Hans-R. Frischknecht

Behavioral effects of hashish in mice

The acute and subchronic effects of hashish extract (20 mg Δ9-THC/kg) on the social interactions between two drug-treated residents and an untreated intruder male were investigated. In this analysis 28 different behavioral elements were recorded.A single drug application suppressed all categories of behavior, except submissive behavior and flight, in dominant and subordinate residents. Treated animals were less active than controls and immobility was very frequent. An elevated total activity, due to an increase in non-social activities, was observed in the untreated intruder males of this group. Social investigation as well as submissive behavior and flight were reduced in these animals.On introduction of an untreated male after the fourth drug treatment of the residents, the drugged males showed tolerance to the sedative and most of the other behavioral effects of the drug, and intruder males behaved quite normally.The formation of a dominant-subordinate relation within the group was influenced neither by a single nor by repeated drug treatment.The acute and subchronic effects of hashish extract on social, especially aggressive behavior of males are compared to those described in previous papers and the variation in the results of the different studies is discussed.

Effects of multiple, chronic and early hashish exposure on mating behavior, nest-building and gestation in mice

1. The effects of hashish extract on social behavior were investigated in pairs of mice living together from mating to parturition. The drug was administered orally to both animals at a dose of 20 mg delta 9-tetrahydrocannabinol/kg three times a week, either (I) during the 3 weeks from mating to parturition, (II) during the 12 weeks from weaning to mating and parturition, or (III) only during the 3 weeks after weaning. 2. In the mating tests, an acute administration (I) caused a general sedation. Chronically treated animals (II) showed decreased sexual behavior and lower social investigations despite significantly more non-social activities. Early drug treatment (III) had no effect on mating behavior. In all three series of experiments the females had conceived by the next morning. 3. The nest-building behavior during pregnancy was suppressed after multiple (I) and chronic (II) drug administration. In early drug-treated animals (III) the transport of nesting material was only slowed down. Non-social activities were normal or increased in all three series. 4. Parturition was significantly delayed by one day after multiple (I) and chronic (II) drug administration. The birth weight was not affected, but the litter size was decreased after chronic drug treatment. Early drug administration (III) had no effects on these parameters. 5. In conclusion, whereas tolerance to the sedative effects of hashish developed very rapidly, the drug influences on social behavior were stable. Therefore, discussions on legalization of cannabis should pay attention to the drug effects on social behavior.

Actions of hallucinogens on ants (Formica pratensis)--III. Social behavior under the influence of LSD and tetrahydrocannabinol.

Abstract 1. 1. Ants were fed with sugar-water containing LSD-tartrate (100 μ/ml), or sugar-water with 10 vol% of Tween-80 containing Δ9-THC (1 mg/ml), using the two solvents as controls. 2. 2. Analyses of social contacts between one drug- or control-fed ant and 10 hungry nestmates showed decreased frequencies and durations of interactions (particularly food-sharing behavior) 9–24 hr following LSD-intake, whereas THC had little influence. 3. 3. Only slight differences from normal behavior were shown by LSD- and THC-fed worker ants in adopting queens from their own nest. 4. 4. With large groups of ants, multiple feedings with LSD always impaired the behavior of foraging workers, whereas domestic workers performed normally. When drugged food was offered, the activity between nest and feeding place was relatively lower in the morning. THC-feedings did not cause any distinct behavioral changes, but the activity between nest and feeding-place increased compared to that preceding and succeeding control periods.

Actions of hallucinogens on ants (Formica pratensis)—II. Effects of amphetamine, LSD and delta-9-tetrahydrocannabinol

Abstract 1. d,l -Amphetamine sulfate, d -lysergic acid diethylamide tartrate (LSD) and delta-9-tetrahydrocannabinol (THC) were administered to ants in several doses either orally in food, or by injection into the abdominal cavity. 2. Amphetamine, injected in doses of 1 or 10 μg/ant caused an increase in intraspecific aggression. Sugar-water containing 1 or more mg/ml amphetamine was generally refused. 3. Application of 20 ng LSD or more by either route typically impaired locomotion. Dependent on the dose administered, these symptoms vanished, or led to death. 4. To dissolve THC, we mixed 10 vol% of Tween-80 with physiological NaCl-solution, or with sugar-water. Drug doses of 2 μg injected, or 3–4 μg orally did not cause conspicuous changes in behavior.

Behavioural effects of hashish in mice in comparison with other psychoactive drugs

1. The behavioural effects of hashish extract (10 mg delta 9-THC/kg) were compared to those of morphine (20 mg/kg), diazepam (10 mg/kg), imipramine (10/kg), amphetamine (10 mg/kg) and chlorpromazine (10 mg/kg) by testing male mice in a resident-intruder situation. 2. The drugs were given either to the resident or to the intruder male. 3. Hashish extract similar to diazepam and chlorpromazine reduced social activities in resident and intruder males. 4. Intruder males treated with hashish or diazepam were more frequently attacked and submission and light was increased. 5. Amphetamine and morphine stimulated locomotion and non-social activities but impaired social behaviour especially in residents. 6. Imipramine increased aggressive behaviour in resident and intruder males.

Actions of hallucinogens on ants (Formica pratensis)—I. Brain levels of LSD and THC following oral administration

Abstract 1. Ants having free access for 2 days to sugar-water containing 500 μg/ml LSD showed (by fluorescence spectrophotometry) drug levels of about 7 ng in their brain. 2. The kinetics of drug uptake into the head-ganglia were determined by liquid scintillation counting after a single oral administration of tritiated LSD or THC. 3. Peak values were found at 12–24 hr (LSD) and at 24–48 hr (THC) respectively after drug application. Related to drug concentrations of 100 μg/ml in the food, the maxima corresponded to 150 pg LSD and 800 pg THC respectively per brain (or about 0.04% and 0.22% of the ingested drug amount). 4. Drug elimination from the nervous system was faster for LSD (half-time about 12 hr) than for THC (half-time 3 days). 5. The results were connected with attributes of the blood-brain barrier and peculiarities of the alimentary tract in ants.