Dronabinol

(USAN, rINN)
Dronabinol Chemical formula
Synonyms: Dronabinolum; NSC-134454; Δ 9 -Tetrahydrocannabinol; Δ 9 -THC. (6aR,10aR)-6a,7,8,10a-Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol.
Cyrillic synonym: Дронабинол.

💊 Chemical information

Chemical formula: C21H30O2 = 314.5.
CAS — 1972-08-3.
ATC — A0 4AD10.
ATC Vet — QA04AD10.

Pharmacopoeias.

In US.

USP 31

(Dronabinol). Store at a temperature between 8° and 15° in airtight glass containers in an inert atmosphere. Protect from light.

💊 Adverse Effects and Precautions

As for Nabilone. The most frequent adverse effects of dronabinol include abdominal pain, nausea and vomiting, dizziness, euphoria, paranoid reactions, and somnolence. Seizures and seizure-like activity have been reported; dronabinol should be used with caution in those with a history of seizure disorders, and therapy should be stopped if seizures occur.

Abuse.

The abuse liability of dronabinol was rated as being substantially lower than that of cannabis.1
1. WHO. WHO expert committee on drug dependence: thirty-third report. WHO Tech Rep Ser 915 2003. Available at: http:// libdoc.who.int/trs/WHO_TRS_915.pdf (accessed 03/07/08)

Breast feeding.

US licensed product information states that dronabinol is concentrated in breast milk and recommends that it should not be used in breast-feeding mothers.

💊 Pharmacokinetics

After oral doses dronabinol is slowly and erratically absorbed from the gastrointestinal tract; the bioavailability of an oral dose is about 10 to 20%, due to extensive first-pass metabolism. Peak plasma concentrations of dronabinol and its 11-hydroxy metabolite are achieved about 2 to 4 hours after a dose by mouth. It is widely distributed and is extensively protein bound, with a volume of distribution of about 10 litres/kg. Elimination is biphasic, with an initial half-life of about 4 hours, and a terminal half-life of about 25 to 36 hours. Dronabinol is extensively metabolised, mainly in the liver by cytochrome P450 isoenzymes; the primary metabolite, 11-hydroxydronabinol is also active. The 11-hydroxy metabolite is converted to other, more polar and acidic compounds which are excreted in faeces via the bile, and in the urine. About 50% of an oral dose is recovered in faeces within 72 hours and 10 to 15% in urine. Many of the metabolites have relatively prolonged halflives, and accumulation may occur with repeated dosage. Dronabinol is distributed into breast milk and crosses the placenta.
1. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 2003; 42: 327–60
2. McGilveray IJ. Pharmacokinetics of cannabinoids. Pain Res Manag 2005; 10: 15A–22A.

💊 Uses and Administration

Dronabinol, the major psychoactive constituent of cannabis, has antiemetic properties and is used for the control of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetics. The usual initial oral dose of dronabinol is 5 mg/m2 given 1 to 3 hours before the first dose of the antineoplastic drug with subsequent doses being given every 2 to 4 hours after chemotherapy to a maximum of 4 to 6 doses daily. If necessary, the dose may be increased by increments of 2.5 mg/m2 to a maximum dose of 15 mg/m2, if adverse effects permit. Dronabinol also has appetite-stimulant effects and is used in the treatment of anorexia associated with weight loss in patients with AIDS. For this purpose 2.5 mg may be taken twice daily, before lunch and supper, reduced to a single 2.5-mg dose in the evening in patients who tolerate the drug poorly. If necessary, and if adverse effects permit, doses may also be increased up to 20 mg daily in divided doses. Dronabinol is used with cannabidiol, another cannabinoid, in a buccal spray preparation as adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis in adults; this combination is also used as adjunctive analgesic treatment in adult patients with advanced cancer and is under investigation for a number of other conditions.
1. Voth EA, Schwartz RH. Medicinal applications of delta-9-tetrahydrocannabinol and marijuana. Ann Intern Med 1997; 126: 791–8
2. Williamson EM, Evans FJ. Cannabinoids in clinical practice. Drugs 2000; 60: 1303–14
3. Tramer MR, et al. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 2001; 323: 16–21
4. Berman JS, et al. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain 2004; 112: 299–306
5. Costa B. On the pharmacological properties of Delta9-tetrahydrocannabinol (THC). Chem Biodivers 2007; 4: 1664–77
6. Beaulieu P, Ware M. Reassessment of the role of cannabinoids in the management of pain. Curr Opin Anaesthesiol 2007; 20: 473–7.

Alzheimer’s disease.

There is some suggestion1 that dronabinol may decrease agitation in patients with

Alzheimer’s disease.

1. Volicer L, et al. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 1997; 12: 913–19.

Anorexia.

Dronabinol is used for the management of anorexia in patients with HIV-associated wasting. However, although dronabinol may stimulate appetite and prevent weight loss,1 it does not appear to produce significant weight gain, and may produce less benefit than megestrol acetate.2 Benefits were also less than those of megestrol in patients with anorexia associated with malignant disease.3
1. Beal JE, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 1995; 10: 89–97
2. Timpone JG, et al. The safety and pharmacokinetics of singleagent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. AIDS Res Hum Retroviruses 1997; 13: 305–15
3. Jatoi A, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol 2002; 20: 567–73.

Multiple sclerosis.

Anecdotal evidence has suggested that cannabinoids might improve symptoms in patients with multiple sclerosis; a review1 considered evidence of effectiveness to be lacking. In a large placebo-controlled study, treatment with dronabinol or oral cannabis extract had no benefit on objective assessment of spasticity;2 however, there were improvements in walking time, and subjective improvements in both spasticity and pain. A subsequent small controlled study found dronabinol to have a modest but clinically relevant effect on central neuropathic pain in patients with multiple sclerosis.3 Dronabinol is used with cannabidiol, another cannabinoid, in a buccal spray preparation for the symptomatic relief of neuropathic pain in multiple sclerosis in adults.
1. Killestein J, et al. Cannabinoids in multiple sclerosis: do they have a therapeutic role? Drugs 2004; 64: 1–11
2. Zajicek J, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet 2003; 362: 1517–26
3. Svendsen KB, et al. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ 2004; 329: 253–7.

Tourette’s syndrome.

Preliminary studies1,2 indicate that dronabinol may reduce tic severity in Tourette’s syndrome.
1. Müller-Vahl KR, et al. Treatment of Tourette’s syndrome with
Δ -tetrahydrocannabinol (THC): a randomized crossover trial.
Pharmacopsychiatry 2002; 35: 57–61
2. Müller-Vahl KR, et al. Δ -Tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J Clin Psychiatry 2003; 64: 459–65.

💊 Preparations

USP 31: Dronabinol Capsules.

Proprietary Preparations

Canad.: Marinol; Israel: Ronabin†; S.Afr.: Elevat†; USA: Marinol. Multi-ingredient: Canad.: Sativex.
Published January 06, 2019.