Daniel J. Brown

Impairment of performance with low doses of marihuana.

Eight volunteers smoked marihuana cigarettes under controlled laboratory conditions on 4 separate occasions. The cigarettes were calibrated to deliver doses of 0, 3, 6, and 9 µg per kilogram of delta‐9‐tetrahydrocannabinol (THC). The experimental design was a double‐blind random block with a 1 week interval between sessions. Analysis of variance revealed a significant linear decrease in stability with increase in dose of THC. The tracking scores with Pursuit Meter (PM) demonstrated a significant increase above control for all three doses of THC. Mental performance, as evaluated by Delayed Auditory Feedback (DAF), and subjective evaluation revealed no consistent change with dose.

Effects of Delta–9–tetrahydrocannabinol on Halothane MAC in Dogs

The effects of acute and subacute administration of delta–9–tetrahydrocannabinol (THC) on halothane requirements (MAC) in four groups of dogs were measured. THC administered intravenously produced a dose–related alteration in MAC. THC, 0.1 mg/kg, did not alter MAC 1, 3, or 24 hours after its administration. THC, 0.5 mg/kg, decreased MAC 32 per cent (P < 0.05) 1 hour after injection, but MAC was not significantly different from control after 3 and 24 hours. MAC was decreased 42, 36, and 18 per cent (P < 0.05) from control 1, 3, and 24 hours after 2.0 mg/kg THC. MAC was not changed from control 24 hours after four daily injections of 0.5 mg/kg THC.

Subacute toxicity of aqueous-suspended Δ9-tetrahydrocannabinol in rats

Abstract Thailand marihuana plant stock was extracted; purity of the Δ 9 -tetrahydrocannabinol (THC) obtained was 99% as determined by nuclear magnetic resonance, mass spectroscopy and gas-liquid chromatography. An aqueous suspension of THC was prepared. Purity of the THC in water remained at 99%. Male albino Holtzman rats were given daily ip injections (3.75–30 mg/kg) of aqueous-suspended THC for 30 days. Animals receiving the highest dose of THC exhibited the following signs approximately 10 min post injection: hypersensitivity to auditory or tactile stimulation, depression, ataxia, lacrimation and diarrhea. Animals receiving lower doses of THC exhibited the same signs but to a lesser degree. At the end of the 30-day test period, the body weight of the highest dose group was significantly less than that of the control group. Increases in the number of large hyperchromatic hepatic cells, some of which were binucleated, were found in some livers at 3 of 4 dose levels. An interesting observation concerning behavior of the animals was that the rats appeared to become more sensitive to THC during the last 10 days of the 30-day test period.

Endocrine effects of cannabis in male rats

Abstract Male Wistar rats were administered either synthetic Δ9-tetrahydrocannabinol (Δ9-THC) or Mexican cannabis extract at doses of 1, 5, 10, 25, and 50 mg of Δ9-THC/kg of body weight. Steroid concentrations in urine and blood were measured using glass capillary gas chromatography and individual metabolites were identified by gas chromatography/mass spectrometry. Plasma corticosterone and its metabolite were elevated in a dose-response fashion up to 25 mg/kg. While testosterone is unaltered by Δ9-THC, except at 50 mg/kg, ⊙ther metabolites with possible relation to androgen metabolism were elevated. Measurable amounts of estrogens were produced by male rats given the drugs. Additional alterations were seen in the concentrations of conjugated steroids.

Propranolol antagonism of marihuana induced tachycardia

Abstract The experiment was conducted on a double blind basis according to a completely randomized design. There were four groups consisting of six subjects each as follows: propranolol pretreatment plus marihuana; propranolol pretreatment plus placebo marihuana; placebo propranolol pretreatment plus marihuana; and placebo propranolol pretreatment plus placebo marihuana. Smoking of active marihuana resulted in a significant increase in heart rate. The prior administration of propranolol antagonized the marihuana induced tachycardia both in magnitude and duration. However, propranolol pretreatment neither decreased the number of responses on the Cornell Medical Index following the smoking of marihuana nor interfered with the subjects ability to distinguish active marihuana from placebo marihuana.

Combined effects of propranolol and ethanol on human psychomotor performance

Twelve male subjects were given placebo or 160 mg propranolol, in divided doses, during a 24-hr period before drinking a beverage containing 0 or 50 ml ethanol/70 kg body weight. Tests designed to measure mental and motor performance were administered 75 min after the last dose of propranolol. The tests performed included the wobble board (WB), pursuit meter (PM), delayed auditory feedback (DAF), pegboard (PB), tapping, time estimation (TE), and a modified Cornell medical index (CMI). A mean blood ethanol concentration of 48.0 +/- 9.1 mg/dl and a mean plasma propranolol level of 33.1 +/- 13.1 ng/ml were achieved. Ethanol alone significantly impaired performance in 12 out of 20 tests (p less than 0.05). Propranolol significantly (p less than 0.05) antagonized the decrement in psychomotor performance induced by ethanol on the PM. In all other tests, there was no significant interaction between ethanol and propranolol. Propranolol alone had no significant effect on the psychomotor tests. When the drugs were combined, the subjective symptoms, as measured by the CMI, showed a trend toward being additive. This study suggests that no adverse interaction occurs between therapeutic doses of propranolol and minimum impairment doses of ethanol.

Ethyl alcohol toxicity in the bat (Myotis lucifugus)

Abstract The toxicity of ethanol to unanesthetized bats was studied because the preparation allows subsequent quantitative studies of arteriole and venule responses to ethanol and to alcohol-drug interactions. The toxicity of ethanol was calculated in the bat ( Myotis lucifugus ) as an LD50, which was found to be 4.3 g/kg. Thus, ethanol appears to be more toxic to the bat than to other species, such as the mouse, rat, and guinea pig. This is a somewhat unexpected finding, since the rate of disappearance of ethanol is higher for the bat than for most other species. Our data indicate that the rate of disappearance of ethanol from the blood of a bat is 55–70 mg/100 ml/hour.

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.