Dronabinol

Dronabinol. Marinol ( ii7R-/n7 j )-6i7,7,8,I0i7-tetrahydro-6,6,9-trimethyl-3-pentyl-6JT-diben2o(B,D) pyran-I-ol is the principal psychoactive substance present in Cannabis sativa F., ie, marijuana. It is a controlled substance, formulated in sesame oil and encapsulated in soft gelatin capsules for oral adrninistration. 

Dronabinol is indicated for the treatment of the nausea and vomiting produced by cancer chemotherapy in patients who have failed to respond adequately to other conventional treatments. This agent may be habit forming and can be expected to produce disturbing psychomimetic reactions. It should only be used under close supervision. 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

Dronabinol is the only currently available derivative of THC, which is a derivative of the active substance found in marijuana Dronabinol is a second-line antiemetic and is used after treatment with other antiemetics has failed. 

Take granisetron (Kytril), dronabinol (Marinol), or ondansetron (Zofran) before antineoplastic chemodierapy (oral, intravenous) about 30 minutes before the chemodierapy treatment. Take dolasetron mesylate (Anzemet) orally at least 1 hour before... 

On the market are two drugs imder the trade names of Dronabinol, which is the generic name of trans-A9-THC, and Marinol, which is a medicine containing synthetic dronabinol in sesame oil for oral intake, distributed by Unimed Pharmaceuticals. 

Fig. 5) with olivetol (5.2) in the presence of boron trifluoride etherate, BF3 0C(C2H5)2 with CBD as a key intermediate. This one-step synthesis of A9-THC is also used for the production of synthetic dronabinol, which is used in the medicinal application named Marinol. The mechanism of this synthesis is particular described by Razdan et al. [71] and is shown in Fig. 5... 

A serious problem in the early Western medicinal use of C. sativa, mainly as a tincture, was its highly variable activity and inconsistent results. Medicinal preparations have to handle several particularities due to the structure of the active ingredients of C. sativa. The identity of the main active constituent of C. sativa, A9-tetrahydrocannabinol (INN dronabinol) remained unknown until 1964 [128] standardized C. sativa preparations were not available. The plant itself is found in several different chemotypes, which added to the unpredictable nature of early medicinal preparations. 

So, the 20th century actually led to an almost total disappearance of C. sativa for medicinal purposes. The only source for THC, which became the focus of scientific research, was fhe rafher fedious exfracfion and purification from confiscated hashish or marihuana. In 1972 the first commercially viable total synthesis of A9-THC was established and it became the first cannabinoid available as a modern medicine in the form of soft gel capsules (the active ingredient being called dronabinol from tetrahydrocannabinol) under the trade name Marinol for the prevention of nausea and vomiting during cancer chemotherapy. 

Standardised preparations of cannabinoid agonists are available for therapeutic use in some countries [238]. Dronabinol (Marinol ), an oral preparation of A -THC (67), is used clinically as an appetite stimulant in AIDS patients and an antiemetic in cancer chemotherapy. A synthetic analogue of (67), nabilone (Cesamet ), (381), is also used to suppress nausea and vomiting in cancer chemotherapy. 

Cannabinoids have antiemetic activity when used alone or in combination with other antiemetics.5 Dronabinol and nabilone are commercially available oral formulations used for preventing and treating refractory CINV.5,10 Dronabinol is also used to treat anorexia and weight loss associated with human immunodeficiency virus (HIV) infection. Cannabinoids are thought to exert their antiemetic effect centrally, although the exact mechanism of action is unknown.1,10 Sedation, euphoria, hypotension, ataxia, dizziness, and vision difficulties can occur with cannabinoids. 

Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, Lefkowitz L, Plasse TF and Shepard KV (1995). Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Journal of Pain and Symptom Management, 10, 89-97. 

When compared with conventional antiemetics, oral nabilone and oral dronabinol were slightly more effective than active comparators in patients receiving moderately emetogenic chemotherapy regimens. 

Chlorpromazine, prochlorperazine, promethazine, methylprednisolone, lorazepam, metoclopramide, dexamethasone, or dronabinol may be used for adult patients. Around the clock dosing should be considered. The choice of specific agent should based on patient specific factors, including potential for adverse drug reactions, and cost. SSRIs are effective for breakthrough nausea and vomiting but they are not superior to the less expensive antiemetics above. 

Much debate has been waged over medicinal uses of cannabis. Several therapeutic uses have been proposed, including antiemetic, analgesic, appetite stimulant, and muscle relaxant. A synthetic cannabinoid, dronabinol (Marinol) has been marketed for clinical treatment of appetite loss, nausea, and vomiting. Although synthetic, it is identical to the main psychoactive chemical constituent of cannabis (A9-THC). 

Cannabinoids produced positive results for treatment of AIDS-related anorexia. Positive results of open trials were later confirmed with methodologically controlled studies. Dronabinol (2.5 mg PO twice daily) produced consistent and substantial improvement in appetite in patients with AIDS (Beal et al. 1995, 1997). Patients also reported improved... 

Beal JE, Olson R, Lefkowitz L, Laubenstein L, Bellman P, Yangco B, Morales JO, Murphy R, Powderly W, Plasse TF, et al. (1997). Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. J Pain Symptom Manage. 14(1) 7-14. 

Calhoun SR, Galloway GP, Smith DE. (1998). Abuse potential of dronabinol (Marinol). J Psychoactive Drugs. 30(2) 187-96. 

Plasse TF, Gorter RW, Krasnow SH, Lane M, Shepard KV, Wadleigh RG. (1991). Recent clinical experience with dronabinol. Pharmacol Biochem Behav. 40(3) 695-700. 

Effect of dronabinol on nutritional status in FIIV infection. Ann Pharmacother. 27(7-8) 827-31. 

Dronabinol (46)/ Cannabidol (47) (Sativex ) Dronabinol (46)/ Cannabidol (47) Cannabinoids NPs Plant Pain Suppresses neurotransmitter release 429 38... 

Dronabinol (46) and cannabidol (47) (Sativex GW Pharmaceuticals, 2005), as a mixture formulation named as Sativex (tradename), the world s first pharmaceutical prescription medicine derived from the cannabis plant Cannabis sativa The drug (a mixture of dronabinol (46) and... 

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