Neither severe physical dependence, nor prominent withdrawal symptoms after abrupt termination of very heavy usage is suggested by some overseas experience (Charen and Perelman, 1946; Fraser, 1949; Ludlow, 1857, Marcovitz and Myers, 1944; Siler et al., 1933; Walton, 1938). Other studies, however, suggest marked psychological dependence from heavy use producing compulsive drug taking in very heavy users (Indian Hemp, 1893; Chopra and Chopra, 1957; Bouquet, 1944; Lambo, 1965).

Psychosomatic abstinence syndromes often reported were physical weakness, intellectual apathy, loss of appetite, flatulence, constipation, insomnia, fatigue, abdominal cramps and nervousness, restlessness, and headache. For most heavy users the syndrome of anxiety and restlessness seem to be comparable to that observed when a, heavy tobacco smoking American attempts to quit smoking.

However, the psychological dependence appears to be severe as evidenced by the f act that one group of subjects were unable to cease their habitual use although the frequency of use, was only eight to 12 times per month (Soueif, 1967). This psychological dependence may have made some users claim physical dependence so that the government did not terminate dispensing them their drug. Studies in the United States using must lower doses for shorter periods of time have revealed little if any evidence of psychological dependence (Bromberg, 1934 Mayors Committee, 1944; Williams et al., 1946).

Tolerance to the subjective and depressant effects of the drug (discussed in an earlier section) does probably occur in man, with heavy use. Thus, increasingly larger and more frequent doses become necessary to experience the desired effects.

Several investigators have recently studied the question of physiological and psychological dependence to Delta 9 THC in monkeys using intravenous self-injection techniques.

Deneau and Kaymakcalan (1971) demonstrated that no monkey initiated self-administration over a three-week period when given the opportunity to self-inject a behaviorly effective dose of 100 micrograms per kilogram of Delta 9 THC in a Tween solution. The researchers subsequently administered to these monkeys this dose every six hours. Tolerance developed to the behavioral effects within a few days. Dose administered was progressively increased up to 400 micrograms per kilogram over the course of a month. When the injections were abruptly discontinued, all six monkeys showed after twelve hours, behavioral and physiological changes described by the researchers as mild abstinence signs. Two of the six monkeys then initiated and maintained for several weeks the self-administration of THC.

The investigators believe these findings are evidence for mild psychological and physiological dependence on THC. However, vehicle controls were not included in the research design. Thus, the abstinence signs and subsequent behavior may possibly be accounted for by the biological effects in of the Tween vehicle.

Harris et al. (1972) utilized several procedures to maximize the possible conditions necessary for developing self-injection in monkeys. These procedures included: spontaneous Delta 9 THC self administration with no previous training to the technique; self-administration of A' THC after training, with cocaine alone and a mixture of cocaine and Delta 9 THC. Doses utilized ranged from 20 to 500 micrograms per kilogram suspended in polyvinylpyrrolidone. In all cases, monkeys failed to self -administer Delta 9 THC.

The researchers conclude that A' THC lacks the reinforcing effects of psychomotor stimulants and depressants which monkeys readily self infuse with no auxiliary incentives. Also Delta 9 THC lacks a reinforcing function even for monkeys that are well-trained with cocaine and have experienced several days of rather large quantities of Delta 9 THC during the early pleases of extinction of the cocaine reinforced response.

Finally, the results demonstrate that a two week period of exposure to Al THC (in a mixed solution with cocaine) does not result in the degree of homeostatic imbalance which occurs with morphine, ethanol, barbiturates and sometimes the amphetamines which accounts for the continued self-administration of these drugs.