 medical marijuana, a panacea, or scourge. For 5,000 years, cannabis has been used throughout the world for medicinal purposes, even prescribed by American physicians early on, a fact that's often used by medical marijuana proponents to justify modern medical applications. But the field of old-timey medicine was fraught with patent medicine snake oil nonsense, not to mention bloodletting and other questionable and harmful remedies. Skeptics criticized the medical marijuana movement as the medical excuse marijuana movement, insinuating that epileptic children and the terminally ill are just being used as props to trojan horse in the legalization of recreational use, or to peddle outlandish claims about miracle cancer cures, frustrating research in the field who just want to get at the science. For example, what about the therapeutic use of cannabis for inflammatory bowel diseases like Crohn's disease and ulcerative colitis? Conventional therapies mainly work by suppressing the immune system to try to tamp down the inflammation. Given the limited therapy options and known adverse side effects from these drugs, often people suffering these diseases ended up having to get inflamed sections of their bowels removed surgically. So you can see whether there's so much interest in alternative approaches. About 1 in 6 IBD patients who use marijuana say it helps with their symptoms. So researchers decided to put it to the test. 13 patients with inflammatory bowel disease were given a third of a pound of marijuana to smoke at their leisure over a period of three months, and they felt significantly better. Now, there's no control groups. You don't know if they would have gotten better anyway, or what role the placebo effect may have played. It's like some of the studies of cannabis used for pediatric epilepsy. Response rates of over 30%, seizure frequency cut in half in a third of the kids. That's amazing! Until you realize you can sometimes get the same kind of amazing response, giving kids nothing, giving them a sugar pill placebo. That's why it's critical to do randomized, double-blind, placebo-controlled trials, but there weren't any on cannabis and IBD until 2013. 21 patients with Crohn's disease, for which nothing seemed to help, so they randomized them to either smoke two joints a day of real pot or a look-alike placebo pot. And 90% of the subjects in the cannabis group got better compared to only 40% in the placebo group. Here's a graph of their symptom scores. No big change in the placebo group over the two-month study, but the cannabis group cut their symptoms in half. They acknowledged that long-term cannabis use is not without risks, but may be a cakewalk compared to the potential adverse and even life-threatening side effects of some of the more powerful conventional therapies, so the study was heralded as offering high hope for digestive disorders. Now the study was funded by a medical marijuana advocacy organization, in fact the main supplier in the country, and so there may have been expectations placed on the subjects on how much better this stuff was going to make them feel, in other words, a setup for the placebo effect. But they controlled for that, right? Those getting the real stuff did significantly better than those randomized to get the placebo pot. Oh, wait a second. The whole point of a placebo is to be indistinguishable from the real thing that the subjects don't know which group they're really in. How do you do that with a psychoactive drug? You can't. Which is the problem? They're trying to hide which group people were in by recruiting only patients who'd never tried pot before in hopes that they wouldn't notice, but of course most of them did. So what we're left with is basically another unblinded study. They asked them a bunch of subjective questions. How are you feeling? And those who mostly knew they were taking the drug said they were feeling better. There was no change in the objective lab values, like CRP, a sign of inflammation. And so maybe the marijuana is just masking symptoms without actually affecting intestinal inflammation. Another indicator of the cannabis may not be affecting the course of the disease itself is how quickly the symptoms rebounded. Two weeks after the study ended, the cannabis group was right back up to where they started. So no difference in objective inflammatory markers. And given the rapid rebound, it seems more plausible that cannabis ameliorated the symptoms of Crohn's disease rather than actually modulating the disease itself. Okay, yeah, but the symptoms are terrible. A reduction in pain is a reduction in pain. From the point of view of the patients, a marked symptomatic improvement and ability to resume normal life is not trivial, whether or not the inflammation persists. I mean, unless, of course, cannabis somehow made the disease worse in the long run, and this survey study published the following year, found that cannabis provided that same immediate symptomatic relief, but was associated with a worse disease prognosis over time. Patients with inflammatory bowel disease reported that cannabis improved their pain, cramping in diarrhea, but used for more than six months in Crohn's patients appeared to be a strong predictor of them ending up in surgery. Five times the odds of them ending up under the knife. Now there's two possible explanations for this. It's quite possible that it was the increased severity that led to the cannabis use, and not the other way around. But the alternative explanation is that cannabis use may worsen the prognosis leading to greater surgeries and hospitalizations. That's why we really need prospective clinical trials where we follow people over time to see which came first. But until then, maybe we should consider cannabis use and IBD as potentially harmful, not just air on the side of caution, but there was this other study on hepatitis C patients that found that daily cannabis use was associated with nearly seven times the odds of worse liver fibrosis, which is like scar tissue. And so, hey, if cannabis really does make fibrosis worse, then that could potentially explain why cannabis users with IBD may be more likely to end up on the operating table.