SCOTTSDALE, ARIZ. – There’s a rapidly growing list of states that have approved marijuana for medical use, but that does not mean that there’s also an expanding body of science to support marijuana’s use for psychiatric indications, according to Dr. Deepak Cyril D’Souza.

Though moderate evidence exists to support the use of medical marijuana for nausea and vomiting in chemotherapy, HIV/AIDS cachexia, neuropathic pain, and spasticity in multiple sclerosis, there’s scant evidence for some other uses. Little evidence exists to support the use of medical marijuana in Tourette syndrome, Crohn’s disease and ulcerative colitis, and epilepsy, and the data are even weaker for Parkinson’s disease, posttraumatic stress disorder, and agitation in Alzheimer’s disease, Dr. D’Souza said at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Even so, he said, medical marijuana has been approved in several states for all of those conditions – and more.

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Different states have required widely varying standards of evidence in making decisions about whether to approve medical marijuana use, and for which conditions. These range, in some cases, from relying on mere anecdotal evidence – as when individuals provide powerful but unscientific testimony about marijuana’s efficacy for a condition – to requiring the gold standard of randomized, double-blind, placebo-controlled trials.

Dr. D’Souza and his collaborators reviewed the data supporting the use of medical marijuana for several of the most commonly approved psychiatric indications, and found many of them hampered by poor design, poor execution, and an overreliance on the subjective effects of the studied compound.

For PTSD, only one randomized controlled study was found, and only one study had an active control, so the quality of evidence was rated as “very low” or “low” by Dr. D’Souza’s group. “Most of the studies were not blinded, and the sample sizes were generally small,” said Dr. D’Souza, professor of psychiatry at Yale University, New Haven, Conn. “It’s notable that many of these studies were with dronabinol, which is a synthetic THC analog. However, one take-home is that many of these studies reported improvement with sleep and a reduction in nightmares. This is something that should be followed up.”

For Tourette syndrome, there were just two studies by the same author, both with small sample sizes and of short duration. One study was rated “low” and the other “very low” for quality; in particular, the placebo effect could not be ruled out.

Four studies, said Dr. D’Souza, examined cannabinoids for dementia, and all had low quality of evidence. One published study had a sample size of two, he said. “The point here is that the only positive finding is that people who were diagnosed with dementia ate more and gained weight. And that wasn’t the objective of the study.”

“When we’re talking about medical marijuana, we’re talking about the whole plant,” he said. The marijuana plant has at least 450 known distinct constituent chemicals; these include about 70 cannabinoids as well as terpenoids and flavonoids. This means that the whole plant as dispensed represents a much more complex compound than medical tetrahydrocannabinol, for example, Dr. D’Souza said.

“We need to think about not just efficacy but side effects,” he said. These can include tolerance, abuse, and withdrawal syndrome. Marijuana’s cognitive effects may contribute to an increased risk of motor vehicle crashes. Though acute psychotic symptoms with quick resolution have long been noted, it’s also now thought that heavy marijuana exposure in adolescence more than doubles the risk for schizophrenia and might decrease adult IQ by about 10 points.

Though cannabis is “neither necessary nor sufficient for developing psychosis” but instead is a factor in a set of complex interactions, “what’s absolutely clear is that people with a psychotic disorder or at risk for developing one are very much more vulnerable to the effects of cannabinoids,” Dr. D’Souza said.

Despite all of those concerns, he said, “public demand and legislators have usurped the [Food and Drug Administration] approval process” when it comes to state-by-state approval of medical marijuana. The current state of affairs stands in contrast to the requirements for drug approvals for new indications, which require at least two adequately powered randomized clinical trials. When it comes to marijuana, Dr. D’Souza said, “For most of the indications the evidence fails to meet FDA standards.”

However, he said, the lack of high quality evidence may reflect the difficulty of conducting medical marijuana research in the United States. If this is so, he said, the “federal and state governments need to support and encourage research to generate high quality evidence to guide decisions.”

Dr. D’Souza reported a financial relationship with Insys Therapeutics, which develops pharmaceutical cannabinoid products.

koakes@frontlinemedcom.com

On Twitter @karioakes

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