Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study

Abstract

Rationale: Dronabinol (Δ(9)tetrahydrocannabinol) is approved for HIV-related anorexia, yet, little is known about its effects in HIV-positive marijuana smokers. HIV-negative marijuana smokers require higher than recommended dronabinol doses to experience expected effects.

Objectives: Employing a within-subjects, double-blind, placebo-controlled design, we assessed the effects of repeated high-dose dronabinol in HIV-positive marijuana smokers taking antiretroviral medication.

Methods: Participants (N = 7), who smoked marijuana 4.2 ± 2.3 days/week, resided in a residential laboratory for two 16-day stays, receiving dronabinol (10 mg QID) in one stay and placebo in the other. Efficacy was assessed with objectively verified food intake and body weight. Tolerability was measured with sleep, subjective, and cognitive assessments. For analyses, each inpatient stay was divided into two phases, days 1-8 and 9-16; we compared dronabinol's effects with placebo in each 8-day phase to investigate tolerance.

Results: Despite sustained increases in self-reported food cravings, dronabinol only increased caloric intake in the initial 8 days of dosing. Similarly, sleep quality was improved only in the first 8 days of dosing. Dronabinol's mood-enhancing effects were sustained across the 16-day inpatient stay. Dronabinol was well tolerated, causing few negative subjective or cognitive effects.

Conclusions: In HIV-positive marijuana smokers, high dronabinol doses safely and effectively increased caloric intake. However, repeated high-dose dronabinol appeared to result in selective tolerance to these effects. These findings indicate that HIV-positive individuals who smoke marijuana may require higher dronabinol doses than are recommended by the FDA. Future research to establish optimal dosing regimens, and reduce the development of tolerance, is required.

Figure 1

Dronabinol effects on daily caloric intake (top) and number of eating occasions (bottom) as a function of time. Data are daily means (± S.E.M.). Dronabinol/PBO was administered 4 times per day. Asterisks denote an increase from placebo (p< 0.01) in the indicated eight-day phase. PBO = Placebo

Figure 2

Dronabinol effects on subjective hunger (top) and fullness (fullness) ratings as a function of time. Data are means (± S.E.M.) of daily maximum scores. Dronabinol/PBO was administered 4 times per day. Asterisks denote an increase from placebo (p< 0.01) in the indicated eight-day phase. HSQ = Hunger and Satiety Questionnaire; PBO = Placebo

Figure 3

Dronabinol effects on self-reported positive affect (top) and sedation (bottom) ratings as a function of time. Data are means (± S.E.M.) of daily maximum scores. Dronabinol/PBO was administered 4 times per day. Asterisks denote an increase from placebo (p< 0.01) in the indicated eight-day phase. VAS = Visual Analogue Scale; PBO = Placebo

Figure 4

Dronabinol effects on objectively-measured sleep efficiency (REM + NREM sleep as a proportion of total time in bed; top left), objectively measured minutes awake (top right), self-rated satisfaction with sleep (bottom left), and self-ratings of frequency of waking (bottom right) as a function of time. Data are daily means (± S.E.M.). Dronabinol/PBO was administered 4 times per day. Asterisks denote an increase from placebo (p< 0.01) in the indicated eight-day phase. & denotes a decrease relative to placebo (p< 0.01). PBO = Placebo. N = 6 top left and top right panels due to equipment failure.