A trial of oral delta-1-(trans)-tetrahydrocannabinol in reversible airways obstruction.

Abstract

(1975). Thorax, 30,[80][81][82][83][84][85]. A trial of oral Jl'-(trans)-tetrahydrocannabinol in reversible airways obstruction. Sixteen patients with proven reversible airways obstruction were admitted to a double-blind study to compare the bronchodilator effects of oral J1-(trans)-tetrahydrocannabinol (z11-THC) and salbutamol. Measurements of forced vital capacity, forced expired volume in one second, peak expiratory flow rate, and maximum expiratory flow rate at 50% vital capacity after 10 mg oral z11-THC did not differ significantly from the effect of placebo, whereas increases after salbutamol were significant. Analyses of mood, pulse rate, blood pressure, and electrocardiogram showed no important changes after oral JP-THC. In vitro studies with isolated tracheal muscle indicate that the activity of Al-TI-fC is 1,000 times less than the equivalent dose of isoprenaline, and the effect of z11-THC is not abolished by ,-adrenoreceptor blocking agents. It is concluded that oral 1l-THC, at a dose of 10 mg, does not produce clinically significant bronchodilatation in patients with reversible airways obstruction.

Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients.

“…Salbutamol in a dose after inhalation of 100 Ag of 100 Kg was rapidly effective, but the two drugs )0 ,ug A'-THC (interrupted were equally effective after one hour, and there ean of the differences be-is reason to hope (Tashkin et al, 1975) that THC 'ter treatment 2-4SD for 10 has a longer duration of action than compounds which stimulate beta-adrenoceptors. The relative potency of the two drugs in this trial (approximately 2: 1 in favour of salbutamol) is different from that found by in vitro testing on guinea-pig ant alteration in resting bronchial muscle (approximately 1000: 1 in or lying blood pressures favour of isoprenaline) (Davies et al, 1975), but no significant difference isoprenaline is many times more potent than salter placebo, THC or salbutamol in such tests, and the insolubility of THC were greater than 01. in water makes interpretation of an assay difficult. By inhalation in humans A1-THC and To statistically significant salbutamol are comparable in efficacy.…”

“…Taken in this way, the drug was less effective than isoprenaline but the action persisted for longer (Tashkin et al, 1975). Until very recently (Olsen et al, 1976) attempts to deliver THC in effective amounts by aerosol were defeated by the difficulty of selecting a suitable non-foaming nonirritant solvent, and orally administered THC in doses which do not cause undue psychic disturbance are not very effective (Davies et al, 1975). The present report concerns the results of a double-blind controlled comparison of aerosols of THC in ethanol, salbutamol, and placebo in drug naive patients.…”

Role of Prostaglandins in Marihuana-Induced Bronchodilation

“…Both adrenergic stimulation [5,6] and atropine-like effect [6,7] have also been eliminated. The exact mechanism of THC-induced bronchodi lation remains unknown, although the possibility of a parasympatholytic site of action other than muscarinic receptors has been raised [25].…”

“…The mechanism of this effect is not known, but it does not seem to be mediated by /?-adrenergic stimulation [5,6] nor by an in hibition of muscarinic receptors [6,7], On the other hand, there is some evidence that cannabinoids (including THC) alter arachidonic acid metabolism and that some of the actions of marihuana could be me diated by a change in prostaglandin (PG) synthesis. For example THC blocks the arachidonic acid-induced rise of intraocular pressure in rabbits, while PGE2 overrides this effect and increases the intraocular pressure [8].…”

Bronchodilator effect of delta1‐tetrahydrocannabinol.

“…The mechanism of action of the drug, though not as yet known, does not appear to be related to fi-adrenoceptor stimulation or to cholinergic blockade Davies, Radcliffe, Seaton & Graham, 1975). Naturally-occurring and synthetic cannabinoid compounds which are without psychological activity are now available, and may hold therapeutic potential if they can be shown to retain bronchodilator activity.…”