC-COOH concentrations in the intention-to-treat population. The study is registered at ClinicalTrials.gov, number NCT01618656. Between Sept 12, 2012, and Jan 18, 2016, 46 men were randomly assigned to PF-04457845 and 24 to placebo. Adherence to study medication was 88%, as confirmed by video-calling and pill count, and corroborated by corresponding drug and anandamide concentrations in blood. Relative to placebo, treatment with PF-04457845 was associated with reduced symptoms of cannabis withdrawal (first day of treatment mean symptom score 11·00 [95% CI 7·78-15·57] vs 6·04 [4·43-8·24]; difference 4·96 [0·71-9·21]; padj=0·048; second day of treatment 11·74 [8·28-16·66] vs 6·02 [4·28-8·47]; difference 5·73 [1·13-10·32]; padj=0·035) and related mood symptoms during the inpatient phase. Additionally, treatment with PF-04457845 was associated with lower self-reported cannabis use at 4 weeks (mean 1·27 joints per day [95% CI 0·82-1·97] vs 0·40 [0·25-0·62]; difference 0·88 [0·29-1·46]; p=0·0003) and lower urinary THC-COOH concentrations (mean 657·92 ng/mL [95% CI 381·60-1134·30] vs 265·55 [175·60-401·57]; difference 392·37 [17·55-767·18)]; p=0·009). Eight (17%) patients in the PF-04457845 group and four (17%) in the placebo group discontinued during the treatment period. During the 4-week treatment phase, 20 (43%) of 46 participants in the PF-04457845 group and 11 (46%) of 24 participants in the placebo group had an adverse event. There were no serious adverse events. PF-04457845, a novel FAAH inhibitor, reduced cannabis withdrawal symptoms and cannabis use in men, and might represent an effective and safe approach for the treatment of cannabis use disorder. United States National Institute of Drug Abuse (NIDA).

Integrated cognitive behavioral therapy for comorbid cannabis use and anxiety disorders: A pilot randomized controlled trial

Cannabis use disorder (CUD) is the most common illicit substance use disorder and individuals with CUD have high rates of comorbid anxiety disorders. Comorbidity between CUD and anxiety disorders is of public health relevance given that although motivation enhancement therapy (MET) combined with cognitive-behavioral therapy (CBT) is an efficacious intervention for CUD, outcomes are worse for patients with elevated anxiety. The current study tested the acceptability and efficacy of the integration of a transdiagnostic anxiety CBT (i.e., treatment of patients with any anxiety disorder) with MET-CBT (integrated cannabis and anxiety reduction treatment, or ICART) for CUD compared to MET-CBT alone. Treatment-seeking cannabis users (56.4% male, Mage = 23.2, 63.3% non-Hispanic White) with CUD and at least one comorbid anxiety disorder were randomly assigned to ICART (n = 27) or MET-CBT (n = 28). Patients in the ICART condition attended significantly more treatment sessions than those in the MET-CBT condition. Patients in the ICART condition were more likely to be abstinent post-treatment than those in MET-CBT. Further, treatment produced decreases in cannabis use and related problems. Notably, therapy type did not moderate the impact of treatment on frequency of use and related problems. Together, these data suggest that ICART may be at least as efficacious as a gold-standard psychosocial CUD treatment, MET-CBT, for a difficult-to-treat subpopulation of cannabis users.

Young adults' perceptions of acceptability and effectiveness of a text message-delivered treatment for cannabis use disorder

ObjectiveThis study collected in-depth treatment satisfaction and effectiveness data to provide insight into the mechanisms of behavior change and to identify aspects of a text message- delivered treatment for cannabis use disorder that could be improved. MethodsData were collected via a web-based survey from 30 young adults (ages 18–25) who were recent participants in a randomized controlled trial of Peer Network Counseling-txt (PNC- txt), a text message treatment for cannabis use disorder. The survey assessed reactions to the text-delivered treatment, changes in cannabis use, reactions to the peer-focused components, and feedback about improvements to the treatment. ResultsNearly all (93%) respondents found PNC-txt to be helpful to their treatment. The majority of the sample (63%) reported that PNC-txt heightened awareness of their cannabis use, and 40% reported a better understanding of problematic use. Fifty percent reported that they use less cannabis than they did prior to the intervention. Seventy percent of respondents stated that it was helpful to answer questions about their close friend group and nearly one- quarter of participants decreased the amount of time spent with “unhealthy” friends.Approximately 85% indicated that thinking about their peer network helped them meet goals of stopping, reducing, or better managing their cannabis use. ConclusionsThese findings provide insight into the acceptability of the text-delivered treatment platform and potential mechanisms of behavior change for PNC-txt. The participants provided positive feedback about the treatment and indicated that it helped reduce their cannabis use.Given the acceptability and promising efficacy of PNC-txt, continued research is warranted, particularly with adolescents and with larger samples.

A Survey of Payer Perspectives on Cannabis Use Disorder

ABSTRACTBackground: Cannabis use disorder (CUD) as described/defined in DSM 5, is characterized by impaired control of marijuana use and related personal, health, and legal consequences. CUD is a serious public health problem, affecting nearly 6 million individuals in the United States. There are no FDA approved medications to treat this disorder. The lack of available treatment options contributes to uncertainties by drug sponsors about formulary and reimbursement decision-making for CUD pharmacotherapies. Objective: To addresses this gap by presenting the first findings on managed care payers' perceptions of CUD treatments and clinical trial end points. Methods: An online survey was conducted with 50 payers from managed care organizations. The survey inquired about perceptions of unmet need in CUD treatment, relevant clinical trial end points, disease knowledge, and likelihood of review of new pharmacotherapies. Results: The majority of payers (62%) reported that they were at least moderately familiar with CUD treatment end points. Most (80%) rated the unmet need for new pharmacotherapies for CUD as at least moderately important. Payers rated the most important end points for clinical trials as abstinence and decreased resource utilization. Most participants said an FDA approved CUD treatment would be formally reviewed by payers within 6 months (58%) or a year (36%). Conclusions: Based on these findings, payers see an unmet need for CUD treatment. Furthermore, FDA-approved pharmacotherapies for CUD will likely be reviewed quickly by payers, especially if data are provided on the likelihood of achieving abstinence and reduced resource utilization.

The role of depressive symptoms in treatment of adolescent cannabis use disorder with N-Acetylcysteine

Relative to adults, adolescents are at greater risk of developing a cannabis use disorder (CUD) and risk may be exacerbated by co-occurring depressive symptoms. N-Acetylcysteine (NAC), an over-the-counter antioxidant, is thought to normalize glutamate transmission. Oxidative stress and glutamate transmission are disrupted in both depression and CUD. Thus, NAC may be particularly effective at promoting cannabis abstinence among adolescents with elevated depressive symptoms. Secondary analyses were conducted using a sub-sample of adolescents with CUD (N = 74) who participated in an 8-week randomized placebo-controlled clinical trial examining the efficacy of NAC for cannabis cessation. It was hypothesized that NAC would reduce severity of depressive symptoms, and that decreases depressive symptom severity would mediate decreases in positive weekly urine cannabinoid tests (11-nor-9-carboxy-Δ9-tetrahydrocannabinol). Additionally, it was expected that adolescents with greater severity of baseline depressive symptoms would be more likely to become abstinent when assigned NAC relative to placebo. Results from linear mixed models and generalized estimating equations did not suggest that NAC reduced severity of depressive symptoms, and the hypothesis that NAC's effect on cannabis cessation would be mediated by reduced depressive symptoms was not supported. However, an interaction between treatment condition and baseline severity of depressive symptoms as a predictor of weekly urine cannabinoid tests was significant, suggesting that NAC was more effective at promoting abstinence among adolescents with heightened baseline depressive symptoms. These secondary findings, though preliminary, suggest a need for further examination of the role of depressive symptoms in treatment of adolescent CUD with NAC.

Cannabis and Mood Disorders.

The present review will provide an overview of the neurobiology, epidemiology, clinical impact, and treatment of cannabis use disorder (CUD) in mood disorders. Patients with mood disorders including major depressive disorder (MDD) and bipolar disorder (BD) have higher rates of cannabis use, and CUD compared to the general population. Reasons for this association are not clear, nor are the putative therapeutic effects of cannabis use, or its components delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in these illnesses. The evidence surrounding treatments for patients with this comorbidity is lacking, with more support for psychotherapeutic treatments compared with pharmacological treatments. Cannabis use may be associated mood disorders, but more research is needed to increase our understanding of the mechanisms for this association, and to develop more effective treatments for this comorbidity.

1000 Targeting Sleep in Adults Seeking Treatment for Cannabis Use Disorder

1000 Targeting Sleep in Adults Seeking Treatment for Cannabis Use Disorder

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration

BackgroundThere is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. MethodsNon-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180–240 mg/day; 60–80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. ResultsParticipants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. ConclusionsChronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders.

Guanfacine decreases symptoms of cannabis withdrawal in daily cannabis smokers.

The α2a-adrenergic agonist, lofexidine, reduced cannabis withdrawal-related sleep disruption in the laboratory, but side effects (e.g. fatigue, hypotension) limit its utility as a treatment for cannabis use disorder. This study tested the potential efficacy and tolerability of a daily bedtime administration of the FDA-approved α2a-adrenergic agonist, guanfacine, in a human laboratory model of cannabis use disorder. Daily, nontreatment-seeking cannabis smokers (13M, 2F) completed a within-subject study comprising two 9-day inpatient study phases. Each phase tested the effects of daily placebo or immediate-release guanfacine (2mg) on cannabis intoxication (5.6 percent THC; 2days), withdrawal (4days of abstinence) and subsequent 'relapse' (3days of cannabis self-administration). Ratings of mood, sleep, cardiovascular effects, food intake, psychomotor performance and cannabis self-administration were assessed. An outpatient phase preceded each inpatient phase for medication clearance or dose induction. Under placebo medication conditions, cannabis abstinence produced significant withdrawal, including irritability, sleep disruption and anorexia. Guanfacine reduced ratings of irritability and improved objective measures of sleep during cannabis withdrawal relative to placebo but did not reduce cannabis self-administration. Guanfacine was well tolerated with little evidence of fatigue and only small decreases in blood pressure: no dose was held due to hypotension. Thus, a single daily administration of guanfacine at bedtime improved sleep and mood during cannabis withdrawal relative to placebo. This positive signal supports further studies varying the guanfacine dose, formulation or frequency of administration, or combining it with other medications to increase the likelihood of having an impact on cannabis use.