Medicinal cannabis 3.0 – a role in treating IBS?

Irritable bowel syndrome (IBS) affects 15-20% of the population worldwide, predominately young professionals in industrialised countries. In the US it is thought to cause $US21b productivity loss. 

A/Prof Alistair Vickery, Cannabinoid Medicine, West Leederville

IBS is diagnosed in those with at least six months intermittent abdominal pain, bloating, diarrhoea, constipation and urgency associated with symptoms of nausea, anorexia, anxiety, and sleep disturbance. Restrictive FODMAP diets have demonstrated efficacy but are difficult to sustain and maintain. Current pharmacotherapy (e.g. hyoscine) is largely inadequate or poorly tolerated.

Emyria has commenced an observational ethics-approved trial to collect longitudinal data for specific IBS symptoms and quality of life in those taking cannabidiol (CBD). This was inspired by first-hand insights from our clinical trial registry of over 6000 patients who reported coincident resolution in IBS symptoms when taking CBD for another primary indication.

In pre-clinical studies, cannabinoid agonists decrease gut motility and transit, while antagonism produces the opposite effect. There have also been anti-inflammatory and analgesic effects for visceral pain in vitro and in vivo for both THC and CBD. Multiple case studies show long-term efficacy and safety in the use of CBD for ameliorating symptoms of IBS and reducing reliance on anticholinergic, antidepressant or other medications.

Is cannabis ready for the mainstream?

Cannabis sativa has been used for millennia as a medicine. Botanicals have historically been a rich source of proprietary medication including aspirin (white willow), quinine (cinchona tree), digoxin (foxglove), and statins (oyster mushroom). The conflation of pre-2016 research using the “marijuana plant” (Cannabis 1.0) with plant derived GMP (pharmaceutical grade) cannabis oil (Cannabis 2.0) has muddied the research regarding clinical efficacy and safety of medicinal cannabis. 

Medicinal cannabis has an admirable safety profile and has level 1 evidence for reduction of pain and spasm associated with multiple sclerosis, chemotherapy induced nausea and vomiting, and seizure disorders. Large observational trials and small RCTs have demonstrated significant reductions in chronic non-cancer pain, anxiety, and insomnia. The longitudinal outcomes from our clinical registry show clearly that medicinal cannabis is a safe, well-tolerated drug with a place in our pharmacopeia for the management of a number of clinical conditions. 

Medicinal cannabis in Australia is generally plant-derived and dispensed in two different forms. 

  1. Oral – suspended in medium chain triglyceride oil, alcohol-based oral spray, dispersible wafers, gel capsules and hard tablets or,
  2. Inhaled – GMP-grade flower for vaporisation or burning.

There are problems associated with both delivery mechanisms. Plant derived medicinal cannabis is a highly purified extract from hydroponically controlled cannabis plants. The only registered non-intoxicant cannabidiol (CBD) in Australia, Epidyolex® contains less than 0.01% impurities. Other scheduled “CBD-only” products contain up to 2% impurities of the multiple other minor cannabinoids including Δ9-tetrahydrocannabinol (THC). In higher doses this may be significant.

TGA compliance ensures scheduled products must contain THC and CBD concentrations within 10% variance of stated levels and less than 2% of the uncontrolled minor cannabinoid, flavonoid, and terpene profiles. 

Issues of stability, absorption, bioavailability, first pass metabolism, pharmacogenomics, active drug exposure and batch-to-batch variability have led to significant inter- and intra-user variability in efficacy and adverse effects, which is exacerbated in inhaled cannabis. Fortunately, the therapeutic index for cannabinoids is wide and the harm risk low. 

A 2021, FreshLeaf Analytics’ report showed a rapid sustained increase in prescriptions in Australia. The growth was in the number of approvals, authorised prescribers (>70,000 active patients), different products available (>220), approved clinical indications (>60), and, interestingly, a steep rise in prescription of mixed THC/CBD flower-based product (Cannabis 1.0). 

Inhaled or vapourised botanical flower I believe is a retrograde step in the development of pharmaceutical uses for medicinal cannabis. It is consistently and rapidly absorbed via the respiratory epithelium, with peak levels experienced in minutes avoiding first-pass metabolism. However, control for dose of active cannabinoids is difficult and not possible for minor cannabinoids and other impurities. 

Claims of different efficacy of “strains” of flower have been shown to be wrong and misleading. Genetic analysis found no distinction between “strains”. Further, dose accuracy and vaping in Canada showed that inconsistencies in dosing (packing and quantities), concentration (THC +/- 20% between batches) and efficiency of vaping devices varied the dose and concentrations between dosing and batches. 

Development of a treatment for IBS, using nature-identical pure cannabinoids that have none of the complexities and impurities of the botanical extracts, are more consistently absorbed, bioavailable, and stable, will allow the pharmacokinetics, efficacy and safety of both CBD and THC to be better defined and the place for this promising medicine to be included in modern mainstream treatment. (Cannabis 3.0).

Key messages
  • IBS is common and current pharmacotherapy is generally inadequate
  • Patients on medicinal cannabis for other indications report improvement in IBS symptoms
  • A new trial is examining the specific use of medicinal cannabis in treating IBS.

– References available on request

Author competing interests – the author is Medical Director of Emyira (Principal Investigator CALM-Gut study)