Journal of clinical pharmacology
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Clinical Trial
The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety.
The anxiolytic properties of nabilone, a synthetic cannabinoid resembling the natural cannabinoids, were studied in 25 outpatients suffering from anxiety. The drug was compared with a placebo in a double-blind manner over a 28-day treatment period. ⋯ Side effects reported were dry mouth, dry eyes, and drowsiness. Patients did not report any of the subjective "altered state" experience of marihuana.
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We conducted a pilot study to ascertain the potential toxicity and possible efficacy of delta 9-tetrahydrocannabinol (THC) at the oral dose of 5 mg/m2. Over one third of the study population, which consisted of 25 patients, reported significant dysphoric reactions. Four patients (16 per cent) elected not to take THC rather than experience loss of motivation which interfered with their professional life. ⋯ By the third administration of THC, one of 14 patients (7 per cent) and two of 14 (14 per cent) noted complete alleviation of nausea and vomiting, respectively. Patients who scored high on the Brief Psychiatric Rating Scale, who reported euphoria, or who had psychogenic nausea and vomiting were most likely to have a favorable antiemetic response. The results of this pilot study suggest that orally administered THC is a toxic but transiently effective antiemetic when administered at 5 mg/m2.
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Reports suggesting that delta 9-tetrahydrocannabinol (THC) had a potent antiemetic effect in patients treated with cancer chemotherapeutic agents led to the synthesis of other cannabinol derivatives with possibly less side effects. We report here our initial observations with the antiemetic levonantradol in 12 patients with advanced solid tumors receiving cytotoxic polychemotherapy. All patients had a history of vomiting and nausea without successful treatment with standard antiemetic drugs in previous, identical chemotherapy cycles. ⋯ When compared to the last course of chemotherapy with alternate antiemetic drugs, we found that 11/12 patients had less nausea and vomiting when treated with levonantradol. 8/12 Patients considered the antiemetic treatment with levonantradol better than the one given before. The following side effects were observed: 4 patients complained of pain and local irritation after injection. 2 patients showed a fall in blood pressure, especially orthostatic hypotension. 8 patients complained of sedation and drowsiness. 7 patients experienced psychic side effects, such as decrease of vigilance and reaction, altered sense of timing, body image distortions and even depersonalization. Levonantradol is a potent antiemetic drug but its applicability, especially in outpatients, may be complicated by a high incidence of side effects.
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Vomiting accompanied by nausea is a serious acute toxicity which occurs after chemotherapy with virtually every class of cancer chemotherapeutic agents. The inability to adequately alleviate this toxicity may lead to serious complications such as general malaise, weight loss, and electrolyte imbalance. We have reviewed 34 studies in which more than 2200 cancer patients were administered 25 different antiemetics for treatment of chemotherapy-induced vomiting. ⋯ The antiemetic agents included phenothiazines, antihistamines, anticholinergics, benzoquinolizines, barbiturates, butyrophenones, procainamides, cannabinoids, steroids, and benzodiazepines. It is apparent from these studies that the use of conventional antiemetic agents for treating cancer chemotherapy-induced vomiting is of marginal value, and the use of investigational antiemetic agents show conflicting results as to efficacy. More quantitative measures for evaluating emesis need to be defined, and the implications that a particular antiemetic therapy may be efficacious for some but not all classes of cancer chemotherapeutic agents need to be evaluated.
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Comparative Study
Comparison of the inotropic and chronotropic effects of metoprolol and propranolol.
The cardiovascular responses to intravenous doses of isoproterenol were measured in eight male volunteers before and during administration of 50 mg metoprolol, orally every 6 hours and 40 mg propranolol, orally every 6 hours for a total of five doses. The dose of isoproterenol required to produce an increase in heart rate of 25 beats/min (the ID25) was 2.0 +/- 1.4 microgram before beta blockade, 6.2 +/- 4.4 microgram during metoprolol, and 44.4 +/- 12.0 microgram during propranolol administration. Similar changes in diastolic blood pressure, QS2I, preejection period, and preejection period/left ventricular ejection time ratio occurred at the ID25 during treatment with both metoprolol and propranolol. In volunteers, propranolol produces a much more intense blockade of the inotropic and chronotropic effects of isoproterenol than does metoprolol.