Effects of 20 mg oral Δ(9) -tetrahydrocannabinol on the olfactory function of healthy volunteers

Abstract

Aims: Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ(9) -tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the olfactory effects of THC to be expected during analgesic treatment.

Methods: The effects of 20 mg oral THC on olfaction were assessed in a placebo-controlled, randomized cross-over study in healthy volunteers. Using an established olfactory test (Sniffin' Sticks), olfactory thresholds, odour discrimination and odour identification were assessed in 15 subjects at baseline and 2 h after THC administration.

Results: Δ(9) -Tetrahydrocannabinol impaired the performance of subjects (n = 15) in the olfactory test. Specifically, olfactory thresholds were increased and odour discrimination performance was reduced. This resulted in a significant drop in composite threshold, discrimination, identification (TDI) olfactory score by 5.5 points (from 37.7 ± 4.2 to 32.2 ± 5.6, 95% confidence interval for differences THC vs. placebo, -7.8 to -2.0, P = 0.003), which is known to be a subjectively perceptible impairment of olfactory function.

Conclusions: Considering the resurgence of THC in medical use for several pathological conditions, the present results indicate that THC-based analgesics may be accompanied by subjectively noticeable reductions in olfactory acuity. In particular, for patients relying on their sense of smell, this might be relevant information for personalized therapy strategies.

Keywords: cannabinoids; olfaction; sensory pharmacology; Δ9-tetrahydrocannabinol.

Figure 1

Effects of Δ⁹-tetrahydrocannabinol (THC; 20 mg oral) on the three major dimensions of olfaction and on the performance score of an established olfactory test (‘Sniffin’ Sticks' test; Burghart Medical Instruments, Wedel, Germany [21]). The olfactory test was applied at baseline and 2 h after oral administration of either 20 mg THC or placebo (‘postmedication’) to 15 healthy volunteers. Individual observations are shown as triangles connected with the respective postmedication observation by a dashed line. Parameter mean values and 95% confidence intervals are overlaid and coloured (blue, placebo condition; red, THC condition). In comparison to placebo, THC significantly increased the detection threshold of phenylethylalcohol (PEA; interaction ‘drug’ by ‘measurement’, P = 0.025), reduced the ability to discriminate between different odours (interaction ‘drug’ by ‘measurement’, P = 0.008) and therefore also decreased the sum TDI score (threshold, discrimination, identification; interaction ‘drug’ by ‘measurement’, P = 0.003), although the identification of 16 different odours was not affected by THC. The asterisks indicate significances (P < 0.05) according to post hoc Student's paired t tests following significant ANOVA effects

Figure 2

Ratings of the sensory intensity (top) and the pleasantness (bottom) of the 16 odours belonging to the identification subtest of the ‘Sniffin'Stick' test (listed at the left side of the heat plot). Left panels show means and 95% confidence intervals of the ratings obtained at baseline and at 2 h following administration of the medication (THC or placebo), averaged across all 16 odorants and 15 subjects. Right panels are heat plots of the ratings of single odorants of the identification subtest. The colour coding from green, unpleasant or low intensity, via black, middle intensity of hedonically inert, to red, pleasant or high intensity, indicates the visual analog scale (VAS) ratings. None of the intensity ratings were changed by THC, and no pattern shift was observed in this cohort. , placebo; , THC

Figure 3

Ratings of the drowsiness and association of THC-induced changes in drowsiness and tiredness with THC-induced changes in olfactory test parameters. Left panel shows means and 95% confidence intervals of the ratings of drowsiness, obtained at baseline and at 2 h following administration of the medication (THC or placebo), averaged across the 15 subjects. Right panel is a scatterplot matrix of the THC-induced changes in selected parameters and olfactory test outcomes, calculated as differences of the ratings in the presence of THC from the baseline ratings, corrected for the respective changes in the presence of placebo. The asterisks indicate significances (P = < 0.001) according to post hoc paired t-test following significant ANOVA effects., placebo; , THC; *** P = < 0.001