The reinforcing, self-reported performance and physiological effects of Delta9-tetrahydrocannabinol, triazolam, hydromorphone, and methylphenidate in cannabis users

Abstract

The use of illicit prescription drugs is common in cannabis users; however, the effects of few psychoactive drugs have been characterized in this population. In this study, Delta-tetrahydrocannabinol (i.e. Delta-THC), triazolam, hydromorphone, and methylphenidate were administered to cannabis users (n=8). Subjects completed the multiple-choice procedure to assess drug reinforcement, as well as self-report questionnaires and performance tasks; physiological assessments were also conducted. Only Delta-THC increased the crossover point on the multiple-choice procedure, but all of the drugs increased ratings on one or more 'positive' drug-effect questionnaire items, as well as items specific for each drug. Triazolam produced the most robust performance impairment, except on a time reproduction task, which was impacted to a greater degree by Delta-THC. Delta-THC elevated heart rate and decreased temperature, triazolam increased heart rate, methylphenidate elevated all cardiovascular indices, and hydromorphone reduced respiration. The effects of the drugs tested in this study were generally consistent with their known pharmacology, although minimal responses to hydromorphone were observed. Future research to directly compare the effects of different psychoactive drugs in cannabis users and nonusers would be useful for identifying potential differences in drug effects as a function of use history.

Figure 1

Left Panel: Peak (maximum value) Visual Analog Scale ratings for Δ⁹-THC on the subject-rated, drug-effect questionnaire items Stoned, Thirsty, Like Drug Effects and Take Again. Middle Panel: Peak (minimum value) effects of Δ⁹-THC on index finger skin temperature. Right Panel: Peak (maximum value) effects of Δ⁹-THC on heart rate. Filled symbols indicate values that are significantly different from placebo. The horizontal axis represents the drug dose in mg; PL denotes placebo. Data points show means of 8 subjects. Uni-directional brackets indicate 1 SEM.

Figure 2

Left Panel: Peak (maximum value) Visual Analog Scale ratings for triazolam on the subject-rated, drug-effect questionnaire item Pay For. Middle Panel: Peak (minimum value) effects of triazolam on the number of chains completed from the acquisition and performance versions of the RA Task. Right Panel: Peak (minimum value) effects of triazolam on the number of correct trials completed and number of correct trials on the DSST. All other details are as in Figure 1.

Figure 3

Left Panel: Peak (maximum value) Visual Analog Scale ratings for methylphenidate on the subject-rated, drug-effect questionnaire items Rush and Stimulated. Middle Panel: Peak (maximum value) effects of methylphenidate on heart rate. Right Panel: Peak (maximum value) effects of methylphenidate on systolic and diastolic blood pressure. All other details are as in Figure 1.

Figure 4

Left Panel: Peak (maximum value) effects of hydromorphone on diastolic blood pressure. Middle Panel: Peak (minimum value) effects of hydromorphone on respiration rate. Right Panel: Peak (minimum value) effects of hydromorphone on the number of chains completed on the RA task. All other details are as in Figure 1.