Cannabinoids in the treatment of epilepsy: current status and future prospects

Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis sativa, differentiating from Δ9-tetrahydrocannabinol (THC) for its non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a multi-target drug whose anti-convulsant properties are supposed to be independent of endocannabinoid receptor CB1 and might be related to several underlying mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of adenosine tone, activation of 5HT1A receptors and modulation of calcium intracellular levels. CBD is a lipophilic compound with low oral bioavailability (6%) due to poor intestinal absorption and high first-pass metabolism. Its exposure parameters are greatly influenced by feeding status (ie, high fatcontaining meals). It is mainly metabolized by cytochrome P 450 (CYP) 3A4 and 2C19, which it strongly inhibits. A proprietary formulation of highly purified, plant-derived CBD has been recently licensed as an adjunctive treatment for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), while it is being currently investigated in tuberous sclerosis complex. The regulatory agencies’ approval was granted based on four pivotal double-blind, placebocontrolled, randomized clinical trials (RCTs) on overall 154 DS patients and 396 LGS ones, receiving CBD 10 or 20 mg/kg/day BID as active treatment. The primary endpoint (reduction in monthly seizure frequency) was met by both CBD doses. Most patients reported adverse events (AEs), generally from mild to moderate and transient, which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and elevation in aminotransferase levels, the last being documented only in subjects on concomitant valproate therapy. The interaction between CBD and clobazam, likely due to CYP2C19 inhibition, might contribute to some AEs, especially somnolence, but also to CBD clinical effectiveness. Cannabidivarin (CBDV), the propyl analogue of CBD, showed anti-convulsant properties in pre-clinical studies, but a plant-derived, purified proprietary formulation of CBDV recently failed the Phase II RCT in patients with uncontrolled focal seizures

Quantum Homodyne Tomography as an Informationally Complete Positive Operator Valued Measure

We define a positive operator valued measure $E$ on $[0,2\pi]\times R$ describing the measurement of randomly sampled quadratures in quantum homodyne tomography, and we study its probabilistic properties. Moreover, we give a mathematical analysis of the relation between the description of a state in terms of $E$ and the description provided by its Wigner transform.Comment: 9 page

Vibrational spectrum of solid picene (C_22H_14)

Recently, Mitsuhashi et al., have observed superconductivity with transition temperature up to 18 K in potassium doped picene (C22H14), a polycyclic aromatic hydrocarbon compound [Nature 464 (2010) 76]. Theoretical analysis indicate the importance of electron-phonon coupling in the superconducting mechanisms of these systems, with different emphasis on inter- and intra-molecular vibrations, depending on the approximations used. Here we present a combined experimental and ab-initio study of the Raman and infrared spectrum of undoped solid picene, which allows us to unanbiguously assign the vibrational modes. This combined study enables the identification of the modes which couple strongly to electrons and hence can play an important role in the superconducting properties of the doped samples

Quantum tomography, phase space observables, and generalized Markov kernels

We construct a generalized Markov kernel which transforms the observable associated with the homodyne tomography into a covariant phase space observable with a regular kernel state. Illustrative examples are given in the cases of a 'Schrodinger cat' kernel state and the Cahill-Glauber s-parametrized distributions. Also we consider an example of a kernel state when the generalized Markov kernel cannot be constructed.Comment: 20 pages, 3 figure