Marijuana has been used by people living with HIV since the early days of the epidemic. Today, a growing number of people with HIV may be using marijuana, and the drug itself has changed dramatically from a plant that's usually smoked to a diverse menu of plant-based and synthetic products.
In the U.S., marijuana is available for medical use in 31 states and for recreational use in nine, "but no matter where you are, patients are using it," said pharmacist Jasjit Gill, Pharm.D., speaking at the 2018 Association of Nurses in AIDS Care Conference in Denver, Colorado.
Gill emphasized why it's important for clinicians to stay up-to-date on the latest science on how weed affects some HIV medications, and to understand where there are gaps in scientific knowledge. Clinicians should realize that many of their patients are using cannabis products, even if they're not disclosing that information.
"It's a difficult topic for patients to talk about with their provider," said Gill.
The demographic of weed users is changing, with 32% of patients 65 and older reporting having used marijuana in the past, 16% of whom reported using since it was legalized in their state.
But today's cannabis products are fundamentally different from the marijuana older people may have smoked in their youth. In 1995, the potency of the average marijuana plant was around 4%. By 2014, growers were cultivating plants with 12% potency out of the ground. And, with the decriminalization and legalization of marijuana in many states, people are increasingly using highly potent products like vapor, edibles, and wax.
In fact, a synthetic product called "shatter" contains 80% THC. Meanwhile, a few pharmaceutical cannabinoid products have been approved, including cannabidiol, dronabinol, nabilone, and nabiximols.
The availability and diversity of today's marijuana products -- paired with a lack of scientific research on their effects -- leaves medical professionals wondering what impact different products may be having on different patients.
HIV clinicians in particular need to take note of their patients' marijuana use, as some drugs can impact the metabolism of HIV antiretrovirals, according to Gill.
Cannabis products "could mess with absorption, metabolism, or excretion of their HIV drugs," said Gill, who became interested in weed when his home state, Colorado, began to liberalize its marijuana criminal laws and eventually legalize the drug.
When it comes to scientific research on weed's effect on the body, "there are studies out there, but a lot of the studies are pro- or anti-marijuana," so it's tough to sift through the literature, he said.
Established medical uses of marijuana include pain relief and treatment of anorexia, anxiety, glaucoma, headaches, and nausea, according to Gill. Research is ongoing for the use of marijuana as a treatment for diabetes, post-traumatic stress disorder (PTSD), and seizures.
In general, marijuana is known to increase blood flow to the right frontal brain, decrease intraocular pressure, and decrease the neurotransmitters acetylcholine and gamma-aminobutyric acid. It is metabolized through the liver and is excreted through the kidneys, breast milk, and feces.
But what effects does marijuana have on patients taking HIV antiretrovirals? According to Gill, that question is complicated, because marijuana isn't just one thing.
"There are over 60 identified chemicals of cannabinoids," he said. "There are over 460 chemicals in the plant, and once they're in your body, they break down into more than 2,000 chemicals."
Here's what we do know: In general, cannabinoids inhibit cytochrome P450, a pathway that's critical for drug metabolism. So, patients taking drugs that are also metabolized this way -- namely, protease inhibitors and NNRTIs -- could see a slowed metabolism and increased drug levels.
Meanwhile, marijuana inhibits the increase of CD4 cells, therefore decreasing the concentration of protease inhibitors like darunavir (Prezista) and atazanavir (Reyataz). Because of these effects, marijuana "should be considered as part of medication history, especially if you have a patient on HIV drugs metabolized through the liver," said Gill.
Marijuana may also interact with other medications and supplements, including kava kava, skullcap, St. John's wort, Valerian root, and Yerba Mansa.
In addition to its potential drug-drug interactions, marijuana is known to increase and/or aggravate psychiatric illness, cardiac disease, and respiratory illnesses, according to Gill. In addition, since it was legalized in Colorado, there's been an uptick in marijuana-related motor vehicle accident deaths and hospital visits. The drug also inhibits brain development, so underage patients should be discouraged from using it. And, because it's excreted in breast milk, it shouldn't be used by people who are breastfeeding.
However, the drug does have other known benefits, especially for people with HIV dealing with nausea and pain. The bottom line, Gill said, is that a significant portion of people living with HIV are going to use marijuana. And because pharmaceutical-grade products are substantially more expensive and are not universally covered by insurance, it's more likely that patients are going to buy recreational-use marijuana from dispensaries or drug dealers.
With all that in mind, Gill said that if clinicians want to recommend marijuana for their HIV-positive patients, they should consider recommending products with higher CBD and lower THC and encouraging patients to avoid smoking cannabis in favor of edible products, start with a low dose and go slowly.