Cannabis sativa (marijuana) is one of the most widely used plants in history. Its cultivation dates back thousands of years, but it was only during the last century that its medical uses were discovered. Since then, cannabis has been found to have many therapeutic properties including anti-inflammatory, antispasmodic and neuroprotective effects.1–3 Although there are hundreds of different cannabinoids,4 these four main classes have received the greatest attention: Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and delta-8-tetrahydrocannabinolic acid A (delta 8-THCA).5–7 Cannabinoids exert their effects through two major mechanisms. First, they act directly on cannabinoid receptors in the central nervous system (CNS), which are present throughout the body. Second, they activate specific enzymes called endocannabinoid degraders (eCBs) that metabolize them into inactive metabolites.8–10 The eCBs play an important role in regulating many physiological processes such as appetite regulation, pain modulation and immune function.9,11 In recent years, there has been heightened interest in the role that eCBs play in inflammation.12,13
The endocannabinoid system and inflammation
The eCBs are a group of lipids (fat-soluble compounds) and the receptors that they bind to that are involved in a wide range of biological functions. The eCBs interact with two major types of receptors: CB1 and CB2.
These are G-protein coupled receptors (GPCRs), meaning that they bind to stimuli and transmit the information to cellular pathways. Both the CB1 and CB2 receptors are widespread throughout the body, but are particularly concentrated within the CNS and immune system. Their presence in these areas suggests that they play an important role in regulating inflammation.14,15 Emerging evidence has demonstrated that the eCB system is a critical player in regulating inflammation during disease and injury. For example, CB1 and CB2 knockout mice models have been found to exhibit severe intestinal inflammation in response to infection with the pathogenic bacteria Citrobacter rodentium.16 In addition, activation of the CB2 receptor reduced inflammation in a mouse model of autoimmune encephalomyelitis (a mouse model of Multiple Sclerosis).17,18 There is increasing evidence from clinical trials that cannabinoids can reduce peripheral inflammatory responses throughout the body.19,20 These immunomodulatory effects are mediated by inputs from the CB2 receptors found on immune cells throughout the body. This CB2 receptor activation inhibits the release of pro-inflammatory cytokines (small proteins that signal cells to respond in a certain way) and promotes anti-inflammatory molecules.
In addition to CB1 and CB2, the endocannabinoid system includes two enzymes: N-acyl transferase (triggers the production of the endocannabinoid anandamide) and monoacyl glycerol lipase (metabolizes the endocannabinoid 2-AG). Emerging evidence has recently demonstrated that the levels of these two crucial enzymes are often decreased in patients who suffer from chronic pain.21,22 This suggests there is a link between endocannabinoid degradation and pain perception.
While this new research into the mechanisms of the endocannabinoid system is very exciting, there have not been any studies directly investigating the role of the eCBs in ileo-colitic pain. There is evidence that levels of the eCBs are altered during inflammatory bowel disease, but more research is needed to determine how this affects the patient experience.
Cannabinoids and the Treatment of Pain: The Psychedelic 90s
In a 2017 national survey of adults in the US, it was found that 20% of adults reported using Cannabis for medical purposes. Of that number, the most common conditions for which cannabis was being used were pain and anxiety.
In fact, over 25% of medical users reported using Cannabis for these purposes.25 The evidence has been mounting for years that cannabinoids have the potential to treat a wide range of conditions including inflammatory bowel diseases (Crohn’s disease and ulcerative colitis).26
The first endocannabinoid isolated was called anandamide (ananda is a Sanskrit word meaning “supreme joy” or “bliss”). It is structurally similar to tetrahydrocannabinol (THC).
It binds to the CB1 and CB2 receptors with highest affinity for the CB1 receptor.
The CB1 receptor was first identified in 1990, and it is chiefly concentrated in the nervous system. While its primary role is in the brain, it is also expressed throughout the immune system.
The CB2 receptor was identified soon after the CB1 receptor and is most highly concentrated in the immune system.
The THC found in Cannabis has a high affinity for both of these receptors, but can also bind to a variety of other receptors throughout the body. This is why Cannabis has such a wide range of psychoactive effects on the user.
It is well known that THC can produce nausea and vomiting, which prevents people from eating toxic substances and aids in clearing out the digestive tract. It also has strong anti-nausea properties.
It can increase appetite and reduce the symptoms of pain, which is why people suffering from illnesses often eat more when they are using Cannabis. A side effect of nausea is vomiting, but it can also lead to more serious conditions such as cessation of eating, depression, and weight loss.
There have been a number of different strategies employed to treat nausea and vomiting in patients with inflammatory bowel diseases. Drugs that block the serotonin receptors have been used for some time with limited success.
Drugs that target the corticotropin releasing factor (CRF) receptors have only recently become available. The most effective drugs have been found to be those that target the cannabinoid receptors. It has been found that patients who use marijuana medicinally are able to control their symptoms and live a more normal life than those who don’t. The most effective cannabinoid is nabilone, which can be used in treatment of nausea and vomiting in patients with inflammatory bowel diseases and prevent them from becoming severely underweight.27
The use of medical marijuana to treat inflammatory bowel diseases can also help patients in a number of other ways. It has been found to be an effective pain reliever for conditions such as arthritis.
It can also be used to treat depression and anxiety that are often associated with these conditions.
Cannabis use has been rising over the past few years for medical reasons. Many states in America have legalized the use of medical marijuana to treat a variety of conditions, and other countries like Canada are following suit.
It is expected that this rise in legalization of medical marijuana will continue, and this will allow patients suffering from inflammatory bowel diseases to seek out treatment that works for them without fear of legal ramifications.
Cannabinoids are safe in moderation and for a limited duration of time. A long term extensive use of Cannabinoids can result in tolerance and the need for higher doses to get the same effects, as well as severe marijuana dependency and addiction.
This is especially true of CBDs because they do not have the psychoactive effects that THC has, so patients tend to overuse or misuse it.
The use of CBDs is not regulated by many states currently, so it is impossible to know the actual concentration or dosage of the CBD. There have been instances reported in which people have overused CBD and suffered from anxiety, fast heartbeat, and paranoia.
These instances are rare but do happen. In addition there have been concerns about the processing of these CBD oils. It has been reported in several instances that people have been hospitalized and in a couple of cases even died due to either consuming products that had a high concentration of THC or products with little to no CBD in them at all.
There have also been concerns about certain companies selling “CBD Oils” that are made from a type of cherry fruit known as “African cherries” or “Peruvian cherries”. These types of cherries have absolutely no cannabinoids in them at all and are not the source of CBD.
These companies tend to advertise their products as “All Natural” and charge a premium for them.
There have also been concerns about certain companies selling a product known as “Rick Simpson Oil” or RSO. This is a specific type of cannabis concentrate that has a high concentration of THC and often little to no CBD.
Patients that use this product tend to feel very strong psychoactive effects. These types of products are not recommended for medical use, and there is no scientific research supporting their use in inflammatory bowel disease treatment.
On the flip side, there are many patients that swear by the use of cannabis and CBD oils in treating their IBD. Many argue that the legalization of medical marijuana should be embraced by the medical community as a legitimate treatment option.
The two most common reasons for this argument are : 1) It is safer than many of the pharmaceutical drugs currently on the market and 2) It has fewer side effects than the current IBD treatments such as steroids.
A lot more research needs to be done on the use of medical marijuana and CBD oils before many doctors will start recommending this treatment option. There is not enough long-term data on the safety and efficacy of CBD oils in inflammatory bowel disease treatment to make it a common recommendation.
It is also important to remember that medical marijuana is an unorthodox treatment for inflammatory bowel diseases, and it should not be seen as a replacement for standard medical treatments.
Sources & references used in this article:
Cannabis oil use by adolescents and young adults with inflammatory bowel disease by EJ Hoffenberg, S McWilliams… – Journal of pediatric …, 2019 – journals.lww.com
Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon by DG Couch, C Tasker, E Theophilidou, JN Lund… – Clinical …, 2017 – portlandpress.com
Towards Better Delivery of Cannabidiol (CBD) by SA Millar, RF Maguire, AS Yates, SE O’Sullivan – Pharmaceuticals, 2020 – mdpi.com
What role do cannabinoids have in modern medicine as gastrointestinal anti-inflammatory drugs? by A Szczepaniak, J Fichna – 2020 – Taylor & Francis
Cannabis, a potential treatment option in pediatric IBD? Still a long way to go by N Halbmeijer, M Groeneweg… – Expert Review of Clinical …, 2019 – Taylor & Francis
Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis by F Borrelli, G Aviello, B Romano, P Orlando… – Journal of molecular …, 2009 – Springer