Angela D. Bryan’s research while affiliated with University of Colorado Boulder and other places

Background As cannabis legalization continues to spread across the United States, average Δ⁹-tetrahydrocannabinol concentrations in recreational products have significantly increased, and no prior study has evaluated effective treatments to reduce cannabis use among high potency cannabis users. Some research has found that the non-intoxicating cannabinoid cannabidiol reduces cannabis use and cannabis use disorder-related symptoms, such as affective disturbance and withdrawal. Results of these studies are promising but limited to synthetic or isolated forms of cannabidiol. Objective Conduct a placebo-controlled randomized control trial comparing the effects of hemp-derived cannabidiol on reducing Δ⁹-tetrahydrocannabinol use in concentrate users with cannabis use disorder. Methods Design. Double-blind, three-arm randomized placebo-controlled trial. Setting. University in the Denver-Boulder, CO, USA area. Study population. Community members who are heavy, stable cannabis concentrate users that meet criteria for at least moderate cannabis use disorder and are seeking to decrease or stop cannabis use. Data. Self-report demographics, substance use, and mental health characteristics, blood and urine based biomarkers and anthropometrics. Outcomes. Affective, physiological, and physical withdrawal symptoms, Δ⁹-tetrahydrocannabinol use. Analysis. Three-group ANOVAs and χ² tests will be used to compare baseline variables between groups. Characteristics that differ between groups will be evaluated as potential covariates in subsequent analyses. A multilevel modeling framework will be used for primary outcome analysis to account for the repeated observations nested within participants over time. Pairwise post-hoc simple effects tests will be conducted to confirm patterns of differences. Trial registration ClinicalTrials.gov NCT06107062.

Introduction Cannabis, commonly known for both therapeutic and intoxicating effects, is gaining accessibility on legal markets and traction as a potential alternative therapy for pain mediation, particularly in those suffering from chronic low back pain. However, the effectiveness in this population of legal market forms of cannabis, particularly commonly used edibles, is unknown. Methods Therefore, this study utilized a naturalistic prospective design where participants with chronic low back pain with intentions to initiate cannabis use for treatment were recruited and self-selected edible cannabis products containing varying amounts of delta- 9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Products were categorized as CBD-dominant, THC-dominant, or combined THC and CBD (THC + CBD). Results 249 participants [140 female (56.62%), mean (SD) age of 46.30 (16.02), 90% White] were tracked over 2 weeks of ad libitum use and assessed during a naturalistic acute cannabis administration session on changes in pain, mood, and subjective drug effects. During acute administration, a significant correlation between THC dose and short-term pain relief was found, suggesting that higher THC doses were associated with greater pain reduction (p < .05). In addition, THC was associated with higher levels of subjective cannabis drug effects (p < .001), regardless of whether CBD was also in the edible product. Acute CBD dose was primarily associated with short-term tension relief (p < .05); however, there were no associations between CBD dose and acute pain. Over the 2-week ad libitum administration period results suggested pain reductions across participants using all forms of cannabis. However, trends suggested that more frequent use of CBD-dominant edible cannabis may be associated with greater reductions in perceived pain over the 2-week observation period (p = .07). Discussion These findings support the short-term analgesic effects of THC and anxiolytic effects of CBD and further suggest that orally-administered THC and CBD should continue to be evaluated for the potential to provide both acute and extended relief from chronic low back pain. Clinical Trial Registration https://clinicaltrials.gov/study/NCT03522324?locStr=Boulder,%20CO&country=United%20States&state=Colorado&city=Boulder&cond=chronic%20low%20back%20pain&intr=Cannabis&rank=1, identifier NCT03522324.

Background It is well-recognized that maintaining a regular yogic practice is associated with numerous physical and psychological health benefits. However, few studies have explored the possible psychological and neurophysiological mediators through which the component parts of yoga—ethics, breath regulation, postures, and meditation—work to produce salutary effects. Purpose To address this gap, we conducted a cluster randomized trial to test the following set of theory-based mechanisms: emotion regulation for ethics, self-control for breath regulation, discomfort and distress tolerance for postures, and mindfulness for meditation. We also explored yoga’s effects on the autonomic nervous system by examining salivary acetylcholinesterase levels. Methods Participants (N = 260) were randomly assigned in clusters (n = 37) to a single, hour-long standard or postures-only yoga class. Results Findings suggest that a single yoga class may confer both psychological and neurophysiological benefits, yet there were few differences between the two types of yoga classes. Pre- to post-session main effects of time, all in the expected direction, emerged for five of eight theoretical mediators, as well as for salivary acetylcholinesterase levels. Time X condition interactions observed for three of the mediators—cognitive reappraisal, discomfort tolerance, and expressive suppression—along with findings from the exploratory mediation analysis suggest potential unique benefits of the two yoga sessions for certain outcomes. Conclusions Additional studies are needed to replicate these results and to test other potential mediators and/or primary outcomes through which yoga might work to promote health.

Background Solitary drinking is a risky drinking pattern associated with increased substance use and psychosocial problems. However, very little is known regarding the associations between drinking alone and broader health status and behaviors. Purpose Accordingly, this study examined the relationship between health metrics and solitary drinking among individuals who currently drink (N = 99, 46.46% female, 88.89% White). Methods U.S. participants between 21 and 40 years old were recruited. Measures included self-reported diet, physical activity, sleep, cannabis use, general and solitary alcohol use, and objective anthropomorphic measures (e.g., body mass index [BMI]) using data from both a baseline appointment and 30 days of daily diary responses. Adjusting for general alcohol use, age, and gender, associations at baseline were assessed through regression analyses, while daily data were analyzed via mixed effects models. Results Several health measures were associated with solitary drinking. Specifically, solitary drinking was related to consuming fewer servings of fruits and vegetables and greater quantities of alcohol based on daily data. Baseline data showed an association between solitary drinking and higher BMIs, poorer sleep quality, greater sugar consumption, and hazardous drinking. Conclusions These findings suggest that beyond substance and psychosocial problems associated with solitary drinking, this drinking behavior may be a warning sign for health risks and, subsequently, broader health problems.

Introduction: In Colorado, both cannabis and psilocybin are legal and becoming more commonly used. However, there is almost no research detailing the public health concerns regarding negative outcomes (e.g., dependence) of cannabis and psilocybin co-use and motives that may perpetuate these negative outcomes (e.g., coping, boredom). Methods: Using data from a larger observational study on cannabis and metabolic processes, regular cannabis users (use ≥7 times/month; n = 97, 35.1% female, 89.7% WHITE) who used psilocybin in the past 3 months (n = 34) were compared with those who had not used psilocybin in the past 3 months (n = 63) on cannabis dependence as measured by the Marijuana Dependence Scale and endorsement of 12 cannabis motives from the Comprehensive Marijuana Motives Questionnaire. Correlations between motives and dependence were also examined and compared across groups. Results: Findings revealed that individuals who had recently used psilocybin had greater cannabis dependence scores than those who had not used recently [F (1, 95) = 5.53, p = 0.02], and more strongly endorsed that their cannabis use was motivated by enjoyment [F (1, 91) = 4.31, p = 0.04], boredom [F (1, 91) = 9.10, p < 0.01], and availability [F (1, 91) = 9.46, p < 0.01]. Correlations between dependence scores and coping and boredom motives were also significantly positive for both groups (all p values <0.05) whereas positive correlations with experimentation, celebration, and availability motives were only significant for recent psilocybin users (all p values <0.05). Discussion: These results suggest there are motivational differences for cannabis use among those who co-use cannabis and psilocybin, and there may be a greater risk for harm for these individuals.

Chronic, low-grade inflammation increases with aging, contributing to functional declines and diseases that reduce healthspan. Growing evidence suggests that transcripts from repetitive elements (RE) in the genome contribute to this “inflammaging” by stimulating innate immune activation, but evidence of RE-associated inflammation with aging in humans is limited. Here, we present transcriptomic and clinical data showing that RE transcript levels are positively related to gene expression of innate immune sensors, and to serum interleukin 6 (a marker of systemic inflammation), in a large group of middle-aged and older adults. We also: (1) use transcriptomics and whole-genome bisulfite (methylation) sequencing to show that many RE may be hypomethylated with aging, and that aerobic exercise, a healthspan-extending intervention, reduces RE transcript levels and increases RE methylation in older adults; and (2) extend our findings in a secondary dataset demonstrating age-related changes in RE chromatin accessibility. Collectively, our data support the idea that age-related RE transcript accumulation may play a role in inflammaging in humans, and that RE dysregulation with aging may be due in part to upstream epigenetic changes.

Despite strong evidence linking anti-fat bias directed toward others with markers of self-directed anti-fat bias, there is a dearth of theory-based research examining the cognitive pathways underlying this relationship, and existing bias-reduction intervention efforts have thus far been conducted with exclusive focus on one domain or the other. Cognitive dissonance (CD)-based interventions have been identified as viable for reducing anti-fat bias directed toward the self and others. However, no study has yet examined whether the effects of these domain-specific interventions (e.g., anti-fat bias towards the self) extend to anti-fat bias in the non-targeted domain (e.g., anti-fat bias towards others). The present study aimed to address these gaps in the literature by comparing effects of brief CD-based interventions targeting anti-fat bias directed toward either the self or others on measures of anti-fat bias. Participants (N = 197, female-identifying undergraduates) were randomized to a writing activity prompting cognitive dissonance about either self-directed or other-directed anti-fat bias, or a bias-consistent control condition. Results indicated that participants in the CD intervention conditions showed significantly greater reductions in both explicit self- and other-directed anti-fat biases than those in the control condition, but results did not significantly differ across CD conditions. This supports the potential utility of interventions simultaneously targeting anti-fat bias in both domains and provides insight into the cognitive pathways underlying these related forms of bias.

Objective: Cannabis has been touted for a host of pharmacological and therapeutic effects and users commonly report reduced symptoms of physical and mental health conditions, including anxiety, depression, and chronic pain. While there is existing empirical evidence supporting these effects of cannabis use, little is known about the extent to which these effects result from pharmacological versus expectancy factors. We evaluated the associations between participants' cannabis expectancies and their acute self-reported reactions after using legal market forms of cannabis with varying levels of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in three domains: anxiety, depression, and pain. Methods: Fifty-five flower and 101 edible cannabis users were randomly assigned and asked to purchase at a local dispensary one of three products containing varying levels of CBD and THC. Participants completed a baseline assessment where they reported expectancies about general health effects of cannabis use and an experimental mobile laboratory assessment where they administered their assigned products. Edible users also reported their domain-specific expectancies about cannabis use in improving anxiety, depression, and pain. Following administration, participants completed acute indicators of anxiety, depression, and pain operationalized through subjective acute tension, elation, and a single-item measure of pain. Results: Among flower users, more positive expectancies for cannabis to improve general health were correlated with greater reductions in tension at acute post-use. This finding was replicated among edible users. Unlike flower users, more positive expectancies for cannabis to improve general health were also correlated with greater increases in elation and greater reductions in pain among edible users. More positive expectancies for cannabis to improve depression and pain were also correlated with greater increases in elation and greater reductions in pain, respectively, among edible users. Conclusions: Cannabis users' expectancies significantly impacted some of the acute subjective effects of legal market cannabis products. Among both flower and edible users, consistent, significant expectancy effects were found. Results were consistent with prior findings and demonstrate the need to measure and control pre-existing expectancies in future research that involves cannabis administration. Clinical trial registration number: NCT03522103.

Objective: Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have varying pharmacological actions with differential effects on acute and extended affective states, incuding anxiety. We aimed to study these effects on anxiety in legal market forms of cannabis. Method: This study makes use of a nonequivalent control group quasiexperimental design. Forty-two participants with anxiety symptions who were not using cannabis were compared to 258 participants with anxiety symptoms who used cannabis flower (∼3-4 times per week). Participants who used cannabis were randomly assigned to one of three legal market cannabis conditions; THC-dominant (24% THC, <1% CBD), THC+CBD (12% THC, 12% CBD), or CBD-dominant (<1% THC, 24% CBD). Changes in anxiety symptoms over 4-weeks were measured by the Patient Global Impression of Change (PGIC) scale and the Depression, Anxiety, and Stress Scale (DASS). Acute changes in subjective mood immediately after cannabis use were measured by the Profile of Mood States (POMS) Elation, Tension, and Paranoia subscales and the Addiction Research Center Inventory intoxication scale. Results: While all participants reported anxiety reductions over the 4-week study on the PGIC (F=30.65, p<0.001) and DASS anxiety measures (F=115.88, p<0.001), ad libitum CBD-dominant cannabis use was associated with lower scores on the DASS anxiety subscale compared to THC-dominant use when accounting for frequency of use (difference=-1.03, SE=0.45, p=0.02). Similarly, acute CBD-dominant cannabis use was associated with lower scores on the POMS tension and paranoia subscales (POMS tension: CBD-dominant vs. THC-dominant: difference=-0.41 SE=0.1, p<0.001; CBD-dominant vs. THC+CBD: difference=-0.28, SE=0.07, p=0.04; POMS paranoia: CBD-dominant vs. THC-dominant: difference=-0.49, SE=0.1, p<0.001; CBD-dominant vs. THC+CBD: difference=-0.33, SE=0.09, p=0.01). Participants in all cannabis conditions experienced acute changes in positive mood and subjective drug effects. Conclusions: This study provides novel information on the impacts of legal market cannabis with varying ratios of THC to CBD in indviduals with anxiety symptoms. Findings suggest that THC did not increase anxiety and that CBD-dominant forms of cannabis were associated with acute tension reduction that may translate to longer-term reductions in anxiety symptoms. Clinical Trial Registration: NCT03491384.