Cardiovascular effects of cocaine.
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Biomedical subjects
Publications and source records attributed to C R Schuster.
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Nine volunteer subjects were tested with intravenously administered cocaine hydrochloride in doses ranging from 4 to 32 mg, as well as 10 mg of dextroamphetamine sulfate. Measures of cardiovascular and subjective effects were made. Generally parallel dose-effect functions were obtained for heart rate, blood pressure, Addiction Research Center Inventory scores, Profile of Mood Scales, and subject ratings. A substantial effect on each of these variables was recorded after 8 mg of cocaine. The increase continued and peaked at approximately 16 mg after which it usually leveled off. Ten milligrams of dextroamphetamine generally had an effect comparable to 8 to 16 mg of cocaine.
The ability of the intravenous administration of mazindol (SaH 42-548) to act as a reinforcer in monkeys previously conditioned to self-administer cocaine was ascertained. Unit dosages i.e. dosage per injection, of 50 and 100 mug/kg resulted in self-administration rates significantly greater than that which occurred with saline. An inverse relationship existed between unit dosage and frequency of self-administration over the unit dosage range 50-200 mug/kg. The total mazindol dosage self-administration per session was however independent of unit dosage. Approximately 2-3 mg/kg was self-administered by each animal during a 4 hr session at each of the 3 unit dosages. This tends to indicate that the 200 mug/kg unit dosage was also reinforcing even though the self-administration rate was similar to that of saline. This study indicates that mazindol can serve as a reinforcer and that the relationship between total session intake, unit dosage, and self-administration frequency of mazindol are similar to these seen with other reinforcing psychomotor stimulant drugs.
The effects of chlorpromazine on shock avoidance and escape responding were determined using four human subjects lever pressing on a modified free operant avoidance schedule. Doses of chlorpromazine ranging from 50 to 100 mg and shock levels ranging from 0.35 to 3.0 mA were used. In general, the results showed that chlorpromazine suppressed avoidance responding at doses which did not suppress escape responding.
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Eleven Rhesus monkeys received injections of intravenous methamphetamine hydrochloride (Desoxyn) and/or intra-arterial 60% iothalamate meglumine (Conray) according to a schedule previously reported to produce marked radiological and pathological changes in the cerebral vasculature of the Rhesus monkey. While radiological changes consistent with impaired cerebral circulation were observed, they could not be correlated directly with the administration of intravenous methamphetamine because of the trauma and variability of the technique utilized. Moreover, significant pathological changes could not be found in animals given intravenous methamphetamine alone, intra-arterial iothalamate meglumine alone, or both drugs together. This was true for both drug naive and drug experienced monkeys. These results suggest: (1) radiological changes consistent with decreased cerebral blood flow are not necessarily pathognomonic for reported morphological lesions, and (2) further investigation is required to determine the specific factors necessary to cause the previously reported changes.
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A choice procedure was developed to compare the reinforcing efficacy of drug solutions delivered via intravenous catheters to rhesus monkeys. Choices were arranged between doses of cocaine or methylphenidate and saline, different doses of the same drug and doses of both drugs. In each session, monkeys were allowed to self-inject one solution five times in the presence of a stimulus. Thirty minutes after the fifth injection, a second solution could be self-injected five times in the presence of a different stimulus. Thirty minutes later, choice trials began in which both stimuli were present and monkeys could choose one of the two solutions. Rate of responding decreased with increases in dose for both cocaine (0.05-1.5 mg/kg) and methylphenidate (0.075-0.7 mg/kg). Response rates maintained by cocaine were 2 to 3 times higher than those maintained by methylphenidate. Drug was always chosen over saline. Higher doses of cocaine were preferred to lower doses except when both were above 0.5 mg/kg, when no preference was shown. Higher doses of methylphenidate were preferred over low doses, but compared to cocaine, a greater absolute difference between dose magnitude was required to demonstrate preference. When equal doses of cocaine and methylphenidate were compared, no preference was shown. On other comparisons between the drugs, the higher dose was generally preferred regardless of the drug. The reinforcing efficacy of drugs must be considered not only in terms of response rate maintained or reinforcement schedule but also with reference to concurrently available drugs.
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1 The pharmacological potencies of the resins from three different samples of Brazilian marihuana (A, B and C) were determined through corneal areflexia in rabbits, decrease of spontaneous motor activity and induction of catatonia in mice, and decrease of rope climbing performance of rats.2 The Delta(9)-tetrahydrocannabinol (Delta(9) THC) content of the marihuanas, measured by gas chromatography, was 0.82, 2.02 and 0.52%, respectively, for samples A, B and C. Approximately 2% cannabinol was present in samples A and B whereas the content of cannabidiol was approximately 0.1%.3 The petroleum ether extraction of the samples A, B and C yielded, respectively, 12.06, 14.56 and 4.26% of resin.4 In all animal tests resin B was nearly twice as active as resin A, whereas C was the weakest.5 The smoke of the marihuana samples was inhaled by 33 human subjects, under a double-blind standardized procedure. Pulse rate, a time production task and an evaluation of psychological effects were recorded.6 The smoke of 250 mg of sample B provoked disruption of the time production task, increased pulse rate, and induced strong psychological reactions in four of the six subjects who received it. Similar effects, although slightly smaller, were obtained with 500 mg of sample A. On the other hand, 500 mg of sample C did not differ from placebo.7 It is suggested that it is possible by means of animal tests to predict the potency of a marihuana sample in man.8 In parallel experiments, Delta(9)-THC was administered to other human subjects and to laboratory animals in a manner similar to that in which the marihuana samples were administered.9 Comparison of the results between the marihuanas and Delta(9)-THC showed that in man and in the laboratory animals marihuanas A and B induced effects two to four times greater than expected from their Delta(9)-THC content.10 It is suggested that there may be potentiation of the effects of Delta(9)-THC by other substances present in these marihuana samples.
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