Effects of oral Δ9-tetrahydrocannabinol on the cerebral processing of olfactory input in healthy non-addicted subjects.
Carmen Walter, Bruno G Oertel, Lisa Felden, Ulrike Nöth, Johannes Vermehren, Ralf Deichmann, Jörn Lötsch
European Journal of Clinical Pharmacology December 2017 DOI: 10.1007/s00228-017-2331-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled randomized crossover pharmacological functional MRI study Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Healthy volunteers |
| Intervention | THC |
| Dose | 20 mg oral THC |
| Topics | Cannabis |
| Keywords | Human experimental study Human olfaction Statistical parametric mapping Translational reseach |
| Key points | Oral THC (20 mg) reduced the pleasantness of vanillin, a pleasurable odor, and this hedonic change correlated with reduced activation in the left amygdala, hippocampus, and superior temporal pole. No effects were seen for hydrogen sulfide. The authors argue these results support THC-induced modulation of central olfactory processing and suggest THC-based medications may have olfactory side effects. |
Abstract
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. 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. 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. 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.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cited by 2
- Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: a neuroimaging meta-regression analysis bioRxiv (Cold Spring Harbor Laboratory) November 3, 2021
- A systematic review of neuroimaging and acute cannabis exposure in age-of-risk for psychosis Translational Psychiatry April 13, 2021