Psychological Medicine

Original Articles

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

P. D. Morrisona1 c1, V. Zoisa1, D. A. McKeowna2, T. D. Leea2, D. W. Holta2, J. F. Powella1, S. Kapura1 and R. M. Murraya1

a1 Institute of Psychiatry, The Biomedical Research Centre, King's College London, UK

a2 Analytical Unit, St George's, University of London, UK


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.

(Received September 30 2008)

(Revised February 04 2009)

(Accepted February 08 2009)

(Online publication April 01 2009)


c1 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: