220 Asthma, cardiovascular disorders, glaucoma Asthma is a chronic disease of the respiratory system in which the learn more airway occasionally constricts, becomes inflamed, and is lined with excessive amounts of mucus. In animal experiments, after

methacholine-induced or exercise-induced bronchospasm, marijuana caused a prompt improvement of the bronchospasm and associated hyperinflation.221 In humans, habitual smoking of marijuana may cause mild, but significant, functional lung impairment222; However, a mild and inconstant bronchodilatory action was found for THC.223 In other clinical trials, smoking marijuana or ingesting THC were Inhibitors,research,lifescience,medical found to increase airway conduction.224,225 Other plant cannabinoids did not provide effective bronchodilation. The daily use of THC was not associated with clinical tolerance.226 THC administered in metered volumes by inhalation from an aerosol device to patients judged to be in a steady state, increased peak expiratory flow rate (PEFR) and forced expiratory volume in Inhibitors,research,lifescience,medical 1 second (FEV1) and produced bronchodilatation.227 In another study, salbutamol and THC significantly improved ventilatory function.

Maximal bronchodilatation was achieved more rapidly with salbutamol, but at 1 hour both drugs Inhibitors,research,lifescience,medical were equally effective. No cardiovascular or mood disturbance was detected, and plasma total cannabinoids at 15 minutes were not detected by radioimmunoassay. The mode of action of THC differed from that of sympathomimetic drugs.228 In another study, THC induced sympathetic stimulation and parasympathetic inhibition of cardiovascular control pathways. Inhibitors,research,lifescience,medical The peak heart rate rise after

THC was attenuated by atropine and by propranolol, and nearly abolished by atropine-propranolol pretreatment.229 Acute THC significantly increased heart rate, shortened pre-ejection period (PEP) and prolonged left ventricular ejection time (LVETc) without any change in afterload; it enhanced cardiac performance. Partial inhibition of this effect was achieved with prior (β-adrenergic blockade.230 In contrast, following the smoking of one to three marijuana cigarettes, Inhibitors,research,lifescience,medical the heart rate rose, cardiac output rose, stroke volume, ejection fraction, PEP and LVET did not change; thus, in long-term heavy users of cannabis, marijuana has no significant effect on myocardial contractility independent of its effect on heart rate.231 Cardiovascular effects of acute THC administration included increased sympathetic and reduced parasympathetic tone; supine tachycardia and increased Terminal deoxynucleotidyl transferase blood pressure with upright hypotension were observed. With repetitive dosing supine bradycardia and decreased blood pressure with tolerance to orthostatic hypotension were observed.232,233 Rimonabant attenuated the hypotensive effect of smoked marijuana in male smokers, suggesting a role for the CB1 receptor in cannabinoid hypotensive action.234 A number of studies suggest that there is a correlative, but not necessarily causal, relationship between glaucoma and systemic hypertension.