Cannabinoids placebo-controlled studies

Cannabinoids appear to have a very complex interaction with seizure activity, exerting both anticonvulsant and proconvulsant effects. Anecdotal testimonies abound (Grinspoon and Bakalar, 1993), but there has been very little controlled human research. In single-case studies both use and withdrawal of marijuana have been linked to the resumption of seizures (Keeler and Reifler, 1967 Consroe et al., 1975). In a randomised placebo-controlled blind study, patients who responded poorly to standard treatments experienced improved seizure control in response to cannabidiol administration. Cannabidiol does not interact with cannabinoid receptors, and animal studies indicate that it has different anticonvulsant effects to other cannabinoids (Cunha et al., 1980). As such it may prove to have useful therapeutic properties. 

Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A and Thompson A (2003). Cannabinoids for the treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study) Multicentre randomised placebo-controlled trial. Lancet, 362, 1517-1526. 

Luo, J., J. H. Yin, H. Z. Wu, and Q. Wei. Extract from Fructus cannabis activating calcineurin improved learning and memory in mice with chemical drug-induced dysmnesia. Acta Pharmacol Sin 2003 24(11) 1137-1142. Degenhardt, L., W. Hall, and M. Lynskey. Exploring the association between cannabis use and depression. Addiction 2003 98(11) 1493-1504. Zajicek, J., P. Pox, H. Sanders, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study) multicentre randomised placebo-controlled trial. Lancet 2003 362(9395) 1517-1526. 

The effects of oral cannabinoids (dronabinol or Cannabis sativa plant extract) in relieving pain and muscle spasticity have been studied in 16 patients with multiple sclerosis (mean age 46 years, mean duration of disease 15 years) in a double-blind, placebo-controlled, crossover... 

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. 

In the studies of acute effects (1-5), marijuana was administered by smoking under double-blind conditions. The research assistant guided the subject in paced smoking procedures. Cigarettes that contained either 10 mg or 19 mg of A -tetrahydrocannabinol (THC) were compared with placebo cigarettes that contained inactive, cannabinoid-extracted marijuana with only trace amounts of THC. In the studies of chronic effects (6,7), chronic marijuana users were compared with nonusers, i.e., control subjects. In the initial study of chronic marijuana users (6), these users were also grouped according to frequency of marijuana use. 

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