Dysphoria cannabinoids

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. 

I. 18-1.62), number-needed-to-treat (NNT) was 6 for complete control of nausea relative risk was 1.28 (Cl 1.08-1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles relative risk 2.39 (2.05-2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids high 10.6 (6.86-16.5), NNT 3 sedation or drowsiness 1.66 (1.46-1.89), NNT 5 euphoria 12.5 (3-52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids dizziness 2.97 (2.31-3.83), NNT 3 dysphoria or depression 8.06 (3.38-19.2), NNT 8 hallucinations 6.10 (2.41-15.4), NNT 17 paranoia 8.58 (6.38-... 

There are two features of the cannabinoids which may ultimately be of therapeutic importance. THC lowers intraocular pressure, which may be of benefit in the treatment of glaucoma. There is also evidence that THC is a moderately effective antiemetic agent. Such a discovery has led to the development of nabilone, a synthetic cannabinoid, as an antiemetic agent, but its use is limited because of the dysphoria, depersonalization, memory disturbance and other effects which are associated with the cannabinoids. Whether the bronchodilator action of THC will ever find therapeutic application in the treatment of asthma remains an open question. 

Cannabinoids Marijuana derivatives, including dronabinol [droe NAB i nol] and nabilone, are effective against moderately emetogenic chemotherapy. However, they are seldom first-line antiemetics because of their serious side effects, including dysphoria, hallucinations, sedation, vertigo, and disorientation. In spite of their psychotropic properties (see p. 105), the antiemetic action of cannabinoids may not involve the brain synthetic cannabinoids having no psychotropic activity, nevertheless are antiemetic. 

Nabilone is a synthetic cannabinoid and has properties similar to tetrahydrocannabinol (the active constituent of marijuana) which has an antiemetic action. It is used to relieve nausea or vomiting caused by cytotoxic drugs. Adverse effects include somnolence, dry mouth, decreased appetite, dizziness, euphoria, dysphoria, postural hypotension, confusion and psychosis. These may be reduced if prochlorperazine is given concomitantly. 

Thirty randomized, controlled trials from 1975 to 1996 were analyzed to quantify the antiemetic efficacy and adverse effects of cannabis when given to 1366 patients receiving chemotherapy. Oral nabUone, oral dronabinol, and intramuscular levonantradol were compared with conventional antiemetics (prochlorperazine, metoclopramide, chlor-promazine, thiethylperazine, haloperidol, domperidone, and aliza-pride) or placebo. Across all trials, cannabinoids were slightly more effective than active comparators and placebo when the chemotherapy regimen was of moderate emetogenic potential, and patients preferred them. No dose-response relationships were evident to the authors. The cannabinoids were also more toxic side effects included euphoria, drowsiness, sedation, somnolence, dysphoria, depression, hallucinations, and paranoia. The efficacy of cannabinoids as compared to SSRls has not been studied. Use of these agents should be considered when other regimens do not provide desired efficacy. 

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