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

  • P. D. Morrison (a1), V. Zois (a1), D. A. McKeown (a2), T. D. Lee (a2), D. W. Holt (a2), J. F. Powell (a1), S. Kapur (a1) and R. M. Murray (a1)...

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.


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.


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.


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.

Corresponding author
*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:
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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.
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.
Ashton CH (2001). Pharmacology and effects of cannabis: a brief review. British Journal of Psychiatry 178, 101106.
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.
Barch DM, Smith E (2008). The cognitive neuroscience of working memory: relevance to CNTRICS and schizophrenia. Biological Psychiatry 64, 1117.
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.
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.
Caspari D (1999). Cannabis and schizophrenia: results of a follow-up study. European Archives of Psychiatry and Clinical Neuroscience 249, 4549.
Chopra GS, Smith JW (1974). Psychotic reactions following cannabis use in East Indians. Archives of General Psychiatry 30, 2427.
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.
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.
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.
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.
Fletcher PC, Honey GD (2006). Schizophrenia, ketamine and cannabis: evidence of overlapping memory deficits. Trends in Cognitive Sciences 10, 167174.
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.
Grech A, Van Os J, Jones PB, Lewis SW, Murray RM (2005). Cannabis use and outcome of recent onset psychosis. European Psychiatry 20, 349353.
Grotenhermen F (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics 42, 327360.
Hall W (2006). Is cannabis use psychotogenic? Lancet 367, 193195.
Hambrecht M, Hafner H (2000). Cannabis, vulnerability, and the onset of schizophrenia: an epidemiological perspective. Australian and New Zealand Journal of Psychiatry 34, 468475.
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.
Iversen L (2003). Cannabis and the brain. Brain 126, 12521270.
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.
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.
Kay SR, Opler LA, Lindenmayer JP (1989). The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. British Journal of Psychiatry (Suppl.) 5967.
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.
Linszen DH, Dingemans PM, Lenior ME (1994). Cannabis abuse and the course of recent-onset schizophrenic disorders. Archives of General Psychiatry 51, 273279.
Mass R (2000). Characteristic subjective experiences of schizophrenia. Schizophrenia Bulletin 26, 921931.
Matthews G, Jones DM, Chamberlain AG (1990). Refining the measurement of mood: the UWIST Mood Adjective Checklist. British Journal of Psychology 81, 1742.
Mechoulam R, Shani A, Edery H, Grunfeld Y (1970). Chemical basis of hashish activity. Science 169, 611612.
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.
Moreau de Tours JJ (1845). Hashish and Insanity [in French]. Fortin, Masson et Cie: Paris.
Murray RM, Morrison PD, Henquet C, Di Forti M (2007). Cannabis, the mind and society: the hash realities. Nature Reviews Neuroscience 8, 885895.
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.
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.
Pertwee RG (2006). Cannabinoid pharmacology: the first 66 years. British Journal of Pharmacology 147 (Suppl. 1), S163S171.
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.
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.
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.
Ranganath C, Minzenberg MJ, Ragland JD (2008). The cognitive neuroscience of memory function and dysfunction in schizophrenia. Biological Psychiatry 64, 1825.
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.
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.
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.
Selzer ML (1971). The Michigan alcoholism screening test: the quest for a new diagnostic instrument. American Journal of Psychiatry 127, 16531658.
Shen W, Flajolet M, Greengard P, Surmeier JD (2008). Dichotomous dopaminergic control of striatal synaptic plasticity. Science 321, 848851.
Skinner HA (1982). The drug abuse screening test. Addictive Behaviours 7, 363371.
Solowij N, Michie PT (2007). Cannabis and cognitive dysfunction: parallels with endophenotypes of schizophrenia? Journal of Psychiatry and Neuroscience 32, 3052.
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.
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.
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.
Van Mastrigt S, Addington J, Addington D (2004). Substance misuse at presentation to an early psychosis program. Social Psychiatry and Psychiatric Epidemiology 39, 6972.
Viveros MP, Marco EM, File SE (2005). Endocannabinoid system and stress and anxiety responses. Pharmacology Biochemistry and Behaviour 81, 331342.
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.
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.
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