Cannabis constituents modulate ∆9-tetrahydrocannabinol-induced hyperphagia in rats

Rationale The hyperphagic effect of ∆9-tetrahydrocannabinol (∆9THC) in humans and rodents is well known. However, no studies have investigated the importance of ∆9THC composition and any influence other non-∆9THC cannabinoids present in Cannabis sativa may have. We therefore compared the effects of purified ∆9THC, synthetic ∆9THC (dronabinol), and ∆9THC botanical drug substance (∆9THC-BDS), a ∆9THC-rich standardized extract comparable in composition to recreationally used cannabis. Methods Adult male rats were orally dosed with purified ∆9THC, synthetic ∆9THC, or ∆9THC-BDS, matched for ∆9THC content (0.34–2.68 mg/kg). Prior to dosing, subjects were satiated, and food intake was recorded following ∆9THC administration. Data were then analyzed in terms of hourly intake and meal patterns. Results All three ∆9THC substances tested induced significant hyperphagic effects at doses ≥0.67 mg/kg. These effects included increased intake during hour one, a shorter latency to onset of feeding and a greater duration and consumption in the first meal. However, while some differences in vehicle control intakes were observed, there were significant, albeit subtle, differences in pattern of effects between the purified ∆9THC and ∆9THC-BDS. Conclusion All ∆9THC compounds displayed classical ∆9THC effects on feeding, significantly increasing short-term intake whilst decreasing latency to the first meal. We propose that the subtle adjustment to the meal patterns seen between the purified ∆9THC and ∆9THC-BDS are due to non-∆9THC cannabinoids present in ∆9THC-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate ∆9THC-induced hyperphagia, making them worth further investigation for their therapeutic potential.

Effect of fluid mechanical stresses and plasma constituents on aggregation of LDL

LDL aggregates when exposed to even moderate fluid mechanical stresses in the laboratory, yet its half-life in the circulation is 2-3 days, implying that little aggregation occurs. LDL may be protected from aggregation in vivo by components of plasma, or by a qualitative difference in flows. Previous studies have shown that HDL and albumin inhibit the aggregation induced by vortexing. Using a more reproducible method of inducing aggregation and assessing aggregation both spectrophotometrically and by sedimentation techniques, we showed that at physiological concentrations, albumin is the more effective inhibitor, and that aggregation is substantially but not completely inhibited in plasma. Heat denatured and fatty-acid-stripped albumin were more effective inhibitors than normal albumin, supporting the idea that hydrophobic interactions are involved. Aggregation of LDL in a model reproducing several aspects of flow in the circulation was 200-fold slower, but was still inhibited by HDL and albumin, suggesting similar mechanisms are involved. Within the sensitivity of our technique, LDL aggregation did not occur in plasma exposed to these flows.jlr Thus, as a result of the characteristics of blood flow and the inhibitory effects of plasma components, particularly albumin, LDL aggregation is unlikely to occur within the circulation.

Permeation of bioactive constituents from Arnica montana preparations through human skin in-vitro

This study investigated and characterised transdermal permeation of bioactive agents from a topically applied Arnica montana tincture. Permeation experiments conducted over 48 h used polyclimethylsiloxane (silastic) and human epidermal membranes mounted in Franz-type diffusion cells with a methanol-water (50:50 v/v) receptor fluid. A commercially available tincture of A. montana L. derived from dried Spanish flower heads was a donor solution. Further donor solutions prepared from this stock tincture concentrated the tincture constituents 1, 2 and 10 fold and its sesquiterpene lactones 10 fold. Permeants were assayed using a high-performance liquid chromatography method. Five components permeated through silastic membranes providing peaks with relative retention factors to an internal standard (santonin) of 0.28, 1.18, 1.45, 1.98 and 2.76, respectively. No permeant was detected within 12 h of applying the Arnica tincture onto human epidermal membranes. However, after 12 h, the first two of these components were detected. These were,shown by Zimmermann reagent reaction to be sesquiterpene lactones and liquid chromatography/diode array detection/mass spectrometry indicated that these two permeants were 11,13-dihydrohelenalin (DH) analogues (methacrylate and tiglate esters). The same two components were also detected within 3 h of topical application of the 10-fold concentrated tincture and the concentrated sesquiterpene lactone extract.

Lethality of essential oil constituents towards the human louse, Pediculus humanus, and its eggs

Essential oils have been widely used in traditional medicine for the eradication of lice, including head lice, but due to the variability of their constitution the effects may not be reproducible. In an attempt to assess the contribution of their component monoterpenoids, a range of common individual compounds were tested in in vitro toxicity model against both human lice (Pediculus humanus, an accepted model of head lice lethality) and their eggs, at different concentrations. No detailed study into the relative potencies of their constituent terpenoids has so far been published. Adult lice were observed for lack of response to stimuli over 3 h and the LT50 calculated, and the percentage of eggs failing to hatch was used to generate ovicidal activity data. A ranking was compiled for adult lice and partially for eggs, enabling structure-activity relationships to be assessed for lethality to both, and showed that, for activity in both life-cycle stages, different structural criteria were required. (+)-Terpinen-4-ol was the most effective compound against adult lice, followed by other mono-oxygenated monocyclic compounds, whereas nerolidol was particularly lethal to eggs, but ineffective against adult lice. (c) 2006 Elsevier B.V. All rights reserved.

Methylxanthines are the psycho-pharmacologically active constituents of chocolate

Rationale: Liking, cravings and addiction for chocolate ("chocoholism") are often explained through the presence of pharmacologically active compounds. However, mere "presence" does not guarantee psycho-activity. Objectives: Two double-blind, placebo-controlled studies measured the effects on cognitive performance and mood of the amounts of cocoa powder and methylxanthines found in a 50 g bar of dark chocolate. Methods: In study 1, participants (n=20) completed a test battery once before and twice after treatment administration. Treatments included 11.6 g cocoa powder and a caffeine and theobromine combination (19 and 250 mg, respectively). Study 2 (n=22) comprised three post-treatment test batteries and investigated the effects of "milk" and "dark" chocolate levels of these methylxanthines. The test battery consisted of a long duration simple reaction time task, a rapid visual information processing task, and a mood questionnaire. Results: Identical improvements on the mood construct "energetic arousal" and cognitive function were found for cocoa powder and the caffeine+theobromine combination versus placebo. In chocolate, both "milk chocolate" and "dark chocolate" methylxanthine doses improved cognitive function compared with "white chocolate". The effects of white chocolate did not differ significantly from those of water. Conclusion: A normal portion of chocolate exhibits psychopharmacological activity. The identical profile of effects exerted by cocoa powder and its methylxanthine constituents shows this activity to be confined to the combination of caffeine and theobromine. Methylxanthines may contribute to the popularity of chocolate; however, other attributes are probably much more important in determining chocolate's special appeal and in explaining related self-reports of chocolate cravings and "chocoholism".

Dynamic shear modulus of isotropic elastomers

We have investigated the dynamic mechanical behavior of two cross-linked polymer networks with very different topologies: one made of backbones randomly linked along their length; the other with fixed-length strands uniformly cross-linked at their ends. The samples were analyzed using oscillatory shear, at very small strains corresponding to the linear regime. This was carried out at a range of frequencies, and at temperatures ranging from the glass plateau, through the glass transition, and well into the rubbery region. Through the glass transition, the data obeyed the time-temperature superposition principle, and could be analyzed using WLF treatment. At higher temperatures, in the rubbery region, the storage modulus was found to deviate from this, taking a value that is independent of frequency. This value increased linearly with temperature, as expected for the entropic rubber elasticity, but with a substantial negative offset inconsistent with straightforward enthalpic effects. Conversely, the loss modulus continued to follow time-temperature superposition, decreasing with increasing temperature, and showing a power-law dependence on frequency.

Effect of drying methods on the phenolic constituents of meadowsweet (Filipendula ulmaria) and willow (Salix alba)

The objective of this study was to investigate the effect of drying conditions on the phenolic constituents and colour of extracts of organically grown white willow and meadowsweet for incorporation into a functional beverage with potential anti-inflammatory properties. The herbs were freeze-dried, air-dried, oven or tray-dried at 30 or 70 °C. The drying kinetics of the herbs was first determined. Both drying temperature and method had a significant effect (p ≤ 0.05) on the drying rate, the samples tray-dried had a faster drying rate than those oven-dried. Results show that for meadowsweet and willow, freeze-drying and oven or tray drying at 30 °C had no significant effect on the phenolic constituents (e.g. total phenols, salicylates, quercetin) or the colour of the extracts in comparison to traditional air-drying. Although increasing the drying temperature to 70 °C resulted in an increase in the drying rate of both herbs it also led to the loss of some phenolic compounds. Also, the extracts from both herbs dried at 70 °C were significantly (p ≤ 0.05) redder than the other drying methods. Therefore, tray drying these herbs at low temperatures may reduce drying time without having a significant effect on the phenolic content and colour of the extracts.

Dielectric relaxation around the nematic-isotropic transition of liquid crystalline polymers

This study is concerned with a series of acrylate based side-chain liquid crystalline (LC) polymers. Previous studies have shown that these LC polymers have a preference for parallel or perpendicular alignment with respect to the polymer chain which depends on the length of the coupling chain joining the mesogenic unit to the polymer backbone. On the other hand, the dielectric relaxation of these side-chain LC polymers shows a strong relaxation associated to the mesogenic unit dynamics. For samples with parallel alignment, it was found that the dielectric relaxation of the nematic is weaker and broader than the relaxation of the isotropic. By contrast, for samples with perpendicular alignment, the isotropic to nematic transition reduces the broadening the relaxation and increases the relaxation strength. These two features are more evident for samples with short coupling units for which the dielectric relaxation observed appears to be strongly coupled with the backbone dynamics.