Inverted U-shaped dose-response curve of the anxiolytic effect of cannabidiol during public speaking in real life

Frontiers in Pharmacology

Volumn 8, Issue MAY, 2017, Pages

  Zuardi, Antonio W ^a,b   Rodrigues, Natália P ^a   Silva, Angélica L ^a   Bernardo, Sandra A ^a   Hallak, Jaime E C ^a,b   Guimarães, Francisco S ^a,b   Crippa, José A S ^a,b  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b Ministério de Ciência Tecnologia e Inovação Salvador   (Brazil)

Author keywords

Anxiety; Cannabidiol; Clonazepam; Dose response; Healthy volunteers; Public speaking

Indexed keywords

CANNABIDIOL; CLONAZEPAM; PLACEBO;

ACUTE DRUG ADMINISTRATION; ADULT; ANXIETY; ARTICLE; ATTENUATION; BLOOD PRESSURE; CONTROLLED STUDY; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; FEMALE; HEART RATE; HUMAN; HUMAN EXPERIMENT; MALE; MEASUREMENT REPEATABILITY; NORMAL HUMAN; PERSONAL EXPERIENCE; PUBLIC SPEAKING; RANDOMIZED CONTROLLED TRIAL; SEDATION; TRANQUILIZING ACTIVITY; VISUAL ANALOG SCALE; VOLUNTEER;

EID: 85019594987     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2017.00259     Document Type: Article

References (57)

1. Agurell, S., Carlsson, S., Lindgren, J. E., Ohlsson, A., Gillespie, H., and 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. doi: 10.1007/BF02085029
2. 1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacol. Rev. 38, 21-43
3. Bandelow, B., Lichte, T., Rudolf, S., Wiltink, J., and Beutel, M. E. (2015). The German guidelinesfor the treatment of anxiety disorders. Eur. Arch. Psychiatry Clin. Neurosci. 265, 363-373. doi: 10.1007/s00406-014-0563-z
4. Bergamaschi, M. M., Queiroz, R. H., Chagas, M. H., de Oliveira, D. C., De Martinis, B. S., Kapczinski, F., et al. (2011a). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology 36, 1219-1226. doi: 10.1038/npp.2011.6
5. Bergamaschi, M. M., Queiroz, R. H., Zuardi, A. W., and Crippa, J. A. (2011b). Safety, and. (side) effects of cannabidiol, a Cannabis sativa constituent. Curr. Drug Saf. 6, 237-249. doi: 10.2174/157488611798280924
6. Bhattacharyya, S., Morrison, P. D., Fusar-Poli, P., Martin-Santos, R., Borgwardt, S., Winton-Brown, T., et al. (2010). Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 35, 764-774. doi: 10.1038/npp.2009.184
7. Borgwardt, S. J., Allen, P., Bhattacharyya, S., Fusar-Poli, P., Crippa, J. A., Seal, M. L., et al. (2008). Neural basis of Δ-9-tetrahydrocannabinol and cannabidiol: effects during response inhibition. Biol. Psychiatry 64, 966-973. doi: 10.1016/j.biopsych.2008.05.011
8. Boychuk, D. G., Goddard, G., Mauro, G., and Orellana, M. F. (2015). The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J. Oral Facial Pain Headache 29, 7-14. doi: 10.11607/ofph.1274
9. Campos, A. C., de Paula Soares, V., Carvalho, M. C., Ferreira, F. R., Vicente, M. A., Brandao, M. L., et al. (2013). Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats. Psychopharmacology (Berl). 226, 13-24. doi: 10.1007/s00213-012-2878-7
10. Campos, A. C., and Guimarães, F. S. (2008). Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology (Berl) 199, 223-230. doi: 10.1007/s00213-008-1168-x
11. Campos, A. C., and Guimarães, 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. Neuropsychopharmacol. Biol. Psychiatry 33, 1517-1521. doi: 10.1016/j.pnpbp.2009.08.017
12. Chagas, M. H., Eckeli, A. L., Zuardi, A. W., Pena-Pereira, M. A., Sobreira-Neto, M. A., Sobreira, E. T., et al. (2014a). Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series. J. Clin. Pharm. Ther. 39, 564-566. doi: 10.1111/jcpt.12179
13. Chagas, M. H., Zuardi, A. W., Tumas, V., Pena-Pereira, M. A., Sobreira, E. T., Bergamaschi, M. M., et al. (2014b). Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial. J. Psychopharmacol. 28, 1088-1098. doi: 10.1177/0269881114550355
14. Crevoisier, C., Delisle, M. C., Joseph, I., and Foletti, G. (2003). Comparative single-dose pharmacokinetics of clonazepam following intravenous, intramuscular and oral administration to healthy volunteers. Eur. Neurol. 49, 173-177. doi: 10.1159/000069089
15. Crippa, J. A., Crippa, A. C., Hallak, J. E., Martín-Santos, R., and Zuardi, A. W. (2016). Δ9-THC intoxication by Cannabidiol-enriched cannabis extract in two children with refractory epilepsy: full remission after switching to purified cannabidiol. Front. Pharmacol. 7:359. doi: 10.3389/fphar.2016.00359
16. Crippa, J. A., Derenusson, G. N., Ferrari, T. B., Wichert-Ana, L., Duran, F. L., Martin-Santos, R., et al. (2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J. Psychopharmacol. 25, 121-130. doi: 10.1177/0269881110379283
17. Crippa, J. A., Zuardi, A. W., Garrido, G. E., Wichert-Ana, L., Guarnieri, R., Ferrari, L., et al. (2004). Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology 29, 417-426. doi: 10.1038/sj.npp.1300340
18. Crippa, J. A., Zuardi, A. W., and Hallak, J. E. (2010). Therapeutical use of the cannabinoids in psychiatry. Rev. Bras. Psiquiatr. 32(Suppl. 1), S56-S66
19. de-Paris, F., Sant'Anna, M. K., Vianna, M. R., Barichello, T., Busnello, J. V., Kapczinski, F., et al. (2003). Effects of gabapentin on anxiety induced by simulated public speaking. J. Psychopharmacol. 17, 184-188. doi: 10.1177/0269881103017002006
20. Devinsky, O., Marsh, E., Friedman, D., Thiele, E., Laux, L., Sullivan, J., et al. (2015). Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 15, 270-278. doi: 10.1016/S1474-4422(15)00379-8
21. Dickerson, S. S., and Kemeny, M. E. (2004). Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol. Bull. 130, 355-391. doi: 10.1037/0033-2909.130.3.355
22. Esposito, G., Filippis, D. D., Cirillo, C., Iuvone, T., Capoccia, E., Scuderi, C., et al. (2013). Cannabidiol in inflammatory bowel diseases: a brief overview. Phytother. Res. 27, 633-636. doi: 10.1002/ptr.4781
23. Fogaça, M. V., Reis, F. M., Campos, A. C., and Guimaraes, F. S. (2014). Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: involvement of 5HT1A receptors and previous stressful experience. Eur. Neuropsychopharmacol. 24, 410-419. doi: 10.1016/j.euroneuro.2013.10.012
24. Fusar-Poli, P., Allen, P., Bhattacharyya, S., Crippa, J. A., Mechelli, A., Borgwardt, S., et al. (2010). Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol. Int. J. Neuropsychopharmacol. 13, 421-432. doi: 10.1017/S1461145709990617
25. Fusar-Poli, P., Crippa, J. A., Bhattacharyya, S., Borgwardt, S. J., Allen, P., Martin-Santos, R., et al. (2009). Distinct effects of Delta9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch. Gen. Psychiatry 66, 95-105. doi: 10.1001/archgenpsychiatry.2008.519
26. Gomes, F. V., Reis, D. G., Alves, F. H., Correa, F. M., Guimaraes, F. S., and Resstel, L. B. (2012). Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT1A receptors. J. Psychopharmacol. 26, 104-113. doi: 10.1177/0269881110389095
27. Gomes, F. V., Resstel, L. B., and Guimaraes, F. S. (2011). The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. Psychopharmacology (Berl) 213, 465-473. doi: 10.1007/s00213-010-2036-z
28. Graeff, F. G., Parente, A., Del-Ben, C. M., and Guimaraes, F. S. (2003). Pharmacology of human experimental anxiety. Braz. J. Med. Biol. Res. 36, 421-432. doi: 10.1590/S0100-879X2003000400003
29. Guimarães, F. S., Carobrez, A. P., De Aguiar, J. C., and Graeff, F. G. (1991). Anxiolytic effect in the elevated plus-maze of the NMDA receptor antagonist AP7 microinjected into the dorsal periaqueductal grey. Psychopharmacology (Berl). 103, 91-94. doi: 10.1007/BF02244080
30. Guimarães, F. S., Chiaretti, T. M., Graeff, F. G., and Zuardi, A. W. (1990). Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology (Berl). 100, 558-559. doi: 10.1007/BF02244012
31. Hetem, L. A., de Souza, C. J., Guimaraes, E. S., Zuardi, A. W., and Graeff, F. G. (1996). Effect of d-fenfluramine on human experimental anxiety. Psychopharmacology (Berl). 127, 276-282. doi: 10.1007/BF02246136
32. Izzo, A. A., Borrelli, F., Capasso, R., DiMarzo, V., and Mechoulam, R. (2009). Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol. Sci. 30, 515-527. doi: 10.1016/j.tips.2009.07.006
33. Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., and Van Ameringen, M. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry 14(Suppl. 1):S1. doi: 10.1186/1471-244X-14-S1-S1
34. Levin, R., Peres, F. F., Almeida, V., Calzavara, M. B., Zuardi, A. W., Hallak, J. E., et al. (2014). Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain. Front. Pharmacol. 6:10. doi: 10.3389/fphar.2014.00010
35. Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C. W., Hoyer, C., et al. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl. Psychiatry 2, e94. doi: 10.1038/tp.2012.15
36. Martin-Santos, R., Crippa, J. A., Batalla, A., Bhattacharyya, S., Atakan, Z., Borgwardt, S., et al. (2012). Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers. Curr. Pharm. Des. 18, 4966-4979. doi: 10.2174/138161212802884780
37. Moreira, F. A., and Guimarães, F. S. (2005). Cannabidiol inhibits the hyperlocomotion induced by psychotomimetic drugs in mice. Eur. J. Pharmacol. 512, 199-205. doi: 10.1016/j.ejphar.2005.02.040
38. Nazario, L. R., Antonioli, R. J., Capiotti, K. M., Hallak, J. E., Zuardi, A. W., Crippa, J. A., et al. (2015). Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio). Pharmacol. Biochem. Behav. 139, 134-140. doi: 10.1016/j.pbb.2015.11.002
39. Palma, S. M., Guimaraes, F. S., and Zuardi, A. W. (1994). Anxiety induced by simulated public speaking and stroop color word test in healthy subjects: effects of different trait-anxiety levels. Braz. J. Med. Biol. Res. 27, 2895-2902
40. Parente, A. C. B. V., Garcia-Leal, C., Del-Ben, C. M., Guimarães, F. S., and Graeff, F. G. (2005). Subjective and neurovegetative changes in healthy volunteers and panic patients performing simulated public speaking. Eur. Neuropsychopharmacol. 15, 663-671. doi: 10.1016/j.euroneuro.2005.05.002
41. Peres, F. F., Levin, R., Suiama, M. A., Diana, M. C., Gouvêa, D. A., Almeida, V., et al. (2016). Cannabidiol prevents motor and cognitive impairments induced by reserpine in rats. Front. Pharmacol. 7:343. doi: 10.3389/fphar.2016.00343
42. Resstel, L. B., Joca, S. R., Moreira, F. A., Correa, F. M., and Guimarães, F. S. (2006). Effects of cannabidiol and diazepam on behavioral and cardiovascular responses induced by contextual conditioned fear in rats. Behav. Brain Res. 172, 294-298. doi: 10.1016/j.bbr.2006.05.016
43. Rock, E. M., Bolognini, D., Limebeer, C. L., Cascio, M. G., Anavi-Goffer, S., Fletcher, P. J., et al. (2011). Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic: autoreceptors in the dorsal raphe nucleus. Br. J. Pharmacol. 2012, 2620-2634. doi: 10.1111/j.1476-5381.2011.01621.x
44. Russo, E. B., Burnett, A., Hall, B., and Parker, K. K. (2005). Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem. Res. 30, 1037-1043. doi: 10.1007/s11064-005-6978-1
45. Sgnaolin, V., Engroff, P., Andrade, C. P., Loureiro, F., Nogueira, E. L., Cataldo Neto, A., et al. (2016). Patterns of chronic benzodiazepine use in the elderly. Arch. Clin. Psychiatry 43, 79-82. doi: 10.1590/0101-60830000000089
46. Soares, V., de, P., Campos, A. C., Bortoli, V. C., Zangrossi, H. Jr., Guimaraes, F. S., et al. (2010). Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors. Behav. Brain Res. 213, 225-229. doi: 10.1016/j.bbr.2010.05.004
47. Spielberger, C. D., Gorsuch, R. L., and Lushene, R. E. (1970). Manual for the Strait-Trait Anxiety Inventory. Palo alto, CA: Consulting Psychologists Press
48. Turner, J. R., Girdler, S. S., Sherwood, A., and Light, K. C. (1990). Cardiovascular responses to behavioral stressors: laboratory-field generalization and inter-task consistency. J. Psychosom. Res. 34, 581-589. doi: 10.1016/0022-3999(90)90033-Z
49. Zanelati, T. V., Biojone, C., Moreira, F. A., Guimarães, F. S., and Joca, S. R. (2010). Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors. Br. J. Pharmacol. 159, 122-128. doi: 10.1111/j.1476-5381.2009.00521.x
50. Zhornitsky, S., and Potvin, S. (2012). Cannabidiol in humans-the quest for therapeutic targets. Pharmaceuticals (Basel). 5, 529-552. doi: 10.3390/ph5050529
51. Zuardi, A. W. (2008). Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev. Bras. Psiquiatr. 30, 271-280. doi: 10.1590/S1516-44462008000300015
52. Zuardi, A. W., Cosme, R. A., Graeff, F. G., and Guimarães, F. S. (1993). Effects of ipsapirone and cannabidiol on human experimental anxiety. J. Psychopharmacol. 7, 82-88. doi: 10.1177/026988119300700112
53. Zuardi, A. W., Crippa, J. A., Hallak, J. E., Campos, A., and Guimarães, F. S. (2017). "The anxiolytic effects of Cannabidiol (CBD), " in Handbook of Cannabis and Related Pathologies, 1st Edn, ed. V. Preedy (Cambridge, MA: AcademicPress)
54. Zuardi, A. W., Crippa, J. A., Hallak, J. E., and Gorayeb, R. (2013). Human experimental anxiety: actual public speaking induces more intense physiological responses than simulated public speaking. Rev. Bras. Psiquiatr. 35, 248-253. doi: 10.1590/1516-4446-2012-0930
55. Zuardi, A. W., Crippa, J. A., Hallak, J. E., Pinto, J. P., Chagas, M. H., Rodrigues, G. G., et al. (2009). Cannabidiol for the treatment of psychosis in Parkinson's disease. J. Psychopharmacol. 23, 979-983. doi: 10.1177/0269881108096519
56. Zuardi, A. W., and Karniol, I. G. (1981). Transcultural evaluation of a self-evaluation scale of subjective states. J. Bras. Psiquiatr. 131, 403-406
57. Zuardi, A. W., Rodrigues, J. A., and Cunha, J. M. (1991). Cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology 104, 260-264. doi: 10.1007/BF02244189