Ran-Nabilone

Uses

Ran-Nabilone is a synthetic delta-9-THC used in the treatment of anorexia and weight loss in HIV patients as well as nausea and vomiting in cancer chemotherapy.

Ran-Nabilone is indicated for the treatment of the nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. This restriction is required because a substantial proportion of any group of patients treated with Ran-Nabilone can be expected to experience disturbing psychotomimetic reactions not observed with other antiemetic agents.

Ran-Nabilone is also used to associated treatment for these conditions: Refractory Nausea and vomiting

How Ran-Nabilone works

Ran-Nabilone is an orally active synthetic cannabinoid which, like other cannabinoids, has complex effects on the central nervous system (CNS). It has been suggested that the antiemetic effect of nabilone is caused by interaction with the cannabinoid receptor system, i.e., the CB (1) receptor, which is a component of the endocannabinoid system of the body.

The endocannabinoid system is widely distributed throughout the central and peripheral nervous system (via the Cannabinoid Receptors CB1 and CB2) and plays a role in many physiological processes such as inflammation, cardiovascular function, learning, pain, memory, stress and emotional regulation, and the sleep/wake cycle among many others . CB1 receptors are found in both the central and peripheral nervous system, and are most abundant in the hippocampus and amygdala, which are the areas of the brain responsible for short-term memory storage and emotional regulation. CB2 receptors are mainly located in the peripheral nervous system and can be found on lymphoid tissue where they are involved in regulation of immune function .

Toxicity

Symptoms of overdose include difficulty in breathing, hallucinations, mental changes (severe), nervousness or anxiety (severe). Monkeys treated with Ran-Nabilone at doses as high as 2mg/kg/day for a year experienced no significant adverse events. This result contrasts with the finding in a planned 1-year dog study that was prematurely terminated because of deaths associated with convulsions in dogs receiving as little as 0.5mg/kg/day. The earliest deaths, however, occurred at 56 days in dogs receiving 2mg/kg/day. The unusual vulnerability of the dog is not understood; it is hypothesised, however, that the explanation lies in the fact that the dog differs markedly from other species (including humans) in its metabolism of Ran-Nabilone.

Food Interaction

• Avoid alcohol.
• Take with or without food. Food does not significantly affect absorption.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Ran-Nabilone Drug Interaction

Moderate: duloxetine, duloxetine, hydromorphone, hydromorphone, hydromorphone, hydromorphone, pregabalin, pregabalin, quetiapine, quetiapine, acetaminophen / codeine, acetaminophen / codeineUnknown: celecoxib, celecoxib, levothyroxine, levothyroxine, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Ran-Nabilone Disease Interaction

Moderate: cardiac disease, psychoses/depression, substance abuse, long QT

Volume of Distribution

The apparent volume of distribution of nabilone is about 12.5 L/kg.

Elimination Route

Ran-Nabilone appears to be completely absorbed from the human gastrointestinal tract when administered orally. Following oral administration of a 2 mg dose of radiolabeled nabilone, peak plasma concentrations of approximately 2 ng/mL nabilone and 10 ng equivalents/mL total radioactivity are achieved within 2.0 hours.

Half Life

The plasma half-life (T1/2) values for nabilone and total radioactivity of identified and unidentified metabolites are about 2 and 35 hours, respectively.

Elimination Route

The route and rate of the elimination of nabilone and its metabolites are similar to those observed with other cannabinoids, including delta-9-THC (dronabinol). When nabilone is administered intravenously, the drug and its metabolites are eliminated mainly in the feces (approximately 67%) and to a lesser extent in the urine (approximately 22%) within 7 days. Of the 67% recovered from the feces, 5% corresponded to the parent compound and 16% to its carbinol metabolite. Following oral administration about 60% of nabilone and its metabolites were recovered in the feces and about 24% in urine. Therefore, it appears that the major excretory pathway is the biliary system.

Innovators Monograph

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