Dronabinol (delta-9-tetrahydrocannabinol), a synthetic cannabinoid, has been used both as an antiemetic (with potency similar to that of prochlorperazine) and as an appetite stimulant in patients with both HIV- and cancer-related weight loss [13-17]. Appetite stimulation with dronabinol treatment was suggested by data from phase II studies in patients with cancer-related anorexia [15]. In a 6-week, dose-ranging study, 30 patients with advanced cancer received 2.5 mg of dronabinol daily, 2.5 mg twice daily, or 5 mg once a day. Weight loss continued in all treatment groups, although the rate of weight loss was decreased compared to baseline weight changes. Mood and appetite were improved in patients who were treated with 5 mg daily.

The only randomised, placebo-controlled study of dronabinol as an appetite stimulant was carried out in patients with AIDS-related wasting [17]. One hundred and thirty-nine patients were enrolled, 88 of whom (63%) were evaluable for efficacy. Dronabinol 2.5 mg twice daily, as compared with placebo, led to greater improvement in patient-reported appetite (p = 0.01), a trend towards weight gain after 6 weeks of treatment (+0.1 kg and -0.4 kg, respectively; p = 0.21), improvement in mood (p = 0.005), and decreased nausea (p = 0.05). Forty-three per cent of the dronabinol-treated patients, as compared with 13% of the placebo-treated patients (p < 0.001), experienced treatment-related toxicities. Neurological toxicity, occurring in 35% of the dronabinol-treated patients versus 9% of those receiving placebo (p < 0.001), was the primary basis for the difference in toxicity rates across the study arms. Dose reductions were required by 18% of the dronabinol-treated group for neurological toxicity. Euphoria, dizziness, thinking abnormalities and somnolence were the most frequent dose-limiting toxicities.

After completion of the 6-week, randomised study, patients were eligible to receive up to 1 year of open-label dronabinol. Of the 90 patients for whom data are available from the study extension, patient-reported appetite stimulation was maintained for at least 6 months and was associated with an increase in body weight of at least 2 kg in 39% of the patients. However, the lack of objective measures of increased appetite (e.g., increases in caloric intake) or evidence of weight gain in the majority of dronabinol-treated patients suggests limited usefulness of this agent.

Appetite stimulation by cannabinoids is highly variable and does not generally translate into weight gain. Toxicities are significant, particularly in elderly patients, who appear more sensitive to dronabinol's neurological toxicity.

If a decision is made to prescribe dronabinol, it has reasonably good tolerance at a dose of dronabi-nol 2.5 mg three times daily. Elderly patients, however, should probably be started at a lower dose, 2.5 mg once daily, with escalation as tolerated.

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