Cannabinoid receptors (CBR) located at presynaptic terminals on GABAergic neurones have been shown to inhibit GABA release at central synapses, temporarily suppressing inhibition during periods of strong glutamatergic excitation. While such effects have been described in the CBR-rich hippocampus, little is known about CBR function in the closely associated entorhinal cortex (EC), which possesses a similarly high density of CBR. In acutely prepared EC-hippocampal slices prepared from humanely killed animals, we recorded spontaneous inhibitory synaptic currents (sIPSCs) using whole-cell voltage clamp, from visually identified neurones in EC layer II prior to and during application of the CBR agonist arahidonylcyclopropylamide (ACPA). Glutamate receptor antagonists and symmetrical Cl- ion concentration were used throughout, and sIPSCs were recorded as inward currents and analysed offline using MiniAnal software. All means quoted are ± standard error of the mean (SEM), the Kolmogorov-Smirnov (KS) test was used for comparison of data (95% confidence level). Bath application of ACPA (1-10 micromolar) caused a dose-dependent, irreversible alteration in the pattern of GABA release such that ACPA increased mean sIPSC amplitude from 61.2 ± 0.9 to 102 ± 1.4 pA, reflecting a significant change in amplitude distribution (p<0.0001 KS). At the same time, the distribution of inter event intervals (IEI) was only slightly altered (mean 77 ± 3 ms for control and 82 ± 2 ms in ACPA; p<0.001 KS n=7). However, whilst amplitude distribution was markedly skewed towards larger sIPSCs and IEI (and hence sIPSC number) remained similar, there was no change in total current passing across the membrane. Data from 14000 sIPSCs (7 neurones) revealed that mean area under the sIPSC was 398 ± 4 pA.ms in control and 386 ± 4 pA.ms in ACPA and total area was 1,812,715 and 1,779,326 pA.ms respectively, a difference of less than 2%. These data indicated an apparent compensation between amplitude and kinetic parameters, such that medium amplitude single sIPSCs were replaced with large amplitude sIPSC bursts and total charge transfer across the neuronal membrane remained constant. Subsequent analysis confirmed such a shift in sIPSC amplitude and kinetics from small, kinetically slow, single events under control conditions to faster, high amplitude burst-like sIPSCs in ACPA. Agonist application skewed the distribution of kinetic parameters towards smaller values (p<0.0001 KS) such that mean rise and decay times were reduced by 8.9 ± 1.1 and 11.9 ± 1.2 % respectively, and half-width (duration of the sIPSC at 50% amplitude) was reduced by 16.1 ± 1.2%. These data indicate that CBR activation may effect a switch between phasic and tonic inhibition in the EC.