Sean P. Barrett

Background: Cannabidiol (CBD) impacts brain regions implicated in anxiety reactivity and stress reactivity (e.g., amygdala, anterior cingulate cortex (ACC), anterior insula (AI)); however, placebo-controlled studies are mixed regarding CBD’s anxiolytic effects. We previously reported that CBD expectancy alone can alter subjective, physiological, and endocrine markers of stress/anxiety; however, it is unclear whether these findings reflect altered brain reactivity. This study evaluated whether CBD expectancy independently alters amygdala resting-state functional connectivity (rsFC) with the ACC and AI following acute stress. Method: Thirty-eight (20 females) healthy adults were randomly assigned to receive accurate or inaccurate information regarding the CBD content of a CBD-free oil administered during a single experimental session. Following a baseline resting state MRI scan, participants administered their assigned oil sublingually, engaged in a stress task (serial subtraction with negative feedback) inside the scanner, and underwent another resting state MRI scan. Amygdala rsFC with the ACC and AI was measured during each scan, and the subjective state was assessed at six time points. Outcomes were analyzed using ANCOVA. Results: CBD expectancy (vs CBD-free expectancy) was associated with significantly weaker rsFC between the left amygdala and right ACC ( p = 0.042), but did not systematically alter amygdala-AI rsFC ( p-values > 0.05). We also replicated our previously reported CBD expectancy effects on subjective stress/anxiety in the scanner context. Conclusion: CBD placebo effects may be sufficient to alter neural responses relevant to its purported anxiolytic and stress-relieving properties. Future work is needed to replicate these results and determine whether CBD expectancy and pharmacology interact to alter neural anxiety reactivity and stress reactivity.

Background: Our group has previously reported that cannabidiol (CBD) expectancy alone blunts markers of stress, particularly during anticipation, but it is not clear the extent to which such findings were specific to the methods utilized. Aims: To examine CBD-related placebo effects on stress reactivity and anticipation and to validate a protocol to be used in a neuroimaging study. Methods: Forty-eight healthy adults (24 female) were randomly assigned to be informed that they ingested a CBD-containing oil or a CBD-free oil despite receiving the same oil (CBD-free). Following oil administration, participants engaged in a laboratory stressor and were then incorrectly informed that they would engage in a second more difficult task following a waiting period. Subjective state (sedation, energy, stress, anxiety) and heart rate were assessed at baseline, post-oil administration, immediately following the first stressor, and while anticipating the second stressor. Results: Subjective stress and anxiety were significantly elevated immediately following the stressor ( p- values < 0.001). CBD expectancy was associated with increased subjective sedation ( p < 0.01) and tended to be associated with blunted subjective stress ( p = 0.053). Post hoc within-condition pairwise compassions suggested a return to pre-stressor levels during the anticipation period in the CBD condition for subjective stress and anxiety ( p = 0.784, 0.845), but not the CBD-free condition ( p = 0.025, 0.045). Conclusion: Results replicate and extend previous findings that CBD expectancy alone can impact stress- and anxiety-relevant responses in the laboratory context.

Background: The three most used substances—alcohol, cannabis, and nicotine—are frequently concurrently. Use of each substance has been connected to an increased probability of use of the other substances, and the problematic use of each substance has been linked to demographic factors, substance use factors, and personality. However, little is known about which risk factors are most important for consumers of all three substances. This study examined the extent to which various factors are associated with dependence on alcohol, cannabis, and/or nicotine in users of all three substances.Methods: 516 Canadian adults with past month use of alcohol, cannabis, and nicotine completed online surveys querying their demographics, personality, substance use history, and levels substance dependence. Hierarchical linear regressions were used to determine which factors best predicted levels of dependence on each substance.Results: Alcohol dependence was associated with levels of cannabis and nicotine dependence, and impulsivity, with 44.9% of variance explained. Cannabis dependence was predicted by alcohol and nicotine dependence levels, impulsivity, and the age of onset of cannabis use, with 47.6% of variance explained. Nicotine dependence was best predicted by alcohol and cannabis dependence levels, impulsivity, and dual use of cigarettes and e-cigarettes, with 19.9% of variance explained.Conclusions: Alcohol dependence, cannabis dependence, and impulsivity were the strongest predictors for dependence on each of the substances. A strong relationship between alcohol and cannabis dependence was evident, warranting further research.

Coronary artery anastomosis training and assessment are vital for patient safety and for conferring a prognostic benefit. A systematic review and meta-analysis were performed to analyse the impact of simulation on coronary anastomosis proficiency in terms of time taken and skill score. This review was conducted in accordance with PRISMA guidelines, searching PubMed, Embase and Cochrane databases on 10 October 2020, using the terms ‘Coronary anastomosis simulation’ or ‘vascular anastomosis simulation’ and ‘anastomosis simulation’. Studies included had objective measurement of scores of before and after simulation. Meta-analysis was performed using RevMan, version 5.4 (Cochrane Library). From a pool of 1687 articles, 12 articles evaluating the use of simulation in teaching coronary anastomosis were identified, with objective scores at baseline and after simulation. The 12 papers included 274 subjects. Data on 223 subjects could be extracted for analysis in performing coronary anastomosis in a simulated environment. Eight trials evaluated improvement in time and 12 trials evaluated performance using an objective evaluation score. In comparison with no formal simulation training, simulation was associated with improved skill in a five-point scale (standardized mean difference 1.68 (95 per cent c.i. 1.23 to 2.13; P < 0.001)) and time (mean difference 205.9 s (95 per cent c.i. 133.62 to 278.18; P < 0.001)) in trials included in the meta-analysis. Furthermore, novice cardiothoracic surgeons benefited more from simulation as regards time improvement compared with senior cardiothoracic surgeons (293 versus 120 s improvement; P = 0.003). Fidelity of simulator did not have a significant effect on rates of improvement. Simulation-based training in coronary anastomosis is associated with improved time efficiency and overall performance in comparison with no intervention. Further studies are necessary to determine the optimum timing of trainees progressing from simulation training to live operating.

Background: Caffeine is the most commonly consumed psychoactive substance, yet its potential reinforcing properties have been understudied. Aims: This study examined the impact of caffeine administration and expectancy on coffee-related craving, withdrawal, and cue reactivity via a balanced-placebo design. Methods: Following 18-h caffeine abstinence, 65 daily coffee consumers (54% male) received either caffeine-containing (100 mg) or placebo gum, along with either accurate or inaccurate information regarding the gum’s caffeine content. Participants were exposed to neutral and coffee-related stimuli using different sensory modalities (visual and combined auditory/olfactory). Craving, withdrawal, and heart rate were assessed at baseline and after each cue presentation. Following the cue-reactivity assessments, participants were provided with an opportunity to self-administer units of coffee. Results: Caffeine expectancy was associated with reduced subjective withdrawal 30 min following the gum administration but was not significantly impacted by actual caffeine administration. The presentation of coffee-related cues was found to increase self-reported craving and heart rate, regardless of the expectation that caffeine had been administered. Visual, but not auditory/olfactory, cue reactivity appeared blunted when participants received a prior dose of caffeine. Prior caffeine ingestion also reduced the probability of subsequent coffee self-administration. Conclusion: To our knowledge, this is the first examination of the impact of caffeine administration and expectancy on cue-elicited coffee craving and coffee consumption. Although there was some evidence that caffeine expectancy and administration were found to impact subjective withdrawal and self-administration respectively, neither was found to exert strong consistent effects on cue reactivity.

Rationale: Cannabidiol (CBD) has been reported to attenuate stress and anxiety, but little is known about the extent to which such effects result from pharmacological versus expectancy factors. Objectives: We evaluated whether CBD expectancy alone could influence stress, anxiety, and mood, and the extent to which beliefs regarding CBD effects predicted these responses. Methods: In this randomized crossover study, 43 health adults (23 women) attended two experimental laboratory sessions, where they self-administered CBD-free hempseed oil sublingually. During one session, they were (incorrectly) informed that the oil contained CBD and in the other session, that the oil was CBD-free. Following administration, participants engaged in the Maastricht Acute Stress Test (MAST). Heart rate variability (HRV) was assessed continuously, and subjective state was assessed at baseline, 90-min following oil administration, immediately following the MAST, and after a 10-min recovery period. Results: The CBD expectancy condition was associated with increased sedation as well as with changes in HRV that were consistent with heightened anticipatory stress regulation. Overall, there were no systematic changes in subjective stress, or anxiety, according to expectancy condition. However, participants who endorsed strong a priori beliefs that CBD has anxiolytic properties reported significantly diminished anxiety in the CBD expectancy condition. Conclusions: CBD expectancy alone impacted several subjective and physiological responses. Additionally, expectancy-related factors were implicated in anxiolytic effects of CBD for those who believed it was helpful for such purposes, emphasizing the need to measure and control for CBD-related expectancies in clinical research that involves the administration of CBD.