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Effects of oral Δ9-tetrahydrocannabinol on the cerebral processing of olfactory input in healthy non-addicted subjects

  • Pharmacodynamics
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Abstract

Background

Considering the increasing acknowledgment of the human sense of smell as a significant component of the quality of life, olfactory drug effects gain potential clinical importance. A recent observation in a human experimental context indicated that Δ9-tetrahydrocannabinol (THC) impaired the subject’s performance in olfactory tests. To further analyze the role of THC in human olfaction, the present report addresses its effects on the central processing of olfactory stimuli.

Methods

Employing a placebo-controlled randomized crossover design, an oral dose of 20 mg THC was administered in 15 healthy volunteers. The central processing of olfactory input, consisting of short pulses of gaseous vanillin or hydrogen sulfide, and for comparison, of non-odorous but painful carbon dioxide, were investigated before and after administration of THC or placebo in a pharmacological functional magnet resonance imaging study.

Results

Following THC administration, the vanillin stimuli lost their pleasantness and became hedonically inert. This observation had its functional correlate in reduced stimulus-associated brain activations located in the left amygdala, the hippocampus and superior temporal pole (peak MNI coordinates x = − 27, y = − 1, z = − 26 mm p = 0.039). Differences in amygdala activations were significantly correlated with the corresponding differences in vanillin pleasantness (p = 0.025). By contrast, no effects were observed on the perception of processing of H2S stimuli.

Conclusions

The results support that THC induced a modulation of the central processing of olfactory input. The THC-induced reduction in the pleasantness of a pleasurable odor was accompanied by reduced activations in the limbic system. Results agree with previous observation of negative effects of cannabinoids on the human sense of smell and strengthen the evidence that THC-based medications will be among drugs with olfactory side effects.

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Acknowledgements

Parts of this complex project have been reported separately with other focus and in a non-redundant manner in J Clin Psychopharmacol 33(5): 699-705, Neuropsychopharmacology 41(6): 1659-1669, Eur J Pain 19(4): 516-518, and Br J Clin Pharmacol 78(5): 961-969.

Funding

This work has been funded by the Deutsche Forschungsgemeinschaft, DFG Lo 612/10-1 (JL), European Graduate School GRK757 (JL), and the Bundesministerium für Bildung und Forschung (Brain Imaging Center Frankfurt, DLR 01GO0203, RD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Fraunhofer Institute of Molecular Biology and Applied Ecology - Project Group Translational Medicine and Pharmacology (IME-TMP), Theodor – Stern - Kai 7, 60590, Frankfurt am Main, Germany

    Carmen Walter & Jörn Lötsch

  2. Institute of Clinical Pharmacology, Goethe – University, Theodor Stern Kai 7, 60590, Frankfurt am Main, Germany

    Bruno G. Oertel, Lisa Felden, Johannes Vermehren & Jörn Lötsch

  3. Brain Imaging Center, Goethe – University, Schleusenweg 2 - 16, 60528, Frankfurt am Main, Germany

    Ulrike Nöth & Ralf Deichmann

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  1. Carmen Walter
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Walter, C., Oertel, B.G., Felden, L. et al. Effects of oral Δ9-tetrahydrocannabinol on the cerebral processing of olfactory input in healthy non-addicted subjects. Eur J Clin Pharmacol 73, 1579–1587 (2017). https://doi.org/10.1007/s00228-017-2331-2

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