The effect of medical cannabis in inflammatory bowel disease: analysis from the UK Medical Cannabis Registry

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“Objectives: Cannabis-based medicinal products (CBMPs) have shown promising preclinical activity in inflammatory bowel disease. However, clinical trials have not demonstrated significant effects on active inflammation. This study aims to analyze changes in health-related quality of life (HRQoL) and adverse events in IBD patients prescribed CBMPs.

Methods: A case series from the UK Medical Cannabis Registry was performed. Primary outcomes included changes from baseline in the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), Generalized Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L Index score at 1 and 3 months. Statistical significance was defined using p<0.050. Secondary outcomes included incidence of adverse events.

Results: Seventy-six patients with Crohn’s disease (n=51; 67.11%) and ulcerative colitis (n=25; 32.89%) were included. The median baseline SIBDQ score improved at 1 and 3 months. EQ-5D-5L index values, GAD-7 and SQS also improved after 3 months (p<0.050). Sixteen (21.05%) patients reported adverse events with the majority being classified as mild to moderate in severity. No life-threatening AEs were reported.

Conclusion: Patients treated with CBMPs for refractory symptoms of Crohn’s disease and ulcerative colitis demonstrated a short-term improvement in IBD-specific and general HRQoL. Prior cannabis consumers reported greater improvement compared to cannabis-naïve individuals.”

https://pubmed.ncbi.nlm.nih.gov/36562418/

https://www.tandfonline.com/doi/abs/10.1080/17474124.2022.2161046?journalCode=ierh20

Cannabinoid Therapeutic Effects in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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“Introduction: Inflammatory Bowel Disease (IBD) patients may benefit from cannabinoid administration supplementary therapy; currently no consensus on its effect has been reached.

Methods: a systematic review of RCTs on cannabinoid supplementation therapy in IBD has been conducted; data sources were MEDLINE, Scopus, ClinicalTrials.

Results: out of 974 papers found with electronic search, six studies have been included into the systematic review, and five of them, for a grand total of 208 patients, were included into the meta-analysis.

Conclusions: cannabinoid supplementation as adjuvant therapy may increase the chances of success for standard therapy of Crohn’s Disease during the induction period; no statement on its potential usage during maintenance period can be derived from retrieved evidence. Its usage in Ulcerative Colitis is not to be recommended. If ever, low-dose treatment may be more effective than higher dosage. Mean CDAI reduction was found stronger in patients treated with cannabinoids (mean CDAI reduction = 36.63, CI 95% 12.27-61.19) than placebo. In future studies, it is advisable to include disease activity levels, as well as patient-level information such as genetic and behavioral patterns.”

https://pubmed.ncbi.nlm.nih.gov/36289701/

https://www.mdpi.com/2227-9059/10/10/2439/htm

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

 

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

Cannabis and Canabidinoids on the Inflammatory Bowel Diseases: Going Beyond Misuse.

ijms-logo“Inflammatory bowel diseases (IBD) are characterized by a chronic and recurrent gastrointestinal condition, including mainly ulcerative colitis (UC) and Crohn’s disease (CD). Cannabis sativa (CS) is widely used for medicinal, recreational, and religious purposes. The most studied compound of CS is tetrahydrocannabinol (THC) and cannabidiol (CBD). Besides many relevant therapeutic roles such as anti-inflammatory and antioxidant properties, there is still much controversy about the consumption of this plant since the misuse can lead to serious health problems. Because of these reasons, the aim of this review is to investigate the effects of CS on the treatment of UC and CD. The literature search was performed in PubMed/Medline, PMC, EMBASE, and Cochrane databases. The use of CS leads to the improvement of UC and CD scores and quality of life. The medical use of CS is on the rise. Although the literature shows relevant antioxidant and anti-inflammatory effects that could improve UC and CD scores, it is still not possible to establish a treatment criterion since the studies have no standardization regarding the variety and part of the plant that is used, route of administration and doses. Therefore, we suggest caution in the use of CS in the therapeutic approach of IBD until clinical trials with standardization and a relevant number of patients are performed.”

https://www.ncbi.nlm.nih.gov/pubmed/32331305

https://www.mdpi.com/1422-0067/21/8/2940

An overview of cannabis based treatment in Crohn’s disease.

 Publication Cover“Cannabis use among inflammatory bowel disease (IBD) patients is common. There are many studies of various laboratory models demonstrating the anti-inflammatory effect of cannabis, but their translation to human disease is still lacking.

Areas covered: The cannabis plant contains many cannabinoids, that activate the endocannabinoid system. The two most abundant phytocannabinoids are the psychoactive Tetrahydrocannabinol (THC), and the (mostly) anti-inflammatory cannabidiol (CBD). Approximately 15% of IBD patients use cannabis to ameliorate disease symptoms. Unfortunately, so far there are only three small placebo controlled study regarding the use of cannabis in active Crohns disease, combining altogether 93 subjects. Two of the studies showed significant clinical improvement but no improvement in markers of inflammation.

Expert opinion: Cannabis seems to have a therapeutic potential in IBD. This potential must not be neglected; however, cannabis research is still at a very early stage. The complexity of the plant and the diversity of different cannabis chemovars create an inherent difficulty in cannabis research. We need more studies investigating the effect of the various cannabis compounds. These effects can then be investigated in randomized placebo controlled clinical trials to fully explore the potential of cannabis treatment in IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/32149543

https://www.tandfonline.com/doi/abs/10.1080/17474124.2020.1740590?journalCode=ierh20

Is Cannabis of Potential Value as a Therapeutic for Inflammatory Bowel Disease?

“Cannabis is commonly used by patients with inflammatory bowel disease (IBD) to ameliorate their symptoms.

Patients claim that cannabis reduces pain, increases appetite, and reduces the need for other medications.

In conclusion, considering the mechanism of action of phytocannabinoids and the accumulating evidence of their anti-inflammatory effects in experimental and in vitro studies, it is reasonable to assume that cannabis can be of benefit in the treatment of IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/31388856

https://link.springer.com/article/10.1007%2Fs10620-019-05763-8

In-hospital outcomes of inflammatory bowel disease in cannabis users: a nationwide propensity-matched analysis in the United States.

“Literature suggests the role of cannabis (marijuana) as an anti-inflammatory agent. However, the impact of recreational marijuana usage on in-hospital outcomes of inflammatory bowel disease (IBD) remains indistinct.

We assessed the outcomes of Crohn’s disease (CD) as well as ulcerative colitis (UC) with vs. without recreational marijuana usage using a nationally illustrative propensity-matched sample.

RESULTS:

Propensity-matched cohorts included 6,002 CD (2,999 cannabis users & 3,003 non-users) and 1,481 UC (742 cannabisusers & 739 non-users) hospitalizations. In CD patients, prevalence of colorectal cancer (0.3% vs. 1.2%, P<0.001), need for parenteral nutrition (3.0% vs. 4.7%, P=0.001) and anemia (25.6% vs. 30.1%, P<0.001) were lower in cannabis users. However, active fistulizing disease or intraabdominal abscess formation (8.6% vs. 5.9%, P<0.001), unspecific lower gastrointestinal (GI) hemorrhage (4.0% vs. 2.7%, P=0.004) and hypovolemia (1.2% vs. 0.5%, P=0.004) were higher with recreational cannabis use. The mean hospital stay was shorter (4.2 vs. 5.0 days) with less hospital charges ($28,956 vs. $35,180, P<0.001) in cannabis users. In patients with UC, cannabis users faced the higher frequency of fluid and electrolyte disorders (45.1% vs. 29.6%, P<0.001), and hypovolemia (2.7% vs.<11) with relatively lower frequency of postoperative infections (<11 vs. 3.4%, P=0.010). No other complications were significant enough for comparison between the cannabis users and non-users in this group. Like CD, UC-cannabis patients had shorter mean hospital stay (LOS) (4.3 vs. 5.7 days, P<0.001) and faced less financial burden ($30,393 vs. $41,308, P<0.001).

CONCLUSIONS:

We found a lower frequency of colorectal cancer, parenteral nutrition, anemia but a higher occurrences of active fistulizing disease or intraabdominal abscess formation, lower GI hemorrhage and hypovolemia in the CD cohort with cannabis usage. In patients with UC, frequency of complications could not be compared between the two cohorts, except a higher frequency of fluid and electrolyte disorders and hypovolemia, and a lower frequency of postoperative infections with cannabis use. A shorter length of stay (LOS)  and lesser hospital charges were observed in both groups with recreational marijuana usage.”

https://www.ncbi.nlm.nih.gov/pubmed/31355219

http://atm.amegroups.com/article/view/25637/24217

Association Between Cannabis Use and Complications Related to Crohn’s Disease: A Retrospective Cohort Study.

“Crohn’s disease is an idiopathic inflammatory process that is occasionally associated with complications, which cause significant morbidity and mortality. The anti-inflammatory effect of cannabis in intestinal inflammation has been shown in several experimental models; it is unknown whether this correlates with fewer complications in Crohn’s disease patients.

AIMS:

To compare the prevalence of Crohn’s disease-related complications among cannabis users and non-users in patients admitted with a primary diagnosis of Crohn’s disease or a primary diagnosis of Crohn’s related complication and a secondary diagnosis of Crohn’s disease between 2012 and 2014.

METHODS:

We used data from the Healthcare Cost and Utilization Project-National Inpatient Sample. Cannabis users (615) were compared directly after propensity score match to non-users, in aspects of various complications and clinical end-points.

RESULTS:

Among matched cohorts, Cannabis users were less likely to have the following: active fistulizing disease and intra-abdominal abscess (11.5% vs. 15.9%; aOR 0.68 [0.49 to 0.94], p = 0.025), blood product transfusion (5.0% vs. 8.0%; aOR 0.48 [0.30 to 0.79], p = 0.037), colectomy (3.7% vs. 7.5%; aOR 0.48 [0.29-0.80], p = 0.004), and parenteral nutrition requirement (3.4% vs. 6.7%, aOR 0.39 [0.23 to 0.68], p = 0.009).

CONCLUSION:

Cannabis use may mitigate several of the well-described complications of Crohn’s disease among hospital inpatients. These effects could possibly be through the effect of cannabis in the endocannabinoid system.”

https://www.ncbi.nlm.nih.gov/pubmed/30825109

https://link.springer.com/article/10.1007%2Fs10620-019-05556-z

Cannabis, cannabinoids and the endocannabinoid system – is there therapeutic potential for inflammatory bowel disease?

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“Cannabis sativa and its extracts have been used for centuries both medicinally and recreationally. There is accumulating evidence that exogenous cannabis and related cannabinoids improve symptoms associated with inflammatory bowel disease such as pain, loss of appetite, and diarrhoea. In vivo, exocannabinoids have been demonstrated to improve colitis, mainly in chemical models. Exocannabinoids signal through the endocannabinoid system, an increasingly understood network of endogenous lipid ligands and their receptors, together with a number of synthetic and degradative enzymes and the resulting products. Modulating the endocannabinoid system using pharmacological receptor agonists, genetic knockout models, or inhibition of degradative enzymes have largely shown improvements in colitis in vivo. Despite these promising experimental results, this has not translated into meaningful benefits for human IBD in the few clinical trials which have been conducted to date. The largest study to date being limited by poor medication tolerance due to the Δ9-tetrahydrocannabinol component. This review article synthesises the current literature surrounding the modulation of the endocannabinoid system and administration of exocannabinoids in experimental and human IBD. Findings of clinical surveys and studies of cannabis use in IBD are summarised. Discrepancies in the literature are highlighted together with identifying novel areas of interest.”

The Role of Cannabis in the Management of Inflammatory Bowel Disease: A Review of Clinical, Scientific, and Regulatory Information: Commissioned by the Crohn’s and Colitis Foundation.

Oxford University Press

“There is significant interest among patients and providers in using cannabis (marijuana) and its derivatives to treat a number of chronic illnesses, including inflammatory bowel disease. Despite the Schedule I classification of cannabis by the federal government, state governments have sought ways to make cannabis available for specific medical conditions, and some states have legalized cannabis outright. This white paper summarizes the preclinical data, clinical data, safety data, and the regulatory landscape as they apply to medical cannabis use in inflammatory bowel disease. Animal models of cannabinoid chemistry and physiology give evidence of anti-inflammatory, antidiarrheal, and nociceptive-limiting properties. Human studies have found benefit in controlling symptoms and improving quality of life, but no studies have established true disease modification given the absent improvement in biomarker profiles or endoscopic healing. Finally, this review describes the legal, regulatory, and practical hurdles to studying the risks and benefits of medical cannabis in the United States.”

https://www.ncbi.nlm.nih.gov/pubmed/30358848

https://academic.oup.com/ibdjournal/advance-article-abstract/doi/10.1093/ibd/izy319/5144402?redirectedFrom=fulltext