A Pilot Study of E-Cigarette Naïve Cigarette Smokers and the Effects on Craving After Acute Exposure to E-Cigarettes in the Laboratory.

BACKGROUND AND OBJECTIVES: Recent surveys confirm continued increases in the use of electronic-cigarettes (e-cigarettes) in adolescents and adults. Users often state that e-cigarettes reduce tobacco craving and withdrawal symptoms in addition to their smoking. Data from laboratory studies and clinical trials have confirmed these statements, though there are inconsistencies in the outcomes. In this pilot study, we set out to evaluate the effects of e-cigarettes, as compared to the participants' own cigarettes, on baseline craving and smoking severity. METHODS: Using a within-subjects, placebo-controlled study design, 15 tobacco-dependent, e-cigarette naïve participants sustained abstinence overnight. They completed distinct phases of this protocol during four separate study sessions. Participants were randomized to an e-cigarette device containing one of three doses of nicotine (0, 18, or 36 mg/ml) or their own cigarette. Each study visit was ~3 hours long and separated by at least 7 days. Visits included assessments of craving and smoking severity. RESULTS: The data showed that after 10 puffs in both the Own cigarette and e-cigarette conditions, breath carbon monoxide levels increased significantly in the former but not the latter. Questionnaire of Smoking Urges and Choices to Smoke scores were not statistically different across groups after two distinct bouts of 10 puffs each. Additionally, E-cigarette Perceptions Questionnaire responses were not significantly different according to dose. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This experiment provides data demonstrating that e-cigarettes did not reduce craving or smoking severity in e-cigarette naïve users. However, since this was a pilot study, the conclusions that can be drawn are limited. (Am J Addict 2019;28:361-366).

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).

Guanfacine Attenuates Adverse Effects of Dronabinol (THC) on Working Memory in Adolescent-Onset Heavy Cannabis Users: A Pilot Study.

The cannabinoid-1 receptor (CB1R) agonist Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, adversely effects working memory performance in humans. The α2A-adrenoceptor (AR) agonist guanfacine improves working memory performance in humans. The authors aimed to determine the effects of short-term (6 days) treatment with guanfacine on adverse cognitive effects produced by THC. Employing a double-blind, placebo-controlled crossover design, the cognitive, subjective, and cardiovascular effects produced by oral THC (20 mg) administration were determined twice in the same cannabis users: once after treatment with placebo and once after treatment with guanfacine (3 mg/day). Compared with performance at baseline, THC negatively affected accuracy on spatial working memory trials while participants were maintained on placebo (p=0.012) but not guanfacine (p=0.497); compared with placebo, accuracy was significantly (p=0.003, Cohen's d=-0.640) improved while individuals were treated with guanfacine. Similarly, compared with baseline, THC increased omission errors on an attentional task while participants were maintained on placebo (p=0.017) but not on guanfacine (p=0.709); compared with placebo, there were significantly (p=0.034, Cohen's d=0.838) fewer omissions while individuals were maintained on guanfacine. Although THC increased visual analog scores of subjective effects and heart rate, these increases were similar during treatment with placebo and guanfacine. THC did not significantly affect performance of a recognition memory task or blood pressure while individuals were maintained on either treatment. Although preliminary, these results suggest that guanfacine warrants further testing as a potential treatment for cannabis-induced cognitive deficits.

Cannabidiol As a Treatment for COVID-19 Symptoms? A Critical Review.

Background: Severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 has caused >211 million infections and >5.5 million deaths within 24 months globally (WHO). Internationally, a debate emerged about potential benefits of cannabidiol (CBD) as treatment of corona virus disease-19 (COVID-19). Objective: To assess the effects of CBD in the treatment of COVID-19-related inflammatory symptoms from the literature. Methods: We searched Cochrane COVID-19 study register, CENTRAL (PubMed, Embase, CINAHL, ClinicalTrials.gov, and the WHO's International Clinical Trials Registry Platform), for studies testing CBD as inflammation intervention. All types of studies and populations were considered. All pre-clinical, clinical, and pharmacological outcomes were of interest. Results: Of 18 articles found, 9 were included: 5 in vivo animal studies, 3 in vitro human tissue studies and, 1 randomized clinical trial. Outcomes in four in vivo animal studies and three human tissue studies were immune response markers, which decreased. One in vivo study showed enhancement of monocytes. One human study did not show group differences in COVID-19 evolution. There was no information on adverse effects or drug interaction. Conclusion: There is not enough evidence to support or refute CBD as a repurpose drug to treat inflammation and other symptoms of COVID-19. Clinical trials are needed to test its efficacy and adverse effects.

Magnetoencephalography in healthy neonates.

OBJECTIVE: To describe magnetoencephalography (MEG) recordings in a cohort of healthy neonates. METHODS: We performed MEG and single channel EEG concomitantly in 21 healthy newborns. MEG and EEG signals were reviewed for gross comparison of general patterns and individual waveform characteristics. Spectral analysis was performed to quantify the signals. RESULTS: Our MEG recordings showed patterns comparable to classical neonatal EEG. Seventy-nine percent of the subjects exhibited the 'continuous polyfrequency activity' at some point in their recording. Sixty-three percent had the 'continuous slow' pattern, and 47% had the 'trace alternant' pattern. Spectral analysis revealed maximal power at frequencies of less than 4 Hz (delta band) in both MEG and EEG with a decline towards higher frequencies. CONCLUSIONS: Neonatal MEG is feasible and shares the basic EEG features and frequency content, with predominant activity in the slow frequency delta band. The latter corresponds to reports from earlier neonatal EEG studies. SIGNIFICANCE: MEG may prove to be useful in studies of neonatal brain functions.

Doxazosin XL reduces symptoms of posttraumatic stress disorder in veterans with PTSD: a pilot clinical trial.

BACKGROUND: Serotonin and norepinephrine reuptake inhibitors are effective first-line agents for the treatment of posttraumatic stress disorder (PTSD), but treatment is associated with a range of side effects that limit treatment adherence. Prazosin, an α1-noradrenergic antagonist with a half-life of roughly 2-3 hours, has shown promise in the treatment of sleep disturbance and nightmares. Doxazosin extended release (XL) is also an α1-noradrenergic antagonist but with a half-life of approximately 15-19 hours. METHODS: We conducted a double-blind, placebo-controlled, within-subjects trial to characterize the impact of doxazosin XL on PTSD symptoms. Participants (N = 8) were diagnosed using DSM-IV criteria. They completed the study twice, once during treatment with doxazosin XL and once during treatment with matched placebo, with a 2-week washout separating the 2 episodes. Doxazosin XL was titrated from 4 mg/d to 16 mg/d over 12 days. After 4 days of treatment at 16 mg/d or the equivalent number of placebo capsules, PTSD symptoms were assessed using the Clinician-Administered PTSD Scale (CAPS17) and the PTSD Checklist-Military version (PCL-M). Repeated measures analysis of variance were used to evaluate effects of treatment, time, and treatment × time. This study was run from November 20, 2013, to June 31, 2014. RESULTS: Doxazosin XL treatment was associated with a nonsignificant treatment × time reduction in ratings on the CAPS hyperarousal subscale (P < .10) (but not on the CAPS Total score) and with significant treatment × time reductions in PCL-M ratings (P = .002). CONCLUSIONS: Doxazosin XL may be an effective alternative to prazosin for the treatment of some PTSD symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:NCT02308202.

Development of auditory evoked fields in human fetuses and newborns: a longitudinal MEG study.

OBJECTIVE: To investigate the maturation of the auditory cortex by non-invasive recording of auditory evoked magnetic fields in human fetuses and newborns with the relatively novel and completely non-invasive technology of MEG. METHODS: Serial recordings were performed every 2 weeks on 18 fetuses beginning from week 27 of gestational age until term with a follow-up recording on the newborn. Auditory stimulation consisted of tone bursts in an oddball design with standard tones and deviant tones. RESULTS: In 52 of 63 fetal and in all of the neonatal recordings an auditory evoked magnetic field was obtained. A decrease in latency with increasing age of the subjects was observed in the combined analysis of fetuses and neonates. CONCLUSIONS: With advanced study using MEG, 83% of the measurements showed auditory evoked fields in fetuses that correspond with existing literature in electrophysiology in the past. These findings indicate that MEG is a technique that can be used to investigate maturation of the auditory cortex based on auditory evoked fields in fetuses and neonates. SIGNIFICANCE: Maturational changes have been examined in the past. With the use of this novel technique, applied to a serial study, it is possible to trace the development of auditory responses in utero and newborns.