Article

A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro.

Department of Pharmacology, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK.
Neuroscience Letters (Impact Factor: 2.03). 08/2004; 365(1):58-63. DOI: 10.1016/j.neulet.2004.04.044
Source: PubMed

ABSTRACT Cannabis is a potential treatment for epilepsy, although the few human studies supporting this use have proved inconclusive. Previously, we showed that a standardized cannabis extract (SCE), isolated Delta9-tetrahydrocannabinol (Delta9-THC), and even Delta9-THC-free SCE inhibited muscarinic agonist-induced epileptiform bursting in rat olfactory cortical brain slices, acting via CB1 receptors. The present work demonstrates that although Delta9-THC (1 microM) significantly depressed evoked depolarizing postsynaptic potentials (PSPs) in rat olfactory cortex neurones, both SCE and Delta9-THC-free SCE significantly potentiated evoked PSPs (all results were fully reversed by the CB1 receptor antagonist SR141716A, 1 microM); interestingly, the potentiation by Delta9-THC-free SCE was greater than that produced by SCE. On comparing the effects of Delta9-THC-free SCE upon evoked PSPs and artificial PSPs (aPSPs; evoked electrotonically following brief intracellular current injection), PSPs were enhanced, whereas aPSPs were unaffected, suggesting that the effect was not due to changes in background input resistance. Similar recordings made using CB1 receptor-deficient knockout mice (CB1-/-) and wild-type littermate controls revealed cannabinoid or extract-induced changes in membrane resistance, cell excitability and synaptic transmission in wild-type mice that were similar to those seen in rat neurones, but no effect on these properties were seen in CB1-/- cells. It appears that the unknown extract constituent(s) effects over-rode the suppressive effects of Delta9-THC on excitatory neurotransmitter release, which may explain some patients' preference for herbal cannabis rather than isolated Delta9-THC (due to attenuation of some of the central Delta9-THC side effects) and possibly account for the rare incidence of seizures in some individuals taking cannabis recreationally.

0 Bookmarks
 · 
131 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, characterisation of the body's endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB(1) receptors by the major pCB, Δ(9)-tetrahydrocannabinol (Δ(9)-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ(9)-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent. In this regard, research focus has recently widened to include other pCBs including cannabidiol (CBD), cannabigerol (CBG), Δ(9)tetrahydrocannabivarin (Δ(9)-THCV) and cannabidivarin (CBDV), some of which show potential as therapeutic agents in preclinical models of CNS disease. Moreover, it is becoming evident that these non-Δ(9)-THC pCBs act at a wide range of pharmacological targets, not solely limited to CB receptors. Disorders that could be targeted include epilepsy, neurodegenerative diseases, affective disorders and the central modulation of feeding behaviour. Here, we review pCB effects in preclinical models of CNS disease and, where available, clinical trial data that support therapeutic effects. Such developments may soon yield the first non-Δ(9)-THC pCB-based medicines.
    Pharmacology [?] Therapeutics 09/2011; 133(1):79-97. · 7.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Wireless multimedia sensor networks (WMSNs) are usually troubled by network congestion due to large packet transmission amounts, and such congestion will not only lose data packets but also lead to too much energy consumption. Therefore, in order to enhance the transmission performance of WMSNs and reduce the delay time, it is necessary to adjust the transmission rate and control network congestion. WMSNs use different kinds of sensor nodes to collect different kinds of data. In multimedia applications, it is necessary to provide a reliable and fair protocol so as to meet the requirements of quality of service (QoS) of different formats of data. In past research, for WMSNs, priority-based rate control (PBRC) algorithms and exponential weight (EW) algorithms were used to control congestion through the adjusting of the transmission rate among different data formats. However, the weight parameter of the EW algorithm is fixed; when the change in data transmission amount is large, the difference between input transmission rate and estimated output transmission rate for the sink node will be large. In this paper, we have proposed an algorithm where a fuzzy logical controller (FLC) is used to estimate the output transmission rate of the sink node. The FLC is associated with the EW algorithm for selecting the appropriate weight parameter, and then, on the basis of the priority of each child node, an appropriate transmission rate is assigned. Simulation results show that the performance of our proposed algorithm has a better transmission rate as compared to that of PBRC, and hence, the transmission delay and loss probability are reduced; in addition, our proposed algorithm can control effectively the different transmission data types in order to achieve the QoS requirement of the system.
    Computers & Mathematics With Applications - COMPUT MATH APPL. 09/2012;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epilepsy is the most prevalent neurological disease and is characterised by recurrent seizures. Here we investigate: (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDS) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors. The anticonvulsant profiles of two CBDV BDSs (50-422 mg kg(-1) ) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip-strength assays. Binding of CBDV BDSs to cannabinoid CB1 receptors was evaluated using displacement binding assays. CBDV BDSs exerted significant anticonvulsant effects in the PTZ (≥100 mg kg(-1) ) and audiogenic seizure models (≥87 mg kg(-1) ), and suppressed pilocarpine-induced convulsions (≥100 mg kg(-1) ). The isobolographic study revealed the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip-strength were found. The Δ(9) -THC and Δ(9) -THCV content of CBDV BDS accounted for its greater affinity for CB1 cannabinoid receptors than purified CBDV. CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor, and were of comparable efficacy to purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for treatment of epilepsy.
    British Journal of Pharmacology 07/2013; · 5.07 Impact Factor

Full-text (2 Sources)

View
41 Downloads
Available from
May 28, 2014