We investigated the pharmacokinetic properties of D 9 -tetrahydrocannabinol (D 9 -THC), the main psychoactive constituent of cannabis, in adolescent and adult male mice. The drug was administered at logarithmically ascending doses (0.5, 1.6, and 5 mg/kg, i.p.) to pubertal adolescent (37-day-old) and adult (70day-old) mice. D 9 -THC and its first-pass metabolites-11hydroxy-D 9 -THC and 11-nor-9-carboxy-D 9 -THC (11-COOH-THC)-were quantified in plasma, brain, and white adipose tissue (WAT) using a validated isotope-dilution liquid chromatography/tandem mass spectrometry assay. D 9 -THC (5 mg/kg) reached 50% higher circulating concentration in adolescent mice than in adult mice. A similar age-dependent difference was observed in WAT. Conversely, 40%-60% lower brain concentrations and brain-to-plasma ratios for D 9 -THC and 50%-70% higher brain concentrations for D 9 -THC metabolites were measured in adolescent animals relative to adult animals. Liver microsomes from adolescent mice converted D 9 -THC into 11-COOH-THC twice as fast as adult microsomes. Moreover, the brains of adolescent mice contained higher mRNA levels of the multidrug transporter breast cancer resistance protein, which may extrude D 9 -THC from the brain, and higher mRNA levels of claudin-5, a protein that contributes to blood-brain barrier integrity. Finally, administration of D 9 -THC (5 mg/kg) reduced spontaneous locomotor activity in adult, but not adolescent, animals. The results reveal the existence of multiple differences in the distribution and metabolism of D 9 -THC between adolescent and adult male mice, which might influence the pharmacological response to the drug. SIGNIFICANCE STATEMENTAnimal studies suggest that adolescent exposure to D 9 -tetrahydrocannabinol (D 9 -THC), the intoxicating constituent of cannabis, causes persistent changes in brain function. These studies generally overlook the impact that age-dependent changes in the distribution and metabolism of the drug might exert on its pharmacological effects. This report provides a comparative analysis of the pharmacokinetic properties of D 9 -THC in adolescent and adult male mice and outlines multiple functionally significant dissimilarities in the distribution and metabolism of D 9 -THC between these two age groups.

Historically, progress in membrane protein research has been hindered due to solubility issues. The introduction of biomembrane mimetics has since stimulated the field’s momentum. One mimetic, the nanodisc, has proved to be an exceptional system for solubilizing membrane proteins. Herein, we critically evaluate the advantages and imperfections from employing nanodiscs in biophysical and biochemical studies. Specifically, we examine the techniques that have been modified to study membrane proteins in nanodiscs. Techniques discussed include fluorescence microscopy, solution state/solid state NMR, electron microscopy, SAXS, and several mass spectroscopy methods. Newer techniques such as SPR, charge sensitive optical detection, and scintillation proximity assays are also reviewed. Lastly, we cover nanodiscs advancing nanotechnology through nanoplasmonic biosensing, lipoprotein-nanoplatelets, and sortase-mediated labeling of nanodiscs.