Does olanzapine inhibit the psychomimetic effects of Δ9-tetrahydrocannabinol?

1Centre for Human Drug Research, Leiden, the Netherlands.
Journal of Psychopharmacology (Impact Factor: 3.59). 05/2012; 26(10):1307-16. DOI: 10.1177/0269881112446534
Source: PubMed


Δ(9)-Tetrahydrocannabinol (THC) produces transient psychomimetic effects in healthy volunteers, constituting a pharmacological model for psychosis. The dopaminergic antagonist haloperidol has previously been shown to reduce these effects. This placebo-controlled, cross-over study in 49 healthy, male, mild cannabis users aimed to further explore this model by examining the effect of a single oral dose of olanzapine (with dopaminergic, serotonergic, adrenergic, muscarinergic and histaminergic properties) or two oral doses of diphenhydramine (histamine antagonist) on the effects of intrapulmonarily administered THC. Transient psychomimetic symptoms were seen after THC administration, as measured on the positive and negative syndrome scale (20.6% increase on positive subscale, p<0.001) and the visual analogue scale for psychedelic effects (increase of 10.7 mm on feeling high). Following the combination of THC and olanzapine, the positive subscale increased by only 13.7% and feeling high by only 8.7 mm. This reduction of THC effects on the positive subscale failed to reach statistical significance (p=0.066). However, one-third of the subjects did not show an increase in psychomimetic symptoms after THC alone. Within responders, olanzapine reduced the effects of THC on the positive subscale (p=0.005). Other outcome measures included pharmacokinetics, eye movements, postural stability, pupil/iris ratio, and serum concentrations of cortisol and prolactin.

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    • "All analyses were performed in SPSS 17.0 (SPSS Inc., Chicago). PANSS and SSPS data did not have a normal distribution and were analysed after log transformation as described previously (Kleinloog et al., 2012). In addition, for the PANSS we followed the approach of D'Souza and colleagues, which is to categorise clinically significant psychosis as increases from baseline of ≥3 points (D'Souza et al., 2005): thereafter the difference in the frequency of clinically significant THC-evoked psychotic reactions between the CBD and placebo groups was analysed using Pearson's Chi-square. "
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