More Research on Cannabinoids is "Urgently" Needed for CNS Disorders

LAS VEGAS—“By legalizing the use of medical marijuana, the cart has been put before the horse,” according to Charles E. Argoff, MD, CPE, Professor of Neurology and Director of the Comprehensive Pain Center at the Albany Medical Center in Albany, New York.

Clinicians have suspected that cannabinoids offer medicinal benefits since at least 1890, when Sir John Russell Reynolds, then president of the British Medical Association, published a paper describing its use for migraine, neuralgia, and dysmenorrhea. But more than a century later, the evidence base is surprisingly scant. Studies are few, small, statistically underpowered, and typically of short duration. No reliable conclusions can yet be drawn about smoked cannabis' or cannabinoids' utility in managing pain, spasticity or other symptoms in epilepsy, cervical dystonia, Tourette syndrome, or Huntington Disease.

Large randomized controlled trials are desperately needed to guide clinical decision-making, he said.

The situation is particularly urgent because 20 states and the District of Columbia have already legalized the use of medical marijuana. “But given the DEA's current scheduling of marijuana as a schedule I narcotic, research in the US will be difficult for the present,” he noted. “That's the same classification as heroin—that there's no medical reason to use it. So that's one of the major stumbling blocks to obtaining really good data in this country.”

The hope, Dr. Argoff said, is that large, high-quality clinical studies can be completed elsewhere to help inform clinical practice here in the United States.

In patients with multiple sclerosis, oral cannabis extract does appear to be effective for reducing patient-reported spasticity symptoms and pain and THC is probably effective for reducing patient-reported symptoms—but oral cannabinoid extracts and THC are probably ineffective for reducing objective spasticity measures and tremors, he noted.

There is also clinical evidence that MS patients' muscle stiffness is worse with oral cannabinoids than placebo, he added. Spasms, pain and sleep were also more likely to be worse than in placebo groups.

Cannabinoids have been found to be associated with several serious adverse events—including death, dizziness, nausea, emesis, cystitis, dehydration, transient psychosis, hallucinations and cognitive impairment, Dr. Argoff was quick to note.

Nevertheless, analysis of published studies regarding the use of cannabinoids for CNS disorders “suggests 6.9% of patients discontinued treatment due to adverse events,” Dr. Argoff noted. “That's not bad. It's certainly lower than what we see with other analgesics, with opioids.”

A double-blind crossover study evaluated the effects of cannabinoids on levodopa-induced dyskinesias in a sample of 19 patients with Parkinsons disease and found that treatment with an average daily dose of 0.146 mg/kg per day “trended toward worsening” dyskinesia, although a subsequent, non-blinded study of 7 patients showed improvement associated with cannabinoids.

“There's a great and urgent need to study cannabinoids in a manner similar to other medications so that these substances can be used as appropriately as possible,” he reported. “We just don't know if it's harmful. When in the United States do we actually allow a medication to be utilized without knowing what its benefits and safety profile might be?”

To consider medical marijuana to have medicinal utility, Dr. Argoff argued, “then at the very least, we should really consider applying the same principles we apply to other analgesics that we might use, to this class of compounds.”

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