Cannabinoids dronabinol

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). 

The synthetic cannabinoids dronabinol and nabilone have antinau-seant/antiemetic effects that may benefit AIDS and cancer patients. 

Cannabinoids Dronabinol is available for use in chemotherapy-induced nausea and vomiting, but is associated with CNS marijuana effects ... 

The effects of oral cannabinoids (dronabinol or Cannabis sativa plant extract) in relieving pain and muscle spasticity have been studied in 16 patients with multiple sclerosis (mean age 46 years, mean duration of disease 15 years) in a double-blind, placebo-controlled, crossover... 

Svendsen KB, Jensen TS, Bach FW. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis Randomised double blind placebo controlled crossover trial. BMJ 2004 329(7460) 253. 

The client with cancer is not eating and has lost 15 lbs in the last month. The health-care provider has prescribed the cannabinoid dronabinol (Marinol). Which statement indicates the client needs more teaching concerning this medication ... 

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... 

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. 

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... 

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

A9-Tetrahydrocannabinol is the major psychoactive cannabinoid in marijuana (Cannabis sativa). Its synthetic form, dronabinol, became available in the U.S. in 1985 as an antiemetic for patients receiving emetogenic chemotherapy. However, it is seldom used as a first-line antiemetic because of its psychoactive effects, and its use is usually limited to patients who have a low tolerance or minimal response to other antiemetic drugs (see Chapter 18). 

Cannabinoids Marijuana derivatives, including dronabinol [droe NAB i nol] and nabilone, are effective against moderately emetogenic chemotherapy. However, they are seldom first-line antiemetics because of their serious side effects, including dysphoria, hallucinations, sedation, vertigo, and disorientation. In spite of their psychotropic properties (see p. 105), the antiemetic action of cannabinoids may not involve the brain synthetic cannabinoids having no psychotropic activity, nevertheless are antiemetic. 

In our 1987 review, we summarized the research and clinical experience in this area [1], Surprisingly, in spite of the enormous public interest in medical marijuana and countless articles in the daily press and magazines focused predominantly on this aspect of marijuana use, little progress has been reported on the antiemetic activity of cannabinoids in the last decade. Plasse et al. have reviewed the clinical experience gained over 7 years with dronabinol (d9-THC) in antiemetic treatment [117]. With doses of 7 mg/m2 or below, complete response was noted in 36% of the patients, 32% showed partial response and 32% showed no response. However, 65% displayed drowsiness and dizziness and 12% had dysphoric effects. Combination treatment of dronabinol with prochlorperazine (a dopamine receptor blocker widely used as an antipsychotic drug with antiemetic effects) was more effective than each drug alone [118]. 

By any standards, THC must be considered to be very safe, both acutely and during long-term exposure. This probably partly reflects the fact that cannabinoid receptors are virtually absent from those regions at the base of the brain that are responsible for such vital functions as breathing and blood pressure control. The available animal data are more than adequate to justify its approval as a human medicine, and indeed it has been approved by the FDA for certain limited therapeutic indications (generic name = dronabinol) (9). 

The use of cannabinoids has been studied in 62 patients with HIV-1 infection (143). Cannabinoids and HIV are of interest because there is the chance of an interaction between tetrahydrocannabinol and antiretroviral therapy. Tetrahydrocannabinol inhibits the metabolism of other drugs (144,145) and cannabinoids are broken down by the same cytochrome P-450 enzymes that metabolize HIV protease inhibitors. The subjects were randomly assigned to marijuana, dronabinol (synthetic delta-9-tet-rahydrocannabinol), or placebo, given three times a day, 1... 

The therapeutic uses of marijuana today arc much more circumscribed. For the most part synthetic products (such as dronabinol [trade name Marinol] and nabilonc [Cesamet]) that chemically resemble the cannabinoids have been used in current treatment efforts because they provide the active elements of THC in a more stable manner (see Joy ct al., 1999 Sussman, Stacy, Dent, Simon, Johnson, 1996). Synthetics also can provide better solubility. Unfortunately, a downside to the synthetics is the absence of the rapid effect experienced when marijuana is smoked. When synthetic THC is taken orally, it is broken down prior to entering the bloodstream and absorption thus is delayed. A recent development with promise is a cannabis oral spray (trade name Sativex), which has been approved in Canada for use as a painkiller for sufferers of multiple sclerosis. 

Delta-9-THC and some synthetic analogs are used therapeutically, for example, for nausea and vomiting produced by antineoplastic chemotherapy, analgesic, anticonvulsant for epilepsy, anti-inflammatory agent, appetite stimulant for patients with AIDS, as well as treatment for conditions such as asthma and glaucoma. Synthetic cannabinoids used therapeutically include dronabinol, nabilone, and levonamtradol. 

Droleptan " droperidol. dromostanolone propionate drostanolone. dronabinol [inn. usan] (NSC 134454 Deltanyne " Marinol ) is a constituent of marijuana. It is the (6aR,10aR)-(-)-trans-form of A -tetrahydrocannabinol. It is a cannabinoid receptor agonist and has euphoric, mild psychotropic (hallucinogenic) and ANTIEMETIC properties. 

The structure-activity relationships of dronabinol (32) on cannabinoid receptor activity have been investigated (see Table 15.14). Both the phenolic hydroxyl group and the C3 alkyl chain in (32) are critical for binding affinity. 

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