Inflammatory Bowel Disease
Seriousness of medical condition(s)
In Australia, IBD is becoming more prevalent, more complex, and more severe. It affects approximately 1 in 250 people aged 5-40. Almost 75,000 Australians have Crohn’s disease or ulcerative colitis, with this number projected to increase to 100,000 by 2022. Australia has one of the highest rates of prevalence and incidence in the world and each year more and more young people are being diagnosed. Over 74,955 Australians are burdened with a constant and often hidden struggle that affects a sufferer’s personal, social and work life. The predominant model of treating only acute IBD flares is at odds with the need for long-term management. (Crohn’s and Colitis Australia. Improving Inflammatory Bowel Disease care across Australia. March 2013)
There are promising studies demonstrating Medicinal Cannabis as a disease modifying drug in IBD and will be used as a supplementary therapy to standard of care therapies.
Who could benefit from this treatment?
Clinical justification for using Medicinal Cannabis
Inflammatory bowel disease (IBD) is a lifelong disease of the gastrointestinal tract whose annual incidence and prevalence is on the rise. Current immunosuppressive therapies available for treatment of IBD offer limited benefits and lose effectiveness, exposing a significant need for the development of novel therapies. In the clinical setting, cannabis has been shown to provide patients with IBD symptomatic relief, although the underlying mechanisms of their anti-inflammatory effects remain unclear (Leinwand et al, 2017).
The first report of cannabis use in Crohn’s disease in humans was published by Naftali and colleagues in 2011. This was a retrospective observational study in 30 patients who used cannabis. Of those 30 patients, 21 improved significantly after treatment with cannabis and the need for other medication was significantly reduced (Naftali et al).
In a subsequent randomized placebo controlled study of 21 patients, complete remission was achieved by 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. Three patients in the cannabis group were weaned from steroid dependency. Subjects reported improved appetite and sleep, with no significant side effects (Naftali et al, 2011).
In a study by Lal and colleagues (2011) a total of 100 patients with ulcerative colitis and 191 patients with Crohn’s disease attending an outpatient clinic completed a questionnaire on cannabis usage and usage of other alternative medicines. A significant number of ulcerative colitis and Crohn’s disease patients reported lifetime (51%) or current (12%) usage of cannabis, particularly those with a history of abdominal surgery or chronic abdominal pain and/or a low quality of life index. (Lal et al, 2011).
Observational studies have also been published by Storr (2014) who reported three months’ treatment with inhaled cannabis improves quality of life measurements, disease activity index, and causes weight gain and rise in BMI in long-standing IBD patients (Lahat et al, 2012) who reported Patients with IBD reported that Cannabis improved abdominal pain (83.9%), abdominal cramping (76.8%), joint pain (48.2%), and diarrhea (28.6%), although side effects were frequent (Storr et al, 2014).
Unknown or expected adverse effects, risks and safety issues & related toxicology:
A systematic review by Whiting et al. (2015) stated in their conclusions that “Cannabinoids were associated with an increased risk of short-term adverse effects”.
According to the Guidance for the Use of Medicinal Cannabis in Australia: Overview, Therapeutics Good Administration
(2017): Cannabis is not appropriate for patients who:
- Are under the age of 25 (with the exception of intractable epilepsy or severe pain syndrome)
- Have a personal history or strong family history of psychosis
- Have a current or past cannabis use disorder, or active substance use disorder
- Have unstable respiratory or cardiovascular disease (including angina, peripheral vascular disease, cerebrovascular disease, arrhythmias)
- Are pregnant, planning to become pregnant, or
Cannabis should be authorized with caution in patients who:
- Smoke tobacco
- Have risk factors for cardiovascular disease
- Are heavy users of alcohol
- Are taking sedating medications or any other medication metabolized by the CYP450 pathway
- At risk or have liver disease
Potential drug interactions
Increasing THC concentration:
Examples of inhibitors:
– Antidepressants (e.g. Fluoxetine, Fluvoxamine)
– Proton Pump Inhibitors (e.g. Omeprazole)
– Macrolides (Clarithromycin, Erythromycin)
– Antimycotics (e.g. Itraconazole, Fluconazole, Ketoconazole, Miconazole)
– Calcium Antagonists (e.g. Diltiazem, Verapamil)
– HIV protease inhibitors (e.g. Ritonavir)
– Grapefruit juice
Increasing CBD concentration:
– Metabolized by CYP 2C19 and CYP 3A4
– Bioavailability could be increased by many of the same substances as for THC
Decreasing THC and CBD concentration:
- CYP 2C9 and 3A4 Inducers accelerate THC and CBD metabolism
- Examples of inducers:
– Saint John’s Wort
Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen in the study by Gaston et al (2017) on interactions between cannabidiol (Epidiolex.) and commonly used antiepileptic
drugs. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with supraphysiological doses of CBD (e.g. 1000mg/kg).
- Caution with blood thinners like Warfarin, Heparin,
- Additionally, pharmacodynamic interactions should be expected between cannabis and drugs with sympathomimetic activity (tachycardia,
hypertension), central nervous system depressants (drowsiness, ataxia), and drugs with anticholinergic effects (tachycardia, drowsiness).
Many of these drug interactions can be mitigated in complex patients with polypharmacy by slowly titrating cannabis.
Approved treatments for this medical condition
- 5-ASA agent (e.g. Pentasa),
- 6-MP/Azathioprine, Biologics (e.g. Infliximab),
Why is medicinal cannabis appropriate for use?
Medicinal cannabis products will be considered for treatment when:
- standard of care medications have been trialed to maximally tolerated dose without acceptable symptom relief or functional improvements.
- Patient is unable to tolerate standard of care medications
- Standard of care medications are contraindicated.
The medicinal cannabis will not be used as sole treatment of condition. Chronic conditions often require polypharmacy to manage and are difficult to treat. In this way, the medicinal cannabis will act as an adjuvant. Tolerability and efficacy of adjuvants must be trialed in individual patients.
- Lahat A, Lang A, Ben-Horin S, Impact of Cannabis Treatment on the Quality of Life, Weight and Clinical Disease Activity in Inflammatory Bowel Disease Patients: A Pilot Prospective Study. Digestion 2012;85:1-8
- Leinwand K, Gerich M, Hoffenberg E, Collins C; Manipulation of the Endocannabinoid System in Colitis: A Comprehensive Review, Inflammatory Bowel Diseases, Volume 23, Issue 2, 1 February 2017, Pages 192–199, https://doi.org/10.1097/MIB.0000000000001004
- Naftali, T., Bar Lev, L., Yablekovitch, D. et al. Treatment of Crohn’s disease with cannabis: an observational study. Isr Med Assoc J. 2011; 13: 455–458.
- Naftali, Timna et al., Cannabis Induces a Clinical Response in Patients With Crohn’s Disease: A Prospective Placebo-Controlled Study. Clinical Gastroenterology and Hepatology, Volume 11, Issue 10, 1276 – 1280.e1
- Simon Lal, Neeraj Prasad, Manijeh Ryan, et al, Cannabis use amongst patients with inflammatory bowel disease. European Journal of Gastroenterology & Hepatology: October 2011 – Volume 23 – Issue 10 – p 891-896 doi: 10.1097/MEG.0b013e328349bb4c
- Storr M, Devlin S, Kaplan G, Panaccione R, Andrews C. Cannabis Use Provides Symptom Relief in Patients with Inflammatory Bowel Disease but Is Associated with Worse Disease Prognosis in Patients with Crohn’s Disease, Inflammatory Bowel Diseases, Volume 20, Issue 3, 1 March 2014, Pages 472–480,
- Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 2015;313(24):2456-73. Errata in: JAMA 2016;315(14):1522, JAMA 2015;314(21):2308, JAMA 2015;314(5):520, JAMA 2015;314(8):837.