, Volume 76, Issue 3, pp 245–250 | Cite as

Action of cannabidiol on the anxiety and other effects produced by δ9-THC in normal subjects

  • A. W. Zuardi
  • I. Shirakawa
  • E. Finkelfarb
  • I. G. Karniol
Original Investigations


The object of the experiment was to verify whether cannabidiol (CBD) reduces the anxiety provoked by Δ9-TCH in normal volunteers, and whether this effect occurs by a general block of the action of Δ9-TCH or by a specific anxiolytic effect. Appropriate measurements and scales were utilized and the eight volunteers received, the following treatments in a double-blind procedure: 0.5 mg/kg Δ9-TCH, 1 mg/kg CBD, a mixture containing 0.5 mg/kg Δ9-TCH and 1 mg/kg CBD and placebo and diazepam (10 mg) as controls. Each volunteer received the treatments in a different sequence. It was verified that CBD blocks the anxiety provoked by Δ9-TCH, however this effect also extended to marihuanalike effects and to other subjective alterations induced by Δ9-TCH. This antagonism does not appear to be caused by a general block of Δ9-TCH effects, since no change was detected in the pulse-rate measurements. Several further effects were observed typical of CBD and of an opposite nature to those of Δ9-TCH.

These results suggest that the effects of CBD, as opposed to those of Δ9-TCH, might be involved in the antagonism of effects between the two cannabinoids.

Key words

Cannabis Cannabinoids CBD Δ9-TCH interaction Anxlety 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agurell S, Levander S, Bindler M, Bader-Bartfai A, Gustafson B, Leander K, Lindgren J, Ohlsson A, Tobisson B (1976) Pharmacokinetics of Δ 8-tetrahydrocannabinol (Δ 6-tetrahydrocannabinol) in man after smoking — Relations to physiological and psychological effects. In: Braude MC, Szara S (eds) The pharmacology of marihuana. Raven Press, New York, pp 49–61Google Scholar
  2. Bech P, Rafaelsen L, Rafaelsen OJ (1974) Cannabis: A psychopharmacological review. Dan Med Bull 21 (3):106–120Google Scholar
  3. Biaggio AMB, Natalício L, Spielberger CD (1977) Desenvolvimento da forma experimental em portugues do Inventário de Ansiedade. Traço — Estado (IDATE), de Spielberger. Arquivos Brasileiros de Psicologia Aplicada 29:31–44Google Scholar
  4. Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218Google Scholar
  5. Borg J, Gerson S, Alpert M (1975) Dose effects of smoked marihuana on human cognitive and motor functions. Psychopharmacologia 42:211–218Google Scholar
  6. Bussab WO (1976) Hierarchical dichotomous partitions in cluster analysis. PhD Thesis, University of LondonGoogle Scholar
  7. Cappell H, Kuchar E (1974) Pharmacologic and nonpharmacologic factors in marijuana intoxication. Clin Toxicol 7:315Google Scholar
  8. Carlin AS, Bakker CB, Halpern L, Post RD (1972) Social facilitation of marijuana intoxication: Impact of social set and pharmacological activity. J Abnorm Psychol 80:132–140Google Scholar
  9. Carlini EA, Leite JR, Tanhauser M, Berardi AC (1973) Cannabidiol and Cannabis sativa extract protect mice and rats against convulsive agents. J Pharm Pharmacol 25:664–665Google Scholar
  10. Carlini EA, Masur J, Magalhães CCPB (1979) Possível efeito hipnótico do canabidiol no ser humano. Estudo preliminar. Cìência e Cultura 31:315–322Google Scholar
  11. Cunha JM (1979) O efeito anti-epiléptico do canabidiol. Tese de doutoramento apresentada a Escola Paulista de Medicina, São PauloGoogle Scholar
  12. Dalton WS, Martz R, Lemberger L, Rodda BE, Forney B (1976) Influence of cannabidiol on Δ 9-tetrahydrocannabinol effects. Clin Pharmacol Ther 19:300–309Google Scholar
  13. Davis WM, Borgen LA (1974) Effects of cannabidiol and Δ 9-tetrahydrocannabinol on operant behavior. Res Commun Chem Pathol Pharmacol 9:453–462Google Scholar
  14. Fernandes M, Schabarek A, Coper H, Hill R (1974) Modification of Δ 9-THC actions by cannabinol and cannabidiol in the rat. Psychopharmacologia 38:329–338Google Scholar
  15. Galanter M, Wyatt RJ, Lemberger L, Weingartner H, Vaughan TB, Roth WT (1972) Effects on humans of Δ 9-tetrahydrocannabinol administered by smoking. Science 176:934–936Google Scholar
  16. Gregg JM, Small EW, Moore R, Raft D, Toomey TC (1976) Emotional response to intravenous Δ 9-tetrahydrocannabinol during oral surgery. J Oral Surg 34:301–313Google Scholar
  17. Grlic L (1976) A comparative study on some chemical and biological characteristics of various samples of cannabis resin. Bull Narcot 14:37–46Google Scholar
  18. Haertzen CA, Hill HE, Belleville RE (1963) Development of the Addiction Research Center Inventory (ARCI): Selection of items that are sensitive to the effects of various drugs. Psychopharmacologia 4:155–166Google Scholar
  19. Hollister LE (1971) Manhuana in man: three yeas later. Science 172:21–29Google Scholar
  20. Hollister LE (1973) Cannabidiol and cannabinol in man. Experientia 29:825–826Google Scholar
  21. Hollister LE, Gillespie H (1975) Interactions in man of Δ 9-tetrahydrocannabinol. II-Cannabinol and Cannabidiol. Clin Pharmacol Ther 18:80–83Google Scholar
  22. Hollister LE, Richards RK, Gillespie H (1968) Comparison of tetrahydrocannabinol and synhexil in human. Clin Pharmacol Ther 9 (6):783–791Google Scholar
  23. Isbell H, Jasinski DR (1969) A comparison of LSD-25 with (-)Δ 9-tetrahydrocannabinol (THC) and attempted cross tolerance between LSD and THC. Psychopharmacologia 14:115–123Google Scholar
  24. Jones RT (1971) Tetrahydrocannabinol and the marijuana — Induced social “high”, or the effects of the mind on marijuana. In: Singer AD (ed) Marijuana. Chemistry, Pharmacology, and Patterns of Social Use. New York Academy of Sciences, pp 155–165Google Scholar
  25. Jones RT (1978) Marihuana: Human effects. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of Psychopharmacology. Drugs of Abuse. Plenum Press, New York, pp 373–412Google Scholar
  26. Karniol IG, Carlini EA (1973) Comparative studies in man and in laboratory animals on Δ 8- and Δ 9-trans-tetrahydrocannabinol. Pharmacology 9:115–126Google Scholar
  27. Karniol IG, Dalton J, Lader M (1976) Comparative psychotropic effects of trazodone imipramine and diazepam in normal subjects. Curr Ther Res 20 (3):337–347Google Scholar
  28. Karniol IG, Dalton J, Lader M (1978) Acute and chronic effects of lithium chloride on physiological and psychological measures in normals. Psychopharmacology 57:289–294Google Scholar
  29. Karniol IG, Shirakawa I, Kasinski N, Pfeferman A, Carlini EA (1974) Cannabidiol interferes with the effects of Δ 9-tetrahydrocannabinol in man. Eur J Pharmacol 28:172–177Google Scholar
  30. Kiplinger GF, Manno JE, Rodda BE, Forney RB (1971) Dose-response analysis of the tetrahydrocannabinols in man. Clin Pharmacol Ther 12:650–657Google Scholar
  31. Klapper JA, McCulloch MA, Sidell RF (1972) The effect on personality of reactivity to 1,2-dimethyl-heptyl tetrahydrocannabinol. Arch Gen Psychiatry 26:483–485Google Scholar
  32. Malit LA, Johnstone RF, Bourke DI, Kulp RA, Klein D, Eng D, Smith DC (1975) Intravenous Δ 9-tetrahydrocannabinol: effects on ventilatory control and cardiovascular dynamics. Anesthesiol 42:666–673Google Scholar
  33. Martz R, Brown DJ, Forney RB, Bright TP, Kiplinger GF, Rodda BE (1972) Propanolol antagonism of marihuana induced tachycardia. Life Sci 11:999–1005Google Scholar
  34. Meyer RE (1978) Behavioral pharmacology of marihuana. In: Lipton MA, Dimascio A, Killam KF (eds) Psychopharmacology: A generation of progress. Raven Press, New York, pp 1634–1652Google Scholar
  35. Miller LL, Cornett TL (1978) Marijuana: dose effects on pulse rate, subjective estimates of intoxication free recall and recognition memory. Pharmacol Biochem Behav 9:573–577Google Scholar
  36. Monti JM (1977) Hypnoticlike effects of cannabidiol in the rat. Psychopharmacology 55:263–265Google Scholar
  37. Naliboff BD, Rickles WH, Cohen MJ, Naimark RS (1976) Interactions of marijuana and induced stress: forearm blood flow heart rate, and skin conductance. Psychophysiology 13:517–522Google Scholar
  38. Norris H (1971) The action of sedatives on brain stem oculomotor systems in man. Neuropharmacology 10:181–191Google Scholar
  39. Perez-Reyes M, Timmons MC, Dauls KH, Wall ME (1973) A comparison of the pharmacological activity in man of the intravenously administered Δ 9-tetrahydrocannabinol, cannabinol and cannabidiol. Experientia 29:1368–1369Google Scholar
  40. Pillard RC, McNair DM, Fisher S (1974) Does marijuana enhance experimental induced anxiety? Psychopharmacologia 40:205–210Google Scholar
  41. Rossi AM, Kuehnle JC, Mendelson JH (1978) Marihuana and mood in human volunteers. Pharmacol Biochem Behav 8:447–455Google Scholar
  42. Scott AJ, Knott M (1974) A cluster analysis method for grouping means in the analysis of variance. Biometrics 30:507–512Google Scholar
  43. Siegel S (1956) Nonparametric statistics for the behavioral sciences. McGraw-Hill e Kogakusha, Ltd., JapanGoogle Scholar
  44. Spielberger CD, Gorsuch RL, Lushene RE (1970) Manual for the State-Trait Anxiety Inventory. Consulting Psychologist Press, Palo Alto, CAGoogle Scholar
  45. Szara S (1976) Clinical pharmacology of cannabis: scientific and nonscientific constrainst. In: Braude MC, Szara S (eds) The pharmacology of marihuana. Raven Press, New York, pp 22–33Google Scholar
  46. Tassinari CA, Ambrosetto G, Peraita-Adrados MR, Gestaut H (1976) The neuropsychiatric syndrome of Δ 9-tetrahydrocannabinol and cannabis intoxication in naive subjects: a clinical and poligraphic study during wakefulness and sleep. In: Braude MC, Szara S (eds) The pharmacology of marihuana. Raven Press, New YorkGoogle Scholar
  47. Weil AT, Zinberg NE, Nelsen JM (1968) Clinical and psychological effects of marihuana in man. Science 162:1234–1242Google Scholar
  48. Zuardi AW, Karniol IG (1981) Estudo transcultural de uma escala de auto-avaliação para estados subjectivos. J Brasileiro de Psiquiatria (in press)Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • A. W. Zuardi
    • 1
    • 2
  • I. Shirakawa
    • 1
    • 2
  • E. Finkelfarb
    • 1
    • 2
  • I. G. Karniol
    • 1
    • 2
  1. 1.Departamento de Psicobiologia da Escola Paulista de MedicinaCampinasBrasil
  2. 2.Departamento de Psicologia Médica e Psiquiatria da-FCM-UNICAMPCampinasBrasil

Personalised recommendations