Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Mechanisms affecting the overturning response in global warming simulations

Climate models used to produce global warming scenarios exhibit widely diverging responses of the thermohaline circulation (THC). To investigate the mechanisms responsible for this variability, a regional Atlantic Ocean model driven with forcing diagnosed from two coupled greenhouse gas simulations has been employed. One of the coupled models (MPI) shows an almost constant THC, the other (GFDL) shows a declining THC in the twenty-first century. The THC evolution in the regional model corresponds rather closely to that of the respective coupled simulation, that is, it remains constant when driven with the forcing from the MPI model, and declines when driven with the GFDL forcing. These findings indicate that a detailed representation of ocean processes in the region covered by the Atlantic model may not be critical for the simulation of the overall THC changes in a global warming scenario, and specifically that the coupled model’s rather coarse representation of water mass formation processes in the subpolar North Atlantic is unlikely to be the primary cause for the large differences in the THC evolution. Sensitivity experiments have confirmed that a main parameter governing the THC response to global warming is the density of the intermediate waters in the Greenland–Iceland–Norwegian Seas, which in turn influences the density of the North Atlantic Deep Water, whereas changes in the air–sea heat and freshwater fluxes over the subpolar North Atlantic are only of moderate importance, and mainly influence the interannual–decadal variability of THC. Finally, as a consequence of changing surface fluxes, the Labrador Sea convection ceases by about 2030 under both forcings (i.e., even in a situation where the overall THC is stable) indicating that the eventual breakdown of the convection is likely but need not coincide with substantial THC changes

Self-administration of edible Δ9-tetrahydrocannabinol and associated behavioral effects in mice

Background With increasing access to legal cannabis across the globe, it is imperative to more closely study its behavioral and physiological effects. Furthermore, with the proliferation of cannabis use, modes of consumption are changing, with edible formulations becoming increasingly popular. Nevertheless, there are relatively few animal models of self-administration of the primary psychoactive component of cannabis, Δ9-tetrahydrocannabinol (THC), and almost all incorporate routes of administration other than those used by humans. The aim of the current study was to develop a model of edible THC self-administration and assess its impact on CB1 receptor-mediated behaviors in female and male mice. Methods Mice were given limited access to a palatable dough which occasionally contained THC in doses ranging from 1 to 10 mg/kg. Following dough consumption, mice were assessed for home cage locomotor activity, body temperature, or analgesia. Locomotor activity was also assessed in conjunction with the CB1 receptor antagonist SR141716A. Results Dough was well-consumed, but consumption decreased at the highest THC concentrations. Edible THC produced dose-dependent decreases in locomotor activity and body temperature in both sexes, and these effects were more pronounced in male mice. Hypolocomotion induced by edible THC was attenuated by SR141716A, indicating mediation by CB1 receptor activation. Conclusions In contrast to other cannabinoid self-administration models, edible THC is relatively low in stress and uses a route of administration analogous to one used by humans. Potential applications include chronic THC self-administration, determining THC reward/reinforcement, and investigating consequences of oral THC use

The economic impact of a shutdown of the Thermohaline Circulation: an application of FUND

The integrated assessment model FUND 2.8n is applied in an analysis of the overall economic consequences in a scenario of a shutdown of the thermohaline circulation (THC). Monetized market and non-market impacts of changes in environmental conditions following a THC collapse are determined for 207 individual countries. Eight different response patterns can be identified. The dominant pattern is that a THC shutdown has an offsetting effect on the underlying warming trend. Depending on whether the impacts of warming are initially beneficial or detrimental, the economic effects of a THC collapse show distinct regional variability. Key economic sectors affected in a THC shutdown scenario are water resources and energy consumption, as well as cardiovascular and respiratory diseases among health impacts. The maximum, national impact of a collapse of the THC turns out to be of the magnitude of a few per cent of GDP, but the global impact is much smaller. Considering the low probability of occurrence, a THC shutdown does not call for drastic action at present.Fisheries, climate change

Two-Way Feedback Interaction between the Thermohaline and Wind-Driven Circulations

The thermohaline circulation (THC) affects the meridional atmospheric temperature gradient and therefore the atmospheric wind and the wind-driven ocean circulation. The wind-driven circulation (WDC), in turn, affects the THC by the advection of salinity anomalies into deep-water formation sites. This paper considers this two-way coupling between the WDC and THC using a simple box-type model and analysis tools from engineering feedback control. The two-way feedback can have a significant effect on the dynamics of the coupled system. For a reasonable choice of parameters, the feedback destabilizes the THC equilibrium for low freshwater forcing. For higher freshwater forcing, the feedback results in a new stable equilibrium instead of the large amplitude oscillation that develops without feedback. It is expected that the analysis approach used here may be broadly applicable to the study of feedback interconnections of other climate systems as well

Tropical Pacific influences on the North Atlantic thermohaline circulation

Most global climate models simulate a weakening of the North Atlantic Thermohaline Circulation (THC) in response to enhanced greenhouse warming. Both surface warming and freshening in high latitudes, the so-called sinking region, contribute to the weakening of the THC. Some models simulate even a complete breakdown of the THC at sufficiently strong forcing. Here results from a state-of-the-art global climate model are presented that does not simulate a weakening of the THC in response to greenhouse warming. Large-scale air-sea interactions in the tropics, similar to those operating during present-day El Niños, lead to anomalously high salinities in the tropical Atlantic. These are advected into the sinking region, thereby increasing the surface density and compensating the effects of the local warming and freshening. The results of the model study are corroborated by the analysis of observations

Robot autonomous navigation

Autonomous vehicle navigation is a very popular research area in the vision and control field. Based on Prof. Dickmanns' philosophy, we implement a navigation algorithm on thc small robot. The robot can rely on its eyes (the camera mounted on thc top of the robot) and control its wheels to walk through the sub-basement hallways of Caltech Moore Lab building. The speed we achieve is robot's mechanical maximum speed 0.5 m/s

ENSO suppression due to weakening of the North Atlantic thermohaline circulation

Changes of the North Atlantic thermohaline circulation (THC) excite wave patterns that readjust the thermocline globally. This paper examines the impact of a freshwater-induced THC shutdown on the depth of the Pacific thermocline and its subsequent modification of the El Niño–Southern Oscillation (ENSO) variability using an intermediate-complexity global coupled atmosphere–ocean–sea ice model and an intermediate ENSO model, respectively. It is shown by performing a numerical eigenanalysis and transient simulations that a THC shutdown in the North Atlantic goes along with reduced ENSO variability because of a deepening of the zonal mean tropical Pacific thermocline. A transient simulation also exhibits abrupt changes of ENSO behavior, depending on the rate of THC change. The global oceanic wave adjustment mechanism is shown to play a key role also on multidecadal time scales. Simulated multidecadal global sea surface temperature (SST) patterns show a large degree of similarity with previous climate reconstructions, suggesting that the observed pan-oceanic variability on these time scales is brought about by oceanic waves and by atmospheric teleconnections

Enzymatic digestion and selective quantification of underivatised [delta]9-tetrahydrocannabinol and cocaine in human hair using gas chromatography-mass spectrometry.

Gas chromatography-mass spectrometric (GC-MS) methods for drug analysis routinely employ derivatising reagents. The aim of this paper was to develop a method for the analysis of two recreational drugs, delta-9-tetrahydrocannabinol ([delta](9)-THC) and cocaine in hair samples using GC-MS, without prior derivatisation, thus allowing the sample to be reanalysed in its original form. An enzymatic digestion technique was also developed. Ten hair samples, that were known positive for either [delta](9)-THC and/or cocaine, were enzymatically digested, extracted, and then analysed by GC-MS. All samples measured contained [delta](9)-THC and one sample contained cocaine. The limits of detection (LOD) and quantification (LOQ) were 0.02 ng/mg and 0.05 ng/mg, respectively, for cocaine and 0.015 ng/mg and 0.02 ng/mg, respectively, for [delta](9)-THC. The wide detection window, ease of direct analysis by GC-MS, lower detection limits of underivatised samples, and the stability of drugs using this technique may offer an improved method of analysis