What is ulcerative colitis?
Ulcerative colitis is a chronic, long-term illness that causes inflammation of the colon and rectum. Symptoms may include diarrhea, rectal bleeding, passage of mucus, and abdominal pain. It is characterized by periods of acute flares when people experience symptoms as well as periods of remission when symptoms stop.
What are cannabis and cannabinoids?
Cannabis is a widely used recreational drug that has multiple effects on the body via the endocannabinoid system. Cannabis contains multiple sub-ingredients called cannabinoids. Cannabis and cannabis oil containing specific cannabinoids can cause cognitive changes such as feelings of euphoria and altered sensory perception. However, some cannabinoids, such as cannabidiol, do not have a psychoactive effect. Cannabis and some cannabinoids have been shown to decrease inflammation in animal and laboratory models which suggests it may help people with ulcerative colitis. For example, cannabidiol is one such cannabinoid that has shown anti-inflammatory activity in mice.
What did the researchers investigate?
The researchers evaluated whether cannabis or cannabis oil (cannabidiol) was better than placebo (e.g. fake drug) for treating adults with active ulcerative colitis or ulcerative colitis that is in remission. The researchers searched the medical literature extensively up to 2 January 2018.
What did the researchers find?
Two studies including 92 adult participants with ulcerative colitis were included. Both studies assessed cannabis therapy in participants who had active ulcerative colitis. No studies that assessed cannabis therapy in participants with ulcerative colitis in remission were identified. One study (60 participants) compared 10 weeks of treatment with capsules containing cannabis oil with up to 4.7% D9-tetrahydrocannabinol (THC) to placebo in participants with mild to moderately active ulcerative colitis. The starting dose of cannabidiol was 50 mg twice daily which was increased, if tolerated, to a target of 250 mg twice daily. The other study (32 participants) compared 8 weeks of treatment with two cannabis cigarettes per day containing 0.5 g of cannabis, corresponding to 11.5 mg THC to placebo cigarettes in participants with ulcerative colitis who did not respond to conventional medical treatment.
The study comparing cannabis oil capsules to placebo found no difference in remission rates at 10 weeks. Twenty four (7/29) percent of cannabidiol participants achieved clinical remission compared to 26% (8/31) of placebo participants. The study also showed higher self reported quality of life scores in cannabis oil participants compared to placebo participants. More side-effects were observed in the cannabis oil participants compared to the placebo participants. These side effects were considered to be mild or moderate in severity. Common reported side effects include dizziness, disturbance in attention, headache, nausea and fatigue. No patients in the cannabis oil group had any serious side effects. Ten per cent (3/31) of the placebo group had a serious side effect. Serious side effects in the placebo group included worsening ulcerative colitis and one complicated pregnancy.
The second study comparing two cannabis cigarettes (23 mg THC/day) to placebo cigarettes showed lower disease activity index scores in the cannabis group compared to the placebo group. C-reactive protein and fecal calprotectin levels (both measures of inflammation in the body) were similar in both groups. No serious side effects were reported. This study did not report on remission rates.
The effects of cannabis and cannabis oil on ulcerative colitis are uncertain, thus no firm conclusions regarding the effectiveness and safety of cannabis or cannabis oil in adults with active ulcerative colitis can be drawn. There is no evidence for cannabis or cannabis oil use for maintenance of remission in ulcerative colitis. Further studies with a larger number of participants are required to assess the effects of cannabis in people with active and inactive ulcerative colitis. Different doses of cannabis and routes of administration should be investigated. Lastly, follow-up is needed to assess the long term safety outcomes of frequent cannabis use.
The effects of cannabis and cannabidiol on UC are uncertain, thus no firm conclusions regarding the efficacy and safety of cannabis or cannabidiol in adults with active UC can be drawn.There is no evidence for cannabis or cannabinoid use for maintenance of remission in UC. Further studies with a larger number of patients are required to assess the effects of cannabis in UC patients with active and quiescent disease. Different doses of cannabis and routes of administration should be investigated. Lastly, follow-up is needed to assess the long term safety outcomes of frequent cannabis use.
Cannabis and cannabinoids are often promoted as treatment for many illnesses and are widely used among patients with ulcerative colitis (UC). Few studies have evaluated the use of these agents in UC. Further, cannabis has potential for adverse events and the long-term consequences of cannabis and cannabinoid use in UC are unknown.
To assess the efficacy and safety of cannabis and cannabinoids for the treatment of patients with UC.
We searched MEDLINE, Embase, WHO ICTRP, AMED, PsychINFO, the Cochrane IBD Group Specialized Register, CENTRAL, ClinicalTrials.Gov and the European Clinical Trials Register from inception to 2 January 2018. Conference abstracts and references were searched to identify additional studies.
Randomized controlled trials (RCTs) comparing any form or dose of cannabis or its cannabinoid derivatives (natural or synthetic) to placebo or an active therapy for adults (> 18 years) with UC were included.
Two authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. The primary outcomes were clinical remission and relapse (as defined by the primary studies). Secondary outcomes included clinical response, endoscopic remission, endoscopic response, histological response, quality of life, C-reactive protein (CRP) and fecal calprotectin measurements, symptom improvement, adverse events, serious adverse events, withdrawal due to adverse events, psychotropic adverse events, and cannabis dependence and withdrawal effects. We calculated the risk ratio (RR) and corresponding 95% confidence interval for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) and corresponding 95% CI. Data were pooled for analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). Data were analyzed on an intention-to-treat basis. GRADE was used to evaluate the overall certainty of evidence.
Two RCTs (92 participants) met the inclusion criteria. One study (N = 60) compared 10 weeks of cannabidiol capsules with up to 4.7% D9-tetrahydrocannabinol (THC) with placebo capsules in participants with mild to moderate UC. The starting dose of cannabidiol was 50 mg twice daily increasing to 250 mg twice daily if tolerated. Another study (N = 32) compared 8 weeks of therapy with two cannabis cigarettes per day containing 0.5 g of cannabis, corresponding to 23 mg THC/day to placebo cigarettes in participants with UC who did not respond to conventional medical treatment. No studies were identified that assessed cannabis therapy in quiescent UC. The first study was rated as low risk of bias and the second study (published as an abstract) was rated as high risk of bias for blinding of participants and personnel. The studies were not pooled due to differences in the interventional drug.
The effect of cannabidiol capsules (100 mg to 500 mg daily) compared to placebo on clinical remission and response is uncertain. Clinical remission at 10 weeks was achieved by 24% (7/29) of the cannabidiol group compared to 26% (8/31) in the placebo group (RR 0.94, 95% CI 0.39 to 2.25; low certainty evidence). Clinical response at 10 weeks was achieved in 31% (9/29) of cannabidiol participants compared to 22% (7/31) of placebo patients (RR 1.37, 95% CI 0.59 to 3.21; low certainty evidence). Serum CRP levels were similar in both groups after 10 weeks of therapy. The mean CRP in the cannabidiol group was 9.428 mg/L compared to 7.638 mg/L in the placebo group (MD 1.79, 95% CI -5.67 to 9.25; moderate certainty evidence). There may be a clinically meaningful improvement in quality of life at 10 weeks, measured with the IBDQ scale (MD 17.4, 95% CI -3.45 to 38.25; moderate certainty evidence). Adverse events were more frequent in cannabidiol participants compared to placebo. One hundred per cent (29/29) of cannabidiol participants had an adverse event, compared to 77% (24/31) of placebo participants (RR 1.28, 95% CI 1.05 to1.56; moderate certainty evidence). However, these adverse events were considered to be mild or moderate in severity. Common adverse events included dizziness, disturbance in attention, headache, nausea and fatigue. None (0/29) of the cannabidiol participants had a serious adverse event compared to 10% (3/31) of placebo participants (RR 0.15, 95% CI 0.01 to 2.83; low certainty evidence). Serious adverse events in the placebo group included worsening of UC and one complicated pregnancy. These serious adverse events were thought to be unrelated to the study drug. More participants in the cannabidiol group withdrew due to an adverse event than placebo participants. Thirty-four per cent (10/29) of cannabidiol participants withdrew due to an adverse event compared to 16% (5/31) of placebo participants (RR 2.14, 95% CI 0.83 to 5.51; low certainty evidence). Withdrawls in the cannabidiol group were mostly due to dizziness. Withdrawals in the placebo group were due to worsening UC.
The effect of cannabis cigarettes (23 mg THC/day) compared to placebo on mean disease activity, CRP levels and mean fecal calprotectin levels is uncertain. After 8 weeks, the mean disease activity index score in cannabis participants was 4 compared with 8 in placebo participants (MD -4.00, 95% CI -5.98 to -2.02). After 8 weeks, the mean change in CRP levels was similar in both groups (MD -0.30, 95% CI -1.35 to 0.75; low certainty evidence). The mean fecal calprotectin level in cannabis participants was 115 mg/dl compared to 229 mg/dl in placebo participants (MD -114.00, 95% CI -246.01 to 18.01). No serious adverse events were observed. This study did not report on clinical remission, clinical response, quality of life, adverse events or withdrawal due to adverse events.
Cochrane What is ulcerative colitis? Ulcerative colitis is a chronic, long-term illness that causes inflammation of the colon and rectum. Symptoms may include diarrhea, rectal bleeding,
Can Marijuana or CBD Help With Ulcerative Colitis?
There’s lots of interest in medical marijuana and CBD to help manage a variety of conditions and symptoms such as pain, nausea, and trouble sleeping. If you or a loved one is struggling with ulcerative colitis (UC) and its symptoms, you might wonder if marijuana or CBD could help with those.
It’s useful to understand the difference between marijuana and CBD. Marijuana comes from a plant that people sometimes use for recreational or medicinal purposes called Cannabis sativa. It contains two main active ingredients: THC (short for delta-9 tetrahydrocannabinol) and CBD (short for cannabidiol).
It’s the THC in marijuana that gives you a high. If you buy CBD products, they come from a cannabis cousin of marijuana called hemp. There shouldn’t be much if any THC in your CBD. So CBD might make you feel tired or make your mouth feel dry, but you won’t get high from taking it.
Does either help with UC? Some researchers and doctors are exploring the possibility that cannabis in one form or another helps people with inflammatory bowel disorders including UC. Based on the evidence so far, the answer isn’t a simple yes or no.
“There is a percentage of patients who use cannabis and feel better,” says Jami Kinnucan, MD, a gastroenterologist at the University of Michigan. “Their symptoms — most commonly abdominal pain or body pain, diarrhea, appetite, and nausea — improve.”
But, Kinnucan says, this doesn’t mean using cannabis is a good way to treat UC. That’s because people with UC have inflammation in their digestive tracts. This inflammation as well as ulcers is tied to UC symptoms, including diarrhea, pain, cramping, bleeding and fatigue. A primary aim of treatment is to stop the inflammation.
There’s some evidence in mice suggesting that cannabis could help with inflammation. This has to do with certain receptors that respond to other cannabinoids our bodies make naturally. Cannabis also may slow the digestive tract. But it isn’t clear that smoking cannabis or taking it in a capsule fights the underlying inflammation in people with UC.
In one small clinical trial, people with UC who took CBD capsules containing a small amount of THC for 10 weeks weren’t any more likely to go into remission than those taking a placebo. Smoking two marijuana cigarettes a day didn’t lower signs of inflammation either.
“If you do blood work, imaging or stool samples, patients’ numbers don’t change,” Kinnucan says. “While they may feel better, their inflammatory burden isn’t improving.”
The CBD study did report that the 10-week treatment improved quality of life. But the study’s participants also reported side effects, including dizziness, trouble paying attention, headache, nausea, and fatigue. Dizziness was the most common reason people in the CBD study dropped out. The marijuana study didn’t report on side effects or quality of life.
A recent review of the two clinical studies concluded that the effects of cannabis and CBD in people with UC remain uncertain. There’s no evidence that it can help to put people with UC into remission.
But it’s too soon to say whether it sometimes helps in other ways and how safe it is.
Kinnucan says it’s possible that cannabis could help some patients with UC and not others. For those with UC that’s controlled by medication, she says there’s no reason to think adding cannabis would help. It’s never a good idea to replace approved medicines with cannabis. There’s a risk that cannabis could hide symptoms and encourage people to stop needed treatments.
“At the end of day, if the hope is to control inflammation, there is no data to support that,” Kinnucan says.
Weigh the Risks
What’s most important for people with UC is to continue with treatments that doctors know work. If you continue to have symptoms, Kinnucan says a doctor should evaluate your disease to make sure the treatments you’re taking are sufficient. But if you or a loved one are taking medications as prescribed to control the UC, there’s a chance that cannabis might help with lingering symptoms like pain or nausea. She recommends taking cannabis orally over smoking it because of the risks of smoking and to start with the lowest THC levels.
Kinnucan says more doctors and patients should talk about cannabis, including how and why patients might be using it on their own. But for now, it’s difficult for doctors to know how to advise people with UC about how they might use cannabis safely. Studies of cannabis for inflammatory bowel diseases including UC are ongoing, so more data is coming.
In addition to whether it works, doctors and patients also have legal issues to consider when it comes to cannabis. CBD is federally legal as long as it contains only very low levels of THC, although the rules in particular states could change.
For marijuana, it’s more complicated. For example, in Michigan, recreational marijuana is legal but medical marijuana requires a confirmed diagnosis from two doctors. UC is on the list of qualifying conditions for medical marijuana. Marijuana can be classified as medicinal or recreational. Both are legal in some states. Other states have only legalized medical marijuana. And in some, no form is legal. The federal Drug Enforcement Administration (DEA) also recognizes marijuana, including medical marijuana, as a controlled substance.
“We have patients who live in one state and drive across state lines to obtain cannabis but then illegally bring it back in,” Kinnucan says. “You should refer to your state laws. Crossing a border can be a criminal activity.”
Mayo Clinic: “ Medical marijuana,” “Ulcerative Colitis,” “What are the benefits of CBD — and is it safe to use?”
Harvard Health: “Cannabidiol (CBD) — what we know and what we don’t.”
Inflammatory Bowel Diseases: “The Role of Cannabis in the Management of Inflammatory Bowel Disease: A Review of Clinical, Scientific, and Regulatory Information.”
Jami Kinnucan, Gastroenterologist, University of Michigan.
The Journal of Clinical Investigation: “Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis.”
Michigan Health: “Cannabis for Treating IBD: Hope or Hype?”
Cochrane Database of Systematic Reviews: “ Cannabis for the treatment of ulcerative colitis.”
Clinical Trials.gov: “Cannabis for Inflammatory Bowel Disease,” “Cannabidiol for Inflammatory Bowel Disease.”
Crohn’s and Colitis Foundation: “Foundation Position Statement: Medical cannabis.”
Can marijuana or CBD help manage the symptoms of ulcerative colitis?