Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse

Abstract

Rationale: Only a small percentage of individuals seeking treatment for their marijuana use achieves sustained abstinence, suggesting more treatment options are needed.

Objectives: We investigated the effects of baclofen (study 1) and mirtazapine (study 2) in a human laboratory model of marijuana intoxication, withdrawal, and relapse.

Methods: In study 1, daily marijuana smokers (n = 10), averaging 9.4 (+/-3.9) marijuana cigarettes/day, were maintained on placebo and each baclofen dose (60, 90 mg/day) for 16 days. In study 2, daily marijuana smokers (n = 11), averaging 11.9 (+/-5.3) marijuana cigarettes/day, were maintained on placebo and mirtazapine (30 mg/day) for 14 days each. Medication administration began outpatient prior to each 8-day inpatient phase. On the first inpatient day of each medication condition, participants smoked active marijuana (study 1: 3.3% THC; study 2: 6.2% THC). For the next 3 days, they could self-administer placebo marijuana (abstinence phase), followed by 4 days in which they could self-administer active marijuana (relapse phase); participants paid for self-administered marijuana using study earnings.

Results: In study 1, during active marijuana smoking, baclofen dose-dependently decreased craving for tobacco and marijuana, but had little effect on mood during abstinence and did not decrease relapse. Baclofen also worsened cognitive performance regardless of marijuana condition. In study 2, mirtazapine improved sleep during abstinence, and robustly increased food intake, but had no effect on withdrawal symptoms and did not decrease marijuana relapse.

Conclusions: Overall, this human laboratory study did not find evidence to suggest that either baclofen or mirtazapine showed promise for the potential treatment of marijuana dependence.

Figures

Figure 1

Mean peak effects during marijuana administration (3.3%) and during marijuana abstinence as a function of baclofen dose (Caloric Intake and Cigarettes Smoked reflect daily means not peak). Maximum score for ratings =100 mm. Each graph represents 10 participants except for the two middle panels, which represent the 8 participants who smoked cigarettes. Asterisks indicate a significant difference between active and placebo medication (*p

Figure 2

Mean peak effects (top panels) and mean effects (bottom panels) during marijuana administration (6.2%) and during marijuana abstinence as a function of mirtazapine dose. Each graph represents 11 participants except for the two panels on the right, which only represent the 7 participants who smoked at least 5 cigarettes/day. See Figure 1 for details.

Figure 3

Mean effects on objective measures of sleep (top panels) and mean peak effects on subjective measures of sleep (bottom panels) during marijuana administration (6.2%) and during marijuana abstinence as a function of mirtazapine dose. See Figure 1 for details.