The impact of cannabidiol placebo on responses to an acute stressor: A replication and proof of concept study.

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.

The Impact of Cannabidiol Expectancy on Cortisol Responsivity in the Context of Acute Stress: Associations with Biological Sex.

Background: Cannabidiol (CBD), a nonpsychoactive cannabinoid found in the cannabis plant, has gained interest for its purported stress- and anxiety-reducing effects. However, the mechanisms underlying these effects remain unclear. Our group previously found that CBD expectancy alone resulted in lower state anxiety (vs. CBD-free expectancy) among those who strongly believed it was helpful for such purposes, in addition to influencing physiological measures (i.e., heart rate variability). Aims: Using data collected as part of this previously published larger study, we aimed to explore the extent to which CBD expectancy alone impacts cortisol in the context of a laboratory stressor. Methods: A sample of 43 healthy adults (23 female) participated in one orientation and two experimental laboratory sessions. They received the same oil (CBD-free) during both experimental sessions but were told they received CBD oil in counterbalanced order in one of their sessions. Participants then engaged in a laboratory stressor (the Maastricht Acute Stress Test; MAST) and salivary cortisol samples were collected throughout [T1: baseline; T2: 90-min postabsorption (PA); T3: poststress (0-PS); T4: 10-min poststress (10-PS); T5: 30-min poststress (30-PS)]. Linear marginal models were used for analyses. Results: Findings indicated that a physiological stress response was elicited in the context of the MAST, which is consistent with what has been reported previously. Interestingly, while cortisol levels were significantly lower in the CBD expectancy condition (vs. CBD-free) immediately following the MAST (0-PS) and 10-min later (10-PS), this effect seems to be largely driven by males, evidenced by a three-way interaction. Cortisol levels did not reliably vary across expectancy conditions at any other time point. Conclusion: Overall, these results suggest that CBD expectancy appears to blunt cortisol in anticipation of a stressor, particularly in males. Findings suggest that it is important to consider the impact of drug-related expectations when assessing CBD-related effects on stress-related processes.

Perceptions about THC and CBD effects among adults with and without prior cannabis experience.

BACKGROUND: Cannabis is associated with a range of therapeutic and non-therapeutic, positive and negative effects. While some benefits and harms may be specific to individual cannabinoid constituents (THC, CBD), individual expectancies may also play a role. OBJECTIVES: Evaluate the extent to which individuals hold expectancies about the effects of CBD, THC, and THC & CBD combined, and whether this differs with prior cannabis experience. METHODS: Canadian adults (N = 345; n = 58 no prior cannabis use, n = 287 prior cannabis use) completed a Qualtrics survey. Participants provided information regarding their expectancies about the effects of cannabinoids (THC, CBD, THC & CBD combined) via a 15-item questionnaire, which included various therapeutic (e.g., helps with pain) and non-therapeutic positive (e.g., enhances positive feelings) and negative (e.g., risk for addiction) effects. They recorded their perceptions about the effects of each cannabinoid on a scale (0="definitely not true", 10="definitely true"). Data was analyzed using linear mixed models. RESULTS: For most therapeutic effects, CBD-containing products (CBD, THC & CBD) were rated higher than THC. For most positive and negative non-therapeutic effects, THC-containing products (THC, THC & CBD) were rated higher than CBD. Those with prior cannabis use (vs no prior use) rated all cannabinoids higher regarding their association with many therapeutic and positive effects, while endorsing weaker expectancies about their role in some negative effects. CONCLUSIONS: Adults endorsed stronger expectancies that CBD-containing products are responsible for producing a rage of therapeutic effects. Those with prior cannabis use experience tended to emphasize the benefits and minimize potential harmful effects of cannabinoids.

Evaluating cannabidiol (CBD) expectancy effects on acute stress and anxiety in healthy adults: a randomized crossover study.

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.

The relative impact of acute nicotine and tobacco administration on craving, withdrawal, and cigarette self-administration in dependent and nondependent smokers.

Negative reinforcement mechanisms, wherein individuals smoke at regular intervals to ameliorate craving and withdrawal, are integral to persistent smoking. This is consistent with the behavior of dependent smokers but does not fully account for the behavior of intermittent smokers, who do not smoke enough to maintain steady nicotine levels. This study examined the independent and combined impacts of nicotine and tobacco consumption on cigarette craving, withdrawal, and subsequent smoking behavior in 18 nondependent light and intermittent smokers (LITS) and 23 daily, dependent smokers (DDS). Participants administered conventional nicotine-containing cigarettes (NC; 18.9 mg nicotine; 1.41 mg deliverable), reduced nicotine content cigarettes (RNC; 0.4 mg nicotine, 0.05 mg deliverable), nicotine inhalers (NI; 10 mg nicotine, 4 mg deliverable), or nicotine-free inhalers (NFI) across 4 sessions following overnight abstinence. Participants rated craving and withdrawal before and after product administration, then completed a cigarette self-administration task. For cigarette self-administration, neither smoking status nor product affected latency to initiate smoking; however, LITS were more likely to abstain from smoking and administered fewer puffs than DDS. Across participants, pharmacologically active products (NC, RNC, NI) were associated with fewer cigarette puffs than the NFI. For subjective measures, only cigarettes (NC, RNC) reduced craving in both LITS and DDS. NC, RNC, and NI reduced withdrawal in DDS, while withdrawal remained at floor levels across time points among LITS. While subjective ratings and smoking behavior were largely comparable across LITS and DDS, differing patterns of withdrawal symptoms suggest that dependent smoking is motivated by negative reinforcement while nondependent smoking is not. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Context matters: Characteristics of solitary versus social cannabis use.

INTRODUCTION AND AIMS: Given the increase in cannabis availability and use in North America, identification of risk factors for cannabis use and dependence is paramount. One factor that may be associated with various cannabis-related adverse outcomes is the context in which it is used. This secondary analysis study sought to examine the extent to which the social context of cannabis use is related to patterns of use and associated harms. DESIGN AND METHODS: One hundred and eighty-eight adult cannabis users were community-recruited in Halifax, Canada. Participants took part in a face-to-face structured interview where they provided information about the social context of their most recent cannabis-using occasion and about their patterns of, and motives for, cannabis use. RESULTS: Compared to individuals reporting their most recent cannabis-using occasion as social, solitary users (n = 55) were significantly more likely to screen positive for psychosis, endorse more symptoms of cannabis abuse/dependence, report using cannabis to cope, and use cannabis on more days within the previous 30 days. On the other hand, social users were significantly more likely to report using alcohol in addition to cannabis during their most recent cannabis-using occasion (all P < 0.05). DISCUSSION AND CONCLUSIONS: Results suggest that solitary cannabis use may be associated with specific motives for use and future adverse consequences. Findings from this study serve as a guide for future investigations which could ultimately inform public policy and the development of targeted harm-reduction strategies.