Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB(1) receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB(1) receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.

Subjective and physiological effects after controlled Sativex and oral THC administration.

Sativex is a cannabis-plant extract delivering nearly 1:1 Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and "good drug effects" with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses.

A prospective, randomized, double-blind, placebo-controlled trial evaluating the effect of nystatin on the development of oral irritation in patients receiving high-dose intravenous interleukin-2.

Interleukin-2 (IL-2) has been used to treat patients with metastatic melanoma and renal cell cancer for nearly two decades, and much progress has been made in ameliorating its adverse effects. One bothersome adverse effect, oral pain or oral irritation, is usually treated with an oral antifungal antibiotic, nystatin. The authors performed a prospective, randomized, double-blind, placebo-controlled trial involving 64 patients to evaluate the effect of prophylactic administration of nystatin or placebo on the development of oral irritation in patients receiving high-dose intravenous IL-2. No difference was found between patients randomized to receive nystatin or placebo in their rates of development of oral irritation, the severity of IL-2 adverse effects, the duration of their treatment, the rate of development of positive studies for oral yeast, or their pattern of experiencing other adverse effects. Thus, patients who receive high-dose intravenous IL-2 should not be treated prophylactically with nystatin to prevent oral irritation, and clinicians should seek evidence of the presence of oral thrush before using antifungal agents to treat oral pain in these patients.

Magnetic resonance imaging of intracranial hypotension syndrome with pathophysiological correlation.

OBJECTIVE: To correlate the pathophysiology of intracranial hypotension syndrome with abnormalities in the brain and spine found through magnetic resonance imaging. METHODS: In a series of 11 patients with intracranial hypotension syndrome, brain magnetic resonance scans were evaluated for the thickness, distribution, morphology, and pattern of meningeal enhancement coincident with subdural fluid collections and the descent of the brain toward the skull base. Spinal magnetic resonance studies were reviewed for extra-arachnoid fluid collections, meningeal enhancement, and distended epidural veins. RESULTS: Diffuse, continuous dural-arachnoid enhancement was present in all patients with abnormal brain studies. The dura was thickest in patients with very low intracranial pressures. Subdural fluid collections and descent of the brain were seen in patients with the thickest meninges and were not present in the absence of meningeal enhancement. Extra-arachnoid or paraspinal fluid collections were found in all patients who had spinal magnetic resonance scans. CONCLUSIONS: In the brain, diffuse dural-arachnoid enhancement is the most common imaging abnormality and is probably the earliest magnetic resonance manifestation of intracranial hypotension syndrome, while subdural fluid collections and descent of the brain are indicators of a more severe hypotensive state. Extra-arachnoid fluid collections are common spinal imaging abnormalities.

Flavonoids with anti-cataract activity from Brickellia arguta.

Six flavonoids were isolated from Brickellia arguta and identified using chemical and spectral methods. The isolation and spectral data of a new flavonoid, 6- methoxykaempferol 3-O-beta-D- robinobioside (3), are reported for the first time. Three of these flavonoids were tested and showed inhibition of rat lens aldose reductase.

Head Orientation position during birth and in infant neonatal period, and hand preference at nineteen weeks.

This study of lateral preferences of normal full-term infants found, as predicted, that infants who were delivered from a left occiput anterior or transverse birth position (head turned to the right) exhibited a neonatal right supine head orientation and a right-hand preference in visually guided reaching tasks at 19 weeks. Contrary to prediction, infants delivered from a right occiput anterior or transverse birth position (head turned to the left) did not exhibit a left-sided preference in either neonatal head position or hand preference. Results are discussed in relation to other research which found a right shift in neonates' head orientations and in the distribution of hand preference in the human population. The findings suggest further investigation into the relationship between prenatal and postnatal postural asymmetries and the continuing development of laterality.