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Bonner Natural Health

Rectal Cancer
and the Endocannabinoid System

An Educational Science Review
A review of the published research on the endocannabinoid system and cannabinoid science. This document is educational and is not medical advice.
"The natural healing force within each one of us is the greatest force in getting well."
Hippocrates
AuthorBarry Bonner
Contact+1 415 515 1665
Emailbarry@bonnerbiotech.com
DocumentBNH-RectalCA-v03

Contents

About this document.

This is an educational document. It is written for people who want to understand the endocannabinoid system and the scientific research surrounding it. It is presented in two clearly separated parts, and understanding the difference between them matters.

How This Document Is Organised
1
Part One: The Science
A review of independent, published, peer-reviewed research on the endocannabinoid system and cannabinoid compounds, including preclinical studies relating to colorectal cancer biology. This is a summary of what researchers have reported. It is not a description of any product.
2
Part Two: Our Formulations
A description of Bonner Natural Health's phytocannabinoid wellness formulations, which are designed to support the body's own endocannabinoid system. These products are not intended to diagnose, treat, cure, or prevent any disease.
Please Read This First

The research summarised in Part One is drawn from independent scientific literature. The great majority of it is preclinical, meaning it was conducted in laboratory cell cultures and in animals, not in human clinical trials. These findings describe what has been observed in research settings. They are not claims about what any Bonner Natural Health product does, and they do not establish that cannabinoids treat, cure, or prevent cancer in people. Nothing in this document is medical advice. If you are managing a cancer diagnosis or any medical condition, decisions about your care belong with you and your physician or oncologist.

Understanding the disease, in plain terms.

The rectum is the final section of the large bowel, ending at the anus. Rectal cancer, together with colon cancer, forms part of colorectal cancer, one of the most commonly diagnosed cancers worldwide. Most rectal cancers are adenocarcinomas that begin as benign polyps in the rectal lining and, over years, accumulate the genetic and metabolic changes that allow them to grow and spread. This overview is provided for general education. It is understood as a spectrum, from pre-cancerous change through to advanced disease.

1. Polyps and Pre-Cancerous Change

Most rectal cancers begin as adenomatous polyps, small growths in the bowel lining. The great majority never become cancer, but over years a minority accumulate mutations, in genes such as APC, KRAS, and TP53, that drive the adenoma-to-carcinoma sequence. This slow progression is why screening and early detection matter so much.

2. Rectal Adenocarcinoma

The overwhelming majority of rectal cancers are adenocarcinomas arising from the glandular cells of the rectal lining. As a tumour grows it invades deeper layers of the bowel wall. Staging, through the TNM system, describes how far it has penetrated, whether nearby lymph nodes are involved, and whether it has spread to distant organs such as the liver or lungs.

3. Inflammatory Bowel Disease and Colitis-Associated Cancer

People with long-standing inflammatory bowel disease, ulcerative colitis in particular, carry a raised risk of colorectal and rectal cancer. Chronic inflammation is recognised in the medical literature as a contributor to malignant change in the bowel.

4. Advanced and Metastatic Disease

When rectal cancer spreads beyond the bowel wall and lymph nodes, care shifts toward controlling the disease and preserving quality of life. Symptom burden, including pain, poor appetite, fatigue, and sleep disturbance, becomes central to a person's wellbeing.

Conventional treatment is delivered by an oncology and colorectal surgical team and may combine surgery, radiotherapy, and chemotherapy. It is powerful and often necessary, and it is the standard of care.

The body's master regulatory system.

The Endocannabinoid System, or ECS, is described in the scientific literature as one of the body's central regulatory systems. Woven into virtually every tissue, it is involved in homeostasis, the state of internal balance in which the body functions well, and it participates in the regulation of inflammation, immune activity, pain signalling, cell turnover, mood, sleep, and metabolic balance. It was first identified by science in the late 1980s and early 1990s, and many practising physicians received little formal training in it.

The system operates through three components: endocannabinoids, the messenger molecules the body makes naturally, principally anandamide and 2-arachidonoylglycerol (2-AG); cannabinoid receptors, chiefly CB1 and CB2, found on cells throughout the body; and the enzymes that build and break down these signals. The ECS also interacts with TRP channels (TRPV1, TRPV2, TRPM8, TRPA1), GPR55, PPAR receptors, and serotonin (5-HT) receptors.

A defining feature of the system is timing. Endocannabinoids are not stored in advance; the body makes them on demand, exactly where and when they are needed, and then clears them within minutes. They also work in reverse, released by the receiving nerve cell and travelling backward across the synapse to quieten the cell signalling to it. This on-demand, retrograde design is how the ECS makes precise, moment-to-moment adjustments rather than blunt, system-wide ones.

Although this document focuses on the gut, the ECS is genuinely body-wide. CB1 is the most abundant receptor of its kind in the brain, concentrated in regions that govern mood, memory, stress, appetite, and pain, and it is also present in fat, liver, pancreas, muscle, bone, skin, heart, and reproductive tissue. CB2 sits mainly on immune cells and in the spleen, with a presence in bone, liver, and the brain's own immune cells. Because the receptors are almost everywhere, the system touches an unusually wide range of functions: mood, memory, stress and anxiety, sleep, appetite, body temperature, immune balance, pain, neuroprotection, bone health, and metabolism.

The gastrointestinal tract is densely populated with ECS components. CB1 and CB2 receptors, endocannabinoids, and their metabolising enzymes are all expressed in the gut lining and its immune tissue, where the literature describes them as helping to regulate motility, secretion, inflammation, and the turnover of the cells that line the bowel. This is why researchers have taken an interest in the ECS in the context of gastrointestinal health and disease.

The Endocannabinoid System A bidirectional, body-wide diagram of the endocannabinoid system, its two sources of cannabinoids, shared receptors and enzymes, cellular actions, homeostasis, the processes it balances, body-wide receptor distribution, and endocannabinoid tone. The Endocannabinoid System A BIDIRECTIONAL, BODY-WIDE REGULATORY SYSTEM TWO SOURCES OF CANNABINOIDS, ONE SYSTEM Your Own Endocannabinoids Anandamide and 2-AG made on demand, on the spot Plant Phytocannabinoids CBD, CBG, CBC, CBN and more exogenous support from hemp THEY ACT THROUGH SHARED RECEPTORS AND TARGETS CB1 CB2 TRPV1 TRPM8 TRPA1 GPR55 GPR18 PPAR 5-HT Signals are built by the enzymes NAPE-PLD and DAGL, and broken down by FAAH and MAGL. AT THE CELLULAR LEVEL Mitochondrial energy Apoptosis Autophagy Oxidative-stress balance Cell proliferation HOMEOSTASIS the internal balance the body maintains up-regulated and down-regulated as needed PROCESSES DIALLED UP OR DOWN Inflammation Immune activity Pain signalling Stress and anxiety Mood Memory and learning Sleep Appetite and energy Body temperature Neuroprotection Bone health Metabolic balance RECEPTORS ARE EXPRESSED THROUGHOUT THE BODY Brain and nerves Immune system Gut Liver Skin Bone and joints Muscle Heart Reproductive ENDOCANNABINOID TONE CAN RUN HIGH OR LOW Some people have a low endocannabinoid tone, a research concept called Clinical Endocannabinoid Deficiency (studied in migraine, fibromyalgia, and IBS). Chronic stress and poor diet can lower it; exercise, omega-3 fats, and plant phytocannabinoids are studied as ways to support it.
Figure 1. The endocannabinoid system as a bidirectional, body-wide regulator, showing its two sources of cannabinoids, its cellular actions, the processes it keeps in balance, and how its tone can run high or low.
100+Body processes the ECS is involved in regulating
CB1 / CB2Receptors expressed throughout the gut
1990sDecade the ECS was first identified

Why the system runs strong in some people and low in others.

Every person has a baseline level of endocannabinoid activity, often called endocannabinoid tone. It reflects how much anandamide and 2-AG you make, how many receptors you carry, and how quickly your enzymes clear these signals away. Tone is not fixed. It rises and falls with how you live.

Clinical Endocannabinoid Deficiency

Researchers led by Dr. Ethan Russo have proposed that some people carry a chronically low endocannabinoid tone, a concept named Clinical Endocannabinoid Deficiency. The strongest research support is in migraine, fibromyalgia, and irritable bowel syndrome, conditions that share heightened pain sensitivity and central sensitisation. This remains a scientific hypothesis under active investigation, not an established diagnosis.

What Lowers Tone, and What Supports It

In research settings, chronic stress and diets low in essential fats are associated with reduced endocannabinoid signalling. On the other side, moderate aerobic exercise raises anandamide, the molecule now thought to underlie the "runner's high," and omega-3 fats supply the raw materials the body uses to build its own endocannabinoids. Lifestyle, in other words, is one of the main levers on this system.

Phytocannabinoids as Exogenous Support

Plant phytocannabinoids such as CBD and CBG are shaped much like the endocannabinoids the body makes, so they can act on the same receptors and pathways. In the scientific literature they are described as cannabimimetic, meaning they mimic or support the activity of the endocannabinoid system from the outside. This is the basis of the research interest in hemp-derived phytocannabinoids as a way to support endocannabinoid tone, particularly where that tone may be running low.

Kept in Context

Clinical Endocannabinoid Deficiency is a research hypothesis, and supporting endocannabinoid tone is a wellness concept, not a treatment for any named disease. Nothing here should be read as a claim that phytocannabinoids, or any product, diagnose, treat, cure, or prevent migraine, fibromyalgia, irritable bowel syndrome, cancer, or any other condition.

The compounds, and what the science describes.

Hemp produces more than a hundred distinct cannabinoids, alongside terpenes that also interact with the endocannabinoid system. Because these plant compounds are shaped much like the body's own endocannabinoids, many of them act on the same receptors and targets. The summaries below describe what published research reports about each compound found in our broad-spectrum profile. This is educational information about the compounds themselves. As with the rest of Part One, much of this research is preclinical, and it is not a statement about the effects of any product.

Major Cannabinoids

CBD (Cannabidiol). The most studied cannabinoid, and non-intoxicating. Rather than binding the CB1 receptor directly, it acts as a negative allosteric modulator of CB1 and raises the body's own anandamide by inhibiting the FAAH enzyme. It also activates TRPV1 (pain and temperature), 5-HT1A serotonin receptors (mood and nausea), and PPAR-gamma (metabolism and inflammation), and blocks GPR55. The purified-CBD medicine Epidiolex is FDA-approved for certain rare epilepsies, and CBD is widely researched for inflammation, anxiety, and pain.

CBDa (Cannabidiolic acid). The raw, acidic form of CBD as it exists in the living plant. It is a selective inhibitor of the COX-2 inflammatory enzyme and a potent activator of 5-HT1A serotonin receptors, which is why it has been studied for nausea and mood. It is often absorbed more readily than CBD itself.

CBG (Cannabigerol). Non-intoxicating. A partial agonist at both CB1 and CB2 receptors, an alpha-2 adrenoceptor agonist, a 5-HT1A antagonist, and a modulator of TRP channels. It is noted in research for antibacterial activity, including against drug-resistant bacteria, and for appetite and neuroprotection.

CBGa (Cannabigerolic acid). The "mother cannabinoid," the acidic precursor from which the plant builds CBD, THC, and CBC. Beyond that structural role, it activates PPAR receptors involved in metabolism and has been studied for metabolic and lipid effects.

Minor Cannabinoids

CBC (Cannabichromene). Non-intoxicating. It binds the classic cannabinoid receptors only weakly, but is a potent activator of TRPA1 channels and slows the reuptake of anandamide, which raises endocannabinoid tone. Research has examined its anti-inflammatory effects and its support of neural stem and progenitor cells.

CBN (Cannabinol). Mildly active at most; it forms naturally as THC ages. It has modest affinity for the CB2 receptor and acts on TRPV2 and TRPA1 channels. It is popularly associated with relaxation and sleep, though robust human sleep data is still limited; preclinical work has looked at appetite and anti-inflammatory effects.

CBNa (Cannabinolic acid). The acidic precursor of CBN, present in small amounts. Dedicated research is sparse, and it is included as a natural part of the full-spectrum profile.

CBDV (Cannabidivarin). A non-intoxicating relative of CBD with a shorter molecular chain. It activates TRPA1, TRPV1, and TRPV2 channels and blocks TRPM8. Its best-studied property is anticonvulsant activity in animal models, and it has been investigated for neurodevelopmental conditions.

THCV (Tetrahydrocannabivarin). A relative of THC. At the low levels found in hemp it behaves as a CB1 antagonist, a property researched in connection with appetite regulation and glucose and metabolic control; at higher doses its behaviour changes. It is non-intoxicating at typical hemp levels.

Rare and Trace Cannabinoids

CBE (Cannabielsoin). An oxidation product and natural metabolite of CBD, meaning the body itself converts some CBD into CBE. Recent laboratory work characterises it as a "biased" CB1 agonist. Research remains early and limited.

CBL (Cannabicyclol). A stable compound that forms when CBC is exposed to light over time. It is well described chemically, but its pharmacology is largely uncharacterised; it is present as a natural component of mature, full-spectrum hemp.

CBT (Cannabicitran). A rare, non-intoxicating cannabinoid that occurs naturally in the plant. Published research is minimal; the main documented finding is a reduction of intraocular (eye) pressure in animal studies.

Trace Delta-9 THC. Present only in the small, federally limited amounts (below 0.3%) characteristic of broad-spectrum hemp. Delta-9 THC is the main activator of the CB1 receptor; at these trace levels it contributes to the entourage effect without intoxication.

Delta-8 THC. Used as a purified isolate in certain formulations only. A milder relative of delta-9 THC that partially activates CB1, studied historically for nausea and appetite. Its legal status varies by state, which is worth confirming market by market.

A Dietary Terpene That Acts Like a Cannabinoid

Beta-Caryophyllene. Not a classical cannabinoid but a dietary terpene found in black pepper, cloves, and hemp. Uniquely among common terpenes, it is a selective full agonist of the CB2 receptor, and also activates PPAR, which is why it is often called a "dietary cannabinoid." It is well researched for anti-inflammatory and pain-related effects mediated specifically through CB2, and is recognised as safe for use as a food flavouring.

What independent researchers have reported.

Over the past two decades, independent research groups have studied how the endocannabinoid system and plant-derived cannabinoids behave in models of colorectal cancer. The findings summarised below are drawn from peer-reviewed publications. Each is a description of what researchers observed in their study. As set out at the start of this document, this work is almost entirely preclinical, conducted in laboratory cell lines and animals, and has not been confirmed in human clinical trials. None of it describes a Bonner Natural Health product.

Endocannabinoid Tone in Colorectal Tissue

Ligresti and colleagues, publishing in Gastroenterology in 2003, reported that endocannabinoid levels were roughly 3-fold higher in adenomas and 2-fold higher in colorectal carcinomas than in normal tissue. In their laboratory work, endocannabinoids and cannabinoid receptor agonists inhibited the proliferation of colorectal cancer cells. The authors interpreted this as the body raising its own endocannabinoid tone in response to abnormal tissue.

Programmed Cell Death in Cancer Cell Lines

Cianchi and colleagues, publishing in Clinical Cancer Research in 2008, reported that activation of either the CB1 or CB2 receptor induced apoptosis, programmed cell death, in colon cancer cells, and identified a molecular pathway involving TNF-alpha and ceramide. This was a laboratory study in cell cultures.

Cannabidiol in Models of Colon Carcinogenesis

Aviello and colleagues, publishing in the Journal of Molecular Medicine in 2012, reported that cannabidiol reduced chemically induced aberrant crypt foci, polyps, and tumours in mice, and inhibited colorectal cancer cell proliferation in culture. A related 2014 study by Romano and colleagues in Phytomedicine reported similar effects from a standardised, high-CBD whole-plant extract, work often cited in discussions of the broad-spectrum, or entourage, approach.

Cannabigerol in Colon Cancer Models

Borrelli and colleagues, publishing in Carcinogenesis in 2014, reported that cannabigerol (CBG) promoted apoptosis and reduced the growth of colorectal cancer cells in culture, and that in animal models it reduced the growth of tumours and of chemically induced colon carcinogenesis. The authors described CBG as worthy of further study in this context.

Cannabidiol and Intestinal Inflammation

Borrelli and colleagues, in the Journal of Molecular Medicine in 2009, reported that cannabidiol reduced markers of colonic inflammation in an animal model of colitis. Because chronic bowel inflammation is a recognised contributor to colorectal cancer risk, this line of research is often discussed alongside the studies above.

How the Evidence Is Summarised

A 2020 systematic review of cannabinoid effects in experimental colorectal cancer models reported that, across the studies reviewed, cannabinoids tended to reduce aberrant crypt foci and tumour volume in laboratory and animal models. Reviews of this kind consistently note the same caveat: the evidence is preclinical, and human clinical trials are needed before any conclusions can be drawn about people.

What This Research Does and Does Not Show

These are independent findings observed in laboratory and animal studies. They show that the endocannabinoid system is an active area of cancer research and that cannabinoids have measurable biological effects in these models. They do not establish that cannabinoids, or any product, treat or prevent cancer in humans, and they are not statements about Bonner Natural Health formulations. Human clinical evidence does not yet exist to support such conclusions.

Why the rectal route is of scientific interest.

Rectal administration is a long-established pharmaceutical delivery route, described in standard pharmacology texts. It is of interest for compounds that are poorly absorbed or heavily broken down when swallowed. This section describes the general pharmacology; it is educational and does not describe the use of any product for any disease.

up to 80%Reported bioavailability via rectal delivery (general pharmacology)
6 to 19%Commonly reported oral CBD bioavailability
~2/3Of rectal venous drainage that bypasses the liver

The Science of Rectal Absorption

The rectum's venous drainage is roughly two-thirds systemic: the middle and inferior rectal veins carry absorbed compounds toward the bloodstream while partly bypassing the first-pass metabolism in the liver that reduces much of a swallowed dose. The pharmacology literature reports that this can result in faster onset and higher bioavailability than the oral route. For cannabidiol, oral bioavailability is commonly reported in the range of 6 to 19%, whereas the rectal route is described in the literature as achieving considerably higher figures.

These are general pharmacological principles. They explain why the rectal route is studied and used across many types of medicine, and why it is a recognised delivery format.

The published studies referenced above.

The research described in Part One is drawn from the peer-reviewed publications below, listed with their source and identifier so that you and your medical team can review them directly.

Endocannabinoid Tone in Colorectal Cancer

Ligresti A, et al. "Possible endocannabinoid control of colorectal cancer growth." Gastroenterology. 2003;125(3):677 to 687. PMID: 12949714.

Cannabinoid-Induced Apoptosis

Cianchi F, et al. "Cannabinoid receptor activation induces apoptosis through tumor necrosis factor alpha-mediated ceramide de novo synthesis in colon cancer cells." Clinical Cancer Research. 2008;14(23):7691 to 7700. PMID: 19047095.

Cannabidiol and Chemoprevention

Aviello G, et al. "Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer." Journal of Molecular Medicine. 2012;90(8):925 to 934. PMID: 22231745.

High-CBD Cannabis Extract

Romano B, et al. "Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol." Phytomedicine. 2014;21(5):631 to 639. PMID: 24373545.

Cannabigerol and Colon Cancer

Borrelli F, et al. "Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid." Carcinogenesis. 2014;35(12):2787 to 2797. PMID: 25269802.

Cannabidiol and Intestinal Inflammation

Borrelli F, et al. "Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis." Journal of Molecular Medicine. 2009;87(11):1111 to 1121. PMID: 19690824.

Systematic Review

Orrego-Gonzalez E, et al. "Cannabinoid effects on experimental colorectal cancer models reduce aberrant crypt foci (ACF) and tumor volume: a systematic review." Evidence-Based Complementary and Alternative Medicine. 2020. PMC7387981.

Part Two · Our Formulations

Everything above is a summary of independent scientific research. What follows is a description of Bonner Natural Health's own formulations. These are wellness products designed to support the body's endocannabinoid system. They are not the subject of the research above, and the following statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

Broad-spectrum phytocannabinoid formulations to support your endocannabinoid system.

Bonner Natural Health produces broad-spectrum phytocannabinoid formulations made from industrial hemp, together with purified single-cannabinoid isolates used in certain products. Our broad-spectrum extracts contain the full range of naturally occurring hemp cannabinoids, including only trace THC below the 0.3% federal hemp limit; our isolate-based products are formulated without THC. All are designed to support the body's own endocannabinoid system and its role in maintaining balance and overall wellbeing, using a broad spectrum of compounds working together, an approach often described as the entourage effect.

Transdermal Oil

A hemp seed oil based topical formulation, applied to the skin, designed to support the endocannabinoid system.

Sublingual Tincture

An MCT oil based tincture taken under the tongue, designed for everyday support of the endocannabinoid system.

Suppository

A rectal suppository format. Rectal administration is a well-established delivery route known for high bioavailability, as described in Part One.

Our formulations draw on the compounds described in Section 05, including the cannabinoids CBD, CBDa, CBG, CBGa, CBC, CBN, CBNa, CBDV, and THCV; the rare, naturally occurring cannabinoids CBE, CBL, and CBT; and the dietary CB2-active terpene beta-caryophyllene. We also use purified isolates of CBD, CBG, CBN, CBGa, CBDa, and, in certain cases, Delta-8. A full scientific overview of what each compound does is set out in Section 05.

Ingredients

  • Broad-spectrum cannabinoids, U.S. grown from the hemp plant
  • Cocoa butter
  • MCT oil
  • Apricot seed oil
Structure and function statement: These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. They are intended to support the body's endocannabinoid system and general wellbeing.

Personalised wellness support, alongside your medical care.

Bonner Natural Health offers a personalised wellness program delivered by telehealth. We work with people who want to support their general wellbeing and their endocannabinoid system as part of a healthy lifestyle. Our program is designed to complement, never to replace, the care of your physician and medical team.

Our philosophy is rooted in the belief that, given good nutrition, a healthy lifestyle, and support for its own regulatory systems, the body has a remarkable capacity to maintain its balance.

Bonner Natural Health
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Learn more about the endocannabinoid system.

Reach out to Barry directly to learn more about the science of the endocannabinoid system and our wellness formulations. There is no obligation, just an honest conversation.

Phone +1 415 515 1665
About Barry Bonner and Bonner Natural Health: Barry Bonner is a health educator and wellness practitioner with a focus on the endocannabinoid system. He is not a licensed physician, and Bonner Natural Health is not a medical practice. Bonner Natural Health is a wellness education and product service. It does not provide medical diagnosis, treatment, or advice, and it is not a substitute for the care of a qualified physician or oncologist.

About the research in this document: Part One summarises independent, published, peer-reviewed scientific research. The great majority of it is preclinical, conducted in laboratory cell cultures and in animals. It is provided for educational purposes only. It does not establish that cannabinoids, or any product, diagnose, treat, cure, or prevent cancer or any other disease in humans, and it does not describe the effects of any Bonner Natural Health product.

About our products: Statements regarding Bonner Natural Health formulations have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. Always consult your physician, and where relevant your oncologist, before making any changes to your diet, supplement regimen, or treatment, particularly while managing a diagnosed medical condition or taking prescription medication.

FDA Disclaimer: These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.