S64 Clinical neuropsychopharmacology Results: Delta-9-THC induced psychotic symptoms and anxiety acutely. There was no change in psychotic symptoms with Cannabidiol but a trend level (p = 0.06) anxiolytic effect. During the verbal memory task, delta-9- THC and Cannabidiol had opposing effects on activation in the striatum bilaterally and in the left anterior cingulate cortex/ medial prefrontal cortex extending laterally to the middle frontal gyrus. The effect of delta-9-THC on striatal activation was indirectly correlated with psychotic symptoms induced by it concurrently, so that the more delta-9-THC attenuated striatal activation, the more severe were the psychotic symptoms induced by it (r = −0.574, p = 0.013; after leaving outliers identified by Cook’s D reliability analysis: r = −0.805, p < 0.001). While viewing fearful faces, delta-9-THC and Cannabidiol had opposing effects on activation in the left amygdala, fusiform and lingual gyrus. Delta-9-THC increased the activation in the amygdala in response to fearful faces which directly correlated with the anxiety induced by it (r = 0.675, p = 0.003), while Cannabidiol attenuated the amygdala response which correlated (r = 0.551, p = 0.017) with its trend level anxiolytic effect. During the response inhibition task, the opposing effects of the drugs were evident in the parahippocampal gyrus bilaterally extending to the left insula and caudate, where delta-9-THC attenuated while Cannabidiol augmented the activation relative to placebo. Conclusions: Modulation of striatal and amygdala activation by delta-9-THC may underlie the acute induction of psychotic and anxiety symptoms respectively by cannabis. Striatum, anterior cingulate, prefrontal and medial temporal cortex and amygdala are key regions implicated in schizophrenia. Opposite effects of Cannabidiol in these regions to that of delta-9-THC, which increases the risk of schizophrenia in the long term, may suggest possible therapeutic role for Cannabidiol in cannabis-induced or cannabis use related psychotic disorders. As cannabis and delta-9-THC can worsen psychotic symptoms in medicated schizophrenic patients and pre-treatment with antipsychotics like Haloperidol fail to prevent induction of psychotic symptoms by delta- 9-THC in healthy volunteers [3], this may open newer treatment options for these conditions. Reference(s) [1] Moore, T.H., Zammit, S., Lingford-Hughes, A., et al., 2007, Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 370(9584): 319–328. [2] Zuardi, A.W., Crippa, J.A., Hallak, J.E., Moreira, F.A. & Guimaraes, F.S., 2006, Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res 39, 421–429. [3] D’Souza, D.C., Braley, G., Blaise, R., et al., 2008, Effects of haloperidol on the behavioural, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans. Psychopharmacology (Berl) 198(4): 587–603. P.3.03 A double-blind, placebo-controlled, parallel group study of the effect of Org 25935 on cognitive performance D. Christmas 1 ° , S. Wilson 1 , A. Diaper 1 , A. Rich 1 , J. Udo do Haes 2 , M. Sjogren 2 , D. Nutt 2 . 1 University of Bristol, Department of Psychopharmacology, Bristol, United Kingdom; 2 Organon, Clinical Research Dept, Molenstraat, The Netherlands Background: Org 25935, a glycine reuptake blocker, may improve cognitive function via its action on the glutamate system. Preliminary results indicate that PCP- induced cognitive deficits in a novel object recognition task are improved by acute administration of Org 25935. The University of Bristol has in the past carried out a human volunteer study (Bailey, Papadopoulos et al. 2007) using a CO2 or air inhalation (anxiety challenge) with d-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor. This demonstrated an effect of improvement on a learning task, the Manikin task, which tests visuospatial performance. The current study uses a broadly comparable design but without the inhalations. Method: This was a randomized, double-blind, placebo- controlled, parallel group, single dose study. Org 25935 or placebo was administered after a light breakfast. The Manikin task was performed at 3 hours post dose. The verbal memory task (word list) acquisition was at 3.5 h post dose and recall at 4 h post dose. The digit span task was assessed at baseline, 1 h and 3.5 h post dose to control for general effects on performance. Visual analogue scales were performed at several time points during the study day. Results: 32 subjects completed the study, 15 received Org 25935 and 17 placebo and 15 in the active group and 16 in the placebo group were evaluable. There were no significant differences between the drug and the control groups on any of the measures of performance that we employed. Org 25935 neither improved nor impaired performance. In particular, on the primary outcome measures (manikin task correct responses and reaction time), the planned analyses revealed no significant effect on performance (ANOVA ‘drug’ effect for correct responses p = 0.98, reaction time p=0.51) or learning (ANOVA drug x block effect for correct responses p = 0.78, reaction time p = 0.38).