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

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

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

    Benjamin J. Whalley, Jonathan D. Wilkinson, , Elizabeth M. Williamson and Andrew Constanti

    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 Δ9-tetrahydrocannabinol (Δ9-THC), and even Δ9-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 Δ9-THC (1 μM) significantly depressed evoked depolarizing postsynaptic potentials (PSPs) in rat olfactory cortex neurones, both SCE and Δ9-THC-free SCE significantly potentiated evoked PSPs (all results were fully reversed by the CB1 receptor antagonist SR141716A, 1 μM); interestingly, the potentiation by Δ9-THC-free SCE was greater than that produced by SCE. On comparing the effects of Δ9-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 Δ9-THC on excitatory neurotransmitter release, which may explain some patients’ preference for herbal cannabis rather than isolated Δ9-THC (due to attenuation of some of the central Δ9-THC side effects) and possibly account for the rare incidence of seizures in some individuals taking cannabis recreationally.