In phase 1 of the study, 3 mg/kg daily of cannabidiol (CBD) was given for 30 days to 8 healthy human volunteers. Another 8 volunteers received the same number of identical capsules containing glucose as placebo in a double-blind setting. Neurological and physical examinations, blood and urine analysis, ECG and EEG were performed at weekly intervals. In phase 2 of the study, 15 patients suffering from secondary generalized epilepsy with temporal focus were randomly divided into two groups. Each patient received, in a double-blind procedure, 200-300 mg daily of CBD or placebo. The drugs were administered for as long as 4½ months. Clinical and laboratory examinations, EEG and ECG were performed at 15- or 30-day intervals. Throughout the experiment the patients continued to take the antiepileptic drugs prescribed before the experiment, although these drugs no longer controlled the signs of the disease. All patients and volunteers tolerated CBD very well and no signs of toxicity or serious side effects were detected on examination. 4 of the 8 CBD subjects remained almost free of convulsive crises throughout the experiment and 3 other patients demonstrated partial improvement in their clinical condition. CBD was ineffective in 1 patient. The clinical condition of 7 placebo patients remained unchanged whereas the condition of 1 patient clearly improved. The potential use of CBD as an antiepileptic drug and its possible potentiating effect on other antiepileptic drugs are discussed.

Clinical trials with cannabidiol (CBD) in healthy volunteers, insomniacs, and epileptic patients conducted in the authors' laboratory from 1972 up to the present are reviewed. Acute doses of cannabidiol ranging from 10 to 600 mg and chronic administration of 10 mg for 20 days or 3 mg/kg/day for 30 days did not induce psychologic or physical symptoms suggestive of psychotropic or toxic effects; however, several volunteers complained of somnolence. Complementary laboratory tests (EKG, blood pressure, and blood and urine analysis) revealed no sign of toxicity. Doses of 40, 80, and 160 mg cannabidiol were compared to placebo and 5 mg nitrazepam in 15 insomniac volunteers. Subjects receiving 160 mg cannabidiol reported having slept significantly more than those receiving placebo; the volunteers also reported significantly less dream recall with the three doses of cannabidiol than with placebo. Fifteen patients suffering from secondary generalized epilepsy refractory to known antiepileptic drugs received either 200 to 300 mg cannabidiol daily or placebo for as long as 4.5 months. Seven out of the eight epileptics receiving cannabidiol had improvement of their disease state, whereas only one placebo patient improved.

The effects of cannabidiol (CBD) were compared to those produced by haloperidol in rats submitted to experimental models predictive of antipsychotic activity. Several doses of CBD (15-480 mg/kg) and haloperidol (0.062-1.0 mg/kg) were tested in each model. First, CBD increased the effective doses 50% (or) ED50 of apomorphine for induction of the sniffing and biting stereotyped behaviors. In addition, both CBD and haloperidol reduced the occurrence of stereotyped biting induced by apomorphine (6.4 mg/kg), increased plasma prolactin levels and produced palpebral ptosis, as compared to control solutions. However, CBD did not induce catalepsy even at the highest doses, in contrast to haloperidol. Such a pharmacological profile is compatible with that of an "atypical" antipsychotic agent, though the mechanism of action is uncertain and may not be identical to that of the dopamine antagonists.

The open field test used to study the behavioral alterations induced by psychotropic drugs is based mainly in the defecation, ambulation, rearing and grooming scores presented by animals subjected to the test. Because of the criticisms raised against the defecation score as a measure of the central effects of drugs, in the present experiment a modification of the test is proposed for the rat. The main points that characterize the new procedure are: (1) defecation scores are not considered; (2) besides ambulation, rearing and grooming, immobility was also recorded; (3) the total time of observation was increased, and (4) the stimuli, usually presented simultaneously in the open field (light and noise), were presented separately. The results obtained suggest that it is possible to differentiate classes of psychotropic drugs, without taking the defecation and grooming scores into consideration. Besides stimulants that evoked a characteristic pattern of behavior, neuroleptics could be differentiated from anxiolytics. Similarities, according to the dose, between barbiturates and anxiolytics were detected. Under LSD a peculiar pattern of behavior characterized by a large reactivity to light was observed.