Nabilone. A preliminary review of its pharmacological properties and therapeutic use.

Abstract

“Nabilone is a new orally active cannabinoid for the treatment of severe gastrointestinal toxicity associated with cancer chemotherapy. The pharmacological profile of nabilone suggests that it acts primarily by preventing emesis controlled by the medulla oblongata, although its secondary mild anxiolytic activity may contribute to the overall efficacy. Nabilone 2mg twice daily starting 12 hours prior to, and continued for the duration of, chemotherapy produces significant reduction in the severity and duration of nausea and the frequency of vomiting in about 50 to 70% of patients with severe symptoms refractory to conventional therapy. Nabilone has proven to be more effective in controlling symptoms and preferred by more patients than prochlorperazine 10mg 2 to 4 times daily in a limited number of studies, despite a higher incidence of side effects. Comparative trials against other new antiemetic agents, such as high dose metoclopramide, and use of nabilone in combination with other antiemetics remain to be undertaken. The incidence of side effects is high with nabilone; drowsiness, dizziness and/or vertigo occur in 60 to 70% of patients, but rarely lead to drug withdrawal, although more troublesome effects, such as postural hypotension, ataxia, vision disturbance and toxic psychoses, may cause discontinuation of therapy. Thus, nabilone offers an effective alternative to the treatment options available in a difficult therapeutic area – those patients with severe gastrointestinal side effects from cancer chemotherapy who are refractory to conventional therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/2863127

Recent advantages in cannabinoid research.

Abstract

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/10575284

Marijuana as antiemetic medicine: a survey of oncologists’ experiences and attitudes.

Abstract

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/2045870

Antiemetic efficacy of levonantradol compared to delta-9-tetrahydrocannabinol for chemotherapy-induced nausea and vomiting.

Abstract

“The antiemetic efficacy of im levonantradol, a synthetic cannabinoid, given at a dose of 1 mg every 4 hours, was compared to oral delta-9-tetrahydrocannabinol (THC) given at a dose of 15 mg every 4 hours in a double-blind crossover study. Twenty-six patients receiving emetogenic cancer chemotherapy were evaluated. For each drug, 28% of treated patients had no nausea. The median number of emetic episodes with levonantradol was 2.0 versus 3.0 for THC (P = 0.06). Side effects occurred in 91.7% and 97.3% of levonantradol and THC patients, respectively, with drowsiness and dizziness most commonly seen. Side effects were generally well-tolerated, with only 13.9% of levonantradol and 21.6% of THC patients discontinuing treatment because of side effects. Levonantradol appears to be at least as effective an antiemetic as THC and is the only cannabinoid available for parenteral use.”

http://www.ncbi.nlm.nih.gov/pubmed/2981616

Levonantradol for the treatment of chemotherapy-induced nausea and vomiting.

Abstract

“Twenty patients with cancer previously unresponsive to antiemetic treatment of chemotherapy-induced nausea and vomiting were treated with the new tetrahydrocannabinoid Levonantradol. 15 patients experienced substantial relief and 10 of them preferred the drug for further courses. These observations suggest that Levonantradol can be beneficial to patients refractory to conventional antiemetic therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/6350696

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

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.

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

 

Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol.

Abstract

“The antinausea and antivomiting effects of delta-9-tetrahydrocannabinol (THC) in children receiving cancer chemotherapy were compared with those of metoclopramide syrup and prochlorperazine tablets in two double-blind studies. THC was found to be a significantly better antinausea and antivomiting agent… In some patients, THC enhanced appetite during a course of chemotherapy. In two patients, a “high” associated with THC administrationwas reported. Drowsiness was reported significantly more frequently with THC.”

http://www.ncbi.nlm.nih.gov/pubmed/231736

An efficient new cannabinoid antiemetic in pediatric oncology.

Abstract

“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

Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting

  “Despite progress in anti-emetic treatment, many patients still suffer from chemotherapy-induced nausea and vomiting (CINV). This is a pilot, randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine (CBM) containing delta-9-tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV.”

“Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial.”

“A systematic review of 30 clinical trials involving orally administered synthetic cannabinoids (nabilone and dronabinol) showed that they were superior to dopamine receptor antagonists in preventing CINV. Both are approved by the US Food and Drug Administration for use in CINV refractory to conventional anti-emetic therapy, but some authors have questioned the appropriateness of orally administered cannabinoids due to the variability in their gastrointestinal absorption, low bioavailability, long half-lives and the difficulties for an adequate self titration of the dose.”

“Animal studies suggest that the combined administration of different cannabinoids may enhance some of the therapeutic effects of delta-9-tetrahydrocannabinol (THC). This might explain why some patients preferred marihuana to synthetic cannabinoids in clinical trials.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997305/