P.4.c. Anxiety disorders, OCD, stress related disorders and treatment − Treatment (basic) S617 [5] Rodriguez, C.I., Kegeles, L.S., Levinson, A., Feng, T., Marcus, S.M., Vermes, D., Flood, P., Simpson, H.B., 2013. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of- concept. Neuropsychopharmacology 38, 2475−83. P.4.c.008 Cannabidiol presents an inverted U-shaped dose-response curve in the simulated public speaking test I. Linares 1° , A.W. Zuardi 2 , L.C.G. Pereira 3 , R.H.C. Queiroz 3 , R. Mechoulam 4 , F.S. Guimar˜ aes 5 , J.A.S. Crippa 2 1 University of S˜ ao Paulo, Sao Paulo, Brazil; 2 University of S˜ ao Paulo, Department of Neuroscience and Behavior- Ribeir˜ ao Preto Medical School- University of S˜ ao Paulo- Brazil, Ribeirao Preto, Brazil; 3 University of S ˜ ao Paulo, Department of Clinical Analysis- Toxicology and Food Sciences- School of Pharmaceutical Sciences of Ribeir˜ ao Preto- University of S˜ ao Paulo- Brazil., Ribeir˜ ao Preto, Brazil; 4 Hebrew University, Institute for Drug Research- Faculty of Medicine- Hebrew University- Jerusalem- Israel., Jerusalem, Israel; 5 University of S˜ ao Paulo, Department of Pharmacology- Ribeir˜ ao Preto Medical School- University of S˜ ao Paulo- Brazil., Ribeir˜ ao Preto, Brazil Background: Cannabidiol (CBD), one of the main non-psychoto- mimetic compounds of Cannabis sativa, causes anxiolytic-like ef- fects in animals with typical bell-shaped dose-response curves [1]. A decrease in anxiety was also observed in clinical studies using single doses of CBD [2]. No study, however, has investigated if increasing doses of this drug would also cause similar curves in humans. Objective: The present study was aimed at comparing the acute effects of different doses of CBD and placebo in healthy volunteers performing the simulated public speaking test, a well- tested anxiety-inducing method. Methods: A total of 57 healthy male subjects were allocated to receive CBD P.O. at the doses of 150 mg (n = 15); 300 mg (n = 15); 600 mg (n = 12) or placebo (n = 15). Each volunteer participated in only one experimental session in a double-blind procedure. During the simulated public speaking test, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure − BP, heart rate − HR) were measured at six different time points. VAMS scores, BP and HR measures were transformed by calculation the difference between the score in each phase of the procedure and the pre-test measures of each participant (delta scores). Delta scores were then analyzed using repeated-measures ANOVA. Whenever a significant phase by group interaction occurred, comparisons among the groups were made at each phase using a one-factor ANOVA followed by multiple comparisons with the Bonferroni’s test. Results: The repeated-measures ANOVA showed effects of phase [F(2.48;131.6) = 13.36; p < 0.001] and group [F(3;53) = 2.714; p = 0.05], as well as a tendency to interaction between group and phase [F(7.45;131.6) = 1.72; p = 0.1]. Comparisons between group in each phases with post hoc tests showed lower anxiety levels in the group treated with CBD 300 mg in phase S relative to the placebo phase (p = 0.042). No significant differences in VAMS scores were observed between groups receiving CBD 150 mg and 600 mg and placebo. Conclusion: The present findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. In conclusion, the optimal therapeutic doses of CBD should be rigorously deter- mined so that research findings can be adequately translated into clinical practice. Table: Phases and procedures of the experimental session Time Phase Procedure 0 Drug/placebo administration VAMS, HR, BP, CBD (150mg, 300mg or 600 mg) or placebo 90 Pre-stress (PS) VAMS, HR, BP +0:10 Video instructions Prepare speech about public transportation; 2nd part of the consent form +0:12 Speech preparation +0:14 Anticipatory anxiety (A) VAMS, HR, BP +0:25 Beginning of speech Speaking in front of the camera while seeing own image on TV screen +0:27 Performance anxiety (S) VAMS, HR, BP +0:33 Speech continues +0:35 End of speech (F1) VAMS, HR, BP +1:05 Post-stress (F2) VAMS, HR, BP References [1] Campos, A.C., Guimaraes, F.S., 2009. Evidence for a potential role for TRPV1 receptors in the dorsolateral periaqueductal gray in the attenuation of the anxiolytic effects of cannabinoids. Prog Neuropsy- chopharmacol Biol Psychiatry, 33(8), 1517−21. [2] Zuardi, A.W., Cosme, R.A., Graeff, F.G., Guimar˜ aes, F.S., 1993. Ef- fects of ipsapirone and cannabidiol on human experimental anxiety. J Psychopharmacology, 7, 82−8. P.4.c.009 Animal model of paresthesia related to panic disorder A.F. Biagioni 1° , G.H.R.D. Santos 1 , N.C. Coimbra 1 1 School of Medicine of Ribeir˜ ao Preto of the University of S˜ ao Paulo, Pharmacology, Ribeir˜ ao Preto, Brazil Introduction: Paroxetine, a selective serotonergic inhibitor reup- take (SSIR), is a first-line treatment for panic disorder. However, that SSIR is not effective in the treatment of paresthesia, a common tingling or numbness symptom during panic attacks. Instead of paroxetine treatment can even intensify the paresthesia symptoms [1]. An animal model of paresthesia related to panic disorder is important to elucidate the physiopathology of panic disorder and to find new treatments. Aim: To evaluate the effect of the naltrexone at 2mg/kg, a non- selective opioide receptor antagonist, in rats treated chronically with paroxetine at 10mg/kg in the defensive behavioural re- sponse characterised by defensive immobility and antinociception induced by chemical stimulation of the ventrolateral column of periaqueductal grey matter (vlPAG). Methods: Rats (n = 7 or 8) were chronically treated with in- traperitoneal (i.p.) injections of paroxetine at 10 mg/kg or vehicle (saline + 2% tween 80). After 14 days, anesthesiated rats were implanted with guide-cannula directed to vlPAG. Seven days later, 0.6nmol of NMDA or physiological saline (0.2 mL) was microinjected into the vlPAG 1 hour after the i.p. treatment with naltrexone 2 mg/kg or saline. Each rat was placed in the open- field test arena where the defensive immobility behaviour was recorded during 5 minutes. Posteriorly, tail-flick latencies were measured for 30 minutes. Data were analysed using one-way and two-way analysis of variance (ANOVA) followed by Newman– Keuls post hoc test or repeated-measures ANOVA, followed by Duncan’s post hoc test. All values were reported as the mean ± standard error of the mean (SEM).