Role of Prostaglandins in Marihuana-Induced Bronchodilation

Abstract

In vitro evidence suggests that physiological effects of marihuana may be mediated by prostaglandins via the stimulation of phospholipase A₂. To verify if marihuana could act by this route in vivo, we tested the effects of acetylsalicylic and mefenamic acids, inhibitors of cyclooxygenase, on marihuana-induced bronchodilation and tachycardia. In 11 healthy volunteers, marihuana smoking (7mg/kg, 1.7% Δ9-tetrahydrocannabinol) produced a significant increase in specific airway conductance (from 0.26210.033 to 0.360 ± 0.050 s^-1 × cm H₂O^-1, mean ± SE, p < 0.01), forced expiratory volume in 1 s (4.02 ± 0.22–4.27 ± 0.25 liter, p < 0.05) and heart rate (73.2 ± 2.0–108.5 ± 5.2 beats/min, p < 0.001). In a second session, acetylsalicylic or mefenamic acid was taken for 30 h before marihuana smoking. No inhibition of marihuana-induced increase of specific airway conductance, forced expiratory volume in 1 s and heart rate was found. These findings suggest that the bronchodilation and the tachycardia induced by marihuana smoking in humans are not mediated by prostaglandins.

Decrease in Efficacy and Potency of Nonsteroidal Anti-Inflammatory Drugs by Chronic Δ9-Tetrahydrocannabinol Administration

“…The present study is based upon previous work that indicate that acute administration of cannabinoids stimulates the release of arachadonic acid resulting in elevation of prostaglandins (Burstein and Hunter, 1981;Burstein et al, 1983;Laviolette and Belanger, 1986;Bhattacharya, 1986;Hunter et al, 1991). Furthermore, cannabinoids induce COX-2 expression in the central nervous system (Ramer et al, 2001).…”

Effect of Mefenamic Acid on Bronchial Tone in vivo

“…We included a larger number of subjects and the study was double-blind and ran domized. The same dose of mefenamic acid than in the previous report [4] was used but no significant effect on SGaw was seen.…”

“…Walters [2] observed a slight increase of the specific airway conductance (SGaw) in normal sub jects with indomethacin, whereas Fish et al [3] did not find any significant changes. Recently, we reported that mefenamic acid seemed to provoke a slight increase of SGaw in healthy subjects [4], These results would suggest that endogenous PG exert a bronchoconstrictive activity in vivo. How ever, that study included a small number of data and was not designed specifically to evaluate the effects of cyclooxygenase inhibitors on the airway tone.…”

“…Our previous study was not double blind and evaluated the effect of cycloox ygenase inhibitors on the marihuana-in duced bronchodilation; we had then noted that mefenamic acid, but not acetylsalicylic acid, seemed to increase the SGaw [4]. Since mefenamic acid is a more potent in hibitor of cyclooxygenase than acetylsalicylic acid, we believed that an efficient in hibition of bronchoconstrictive PG release could be a possible explanation for the slight bronchodilation measured by the in crease of SGaw.…”

Cannabinoid effects on ventilation and breathlessness: A pilot study of efficacy and safety

“…The patients may have perceived relatively larger breaths after cannabinoids as a result of changes in airway resistance. Cannabinoids are known to reduce airways resistance specially when administered by inhalation, 32 but a small and inconsistent effect has also been reported with oral doses. 33 No such effect will be expected in normal subjects as they already have a low airways resistance at baseline.…”