Nausea cannabinoids

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. 

The reduction of nausea in patients taking anti-cancer drug therapy is probably the most widely researched area for cannabis therapy. A number of these studies have shown that oral administration of isolated cannabinoids produce significant improvements, particularly for those patients who have failed to respond to standard antinausea treatments during chemotherapy (see Tortorice and O Connell, 1990 for a comprehensive review). Patients and oncologists have subjectively reported that smoked marijuana is as safe (in this patient group) and effective as isolated oral cannabinoids, but more systematic research trials are required. 

The efficacy of cannabinoids as compared to SSRIs for CINV has not been studied. They should be considered for the treatment of refractory nausea and vomiting in patients receiving chemotherapy. 

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). 

I. 18-1.62), number-needed-to-treat (NNT) was 6 for complete control of nausea relative risk was 1.28 (Cl 1.08-1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles relative risk 2.39 (2.05-2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids high 10.6 (6.86-16.5), NNT 3 sedation or drowsiness 1.66 (1.46-1.89), NNT 5 euphoria 12.5 (3-52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids dizziness 2.97 (2.31-3.83), NNT 3 dysphoria or depression 8.06 (3.38-19.2), NNT 8 hallucinations 6.10 (2.41-15.4), NNT 17 paranoia 8.58 (6.38-... 

The cannabinoids have previously been noted to have anti-emetic properties and nabilone has been available for the treatment of emesis due to chemotherapy for some years. Recently, there have been reports of its use in preventing postoperative nausea and vomiting in gynaecological patients with some limited success. 

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

However A9-tetrahydrocannabinol anatagonizes the peripheral CB2 receptor while acting as an agonist for the CNS CB1 receptor [133]. Cannabinoid receptors mediate the appetite stimulant and psychoactive effects of cannabinoids which have therapeutic potential for relief from nausea and pain [132]. 

Adverse effects Its adverse effects include severe nausea and vomiting (centrally mediated). [Note These effects can be diminished by pretreatment with cannabinoids (see p. 243) or pheno-thiazine (see p. 242).] Severe bone marrow depression limits extensive use. Latent viral infections (for example, Herpes zoster] may appear because of immunosuppression. Extravasation is a serious problem. If it occurs, the area should be infiltrated with isotonic sodium thiosulfite to inactivate the drug. 

Cannabinoid receptors include the CB1 receptors (which have a high incidence in the CNS and inhibit adenylyl cyclase, close Ca2+ channels and open K+ channels via Gai) and CB2 receptors (which are present in immune cells and act via Gai proteins to inhibit adenylyl cyclase). CB1 and CB2 receptors bind the endogenous ligand anandamide (arachi-donylethanolamide) as well as A9-tetrahydroc.annabinol from marijuana (Cannabis saliva). A9-Tetrahydroc,annabinol antagonizes the peripheral CB2 receptor but acts as an agonist for the CNS CB1 receptor. Cannabinoid receptor agonists have appetite stimulant and psychoactive effects and have therapeutic potential for relief from nausea and pain. 

Tramer MR et al 2001 Cannabinoids for control of chemotherapy induced nausea and vomiting quantitative systematic review. British Medical Journal 323 16-20. 

Nabilone is a synthetic cannabinoid and has properties similar to tetrahydrocannabinol (the active constituent of marijuana) which has an antiemetic action. It is used to relieve nausea or vomiting caused by cytotoxic drugs. Adverse effects include somnolence, dry mouth, decreased appetite, dizziness, euphoria, dysphoria, postural hypotension, confusion and psychosis. These may be reduced if prochlorperazine is given concomitantly. 

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. 

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