Abstract
Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naïve SAD patients who received a single dose of CBD or placebo. A total of 24 never-treated patients with SAD were allocated to receive either CBD (600 mg; n=12) or placebo (placebo; n=12) in a double-blind randomized design 1 h and a half before the test. The same number of HC (n=12) performed the SPST without receiving any medication. Each volunteer participated in only one experimental session in a double-blind procedure. Subjective ratings on the Visual Analogue Mood Scale (VAMS) and Negative Self-Statement scale (SSPS-N) and physiological measures (blood pressure, heart rate, and skin conductance) were measured at six different time points during the SPST. The results were submitted to a repeated-measures analysis of variance. Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech. The placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group as assessed with the VAMS. The SSPS-N scores evidenced significant increases during the testing of placebo group that was almost abolished in the CBD group. No significant differences were observed between CBD and HC in SSPS-N scores or in the cognitive impairment, discomfort, and alert factors of VAMS. The increase in anxiety induced by the SPST on subjects with SAD was reduced with the use of CBD, resulting in a similar response as the HC.
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References
Agurell S, Carlsson S, Lindgren JE, Ohlsson A, Gillespie H, Hollister L (1981). Interactions of delta 1-tetrahydrocannabinol with cannabinol and cannabidiol following oral administration in man. Assay of cannabinol and cannabidiol by mass fragmentography. Experientia 37: 1090–1092.
Agurell S, Halldin M, Lindgren JE, Ohlsson A, Widman M, Gillespie H et al (1986). Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacol Rev 38: 21–43.
Blanco C, Antia SX, Liebowitz MR (2002). Pharmacotherapy of social anxiety disorder. Biol Psychiatry 51: 109–120.
Borgwardt SJ, Allen P, Bhattacharyya S, Fusar-Poli P, Crippa JA, Seal ML et al (2008). Neural basis of Delta-9-tetrahydrocannabinol and cannabidiol: effects during response inhibition. Biol Psychiatry 64: 966–973.
Brunello N, den Boer JA, Judd LL, Kasper S, Kelsey JE, Lader M et al (2000). Social phobia: diagnosis and epidemiology, neurobiology and pharmacology, comorbidity and treatment. J Affect Disord 60: 61–74.
Buckner JD, Schmidt NB, Lang AR, Small JW, Schlauch RC, Lewinsohn PM (2008). Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence. J Psychiatr Res 42: 230–239.
Campos AC, Guimaraes FS (2008). Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology 199: 223–230.
Canadian Psychiatric Association (2006). Clinical practice guidelines. Management of anxiety disorders. Can J Psychiatryi 51 (Suppl 2): 9–91.
Chagas MH, Nardi AE, Manfro GG, Hetem LA, Andrada NC, Levitan MN et al (2010). Guidelines of the Brazilian medical Association for the diagnosis and differential diagnosis of social anxiety disorder. Rev Bras Psiquiatr 32: 444–452.
Connor KM, Davidson JR, Churchill LE, Sherwood A, Foa E, Weisler RH (2000). Psychometric properties of Social Phobia Inventory (SPIN). Br J Psychiatry 176: 379–386.
Connor KM, Kobak KA, Churchill LE, Katzelnick D, Davidson JR (2001). Mini-Spin: a brief screening assessment for generalized social anxiety disorder. Depress Anxiety 14: 137–140.
Crippa JA, de Lima Osrio F, Del-Ben CM, Filho AS, da Silva Freitas MC, Loureiro SR (2008a). Comparability between telephone and face-to-face structured clinical interview for DSM-IV in assessing social anxiety disorder. Perspect Psychiatr Care 44: 241–247.
Crippa JA, Derenusson GN, Ferrari TB, Wichert-Ana L, Duran F, Marti N-Santos RO et al (2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder—a preliminary report. J Psychopharmacol 25: 121–130.
Crippa JA, Loureiro SR, Baptista CA, Osório F (2007). Are there differences between early- and late-onset social anxiety disorder? Rev Bras Psiquiatr 29: 195–196.
Crippa JA, Zuardi AW, Busatto GF, Santos-Filho A, Graeff FG, Borduqui T et al (2008b). Grey matter correlates of cognitive measures of the simulated public speaking test in social anxiety spectrum: a voxel-based study. Eur Psychiatry 23 (Suppl 2): 212.
Crippa JA, Zuardi AW, Garrido GE, Wichert-Ana L, Guarnieri R, Ferrari L et al (2004). Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology 29: 417–426.
Crippa JA, Zuardi AW, Hallak JE (2010). Therapeutical use of the cannabinoids in psychiatry. Rev Bras Psiquiatr 32 (Suppl 1): S56–S66.
Crippa JA, Zuardi AW, Martín-Santos R, Bhattacharyya S, Atakan Z, McGuire P (2009). Cannabis and anxiety: a critical review of the evidence. Hum Psychopharmacol 24: 515–523.
de Lima Osório F, Crippa JA, Loureiro SR (2007). A study of the discriminative validity of a screening tool (MINI-SPIN) for social anxiety disorder applied to Brazilian university students. Eur Psychiatry 22: 239–243.
de Lima Osório F, Crippa JA, Loureiro SR (2008). Self statements during public speaking scale (SSPS): cross-cultural adaptation for Brazilian Portuguese and internal consistency. Rev Psiq Clín 35: 207–211.
Del-Ben CM, Vilela JAA, Crippa JAS, Hallak JEC, Labate CM, Zuardi AW (2001). Confiabilidade teste-reteste da Entrevista Clínica Estruturada para o DSM-IV—Versão Clínica (SCID-CV) traduzida para o português. Rev Bras Psiquiatr 23: 156–159.
Filho AS, Hetem LA, Ferrari MC, Trzesniak C, Martín-Santos R, Borduqui T et al (2010). Social anxiety disorder: what are we losing with the current diagnostic criteria? Acta Psychiatr Scand 121: 216–226.
First MB, Spitzer RL, Gibbon M, Williams JBW (1997). Structured Clinical Interview for DSM-IV Axis I Disorders—Clinican Version (SCID-CV). American Psychiatric Press: Washington, DC, USA.
Fusar-Poli P, Allen P, Bhattacharyya S, Crippa JA, Mechelli A, Borgwardt S et al (2009a). Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol. Int J Neuropsychopharmacol 13: 421–432.
Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R et al (2009b). Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry 66: 95–105.
Graeff FG, Parente A, Del-Ben CM, Guimarães FS (2003). Pharmacology of human experimental anxiety. Braz J Med Biol Res 36: 421–432.
Hayakawa K, Mishima K, Nozako M, Ogata A, Hazekawa M, Liu AX et al (2007). Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance. Neuropharmacology 52: 1079–1087.
Hallak JE, Crippa JA, Quevedo J, Roesler R, Schröder N, Nardi AE et al (2010). National science and technology institute for translational medicine (INCT-TM): advancing the field of translational medicine and mental health. Rev Bras Psiquiatr 32: 83–90.
Hoffmann SG, Di Bartolo PM (2000). An instrument to assess self-statements during public speaking: scale development and preliminary psychometric properties. Behav Ther 31: 499–515.
Kessler RC (2007). The global burden of anxiety and mood disorders: putting the European Study of the Epidemiology of Mental Disorders (ESEMeD) findings into perspective. J Clin Psychiatry 68 (Suppl 2): 10–19.
McNair DM, Frankenthaler LM, Czerlinsky T, White TW, Sasson S, Fisher S (1982). Simulated public speaking as a model of clinical anxiety. Psychopharmacology (Berl) 77: 7–10.
Montgomery SA, Lecrubier Y, Baldwin DS, Kasper S, Lader M, Nil R et al (2004). European college of neuropsychopharmacology. ECNP Consensus Meeting, March 2003. Guidelines for the investigation of efficacy in social anxiety disorder. Eur Neuropsychopharmacol 14: 425–433.
Morgan CJ, Freeman TP, Schafer GL, Curran HV (2010). Cannabidiol attenuates the appetitive effects of Delta 9-tetrahydrocannabinol in humans smoking their chosen cannabis. Neuropsychopharmacology 35: 1879–1885.
Norris H (1971). The action of sedatives on brain stem oculomotor systems in man. Neuropharmacology 10: 181–191.
Osório Fde L, Crippa JA, Loureiro SR (2010). Further study of the psychometric qualities of a brief screening tool for social phobia (MINI-SPIN) applied to clinical and nonclinical samples. Perspect Psychiatr Care 46: 266–278.
Parente ACBV, Garcia-Leal C, Del-Ben C, Guimarães FS, Graeff FG (2005). Subjective and neurovegetative changes in health volunteers and panic patients performing simulated public speaking. Eur Neuropsychopharmacol 15: 663–671.
Parker LA, Burton P, Sorge RE, Yakiwchuk C, Mechoulam R (2004). Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmacology (Berl) 175: 360–366.
Ren Y, Whittard J, Higuera-Matas A, Morris CV, Hurd YL (2009). Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. J Neurosci 29: 14764–14769.
Russo EB, Burnett A, Hall B, Parker KK (2005). Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res 30: 1037–1043.
Schneier FR (2001). Treatment of social phobia with antidepressants. J Clin Psychiatry 62 (Suppl 1): 43–48.
Soares VDEP, Campos AC, Bortoli VC, Zangrossi Jr H, Guimarães FS, Zuardi AW (2010). Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors. Behav Brain Res 213: 225–229.
Zuardi AW (2008). Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev Bras Psiquiatr 30: 271–280.
Zuardi AW, Cosme RA, Graeff FG, Guimarães FS (1993). Effects of ipsapirone and cannabidiol on human experimental anxiety. J Psychopharmacol 7: 82–88.
Zuardi AW, Karniol IG (1981). Transcultural evaluation of a self-evaluation scale of subjective states. J Brasileiro Psiquiatr 131: 403–406.
Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG (1982). Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl) 76: 245–250.
Acknowledgements
This work received grants from FAPESP. FK, JQ, RR, AEN, JECH, AWZ and JASC are recipients of CNPq Productivity Awards.
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Professor Kapczinski has received grant/research support from Astra-Zeneca, EliLilly, the Janssen-Cilag, Servier, CNPq, CAPES, NARSAD and the Stanley Medical Research Institute; he has been a member of the speakers’ boards for Astra-Zeneca, EliLilly, Janssen and Servier; and he has served as a consultant for Servier.
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Bergamaschi, M., Queiroz, R., Chagas, M. et al. Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients. Neuropsychopharmacol 36, 1219–1226 (2011). https://doi.org/10.1038/npp.2011.6
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DOI: https://doi.org/10.1038/npp.2011.6
