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


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.

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Available from: Elizabeth M Williamson, Oct 04, 2015
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    • "Difficulties in standardization arise due to: (i) often the active principle is unknown; (ii) synergy between two or more compounds;[57] (iii) a common approach is to standardize extracts on the basis of the quantitative presence of one or more marker compounds. However, presence of marker compounds alone may not assure consistency in the biological activities as non reproducibility results from variations in the unknown active principle.[58] Although in vitro assays are necessary for pre-clinical screening they are not ideal for routine quality control as they are laborious, time consuming and expensive since high throughput assays are not always suitable. "
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    ABSTRACT: India is among the important megabiodiversity centers of the world with nearly 45,000 known plant species. This diversity coupled with a rich heritage of traditional knowledge has made India a home to several important time-honored systems of health care such as Ayurveda, Siddha and Unani. Herbal medicines, however, are associated with a number of shortcomings including uniform efficacy and lack of appropriate quality control measures at various stages of product development. The review intends to outline the importance of fostering quality parameters towards standardization and manufacturing of botanicals for India to emerge as a leader in global market of herbal products. Literature survey was carried out on important parameters for processing and manufacturing of botanicals. The review highlights that there have been constant efforts for developing state of the art technologies in the field of herbal research. It also reflects that Government authorities have also taken a number of initiatives to formulate appropriate guidelines from standardization of raw materials to obtaining botanical products. However, in the Indian context, there exist certain lacunae in the current regulatory mechanisms which need to be strengthened and stringently implemented to ensure safety, purity and efficacy of herbal medicines. Towards this the approaches being developed globally can be adopted. Based on the literature reviewed, in our opinion, four areas viz., benefit sharing, investment by industry, standardization and national/international networking structure need immediate attention for strengthening Traditional Systems of Medicine in India.
    Indian Journal of Pharmacology 03/2014; 46(4):363-371. DOI:10.4103/0253-7613.135946 · 0.69 Impact Factor
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    • "This is well 15 illustrated by SR141716A (Acomplia/Rimonabant), a well-known selective CB 1 R 16 antagonist/inverse agonist which has recently been found by Kapur et al. to agonise 17 GPR55, and which the authors suggest may have played a part in some of the 'off- 18 target' effects that led to its withdrawal as an anti-obesity drug (Kapur et al., 2009). 19 There is still much to clarify about how cannabinoids produce their endogenous 20 effects, and how they might interact with each other in vivo (Ben Amar, 2006; Whalley 21 et al., 2004). Furthermore, adding to this complexity is the eCB system's interaction 22 with other systems, in particular the opioid system which itself has been linked to 23 appetite regulation for some time (for an early review of opiates and appetite regulation 24 "
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    ABSTRACT: The herb Cannabis sativa (C. sativa) has been used in China and on the Indian subcontinent for thousands of years as a medicine. However, since it was brought to the UK and then the rest of the western world in the late 19th century, its use has been a source of controversy. Indeed, its psychotropic side effects are well reported but only relatively recently has scientific endeavour begun to find valuable uses for either the whole plant or its individual components. Here, we discuss evidence describing the endocannabinoid system, its endogenous and exogenous ligands and their varied effects on feeding cycles and meal patterns. Furthermore we also critically consider the mounting evidence which suggests non-Δ(9) tetrahydrocannabinol phytocannabinoids play a vital role in C. sativa-induced feeding pattern changes. Indeed, given the wide range of phytocannabinoids present in C. sativa and their equally wide range of intra-, inter- and extra-cellular mechanisms of action, we demonstrate that non-Δ(9) tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential.
    Phytotherapy Research 02/2011; 25(2):170-88. DOI:10.1002/ptr.3375 · 2.66 Impact Factor
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    • "Phytocannabinoids have received considerable attention as potential therapeutic agents. Data from our recent studies suggest that these cannabinoids could have a therapeutic role in the treatment of pathophysiological hyperexcitability disorders associated with either the cerebellum, such as cerebellar ataxia (Smith and Dar, 2007), or the PC, such as cortical epilepsies (Whalley et al., 2004). D "
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    ABSTRACT: We have recently shown that the phytocannabinoid Delta9-tetrahydrocannabivarin (Delta9-THCV) and the CB1 receptor antagonist AM251 increase inhibitory neurotransmission in mouse cerebellum and also exhibit anticonvulsant activity in a rat piriform cortical (PC) model of epilepsy. Possible mechanisms underlying cannabinoid actions in the CNS include CB1 receptor antagonism (by displacing endocannabinergic tone) or inverse agonism at constitutively active CB1 receptors. Here, we investigate the mode of cannabinoid action in [35S]GTPgammaS binding assays. Effects of Delta9-THCV and AM251 were tested either alone or against WIN55,212-2-induced increases in [35S]GTPgammaS binding in mouse cerebellar and PC membranes. Effects on non-CB receptor expressing CHO-D2 cell membranes were also investigated. Delta9-THCV and AM251 both acted as potent antagonists of WIN55,212-2-induced increases in [35S]GTPgammaS binding in cerebellar and PC membranes (Delta9-THCV: pA2=7.62 and 7.44 respectively; AM251: pA2=9.93 and 9.88 respectively). At micromolar concentrations, Delta9-THCV or AM251 alone caused significant decreases in [35S]GTPgammaS binding; Delta9-THCV caused larger decreases than AM251. When applied alone in CHO-D2 membranes, Delta9-THCV and AM251 also caused concentration-related decreases in G protein activity. Delta9-THCV and AM251 act as CB1 receptors antagonists in the cerebellum and PC, with AM251 being more potent than Delta9-THCV in both brain regions. Individually, Delta9-THCV or AM251 exhibited similar potency at CB1 receptors in the cerebellum and the PC. At micromolar concentrations, Delta9-THCV and AM251 caused a non-CB receptor-mediated depression of basal [35S]GTPgammaS binding.
    British Journal of Pharmacology 08/2008; 154(6):1349-58. DOI:10.1038/bjp.2008.190 · 4.84 Impact Factor
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