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Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo-controlled, cross-over study assessed the acute influence of cannabis on the brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional and 12 chronic cannabis users received acute doses of cannabis (300-μg/kg delta-9-tetrahydrocannabinol) and placebo and underwent ultrahigh field functional magnetic resonance imaging and magnetic resonance spectroscopy. In occasional users, cannabis induced significant neurometabolic alterations in reward circuitry, namely, decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in chronic users. The finding that cannabis altered circuitry and distorted behavior in occasional, but not chronic users, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users. Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment, of which is important to understand in the context of the long-term therapeutic use of cannabis-based medications, as well as in the context of public health and safety of cannabis use when performing day-to-day operations.
Problém tolerance se v posledních desetiletích v kontextu procesů globalizace a integrace národnostních menšin jeví jako jeden z klíčových problémů politické teorie. Autorem jedné z nejvlivnějších současných teorií tolerance je pak bezpochyby člen „čtvrté generace“ frankfurtské školy Rainer Forst. Článek předkládá kritickou recepci jeho teorie, lze ho ovšem zároveň chápat jako prostředek k získání obecné systematické a normativní orientace ve struktuře komplexní problematiky tolerance, která v současnosti významně rezonuje ve veřejném prostoru. Výklad za pomoci historických příkladů osvětluje Forstovo rozlišení pojmu a pojetí tolerance a následně se věnuje originálnímu normativnímu ospravedlnění tolerance, s důrazem na Forstem předložená řešení s tímto pojmem spojených paradoxů. Následuje kritické zhodnocení Forstovy argumentace, které poukazuje mimo jiné na obtíže vyplývající z Forstovy návaznosti na tradici liberalismu a konstruktivismu, a tím se dotýká problémů ležících v základech nejen Forstova myšlení, ale v základech těchto myšlenkových směrů vůbec.
Larinioides sclopetarius is one of very few Central European spiders known to be found in colonies in which the orb-webs are attached to each other. Individuals of different generations cooperate at least in web-building, i.e. they share the same framework or irregular “web carpet”. This behaviour is called parasocial and up to now it has been studied mainly in subtropical and tropical species. Parasocial (colonial) life can lead to total degeneration of the orb-webs and is the result of increased tolerance, which depends on local superabundance of prey. Initial surveys in Essen (Germany) showed that groups of 60 to 200 individuals do not seem to be exceptional. More detailed studies on the group-living of L. sclopetarius are needed.
Purpose: Subcutaneous allergen-specific immunotherapy (SCIT) is a well-established and clinically effective method to treat allergic diseases, such as rhinitis and asthma. It remains unclear how soon after initiation of an ultra-short course of grass pollen immunotherapy adjuvanted with monophosphoryl lipid A (MPL)-specific bronchial tolerance can be induced.
Methods: In a prospective study of 69 children double-sensitized to birch and grass pollens (51 males, average age 11.1 years), development of bronchial tolerance after 1 cycle of SCIT for grass was evaluated. In all the patients, the bronchial allergen provocation test (BAP) was performed before and after treatment. According to the results of the first BAP, the patients were divided into 2 groups: those showing a negative BAP with a decrease in FEV1 of <20% (seasonal allergic rhinitis [SAR] group, n=47); and those showing a positive BAP with a decrease in FEV1 of ≥20% (SAR with allergic asthma [SAR and Asthma] group, n=22). All the patients received MPL-adjuvanted, ultra-short course immunotherapy for birch, but only those with a positive BAP to grass received MPL-SCIT for grass.
Results: After the pollen season, the BAP in the SAR group remained unchanged, while it was improved in the SAR and Asthma group (decrease in FEV1 of 28.8% vs 12.5%, P<0.01). The IgG4 levels increased after SCIT (median before SCIT 0.34 to 11.4 after SCIT), whereas the total and specific IgE levels remained unchanged.
Conclusions: After 1 cycle of MPL-SCIT, specific bronchial tolerance may be significantly induced, whereas in patients without SCIT, bronchial hyperactivity may remain unchanged.