1,721,007 research outputs found
Scopolamine and MK801-induced working memory deficits in rats are not reversed by CBD-rich cannabis extracts
No full textSmoking marijuana causes working and short-term memory deficits, an effect that is mediated by cannabinoid receptor (CBI) activation in the brain. While this may be due to the main psychoactive constituent Delta(9)-tetrahydrocannabinol (Delta(9)-THC), plantextracts also contain other cannabinoid and terpenoid compounds with unknown properties. Towards this end, we have recently shown that high concentrations of plant extracts rich in cannabidiol (CBD) can reverse working memory deficits induced by Delta(9)-THC which is a remaining contaminant of this extract [Fadda P, Robinson L, Fratta W. Pertwee RG, Riedel G. Differential effects of THC- and CBD-rich cannabis-ex tracts on working memory in rats. Neuropahrmacology 2004:47:1170-9]. Since this effect was dose-dependent and indicative of memory enhancing qualities of the CBD-rich extract, this prompted a wider investigation into the effects of CBD on other forms of amnesia in order to determine the mechanism of action and to reveal its potency against anticholinergic and antiglutamatergic agents.
We employed a spatial delayed matching to position task in the open-field water maze. Both scopolamine (0.2 mg/kg i.p.) and dizocilpine (MK801: 0.1 mg/kg i.p.) impaired working memory at delays of 30 s and 4 h. Two doses of CBD-rich extracts (5 and 10 mg/kg), which did not affect working memory when given alone, were unable to reverse these deficits when co-administered with scopolamine or MK801.
These data suggest that reversal of working memory deficits by CBD-rich extracts are specific to the cannabinoid system and do not compensate for acutely induced cholinergic or glutamatergic receptor hypoactivity. (c) 2005 Elsevier B.V. All rights reserved
CBD-rich cannabis extracts do not reverse memory impairments induced by scopolamine and MK801 in rats
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Differential effects of THC-or CBD-rich cannabis extracts on working memory in rats
No full textCannabinoid receptors in the brain (CB1) take part in modulation of learning, and are particularly important for working and short-term memory. Here, we employed a delayed-matching-to-place (DMTP) task in the open-field water maze and examined the effects of cannabis plant extracts rich in either Delta(9)-tetrahydrocannabinol (Delta(9)-THC), or rich in cannabidiol (CBD), on spatial working and short-term memory formation in rats. Delta(9)-THC-rich extracts impaired performance in the memory trial (trial 2) of the DMTP task in a dose-dependent but delay-independent manner. Deficits appeared at doses of 2 or 5 mg/kg (i.p.) at both 30 s and 4 h delays and were similar in severity compared with synthetic Delta(9)-THC. Despite considerable amounts of Delta(9)-THC present, CBD-rich extracts had no effect on spatial working/short-term memory, even at doses of up to 50 mg/kg. When given concomitantly, CBD-rich extracts did not reverse memory deficits of the additional Delta(9)-THC-rich extract. CBD-rich extracts also did not alter Delta(9)-THC-rich extract-induced catalepsy as revealed by the bar test. It appears that spatial working/short-term memory is not sensitive to CBD-rich extracts and that potentiation and antagonism of Delta(9)-THC-induced spatial memory deficits is dependent on the ratio between CBD and Delta(9)-THC. (C) 2004 Elsevier Ltd. All rights reserved
Sativex-like Combination of Phytocannabinoids is Neuroprotective in Malonate-Lesioned Rats, an Inflammatory Model of Huntington's Disease: Role of CB1 and CB2 Receptors
No full textWe have investigated whether a 1:1 combination of botanical extracts enriched in either Delta(9)-tetrahydrocannabinol (Delta(9.)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, is neuroprotective in Huntington's disease (HD), using an experimental model of this disease generated by unilateral lesions of the striatum with the mitochondrial complex II inhibitor malonate. This toxin damages striatal neurons by mechanisms that primarily involve apoptosis and microglial activation. We monitored the extent of this damage and the possible preservation of the striatal parenchyma by treatment with a Sativex-like combination of phytocannabinoids using different histological and biochemical markers. Results were as follows: (i) malonate increased the volume of edema measured by in vivo NMR imaging and the Sativex-like combination of phytocannabinoids partially reduced this increase; (ii) malonate reduced the number of Nissl-stained cells, while enhancing the number of degenerating cells stained with FluoroJade-B, and the Sativex-like combination of phytocannabinoids reversed both effects; (iii) malonate caused a strong glial activation (i.e., reactive microglia labeled with Iba-1, and astrogliosis labeled with GFAP) and the Sativex-like combination of phytocannabinoids attenuated both responses; and (iv) malonate increased the expression of inducible nitric oxide synthase and the neurotrophin IGF-1, and both responses were attenuated after the treatment with the Sativex-like combination of phytocannabinoids. We also wanted to establish whether targets within the endocannabinoid system (i.e., CB1 and CB2 receptors) are involved in the beneficial effects induced in this model by the Sativex-like combination of phytocannabinoids. This we did using selective antagonists for both receptor types (i.e., SR141716 and AM630) combined with the Sativex-like phytocannabinoid combination. Our results indicated that the effects of this combination are blocked by these antagonists and hence that they do result from an activation of both CB1 and CB2 receptors. In summary, this study provides preclinical evidence in support of a beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying signs of disease progression in a proinflammatory model of HD, which adds to previous data obtained in models priming oxidative mechanisms of striatal injury. However, the interest here is that, in contrast with these previous data, we have now obtained evidence that both CB1 and CB2 receptors appear to be involved in the effects produced by a Sativex-like phytocannabinoid combination, thus stressing the broad-spectrum properties of Sativex that may combine activity at the CB1 and/or CB2 receptors with cannabinoid receptor-independent actions
Neuroprotective Effects of Phytocannabinoid-Based Medicines in Experimental Models of Huntington's Disease
No full textWe studied whether combinations of botanical extracts enriched in either Delta(9)-tetrahydrocannabinol (Delta(9)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, provide neuroprotection in rat models of Huntington's disease (HD). We used rats intoxicated with 3-nitropropionate (3NP) that were given combinations of Delta(9)-THC-and CBD-enriched botanical extracts. The issue was also studied in malonate-lesioned rats. The administration of Delta(9)-THC-and CBD-enriched botanical extracts combined in a ratio of 1: 1 as in Sativex attenuated 3NP-induced GABA deficiency, loss of Nissl-stained neurons, down-regulation of CB1 receptor and IGF-1 expression, and up-regulation of calpain expression, whereas it completely reversed the reduction in superoxide dismutase-1 expression. Similar responses were generally found with other combinations of Delta(9)-THC- and CBD-enriched botanical extracts, suggesting that these effects are probably related to the antioxidant and CB(1) and CB(2) receptor-independent properties of both phytocannabinoids. In fact, selective antagonists for both receptor types, i.e., SR141716 and AM630, respectively, were unable to prevent the positive effects on calpain expression caused in 3NP-intoxicated rats by the 1: 1 combination of Delta(9)-THC and CBD. Finally, this combination also reversed the up-regulation of proinflammatory markers such as inducible nitric oxide synthase observed in malonate-lesioned rats. In conclusion, this study provides preclinical evidence in support of a beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying disease progression in HD, a disorder that is currently poorly managed in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies. (C) 2011 Wiley-Liss, Inc
Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.
No full textSYNTHETIC AND PLANT-DERIVED CANNABINOID RECEPTOR ANTAGONISTS SHOW HYPOPHAGIC PROPERTIES IN FASTED AND NON-FASTED MICE
No full textObesity is a severe health problem in the modernized world and understanding the central nervous mechanisms underlying food-seeking behaviour and reward are at the forefront of medical research. Cannabinoid receptors have proven an efficient target to suppress hunger and weight gain by their pharmacological inactivation.
A standard fasted protocol and a novel long-term home-cage observation system with free-feeding animals were used to assess the feeding behaviour of mice treated with the CB(1) antagonist AM251. Similarly, the effects of the phytocannabinoid Delta(9)-tetrahydrocannabivarin (Delta(9)-THCV), which behaves like a CB(1) antagonist, were also determined in free-feeding animals.
AM251 suppressed food intake and weight gain in fasted and non-fasted animals. The suppression of food intake by AM251 (10 mg.kg(-1)) endured for a period of 6-8 h when administered acutely, and was continuous when injected for four consecutive days. Pure Delta(9)-THCV also induced hypophagia and weight reduction at doses as low as 3 mg.kg(-1). No rebound was observed on the following day with all drug groups returning to normal activity and feeding regimes. However, a Delta(9)-THCV-rich cannabis-extract failed to suppress food intake and weight gain, possibly due to residual Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in the extract. This Delta(9)-THC effect was overcome by the co-administration of cannabidiol
In vitro and in vivo pharmacological characterization of two novel selective cannabinoid CB(2) receptor inverse agonists
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