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Questions remain as marijuana enters clinic use



– Medical marijuana skipped the usual phased testing of pharmaceuticals, so questions abound about how to counsel patients as legalization rolls out across the country, speakers said at the American Psychiatric Association annual meeting.

Dr. Arthur Williams, Columbia University, New York M. Alexander Otto/MDedge News

Dr. Arthur Williams

Drug interactions are an issue but remain under the radar. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are inhibitors of cytochrome P450, specifically the CYP2C enzyme and CYP3A liver enzymes, which means possible interactions with drug classes such as antidepressants and antipsychotics might come into play.

Concomitant use could affect, or be affected by, fluoxetine, clozapine, duloxetine, and olanzapine, among other medications. One case study suggested that warfarin doses should be reduced by 30% in a patient who had started with a liquid formulation of CBD for managing epilepsy (Basic Clin Pharmacol Toxicol. 2019 Jan;124[1]:28-31).

At this point, it’s “not clear what the clinic implications are,” but “it’s not unreasonable to consider that your patients’ response to their psychiatric medications might change based on the introduction of cannabinoids,” said Arthur Williams, MD, assistant professor of clinical psychiatry at Columbia University, New York, and one of many researchers playing catch-up as marijuana and its derivatives enter the clinic.

Another question is what, exactly, is a standard dose?

Dosing mostly has been a question of THC, the psychoactive component of marijuana. Washington state and Colorado opted for 10-mg THC when those jurisdictions legalized recreational use; Oregon chose 5 mg. Both are in line with Food and Drug Administration formulations already on the market, including dronabinol (Marinol), a synthetic THC approved in 2.5-mg, 5-mg, and 10-mg doses for AIDS wasting, and chemotherapy nausea and vomiting.

A typical .7-g joint of 8% THC delivers about 5 mg or so, but newer strains range up to 20% THC, and could deliver over 13 mg per joint; occasional users, meanwhile, feel high from just 2-3 mg.

The ratio of THC to CBD matters, as well. Generally, “whole plant marijuana on the black market is much higher in THC and much lower in CBD,” Dr. Williams said. CBD is thought to deliver most of the medical benefits of marijuana.

It’s best to ask people what they’re using, and to counsel new users – especially the elderly – to start low and go slow. But keep in mind that many medical users have years of recreational use and have built up tolerance, he said.

Vaping is not a bad idea for those interested. It heats the plant material to high enough temperatures to release cannabinoids but without combusting. It’s a much more efficient THC delivery system than smoking, and there’s no smoke in the lungs. Vape patients often feel they can titrate their dose exactly.

Edibles are another matter. It can take hours for them to hit. Although THC levels do not spike with edibles as they do when the substance is inhaled, the effects last longer. A lot depends on how much food is in the gut.

The risk with edibles is that people may keep popping gummy bears and brownies because they don’t feel anything but end up overdosing. Children might be tempted by the treats, too, and for those under 4 years old, overdose can lead to fatal encephalopathic comas, “something we never really saw until edibles came around,” Dr. Williams said.

With edibles, “you have no idea what’s actually in the product.” Labels can be “inaccurate by an order of magnitude. Patients should be cautioned about that,” he said.

Pregnant and breastfeeding women, especially, should be warned away from marijuana. Some of the literature suggests a link between exposure to marijuana and preterm birth – in addition to early psychosis in vulnerable children.

Dr. Williams had no relevant disclosures.

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