Sat. Feb 4th, 2023
What do we know about the effects of medical marijuana?

BOSTON — Harvard Medical School’s Stacy Gruber explained the numbers: 28 states and the District of Columbia have medical marijuana laws, 17 others allow some cannabis-based products, and eight states now allow recreational use. The US has become a grand experiment in the medical use of marijuana, even though the federal government’s classification of the drug makes it extremely difficult to conduct proper research.

But that doesn’t mean no research is being done. Gruber and two other researchers described what they are learning about medical marijuana at the meeting of the American Association for the Advancement of Science. “This is the direction we’re going,” Gruber said, “and it’s good to be prepared.”

Canadian vigilance

Mark Ware of McGill University had a term for one way of tracking the effect of cannabis use: pharmacovigilance. Harmful side effects of medications such as acetaminophen and Vioxx were not noted during clinical trials. Instead, they were identified by tracking the use of these drugs as soon as they became available to the general population. He called this regular monitoring of drug users pharmacovigilance. It is the same process that has made us aware of the widespread misuse of prescription opioids.

So far the indications are positive. Cannabis users report less use of other drugs, such as selective serotonin reuptake inhibitors (SSRIs) and other antidepressants. There is also a decline in pain prescriptions in states that allow medical use. That, in turn, has led to a 25 percent drop in opioid deaths in these states compared to those where medical use remains banned. While the data is correlative, it certainly points to significant changes due to the legalization of medical use.

Canada, Ware suggested, is also a great place to do marijuana pharmacovigilance. It has a federally regulated medical use program administered by 38 licensed manufacturers. These manufacturers offer 160 different strains in various forms, making it possible (albeit difficult) to identify the key components of what patients are taking. So he’s involved in two Canadian studies that intend to do careful pharmacovigilance.

Ware also described a number of ongoing studies that intend to build on this type of approach. In one of the chronic pain clinics, patients, both marijuana users and controls, enrolled in a year-long follow-up study to track side effects. Ware’s team has also trained physicians in the Quebec area to enroll patients in a long-term follow-up study; they are currently at 1,000 of their planned 3,000.

South of the border

Ryan Vandrey of Johns Hopkins did something similar here in the US thanks to collaboration with the Realm of Caring (RoC) registry. The research cohort that Hopkins and RoC set up includes people in all 50 states, ranging in age from one to 86. People who use cannabis products for cancer, autoimmune problems, behavioral problems, neural and psychological problems, pain and autoimmune diseases are all represented .

One thing is clear: cannabis is not the drug of choice for many of these people. That idea is reflected in both raw numbers: 35 percent participation it’s a last resort – and in many other metrics. Patients in the cohort use an average of three other prescription and two over-the-counter medications. And only a quarter of the people on the registry had a history of previous cannabis use, which is about half the national average.

As for the products they use, well… Vandrey said only 17 percent of the products they tested are labeled accurately. A quarter had more drugs than promised, and a few appeared to have no active ingredients. The median dose was 55 mg, which Vandrey called “a hefty dose,” but ran up to more than 1200 mg.

Given the chaos in the products on the market, the Johns Hopkins group has turned to the federal government to obtain a supply of marijuana to test its behavior after ingestion. The pot was ingested via a single method (passive exposure, vaporized, ingested or smoked), and the participants then provided blood and urine samples over the following hours and provided self-assessments of their mental and physical state. Vandrey showed a hilarious image of a dozen people in sterile gowns and caps in a room filled with the smoke coming from the six who were allowed to smoke as much weed as they wanted.

The work showed that passive ingestion occurs in the blood (enough to fail a blood test), but the effects are minor. 10mg doses are also relatively weak; dosages only started to show effects that were consistently stronger than placebo up to 25 mg. Both smoking and vaping showed a similar effect, with a rapid spike in blood drug levels followed by a fairly rapid drop; the peak was larger when a vaporizer was used. Cannabis intake did not show any spike, but taking it helps to maintain a long-term presence of the drug in the bloodstream. This finding is important, as it allows us to tailor the recording route to whether the event occurs suddenly or is a chronic problem.

Side effects were about what you would expect: some vomiting and a few panic and anxiety issues.

Your brain on drugs

Ultimately, though, researchers want proof that marijuana actually treats something, which is where Stacy Gruber’s speech came in. A recent review of medical applications suggested that there was substantial evidence that marijuana is effective for chronic pain, chemotherapy side effects, and some symptoms. of multiple sclerosis. There is limited evidence that it helps many other problems, but these studies need a lot more work. Gruber is leading efforts to close the evidence gap through the MIND Program: Marijuana Studies for Neuroscience Discovery.

She described an observational study of people already using medical marijuana. Samples of their drug are sent to laboratories for analysis, and her group monitors their neurological condition, using a baseline run prior to treatment. At this point, 33 participants have completed their first three-month follow-up, which consists of surveys, a series of tests and some MRI scans.

Most of the results are not significant after three months of use, but some are noticeable. For starters, opioid use is down 43 percent, consistent with some population-level measures. Users also report improvements in pain management, social functioning, and fatigue, although self-reported measures should always be viewed with caution.

However, the big results come in tests of executive function – the ability of our more detailed thought processes to suppress our gut reactions. Things like the ability to quickly choose the word “green,” even if it’s shown in red letters. Here many tests show significant improvements; the rest are all statistically insignificant. There are no drops. This is about the opposite of what you would expect from marijuana use, but Gruber reminded the audience that many of these patients have chronic pain, which we know impairs executive function. Successfully treating the pain has the potential to restore more careful thinking.

Interestingly, the effects were supported by a functional MRI study that looked at brain activity in areas known to be involved in executive control. Healthy controls showed a strong response in those brain regions when performing executive function tests, a response that was absent in the patients during the baseline study. Three months later, activity in those areas appeared indistinguishable from that of controls.

It is important to note that this does not mean that cannabis improves people’s mental acuity. But it does indicate that the drug can effectively treat a condition that would otherwise rob us of it. And in these early days of the great US cannabis experiment, that kind of detailed information is hard to come by.

By akfire1

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