Effects of oral Δ 9-tetrahydrocannabinol on the cerebral processing of olfactory input in healthy non-addicted subjects

Eur J Clin Pharmacol. 2017 Dec;73(12):1579-1587. doi: 10.1007/s00228-017-2331-2. Epub 2017 Sep 2.


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.

Keywords: Cannabis; Human experimental study; Human olfaction; Pharmacological functional magnet resonance immaging; Statistical parametric mapping; Translational reseach.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / physiology
  • Cross-Over Studies
  • Dronabinol / administration & dosage
  • Dronabinol / pharmacology*
  • Humans
  • Magnetic Resonance Imaging
  • Placebos
  • Smell / drug effects*
  • Young Adult


  • Placebos
  • Dronabinol