Should gastroenterologists prescribe cannabis? The highs, the lows and the unknowns

Table 1 Use of cannabis on gastrointestinal disorders and symptoms

Ref.	GI disorders/symptoms	Study type	Number of subjects	Cannabis type and modality	Outcome
Irving et al[32], 2018	Ulcerative colitis	RCT	60	CBD-rich extract (3.2%-4.7% THC) 500 mg/day	Improvement in quality of life, symptoms
Naftali et al[148], 2018	Ulcerative colitis	RCT	28	Cannabis cigarettes (11.5 mg THC; 23 mg THC/day daily)	Endoscopic and clinical improvement in moderately active ulcerative colitis
Naftali et al[21], 2011	Crohn’s disease	Retrospective observational	30	Inhaled or oral cannabis	Reduction in disease activity index, need for other drugs and surgeries
Naftali et al[28], 2013	Crohn’s disease	Prospective RCT	21	Cannabis sativa cigarette (23% THC, 0.5% cannabidiol)	Significant clinical response, no decrease in CRP
Naftali et al[29], 2017	Crohn’s disease	RCT	19	Oral CBD 10 mg BID	CBD safe but no beneficial effect
Naftali et al[31], 2021	Crohn’s disease	RCT	56	CBD rich oil 160/40 mg/mL (CBD/THC); placebo	Clinical and quality of life improvement without change in inflammatory markers or endoscopic scores
Naftali et al[25], 2019	IBD	Prospective	127	30 g per month or THC 21 mg and CBD 170 mg daily	Clinical improvement, reduced use of medication and slight weight gain
Lahat et al[20], 2012	IBD	Prospective	13	Inhaled cannabis 50 g/month	Improved quality of life measurements and disease activity index and weight gain
Lal et al[23], 2011	IBD	Cross-sectional survey	291	Cannabis (reported)	Used for symptom relief particularly those with history of abdominal surgery, low quality of life index and/or chronic abdominal pain
Storr et al[24], 2014	IBD	Cross-sectional survey	313	Cannabis (reported)	Pain and diarrheal relief but associated with higher risk of surgery
Hoffenberg et al[149], 2019	IBD	Prospective/descriptive	15	Oral or sublingual cannabis oil plus other forms (varying contents CBD:THC)	Adolescents and young adults improvement in sleep. Nausea and appetite. No weight gain.
Kerlin et al[27], 2018	IBD	Survey	1666	Cannabis (reported)	Improvement in pain, appetite and anxiety but had higher baseline anxiety, IBD symptoms and pain that nonusers
Desai et al[30], 2019	IBD	Retrospective	7483	Cannabis (reported)	Decreased length of hospital stay. In Crohn’s disease, lower need for parenteral nutrition but increased risk of intrabdominal abscess or active fistulizing disease
Dalavaye et al[22], 2023	IBD	Prospective case series	76	Oral, sublingual or vaping. THC and CBD variable dosages	Improved quality of life including sleep and anxiety
Bateman[37], 1983	Motility	RCT	7	THC 0.5 or 1 mg injections	No significance in gastric emptying of liquid
McCallum et al[35], 1999	Motility	RCT	13	THC 10 mg/m2 of body surface area (unclear route)	Significant delay in gastric emptying with solid food but no correlation between plasma THC level and delay in gastric emptying
Klooker et al[43], 2011	IBS	RCT	22	Oral THC: DRO 5 and 10 mg	No alteration in baseline visceral perception in rectal distension
Wong et al[45], 2011	IBS	RCT	75	Oral THC: DRO 2.5 and 5 mg	Increase in colonic compliance, decrease colonic motility index in IBS-D and IBS-A, no effect on sensation or tone
Wong et al[44], 2012	IBS	RCT	36	Oral THC: DRO 2.5 and 5 mg BID	No effect on gut transit. DRO delays colonic transit in those with CNR1 genotype variant
Patel et al[46], 2020	IBS	Retrospective study	31272	Cannabis (reported)	Higher odds of IBS-hospitalizations and rising trend of cannabis use and related psychiatric comorbidities
Desai et al[42], 2020	IBS	Retrospective study	9363	Cannabis (reported)	Decreased healthcare utilization and costs
Choi et al[150], 2022	IBS	Retrospective study	7163	Cannabis (reported)	No difference in readmission rates for IBS-specific causes for cannabinoid users and non-users
Beaumont et al[51], 2009	GERD	RCT	18	Oral THC: DRO 10 mg/20 mg	Inhibits post-prandial increase in transient LES relaxation and reduces LES basal pressure
Smith et al[56], 2015	Nausea and vomiting	Meta analysis of 23 studies	N/A	Cannabis (reported)	Cannabinoids are effective in treating nausea and vomiting but not concluded as superior to traditional anti-emetics
Grimison et al[60], 2020	Nausea and vomiting	RCT	81	Oral THC 2.5 mg/CBD 2.5 mg	Less nausea and vomiting but additional side effects in chemotherapy induced nausea and vomiting
Jatoi et al[72], 2002	Cancer-related anorexia/cachexia	RCT	469	Oral THC: DRO 2.5 mg BID	Megestrol acetate was superior to anorexia palliation compared to dronabinol alone
Strasser et al[71], 2006	Cancer-related anorexia/cachexia	RCT	164	Oral cannabis extract (2.5 mg THC and 1 mg cannabidiol); or oral 2.5 mg THC	No difference in appetite or quality of life in cancer patients
Brisbois et al[70], 2011	Cancer-related anorexia/cachexia	RCT	21	Oral DRO 2.5 mg BID	Improved chemosensory perception, improved appetite and increased protein caloric intake
Foltin et al[151], 1998	Weight gain	RCT	6	Smoked marijuana cigarettes (2.3% THC)	40% increase in daily caloric intake due to increased snacking
Timpone et al[69], 1997	Anorexia in HIV	RCT	39	Oral DRO 2.5 mg BID	Megastrol acetate had greater weight gain than dronabinol and combination did not show additional weight gain in HIV patients
Haney et al[66], 2005	Anorexia in HIV	RCT	30	Smoked marijuana cigarettes (1.8, 2.9, 3.9% THC); oral DRO 10, 20 and 30 mg	Calorie intake increased in cannabis use in HIV patients
Haney et al[67], 2007	Anorexia in HIV	RCT	10	Smoked marijuana cigarettes (2.0, 3.9% THC); oral DRO 5 mg and 10 mg	Calorie intake and weight increased in a dose dependent response in cannabis use in HIV patients
Bedi et al[68], 2010	Anorexia in HIV	RCT	7	Oral DRO 10 mg QID	Increased caloric intake but repeated high dose led to selective tolerance without increase in body weight in HIV patients
Ngueta et al[79], 2015	Obesity	Cross sectional/Observational	786	Cannabis (reported)	Cannabis use association with lower BMI and lower percent fat mass
Jin et al[82], 2017	Obesity	Observational/Longitudinal	712	Cannabis (reported)	No association in adolescent cannabis use and weight change from adolescence to midlife
Ross et al[81], 2020	Obesity	Longitudinal/Observational	401	Cannabis (reported)	Higher baseline BMI led to increased cannabis use in adolescents. Increased cannabis use led to small decrease in BMI over 2 years
ElTelbany et al[90], 2022	Hepato-cellular carcinoma	Observational study	101231036	Cannabis (reported)	Cannabis users 55% less likely to have hepatocellular carcinoma than nonusers
Adejumo et al[99], 2017	NAFLD	Case control study	5950391	Cannabis (reported)	Dose dependent reduction in prevalence of NAFLD with cannabis use
Vazquez et al[100], 2019	NAFLD	Observational longitudinal study	390	Cannabis (reported)	Cannabis consumption led to lower fatty liver index demonstrating lower risk of developing NAFLD over 3 yr in psychosis patients
Adejumo et al[101], 2018	Alcohol-associated liver disease	Cross-sectional study	318514	Cannabis (reported)	Cannabis use associated with decreased incidence of alcoholic liver disease
Nordmann et al[106], 2018	Hepatic steatosis	Prospective cohort study	838	Cannabis (reported)	Cannabis use associated with reduced prevalence of steatosis in HIV-HCV co-infected patients
Barré et al[105], 2021	Hepatic steatosis	Observational longitudinal study	997	Cannabis (reported)	Cannabis use associated with reduced risk of elevated fatty liver index in HIV-HCV co-infected patients
Ishida et al[97], 2008	Hepatitis C and fibrosis	Cohort study	204	Cannabis (reported)	Daily cannabis use associated with moderate to severe fibrosis in HCV infected individuals
Liu et al[104], 2014	Hepatitis C and fibrosis	Retrospective cross-sectional study	550	Cannabis (reported)	No association between cannabis use and fibrosis in HCV infected patients
Simons-Linares et al[113], 2018	Acute pancreatitis	Retrospective cohort study	460	Cannabis (reported)	Cannabis has potential association with acute pancreatitis but does not affect mortality or disease severity

IBD: Inflammatory bowel disease; IBS: Irritable bowel syndrome; GERD: Gastroesophageal reflux disease; NAFLD: Nonalcoholic fatty liver disease; HCV: Hepatitis C virus; CBD: Cannabidiol; THC: Tetrahydrocannabinol; DRO: Dronabinol; RCT: Randomized controlled trial; BID: Twice daily; HIV: Human immunodeficiency virus.

Table 2 Risks and side effects from cannabis use

No.	Risks and side effects
1	Decreased cognition, learning and memory[118,119]
2	Schizophrenia and psychosis[116,143]
3	High tar and carbon monoxide concentrations[120]
4	Cannabis use disorder/addiction/dependence[131]
5	Drug addiction[137]
6	Cannabis withdrawal symptoms[132]
7	Anxiety[133,135]
8	Cannabinoid hyperemesis syndrome[139,140]
9	Chronic bronchitis and chronic cough[121,122]
10	Increased risk of motor vehicle accidents[125,126]
11	Unintentional overdose in children[128,129]