Effects of marijuana extract and tetrahydrocannabinol on electroencephalographic sleep patterns.

Marijuana extract, given in daily doses containing 70 to 210 mg delta-9-tetrahydrocannabinol (THC), induced effects on sleep that were virtually identical to those produced by the same doses of relatively pure (96%) THC. Both drugs reduced eye movements density with some tolerance developing to this effect. Stage 4 tendend to increase with drug administration. Abrupt withdrawal led to extremely high densities of eye movement, increased rapid eye movement (REM) durations, and a sharp but transient fall in stage 4 to baseline levels. These effects may be useful in the elucidation of the pharmacology of sleep. The effects on sleep of THC administration (but not withdrawal) closely resemble those induced by lithium. For this reason, we suggest further studies of THC in affective disorders. Evidence available thus far suggests that THC produces dysphoric symptoms in unipolar but not in bipolar depressed patients; these differences in response may prove of diagnostic value. An adequate therapeutic trial of THC in bipolar depressed patients has not yet been carried out.

Effects of delta9-tetrahydrocannabinol on social behaviour in mice: comparison between two vehicles.

Two vehicles for the intraperitoneal administration of delta9-tetrahydrocannabinol (delta9-THC) were compared, using aspects of social behaviour in mice and 5 doses of delta9- THC, with vehicle alone and saline control groups. 10% propane-1,2-diol-1% Tween 80-saline (vehicle B) seemed to be more effective than 1% Tween 80-saline (vehicle A) since depressant effects of --1 delta9-THC on behaviour tended to occur at lower doses with this vehicle. Few differences in behaviour could be detected among the three control groups. In general the overall number of behavioural acts decreased with increasing doses of delta9-THC, but with vehicle B low doses selectively decreased the number of 'social' (including aggressive) as distinct from 'individual' acts. Low doses of the drug in vehicle A sometimes stimulated behaviour, whereas with vehicle B such doses mostly produced depression; however, 2.5 mg/kg delta9-THC, in either vehicle, markedly increased the percentage of animals which showed both aggression and flight acts--a rare combination among controls. Our findings are consistent with other evidence that propylene glycol is an effective vehicle for the i.p. administration of delta9-THC.

Chronic hashish use and mental disorder.

The authors compared 47 long-term users of hashish with a control group of 40 subjects matched for age, ethnic origin, education, etc., in order to determine whether they differed significantly on psychiatric, physical health, and demographic variables. There was a significantly higher incidence of personality disorders, unemployment, and prison sentences in the group of chronic users. However, in contrast to the findings of other researchers, the hashish users did not have organic psychoses, nor did they differ from control subjects in neurologic signs or EEG and echo encephalogram patterns.

Antitussive activity of some naturally occurring cannabinoids in anesthetized cats.

Experimental cough was elicited in pentobarbital-anesthetized cats by either electrical stimulation of the superior laryngeal nerve or by mechanical stimulation of the tracheal mucosa. Intravenous administration of delta9-tetrahydrocannabinol (THC) effectively reduced the amplitude of the cough response in both these models of experimentally induced cough with ED50 values (AtD50) of 1.84 and 0.78 mg/kg, respectively. This cough suppressant activity of THC was more similar to codeine-PO4 than dextromethorphan-HBr. On the other hand, both cannabinol (CBN) and cannabidiol (CBD) were devoid of antitussive activity at doses as high as 10.0 mg/kg.

Hepatitis B in Nuremberg, Germany. Epidemiology of a drug-associated epidemic. Among US Army soldiers.

Beginning in 1971, acute viral hepatitis was epidemic among US soldiers stationed in Europe, with a total of over 8,700 cases reported between 1971 and 1974. Hepatitis B surface antigen (HBsAg) determinations suggest a predominance of hepatitis B. In the Nuremberg area, primary association was with the illicit use of drugs. This association was demonstrated by a chronologic relationship between measurable community drug use and the number of hepatitis admissions three to six months later and by a case-control study. Parenteral drug use and, to a lesser degree, cannabis smoking appeared to be factors in disease transmission. Sharing of illicit drugs with a hepatitis contact, whether parenterally or orally, was associated with increased risk of contracting the disease.

Spontaneous behavior and sleep-wakefulness cycle in isolated and paired REM sleep deprived-marihuana treated rats.

The correlation between marihuana-induced aggressive behavior and changes in the sleep-wakefulness cycle was studied in chronically implanted rats. Marihuana injection in non-REM deprived rats did not induce aggressiveness irrespective of the animals being caged in isolation or paired. During this procedure quantization of the sleep-awake cycle revealed that wakefulness was increased while slow wave and REM sleep were decreased, mainly in the paired animals. REM deprived-marihuana injected animals recorded in isolation behaved like the control solution-injected rats. They showed a large rebound of REM and were not aggressive at the end of the 8 hr sessions. Conversely, when these animals were paired during the recording periods, they remained continuously awake and showed numerous episodes of aggressiveness. These results suggest that the aggressiveness inducing properties of marihuana are related to the REM deprivation and to the increased environmental stimulation achieved by pairing the animals.

Alcohol and marijuana effects on static visual acuity.

Static visual acuity was measured at two contrast levels (12 and 49%) in ten subjects in a double blind experiment involving five drug conditions of alcohol and marijuana (0.5 ml and 1.0 ml/kg body weight of 95% ethanol, 8 and 15 mg delta-9-tetrahydrocannabinol (THC), and a placebo). We found no statistically significant change in static visual acuity for any of the dose levels at any of the measurement time up to six hours following drug ingestion; this is sharply contrasted with the marked decrements in acuity which were found in the same subjects under the same drug conditions when the targets were in motion and required corrdinated eye movements for their resolution.

Cannabis intoxication: effects of monetary incentive on performance, a controlled investigation of behavioural tolerance in moderate users of cannabis.

The study examined the effect of monetary incentive on the performance of five tasks after two heterogeneous groups of experienced users of cannabis and previously naive subjects had smoked placebo material and two dose levels of cannabis. The performance of the motivated subjects was compared with that of two non-motivated matched groups. Dose-related impairment was found on four of the five tasks, supporting previous findings of cannabis-induced impairment of short-term memory, goal-directed behavior and choice reaction times. Results for three of the tasks suggested that the performance of the motivated subjects was less affected by the drug than was the performance of the non-motivated subjects. There was no difference between the performance of subjects naive and experienced with respect to drug use.

Liver disease in nonparenteral drug abusers.

Liver function tests were performed in 500 young servicemen with a history of drug abuse. Serum glutamic oxaloacetic transaminase (SGOT) level was abnormal in 66% of 68 patients with a history of parenteral drug abuse. Forty-one percent of 432 patients with a history of only nonparenteral drug abuse also had elevated SGOT levels. A high incidence of liver disease in parenteral drug abusers is well established; however, to our knowledge, the magnitude of the problem in nonparenteral drug abusers has not been noted previously. Liver biopsy specimens in 34 of our patients showed either a classic viral hepatitis or a mild nonspecific hepatitis. Limited follow-up suggested a slowly resolving process. We conclude that hepatitis may be a common sequel to epidemic nonparenteral drug abuse.

Antineoplastic activity of cannabinoids.

Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-tetrahydrocannabinol (delta9-THC), delta8-tetrahydrocannabinol (delta8-THC), and cannabinol (CBN), but not cannabidiol (CBD). Animals treated for 10 consecutive days with delta9-THC, beginning the day after tumor implantation, demonstrated a dose-dependent action of retarded tumor growth. Mice treated for 20 consecutive days with delta8-THC and CBN had reduced primary tumor size. CBD showed no inhibitory effect on tumor growth at 14, 21, or 28 days. Delta9-THC, delta8-THC, and CBN increased the mean survival time (36% at 100 mg/kg, 25% at 200 mg/kg, and 27% at 50 mg/kg, respectively), whereas CBD did not. Delta9-THC administered orally daily until death in doses of 50, 100, or 200 mg/kg did not increase the life-spans of (C57BL/6 times DBA/2)F1 (BDF1) mice hosting the L1210 murine leukemia. However, delta9-THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for actinomycin D. Experiments with bone marrow and isolated Lewis lung cells incubated in vitro with delta9-THC and delta8-THC showed a dose-dependent (10(-4)-10(-7)) inhibition (80-20%, respectively) of tritiated thymidine and 14C-uridine uptake into these cells. CBD was active only in high concentrations (10(-4)).

Marijuana-produced impairments in coordination. Experienced and nonexperienced subjects.

The effects of marijuana and a placebo on perceptual-motor coordination, motor ability, and visual perception were compared in cannabis-experienced and naïve subjects. Impairments in coordination were observed in both groups. However, the impairment was greater in the experienced than in the naïve group.

The toxicity of intravenously used marihuana.

While no unanimity of opinion exists regarding the risk to physical health from smoking marihuana, we have seen four cases that demonstrate clearly that intravenous usage is hazardous. The severity of the multisystemic involvement is dose-related. On initial examination, signs of most severe overdosage included fulminant gastroenteritis, hypoalbuminemia, toxic hepatitis confirmed by serial biopsy, acute renal failure, electrolyte disturbances, leukocytosis, anemia, and a relative thrombocytopenia. In three patients who shared a common needle, gingivostomatitis also developed.

Interactions in man of delta-9-tetrahydrocannabinol. II. Cannabinol and cannabidiol.

Oral doses of delta-9-tetrahydrocannabinol (THC) 20 mg, combined with placebo or with 40 mg dses of cannabinol (CBN) and cannabidiol (CBD), were given to volunteers. The combination of THC with CBN produced no detectable changes in the quality, intensity, or duration of the effects of THC alone. The THC-CBD combination tended to delay onset and prolong effects of THC, while making them somewhat more intense. Even this interactive effect was slight, providing no reason to abandon the current practice of basing doses of marihuana for clinical studies solely on THC content.