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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    • "Klumpers et al., 2013a) and as a model for psychosis (i.e. Liem-Moolenaar et al., 2010; Kleinloog et al., 2012). Cannabis contains many other constituents than THC, some with opposing effects, such as cannabidiol (CBD; Ashton, 2001). "
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    ABSTRACT: The effects of drugs are not only determined by their pharmacological action, but also by user characteristics. This analysis explored the influence of personality on the differences in subjective effects in response to a standardized pharmacological challenge with the cannabinoid CB1/CB2 partial agonist Δ(9)-tetrahydrocannabinol (THC). Methods: To express the sensitivity to THC, pharmacokinetic-pharmacodynamic (PK-PD) non-linear mixed effects modelling was applied to the subjective response of 184 healthy subjects to a pharmacological challenge with inhalation of THC. The subjective effects were measured using visual analogue scales and described by three clusters: 'perception', 'relaxation' and 'dysphoria'. The sensitivity for THC (described as EC50) was related to scores on Cloninger׳s temperament and character inventory (TCI) using multiple linear regression. Results: Effect compartment models were used to describe the PK-PD relations of THC. Within the multivariate model, 'harm avoidance' was significantly correlated with changes in 'perception', and 'self-transcendence' with changes in 'dysphoria'. Conclusions: Within the psychobiological model of personality, 'harm avoidance' is related to serotonergic systems. Subjects with either very low (easy-going) or very high (cautious) scores were less sensitive to THC-induced changes in 'perception'. 'Self-transcendence' relates to schizotypy. Subjects with more schizotypy were more sensitive to the dysphoric subjective effects of THC. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research 10/2014; 220(3):945-953. DOI:10.1016/j.psychres.2014.10.010 · 2.47 Impact Factor
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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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