Synthetic 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... 

Di Marzo V, De Petrocellis L (2005) Plant, synthetic and endogenous cannabinoids in medicine. Annu Rev Med 57 553-574... 

Until today only a few synthetic cannabinoids have made their way into clinical use. 

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 advent of synthetic cannabimimetics with a high degree of enantioselectivity (Johnson, 1986 Little, 1988) paved the road for the identification of specific cannabinoid binding sites in rat brain (Devane, 1988). This discovery marked the onset of a revolution in the understanding of cannabinoid biology. 

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). 

THC is effective in several chemotherapy regimens, including methotrexate and the doxorubicin/cyclophosphamide/fluorouracil combination. Cisplatin treatment, however, is more resistant. Side effects of THC are generally well tolerated, and use may be limited in the elderly or with higher doses. Nabilone is a synthetic cannabinoid that is more effective than prochlorperazine in chemotherapy-induced emesis, including cisplatin. Its side effects are similar to THC. Levonantradol is another synthetic cannabinoid with antiemetic effects, and may be administered orally or intramuscularly. The side effect of dysphoria may limit its use. 

Collins DR, Pertwee RG, Davies SN. (1994). The action of synthetic cannabinoids on the induction of long-term potentiation in the rat hippocampal slice. EurJ Pharmacol. 259(3) R7-8. 

Ajulemic acid (77) Cannabinoid CP 7075 (IP 751, ajulemic acid, CT-3) (synthetic version) Neurological (neuropathic pain) Suppresses IL-lp and mahix metalloproteinases (MMPs) through a peroxisome proliferator-activated receptor (PPAR) y-mediated mechanism Phase I Cervelo Pharmaceuticals 615-618... 

Burstein H, Andette CA, Breurr A, Devane WA, Colodner S, Doyle SA, Mechoulam R. (1992) Synthetic nonpsychotropic cannabinoids with potent antiinflammatory, analgesic, and leukocyte antiadhesion activities. J Med Chem35 3135-3141. 

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

The anandamide precursor, phosphatidylethanol amine, is present in membranes almost always accompanied by phophatidylserine. It seemed reasonable to expect the formation of anandamide from its precursor will be paralleled by formation of N-arachidinoylserine from phosphatidyl serine. Indeed, A -arachidonoyl-L-serine (ARA-S) was found to be formed alongside anandamide (Fig. 4). This compound was isolated from bovine brain and its structure was elucidated by comparison with synthetic ARA-S. Contrary to anandamide, ARA-S binds very weakly to the known cannabinoid CBi and CB2 or vanilloid TRPVl receptors. However, it produces endothelium-dependent vasodilation of rat isolated mesenteric... 

Conti S, Costa B, CoUeoni M, Parolaro D, Giagnoni G, Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid... 

Natural and Synthetic Cannabinoids 9orinfia Mauland Bernd... 

Bridges, D., Ahmad, K., Rice, A.S. The synthetic cannabinoid WIN55,212-2 attenuates hyperalgesia and allodynia in a rat model of neuropathic pain, Br. J. Pharmacol. 2001, 133, 586-594. 

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