A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers

Abstract

Marijuana withdrawal contributes to the high relapse rates in individuals seeking treatment for marijuana-use disorders. Quetiapine, an atypical antipsychotic, reduces characteristic symptoms of marijuana withdrawal in a variety of psychiatric conditions, including mood lability, sleep disruption and anorexia. This human laboratory study investigated the effectiveness of quetiapine to decrease marijuana withdrawal and relapse to marijuana use in non-treatment-seeking marijuana smokers. Volunteers were maintained on placebo or quetiapine (200 mg/day) in this double-blind, counter-balanced, within-subject study consisting of two 15-day medication phases, the last 8 days of which were in-patient. On the first in-patient day, active marijuana [6.2% delta (9)-tetrahydrocannabinol (THC)] was repeatedly smoked under controlled conditions. For the next 3 days, inactive marijuana (0.0% THC) was available for self-administration (withdrawal). On the subsequent 4 days, active marijuana (6.2% THC) was available for self-administration (relapse). Volunteers (n = 14) who smoked an average of 10 marijuana cigarettes/day, 7 days/week, completed the study. Under placebo, withdrawal was marked by increased subjective ratings of negative mood, decreased sleep quality, and decreased caloric intake and weight loss. Compared with placebo, quetiapine improved sleep quality, increased caloric intake and decreased weight loss. However, quetiapine increased marijuana craving and marijuana self-administration during the relapse phase. These data do not suggest that quetiapine shows promise as a potential treatment for marijuana dependence.

Keywords: Marijuana; relapse; withdrawal.

Figure 1

Peak (mean ± SEM) subjective ratings of ‘Alert’ and marijuana and alcohol craving during experimenter-administered marijuana (MJ) smoking (6.2% THC) and marijuana withdrawal as a function of quetiapine dose. Participants rated each effect on a 100 mm line (0 mm = ‘not at all’; 100 mm = ‘extremely’). Data obtained from participants endorsing alcohol intake at least 1/week are portrayed for alcohol craving (N = 7). Under placebo conditions, significant differences between active marijuana administration and marijuana withdrawal are indicated by a bracket. A line above two adjacent bars indicates a significant difference between placebo and quetiapine conditions (* = p ≤ 0.05; ** = p ≤ 0.01; *** = p ≤ 0.001).

Figure 2

Representative peak (mean ± SEM) sleep ratings and Actiwatch sleep measure during active marijuana administration (6.2% THC) and marijuana withdrawal as a function of quetiapine dose. See Figure 1 legend for details.

Figure 3

Peak (mean ± SEM) subjective ratings of ‘Hungry,’ daily kcal intake (mean ± SEM), number of daily eating occasions (mean ± SEM), and change in body weight from baseline (mean ± SEM) during experimenter- administered marijuana (MJ) smoking (6.2% THC) and marijuana withdrawal as a function of quetiapine dose. See Figure 1 legend for details.

Figure 4

Representative peak (mean± SEM) performance on tasks during experimenter-administered marijuana (MJ) smoking (6.2% THC) and marijuana withdrawal as a function of quetiapine dose. See Figure 1 legend for details.

Figure 5

Number of puffs (mean ± SEM) and dollars spent (mean ± SEM) on active marijuana when participants were maintained on placebo or quetiapine. Significant differences between placebo and quetiapine condition indicated by * = p ≤ 0.05.