Cannabis use has been associated with altered sensory gating and neural oscillations. However, it is unclear which constituent in cannabis is responsible for these effects, or whether these are cannabinoid receptor 1 (CB1R) mediated. Therefore, the present study in humans and rats examined whether cannabinoid administration would disrupt sensory gating and evoked oscillations utilizing electroencephalography (EEG) and local field potentials (LFPs), respectively. Human subjects (n = 15) completed four test days during which they received intravenous delta-9-tetrahydrocannabinol (Δ-THC), cannabidiol (CBD), Δ-THC + CBD, or placebo. Subjects engaged in a dual-click paradigm, and outcome measures included P50 gating ratio (S2/S1) and evoked power to S1 and S2. In order to examine CB1R specificity, rats (n = 6) were administered the CB1R agonist CP-55940, CP-55940+AM-251 (a CB1R antagonist), or vehicle using the same paradigm. LFPs were recorded from CA3 and entorhinal cortex. Both Δ-THC (p < 0.007) and Δ-THC + CBD (p < 0.004) disrupted P50 gating ratio compared to placebo, while CBD alone had no effect. Δ-THC (p < 0.048) and Δ-THC + CBD (p < 0.035) decreased S1 evoked theta power, and in the Δ-THC condition, S1 theta negatively correlated with gating ratios (r = -0.629, p < 0.012 (p < 0.048 adjusted)). In rats, CP-55940 disrupted gating in both brain regions (p < 0.0001), and this was reversed by AM-251. Further, CP-55940 decreased evoked theta (p < 0.0077) and gamma (p < 0.011) power to S1, which was partially blocked by AM-251. These convergent human/animal data suggest that CB1R agonists disrupt sensory gating by altering neural oscillations in the theta-band. Moreover, this suggests that the endocannabinoid system mediates theta oscillations relevant to perception and cognition.

Background: Binding studies have demonstrated that levels of the cannabinoid receptor type-1 are highest in the basal ganglia and cerebellum, two areas critical for motor control. However, no studies have systematically examined the dose-related effects of intravenous delta-9-tetrahydrocannabinol, the primary cannabinoid receptor type-1 partial agonist in cannabis, on broad domains of psychomotor function in humans. Aims: Therefore, three domains of psychomotor function were assessed in former cannabis users (cannabis abstinent for a minimum of three months; n=23) in a three test-day, within-subject, double-blind, randomized, cross-over, and counterbalanced study during which they received intravenous delta-9-tetrahydrocannabinol (placebo, 0.015 mg/kg, and 0.03 mg/kg). Methods: Gross motor function was assessed via the Cambridge Neuropsychological Test Automated Battery Motor Screening Task, fine motor control via the Lafayette Instrument Grooved Pegboard task, and motor timing via a Paced Finger-Tapping Task. In addition, the Cambridge Neuropsychological Test Automated Battery Rapid Visual Processing Task was utilized to determine whether delta-9-tetrahydrocannabinol-induced motor deficits were confounded by disruptions in sustained attention. Results/outcomes: Delta-9-tetrahydrocannabinol resulted in robust dose-dependent deficits in fine motor control (Grooved Pegboard Task) and motor timing (Paced Finger-Tapping Task), while gross motor performance (Motor Screening Task) and sustained attention (Rapid Visual Processing Task) were unimpaired. Interestingly, despite the observed dose-dependent increases in motor impairment and blood levels of delta-9-tetrahydrocannabinol, subjects reported similar levels of intoxication in the two drug conditions. Conclusions/interpretation: These data suggest that while several domains of motor function are disrupted by delta-9-tetrahydrocannabinol, subjective feelings of intoxication are dissociable from cannabinoid-induced psychomotor effects. Results are discussed in terms of the potential neural mechanisms of delta-9-tetrahydrocannabinol in motor structures.

Disulfiram has shown promise in several clinical trials for cocaine addiction, but its potential utility in the treatment of amphetamine addiction has not been examined. The goal of this study was to determine the effects of disulfiram on acute physiological and subjective responses to dextroamphetamine in healthy volunteers. Five male and 5 female subjects participated in an outpatient double-blind, placebo-controlled, crossover study. Subjects were randomly assigned to a sequence of disulfiram (250 mg/day) or placebo treatments each lasting for 4 days. Day four of each treatment period was the experimental session, in which subjects orally ingested a single dose of dextroamphetamine (20 mg/70 kg). Outcome measures included heart rate, blood pressure, plasma cortisol and prolactin, subjective and performance on the Sustained Attention to Response Test (SART). Disulfiram did not affect dextroamphetamine-induced increases in heart rate, blood pressure, cortisol, or prolactin. Disulfiram did enhance some of the subjective effects of dextroamphetamine including ratings of "high," "anxious," "bad drug effects," "want more drug" and "drug liking" and was also associated with decreased performance in the SART test. How these enhanced subjective amphetamine responses affect cocaine use behavior remains to be determined in future clinical trials.Disulfiram enhances subjective effects of dextroamphetamine in humans. Amphetamine abuse, especially methamphetamine, is an important public health problem in the US, with an estimated 1.4 million have reported methamphetamine use during the past year (SAMHSA, 2004). There are no approved pharmacotherapies for the treatment of amphetamine (Hill and Sofuoglu, 2007) or cocaine addiction, the other commonly used stimulant (Sofuoglu and Kosten, 2006). Given the similarities between the pharmacological effects of cocaine and amphetamines (Fischman et al., 1976), it is plausible that potential pharmacotherapies may be effective for both cocaine and amphetamine addiction. One of the promising medications for cocaine addiction is disulfiram (Antabuse), which has been shown to reduce cocaine abuse and relapse in outpatient clinical trials (Carroll et al., 1993;Carroll et al., 2004;Carroll et al., 1998;George et al., 2000;Petrakis et al., 2000). Disulfiram is approved by the Food and Drug Mehmet Sofuoglu, Yale University, Department of Psychiatry, VA Connecticut Healthcare System, 950 Campbell Ave., Bldg. 36/116A4, West Haven, CT 06516, Phone: (203) Fax: (203) 937-3478, e-mail: Mehmet.Sofuoglu@yale.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the j...

Intravestibular schwannomas are a rare cause of unilateral sensorineural hearing loss. Management of these tumors involves translabyrinthine resection, for which complete visualization around the angles of the vestibule may be limited under an operating microscope. We present the first reported case of an endoscope‐assisted resection of an intravestibular schwannoma, along with the operative video recording. Using additional information gained from endoscopic examination of the tumor and its resection site, we also propose a mechanism by which this patient's intravestibular schwannoma caused hearing loss. Use of the endoscope in resection of intravestibular schwannomas may have advantages over the traditional operating microscope in improving visualization of the narrow and angled vestibule, confirming the integrity of surrounding structures, and ensuring complete tumor removal. Laryngoscope, 129:986–988, 2019