Comparison of the effects of marihuana and alcohol on simulated driving performance.

The effects of marihuana, alcohol, and no treatment on simulated driving performance were determined for experienced marihuana smokers. Subjects experiencing a "social marihuana high" accumulated significantly more speedometer errors than when under control conditions, whereas there were no significant differences in accelerator, brake, signal, steering, and total errors. The same subjects intoxicated from alcohol accumulated significantly more accelerator, brake, signal, speedometer, and total errors than under normal conditions, whereas there was no significant difference in steering errors. Impairment in simulated driving performance does not seem to be a function of increased marihuana dosage or inexperience with the drug.

Mitogen-induced blastogenic responses of lymphocytes from marihuana smokers.

Blastogenic responses in vitro to phytohemagglutinin and pokeweed mitogen were examined in microcultures of peripheral blood lymphocytes from a group of 12 healthy, long-term marihuana smokers and a group of matched control subjects. With either mitogen, no significant difference in cellular incorporation of (3H)thymidine was noted between the groups. These results were interpreted to indicate that the functional status of blood lymphocytes was not altered by long-term smoking of marihuana.

Marihuana and temporal disintegration.

High oral doses of marihuana extract, calibrated for content of 1 (-)-Delta(1)-tetrahydrocannabinol, significantly impaired the serial coordination of cognitive operations during a task that required sequential adjustments in reaching a goal. This disintegration of sequential thought is related to impaired immediate memory.

Marihuana and memory: acquisition or retrieval?

Two experiments were conducted to determine the means by which marihuana affects human memory. The results of these studies indicated that marihuana did not affect retrieval of information in memory when the method of free recall was used, but did affect recognition processes such that subjects were less able to discriminate between items that had been presented previously and items that had not appeared a short time before. With respect to initial learning, marihuana was shown to affect acquisition processes involved in the storage of information.

Marihuana: standardized smoke administration and dose effect curves on heart rate in humans.

A spirometer was used to deliver marihuana and placebo smoke to human subjects. This procedure produced linear dose-effect curves on heart rate and replicable dose effects in individual subjects. No differences were observed between experienced and inexperienced smokers in responsiveness to heart rate increases produced by marihuana.

Electroencephalographic and behavioral alterations produced by delta-1-tetrahydrocannabinol.

The administration of small doses of Delta(l)-tetrahydrocannabinol to cats with indwelling electrodes produced a disruption of both the electroencephalogram and behavior. Some of these alterations, including the appearance of a high-voltage slow wave electroencephalogram in the awake and moving animal, have been observed in cats that had been administered other drugs known to cause hallucinogenic states in man.

Delta-9-tetrahydrocannabinol: metabolism and disposition in long-term marihuana smokers.

Radioactively labeled delta-9-tetrahydrocannabinol (delta(9)THC) administered intravenously to chronic marihuana smokers disappeared from the blood plasma with a half-life of 28 hours as compared to 57 hours for nonusers of marihuana. Apparent volumes of distribution did not significantly differ between the two groups. Within 10 minutes after administration of delta(9)THC, 11-hydroxy-delta(9)THC is present in the plasma of nonusers and chronic users. This metabolite was also present in urine and feces of nonusers and long-term marihuana smokers. In addition, polar metabolites were excreted in urine and feces of both groups for more than 1 week.

Activity of delta8- and delta9-tetrahydrocannabinol and related compounds in the mouse.

The 11-hydroxy metabolites of Delta(8).- and Delta(9)-tetrahydrocannabinol are more active than the parent compounds when administered to mice by either the intravenous or intracerebral route. Both Delta(8)- and Delta(9)-tetrahydrocannabinol are rapidly and extensively metabolized by the liver and not by the brain. The hypothesis that the 11-hydroxy metabolites may be the active form of tetrahydrocannabinol is discussed

Delta 9 -tetrahydrocannabinol and ethanol: differential effects on sympathetic activity in differing environmental setting.

Serum dopamine beta-hydroxylase activity, a useful biochemical index of peripheral sympathetic nervous activity, was measured in rats treated with Delta(9)-tetrahydrocannabinol or ethanol or both substances. After 7 days of treatment with either substance, serum dopamine beta-hydroxylase activity decreased significantly. Combined treatment with both agents enhanced the effects of each given alone. In rats subjected to immobilization stress, treatment with Delta(9)- tetrahydrocannabinol appeared to potentiate the stress-induced increase in serum enzyme activity. Treatment with ethanol, with or without Delta(9)-tetrahydrocannabinol, effectively blocked this increase in enzyme activity. These results show that both substances have significant effects on the sympathetic nervous system which are critically influenced by environmental setting.

9 -tetrahydrocannabinol: dose-related effects on timing behavior in chimpanzee.

Delta(9)-Tetrahydrocannabinol, at doses within the effective range for humans, was administered orally to chimpanzees with stable, efficient timing performances maintained by multilink chained schedules of food reinforcement. Reinforcements decreased with increasing dose, because of decreased frequencies of total operant timing responses and decreased accuracy of the timing performances which did occur. Higher doses exerted an effect for up to 3 days.

9 -Tetrahydrocannabinol: effects on mammalian nonmyelinated nerve fibers.

Delta(9)-Tetrahydrocannabinol can be applied to tissue in vitro by dissolving it in Pluronic F68 and ethanol. It causes a decrease in size of the compound action potential of the nonmnyelinated fibers of the vagus nerve of the rabbit. This effect appears to be dose-related and chloride-dependent. Effects on other measurable parameters of nerve function seem to be minimal. Although the amounts required seem to be higher than those required to produce hallucinogenic effects in man, this effect is consistent with other work on Delta(9)-tetrahydrocannabinol and may ultimately account for a significant portion of the pharmacological activity of this drug.

9 -Tetrahydrocannabinol and ethyl alcohol: evidence for cross-tolerance in the rat.

Rats trained in a one-way avoidance situlation were made tolerant to the depressant effects of Delta(9)-tetrahydrocannabinol. Ethyl alcohol (3.2 grams per kilogram, intraperitoneally) did not greatly affect rats that were tolerant to delta(9)tetrahydrocannabinol but depressed the behavior of nontolerant rats. Rats made tolerant to ethyl alcohol were less affected by Delta(9)-tetrahydrocannabinol.

Residual learning deficit after heavy exposure to cannabis or alcohol in rats.

Acute oral administration of cannabis extract to rats (tetrahydrocannabinol dose, 10 milligrams per kilogram) impaired maze learning. The impairment was more marked after ten daily doses of the same size. After 1, 2, or 3 months' pretreatment with the same daily dose, followed by a 25-day drug-free period, no residual learning impairment was found. However, 6 months of daily administration of cannabis (tetrahydrocannabinol, 20 milligrams per kilogram) or alcohol (6 grams per kilogram) produced significant residual impairment of learning of maze and motor coordination tasks, 2 months or more after the last drug administration.

Phytohemagglutinin-induced lymphocyte transformation in humans receiving delta9-tetrahydrocannabinol.

Eight otherwise healthy male chronic marijuana smokers were hospitalized for a period of 30 days. Initially they received placebo, then a sustained dose of 210 milligrams of delta9-tetrahydrocannabinol (delta9-THC) per day for 18 days, followed by placebo. Lymphocyte responses to phytohemagglutinin were examined during each of these periods. Neither the daily ingestion of marijuana extract containing 210 milligrams of delta9-THC for 18 days nor the history of chronic marijuana smoking had a depressive effect on the lymphocyte responses of these subjects to phytohemagglutinin.

Behavioral effects in monkeys of racemates of two biologically active marijuana constituents.

Both dl-Delta(8)- and dl-Delta(9)-tetrahydrocannabinol produced marked alterations of behavior in rhesus and squirrel monkeys. Squirrel monkeys appeared to have visual hallucinations. Continuous avoidance behavior of squirrel monkeys was stimulated by both drugs, but high doses of dl-Delta(9)-tetrahydrocannabinol also caused depression after the stimulant phase. Complex behavior involving memory and visual discrimination in rhesus monkeys was markedly disrupted by both drugs.

Marijuana and driving in real-life situations.

It is evident that the smoking of marijuana by human subjects does have a detrimental effect on their driving skills and performance in a restricted driving area, and that this effect is even greater under normal conditions of driving on city streets. The effect of marijuana on driving is not uniform for all subjects, however, but is in fact bidirectional; whether or not a significant decline occurs in driving ability is dependent both on the subject's capacity to compensate and on the dose of marijuana. For those subjects who improved their performance, the explanation may lie in overcompensation and possibly the sedative effect of the drug. Whereas the street portion of this study approximated normal driving conditions, it should be emphasized that the context of the driving experience een on city streets was experimental. the design of this study maximal safeguards in terms of a dual control vehicle and a driver observr; in addition, the subjects were proffessionally screened and, with rare exception, they were emotionally stable. Given the experimental setting and set, the safeguards, and the nature of the study sample, idiosyncratic behaviour that might occure under normal driving condition would be less likely to occur in a study such as this. Other identified factors might lead to more stringent conclussions regarding the effects of marijuana on driving.The first is night driving, which may be more stressful. But an even more important unanswered question is the cumulative effect of alcohol and marijuana on driving (64 percent of the study sample reported alcohol in combination with marihjuana before driving). Third, the doses of marijuana used in this study were within the range of social marijuana usage(1); more heroic doses might be taken before driving. Fourth, the effect of marijuana on reactions and decision during high speed is still another unknown. What are the recommendations that emarge from this study? Driving under the influence of marijuana should be avoided as much as should driving under the influence of alcohol. More investigation is urgently required-and high priority should be given to studies that approximate normal conditions of driving and in which alcohol and marijuana are administered to the same subjects.

Chemical basis of hashish activity.

A sample of hashish was extracted consecutively with petroleum ether, benzene, and methanol. When tested intravenously in monkeys only the petroleum-ether fraction was active. This material was further fractionated. The only active compound isolated was Delta(1)-tetrahydrocannabinol. Cannabinol, cannabidiol, cannabichromene, cannabigerol, and cannabicyclol when administered together with Delta(1)-tetrahydrocannabinol do not cause a change in the activity of the latter, under the experimental conditions used. These results provide evidence that, except for Delta(1)-tetrahydrocannabinol, no other major, psychotomimetically active compounds are present in hashish.

1-delta9-tetrahydrocannabinol: neurochemical and behavioral effects in the mouse.

Administration of pure 1-delta(9)-tetrahydrocannabinol to mice had the following dose-dependent nzeurochemical and behavioral effects: a slight but significant increase in concentrations of 5-hydroxytryptamine in whole brain; a decrease in concentration of norepinephrine in brain after administration of low doses and an increase after high doses; diminished spontaneous activity, mloderate hypothermnia, hypersetisitivity to tactile and auditory stimiuli, and ataxia after low doses; and sedation, pronounced hypothermia, and markedly diminished spon taneous activity and reactivity after high doses. The duration of the effects on body temperature and spontaneous activity correlated generally with the changes in brain amines. The characteristic changes in brain amines do not correspond exactly to those observed with other psychotropic drugs.

Inhibition of normal growth by chronic administration of delta-9-tetrahydrocannabinol.

Body weight, food and water intake, and feces weight of 20 albino rats were recorded daily for 70 days. On days 11 to 40, 12 rats received behaviorally effective doses of Delta-9-tetrahydrocannabinol, either orally or intraperitoneally. These rats ate significantly less than placebo-dosed controls during the treatment period, and gained significantly less weight. Food intake recovered in the 30-day posttreatment period, but the former drug group still weighed less than the controls on day 70. In addition, all rats who had received intraperitoneal injections of Delta-9-tetrahydrocannabinol showed evidence of chronic diffuse nonsuppurative peritonitis.

Cannabis and alcohol: effects on stimulated car driving.

The effects of cannabis and alcohol on simulated car driving were studied. Cannabis resin containing 4 percent Delta(1)-tetrahydrocannabinol was administered orally in three doses equivalent to 8, 12, and 16 milligrams of that component. Alcohol was given orally in one standard dose of 70 grams. Both cannabis and alcohol increased the time required to brake and start, whereas alcohol increased while cannabis decreased the number of gear changes. An effect of dosage on response was observed with cannabis.