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Pharmacopsychiatry 2010; 43(1): 24-32
DOI: 10.1055/s-0029-1237397
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Acute Psychotropic Effects of Oral Cannabis Extract with a Defined Content of Δ9-Tetrahydrocannabinol (THC) in Healthy Volunteers

R. M. Kaufmann1 , B. Kraft2 , R. Frey1 , D. Winkler1 , S. Weiszenbichler1 , C. Bäcker1 , S. Kasper1 , H. G. Kress2
  • 1Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
  • 2Division of Special Anesthesia and Pain Therapy, Department of Anesthesia, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria
Further Information

Publication History

received 13.01.2009 revised 16.07.2009

accepted 23.07.2009

Publication Date:
10 December 2009 (online)

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Abstract

Introduction: The medical use of cannabinoids is limited mainly by their undesirable effects. With respect to acute psychotropic effects, the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment in drug-naïve healthy women.

Methods: Sixteen healthy females participated in this randomized, double-blind, active comparator-controlled, single-dose, balanced 2-way cross-over study. Cannabis extract with standardised Δ9-tetrahydrocannabinol (THC) content (20 mg) or active placebo (5 mg diazepam) was administered orally. Subjects were assessed by self- and observer-rated visual analogue scales (VAS), the brief psychiatric rating scale (BPRS) and three psychomotor tests up to 6 h after administration.

Results: VAS showed significantly elevated fatigue, drowsiness, dizziness, and “feeling high” after cannabis as compared to baseline and diazepam. BPRS scores were significantly higher after cannabis intake. Only in one psychomotor test a decrease of psychomotor activity after cannabis was evident. One subject in the cannabis condition experienced severe transient psychotic symptoms.

Discussion: Orally administered cannabis produced significant central depressant side-effects compared to diazepam, mostly subjective effects (VAS) but marginal effects in psychomotor performance in 15 healthy females. Regarding the medical use of cannabis, a rigorous benefit-risk analysis and an exact psychiatric assessment before and during treatment are necessary.

References

  • 1 Adams IB, Martin BR. Cannabis: pharmacology and toxicology in animals and humans.  Addiction. 1996;  91 1585-1614
    CrossrefPubMedGoogle Scholar
  • 2 Andreasson S, Allebeck P, Rydberg U. Schizophrenia in users and nonusers of cannabis.  Acta Psychiatr Scand. 1989;  79 505-510
    CrossrefPubMedGoogle Scholar
  • 3 Ashton CH. Pharmacology and effects of cannabis: a brief review.  Br J Psychiatry. 2001;  178 101-106
    CrossrefPubMedGoogle Scholar
  • 4 Baigent M, Holme G, Hafner RJ. Self reports of the interaction between substance abuse and schizophrenia.  Aust N Zealand J Psychiatry. 1995;  29 69-74
    PubMedGoogle Scholar
  • 5 Barnett G, Licko V, Thompson T. Behavioral pharmacokinetics of marijuana.  Psychopharmacology. 1985;  85 51-56
    CrossrefPubMedGoogle Scholar
  • 6 Bird KD, Boleyn T, Chesher GB. et al . Intercannabinoid and cannabinoid-ethanol interactions and their effects on human performance.  Psychopharmacology. 1980;  71 181-188
    CrossrefPubMedGoogle Scholar
  • 7 Block RI, Erwin WJ, Farinpour R. et al . Sedative, stimulant, and other subjective effects of marijuana: relationships to smoking techniques.  Pharmacol Biochem Behav. 1998;  59 405-412
    CrossrefPubMedGoogle Scholar
  • 8 Bond AJ, Lader MH. The use of analogue scales in rating subjective feelings.  Br J Med Psychol. 1974;  47 211-218
    PubMedGoogle Scholar
  • 9 Borland RG, Nicholson AN. Immediate effects on human performance of a 1,5-benzodiazepine (clobazam) compared with the 1,4-benzodiazepines, chlordiazepoxide hydrochloride and diazepam.  Br J Clin Pharmacol. 1975;  2 215-221
    PubMedGoogle Scholar
  • 10 Campell FA, Tramer MR, Carroll D. et al . Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review.  BMJ. 2001;  323 13-16
    CrossrefPubMedGoogle Scholar
  • 11 Carney MWP, Bacelle L, Robinson B. Psychosis after cannabis abuse.  BMJ. 1984;  288 1047
    CrossrefPubMedGoogle Scholar
  • 12 Chait LD, Pierri J. Effects of smoked marijuana on human performance: a critical review. In: Murphy LL, Bartke A (eds.) Marijuana/Cannabinoids: Neurobiology and Neurophysiology. Boca Raton, CRC Press 1992: 387-423
    PubMedGoogle Scholar
  • 13 Chaudry HR, Moss HB, Bashir A. et al . Cannabis psychosis following bhang ingestion.  Br J Addiction. 1991;  86 1075-1081
    CrossrefPubMedGoogle Scholar
  • 14 Craft RM. Sex differences in behavioral effects of cannabinoids.  Life Sci. 2005;  77 2471-2478
    CrossrefPubMedGoogle Scholar
  • 15 Curran HV. Benzodiazepines, memory and cognitive function. In: Trimble M, Hindmarch I (eds.) Benzodiazepines. Hampshire: Wrightson Biomedical Publishers 2000: 17-29
    PubMedGoogle Scholar
  • 16 Curran HV, Brignell C, Fletcher S. et al . Cognitive and subjective dose-response effects of acute oral Δ9-tetrahydrocannabinol (THC) in infrequent cannabis users.  Psychopharmacology. 2002;  164 61-70
    CrossrefPubMedGoogle Scholar
  • 17 Devane WA, Dysarz FA, Johnson MR. et al . Determination and characteristics of a cannabinoid receptor in rat brain.  Mol Pharmacology. 1988;  34 605-613
    PubMedGoogle Scholar
  • 18 Devane WA, Hanus L, Breuer A. et al . Isolation and structure of a brain constituent that binds to the cannabinoid receptor.  Science. 1992;  258 1946-1949
    CrossrefPubMedGoogle Scholar
  • 19 D’Souza DC, Perry E, MacDougall L. et al . The pychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis.  Neuropsychopharmacology. 29;  2004 1558-1572
    PubMedGoogle Scholar
  • 20 ElSohly MA, Slade D. Chemical constituents of marijuana: the complex mixture of natural cannabinoids.  Life Sci. 78;  2005 539-548
    PubMedGoogle Scholar
  • 21 Fant RV, Heishman SJ, Bunker EB. et al . Acute and residual effects of marijuana in humans.  Pharmacol Biochem Behav. 1998;  60 777-784
    CrossrefPubMedGoogle Scholar
  • 22 Favrat B, Menetrey A, Augsburger M. et al . Two cases of “cannabis acute psychosis” following the administration of oral cannabis.  BMC Psychiatry. 2005;  5 17-22
    CrossrefPubMedGoogle Scholar
  • 23 Frey R, Decker K, Reinfried L. et al . Effect of rest on physicians` performance in an emergency department, objectified by electroencephalographic analyses and psychometric tests.  Crit Care Med. 2002;  30 2322-2329
    CrossrefPubMedGoogle Scholar
  • 24 Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish.  J Am Chem Soc. 1964;  86 1646-1647
    CrossrefPubMedGoogle Scholar
  • 25 Gerrard L, Wheeldon NM, McDevitt DG. Effect of combined atenolol and nifedipine administration on psychomotor performance in normal subjects.  Eur J Clin Pharmacol. 1995;  48 229-233
    PubMedGoogle Scholar
  • 26 Ghodse AH. Cannabis psychosis.  Br J Addiction. 1986;  81 473-478
    CrossrefPubMedGoogle Scholar
  • 27 Gonzalez R. Acute and non-acute effects of cannabis on brain functioning and neuropsychological performance.  Neuropsychol Rev. 2007;  17 347-361
    CrossrefPubMedGoogle Scholar
  • 28 Green B, Kavanagh D, Young R. Being stoned: a review of self-reported cannabis effects.  Drug Alc Rev. 2003;  22 453-460
    CrossrefPubMedGoogle Scholar
  • 29 Grünberger J. [Psychodiagnostik des Alkoholkranken. Methodischer Beitrag zur Bestimmung der Organizität in der Psychiatrie. Article in German]. Maudrich, Wien, Austria 1977
    PubMed
  • 30 Grünberger J, Linzmayer L, Dietzl M. et al . The effect of biologically-active light on the noo- and thymopsyche and on psychophysiological variables in healthy volunteers.  Int J Psychophysiol. 1993;  15 27-37
    CrossrefPubMedGoogle Scholar
  • 31 Hall W, Solowij N. Long-term cannabis use and mental health.  Br J Psychiatry. 1997;  171 107-108
    CrossrefPubMedGoogle Scholar
  • 32 Hall W, Solowij N. Adverse effects of cannabis.  Lancet. 1998;  352 1611-1616
    CrossrefPubMedGoogle Scholar
  • 33 Hambrecht M, Häfner H. Cannabis, vulnerability, and the onset of schizophrenia: an epidemiological perspective.  Aust NZ J Psychiatry. 2000;  34 468-475
    PubMedGoogle Scholar
  • 34 Heishman SJ, Huestis MA, Henningfield JE. et al . Acute and residual effects of marijuana: profiles of plasma thc levels, physiological, subjective, and performance measures.  Pharmacol Biochem Behav. 1990;  37 561-565
    CrossrefPubMedGoogle Scholar
  • 35 Hindmarch I. Psychomotor function and psychoactive drugs.  Br J Clin Pharmacol. 1980;  10 189-209
    PubMedGoogle Scholar
  • 36 Holdcroft A, Maze M, Dore C. et al . A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management.  Anesthesiology. 2006;  104 1040-1046
    CrossrefPubMedGoogle Scholar
  • 37 Imade AGT, Ebie JC. A retrospective study of symptom patterns of cannabis-induced psychosis.  Acta Psychiatr Scand. 1991;  83 134-136
    CrossrefPubMedGoogle Scholar
  • 38 Johns A. Psychiatric effects of cannabis.  Br J Psychiatry. 2001;  178 116-122
    CrossrefPubMedGoogle Scholar
  • 39 Kalant H. Medicinal use of cannabis: history and current status.  Pain Res Manag. 2001;  6 80-91
    PubMedGoogle Scholar
  • 40 Kalant H. Adverse effects of cannabis on health: an update of the literature since 1996.  Prog Neuropsychopharmacol Biol Psychiatry. 2004;  28 849-863
    CrossrefPubMedGoogle Scholar
  • 41 Kaufmann RM, Frey R, Battista HJ. et al . Flunitrazepam and driving ability.  Fortschr Neurol Psychiatr [Article in German]. 2004;  72 503-515
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Kopelowicz A, Vendura J, Libermann RP. et al . Consistency of brief psychiatric rating scale factor structure across a broad spectrum of schizophrenia patients.  Psychopathology. 2007;  41 77-84
    PubMedGoogle Scholar
  • 43 Kraft B, Frickey NA, Kaufmann RM. et al . Lack Of Analgesia By Oral Standardized Cannabis Extract On Acute Inflammatory Pain And Hyperalgesia In Volunteers.  Anesthesiology. 2008;  109 101-110
    CrossrefPubMedGoogle Scholar
  • 44 Kreuz DS, Axelrod J. delta-9-Tetrahydrocannabinol: localization in body fat.  Science. 1973;  179 391-393
    CrossrefPubMedGoogle Scholar
  • 45 Kumar RN, Chambers WA, Pertwee RG. Pharmacological actions and therapeutic uses of cannabis and cannabinoids.  Anaesthesia. 2001;  56 1059-1068
    CrossrefPubMedGoogle Scholar
  • 46 Linzmayer L, Arnold O, Saletu-Zylarz GM. et al . Daytime noopsychic and thymopsychic dysfunctions in nonorganic insomnia related to different mental disorders.  Somnologie. 2002;  6 141-148
    CrossrefPubMedGoogle Scholar
  • 47 Mason AP, McBay AJ. Cannabis: pharmacology and interpretation of effects.  J Forensic Sci. 1985;  30 615-631
    PubMedGoogle Scholar
  • 48 Mason OJ, Morgan CJM, Stefanovic A. et al . The psychotomimetic states inventory (PSI): Measuring psychotic-type experiences from ketamine and cannabis.  Schizophrenia Res. 2008;  103 138-142
    PubMedGoogle Scholar
  • 49 Mattila MJ, Vanakoski J, Kalska H. et al . Effects of alcohol, zolpidem, and some other sedatives and hypnotics on human performance and memory.  Pharmacol Biochem Behav. 1998;  59 917-923
    CrossrefPubMedGoogle Scholar
  • 50 McGilveray IJ. Pharmacokinetics of cannabinoids.  Pain Res Manag. 2005;  10 15A-22A
    PubMedGoogle Scholar
  • 51 Mechoulam R, Fride E, Di Marzo V. Endocannabinoids.  Eur J Pharmacol. 1998;  359 1-18
    CrossrefPubMedGoogle Scholar
  • 52 Moore THM, Zammit S, Lingford-Hughes A. et al . Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review.  Lancet. 2007;  370 319-328
    Google Scholar
  • 53 Negrete JC. Psychological adverse effects of cannabis smoking: a tentative classification.  CMAJ. 1973;  108 195-202
    PubMedGoogle Scholar
  • 54 Nicholson AN, Turner C, Stone BM. et al . Effect of Δ9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults.  J Clin Psychopharmacology. 2004;  24 305-313
    CrossrefPubMedGoogle Scholar
  • 55 O’Leary DS, Block RI, Koeppel JA. et al . Effects of smoking marijuana on brain perfusion and cognition.  Neuropsychopharmacology. 2002;  26 802-816
    CrossrefPubMedGoogle Scholar
  • 56 Overall JE, Gorham DR. The brief psychiatric rating scale (BPRS): Recent developments in ascertainment and scaling.  Psychopharmac Bull. 1988;  24 97-99
    PubMedGoogle Scholar
  • 57 Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors.  Pharmacol Ther. 1997;  74 129-180
    PubMedGoogle Scholar
  • 58 Peters BA, Lewis EG, Dustman RE. et al . Sensory, perceptual, motor and cognitive functioning and subjective reports following oral administration of Δ9-tetrahydrocannabinol.  Psychopharmacology. 1976;  47 141-148
    CrossrefPubMedGoogle Scholar
  • 59 Pickworth WB, Rohrer MS, Fant RV. Effects of abused drugs on psychomotor performance.  Exp Clin Psychopharmacol. 1997;  5 235-241
    PubMedGoogle Scholar
  • 60 Ramaekers J, Kauert G, Theunissen E. et al . Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users.  J Psychopharmacol. 2009;  23 266-277
    CrossrefPubMedGoogle Scholar
  • 61 Ranganathan M, D’Souza DC. The acute effects of cannabinoids on memory in humans: A review.  Psychopharmacology. 2006;  188 425-466
    CrossrefPubMedGoogle Scholar
  • 62 Saletu B, Grünberger J, Cepko H. Pharmaco-EEG and psychometric studies with a novel selective benzodiazepine agonist/antagonist Ro-23-0364.  Int J Clin Pharmacol Ther Toxicol. 1987;  25 421-437
    PubMedGoogle Scholar
  • 63 Sheehan DV, Lecrubier Y, Sheehan KH. et al . The mini-international neuropsychiatric interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.  J Clin Psychiatry. 1998;  59 ((Suppl 20)) 22-33
    Google Scholar
  • 64 SPSS Inc .SPSS for Windows. Release 15.0. Chicago, IL, USA 1989–2006
    PubMed
  • 65 Tennant FS, Groesbeck CJ. Psychiatric effects of hashish.  Arch Gen Psychiatry. 1972;  27 133-136
    PubMedGoogle Scholar
  • 66 Thomas H. Psychiatric symptoms in cannabis users.  Br J Psychiatry. 1993;  163 141-149
    CrossrefPubMedGoogle Scholar
  • 67 Tseng AH, Harding JW, Craft RM. Pharmacokinetic factors in sex differences in delta 9-tetrahydrocannabinol-induced behavioral effects in rats.  Behav Brain Res. 2004;  154 77-83
    CrossrefPubMedGoogle Scholar
  • 68 Tunving K. Psychiatric effects of cannabis use.  Acta Psychiatr Scand. 1985;  72 209-217
    CrossrefPubMedGoogle Scholar
  • 69 Turner JM, de Wit H. Menstrual cycle phase and responses to drugs of abuse.  Drug and Alcohol Dependence. 2006;  84 1-13
    CrossrefPubMedGoogle Scholar
  • 70 Vachon L, Sulkowski A, Rich E. Marijuana effects on learning, attention, and time estimation.  Psychopharmacologia. 1974;  39 1-11
    CrossrefPubMedGoogle Scholar
  • 71 Webb E, Ashton CH, Kelly P. et al . Alcohol and drug use in UK university students.  Lancet. 1996;  348 922-925
    CrossrefPubMedGoogle Scholar
  • 72 Zajicek J, Fox P, Sanders H. et al . Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial.  Lancet. 2003;  362 1517-1526
    CrossrefPubMedGoogle Scholar

Correspondence

R. M. KaufmannMD 

Division of Biological Psychiatry

Department of Psychiatry and Psychotherapy

Medical University of Vienna

Waehringer Guertel 18–20

1090 Vienna

Austria

Phone: +43/1/40400/35 68

Fax: +43/1/40400/30 99

Email: rainer.kaufmann@meduniwien.ac.at