Hostname: page-component-7c8c6479df-r7xzm Total loading time: 0 Render date: 2024-03-28T19:55:20.079Z Has data issue: false hasContentIssue false

The acute effects of synthetic intravenous Δ9-tetrahydrocannabinol on psychosis, mood and cognitive functioning

Published online by Cambridge University Press:  01 April 2009

P. D. Morrison*
Affiliation:
Institute of Psychiatry, The Biomedical Research Centre, King's College London, UK
V. Zois
Affiliation:
Institute of Psychiatry, The Biomedical Research Centre, King's College London, UK
D. A. McKeown
Affiliation:
Analytical Unit, St George's, University of London, UK
T. D. Lee
Affiliation:
Analytical Unit, St George's, University of London, UK
D. W. Holt
Affiliation:
Analytical Unit, St George's, University of London, UK
J. F. Powell
Affiliation:
Institute of Psychiatry, The Biomedical Research Centre, King's College London, UK
S. Kapur
Affiliation:
Institute of Psychiatry, The Biomedical Research Centre, King's College London, UK
R. M. Murray
Affiliation:
Institute of Psychiatry, The Biomedical Research Centre, King's College London, UK
*
*Address for correspondence: Dr P. D. Morrison, Institute of Psychiatry, The Biomedical Research Centre, King's College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. (Email: paul.morrison@iop.kcl.ac.uk)

Abstract

Background

Recent work suggests that heavy use of cannabis is associated with an increased risk of schizophrenia-like psychosis. However, there is a dearth of experimental studies of the effects of the constituents of cannabis, such as Δ9-tetrahydrocannabinol (THC). In a study of intravenous (i.v.) synthetic THC in healthy humans, we aimed to study the relationship of the psychotic symptoms induced by THC to the consequent anxiety and neuropsychological impairment.

Method

Twenty-two healthy adult males aged 28±6 years (mean±s.d.) participated in experimental sessions in which i.v. THC (2.5 mg) was administered under double-blind, placebo-controlled conditions. Self-rated and investigator-rated measurements of mood and psychosis [the University of Wales Institute of Science and Technology Mood Adjective Checklist (UMACL), the Positive and Negative Syndrome Scale (PANSS) and the Community Assessment of Psychic Experiences (CAPE)] were made at baseline and at 30, 80 and 120 min post-injection. Participants also completed a series of neuropsychological tests [the Rey Auditory Verbal Learning Task (RAVLT), Digit Span, Verbal Fluency and the Baddeley Reasoning Task] within 45 min of injection.

Results

THC-induced positive psychotic symptoms, and participant- and investigator-rated measurements of these were highly correlated. Participants showed an increase in anxiety ratings but there was no relationship between either self- or investigator-rated positive psychotic symptoms and anxiety. THC also impaired neuropsychological performance but once again there was no relationship between THC-induced positive psychotic symptoms and deficits in working memory/executive function.

Conclusions

These findings confirm that THC can induce a transient, acute psychotic reaction in psychiatrically well individuals. The extent of the psychotic reaction was not related to the degree of anxiety or cognitive impairment.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ames, F (1958). A clinical and metabolic study of acute intoxication with Cannabis sativa and its role in the model psychoses. Journal of Mental Science 104, 972999.CrossRefGoogle ScholarPubMed
Arseneault, L, Cannon, M, Witton, J, Murray, RM (2004). Causal association between cannabis and psychosis: examination of the evidence. British Journal of Psychiatry 184, 110117.CrossRefGoogle ScholarPubMed
Ashton, CH (2001). Pharmacology and effects of cannabis: a brief review. British Journal of Psychiatry 178, 101106.CrossRefGoogle ScholarPubMed
Azorlosa, JL, Greenwald, MK, Stitzer, ML (1995). Marijuana smoking: effects of varying puff volume and breathhold duration. Journal of Pharmacology and Experimental Therapeutics 272, 560569.Google ScholarPubMed
Barch, DM, Smith, E (2008). The cognitive neuroscience of working memory: relevance to CNTRICS and schizophrenia. Biological Psychiatry 64, 1117.Google Scholar
Barnes, TR, Mutsatsa, SH, Hutton, SB, Watt, HC, Joyce, EM (2006). Comorbid substance use and age at onset of schizophrenia. British Journal of Psychiatry 188, 237242.CrossRefGoogle ScholarPubMed
Barnett, JH, Werners, U, Secher, SM, Hill, KE, Brazil, R, Masson, K, Pernet, DE, Kirkbride, JB, Murray, GK, Bullmore, ET, Jones, PB (2007). Substance use in a population-based clinic sample of people with first-episode psychosis. British Journal of Psychiatry 190, 515520.CrossRefGoogle Scholar
Caspari, D (1999). Cannabis and schizophrenia: results of a follow-up study. European Archives of Psychiatry and Clinical Neuroscience 249, 4549.CrossRefGoogle ScholarPubMed
Chopra, GS, Smith, JW (1974). Psychotic reactions following cannabis use in East Indians. Archives of General Psychiatry 30, 2427.CrossRefGoogle ScholarPubMed
Curran, HV, Brignell, C, Fletcher, S, Middleton, P, Henry, J (2002). Cognitive and subjective dose-response effects of acute oral delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology (Berlin) 164, 6170.CrossRefGoogle ScholarPubMed
D'Souza, DC, Abi-Saab, WM, Madonick, S, Forselius-Bielen, K, Doersch, A, Braley, G, Gueorguieva, R, Cooper, TB, Krystal, JH (2005). Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biological Psychiatry 57, 594608.CrossRefGoogle ScholarPubMed
D'Souza, DC, Perry, E, MacDougall, L, Ammerman, Y, Cooper, T, Wu, YT, Braley, G, Gueorguieva, R, Krystal, JH (2004). The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 29, 15581572.CrossRefGoogle ScholarPubMed
D'Souza, DC, Ranganathan, M, Braley, G, Gueorquieva, R, Zimolo, Z, Cooper, T, Perry, E, Krystal, J (2008). Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology 33, 25052516.CrossRefGoogle ScholarPubMed
Fletcher, PC, Honey, GD (2006). Schizophrenia, ketamine and cannabis: evidence of overlapping memory deficits. Trends in Cognitive Sciences 10, 167174.CrossRefGoogle ScholarPubMed
Goldberg, DP, Blackwell, B (1970). Psychiatric illness in general practice. A detailed study using a new method of case identification. British Medical Journal 1, 439443.CrossRefGoogle ScholarPubMed
Grech, A, Van Os, J, Jones, PB, Lewis, SW, Murray, RM (2005). Cannabis use and outcome of recent onset psychosis. European Psychiatry 20, 349353.CrossRefGoogle ScholarPubMed
Grotenhermen, F (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics 42, 327360.Google Scholar
Hall, W (2006). Is cannabis use psychotogenic? Lancet 367, 193195.CrossRefGoogle ScholarPubMed
Hambrecht, M, Hafner, H (2000). Cannabis, vulnerability, and the onset of schizophrenia: an epidemiological perspective. Australian and New Zealand Journal of Psychiatry 34, 468475.Google Scholar
Henquet, C, Rosa, A, Krabbendam, L, Papiol, S, Fananas, L, Drukker, M, Ramaekers, JG, van Os, J (2006). An experimental study of catechol-O-methyltransferase Val(158)Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 31, 27482757.CrossRefGoogle ScholarPubMed
Iversen, L (2003). Cannabis and the brain. Brain 126, 12521270.CrossRefGoogle ScholarPubMed
Juckel, G, Roser, P, Nadulski, T, Stadelmann, AM, Gallinat, J (2007). Acute effects of Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory evoked mismatch negativity. Schizophrenia Research 97, 109117.CrossRefGoogle ScholarPubMed
Kapur, S (2003). Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 160, 1323.CrossRefGoogle ScholarPubMed
Kay, SR, Opler, LA, Lindenmayer, JP (1989). The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. British Journal of Psychiatry (Suppl.) 5967.CrossRefGoogle ScholarPubMed
Koethe, D, Gerth, CW, Neatby, MA, Haensel, A, Thies, M, Schneider, U, Emrich, HM, Klosterkotter, J, Schultze-Lutter, F, Leweke, FM (2006). Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness. Schizophrenia Research 88, 142150.CrossRefGoogle ScholarPubMed
Linszen, DH, Dingemans, PM, Lenior, ME (1994). Cannabis abuse and the course of recent-onset schizophrenic disorders. Archives of General Psychiatry 51, 273279.CrossRefGoogle ScholarPubMed
Mass, R (2000). Characteristic subjective experiences of schizophrenia. Schizophrenia Bulletin 26, 921931.CrossRefGoogle ScholarPubMed
Matthews, G, Jones, DM, Chamberlain, AG (1990). Refining the measurement of mood: the UWIST Mood Adjective Checklist. British Journal of Psychology 81, 1742.CrossRefGoogle Scholar
Mechoulam, R, Shani, A, Edery, H, Grunfeld, Y (1970). Chemical basis of hashish activity. Science 169, 611612.Google Scholar
Moore, TH, Zammit, S, Lingford-Hughes, A, Barnes, TR, Jones, PB, Burke, M, Lewis, G (2007). Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 370, 319328.CrossRefGoogle ScholarPubMed
Moreau de Tours, JJ (1845). Hashish and Insanity [in French]. Fortin, Masson et Cie: Paris.Google Scholar
Murray, RM, Morrison, PD, Henquet, C, Di Forti, M (2007). Cannabis, the mind and society: the hash realities. Nature Reviews Neuroscience 8, 885895.CrossRefGoogle Scholar
Naef, M, Russmann, S, Petersen-Felix, S, Brenneisen, R (2004). Development and pharmacokinetic characterization of pulmonal and intravenous delta-9-tetrahydrocannabinol (THC) in humans. Journal of Pharmacological Sciences 93, 11761184.CrossRefGoogle ScholarPubMed
Ohlsson, A, Lindgren, JE, Wahlen, A, Agurell, S, Hollister, LE, Gillespie, HK (1980). Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clinical Pharmacology and Therapeutics 28, 409416.CrossRefGoogle ScholarPubMed
Pertwee, RG (2006). Cannabinoid pharmacology: the first 66 years. British Journal of Pharmacology 147 (Suppl. 1), S163S171.CrossRefGoogle ScholarPubMed
Pertwee, RG (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British Journal of Pharmacology 153, 199215.CrossRefGoogle ScholarPubMed
Potter, DJ, Clark, P, Brown, MB (2008). Potency of delta 9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology. Journal of Forensic Science 53, 9094.CrossRefGoogle ScholarPubMed
Ramaekers, JG, Kauert, G, van Ruitenbeek, P, Theunissen, EL, Schneider, E, Moeller, MR (2006). High-potency marijuana impairs executive function and inhibitory motor control. Neuropsychopharmacology 31, 22962303.Google Scholar
Ranganath, C, Minzenberg, MJ, Ragland, JD (2008). The cognitive neuroscience of memory function and dysfunction in schizophrenia. Biological Psychiatry 64, 1825.Google Scholar
Rubino, T, Guidali, C, Vigano, D, Realini, N, Valenti, M, Massi, P, Parolaro, D (2008). CB1 receptor stimulation in specific brain areas differently modulate anxiety-related behaviour. Neuropharmacology 54, 151160.CrossRefGoogle ScholarPubMed
Ryan, D, Drysdale, AJ, Pertwee, RG, Platt, B (2006). Differential effects of cannabis extracts and pure plant cannabinoids on hippocampal neurones and glia. Neuroscience Letters 408, 236241.CrossRefGoogle ScholarPubMed
Schimmack, U, Grob, A (2000). Dimensional models of core affect: a quantitative comparison by means of structural equation modeling. European Journal of Personality 14, 325345.Google Scholar
Selzer, ML (1971). The Michigan alcoholism screening test: the quest for a new diagnostic instrument. American Journal of Psychiatry 127, 16531658.Google Scholar
Shen, W, Flajolet, M, Greengard, P, Surmeier, JD (2008). Dichotomous dopaminergic control of striatal synaptic plasticity. Science 321, 848851.CrossRefGoogle ScholarPubMed
Skinner, HA (1982). The drug abuse screening test. Addictive Behaviours 7, 363371.CrossRefGoogle ScholarPubMed
Solowij, N, Michie, PT (2007). Cannabis and cognitive dysfunction: parallels with endophenotypes of schizophrenia? Journal of Psychiatry and Neuroscience 32, 3052.Google ScholarPubMed
Startup, M, Owen, DM, Parsonage, RK, Jackson, MC (2003). Anomalous experiences and the contents of persecutory delusions during acute psychotic episodes. Psychology and Psychotherapy: Theory, Research and Practice 76, 315322.CrossRefGoogle ScholarPubMed
Steinmeyer, S, Bregel, D, Warth, S, Kraemer, T, Moeller, MR (2002). Improved and validated method for the determination of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC and 11-nor-9-carboxy-THC in serum, and in human liver microsomal preparations using gas chromatography-mass spectrometry. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 772, 239248.CrossRefGoogle Scholar
Talbott, JA, Teague, JW (1969). Marihuana psychosis. Acute toxic psychosis associated with the use of cannabis derivatives. Journal of the American Medical Association 210, 299302.CrossRefGoogle ScholarPubMed
Van Mastrigt, S, Addington, J, Addington, D (2004). Substance misuse at presentation to an early psychosis program. Social Psychiatry and Psychiatric Epidemiology 39, 6972.CrossRefGoogle Scholar
Viveros, MP, Marco, EM, File, SE (2005). Endocannabinoid system and stress and anxiety responses. Pharmacology Biochemistry and Behaviour 81, 331342.CrossRefGoogle ScholarPubMed
Volkow, ND, Gillespie, H, Mullani, N, Tancredi, L, Grant, C, Ivanovic, M, Hollister, L (1991). Cerebellar metabolic activation by delta-9-tetrahydro-cannabinol in human brain: a study with positron emission tomography and 18F-2-fluoro-2-deoxyglucose. Psychiatry Research 40, 6978.CrossRefGoogle Scholar
Zuardi, AW, Shirakawa, I, Finkelfarb, E, Karniol, IG (1982). Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berlin) 76, 245250.CrossRefGoogle ScholarPubMed