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Biomedical subjects

L Lemberger

Publications and source records attributed to L Lemberger.

At least 55 records · Page 3Linked to original sources

Subjective responses and excretion patterns of dextroamphetamine after the administration of therapeutic doses.

Twelve male medical and graduate students received dextroamphetamine sulfate in doses of 0, 5, 10, and 15 mg/70 kg body weight. The study was conducted in a double-blind manner, and treatments were assigned according to randomized, complete block design. The drug was given orally and subjects were instructed not to eat 3 1/2 h prior to administration. After administration, total urine output was collected for 12 h; no attempt was made to control urinary pH to more realistically approach the general clinical usage of amphetamines. The urine was pooled into two 6-h segments and analyzed for amphetamine concentration. Subjective impressions of the treatments were also evaluated by means of the Cornell Medical Index Questionnaire. Results showed that approximately 30% of the total dose was excreted unchanged within 12 h after administration. The amount excreted agreed very closely with the doses given and paralleled the scores for subjective impressions by the subjects. None of the subjects felt that their driving would be impaired for any of the doses administered. This study indicates that under ordinary conditions (in which pH is not artificially controlled), therapeutic doses of dextroamphetamine can be detected in urine for up to 12 h after oral administration.

Administration, Oral↗

Influence of cannabidiol on delta-9-tetrahydrocannabinol effects.

Experiments investigating the possible interaction of tetrahydrocannabinol (THC) and cannabidiol (CBD), two major components of marihuana, were conducted under controlled laboratory conditions in a double-blind manner. In one study, 15 male volunteers were given placebo or 25 mug/kg of THC together with either placebo or 150 mug/kg of CBD by inhalation of the smoke of a single cigarette. All four treatments were assigned to each subject according to a series of Latin-square designs. CBD significantly attenuated the subjective euphoria of THC. Psychomotor impairment due to THC was not significantly altered by the simultaneous administration of CBD, but a trend indicating a decrease in THC-like effects was observed after the combination. When administered alone CBD was inactive for all the parameters measured. In a second study, 8 male subjects were given CBD (0 or 150 mug/kg) by smoke inhalation 30 min before THC (0 or 25 mug/kg) in a second cigarette. In contrast to the simultaneous administration of both drugs, CBD pretreatment did not alter the effects of THC on the parameters observed.

Adult↗

Effects of dextroamphetamine on psychomotor skills.

Twelve healthy male volunteers were given 0, 5, 10, 15 mg/70 kg dextroamphetamine orally in a randomized double-blind fashion. Blood pressure increased linearly with dose while heart rate was unchanged. Although selected individual tests of stance stability and motor function improved in a dose-related fashion, a generalized improvement in performance was not found. Delayed Auditory Feedback (DAF) failed to show improvement in mental performance after dextroamphetamine.

Acoustic Stimulation↗

Effects of marihuana-dextroamphetamine combination.

Under a double blind, randomized, complete block design, subjects were given either placebo and 10 mg/70 kg dextroamphetamine sulfate (A) orally followed 1 1/2 hr later by a marihuana cigarette (M) prepared to deliver 50 mug/kg delta-9-tetrahydrocannabinol (THC). Statistical analyses suggested that heart rate and blood pressure increased in an additive manner when both drugs were given. Electrocardiogram changes, when present, were nonspecific in character and appeared to be associated with marihuana. In a second study, psychomotor performance was evaluated by a similar design using doses of 10 mg/70 kg of A and M prepared to deliver 25 mug/kg THC. Impairment was related to smoking of M, and no difference could be distinguished between M alone and M-A combination. Subjective evaluation, as measured by the modified Cornell Medical Index (CMI) demonstrated only additive effects for the combination.

Adult↗

Influence of cannabidiol on secobarbital effects and plasma kinetics.

To investigate the possible metabolic interaction between cannabidiol (CBD) and secobarbital, 6 male volunteers received 150 mg/70 kg sodium secobarbital orally immediately after smoking a marihuana cigarette prepared to deliver 0, 150, or 500 mug/kg CBD. The study was performed in a double-blind manner with each of the three treatments being assigned to every subject. Clinical effects and plasma secobarbital concentrations were recorded at periodic intervals. CBD did not alter the summary parameters which describe the secobarbital plasma concentration time curve. Secobarbital half-life, peak concentration, time of peak concentration, and area under the curve were unchanged by the coadministration of CBD. Clinical effects of secobarbital were also unaltered by CBD pretreatment. Thus at the doses administered, CBD does not appear to inhibit secobarbital metabolism in man.

Adult↗

The effect of nisoxetine (Lilly compound 94939), a potential antidepressant, on biogenic amine uptake in man.

Preclinical studies with nisoxetine (Compound 94939) (3-[o-Methoxyphenoxy]-N-methyl-3-phenylpropylamine HCl) had shown it to have antidepressant properties and to be almost devoid of anticholinergic activity and depressant effects on cardiac conduction (in contrast to the commonly used tricyclic antidepressants from which nisoxetine significantly differs in structure). Placebo and nisoxetine (10-20 mg b.d. for 7 days) were administered to normal volunteers in a single-bind crossover study. Adverse side effects were minimal. There were no significant changes in heart rate or blood pressure seen when no other drugs were given. The effect of nisoxetine on uptake of biogenic amines was utilized to study its mechanism of action. The transient rise in blood pressure seen after an intravenous bolus of tyramine decreased by one-half to two-thirds while the rise in blood pressure upon continuous noradrenaline infusion was enhanced some two-to eight-fold. Both effects occurred after on dose and were greater with larger doses and chronic administration. In vitro, nisoxetine inhibits 5-HT uptake into platelets. However, platelets harvested from subjects receiving chronic nisoxetine administration did accumulate 5-HT. Plasma concentration of nisoxetine in these individuals was shown to be lower than that needed to block 5-HT uptake. We concluded that nisoxetine, in safe doses, specifically increased the sensitivity of noradrenaline and decreased tyramine responsiveness, presumably by blocking uptake at the axonal membrane. In contrast, in these clinical doses it had virtually no effect on 5-HT uptake into platelets.

Adult↗

The combined effect of marihuana and dextroamphetamine.

The studies in mice indicated that locomotor activity could be stimulated THC and that this would enhance the effect produced by MAMP. We have previously shown that when 3, 6, or 9 mug/kg THC were administered to young adult males by MJ smoking, a dose-related impairment in standing steadiness (WB) and attentive motor performance (PM) resulted, although DAF and subjective evaluations were insensitive to these treatments. These same testing procedures after d-AMP 5, 10, and 15 mg/70 kg revealed no important performance effect. Systolic blood pressure was elevated with 15 mg/70 kg d-AMP, and subjective detection was positive and dose related. A combination of 25 mug/kg THC delivered by smoking an appropriate MJ cigarette and 10 mg/70 kd d-AMP taken orally produced subjective effects and psychomotor performance decrements not different from those with the MJ alone. The doses used were modest, yet most subjects believed their driving performance, a representative motor and metal skill, would be impaired. This judgment is supported by the laboratory measurements made. It is reasonable that realistically higher doses may not only have adverse psychological and cardiovascular effects but increase an accident potential.

Adult↗

Effects of marihuana combined with secobarbital.

Twelve male volunteers smoked a marihuana cigarette prepared to deliver 0 or 25 mug/kg tetrahydrocannabinol (THC) 50 min after ingesting a capsule containing either placebo or 150 mg/70 kg sodium secobarbital. Drugs were administered in a double-blind manner, and all treatments were assigned to each subject in a randomized complete block design. Objective and subjective tests designed to measure mental and motor performance indicated that marihuana impaired stability, hand-eye coordination, and mental performance. Secobarbital affected motor performance, manual coordination, and mental performance. In combination, marihuana and secobarbital had an additive effect on subjective responses and impairment in certain psychomotor performance tests.

Adult↗

Clinical pharmacology of nabilone, a cannabinol derivative.

Nabilone is a modified cannabinol derivative with central nervous system activity. Administration of nabilone in single doses of 1 to 5 mg results in dose-related pharmacologic effects in man. One and 2.5 mg doses of nabilone induced relaxant and sedative effects in all subjects. No euphoria, dry mouth, tachycardia, or postural hypotension was seen after 1 mg, minimal effects were seen after 2.5 mg, and marked effects were seen after 5 mg. Effects were evident within 60 to 90 min and persisted for 8 to 12 hr. Nabilone produced no significant tachycardia. There were no changes in supine blood pressure; however, marked postural hypotension occurred after the 5-mg dose. The administration of nabilone at doses of 1 mg or 2 mg two times daily resulted in euphoria and dry mouth during the first two days of drug; thereafter tolerance developed to these effects but there was no apparent decrease in relaxation. Subjects challenged with a single 5-mg dose of nabilone showed a 66% reduction in symptoms and signs after the 7-day drug period compared to that of the same dose after 1 wk of placebo. Comparison of nabilone with other cannabinol derivatives suggests that some of the undesirable pharmacologic effects can be separated within the group.

Adult↗

The effect of lergotrile on galactorrhea and gonadotropin secretion.

Lergotrile (Compound 83636), a specific inhibitor of prolactin release, was administered to 5 women with galactorrhea. Only 1 of the 5 had an elevated serum prolactin (hPRL) value, but Compound 83636 induced a decrease in serum hPRL in all cases. All patients had cessation of breast secretion within 72 days after initiation of lergotrile. LRH administration (100 pg) evoked a variable gonadotropin response before and during treatment with the ergot alkaloid. By contrast, serum prolactin values remained essentially unaltered after injection of LRH under the same conditions.

Acetonitriles↗

Alterations in the cellular-mediated immune responsiveness of chronic marihuana smokers.

Chronic marihuana smokers and matched nonsmokers were compared with respect to several aspects of both their humoral and cellular immune system. Immunoglobulin and complement levels, SMA 12 and hematologic values from marihuana smokers did not differ significantly from those obtained from nonsmokers. However, the number of T-lymphocytes with respect to the ratio of T and B-lymphocytes in the peripheral blood was lowered in marihuana smokers. In addition, phytohemagglutinin stimulation of lymphocytes was apparently less effective in smokers. The polymorphonuclear leukocytes (PNM) from the blood of smokers contained fewer cells capable of phagocytizing yeast cells than did PMN from nonsmokers. While marihuana smoking does appear to affect immune mechanisms at no time in these studies were any deleterious physiological effects that could be directly associated with the alterations in the immune system observed in the marihuana smokers.

Adult↗