In a recent study of human subjects, researchers used drug discrimination testing to evaluate the role of the GABA_B receptor subtype (you will learn more about GABA receptors in Chapter 8) in the discriminative-stimulus effects of Δ⁹-tetrahydrocannabinol (THC), the active ingredient in marijuana (Lile et al., 2012). Subjects were evaluated for psychomotor performance with tests of balance, finger-to-nose coordination, and gait, as well as several cognitive tasks. Physiological assessments such as heart rate and body temperature were made, and self-report questionnaires of their subjective experience (anxious, forgetful, stoned, and others) were used. The subjects were 18-to-30-year-old marijuana users from the community. The subjects learned to discriminate orally administered (30 mg) THC from placebo, using computer-displayed circles labeled “Drug X” and “Not Drug X” on a fixed-interval, 1-second schedule for 60 seconds. Points accumulated on the correct selections were exchanged for money (28 cents per point up to a maximum of $50 per session). On average, it took 4.3 training sessions to achieve discrimination.

On the test day, administration of the GABA_B agonist baclofen produced THC-appropriate responding, which suggests that baclofen was subjectively experienced as similar to THC. Furthermore, when baclofen was given along with THC, drug-appropriate responding was enhanced, indicating that baclofen potentiated the effect of THC. Surprisingly, although baclofen alone produced THC responding, it did not produce subjective interoceptive effects according to the self-reporting. This difference suggests that drug discrimination testing was more sensitive in detecting internal cues than was self-reporting. Apparently, the subjects were not aware of the internal cues that guided their behavior. However, the GABA_B agonist did enhance self-reported subjective effects when administered along with THC. The fact that baclofen potentiated some of the physiological effects of THC suggests a role for the GABA_B receptor in those effects. It also suggests that concomitant administration of low doses of the two drugs might be useful therapeutically because side effects of each of the drugs would be minimized. Baclofen is currently used to reduce the spasticity associated with multiple sclerosis, and THC (Dronabinol) is useful for reducing anorexia in patients with AIDS and for reducing nausea and vomiting in patients undergoing chemotherapy (see Web Box 14.1). Because baclofen can be substituted for THC, others have suggested the potential use of baclofen for reducing some of the signs of withdrawal from THC, which would encourage further abstinence. Clearly, this preliminary research is only the first step toward practical application.

Reference

Lile, J. A., Kelly, T. H., and Hays, L. R. (2012). Separate and combined effects of the GABA_B agonist baclofen and Δ⁹-THC in humans discriminating Δ⁹-THC. Drug Alcohol Depend., 126, 216–223.