A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers.

PT150, a novel competitive glucocorticoid receptor (GR) antagonist, has proven safe in animal models, healthy volunteers, and people with depression. Our study is the first to investigate PT150's safety with alcohol use. The primary objective of this study was to evaluate pharmacodynamic interactions between ethanol and PT150 in healthy subjects. This single-site, Phase I pilot trial consisted of community-recruited, healthy, alcohol-experienced participants aged 21-64 years. Of 32 participants screened, 11 were enrolled and randomized, one of which withdrew before intervention. PT150 (900 mg/day) was administered orally to all participants for five days. All participants received two beverage challenges on Day 1 (before PT150 administration) and Day 5 (after PT150 administration). On challenge days, they received both alcohol (16% ethanol) and placebo (1% ethanol) beverages in random order. Primary outcomes included breath alcohol level, blood pressure, heart rate, adverse events, and electrocardiogram changes. There were no statistically significant differences in vital signs or estimated blood alcohol concentrations between PT150 non-exposed and exposed groups during the ethanol challenge. There were no clinically significant abnormal electrocardiograms or serious adverse events. These data show that administration of PT150 with concurrent alcohol use is safe and well-tolerated. This study supports a future pharmacokinetic interaction study between PT150 and alcohol.Trial Registration ClinicalTrials.gov Identifier: NCT03548714.

Suicidal behaviors and attention deficit hyperactivity disorder (ADHD): a cross-sectional study among Chinese medical college students.

BACKGROUNDS: Associations between attention deficit hyperactivity disorder (ADHD) subtypes and suicidal behaviors remains unclear. The current study explored the prevalence of suicidal behaviors, and its association with ADHD among Chinese medical students. METHODS: Five thousand six hundred ninety-three medical college students participated. Symptoms of suicidal behaviors, ADHD, anxiety, depression, tobacco and alcohol use were assessed using online questionnaires. RESULTS: The prevalence of lifetime suicidal ideation, suicide plans, and suicide attempts among medical college students were 27.5, 7.9 and 14.8% respectively. Participants with ADHD predominantly inattentive type (ADHD-I) had more than fivefold increased odds of suicidal behaviors, the adjusted odds ratios (ORs) of ADHD-I and ADHD combined type (ADHD-C) remained significant after controlling for confounding factors. CONCLUSIONS: ADHD is associated with high risk of suicidal behaviors. ADHD-I and ADHD-C were strongly associated with suicidal behaviors independent of comorbidities. The finding suggests the importance of addressing ADHD symptoms in suicide prevention.

Use of Guanfacine for Cannabis Use Disorder and Related Symptomology.

BACKGROUND AND OBJECTIVES: No medication has Food and Drug Administration approval for cannabis use disorder (CUD), and most medication development focuses on the withdrawal syndrome. We evaluated the effects of short-term treatment using the α-2A-adrenergic receptor agonist, guanfacine, on withdrawal symptoms in volunteers with CUD and a history of early onset of cannabis use. METHODS: Non-treatment-seeking healthy volunteers (n = 7) who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for CUD participated in a two-phase, within-subjects study. Volunteers received placebo or guanfacine (3 mg/day) for the first 8-day inpatient study and the alternative medication for the second 8-day inpatient study. On day 1 of both treatment periods, participants received 30 mg of synthetic Δ9 -tetrahydrocannabinol for standardization of abstinence onset. On days 2 to 7, participants received study medication. Cannabis withdrawal symptoms, sleep, craving, and physiology were assessed on all inpatient days. RESULTS: Compared with placebo, guanfacine did not show significant effects on withdrawal, craving, or sleep, although there were trends for guanfacine to increase positive mood symptoms and decrease craving-associated compulsivity. DISCUSSION AND CONCLUSIONS: Compared with former studies, we could not prove significant improvement in sleep or decrease of negative symptoms, but we found trends for increased positive mood symptoms. Our data did not show significant effects of guanfacine on withdrawal symptoms or craving. Due to early and longer cannabis use, our subjects indicate a great severity of illness increasing the likelihood of treatment resistance. SCIENTIFIC SIGNIFICANCE: On the basis of trends demonstrated here and other lines of evidence, further investigation is warranted regarding the utility of guanfacine as a potential treatment for CUD. (Am J Addict 2019;00:1-10).

The prevalence, metabolic disturbances and clinical correlates of recent suicide attempts in Chinese inpatients with major depressive disorder.

BACKGROUND: Metabolic disturbances have been correlated with suicidality, but little is known about the association between suicide risk and metabolic disturbances among individuals with depression. This study was to evaluate the prevalence and clinical correlations, especially cardio-metabolic associated factors of recent suicide attempts in Chinese patients with major depressive disorder (MDD). METHODS: A total of 288 MDD inpatients were recruited. Their clinical and demographic data together with plasma glucose, lipid and thyroid function parameters were collected. Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS) and Eysenck Personality Questionnaire (EPQ) were rated for most of the patients. RESULTS: Of these MDD inpatients, 20.14% had attempted suicide during the past 1 month. Compared to those who had not attempted suicide, the suicide attempters had a significantly longer duration of illness, lower low-density lipoprotein (LDL) cholesterol, lower total cholesterol, and more psychotic symptoms. However, all these significant results did not survive after the bonferroni correction (all p > 0.05). A logistic regression analysis indicated that suicide attempts were associated with the lower total cholesterol and more psychotic symptoms. CONCLUSIONS: Our findings support the hypothesis of the association of low plasma cholesterol level and recent suicidal attempts in patients with MDD.

FAAH variant Pro129Thr modulates subjective effects produced by cocaine administration.

BACKGROUND AND OBJECTIVES: The endogenous cannabinoid anandamide (AEA), an agonist at type-1 cannabinoid (CB1) receptors, is metabolized by fatty acid amide hydrolase (FAAH). The common variant rs324420 C->A within the FAAH gene on chromosome 1 codes for a missense substitution (Pro129Thr), resulting in decreased FAAH activity and increased endocannabinoid potentiation. This FAAH variant has been linked to alterations in mood and stress reactivity, as well as being independently linked to increased risk for addiction. We hypothesized that cocaine use disordered (CUD) participants with the FAAH Pro129 Thr variant would exhibit a distinct profile of cocaine-induced subjective effects in the laboratory. METHODS: A total of 70 CUD participants received intravenous doses of saline (placebo, 0 mg) and cocaine (20, 40 mg) in a lab-controlled setting and rated 10 subjective effect measures prior to and following saline and cocaine administration, using a Visual Analog Scale (VAS). RESULTS: The variant allele was associated with increased cocaine-induced subjective ratings for "Drug Effect," "High," and "Depressed." The prevalence of the variant allele A and the AA genotypes were greater in our CUD group than in the general population (A allele: 47% vs. 34%; AA genotype: 30% vs. 13%; p < .05). Finally, the reported amount and frequency of tobacco and cocaine use was higher in subjects with the AC/AA allele. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These results add to existing evidence that this variant of the FAAH genotype may be over-represented among those who have CUD, and this over-representation may result from greater subjective responses to cocaine administration. (Am J Addict 2018;27:567-573).

Inter-Rater Agreement in the Assessment of Video Recordings of Eye Drop Instillation by Glaucoma Patients.

PURPOSE: To create a standardized method for evaluating the video recordings of patients self-instilling eye drops and to determine the level of agreement of eye drop instillation efficacy, safety and efficiency ratings by three masked graders. DESIGN: Prospective cross-sectional study. PARTICIPANTS: 78 patients with open-angle glaucoma or ocular hypertension who had at least 6 months of experience with the use of eye drop medications. METHODS: Participants were video recorded while self-instilling artificial tears sequentially to both eyes. Three masked observers graded these video recordings on three criteria: efficacy (the determination of whether an eye drop was instilled on the ocular surface), safety (assessment of whether the tip of the medication bottle made contact with the ocular surface or eyelids), and efficiency (the number of eye drops expressed from the bottle). MAIN OUTCOME MEASURES: After grading the video recordings based on efficacy, safety, and efficiency, kappa statistics were used to estimate inter-rater agreement. RESULTS: The mean kappa level of agreement for efficacy, safety, and efficiency was 0.64 (95% confidence interval (CI), 0.42-0.87), 0.73 (95% CI, 0.58-0.88), and 0.62 (95% CI, 0.42-0.81), respectively. CONCLUSIONS: We demonstrated good inter-rater reproducibility of the masked analysis of video recordings of patients self-instilling eye drops based on three criteria: efficiency, safety, and efficacy.