Skip to main content

Interaction between cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC): influence of administration interval and dose ratio between the cannabinoids

This is a preview of subscription content, access via your institution.


  • Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S, Winton-Brown T, Nosarti C, O' Carroll CM, Seal M, Allen P, Mehta MA, Stone JM, Tunstall N, Giampietro V, Kapur S, Murray RM, Zuardi AW, Crippa JA, Atakan Z, McGuire PK (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

    PubMed  Article  CAS  Google Scholar 

  • Bhattacharyya S, Crippa JA, Allen P, Martin-Santos R, Borgwardt SJ, Fusar-Poli P, Rubia K, Kambweitz J, O'Carroll C, Seal ML, Giampietro V, Brammer M, Zuardi AW, Atakan Z, McGuire PK (2011) Delta 9-tetrahydrocannabinol modulates hippocampal and striatal function during oddball salience processing. Arch Gen Psychiatr (in press)

  • Deiana S, Watanabe A, Yamasaki Y, Amada N, Arthur M, Fleming S, Woodcock H, Dorward P, Pigliacampo B, Close S, Platt B, Riedel G (2011) Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ(9)-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour. Psychopharmacology (Berl). doi:10.1007/s00213-011-2415-0

  • Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R, Seal M, Surguladze SA, O'Carrol C, Atakan Z, Zuardi AW, McGuire PK (2009) Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatr 66:95–105

    PubMed  Article  CAS  Google Scholar 

  • Guimaraes FS, Chiaretti TM, Graeff FG, Zuardi AW (1990) Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology (Berl) 100:558–559

    Article  CAS  Google Scholar 

  • Jones G, Pertwee RG (1972) A metabolic interaction in vivo between cannabidiol and 1-tetrahydrocannabinol. Br J Pharmacol 45:375–377

    PubMed  CAS  Google Scholar 

  • Karschner EL, Darwin WD, Goodwin RS, Wright S, Huestis MA (2011a) Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin Chem 57:66–75. doi:10.1373/clinchem.2010.152439

    PubMed  Article  CAS  Google Scholar 

  • Karschner EL, Darwin WD, McMahon RP, Liu F, Wright S, Goodwin RS, Huestis MA (2011b) Subjective and physiological effects after controlled Sativex and oral THC administration. Clin Pharmacol Ther 89:400–407. doi:10.1038/clpt.2010.318

    PubMed  Article  CAS  Google Scholar 

  • Klein C, Karanges E, Spiro A, Wong A, Spencer J, Huynh T, Gunasekaran N, Karl T, Long LE, Huang XF, Liu K, Arnold JC, McGregor IS (2011) Cannabidiol potentiates Δ(9)-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. Psychopharmacology (Berl). doi:10.1007/s002-011-2342-0

  • Paton WD, Pertwee RG (1972) Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism. Br J Pharmacol 44:250–261

    PubMed  CAS  Google Scholar 

  • Reid MJ, Bornheim LM (2001) Cannabinoid-induced alterations in brain disposition of drugs of abuse. Biochem Pharmacol 61:1357–1367

    PubMed  Article  CAS  Google Scholar 

  • Winton-Brown TT, Allen P, Bhattacharrya S, Borgwardt SJ, Fusar-Poli P, Crippa JA, Seal ML, Martin-Santos R, Ffytche D, Zuardi AW, Atakan Z, McGuire PK (2011) Modulation of auditory and visual processing by delta-9-tetrahydrocannabinol and cannabidiol: an FMRI study. Neuropsychopharmacology 36:1340–1348. doi:10.1038/npp.2011.17

    PubMed  Article  CAS  Google Scholar 

  • Zuardi AW (2008) Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev Bras Psiquiatr 30:271–280

    PubMed  Article  Google Scholar 

  • Zuardi AW, Karniol IG (1983) Effects on variable-interval performance in rats of delta 9-tetrahydrocannabinol and cannabidiol, separately and in combination. Braz J Med Biol Res 16(2):141–146

    PubMed  CAS  Google Scholar 

  • Zuardi AW, Karniol IG (1984) Pharmacological interaction between 9-tetrahydrocannabinol and cannabidiol, two active constituents of Cannabis sativa. Ciência e Cultura 36(6):386–394

    CAS  Google Scholar 

  • Zuardi AW, Finkelfarb E, Bueno OF, Musty RE, Karniol IG (1981) Characteristics of the stimulus produced by the mixture of cannabidiol with delta 9-tetrahydrocannabinol. Arch Int Pharmacodyn Ther 249:137–146

    PubMed  CAS  Google Scholar 

  • Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG (1982) Action of cannabidiol on the anxiety and other effects produced by delta9-THC in normal subjects. Psychopharmacology (Berl) 76:245–250

    Article  CAS  Google Scholar 

  • Zuardi AW, Teixeira NA, Karniol IC (1984) Pharmacological interaction of the effects of delta 9-trans-tetrahydrocannabinol and cannabidiol on serum corticosterone levels in rats. Arch Int Pharmacodyn Ther 269(1):12–19

    PubMed  CAS  Google Scholar 

Download references


This work received grants from “Fundação de Amparo a Pesquisa do Estado de São Paulo” (FAPESP 2007/03685-3). AWZ, JASC, and JECH are recipients of CNPq Productivity Awards.

Conflict of interest

The authors have no competing interests.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Antonio Waldo Zuardi.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zuardi, A.W., Hallak, J.E.C. & Crippa, J.A.S. Interaction between cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC): influence of administration interval and dose ratio between the cannabinoids. Psychopharmacology 219, 247–249 (2012).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Pharmacokinetic Interaction
  • Corticosterone Level
  • Anandamide
  • Simultaneous Administration
  • Dose Ratio