Absence of Evidence for Sustained Effects of Daily Cannabidiol Administration on Anandamide Plasma Concentration in Individuals with Cocaine Use Disorder: Exploratory Findings from a Randomized Controlled Trial.

Background: Cannabidiol (CBD) has been proposed to have a therapeutic potential over a wide range of neuropsychiatric disorders, including substance use disorders. Pre-clinical evidence suggests that CBD can increase anandamide (AEA) plasma concentration, possibly mediating some of its therapeutic properties. Whether CBD exerts such an effect on AEA in individuals with cocaine use disorder (CUD) remains unknown. Aims: To explore the sustained effects of daily CBD administration on AEA plasma concentrations compared with placebo in CUD. Methods: We used data from a randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in CUD. Seventy-eight individuals were randomized to receive a daily oral dose of 800 mg CBD (n = 40) or a placebo (n = 38). Participants stayed in an inpatient detoxification setting for 10 days, after which they were followed in an outpatient setting for 12 weeks. AEA plasma concentration was measured at baseline and at 23-h post CBD ingestion on day 8 and week 4. A generalized estimating equation model was used to assess CBD's effects on AEA, and sensitivity analyses were computed using Bayesian linear regressions. Results: Sixty-four participants were included in the analysis. Similar mean AEA plasma concentrations in both treatment groups (p = 0.357) were observed. At day 8, mean AEA plasma concentrations (± standard deviation) were 0.26 (± 0.07) ng/mL in the CBD group and 0.29 (± 0.08) ng/mL in the placebo group (p = 0.832; Bayes factor [BF] = 0.190). At week 4, they were 0.27 (± 0.09) ng/mL in the CBD group and 0.30 (± 0.09) ng/mL in the placebo group (p = 0.181; BF = 0.194). Conclusion: While not excluding any potential acute and short-term effect, daily CBD administration did not exert a sustained impact on AEA plasma concentrations in individuals with CUD compared with placebo. Registration: clinicaltrials.gov (NCT02559167).

Variations of cannabis-related adverse mental health and addiction outcomes across adolescence and adulthood: A scoping review.

Introduction: Evidence supporting associations between cannabis use and many health outcomes is growing, however it remains unclear how such associations vary across the lifespan. We therefore aim to answer the following questions: (1) Are the risks of cannabis's adverse effects on mental health and addiction-related outcomes different in adolescents than in adults? (2) What are the relationships between these cannabis's adverse effects and (a) an individual's age at first cannabis use, (b) age at assessment, and (c) duration of cannabis use? Methods: We searched Medline, Embase, CINAHL, and PsychINFO from inception to 18 October 2021. Two reviewers independently screened studies and descriptively synthesized results. Results: We included 140 studies. Cannabis effects on mental health and addiction-related outcomes were worse in adolescents, early cannabis initiators and cannabis users who consumed for longest periods. Evidence of worse long-term adverse effects in adolescents was substantial for psychosis, cannabis, and nicotine use disorders; mixed for depression, suicidality, other substance use and disorders; and limited for anxiety. Additionally, acute cannabis exposure had the opposite trend with adults more often reporting adverse effects than adolescents. Conclusion: The available evidence suggests that cannabis use should be delayed as late as possible in adulthood and shortened in duration across the lifespan to decrease the risk of negative outcomes, while emphasizing the need for adapted harm reduction approaches. This scoping review provides evidence on the role of age and duration of exposure as determinants of cannabis-related adverse effects, which may inform prevention and harm reduction strategies. Systematic review registration: https://doi.org/10.17605/OSF.IO/BYG72.

Cannabidiol Effect on Anxiety Symptoms and Stress Response in Individuals With Cocaine Use Disorder: Exploratory Results From a Randomized Controlled Trial.

OBJECTIVES: Individuals with a cocaine use disorder (CUD) are more likely to present anxiety, which in turn negatively impacts substance use outcomes. Some evidence suggests that cannabidiol (CBD) presents anxiolytic properties and could be a treatment for substance use disorders. This study explores CBD's effect on stress biomarker (cortisol) and anxiety symptoms in people with CUD. METHODS: Exploratory analyses were conducted using data from a randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy to treat CUD. We randomized 78 individuals with CUD into receiving a daily oral dose up to 800 mg CBD (n = 40) or placebo (n = 38). The trial was divided into 2 phases: an inpatient detoxification lasting 10 days and an outpatient follow-up lasting 12 weeks. Anxiety symptoms and stress response were assessed using a visual analog scale, the Beck Anxiety Inventory, and cortisol levels at multiple time points throughout the study. We also measured anxiety after a stressful and a cocaine-cue scenarios. We used generalized estimating equations models and multiple linear regression to assess CBD's effects on anxiety and cortisol levels. RESULTS: Both treatment groups had similar mean anxiety scores according to the Beck Anxiety Inventory ( P = 0.27) and the visual analog scale ( P = 0.18). CBD did not decrease anxiety after a stressful ( P = 0.14) and a cocaine ( P = 0.885) scenarios compared with placebo. No statistically significant group difference was found in cortisol levels ( P = 0.76). CONCLUSIONS: We found no evidence for 800 mg of CBD to be more efficacious than placebo for modulating anxiety symptoms and cortisol levels in individuals with CUD.

Cannabidiol effects on cognition in individuals with cocaine use disorder: Exploratory results from a randomized controlled trial.

BACKGROUND: Cocaine use disorder (CUD) is associated with various cognitive deficits that impede patients' functionality, prognosis and therapeutic outcomes. New pharmacological treatments for CUD that could improve cognition are needed. OBJECTIVE: To explore whether cannabidiol (CBD) is superior to placebo to improve cognitive functioning in individuals with CUD. METHODS: We conducted an exploratory analysis of a single site, randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in reducing craving, cocaine use and relapse in individuals with CUD. Seventy-eight individuals diagnosed with CUD were randomized to receive either CBD (800 mg) or placebo for 92 days. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess inhibition (Stop Signal Task; SST), risky decision making (Cambridge Gambling Task; CGT) and visual memory (Pattern Recognition Memory; PRM). This assessment was made on day 1, day 7 and at week 6. We controlled for sex, severity of dependence and baseline cognitive scores in our generalized estimating equation models. RESULTS: Both groups performed similarly on the PRM (correct answers: p = 0.080), SST (stop signal reaction time: p = 0.644) and CGT (quality of decision making: p = 0.994; deliberation time: p = 0.507; delay aversion: p = 0.968; risk taking: p = 0.914) tests. CONCLUSIONS: We found no evidence for 800 mg of CBD to be more efficacious than placebo for improving cognitive outcomes. Clinical trials evaluating pharmacological treatments for CUD should continue to be a research priority.

Changes in Alcohol Habits Among Workers During the Confinement of COVID-19: Results of a Canadian Cross-Sectional Survey.

BACKGROUND: The restrictions implemented around the world to contain the spread of the coronavirus disease 2019 (COVID-19) impact workers. Emotional distress and maladaptive behaviors such as alcohol misuse are expected, particularly in vulnerable groups such as front-line health workers. In the present study, we examined if alcohol consumption behaviors in Quebec workers changed during confinement of the COVID-19 pandemic, and whether healthcare workers reported specific patterns of changes. METHODS: Data were obtained from an anonymous online survey conducted among adult workers aged ⩾18 years in the province of Quebec, Canada, between May 25, 2020 and June 26, 2020. Participants provided self-reported data regarding sociodemographic including field of work, as well as mental health disorders, alcohol use, alcohol craving, and type of alcohol consumed. Changes in alcohol behaviors were assessed using Wilcoxon signed rank test for categorial variables and paired-t tests for continuous variables. RESULTS: The survey was completed by 847 participants (77.8% women), with 42.5% healthcare workers. Participants reported increased daily alcohol use (Z = -10.60; P < .001, r = -.372) and alcohol craving (P < .001, d = 0.485) during the confinement. Only the type of alcohol consumed during the confinement differed between health care workers and other workers (OR = 0.45, P = .003). Health care workers used less high alcohol products during the confinement. CONCLUSION: Our results show a significant increase in daily alcohol consumption and in alcohol craving during the confinement in the Quebec working population.

Technology-Based Psychological Interventions for Young Adults With Early Psychosis and Cannabis Use Disorder: Qualitative Study of Patient and Clinician Perspectives.

BACKGROUND: The persistence of cannabis use disorder (CUD) in young adults with first-episode psychosis (FEP) is associated with poor clinical and functional outcomes. Face-to-face psychological interventions are effective in treating CUD. However, their use in early intervention services (EISs) for psychosis is inconsistent because of barriers, including high workload and heterogeneity in training of clinicians and lack of motivation for treatment among patients. Tailoring new technology-based psychological interventions (TBPIs) to overcome these barriers is necessary to ensure their optimal acceptability. OBJECTIVE: The aim of this study is twofold: to explore psychological intervention practices and intervention targets that are relevant for treating CUD in individuals with early psychosis and to explore factors related to the development and implementation of a technology-assisted psychological intervention. METHODS: A total of 10 patients undergoing treatment for FEP and CUD in EISs participated in a focus group in June 2019. Semistructured individual interviews were conducted with 10 clinicians working in first-episode clinics in the province of Québec, Canada. A hybrid inductive-deductive approach was used to analyze data. For the deductive analysis, we used categories of promoting strategies found in the literature shown to increase adherence to web-based interventions for substance use (ie, tailoring, reminders, delivery strategies, social support, and incentives). For the inductive analysis, we identified new themes through an iterative process of reviewing the data multiple times by two independent reviewers. RESULTS: Data were synthesized into five categories of factors that emerged from data collection, and a narrative synthesis of commonalities and differences between patient and clinician perspectives was produced. The categories included attitudes and beliefs related to psychological interventions (eg, behavioral stage of change), strategies for psychological interventions (eg, motivational interviewing, cognitive behavioral therapy, psychoeducation, stress management), incentives (eg, contingency management), general interest in TBPIs (eg, facilitators and barriers of TBPIs), and tailoring of TBPIs (eg, application needs and preferences, outcome measures of interest for clinicians). CONCLUSIONS: This study provides a comprehensive portrait of the multifaceted needs and preferences of patients and clinicians related to TBPIs. Our results can inform the development of smartphone- or web-based psychological interventions for CUD in young adults with early psychosis.

Cannabidiol as a treatment for craving and relapse in individuals with cocaine use disorder: a randomized placebo-controlled trial.

BACKGROUND AND AIMS: Cocaine use disorder (CUD) is a significant public health concern for which no efficacious pharmacological interventions are available. Cannabidiol (CBD) has attracted considerable interest as a promising treatment for addiction. This study tested CBD efficacy for reducing craving and preventing relapse in people with CUD. DESIGN: Single-site double-blind randomized controlled superiority trial comparing CBD with placebo. SETTING AND PARTICIPANTS: Centre Hospitalier de l'Université de Montréal, Canada. Seventy-eight adults (14 women) with moderate to severe CUD participated. INTERVENTION: Participants were randomly assigned (1 : 1) by stratified blocks to daily 800 mg CBD (n = 40) or placebo (n = 38). They first underwent an inpatient detoxification phase lasting 10 days. Those who completed this phase entered a 12-week outpatient follow-up. MEASUREMENTS: Primary outcomes were drug-cue-induced craving during detoxication and time-to-cocaine relapse during subsequent outpatient treatment. FINDINGS: During drug-cue exposure, craving scores [mean ± standard deviation (SD)] increased from baseline by 4.69 (2.89) versus 3.21 (2.78) points, respectively, in CBD (n = 36) and placebo (n = 28) participants [confidence interval (CI) = -0.33 to 3.04; P = 0.069; Bayes factor = 0.498]. All but three participants relapsed to cocaine by week 12 with similar risk for CBD (n = 34) and placebo (n = 27) participants (hazard ratio = 1.20, CI = 0.65-2.20, P = 0.51; Bayes factor = 0.152). CBD treatment was well tolerated and associated mainly with diarrhoea. CONCLUSIONS: CBD did not reduce cocaine craving or relapse among people being treated for CUD.

Exploring cannabidiol effects on inflammatory markers in individuals with cocaine use disorder: a randomized controlled trial.

Cocaine use disorder (CUD) is a major public health issue associated with physical, social, and psychological problems. Excessive and repeated cocaine use induces oxidative stress leading to a systemic inflammatory response. Cannabidiol (CBD) has gained substantial interest for its anti-inflammatory properties, safety, and tolerability profile. However, CBD anti-inflammatory properties have yet to be confirmed in humans. This exploratory study is based on a single-site randomized controlled trial that enrolled participants with CUD between 18 and 65 years, randomized (1:1) to daily receive either CBD (800 mg) or placebo for 92 days. The trial was divided into a 10-day detoxification (phase I) followed by a 12-week outpatient follow-up (phase II). Blood samples were collected from 48 participants at baseline, day 8, week 4, and week 12 and were analyzed to determine monocytes and lymphocytes phenotypes, and concentrations of various inflammatory markers such as cytokines. We used generalized estimating equations to detect group differences. Participants treated with CBD had lower levels of interleukin-6 (p = 0.017), vascular endothelial growth factor (p = 0.032), intermediate monocytes CD14+CD16+ (p = 0.024), and natural killer CD56negCD16hi (p = 0.000) compared with participants receiving placebo. CD25+CD4+T cells were higher in the CBD group (p = 0.007). No significant group difference was observed for B lymphocytes. This study suggests that CBD may exert anti-inflammatory effects in individuals with CUD.

Converting scores between the PANSS and SAPS/SANS beyond the positive/negative dichotomy.

Previous work provided conversion equations for overall indices of positive and negative symptomatology between the Positive and Negative Syndrome Scale (PANSS) and the Scales for the Assessment of Positive/Negative Symptoms (SAPS/SANS). Our objective was to provide such conversion equations for subdomains of positive and negative symptomatology in order to better account for the diversity of symptom profiles in schizophrenia. Symptoms severity was assessed using both the PANSS and SAPS/SANS in 205 patients with schizophrenia. Two exploratory factor analyses combining items from both scales were first performed separately in the positive and negative symptom domains. Positive factors were termed 'Hallucinations', 'Delusions' and 'Disorganization', while negative factors were associated with 'Expressivity', 'Amotivation' and 'Cognition', consistent with current descriptions of symptom dimensions in schizophrenia. For each factor, linear regression analyses were conducted on 80% of the data to obtain conversion equations from the PANSS to the SAPS/SANS and vice versa. Reliability was then evaluated on the 20% remaining data, with good to excellent intra-class correlation coefficients between the original and predicted scores for all but the cognition factor. These findings show that symptom severity scores can be converted with good accuracy between clinical scales beyond the positive/negative symptom dichotomy.

Multisite generalizability of schizophrenia diagnosis classification based on functional brain connectivity.

Our objective was to assess the generalizability, across sites and cognitive contexts, of schizophrenia classification based on functional brain connectivity. We tested different training-test scenarios combining fMRI data from 191 schizophrenia patients and 191 matched healthy controls obtained at 6 scanning sites and under different task conditions. Diagnosis classification accuracy generalized well to a novel site and cognitive context provided data from multiple sites were used for classifier training. By contrast, lower classification accuracy was achieved when data from a single distinct site was used for training. These findings indicate that it is beneficial to use multisite data to train fMRI-based classifiers intended for large-scale use in the clinical realm.