A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro.
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.
Whalley
Benjamin J
BJ
Department of Pharmacology, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK.
Wilkinson
Jonathan D
JD
Williamson
Elizabeth M
EM
Constanti
Andrew
A
D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009833:Olfactory Pathways / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D002186:Cannabinoids; D010936:Plant Extracts; D043884:Receptor, Cannabinoid, CB1