Separate and combined effects of gabapentin and [INCREMENT]9-tetrahydrocannabinol in humans discriminating [INCREMENT]9-tetrahydrocannabinol

Abstract

The aim of the present study was to examine a potential mechanism of action of gabapentin to manage cannabis-use disorders by determining the interoceptive effects of gabapentin in cannabis users discriminating [INCREMENT]-tetrahydrocannabinol ([INCREMENT]-THC) using a pharmacologically selective drug-discrimination procedure. Eight cannabis users learned to discriminate 30 mg oral [INCREMENT]-THC from placebo and then received gabapentin (600 and 1200 mg), [INCREMENT]-THC (5, 15, and 30 mg), and placebo alone and in combination. Self-report, task performance, and physiological measures were also collected. [INCREMENT]-THC served as a discriminative stimulus, produced positive subjective effects, elevated heart rate, and impaired psychomotor performance. Both doses of gabapentin substituted for the [INCREMENT]-THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of [INCREMENT]-THC when administered alone. When administered concurrently, gabapentin shifted the discriminative-stimulus effects of [INCREMENT]-THC leftward/upward, and combinations of [INCREMENT]-THC and gabapentin generally produced larger effects on cannabinoid-sensitive outcomes relative to [INCREMENT]-THC alone. These results suggest that one mechanism by which gabapentin might facilitate cannabis abstinence is by producing effects that overlap with those of cannabinoids.

Figure 1

Separate and combined effects of Δ⁹-THC and gabapentin on Δ⁹-THC-appropriate responding on the drug-discrimination task. Filled symbols indicate values that are significantly different from placebo. Asterisks indicate combinations of Δ⁹-THC and gabapentin that are significantly different from that dose of Δ⁹-THC alone. The x-axis represents the Δ⁹-THC dose in mg; PL denotes placebo. Data points show means of 8 subjects. Uni-directional brackets indicate 1 SEM.

Figure 2

Peak (maximum value) Visual Analog Scale ratings for Δ⁹-THC and gabapentin, alone and in combination, on the drug-effect questionnaire items Good Effects, High, Like Drug and crossover point values (square root transformation) from a Multiple Choice Procedure. All other details are as in Figure 1.

Figure 3

Peak number of chains completed and total responses during the acquisition component of the repeated acquisition task (minimum value) for Δ⁹-THC and gabapentin, alone and in combination. All other details are as in Figure 1.

Figure 4

Peak (maximum value) heart rate and systolic blood pressure for Δ⁹-THC and gabapentin, alone and in combination. All other details are as in Figure 1.