Depression and anxiety are pathologies that affect human beings in many aspects of life, including social life, productivity and health. Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa with great psychiatric potential, including uses as an antidepressant-like and anxiolytic-like compound. The pharmacological effects of CBD are different and often opposite to those of tetrahydrocannabinol (THC), psychoactive constituent of Cannabis sativa1. The number of publications on CBD has increased remarkably over the last years and support the view that CBD has a vast array of possible therapeutic effects. Among these possibilities, the anxiolytic and antipsychotic properties of CBD stand out2-5. CBD’s anxiolytic effects are apparently similar to those of approved drugs to treat anxiety6 although its effective doses have not been clearly established and the mechanisms underlying these effects are not fully understood. Most studies on CBD have been conducted with rodents, but studies with human samples have also provided promising results7, 8.
The first evidence of CBD’s anxiolytic effects in humans, documented with assessment scales, was published in 1982 in a study on the interaction between CBD and THC2. The study sample consisted of eight volunteers with a mean age of 27 years. In a double-blind procedure, the volunteers received CBD, THC, THC + CBD, diazepam (anxiolytic drug), and placebo in different sequences and days. The results showed that the increased anxiety following the administration of THC was significantly attenuated with the simultaneous administration of CBD (THC + CBD).
Other investigation of possible anxiolytic action of CBD was performed in experimentally induced anxiety in healthy volunteers using the simulated public speaking (SPS) model9. The procedure consists of asking a subject to speak in front of a video camera for a few minutes, while subjective anxiety is measured with self-rated scales and physiological correlates of anxiety are recorded (heart rate, blood pressure, skin conductance). CBD (300 mg), as well as the anxiolytic drugs diazepam (10 mg) and ipsapirone (5 mg), administered in a double-blind design, significantly attenuated SPS-induced anxiety. The SPS test may be regarded as a good model of anxiety and has apparent validity for social anxiety disorder (SAD), as the fear of speaking in public is considered a central feature in this condition. Therefore, the anxiolytic effect of CBD in healthy volunteers observed in this test led to the hypothesis that this cannabinoid could be effective to treat SAD.
This hypothesis was recently tested in 24 patients with SAD who had their performance in the SPS test compared to that of a group of 12 healthy controls10. The patients with SAD were divided into two groups of 12, one of which received CBD 600 mg and the other placebo, in a double-blind procedure. The results showed that the levels of anxiety, somatic symptoms, and negative self-assessment were higher in patients who took placebo than in those of the CBD group who performed similarly to healthy controls in some measures.
In another study that investigated the effects of CBD on regional cerebral blood flow (rCBF) in healthy volunteers using single photon emission computed tomography (SPECT), SPS-induced anxiety was reduced in patients receiving CBD11. In that study, patients received either CBD (400 mg) or placebo, in a crossed double-blind design, in two experimental sessions with an interval of one week. CBD significantly reduced subjective anxiety as measured by rating scales, while brain activity was increased in the left parahippocampal gyrus and decreased in the left amygdala-hippocampus complex, including the fusiform gyrus. This pattern of SPECT results is compatible with an anxiolytic action.
Together, the results from healthy volunteers, and patients with anxiety disorders support the proposition of CBD as a new drug with anxiolytic properties. Because it has no psychoactive effects and does not affect cognition; has an adequate safety profile, good tolerability, positive results in trials with humans, and a broad spectrum of pharmacological actions, CBD appears to be the cannabinoid compound that is closer to have its preliminary findings in anxiety translated into clinical practice12. Future studies should test this possibility in clinical trials involving patients with different anxiety disorders.
- Mechoulam R, Petersa M, Murillo-Rodriguez E, Hanus LO. Cannabidiol – recent advances. Chem Biodivers. 2007;4:1678-92
- Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 1982;76:245-50
- Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimaraes FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res. 2006;39(4):4219
- Guimarães FS, Chiaretti TM, Graeff FG, Zuardi AW. Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology (Berl). 1990;100:558-9
- Resstel LB, Joca SR, Moreira FA, Correa FM, Guimarães FS. Effects of cannabidiol and diazepam on behavioral and cardiovascular responses induced by contextual conditioned fear in rats. Behav Brain Res. 2006;172(2):294-8.
- Resstel, LB, Tavares RF, Lisboa SF. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in ratscardiovascular responses to acute restraint stress in rats. Br J Pharmacol. 2009;156(1):181-8.
- Fusar-Poli P, Allen P, Bhattacharyya S, Crippa JA, Mechelli A, Borgwardt S, Martin-Santos R, Seal ML, O’Carrol C, Atakan Z, Zuardi AW, McGuire P. Modulation of effective connectivity during emotional processing by Delta(9)-tetrahydrocannabinol and cannabidiol. Int J Neuropsychopharmacol. 2010;13(4):421-32
- Crippa JAS, Derenusson GN, Ferrari TB, Wichert-Ana L, Duran FL, Martin-Santos R, Simões MV, Bhattacharyya S, Fusar-Poli P, Atakan Z, Santos Filho A, Freitas-Ferrari MC, McGuire PK, Zuardi AW, Busatto GF, Hallak JE. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol. 2011;25(1):121-30
- Zuardi AW, Cosme RA, Graeff FG, Guimarães FS. Effects of ipsapirone and cannabidiol on human experimental anxiety. J Psychopharmacol 1993;7:82-8
- Bergamaschi MM, Queiroz RH, Chagas MHN, de Oliveira DCG, De Martinis BS, Kapczinski F, Quevedo J, Roesler R, Schroder N, Nardi AE, Martin-Santos R, Hallak JEC, Zuardi AW, Crippa JAS. Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients. Neuropsychopharmacol. 2011;36(6):1219-26
- Crippa JA, Zuardi AW, Garrido GE, Wichert-Ana L, Guarnieri R, Ferrari L, Azevedo-Marques PM, Hallak JE, McGuire PK, Filho Busatto G. Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacol. 2004;29(2):417-26
- Crippa JA, Zuardi AW, Hallak JE. [Therapeutical use of the cannabinoids in psychiatry]. Rev Bras Psiquiatr. 2010;32(Suppl1):S56-66
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