How Cannabis Causes Paranoia: Using the Intravenous Administration of Δ9-Tetrahydrocannabinol (THC) to Identify Key Cognitive Mechanisms Leading to Paranoia

Daniel Freeman; Graham Dunn; Robin M. Murray; Nicole Evans; Rachel Lister; Angus Antley; Mel Slater; Beata Godlewska; Robert Cornish; Jonathan Williams; Martina Di Simplicio; Artemis Igoumenou; Rudolf Brenneisen; Elizabeth M. Tunbridge; Paul J. Harrison; Catherine J. Harmer; Philip Cowen; Paul D. Morrison


Schizophr Bull. 2015;41(2):391-399. 

In This Article


The basic demographic data for the participant groups can be seen in Table 1.


An ANCOVA with the paranoia principal component as the dependent variable, and controlling for baseline paranoia and anxiety levels, showed that THC significantly increases paranoia, THC coefficient = 0.91, SE = 0.43, t = 2.15, P = .034, and that the cognitive awareness condition, if it actually has any effects, may increase paranoia but not significantly, Cognitive Awareness coefficient = 0.51, SE = 0.44, t = 1.16, P = .247 (see figure 2). Controlling for previous cannabis use did not affect the findings. (see supplementary table S2 for individual paranoia outcome scores). Consistent with the analysis, there was a significant effect on self-reported psychotic symptoms as assessed by the CAPE (controlling for baseline anxiety and paranoia), THC coefficient = 4.20, SE = 1.19, t = 3.54, P = .001, Cognitive Awareness coefficient = 1.02, SE = 1.23, t = 0.83, P = .407.

Figure 2.

Composite scores for paranoia and the main mediator by randomization group.

Effects on Mediators

ITT effects of the randomization condition on the mediation variables are reported in Table 2. THC significantly increased scores on component 1 (anomalous experiences and negative affect) and decreased scores on component 3 (working memory). The cognitive awareness condition decreased component 8 (catastrophizing and jumping to conclusions).

Mediation Analysis

Table 3 shows the results when the ITT effect for randomization condition on paranoia includes each mediator in turn. The key tests are for components 1 and 3, for which ITT effects on these mediators have been established. It can be seen that there is full mediation for component 1 (anomalous experiences and negative affect), since the effect of THC on paranoia becomes nonsignificant but the effect of component 1 is highly significant. Consistent with this finding, there is little evidence of mediation by component 3 (working memory).