Failure obtain “cannabis-directed behavior” and abstinence syndrome in rats chronically treated with Cannabis sativa extracts

Experiments were performed to verify whether chronic treatment with Cannabis saliva extracts would induce dependence and/or abstinence symptoms in rats. In Experiment one, rats ingested cannabis extract as the only fluid for 126 days. On days 1, 43, 48, 62, 80, 92 and 119 when the animals were in abstinence from previous administration of marihuana for 0 to 96 h, behavioral measures and choice tests between marihuana suspension and control solution were carried out; the rats preferred to drink the control solution and no behavioral symptoms indicating abstinence were noted. In Experiment two, rats were trained to drink a marihuana suspension or control solution in order to be rewarded with sweetened milk. After 22 sessions water was substituted for the milk. Extinction curves for both groups were similar, and in choice tests among cannabis suspension, water and control solution, the animals refused to drink the marihuana suspension. In Experiment three, rats received i.p. injections of a cannabis extract or control solution during 36 days. From days 37–40 the drugs were withheld and sensitivity to penty-lenetetrazol was assessed. Marihuana chronically treated rats were more resistant to convulsions and fewer died after pentylenetetrazol. In Experiment four, rats were treated with marihuana extract, control solution or sodium barbitone during 73 days. At days 74–76, when undergoing 24, 48 and 72 h of abstinence, the animals were exposed to sound from a bell. Animals in abstinence from barbitone showed a high incidence of convulsions; marihuana treated rats did not differ from control animals.