BACKGROUND There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ9-tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. METHODS We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. RESULTS Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. CONCLUSIONS Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513

A decrease in density of GFAP immunoreactive astrocytes in the amygdala of depressed subjects is consistent with prior histologic reports and might contribute to amygdala volume reductions reported in several in vivo neuroimaging studies.

BackgroundDeep Brain Stimulation (DBS) of the nucleus accumbens (NAc) has previously been investigated clinically for the treatment of several psychiatric conditions, including obsessive-compulsive disorder and treatment resistant depression. However, the mechanism underlying the therapeutic benefit of DBS, including the brain areas that are activated, remains largely unknown. Here, we utilized 3.0 T functional Magnetic Resonance Imaging (fMRI) changes in Blood Oxygenation Level-Dependent (BOLD) signal to test the hypothesis that NAc/internal capsule DBS results in global neural network activation in a large animal (porcine) modelMethodsAnimals (n = 10) were implanted in the NAc/internal capsule with DBS electrodes and received stimulation (1, 3, and 5 V, 130 Hz, and pulse widths of 100 and 500 µsec). BOLD signal changes were evaluated using a gradient echo-echo planar imaging (GRE-EPI) sequence in 3.0 T MRI. We used a normalized functional activation map for group analysis and applied general linear modeling across subjects (FDR<0.001). The anatomical location of the implanted DBS lead was confirmed with a CT scanResultsWe observed stimulation-evoked activation in the ipsilateral prefrontal cortex, insula, cingulate and bilateral parahippocampal region along with decrease in BOLD signal in the ipsilateral dorsal region of the thalamus. Furthermore, as the stimulation voltage increased from 3 V to 5 V, the region of BOLD signal modulation increased in insula, thalamus, and parahippocampal cortex and decreased in the cingulate and prefrontal cortex. We also demonstrated that right and left NAc/internal capsule stimulation modulates identical areas ipsilateral to the side of the stimulationConclusionsOur results suggest that NAc/internal capsule DBS results in modulation of psychiatrically important brain areas notably the prefrontal cortex, cingulate, and insular cortex, which may underlie the therapeutic effect of NAc DBS in psychiatric disorders. Finally, our fMRI setup in the large animal may be a useful platform for translational studies investigating the global neuromodulatory effects of DBS

Purpose:To assess the feasibility of a perfusion magnetic resonance (MR) imaging technique that uses Overhauser dynamic nuclear polarization (DNP) to provide contrast during the continuous delivery of hyperpolarized water in rats. Materials and Methods:Protocols approved by the local institutional animal care and use committees were followed. Twelve male Wistar rats were anesthetized and prepared by placing injection tubing in the subcutaneous layer (n = 3), peritoneum (n = 3), aorta (n = 3), or carotid artery (n = 3). Water was hyperpolarized by means of Overhauser DNP in the 0.35-T fringe field of a 1.5-T MR imaging magnet by using a custom-built system to continuously deliver radical-free hyperpolarized water to the subject. Fast gradient-echo and spoiled gradient-recalled-echo MR imaging sequences were used. The signal-to-noise ratio (SNR) of the images was calculated and compared. Results:Images showed greatly altered SNR and enhanced flow contrast at all injection locations. For subcutaneous and intraperitoneal injections, the water perfusion trajectory was observed for approximately 5 seconds after injection. Flow through a 4.2-cm length of artery was seen during intra-aortic injection. The right hemisphere of the brain was seen during injection into the right carotid artery. Images with hyperpolarized water had greatly altered SNR compared with images without injection or with the injection of nonhyperpolarized water, with a range of 13%-27% for the carotid and 444%-2900% for the other regions. Conclusion:Perfusion contrast for MR imaging can be obtained by continuously infusing hyperpolarized water, providing localized angiography or brain perfusion information in vivo for rat models.q RSNA, 2012Supplemental material: http://radiology.rsna.org/lookup /suppl