Tag Archives: antiemetic

Delta-9-tetrahydrocannabinol in cancer chemotherapy: research problems and issues.

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Abstract

“A critical review of the literature assessing the antiemetic efficacy of delta-9-tetrahydrocannabinol (THC) in patients receiving cancer chemotherapy showed considerable inconsistency in results. The equivocal nature of these results partly reflects the difficulty of doing research on antiemetic therapies, but also can be attributed to differences in the adequacy and nature of the research designs, procedures, and assessment instruments that have been used. Several factors were also identified that are seldom studied but may be important in determining whether THC will be effective: patient variables, such as chemotherapy regimen and age; pharmacologic variables, such as drug tolerance, dose, schedule, toxicity, route of administration, and drug interactions; and environmental variables associated with administration setting. The need to differentiate pharmacologically induced from conditioned nausea and vomiting was also pointed out. We believe that THC does have antiemetic efficacy, but the lack of controlled research does not allow precise knowledge of its true effectiveness and toxicity. Well-controlled trials are needed to help answer some of these questions.”

http://www.ncbi.nlm.nih.gov/pubmed/6305249

Antiemetic effect of tetrahydrocannabinol. Compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis.

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Abstract

“Fifty-five patients harboring a variety of neoplasms and previously found to have severe nausea or emesis from antitumor drugs were given antiemetic prophylaxis in a double-blind, randomized, crossover fashion. Tetrahydrocannabinol (THC), prochlorperazine, and placebo were compared. Nausea was absent in 40 of 55 patients receiving THC, eight of 55 patients receiving prochlorperazine, and five of 55 in the placebo group.

The antiemetic effect of THC appeared to be more efficacious for cyclophosphamide, fluorouracil, and doxorubicin hydrochloride, and less so for mechlorethamine hydrochloride and the nitrosureas.

Tetrahydrocannabinol appears to offer significant control of nausea in most patients and exceeding by far that provided by prochlorperazine.”

http://www.ncbi.nlm.nih.gov/pubmed/6254456

 

An efficient new cannabinoid antiemetic in pediatric oncology.

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“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.”

http://www.ncbi.nlm.nih.gov/pubmed/7776837

Review of cannabinoids and their antiemetic effectiveness.

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“Marijuana has been used for over 2 centuries. Its major psychoactive constituent, delta-9-tetrahydrocannabinol (THC) was isolated in 1964 and first used to control nausea and vomiting during chemotherapy in the 1970s. THC has cardiovascular, pulmonary and endocrinological effects as well as actions on the central nervous system. Alterations in mood, memory, motor coordination, cognitive ability, sensorium, spatial- and self-perception are commonly experienced. The precise antiemetic mechanism is unknown. THC and nabilone act at a number of sites within the central nervous system. Cannabinoids have also been shown to inhibit prostaglandin synthesis in vitro. In controlled clinical trials, THC is superior to placebo and prochlorperazine in antiemetic effectiveness. Effectiveness of THC correlates to a ‘high’ experienced by the patient. A variety of chemotherapy regimens respond to THC including high-dose methotrexate and the doxorubicin, cyclophosphamide, fluorouracil combination. Cisplatin is more resistant. Side effects are generally well tolerated but may limit THC use in the elderly or when high doses are administered. Nabilone, a synthetic cannabinoid, is also an effective antiemetic which is more active than prochlorperazine in preventing chemotherapy-induced emesis, including cisplatin-containing regimens. Side effects are similar to THC and may be dose-limiting. Levonantradol, another synthetic cannabinoid, is an effective antiemetic. It may provide more flexibility in the outpatient setting since it can be administered orally or intramuscularly. Most side effects are mild except for dysphoria which may be dose-limiting.”

http://www.ncbi.nlm.nih.gov/pubmed/6301800

Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis.

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Abstract

“This paper aims to evaluate the anti-emetic efficacy of cannabinoids in cancer patients receiving chemotherapy using a systematic review of literature searched within electronic databases such as PUBMED, EMBASE, PSYCINFO, LILACS, and ‘The Cochrane Collaboration Controlled Trials Register’. Studies chosen were randomized clinical trials comprising all publications of each database until December 2006. From 12 749 initially identified papers, 30 fulfilled the inclusion criteria for this review, with demonstration of superiority of the anti-emetic efficacy of cannabinoids compared with conventional drugs and placebo. The adverse effects were more intense and occurred more often among patients who used cannabinoids. Five meta-analyses were carried out: (1) dronabinol versus placebo [n=185; relative risk (RR)=0.47; confidence interval (CI)=0.19-1.16]; (2) Dronabinol versus neuroleptics [n=325; RR=0.67; CI=0.47-0.96; number needed to treat (NNT)=3.4]; (3) nabilone versus neuroleptics (n=277; RR=0.88; CI=0.72-1.08); (4) levonantradol versus neuroleptics (n=194; RR=0.94; CI=0.75-1.18); and (5) patients’ preference for cannabis or other drugs (n=1138; RR=0.33; CI=0.24-0.44; NNT=1.8). The superiority of the anti-emetic efficacy of cannabinoids was demonstrated through meta-analysis.”

http://www.ncbi.nlm.nih.gov/pubmed/18625004

Regulation of nausea and vomiting by cannabinoids.

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“Anti-emetic effects of cannabinoids in human clinical trials”

  “Considerable evidence demonstrates that manipulation of the endocannabinoid system regulates nausea and vomiting in humans and other animals. The anti-emetic effect of cannabinoids has been shown across a wide variety of animals that are capable of vomiting in response to a toxic challenge. CB1 agonism suppresses vomiting, which is reversed by CB1 antagonism, and CB1 inverse agonism promotes vomiting. Recently, evidence from animal experiments suggests that cannabinoids may be especially useful in treating the more difficult to control symptoms of nausea and anticipatory nausea in chemotherapy patients, which are less well controlled by the currently available conventional pharmaceutical agents. Although rats and mice are incapable of vomiting, they display a distinctive conditioned gaping response when re-exposed to cues (flavours or contexts) paired with a nauseating treatment. Cannabinoid agonists (Δ9-THC, HU-210) and the fatty acid amide hydrolase (FAAH) inhibitor, URB-597, suppress conditioned gaping reactions (nausea) in rats as they suppress vomiting in emetic species. Inverse agonists, but not neutral antagonists, of the CB1 receptor promote nausea, and at subthreshold doses potentiate nausea produced by other toxins (LiCl). The primary non-psychoactive compound in cannabis, cannabidiol (CBD), also suppresses nausea and vomiting within a limited dose range. The anti-nausea/anti-emetic effects of CBD may be mediated by indirect activation of somatodendritic 5-HT1A receptors in the dorsal raphe nucleus; activation of these autoreceptors reduces the release of 5-HT in terminal forebrain regions. Preclinical research indicates that cannabinioids, including CBD, may be effective clinically for treating both nausea and vomiting produced by chemotherapy or other therapeutic treatments.”

“The cannabis plant has been used for several centuries for a number of therapeutic applications, including the attenuation of nausea and vomiting. Ineffective treatment of chemotherapy-induced nausea and vomiting prompted oncologists to investigate the anti-emetic properties of cannabinoids in the late 1970s and early 1980s, before the discovery of the 5-HT3 antagonists. The first cannabinoid agonist, nabilone (Cesamet), which is a synthetic analogue of Δ9-THC was specifically licensed for the suppression of nausea and vomiting produced by chemotherapy. Furthermore, synthetic Δ9-THC, dronabinol, entered the clinic as Marinol in 1985 as an anti-emetic and in 1992 as an appetite stimulant. In these early studies, several clinical trials compared the effectiveness of Δ9-THC with placebo or other anti-emetic drugs. Comparisons of oral Δ9-THC with existing anti-emetic agents generally indicated that Δ9-THC was at least as effective as the dopamine antagonists, such as prochlorperazine.”

“There is some evidence that cannabis-based medicines may be effective in treating the more difficult to control symptoms of nausea and delayed nausea and vomiting in children. Abrahamov et al. (1995) evaluated the anti-emetic effectiveness of Δ8-THC, a close but less psychoactive relative of Δ9-THC, in children receiving chemotherapy treatment. Two hours before the start of each cancer treatment and every six hours thereafter for 24 h, the children were given Δ8-THC as oil drops on the tongue or in a bite of food. After a total of 480 treatments, the only side effects reported were slight irritability in two of the youngest children (3.5 and 4 years old); both acute and delayed nausea and vomiting were controlled.”

“Chemotherapy-induced vomiting is well controlled in most patients by conventionally available drugs, nausea (acute, delayed and anticipatory) continues to be a challenge. Nausea is often reported as more distressing than vomiting, because it is a continuous sensation. Indeed, this distressing symptom of chemotherapy treatment (even when vomiting is pharmacologically controlled) can become so severe that as many as 20% of patients discontinue the treatment. Both preclinical and human clinical research suggests that cannabinoid compounds may have promise in treating nausea in chemotherapy patients.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165951/

The emerging role of cannabinoid neuromodulators in symptom management.

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Abstract

“INTRODUCTION:

The cannabinoids nabilone (Cesamet) and dronabinol (Marinol) are indicated for the management of chemotherapy-induced nausea and vomiting (CINV) in cancer patients who have failed to respond adequately to conventional antiemetic therapy.

DISCUSSION:

The endocannabinoid (CB) system interacts with numerous other systems and pharmaceutical cannabinoids target ubiquitous CB1 and CB2 receptors in the central nervous system and periphery, relieving nausea and vomiting and pain.

SUMMARY:

The benefits of this novel class of medications in cancer may extend beyond CINV, as indicated by data from preclinical studies and animal models.”

http://www.ncbi.nlm.nih.gov/pubmed/17139494

Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

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“Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, antioxidant, antiemetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and antioxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ(9) -tetrahydrocannabinol is already under clinical evaluation in patients with Huntington’s disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ(9) -tetrahydrocannabinol, i.e. CB(1) and CB(2) receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB(2) receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.”

http://www.ncbi.nlm.nih.gov/pubmed/22625422

Safety and side effects of cannabidiol, a Cannabis sativa constituent.

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“Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were “cannabinoids”, “cannabidiol” and “side effects”. Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.”

[The endogenous cannabinoid system. Therapeutic implications for neurologic and psychiatric disorders].

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Abstract

“For about 5,000 years, cannabis has been used as a therapeutic agent. There has been growing interest in the medical use of cannabinoids. This is based on the discovery that cannabinoids act with specific receptors (CB1 and CB2). CB1 receptors are located in specific brain areas (e.g. cerebellum, basal ganglia, and hippocampus) and CB2 receptors on cells of the immune system. Endogenous ligands of the cannabinoid receptors were also discovered (e.g. anandamids). Many physiologic processes are modulated by the two subtypes of cannabinoid receptor: motor functions, memory, appetite, and pain. These innovative neurobiologic/pharmacologic findings could possibly lead to the use of synthetic and natural cannabinoids as therapeutic agents in various areas. Until now, cannabinoids were used as antiemetic agents in chemotherapy-induced emesis and in patients with HIV-wasting syndrome. Evidence suggests that cannabinoids may prove useful in some other diseases, e.g. movement disorders such as Gilles de la Tourette’s syndrome, multiple sclerosis, and pain. These new findings also explain the acute adverse effects following cannabis use.”

http://www.ncbi.nlm.nih.gov/pubmed/15776259