Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A random-sample, anonymous survey of the members of the American Society of Clinical Oncology (ASCO) was conducted in spring 1990 measuring the attitudes and experiences of American oncologists concerning the antiemetic use of marijuana in cancer chemotherapy patients. The survey was mailed to about one third (N = 2,430) of all United States-based ASCO members and yielded a response rate of 43% (1,035). More than 44% of the respondents report recommending the (illegal) use of marijuana for the control of emesis to at least one cancer chemotherapy patient. Almost one half (48%) would prescribe marijuana to some of their patients if it were legal. As a group, respondents considered smoked marijuana to be somewhat more effective than the legally available oral synthetic dronabinol ([THC] Marinol; Unimed, Somerville, NJ) and roughly as safe. Of the respondents who expressed an opinion, a majority (54%) thought marijuana should be available by prescription. These results bear on the question of whether marijuana has a "currently accepted medical use," at issue in an ongoing administrative and legal dispute concerning whether marijuana in smoked form should be available by prescription along with synthetic THC in oral form. This survey demonstrates that oncologists' experience with the medical use of marijuana is more extensive, and their opinions of it are more favorable, than the regulatory authorities appear to have believed.
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PMID:Marijuana as antiemetic medicine: a survey of oncologists' experiences and attitudes. 165 43

The (+) enantiomer of the synthetic cannabinoid, 7-hydroxy-delta-6-tetrahydrocannabinol, dimethylheptyl homolog (HU-211), possesses significant antimetic efficacy in the pigeon. However, unlike all anti-emetic cannabinoids tested in the past, it is devoid of psychotropic (cannabimimetic) activity. The anti-emetic activity of HU-211 was determined in pigeons given 10 mg/kg i.v. cisplatin, a widely used antitumour agent, which is also a potent emetogenic agent at this dose. This activity was compared with that of delta-1-tetrahydrocannabinol (delta-1-THC). HU-211 pretreatment elicited a dose-related inhibition of cisplatin vomiting, with the optimal dose of HU-211 (2.5 mg/kg) inhibiting emesis by nearly 90%. Delta-1-THC in doses up to 5 mg/kg caused only an insignificant reduction in vomiting. The activity was increased in the presence of cupric chloride (0.8 mg/kg). The optimal dose of delta-1-THC (5.0 mg/kg) with CuCl2 very significantly diminished the total amount of vomitus expelled (up to 90%). However, it failed to inhibit emesis in 50% of all animals tested, did not significantly affect the time of onset of emesis and was highly psychotropic. The optimal dose of HU-211 (2.5 mg/kg) with CuCl2 inhibited emesis by 97%, significantly delayed the time on onset of emesis in the very few animals that did vomit and was completely non-psychotropic. The curve for the antiemetic effect of HU-211 was U-shaped over a narrow dose range. The present report demonstrates that complete separation of psychotropic and antiemetic activities is possible in the cannabinoid series.
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PMID:Inhibition of cisplatin-induced emesis in the pigeon by a non-psychotropic synthetic cannabinoid. 255 22

Evaluation of the activity of anti-emetic drugs in randomized controlled trials has, in most cases, demonstrated the superiority of treatment over placebo administration for the control of chemotherapy-induced emesis (see Table 15). The degree of control of emesis relates both to the intensity of the emetogenic stimulus and to the effectiveness of the anti-emetic agent employed. Prochlorperazine is a relatively weak anti-emetic. The drug exhibits modest activity in the treatment of emesis produced by mild emetogenic stimuli, but is relatively ineffective in the treatment of patients on moderate to severely emetogenic drugs. Domperidone has demonstrated activity against moderately emetogenic stimuli but has not been evaluated in cisplatin-treated patients. The cannabinoids have proved efficacious in the treatment of emesis induced by more severe emetogenic stimuli. THC therapy, however, has been limited in some studies by toxicity. High-dose metoclopramide has demonstrated efficacy in small series of patients in the treatment of cisplatin-induced vomiting. Dexamethasone activity as a single agent is in doubt but the drug may improve the efficacy of metoclopramide when used in combination. For the future, the use of combinations of anti-emetics with differing sites of action and non-overlapping toxicities, may lead to further improvement in efficacy. Combinations of centrally-acting drugs such as the cannabinoids plus dopamine antagonists such as metoclopramide or domperidone, are worth evaluating. The control of anticipatory nausea and vomiting is another major area of interest which has, as yet, not been studied in any depth. A single comparative trial has been reported in the literature (50) and in this study, behavioural therapy rather than drug therapy was evaluated. There may be a place for the evaluation of behavioural therapy in combination with drugs exhibiting anxiolytic properties such as the benzodiazepines and the cannabinoids. Finally, new anti-emetic drugs with an improved therapeutic index will be welcomed by the patient.
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PMID:Advances in anti-emetic therapy. 609 68

BRL-4664, a THC analog, has been administered to 23 patients at a dose of 10 or 15 mg repeated twice. All patients were on cisplatin therapy, and 16 of them had experienced severe vomiting during the previous course of cisplatin. There was a statistically significant difference between the group with prior cisplatin therapy and without prior therapy in terms of number of vomiting episodes, emphasizing the role of conditioned reflexes. The dose of 15 mg administered before and twice after the infusion of cisplatin was well tolerated. Only minor side effects were observed.
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PMID:Clinical studies with a THC analog (BRL-4664) in the prevention of cisplatin-induced vomiting. 719 92

Delta-8-tetrahydrocannabinol (delta-8-THC), a cannabinoid with lower psychotropic potency than the main Cannabis constituent, delta-9-tetrahydrocannabinol (delta-9-THC), was administered (18 mg/m2 in edible oil, p.o.) to eight children, aged 3-13 years with various hematologic cancers, treated with different antineoplastic drugs for up to 8 months. The total number of treatments with delta-8-THC so far is 480. The THC treatment started two hours before each antineoplastic treatment and was continued every 6 hrs for 24 hours. Vomiting was completely prevented. The side effects observed were negligible.
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PMID:An efficient new cannabinoid antiemetic in pediatric oncology. 777 37

A broad range of therapeutic applications has been suggested for cannabis or its pharmacologically active compound (tetrahydrocannabinol; THC) in many publications. Psychotropic side effects and the anecdotal character of the research have limited the pharmacotherapeutic use of THC until now. Therefore, the Netherlands Health Council recently decided negatively on this matter. Besides several cannabinoid receptor subtypes present in the central nervous system and peripheral tissues endogenous cannabinoids have been detected. These endogenous cannabinoids appear to play an important role in signal transduction, which may be starting points for therapy regarding: cardiovascular diseases, multiple sclerosis and spinal cord disorders. cerebrovascular accident and brain trauma, neurodegenerative diseases, epilepsy, pain management, glaucoma, oncologic and aids-related disorders such as nausea, vomiting and appetite problems.
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PMID:[Therapeutic applications and biomedical effects of cannabinoids; pharmacological starting points]. 954 85

Although the active component of cannabis Delta9-THC was isolated by our group 35 years ago, until recently its mode of action remained obscure. In the last decade it was established that Delta9-THC acts through specific receptors - CB1 and CB2 - and mimics the physiological activity of endogenous cannabinoids of two types, the best known representatives being arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG). THC is officially used against vomiting caused by cancer chemotherapy and for enhancing appetite, particularly in AIDS patients. Illegally, usually by smoking marijuana, it is used for ameliorating the symptoms of multiple sclerosis, against pain, and in a variety of other diseases. A synthetic cannabinoid, HU-211, is in advanced clinical tests against brain damage caused by closed head injury. It may prove to be valuable against stroke and other neurological diseases.
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PMID:Recent advantages in cannabinoid research. 1057 84

Two subtypes of cannabinoid receptors have been identified to date, the CB1 receptor, essentially located in the CNS, but also in peripheral tissues, and the CB2 receptor, found only at the periphery. The identification of delta9-tetrahydrocannabinol (delta9-THC) as the major active component of marijuana (Cannabis sativa), the recent emergence of potent synthetic ligands and the identification of anandamide and sn-2 arachidonylglycerol as putative endogenous ligands for cannabinoid receptors in the brain, have contributed to advancing cannabinoid pharmacology and approaching the neurobiological mechanisms involved in physiological and behavioral effects of cannabinoids. Most of the agonists exhibit nonselective affinity for CB1/CB2 receptors, and delta9-THC and anandamide probably act as partial agonists. Some recently synthesized molecules are highly selective for CB2 receptors, whereas selective agonists for the CB1 receptors are not yet available. A small number of antagonists exist that display a high selectivity for either CB1 or CB2 receptors. Cannabinomimetics produce complex pharmacological and behavioral effects that probably involve numerous neuronal substrates. Interactions with dopamine, acetylcholine, opiate, and GABAergic systems have been demonstrated in several brain structures. In animals, cannabinoid agonists such as delta9-THC, WIN 55,212-2, and CP 55,940 produce a characteristic combination of four symptoms, hypothermia, analgesia, hypoactivity, and catalepsy. They are reversed by the selective CB1 receptor antagonist, SR 141716, providing good evidence for the involvement of CB1-related mechanisms. Anandamide exhibits several differences, compared with other agonists. In particular, hypothermia, analgesia, and catalepsy induced by this endogenous ligand are not reversed by SR 141716. Cannabinoid-related processes seem also involved in cognition, memory, anxiety, control of appetite, emesis, inflammatory, and immune responses. Agonists may induce biphasic effects, for example, hyperactivity at low doses and severe motor deficits at larger doses. Intriguingly, although cannabis is widely used as recreational drug in humans, only a few studies revealed an appetitive potential of cannabimimetics in animals, and evidence for aversive effects of delta9-THC, WIN 55,212-2, and CP 55,940 is more readily obtained in a variety of tests. The selective blockade of CB1 receptors by SR 141716 impaired the perception of the appetitive value of positive reinforcers (food, cocaine, morphine) and reduced the motivation for sucrose, beer and alcohol consumption, indicating that positive incentive and/or motivational processes could be under a permissive control of CB1-related mechanisms. There is little evidence that cannabinoid systems are activated under basal conditions. However, by using SR 141716 as a tool, a tonic involvement of a CB1-mediated cannabinoid link has been demonstrated, notably in animals suffering from chronic pain, faced with anxiogenic stimuli or highly motivational reinforcers. Some effects of SR 141716 also suggest that CB1-related mechanisms exert a tonic control on cognitive processes. Extensive basic research is still needed to elucidate the roles of cannabinoid systems, both in the brain and at the periphery, in normal physiology and in diseases. Additional compounds, such as selective CB1 receptor agonists, ligands that do not cross the blood brain barrier, drugs interfering with synthesis, degradation or uptake of endogenous ligand(s) of CB receptors, are especially needed to understand when and how cannabinoid systems are activated. In turn, new therapeutic strategies would likely to emerge.
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PMID:Behavioral effects of cannabinoid agents in animals. 1080 37

There is substantial clinical evidence that Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and its synthetic analogs (nabilone and levonantradol) can prevent emesis in cancer patients receiving chemotherapy. Limited available animal studies also support the antiemetic potential of these cannabinoids. The present study investigates the mechanism of antiemetic action of cannabinoids in an established animal model of emesis, the least shew (Cryptotis parva). Since cannabinoid agonists prevent emesis, it was hypothesized that blockade of either the cannabinoid CB(1) receptor or the cannabinoid CB(2) receptor would induce vomiting. Thus, the emetic potential of SR 141716A (CB(1) receptor antagonist) or SR 144528 (CB(2) receptor antagonist) was investigated. Both intraperitoneal (0, 1, 2.5, 5, 10 and 20 mg/kg, n = 7-15 per group) and subcutaneous (0, 10, 20 and 40 mg/kg, n = 6-9 per group) administration of SR 141716A caused emesis (ED(50) = 5.52 +/- 1.23 and 20.2 +/- 1.02 mg/kg, respectively) in the least shrew in a dose-dependent manner. Indeed, both the frequency of emesis and the percentage of animals vomiting increased with increasing doses of SR 141716A. Significant effects were seen at the 10- and 20-mg/kg doses for the IP route, while only the 40-mg/kg dose produced significant emesis via the SC route. The CB(2) antagonist failed to produce emesis via either route of administration. SR 141716A at an IP dose of 20 mg/kg was used to induce emesis for drug interaction studies. Thus, varying doses of three different classes of cannabinoid agonists [CP 55, 940 (0, 0.1, 0.5 and 1 mg/kg), WIN 55, 212-2 (0, 1, 5 and 10 mg/kg), and Delta(9)-THC (0, 5, 10 and 20 mg/kg)], were administered IP to different groups of shrews 10 min prior to SR 141716A injection. The frequency of emesis was recorded for 30 min following the administration of SR 141716A. The order of potency for redcing both the frequency of emesis and the percentage of shrews vomiting was CP 55, 940 > WIN 55, 212-2 > Delta(9)-THC which is consistent with an action on the CB(1) receptor. These results suggest that the antiemetic activity of Delta(9)-THC and its synthetic analogs reside in their ability to stimulate the cannabinoid CB(1) receptor. Furthermore, the antiemetic potency of CP 55, 940 is 45 times greater than Delta(9)-THC. On the other hand, blockade of CB(1) receptors can induce vomiting, which implicates an important role for endogenous cannabinoids in emetic circuits.
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PMID:Delta(9)-tetrahydrocannabinol and synthetic cannabinoids prevent emesis produced by the cannabinoid CB(1) receptor antagonist/inverse agonist SR 141716A. 1112 Apr 2

Cannabis has a potential for clinical use often obscured by unreliable and purely anecdotal reports. The most important natural cannabinoid is the psychoactive tetrahydrocannabinol (delta9-THC); others include cannabidiol (CBD) and cannabigerol (CBG). Not all the observed effects can be ascribed to THC, and the other constituents may also modulate its action; for example CBD reduces anxiety induced by THC. A standardised extract of the herb may be therefore be more beneficial in practice and clinical trial protocols have been drawn up to assess this. The mechanism of action is still not fully understood, although cannabinoid receptors have been cloned and natural ligands identified. Cannabis is frequently used by patients with multiple sclerosis (MS) for muscle spasm and pain, and in an experimental model of MS low doses of cannabinoids alleviated tremor. Most of the controlled studies have been carried out with THC rather than cannabis herb and so do not mimic the usual clincal situation. Small clinical studies have confirmed the usefulness of THC as an analgesic; CBD and CBG also have analgesic and antiinflammatory effects, indicating that there is scope for developing drugs which do not have the psychoactive properties of THC. Patients taking the synthetic derivative nabilone for neurogenic pain actually preferred cannabis herb and reported that it relieved not only pain but the associated depression and anxiety. Cannabinoids are effective in chemotherapy-induced emesis and nabilone has been licensed for this use for several years. Currently, the synthetic cannabinoid HU211 is undergoing trials as a protective agent after brain trauma. Anecdotal reports of cannabis use include case studies in migraine and Tourette's syndrome, and as a treatment for asthma and glaucoma. Apart from the smoking aspect, the safety profile of cannabis is fairly good. However, adverse reactions include panic or anxiety attacks, which are worse in the elderly and in women, and less likely in children. Although psychosis has been cited as a consequence of cannabis use, an examination of psychiatric hospital admissions found no evidence of this, however, it may exacerbate existing symptoms. The relatively slow elimination from the body of the cannabinoids has safety implications for cognitive tasks, especially driving and operating machinery; although driving impairment with cannabis is only moderate, there is a significant interaction with alcohol. Natural materials are highly variable and multiple components need to be standardised to ensure reproducible effects. Pure natural and synthetic compounds do not have these disadvantages but may not have the overall therapeutic effect of the herb.
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PMID:Cannabinoids in clinical practice. 1115 13


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