Archive for the ‘Nausea’ Category

Four years following resection of a Clark’s level IV malignant melanoma, a 50-year-old man developed widespred metastatic disease involving the liver, bones, brain, gastrointestinal mucosa, and lungs. One week after whole brain radiation therapy, he was admitted to the hospital for nausea, vomiting, and pain. He was treated with several antiemetic drugs, but it was not until dronabinol was added that the nausea and vomiting stopped. Dronabinol was an effective antiemetic used in combination with prochlorperazine in nausea and vomiting unresponsive to conventional antiemetics.

Background Review commissioned in 1996 by the Department of Health (DOH).

Aims Assess therapeutic profile of cannabis and cannabinoids.

Method Medline search, references supplied by DOH and others, and personal communications.

Results and Conclusions Cannabis and some cannabinoids are effective anti-emetics and analgesics and reduce intra-ocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.

In 1996 I was commissioned by the Department of Health (DOH) to review the scientific literature regarding the potential therapeutic utility of cannabis and its derivatives. The review was based upon primary sources (identified from a Medline literature search, reference lists supplied by the DOH and the Institute for the Study of Drug Dependence, and personal communications with relevant academics and clinicians). This paper is a greatly shortened version of the review. The 4 years which have elapsed have seen little in the way of new clinical results but considerable advances in cannabinoid basic science (Institute of Medicine, 1999). Government licences have recently been granted for several controlled trials of both synthetic and plant-derived cannabinoids in multiple sclerosis and chronic pain. In January 2000, I was appointed Medical Director of GW Pharmaceuticals, a company established to derive medicinal extracts from standardised cannabis plants.

Although the public debate about the legalization of marijuana has continued for as long as 25 years, few controlled studies have been conducted to assess its potential medical benefits. The present study examined the antiemetic effect of smoked marijuana cigarettes (8.4 and 16.9 mg Delta(9)-tetrahydrocannabinol [THC]) compared to a highly potent antiemetic drug, ondansetron (8 mg) in 13 healthy volunteers. Nausea and emesis were induced by syrup of ipecac. Marijuana significantly reduced ratings of “queasiness” and slightly reduced the incidence of vomiting compared to placebo. Ondansetron completely eliminated the emetic effects of ipecac. These findings support and extend previous results, indicating that smoked marijuana reduces feelings of nausea and also reduces emesis in this model. However, its effects are very modest relative to ondansetron, and the psychoactive effects of marijuana are likely to limit its clinical usefulness in the general population.

Hyperemesis gravidarum (HG), a debilitating ailment characterized by severe nausea and vomiting, malnutrition, and weight loss during pregnancy, occurs to 1-2% of pregnant women globally. Although the medical community offers clinical and pharmaceutical intervention, the procedures are: (1) partially effective, if at all, (2) costly and unaffordable without health insurance, (3) questionable in their long-term safety for the fetus, as most have not been scientifically tested, and (4) in more severe cases, physically painful and psychologically disempowering for the pregnant woman. This study unveils the deep suffering endured by women undergoing HG from a folkloristic perspective and proposes the use of medical cannabis as an effective natural remedy for the symptoms of HG. Due to the criminalization of cannabis and the stigma of its use during pregnancy, no formalized testing has been conducted, thus far, to investigate such a claim. While a small, underground, pilot study of cannabis treatment for HG has proven relatively promising, clinical trials are necessary for a more conclusive answer.

Xenobiotic cannabinoid CB1/CB2-receptor agonists appear to possess broad-spectrum antiemetic activity since they prevent vomiting produced by a variety of emetic stimuli including the chemotherapeutic agent cisplatin, serotonin 5-HT3-receptor agonists, dopamine D2/D3-receptor agonists and morphine, via the stimulation of CB1-receptors. The purpose of this study was to evaluate whether structurally-diverse cannabinoids [Delta9-THC, (delta-9-tetrahydrocannabinol); (Delta8-THC, delta-8-tetrahydrocannabinol); WIN55,212-2, (R (+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)), methyl] pyrolol [1,2,3-de]-1,4 benzoxazinyl]-(1-naphthalenyl) methenone mesylate); and CP55,940, ((-)-3-[2-hydroxy-4-(1,1-dimethylheptyl]-4-[3-hydroxypropyl] cyclohexane-1-ol)), can prevent radiation-induced emesis. Exposure to total body radiation (0, 5, 7.5 and 10 Gy) caused robust emesis in the least shrew (Cryptotis parva) in a dose-dependent manner (ED50=5.99 (5.77-6.23) Gy) and all animals vomited at the highest tested dose of radiation. In addition, the radiation exposure reduced locomotor behaviors to a significant but mild degree in a non-dose-dependent fashion up to one hour post-treatment. Radiation-induced emesis (10 Gy) was blocked in a dose-dependent manner by the CB1/CB2-receptor agonists with the following ID50 potency order: CP55,940 (0.11 (0.09-0.12) mg/kg)>WIN55,212,2 (3.65 (3.15-4.23) mg/kg)=Delta8-THC (4.36 (3.05-6.22) mg/kg)>Delta9-THC (6.76 (5.22-8.75) mg/kg). Although the greater antiemetic potency and efficacy of Delta8-THC relative to its isomer Delta9-THC is unusual as the latter cannabinoid possesses higher affinity and potency for cannabinoid receptors in functional assays, the current data support the results of a clinical study in children suggestive of complete protection from emesis by Delta8-THC. This effect has not been clinically observed for Delta9-THC in cancer patients receiving chemo- or radiation-therapy. Cannabinoids prevented the induced emesis via the stimulation of cannabinoid CB1-receptors because the CB1 (SR141716A)–and not the CB2 (SR144528)–receptor antagonist reversed both the observed reduction in emesis frequency and shrew emesis protection afforded by either Delta9-THC or CP55,940 against radiation-induced emesis. These findings further suggest that the least shrew can be utilized as a versatile and inexpensive small animal model to rapidly screen the efficacy of investigational antiemetics for the prevention of radiation-induced emesis.