Buccally Absorbed Cannabidiol Shows Significantly Superior Pain Control and Improved Satisfaction Immediately After Arthroscopic Rotator Cuff Repair: A Placebo-Controlled, Double-Blinded, Randomized Trial.

BACKGROUND: Despite the widespread use and sales of cannabidiol (CBD) products in the United States, there is a paucity of literature to evaluate its effectiveness, safety, or ideal route of administration for postoperative pain. PURPOSE: To evaluate the potential analgesic effects of buccally absorbed CBD in patients who have undergone arthroscopic rotator cuff repair (ARCR). STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This was a US Food and Drug Administration-sanctioned, multicenter, placebo-controlled, randomized, double-blinded trial conducted in patients undergoing ARCR. Patients aged from 18 to 75 years undergoing ARCR were prospectively enrolled and randomized to the control and experimental groups. The experimental group received an oral, buccally absorbed tablet containing 25 mg of CBD 3 times a day if <80 kg, or 50 mg of CBD 3 times a day if >80 kg, for 14 days postoperatively, while the control group received an identical placebo. Patients were followed up on days 1, 2, 7, and 14, and visual analog scale (VAS) for pain scores, opioid consumption, and satisfaction with pain control were recorded. Additionally, liver function tests were conducted on days 7 and 14 to assess safety, and nausea was monitored. P < .05 was considered to be statistically significant. RESULTS: Overall, 100 patients were recruited, with 1 patient being excluded, for a total of 99 patients. There were no significant differences in patient demographics between the 2 groups. On day 1, the VAS pain score was significantly lower in the CBD group than in the control group (4.4 ± 3.1 vs 5.7 ± 3.2, respectively; P = .04), although this difference was no longer present on day 2 (4.7 ± 2.8 vs 5.3 ± 2.6, respectively; P = .32). On both days 1 and 2, patient satisfaction with pain control was significantly higher in the CBD group than in the control group (day 1: 7.0 ± 3.0 vs 5.6 ± 3.7, respectively [P = .04]; day 2: 7.3 ± 2.5 vs 6.0 ± 3.3, respectively [P = .03]). The quantity of opioids consumed was low in both groups, and there were no statistically significant differences in opioid consumption (P > .05). On days 7 and 14, there were no statistically significant differences in VAS scores, opioid consumption, or patient satisfaction with pain control between the CBD and control groups (P > .05 for all). There were no significant differences in liver function test results postoperatively (P > .05). CONCLUSION: Buccally absorbed CBD demonstrated an acceptable safety profile and showed significant promise in the reduction of pain in the immediate perioperative period after ARCR compared with the control. Further studies are currently ongoing to confirm dosing and effectiveness in other orthopaedic conditions. REGISTRATION: NCT04672252 (ClinicalTrials.gov identifier).

Low cardiac vagal tone index by heart rate variability differentiates bipolar from major depression.

Objectives: Major depressive disorder (MDD) and depression in bipolar disorder (BD) are often difficult to distinguish from each other. Autonomic nervous system (ANS) dysregulation is associated with various depressive symptoms and inflammatory response disinhibition. The beat-to-beat pattern of heart rate (heart rate variability, HRV) offers a non-invasive portal to ANS function and provides a reliable index of resting cardiac vagal tone. We quantified HRV and measured inflammatory biomarkers in MDD and BD patients in an effort to derive potential diagnostic criteria for MDD and BD. Methods: Sixty-four MDD and 37 BD patients were enrolled. HRV was assessed and blood was drawn at baseline after antidepressant washout and prior to study initiation. HRV was quantified and corrected for artefacts. Results: MDD subjects had significantly higher baseline respiratory sinus arrhythmia (P = 0.05) and LF-HRV (P < 0.01) in comparison to BD subjects. Compared to MDD subjects, BD subjects had significantly higher baseline levels of IL-10 (P < 0.01) and MCP-1 (P < 0.01). In the MDD group only, baseline LF-HRV was significantly positively correlated to baseline levels of IL-10 (r = 0.47, P < 0.01). Conclusions: Reduced vagal tone and higher levels of inflammatory biomarkers may distinguish BD from MDD and reveal an underlying pathophysiology of depression involving ANS dysfunction and chronic immune system dysregulation.

Diminution of Heart Rate Variability in Bipolar Depression.

Autonomic nervous system (ANS) dysregulation in depression is associated with symptoms associated with the ANS. The beat-to-beat pattern of heart rate defined as heart rate variability (HRV) provides a noninvasive portal to ANS function and has been proposed to represent a means of quantifying resting vagal tone. We quantified HRV in bipolar depressed (BDD) patients as a measure of ANS dysregulation seeking to establish HRV as a potential diagnostic and prognostic biomarker for treatment outcome. Forty-seven BDD patients were enrolled. They were randomized to receive either escitalopram-celecoxib or escitalopram-placebo over 8 weeks in a double-blind study design. Thirty-five patients completed the HRV studies. Thirty-six healthy subjects served as controls. HRV was assessed at pretreatment and end of study and compared with that of controls. HRV was quantified and corrected for artifacts using an algorithm that incorporates time and frequency domains to address non-stationarity of the beat-to-beat heart rate pattern. Baseline high frequency-HRV (i.e., respiratory sinus arrhythmia) was lower in BDD patients than controls, although the difference did not reach significance. Baseline low-frequency HRV was significantly lower in BDD patients (ln4.20) than controls (ln = 5.50) (p < 0.01). Baseline heart period was significantly shorter (i.e., faster heart rate) in BDD patients than controls. No significant change in HRV parameters were detected over the course of the study with either treatment. These findings suggest that components of HRV may be diminished in BDD patients.

The Influence of Exercise Environment and Gender on Mood and Exertion.

This study examined the influence of exercise environment and gender on post-exercise mood and exertion. College student participants (55 females, 49 males) were instructed to pedal a stationary bike at a moderate pace for 20 minutes. Participants were randomly assigned to one of three laboratory conditions: (1) exercising in front of a mirror and posters showing ideal fit body types (i.e., celebrity male and female personal trainers), (2) exercising in front of a mirror only, or (3) a control condition in which participants exercised without a mirror or posters. The Activation-Deactivation Adjective Check List (AD-ACL), measuring exercise-induced mood states, was administered both before and after exercise. Average bike speed throughout the exercise session measured exertion. Mirrors and posters of ideally fit celebrities did interact with gender on post-exercise tension in that women felt most tense after exercising in front of the mirror and posters while men were most tense after exercising in front of the mirror only. Exercise exertion was also impacted by experimental condition such that participants rode significantly faster in the mirror and posters condition. There was no significant interaction of gender and condition on exercise exertion, but women pedaled fastest in the mirror and poster condition relative to the other conditions. Results suggest that exercise exertion and tension reduction are partially a by-product of gender and exercise environment.