Effect of cannabis on pentobarbital-induced sleeping time and pentobarbital metabolism in the rat

The effects of two cannabis extracts with different cannabinoid compositions, as well of as pure Δ¹-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD), on pentobarbital metabolism were studied in the rat. Extract I, with high proportions of CBN and CBD relative to THC, when given by gavage 21·5, 40 or 63 hr before pentobarbital (30 mg/kg, i.p.), prolonged the sleeping time by 53, 42 and 21 per cent respectively. This effect was paralleled by decreases in the rate of disappearance of [¹⁴C]pentobarbital from the blood, and of pentobarbital metabolism by liver microsomal preparations in vitro. Extract II, with low relative proportions of CBN and CBD, did not have any significant effect on penobarbital metabolism or sleeping time. CBD alone, in the same dose as that given in Extract I, had very similar effects, while a dose of CBD equivalent to that given in Extract II had no effect. THC, CBN and CBD added to normal rat liver microsomes in vitro inhibited pentobarbital metabolism competitively, CBD being a much more potent inhibitor than THC and CBN. The CBD content may, therefore, be a significant factor in interactions between marijuana and other drugs.     

Effect of p-chlorophenylalanine on the loss and maintenance of tolerance to ethanol

Rats were rendered tolerant to the motor-impairing effects of ethanol by daily oral administration. Subsequently, ethanol was withdrawn and the effect of p-chlorophenylalanine (p-CPA) on tolerance loss was examined. In two separate studies it was demonstrated that p-CPA, in a dosage regimen that produces extensive depletion of brain serotonin (5-HT), accelerated tolerance loss. These experiments suggest that at least part of p-CPA's inhibitory effect on net tolerance development to ethanol can be accounted for by its accelerating effect on tolerance loss; however, an inhibitory effect on tolerance acquisition cannot be excluded. On the other hand, once tolerance was established, p-CPA did not affect the maintenance of tolerance to ethanol.     

Extent of possible rehabilitation of service personnel with ischaemic heart disease

Sixty unselected survivors from ischaemic heart disease, all male service personnel, were treated, within 1 to 6 months of recovery from the acute episode, by promotion of physical activity, correction of coronary risk factors, and routine use of nicoumalone and prenylamine lactate. The results showed that this approach was conducive to more rewarding rehabilitation than was obtained in 89 patients who, in the past, were on conventional treatment based on advice regarding weight, diet, and physical and mental activity. Thus within 1 to 30 months of treatment by this approach, out of 60 patients, 12 were fit for medical category A active service duties in operational areas in any part of the world in any terrain, including altitudes between 10,000 and 18,000 feet, 30 were fit for medical category B service duties in non-operational communication zones in any part of the world including altitudes below 10,000 feet, and 17 were fit for medical category C sedentary duties in non-operational areas in India only. One patient, who initially recovered from congestive heart failure, died while in a state of temporary unfitness for service. No patient was released from service on account of ischaemic heart disease. Against this, by the conventional approach, out of 89 patients, 81 were fit for medical category C sedentary duties in non-operational areas in India only, 4 were released from service, and 4 died.