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.

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.

Preventive interventions targeting cannabis use and related harms in people with psychosis: A systematic review.

AIM: While most users will not experience severe adverse health outcomes from cannabis, it can be associated with negative outcomes in people with psychosis. People with psychosis who use cannabis have more severe psychiatric symptoms, higher rates of hospitalization, and diminished psychosocial functioning compared to those who do not use cannabis. Most studies of people with psychotic disorders have focused on cannabis use treatments and only a few on preventive interventions for cannabis. This systematic review aims to evaluate the effectiveness of preventive interventions focusing on cannabis use for people with psychosis. METHODS: We searched CINAHL Plus, EBM reviews, EMBASE, MEDLINE, PsycInfo and PubMed databases for controlled studies assessing the effects of preventive interventions on cannabis use and related harms in people with psychosis. We conducted the search using a combination of the following concepts: cannabis, psychosis, intervention and prevention. Risk of bias was assessed. RESULTS: The search yielded 11 460 unique studies. Of these, five studies met our eligibility criteria. None of the studies demonstrated clear efficacy of prevention interventions in reducing cannabis use, and none measured cannabis-related harms. All studies had high risk of bias. CONCLUSION: The small number of studies and the considerable risk of bias made it difficult to conclude whether any of the existing interventions were promising. With increased acceptance and accessibility of cannabis due to liberalizing cannabis policies, it is imperative to improve the evidence base for preventive interventions, in particular their effectiveness in decreasing the risk of cannabis-related harms in people with psychosis.