. (1976). Thorax, 31,[720][721][722][723]. Bronchodiator effect of Al-tetrahydrocannabinol administered by aerosol to asthmatic patien. Ten volunteer inpatient asthmatics in a steady state were given a single inhalation of an aerosol (63 ,ul) delivered in random order, on each of three consecutive days, in the laboratory of a respiratory unit. Before, and for one hour after treatment the pulse, blood pressure (lying and standing), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak flow rate (PFR), and self-rating mood scales (SRMS) were recorded. Treatments were placebo-ethanol only; Al-tetrahydrocannabinol (THC) 200 ,Mg in ethanol; or salbutamol 100 Mug (Ventolin inhaler), administered double blind. Salbutamol and THC significantly improved ventilatory function. Maximal bronchodilatation was achieved more rapidly with salbutamol, but at 1 hour both drugs were equally effective. No cardiovascular or mood disturbance was detected, and plasma total cannabinoids at 15 minutes were undetectable by radioimmunoassay. The mode of action of THC differs from that of sympathomimetic drugs, and it or a derivative may make a suitable adjuvant in the treatment of selected asthmatics.

1 delta1‐trans‐tetrahydrocannabinol, (delta1‐THC) produces bronchodilatation in asthmatic patients. 2 Administered in 62 microliter metered volumes containing 50–200 microgram by inhalation from an aerosol device to patients judged to be in a steady state, it increased peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1). 3 The rate of onset, magnitude, and duration of the bronchodilator effect was dose related.

(1978). Thorax, 33, 479482 Bronchodilatation after inhalation of the antihistamine clemastine. H, receptor blocking antihistamines administered by mouth have not found a clear place in the management of bronchial asthma. We investigated the possibility that higher concentrations of these drugs, administered directly to the bronchial tree, might produce bronchodilatation.Twelve asthmatic patients inhaled aerosols generated from solutions of clemastine (0 05%0), salbutamol (0 5%), and placebo. Bronchodilatation was assessed by changes in the forced expiratory volume in one second (FEVY) and peak expiratory flow rate (PEFR) over four hours.Both clemastine and salbutamol caused significant bronchodilatation. The mean maximum percentage increases in FEV, for clemastine and salbutamol were 21 1 % and 29 2% respectively. The mean maximum percentage increases in PEFR were 31-2% and 35-2% respectively. There was no significant difference in the maximum bronchodilatation produced by the two drugs.Clemastine, when administered by aerosol inhalation, appears to be an effective bronchodilator.The role of histamine in the production of acute asthma is controversial. There is evidence that histamine is released in allergic reactions in the lung (Schild et al, 1951), and challenge studies have shown that the bronchi of asthmatics are more sensitive to histamine than those of nonasthmatics (Curry, 1947;Tiffenau, 1958;Townley et al, 1965). Oral antihistamine drugs have not found a place in treating asthma, however, and are widely thought to be ineffective (Lancet, 1955).Assuming that histamine plays a role in asthma, the therapeutic failure of antihistamines could be due either to the failure to block the H2 receptor sites or to incomplete H, receptor blockade caused by inadequate local concentrations of drugs. Indeed, higher doses of antihistamines, given by mouth or parenterally, have caused bronchodilatation (Popa, 1977), but central nervous system depression limits their use by this route.We have attempted to assess whether the administration of an H, receptor blocking antihistamine, clemastine, given directly to the bronchi as an aerosol, could cause therapeutically useful bronchodilatation. PatientsTwelve patients (age range 29-70, mean 46) gave informed consent. All were in hospital having recovered from a severe exacerbation of bronchial asthma and were in a relatively stable clinical state. All had previously shown reversibility of airways obstruction by a greater than 15% increase in peak expiratory flow rate (PEFR) after inhaling salbutamol aerosol 200 ,ug. Six of the twelve patients were atopic by prick skin testing. On three consecutive mornings each patient had baseline measurements of PEFR (the best of three recordings) using a Wright peak flow meter and forced expiratory volume in one second (FEV1) using a dry wedge spirometer (Vitalograph). Each subject then inhaled from a Wright's nebuliser 1 ml each of either clemastine 0-05% in saline, salbutamol 0 5%, or physiological saline as 479 on 10 May 2018 by guest....

1 There is evidence that H2 receptors are present in the lung, both on bronchial smooth muscle and mast cells. In animal studies, stimulation of H2 receptors causes a diminution, and conversely H2 receptor blockade can increase, smooth muscle contraction and mediator release. 2 The effects of H2 receptor blockade in ten patients with asthma has been studied using oral cimetidine in a dose of lg daily for 1 week. Treatment was compared with placebo and the H1 receptor antagonist chlorpheniramine. 3 There was no alteration in the severity of naturally-occurring or exercise-induced asthma with cimetidine or chlorpheniramine. 4 H2 receptor blockade with oral cimetidine in conventional doses is without ill effect in asthma. The use of larger parenteral doses is discussed.

1. Arterial plasma histamine concentrations, forced expiratory volume in 1.0 s (FEV1.0) and peak expiratory flow rate were determined in nine patients with exercise-induced asthma and in five control subjects before and after 8 min of cycle-ergometer exercise. 2. In the controls neither FEV1.0 nor peak expiratory flow rate fell by more than 5% in any individual during the 30 min postexercise period. The asthmatic patients all experienced a fall in FEV1.0 or peak expiratory flow rate, or both, of 15% or more in the period 5-20 min after completion of the exercise. 3. There was no difference between the control subjects and the asthmatic patients in the plasma histamine response to exercise. In both groups there was an insignificant rise of about 40% during exercise, although the initial levels were higher in the asthmatic patients. 4. The mean plasma histamine peak of the asthmatic patients preceded the mean maximal fall of FEV1.0 and peak expiratory flow rate by approximately 15 min. However, no positive correlation was found between rise in, or peak, plasma histamine levels and decrease in lung function. 5. Three non-atopic asthmatic patients had a significantly higher mean plasma histamine concentration during exercise than had the atopic subjects. 6. A strong positive correlation in asthmatic patients, and asthmatic and control subjects together was found between age and mean postexercise plasma histamine concentrations. 7. The results do not support a direct role for histamine in the production of exercise-induced asthma.