cbd oil for crohn’s

Cannabis and cannabis oil for the treatment of Crohn's disease

Crohn’s disease is a long-term condition that results in inflammation of the gastrointestinal tract, occurring anywhere from the mouth to the anus. Common symptoms include fever, diarrhoea, abdominal pain and weight loss. Crohn’s disease is characterized by periods of relapse when people are actively experiencing symptoms and periods of remission when the symptoms stop.

What are Cannabis and Cannabinoids?

Cannabis is a widely used drug which acts on the endocannabinoid system. Cannabis contains multiple components called cannabinoids. The use of cannabis and cannabis oil containing specific cannabinoids produces mental and physical effects such as altered sensory perception and euphoria when consumed. Some cannabinoids, such as cannabidiol, do not have a psychoactive effect. Cannabis and cannabidiol have some anti-inflammatory properties that might help people with Crohn’s disease.

What did the researchers investigate?

The researchers studied whether cannabis is better than placebo (e.g. a sugar pill) therapy for treating adults with active Crohn’s disease or Crohn’s disease that is in remission.

What did the researchers find?

The researchers extensively searched the literature up to 17 October 2018 and found three studies (93 participants) that met the inclusion criteria. One ongoing study was also identified. All of the studies were small in size and had some quality issues. One small study (21 participants) compared eight weeks of treatment with cannabis cigarettes containing 115 mg of D9-tetrahydrocannabinol (THC) to placebo cigarettes containing cannabis with the THC removed in participants with active Crohn’s disease who had failed at least one medical treatment. Although no difference in clinical remission rates was observed, more participants in the cannabis group had improvement in their Crohn’s disease symptoms than participants in the placebo group. More side effects were observed in the cannabis cigarette group compared to placebo. These side effects were considered to be mild in nature and included sleepiness, nausea, difficulty with concentration, memory loss, confusion and dizziness. Participants in the cannabis cigarette group reported improvements in pain, appetite and satisfaction with treatment.

One small study (22 participants) compared cannabis oil (10 mg of cannabidiol twice daily) to placebo oil (i.e. olive oil) in participants with active Crohn’s disease who had failed at least one medical treatment. No difference in clinical remission rates was observed. There was no difference in serious side effects. Serious side effects included worsening Crohn’s disease in one participant in each group.

One small study (50 participants) compared cannabis oil (composed of 15% cannabidiol and 4% THC) to placebo oil in participants with active Crohn’s disease. Positive differences in quality of life and the Crohn’s disease activity index were observed.

Conclusions

The effects of cannabis and cannabis oil on Crohn’s disease are uncertain. No firm conclusions regarding the benefits and harms (e.g. side effects) of cannabis and cannabis oil in adults with Crohn’s disease can be drawn. The effects of cannabis and cannabis oil in people with Crohn’s disease in remission have not been investigated. Further studies with larger numbers of participants are required to assess the potential benefits and harms of cannabis in Crohn’s disease. Future studies should assess the effects of cannabis in people with active and inactive Crohn’s disease. Different doses of cannabis and formulations (e.g. cannabis oil or pills) should be investigated.

The effects of cannabis and cannabis oil on Crohn’s disease are uncertain. Thus no firm conclusions regarding the efficacy and safety of cannabis and cannabis oil in adults with active Crohn’s disease can be drawn. The effects of cannabis or cannabis oil in quiescent Crohn’s disease have not been investigated. Further studies with larger numbers of participants are required to assess the potential benefits and harms of cannabis in Crohn’s disease. Future studies should assess the effects of cannabis in people with active and quiescent Crohn’s disease. Different doses of cannabis and delivery modalities should be investigated.

Crohn’s disease (CD) is a chronic immune-mediated condition of transmural inflammation in the gastrointestinal tract, associated with significant morbidity and decreased quality of life. The endocannabinoid system provides a potential therapeutic target for cannabis and cannabinoids and animal models have shown benefit in decreasing inflammation. However, there is also evidence to suggest transient adverse events such as weakness, dizziness and diarrhea, and an increased risk of surgery in people with CD who use cannabis.

The objectives were to assess the efficacy and safety of cannabis and cannabinoids for induction and maintenance of remission in people with CD.

We searched MEDLINE, Embase, AMED, PsychINFO, the Cochrane IBD Group Specialized Register, CENTRAL, ClinicalTrials.Gov, and the European Clinical Trials Register up to 17 October 2018. We searched conference abstracts, references and we also contacted researchers in this field for upcoming publications.

Randomized controlled trials comparing any form of cannabis or its cannabinoid derivatives (natural or synthetic) to placebo or an active therapy for adults with Crohn’s disease 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. Remission is commonly defined as a Crohn’s disease activity index (CDAI) of < 150. Relapse is defined as a CDAI > 150. Secondary outcomes included clinical response, endoscopic remission, endoscopic improvement, histological improvement, quality of life, C-reactive protein (CRP) and fecal calprotectin measurements, adverse events (AEs), serious AEs, withdrawal due to AEs, and cannabis dependence and withdrawal effects. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) and 95% CI. Data were combined for analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). Data were analyzed on an intention-to-treat basis and the overall certainty of the evidence supporting the outcomes was evaluated using the GRADE criteria.

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Three studies (93 participants) that assessed cannabis in people with active CD met the inclusion criteria. One ongoing study was also identified. Participants in two of the studies were adults with active Crohn’s disease who had failed at least one medical treatment. The inclusion criteria for the third study were unclear. No studies that assessed cannabis therapy in quiescent CD were identified. The studies were not pooled due to differences in the interventional drug.

One small study (N = 21) compared eight weeks of treatment with cannabis cigarettes containing 115 mg of D9-tetrahydrocannabinol (THC) to placebo cigarettes containing cannabis with the THC removed in participants with active CD. This study was rated as high risk of bias for blinding and other bias (cannabis participants were older than placebo). The effects of cannabis on clinical remission were unclear. Forty-five per cent (5/11) of the cannabis group achieved clinical remission compared with 10% (1/10) of the placebo group (RR 4.55, 95% CI 0.63 to 32.56; very low certainty evidence). A difference was observed in clinical response (decrease in CDAI score of >100 points) rates. Ninety-one per cent (10/11) of the cannabis group achieved a clinical response compared to 40% (4/10) of the placebo group (RR 2.27, 95% CI 1.04 to 4.97; very low certainty evidence). More AEs were observed in the cannabis cigarette group compared to placebo (RR 4.09, 95% CI 1.15 to 14.57; very low certainty evidence). These AEs were considered to be mild in nature and included sleepiness, nausea, difficulty with concentration, memory loss, confusion and dizziness. This study did not report on serious AEs or withdrawal due to AEs.

One small study (N = 22) compared cannabis oil (5% cannabidiol) to placebo oil in people with active CD. This study was rated as high risk of bias for other bias (cannabis participants were more likely than placebo participants to be smokers). There was no difference in clinical remission rates. Forty per cent (4/10) of cannabis oil participants achieved remission at 8 weeks compared to 33% (3/9) of the placebo participants (RR 1.20, 95% CI 0.36 to 3.97; very low certainty evidence). There was no difference in the proportion of participants who had a serious adverse event. Ten per cent (1/10) of participants in the cannabis oil group had a serious adverse event compared to 11% (1/9) of placebo participants (RR 0.90, 95% CI 0.07 to 12.38, very low certainty evidence). Both serious AEs were worsening Crohn’s disease that required rescue intervention. This study did not report on clinical response, CRP, quality of life or withdrawal due to AEs.

One small study (N= 50) compared cannabis oil (15% cannabidiol and 4% THC) to placebo in participants with active CD. This study was rated as low risk of bias. Differences in CDAI and quality of life scores measured by the SF-36 instrument were observed. The mean quality of life score after 8 weeks of treatment was 96.3 in the cannabis oil group compared to 79.9 in the placebo group (MD 16.40, 95% CI 5.72 to 27.08, low certainty evidence). After 8 weeks of treatment, the mean CDAI score was118.6 in the cannabis oil group compared to 212.6 in the placebo group (MD -94.00, 95%CI -148.86 to -39.14, low certainty evidence). This study did not report on clinical remission, clinical response, CRP or AEs.

SNL Star Treats Crohn’s Disease with Marijuana

— "I wouldn’t be able to do [the show] if I didn’t smoke weed"

by Michele R. Berman, MD, and Mark S. Boguski, MD, PhD December 6, 2018

Saturday Night Live cast member Pete Davidson has had a roller-coaster year. In June, it was announced that he was engaged to pop star Ariana Grande. By October, the engagement was off. Then he received harsh criticism over a bad joke he made about Texas congressional candidate Dan Crenshaw — a Navy Seal veteran who had lost an eye in Afghanistan. A week later, congressman-elect Crenshaw accepted Davidson’s apology and took a few swipes back at him on SNL’s Weekend Update.

But this past year was, unfortunately, emblematic of Davidson’s life. Pete lost his father, a New York City firefighter at the World Trade Center on 9/11. His father’s death took a heavy toll on him. In a New York Times article, his mother Amy said, “It was sad how sad he was growing up . In school, he would act out.” “At one point, he said, he ripped all his hair out until he was bald. He became a ‘lab rat’ for doctors studying the children of Sept. 11 victims. ‘It was overwhelming,’ he said.”

Davidson was diagnosed with Crohn’s disease when he was 17 or 18. In a recent interview with Nicki Swift, he explained, “Whenever I wake up, if I don’t hit the bowl or something, it’ll feel like someone punched me in the stomach.” He’s been treated with oral drugs as well as the monoclonal antibody drug infliximab (Remicade). He’s tried nutritional therapy, but Davidson told the Breakfast Club crew that “healthy stuff” doesn’t help him, but instead “just goes right through” his body.

But he did eventually find something that seemed to help. In an interview with High Times Davidson said:

“And I found that the medicines that the doctors were prescribing me and seeing all these doctors and trying new things . weed [cannabis] would be the only thing that would help me eat.”

“My stomach would be in pain all day, and I wouldn’t be able to eat, but then I’d smoke and I can eat and do my shows . I wouldn’t be able to do SNL if I didn’t smoke weed. I wouldn’t be able to do anything really. Me performing not high has gone awful. It’s awful for me because I don’t feel well.”

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What is Crohn’s Disease?

Crohn’s disease (CD) is one of two varieties of inflammatory bowel disease or IBD (ulcerative colitis being the other). Both are disorders that involve chronic inflammation of the digestive tract. CD can involve any portion of the digestive tract, from the mouth to anus, however, it most commonly affects the small intestine and proximal colon. Unlike ulcerative colitis, in which the inflammation is relatively superficial, inflammation in CD can involve the entire thickness of intestine.

Researchers estimate that more than half a million people in the United States have Crohn’s disease. Studies show that, over time, Crohn’s disease has become more common in the United States and other parts of the world. The reason for this increase is unknown.

Crohn’s disease can develop in people of any age and is more likely to develop in people

  • between the ages of 20 and 29
  • who have a family member, most often a sibling or parent, with IBD
  • who smoke cigarettes

The most common symptoms of Crohn’s disease are

  • diarrhea
  • abdominal cramping and pain
  • weight loss

Other symptoms include

  • anemia
  • eye redness or pain (uveitis)
  • fatigue
  • fever
  • joint pain or soreness
  • nausea or loss of appetite
  • skin changes including erythema nodosum and pyoderma gangrenosum

What are the complications of Crohn’s disease?

Complications of Crohn’s disease can include the following:

  • Intestinal obstruction. CD can thicken the intestinal wall which, over time, can cause intestinal narrowing and blockage.
  • Fistulas. Inflammation which extends the full thickness of the intestinal wall creates tunnels, or fistulas. Fistulas may become infected.
  • Abscesses
  • Anal fissures may cause itching, pain, or bleeding.
  • Ulcers. Inflammation anywhere along the digestive tract can lead to ulcers in the mouth, intestines, anus or perineum.
  • Malnutrition
  • Extraintestinal inflammation. CD can cause inflammation in the joints, eyes and skin.
  • Colon cancer. There is an increased rate of intestinal cancer in Crohn’s disease, including both colon and small bowel sites. (Freeman, 2008)

How is Crohn’s disease treated?

Although there is yet no cure for Crohn’s disease, there are many drugs that can reduce symptoms. According to the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), drugs to treat Crohn’s disease include:

Aminosalicylates contain 5-aminosalicylic acid (5-ASA), which helps control inflammation. Doctors use aminosalicylates to treat people newly diagnosed with Crohn’s disease who have mild symptoms. Aminosalicylates include balsalazide, mesalamine, olsalazine, and sulfasalazine.

Corticosteroids are prescribed for people with moderate to severe symptoms. Corticosteroids include budesonide, hybrocortisone, methylprednisolone, and prednisone.

Immunomodulators reduce immune system activity, resulting in less inflammation. Immunomodulators can take several weeks to 3 months to start working. Immunomodulators include 6-mercaptopurine, azathioprine, cyclosporine, and methotrexate.

Biologic therapies target proteins made by the immune system. Neutralizing these proteins decreases inflammation in the intestines.

Even with these medicines, however, surgery is often needed to treat complications.

The role of cannabinoids in the treatment of Crohn’s Disease

People have used cannabis for a variety of health conditions for at least 3,000 years. More recently, individual components of marijuana or similar synthetic substances, called cannabinoids, have also been used for health purposes. Cannabinoids are active chemicals in cannabis that cause drug-like effects throughout the body, including the central nervous system and the immune system. The main active cannabinoid in cannabis is delta-9-THC. Another active cannabinoid is cannabidiol (CBD), which may relieve pain, lower inflammation, and decrease anxiety without causing the “high” of delta-9-THC.

Research into the effects of cannabinoids lead to the discovery of the endocannabinoid system (ECS). The ECS is a biological system composed of endocannabinoids, which are endogenous lipid-based neurotransmitters that bind to cannabinoid receptors, the cannabinoid receptor proteins that are expressed throughout the central and peripheral nervous systems and the enzymes responsible for synthesis and degradation of the endocannabinoids. ECS has emerged as an important neuromodulatory system.

Endocannabinoids exert their effects by finding to specific receptors on their target cells. There are two main types of cannabinoid receptors, CB1 and CB2. CB1 receptors, the most predominant form, are found mostly in neurons in the CNS and PNS, while CB2 receptors are commonly identified in immune cells. The best characterized endocannabinoids are N-arachidonoylethanolamide (anandamide) and two-arachidonolyl glycerol (2-AG).

In the gastrointestinal system, CB1 and CB2 are found in all layers of the intestinal wall. According to Ahmed and Katz, “Cannabinoids predominately mediate inhibitory pathways in the GI tract through reduction of vagal cholinergic tone. CB2 modulate inflammation, whereas CB1 control central functions, including pain control, satiety, nausea, and vomiting.”

Surveys by Garcia-Planella, Lal, and Allegretti found significant proportions of patients with IBD use complementary and alternative medicine (CAM) for additional management of symptoms. Ten to 16% of patients reported active use, while 32-50% of patients reported lifetime use of medical cannabis specifically for symptom relief of IBD. The patients cite ineffectiveness of current therapy, fewer side effects, and a sense of gaining control over their illness as motives for CAM use. It should be noted that the surveys also showed that patients infrequently reported their cannabis use to their physicians.

Is there any scientific evidence to support the use of cannabis in IBD? A 2014 Canadian study by Storr et al had 313 patients with IBD seen at the University of Calgary fill out a questionnaire covering motives, pattern of use, and subjective beneficial and adverse effects associated with self-administration of cannabis. “Cannabis had been used by 17.6% of respondents specifically to relieve symptoms associated with their IBD, the majority by inhalational route (96.4%). Patients with IBD reported that cannabis improved abdominal pain (83.9%), abdominal cramping (76.8%), joint pain (48.2%), and diarrhea (28.6%),” However, they also found that in patients with CD with a prolonged use of cannabis (>6 months), there was an increased history of surgery. But they acknowledge that it was not possible to associate the time of cannabis use with surgery, so temporal relationships or causation could not be made.

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Naftali and her colleagues in Israel have presented several studies on the response of patients with CD to cannabis. The first, a retrospective observational study in 2011, interviewed 30 patients with CD who had been prescribed cannabis. Disease activity before and after cannabis was estimated using a Harvey Bradshaw index (a simplification of the Crohn’s Disease Activity Index-CDAI). They found that “Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 ± 6.7 to 7 ± 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use.

Her second study in 2014, was a prospective placebo-controlled study with 21 patients with CD who did not respond to therapy with steroids, immunomodulators, or anti-tumor necrosis factor-α agents. They were divided into two groups, one given cannabis, twice daily for 8 weeks, in the form of THC-containing cigarettes or placebo containing cannabis flowers from which the THC had been extracted. “Complete remission (CDAI score, <150) was achieved by 5 of 11 subjects in the cannabis group (45%) and 1 of 10 in the placebo group (10%; P = .43). A clinical response (decrease in CDAI score of >100) was observed in 10 of 11 subjects in the cannabis group and 4 of 10 in the placebo group. Three patients in the cannabis group were weaned from steroid dependency. Subjects receiving cannabis reported improved appetite and sleep, with no significant side effects.

At the United European Gastroenterology conference in Vienna, October 2018, Naftali reported her latest findings. Forty-six people with moderately severe CD were randomized to receive wither cannabis oil (15% cannabidiol and 4% THC) or placebo for 8 weeks.” The group receiving the cannabis oil had a significant reduction in their Crohn’s disease symptoms compared with the placebo group, and 65%met strict criteria for clinical remission (versus 35% of the placebo recipients).”

But the most surprising aspect of the study came when they measured inflammation in the gut using endoscopy and measuring inflammatory markers. “We have previously demonstrated that cannabis can produce measurable improvements in Crohn’s disease symptoms but, to our surprise, we saw no statistically significant improvements in endoscopic scores or in the inflammatory markers we measured in the cannabis oil group compared with the placebo group,” said Dr. Naftali. “We know that cannabinoids can have profound anti-inflammatory effects, but this study indicates that the improvement in symptoms may not be related to these anti-inflammatory properties.”

Although the early scientific evidence is promising, larger scale, longer follow-up trials are needed.

Do any of you have any patients using cannabis as a complementary treatment for Crohn’s disease? What has been your experience?

Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.

Cannabis oil improves Crohn’s disease symptoms: study

According to a new study, cannabis oil can “significantly” improve Crohn’s disease symptoms.

“(S)tudies have shown that many people with Crohn’s disease use cannabis regularly to relieve their symptoms,” Dr. Timna Naftali, an Israeli gastroenterologist who also teaches at Tel Aviv University, said in a written statement. “It has always been thought that this improvement was related to a reduction in inflammation in the gut and the aim of this study was to investigate this.”

Crohn’s disease is a lifelong inflammatory bowel disease (IBD) that can cause severe belly pain and chronic diarrhea.

Dr. Naftali, whose study is being billed as the first of its kind, found that an eight-week treatment with cannabis oil containing a four to one CBD to THC ratio produced clinical remission in up to 65 per cent of individuals with Crohn’s disease. The randomized, placebo-controlled study involved 50 people with moderately severe forms of the disease. The group that received cannabis oil also reported significant improvements in their quality of life.

Interestingly, however, cannabis was found to have no effect on the gut inflammation that underscores the disease.

"We have previously demonstrated that cannabis can produce measurable improvements in Crohn’s disease symptoms but, to our surprise, we saw no statistically significant improvements in endoscopic scores or in the inflammatory markers we measured in the cannabis oil group compared with the placebo group," Dr. Naftali explained. "We know that cannabinoids can have profound anti-inflammatory effects but this study indicates that the improvement in symptoms may not be related to these anti-inflammatory properties."

Going forward, Dr. Naftali and her research team plan to further investigate cannabis’ potential anti-inflammatory properties to treat IBDs.

"There are very good grounds to believe that the endocannabinoid system is a potential therapeutic target in Crohn’s disease and other gastrointestinal diseases," Dr. Naftali said. "For now, however, we can only consider medicinal cannabis as an alternative or additional intervention that provides temporary symptom relief for some people with Crohn’s disease.”

Workers package cannabis oil at Canopy Growth Corporation’s Tweed facility in Smiths Falls, Ont., on Monday, Feb. 12, 2018. (THE CANADIAN PRESS/Sean Kilpatrick)