Longitudinal Relationship between the Introduction of Medicinal Cannabis and Polypharmacy: An Australian Real-World Evidence Study.

Background: Recent studies recommend medicinal cannabis (MC) as a potential treatment for chronic pain (CP) when conventional therapies are not successful; however, data from Australia is limited. This real-world evidence study explored how the introduction of MC related to concomitant medication use over time. Long-term safety also was examined. Methods: Data were collected by the Emerald Clinics (a network of seven clinics located across Australia) as part of routine practice from Jan 2020 toJan 2021. Medications were classified by group: antidepressants, benzodiazepines, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and total number of medications. Adverse events (AEs) were collected at each visit and subsequently coded using the Medical Dictionary for Regulatory Activities version 23 into the system organ class (SOC) and preferred term (PT). A total of 535 patients were analyzed. Results: The most common daily oral dose was 10 mg for delta-9-tetrahydrocannabinol (THC) and 15 mg for cannabidiol (CBD). With the introduction of MC, patients' total number of medications consumed decreased over the course of one year; significant reductions in NSAIDs, benzodiazepines, and antidepressants were observed (p < .001). However, the number of prescribed opioid medications did not differ from baseline to the end of one year (p = .49). Only 6% of patients discontinued MC treatment during the study. A total of 600 AEs were reported in 310 patients during the reporting period and 97% of them were classified as nonserious. Discussion. Though observational in nature, these findings suggest MC is generally well-tolerated, consistent with the previous literature, and may reduce concomitant use of some medications. Due to study limitations, concomitant medication reductions cannot be causally attributed to MC. Nevertheless, these data underscore early signals that warrant further exploration in randomized trials.

Greater adolescent tiredness is related to more emotional arousal during a hyperventilation task: An area under the curve approach.

INTRODUCTION: Approximately 36% of adolescents report sleep problems (Crowley et al., 2018). Understanding the relation between sleep and emotional experience is crucial in understanding the high incidence of mental health concerns during adolescence. The current study sought to expand understanding in the area by testing the hypothesis that baseline tiredness ratings would predict greater emotional arousal and negative valence across the course of emotional response elicited by a voluntary hyperventilation procedure. METHODS: A community sample of 110 youth (10-18 years; 47.8% girls) provided baseline tiredness ratings and ratings of emotional valence and arousal, 2 min before, immediately after, and 3 min after a hyperventilation task. The area under the curve (AUC) was calculated using the repeated measures of valence and arousal, and correlations between the response curves and baseline tiredness were examined. RESULTS AND CONCLUSIONS: Findings indicated baseline tiredness was positively associated with AUC arousal (r = 0.23), but not valence. This suggests daytime tiredness is associated with the degree of emotional arousal elicited by a psychobiological stressor. By extension, adolescents may experience more arousing emotional reactions when tired, and thus the common sleep deprivation observed during this developmental period may increase risk for mental health problems associated with elevated emotional reactivity.

The interaction between anxiety sensitivity and cigarette smoking level in relation to sleep onset latency among adolescent cigarette smokers.

Cigarette smoking during adolescence is linked to a number of sleep disturbances and has been consistently linked to sleep onset latency among adults. However, little research has examined factors that may influence the relation between cigarette smoking level and sleep onset latency among adolescents. One factor that may be particularly important in this regard is anxiety sensitivity (AS). The current study examined whether cigarette smoking level interacted with AS in its association with sleep onset latency among 94 adolescent (Mage = 15.72) cigarette smokers. As hypothesized, AS interacted with smoking level to relate to sleep onset latency, even after controlling for age and gender. This relation was specific to sleep onset latency as opposed to other types of sleep disturbances, and that adolescents who smoked at higher levels tended to go to sleep later and wake up later than adolescents who smoked at relatively lower levels.

Posttraumatic Stress Symptoms and Nonmedical Prescription Drug Use Among College Students With Trauma Exposure.

OBJECTIVE: Nonmedical prescription drug use, defined as using the drug without a prescription or in ways for which it is not prescribed, and traumatic event exposure are highly prevalent among college students. Despite evidence that posttraumatic stress symptoms could place college students at risk for nonmedical prescription drug problems, no studies have examined this relationship. This study was a preliminary examination of posttraumatic stress symptoms, lifetime nonmedical prescription drug use, hazardous use, and dependence symptoms among college students with trauma exposure. METHODS: Participants were students attending a rural college in Virginia, recruited through psychology classes, flyers, LISTSERVs, and announcements at student events. All students who reported experiencing at least one traumatic event were included (N = 119); participants' mean age was 19.7 years (SD = 1.90), about half were women (n = 63, 53%), and most were Caucasian (n = 103, 87%). RESULTS: Nearly 60% of participants (n = 71) reported using nonmedical prescription drugs at least once during their lifetime and were more likely than those with no use to report hazardous alcohol use (p < .01) and depressive symptoms (p < .05). There were no other significant differences between those who did and did not report use of nonmedical prescription drugs. Regression analyses showed that posttraumatic stress symptom frequency was positively associated with hazardous nonmedical prescription drug use, after controlling for gender, depressive symptoms, and hazardous alcohol use (p < .001). Posttraumatic stress symptom frequency was higher for those with any nonmedical prescription drug dependence symptoms (p < .001), but was unrelated to whether the student had ever engaged in nonmedical prescription drug use. CONCLUSIONS: Findings suggest that consideration of the types of behaviors and problems a college student is experiencing related to nonmedical prescription drug use may be more relevant to posttraumatic stress symptom frequency than dichotomous measures of nonmedical prescription drug use alone. Further, the association between the frequency of posttraumatic stress symptoms and both hazardous nonmedical prescription drug use and dependence symptoms among college students with a trauma history deserves further investigation due to the resulting vulnerability to increasingly negative outcomes.

Preliminary evidence for a unique role of disgust-based conditioning in posttraumatic stress.

Independent lines of evidence have linked posttraumatic stress symptomatology to both peritraumatic disgust (i.e., disgust experienced during a traumatic event) and posttraumatic disgust reactivity in response to traumatic event cues among individuals exposed to traumatic events. Much of this work suggests disgust, defined as a rejection/revulsion response aimed at distancing oneself from a potential source of contamination, may be important in understanding the nature of posttraumatic stress reactions even after accounting for the more frequently studied affective states of fear and anxiety. The current investigation provided a preliminary test of a model of disgust in posttraumatic stress among a sample of 54 community-recruited women with a history sexual victimization. Both peritraumatic disgust (r = .31) and posttraumatic disgust reactivity (r = .42) in response to an idiographic traumatic event script were significantly associated with posttraumatic stress symptom severity. After accounting for variability-associated peritraumatic fear and posttraumatic anxious reactivity, an indirect effect of peritraumatic disgust through posttraumatic disgust reactivity also was found, suggesting that one mechanism through which peritraumatic disgust relates to posttraumatic stress is through its relation with increased posttraumatic disgust reactivity. These findings highlight the importance of further elucidating the nature of disgust in relation to traumatic events and subsequent posttraumatic stress reactions.

A Two-Phase, Dose-Ranging, Placebo-Controlled Study of the Safety and Preliminary Test of Acute Effects of Oral Δ8-Tetrahydrocannabivarin in Healthy Participants.

Introduction: Tetrahydrocannabivarin (THCV) is an understudied cannabinoid that appears to have effects that vary as a function of dose. No human study has evaluated the safety and nature of effects in a wide range of THCV doses. Methods: This was a two-phase, dose-ranging, placebo-controlled trial of the Δ8 isomer of oral THCV in healthy adults. Phase 1 utilized an unblinded, single-ascending dose design (n=3). Phase 2 used a double-blind, randomized, within-participant crossover design (n=18). Participants received single acute doses of placebo and 12.5, 25, 50, 100, and 200 mg of THCV. Safety measures and subjective and cognitive effects were assessed predose and up to 8 h postdose. Results: Most adverse events (AEs; 55/60) were mild. Euphoric mood was the most common AE. The 12.5, 25, and 200 mg doses produced significantly lower minimum times to complete the digit vigilance test (ps=0.01). The 25 mg dose showed elevations on mean ratings of "energetic" at 1-, 2-, and 4-h postdose, but the maximum postdose rating for this dose did not achieve statistical significance relative to placebo ([95% confidence interval]=3.2 [-0.5 to 6.9], p=0.116). The 100 and 200 mg doses showed elevations on ratings of "feel a drug effect" and "like the drug effect." Almost all urine drug screens (78/79) at 8 h postdose in the active THCV conditions tested positive for tetrahydrocannabinol (THC). Conclusion: All THCV doses displayed a favorable safety profile. Several THCV doses showed a preliminary signal for improved sustained attention, but the effect was not dose dependent. Though mild and not associated with impairment, THC-like effects were observed at higher THCV doses. Oral THCV-containing products could lead to positive urine drug screens for THC. ClinicalTrials.gov ID: NCT05210634.

A preliminary investigation of the simultaneous effects of cannabidiol and caffeine.

Caffeine and cannabidiol (CBD) are commonly consumed by the general population, particularly among young adults; however, there is little research on the simultaneous effects of caffeine and CBD. The present study aimed to examine the simultaneous self-reported effects of caffeine and CBD in young healthy adults. Participants (N = 54) who reported daily caffeine use (> 200 mg) attended one experimental session via Zoom and were assigned randomly to receive caffeine (200 mg) combined with either a placebo or CBD (25, 50, 80, 160, or 240 mg). Participants completed subjective drug effects measures at baseline and then ingested caffeine and their assigned CBD dose. Throughout the 140-min session, participants completed self-report measures. The primary outcomes of this study were measures of general drug effects and anxiety. After caffeine and CBD administration, few effects were observed in self-reported measures of general drug effects. No negative effects emerged as a result of combined caffeine and CBD administration. These results should be interpreted cautiously given the preliminary nature and variability in outcomes. The present study findings suggest that combinations of the tested doses of caffeine and CBD do not alter subjective drug effects; further, no negative effects emerged, providing preliminary safety evidence for using these products simultaneously. Further research is needed to examine the simultaneous and/or interactive nature of caffeine and CBD on other caffeine-induced outcomes (e.g., cognition and physiological effects) and will be critical for informing future regulatory decisions regarding caffeine: CBD mixtures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A double-blind, randomized, placebo-controlled study of the safety and effects of CBN with and without CBD on sleep quality.

The present study sought to determine the effects of cannabinol (CBN) alone and in combination with cannabidiol (CBD) on sleep quality. This was a double-blind, randomized, placebo-controlled study conducted between May and November 2022. Participants were randomized to receive either (a) placebo, (b) 20 mg CBN, (c) 20 mg CBN + 10 mg CBD, (d) 20 mg CBN + 20 mg CBD, or (e) 20 mg CBN + 100 mg CBD for seven consecutive nights. Participants were 18-55 years of age who self-rated sleep quality as "very poor" or "poor." The primary endpoint was sleep quality, while secondary endpoints included sleep onset latency, number of awakenings, wake after sleep onset (WASO), overall sleep disturbance, and daytime fatigue. In a modified intent-to-treat analyses (N = 293), compared to placebo, 20 mg CBN demonstrated a nonsignificant but potentially meaningful effect on sleep quality (OR [95% CI] = 2.26 [0.93, 5.52], p = .082) and significantly reduced number of awakenings (95% CI [-0.96, -0.05], p = .025) and overall sleep disturbance (95% CI [-2.59, -0.14], p = .023). There was no difference from placebo among any group for sleep onset latency, WASO, or daytime fatigue (all p > .05). Individuals receiving 20 mg CBN demonstrated reduced nighttime awakenings and overall sleep disturbance relative to placebo, with no impact on daytime fatigue. The addition of CBD did not positively augment CBN treatment effects. No differences were observed for latency to sleep onset or WASO. Findings suggest 20 mg of CBN taken nightly may be helpful for improving overall sleep disturbance, including the number of times one wakes up throughout the night, without impacting daytime fatigue. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The relationship of sleep quality and PTSD to anxious reactivity from idiographic traumatic event script-driven imagery.

Poor sleep quality has been linked to posttraumatic stress disorder (PTSD). This study provided a test of how poor sleep quality relates to real-time assessment of anxious reactivity to idiographic traumatic event cues. Script-driven imagery (SDI) was employed to examine reactivity to traumatic event cues among 46 women (mean age = 27.54 years, SD = 13.62; 87% Caucasian) who had experienced either physical or sexual assault. We tested 3 hypotheses: (a) individuals with PTSD would report greater anxiety reactions to SDI than trauma-exposed individuals without PTSD, (b) poorer sleep quality would be positively related to anxiety reactions to SDI, and (c) there would be an interaction between PTSD and sleep quality such that individuals with PTSD and relatively poor sleep quality would report greater anxious reactivity to SDI than would be expected from each main effect alone. Poor sleep quality and PTSD were related to elevated anxious reactivity to trauma cues (sr(2) = .06). In addition, sleep quality was negatively associated with anxious reactivity among people without PTSD (sr(2) =.05). The current findings, in combination with longitudinal evidence, suggest that poor sleep quality following exposure to a traumatic event may be a risk factor for anxious reactivity to traumatic event cues.

An experimental test of the effects of acute sleep deprivation on affect and avoidance.

BACKGROUND AND OBJECTIVES: Avoidance and sleep have been identified as mechanisms involved in the development and maintenance of many mental health disorders. However, there has been little research into the relation between sleep and avoidance. METHODS: To address this, a randomized controlled experiment using behavioral and self-report measures of affect and avoidance was conducted. Compared to a control group, we hypothesized that sleep-deprived individuals would demonstrate increased negative, and decreased positive, affectivity, more avoidance behavior toward a negatively valenced stimulus, as well as increased self-reported avoidance. Fifty-two healthy individuals ages 18-30 years old were randomly assigned to a full night of sleep deprivation or normal sleep. They completed a baseline and post-manipulation behavioral avoidance task (BAT) using a disgusting stimulus and self-reports of avoidance and state affect. RESULTS: Repeated measures ANOVAs demonstrated negative affectivity and self-reported avoidance increased, and positive affectivity decreased, from pre-to post-manipulation in the sleep loss condition as expected. However, there were no effects of sleep deprivation on avoidance behaviors. LIMITATIONS: This study emphasized internal validity over generalizability. Additionally, the at-home sleep deprivation limited researcher control over the overnight activities of participants. CONCLUSIONS: Results replicate prior work on the affective consequences of sleep deprivation and highlight a discrepancy between the effect of sleep deprivation on behavioral avoidance toward a specific stimulus compared to self-reported cognitive and social avoidance behaviors.