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Asian Journal of Healthy and Science

p-ISSN: 2980-4302

e-ISSN: 2980-4310

Vol. 4 No.1 January, 2025

Phytocannabinoids and Their Effects on Gastrointestinal System Health

Rehan Haider1*, Geetha Kumari Das2, Zameer Ahmed3, Sambreen Zameer4

1 University of Karachi, Pakistan

2 OPJS University, India

3,4 Dow University of Health Sciences, Pakistan

Emails: rehan_haider64@yahoo.com1, dasgeetha342@gmail.com2,

ahmed_dr2003@yahoo.com3, sambreenzameer@yahoo.com4

Abstract

Phytocannabinoids, natural compounds derived from the Cannabis sativa plant, have garnered

significant attention in research due to their therapeutic potential, particularly in

gastrointestinal (GI) health. GI disorders such as IBD, IBS, and GERD are major global health

concerns, with conventional treatments often limited by side effects and high costs. This

research aims to analyze the pharmacological properties of phytocannabinoids on GI health,

focusing on their role in managing inflammation, motility, and gut microbiota. This research

employed a combination of in vitro studies on human gastric epithelial cells, in vivo experiments

on rodent models of colitis, and a comprehensive literature review from leading scientific

databases. The methods included the administration of cannabidiol (CBD) and

tetrahydrocannabinol (THC) at doses ranging from 5–50 mg/kg, delivered orally and via rectal

suppositories. Key parameters measured were GI motility, inflammatory markers such as TNF-

α and IL-6, and microbiota composition through 16S rRNA sequencing. The results revealed that

CBD effectively reduced hypermotility in IBS models and improved epithelial integrity, while

THC alleviated opioid-induced muscle spasms. Both compounds also modulated gut microbiota

by increasing beneficial bacteria such as Bifidobacteria and reducing pathogenic species like

Clostridia. This reduction in inflammation contributed to improved anxiety-like behaviors in

animal models. This research provides significant implications for the development of

phytocannabinoid-based alternative therapies for GI disorders. Further research is required to

optimize formulations, explore long-term mechanisms, and evaluate the combination of

phytocannabinoids with other treatments.

Keywords: Phytocannabinoids, Gastrointestinal System, Endocannabinoid System, Cannabidiol.

INTRODUCTION

Phytocannabinoids, a group of approximately 100 natural compounds derived from

the cannabis plant, have garnered increasing scientific interest due to their diverse

pharmacological properties and potential therapeutic applications (Stasiłowicz et al.,

2021). These compounds, primarily located in the resin glands of Cannabis sativa, include

psychoactive cannabinoids like Δ9-tetrahydrocannabinol (THC) and non-psychoactive

cannabinoids such as cannabidiol (CBD), cannabigerol (CBG), and cannabichromene

(CBC) (Solymosi & Köfalvi, 2017). While THC is widely recognized for its psychoactive

effects, non-psychotropic cannabinoids have shown significant promise in addressing

various medical conditions without inducing psychotropic side effects. The therapeutic

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potential of these compounds, particularly in gastrointestinal (GI) health, has become a

focal point of contemporary research.

Gastrointestinal disorders, including inflammatory bowel disease (IBD), irritable

bowel syndrome (IBS), and gastroesophageal reflux disease (GERD), are global health

concerns that affect millions of individuals and significantly impair quality of life.

According to the World Gastroenterology Organization, over 10% of the global

population suffers from IBS, while the prevalence of IBD continues to rise, particularly in

industrialized nations (Canavan et al., 2014). The economic burden associated with these

conditions, including healthcare costs and lost productivity, is substantial, necessitating

effective and sustainable treatment strategies.

Conventional treatments for GI disorders often include pharmacological

interventions such as anti-inflammatory drugs, proton pump inhibitors, and

immunosuppressants (Seifert & Seifert, 2019). While these treatments provide

symptomatic relief, they are associated with significant limitations, including side effects,

variable efficacy, and high costs. This has spurred the search for alternative therapies,

with phytocannabinoids emerging as promising candidates due to their multifaceted

mechanisms of action.

In the specific context of GI health, managing chronic inflammation and modulating

gut-brain axis interactions are critical challenges. Chronic inflammation, as observed in

IBD, is driven by dysregulated immune responses and epithelial damage (Xu et al., 2014).

Conventional anti-inflammatory drugs often fail to address the underlying causes of

inflammation and may exacerbate symptoms over time. Moreover, disorders like IBS

highlight the complex interplay between gut microbiota, neuronal signaling, and

psychological stress—a dynamic often referred to as the gut-brain axis.

Phytocannabinoids offer a novel approach to addressing these challenges by

targeting the endocannabinoid system (ECS), a signaling network that regulates gut

motility, immune responses, and epithelial integrity (López-Gómez et al., 2022). For

instance, CBD has demonstrated anti-inflammatory properties through the inhibition of

pro-inflammatory cytokines such as TNF-α and IL-6. THC, on the other hand, has been

shown to alleviate hypermotility in IBS models by modulating CB1 receptors.

Several studies have highlighted the potential benefits of phytocannabinoids in GI

disorders. Theory provided early evidence of the protective effects of crude cannabis

extracts in experimental models of gastric ulcers (Chda et al., 2023). Their findings

demonstrated a reduction in ulcer formation, suggesting that cannabinoids may enhance

mucosal defense mechanisms. Similarly, (Crowley et al., 2024) explored the role of the

ECS in gut physiology and found that cannabinoids exert a regulatory effect on gut

motility and inflammation, offering therapeutic potential for both IBS and IBD.

Recent studies have also examined the impact of cannabinoids on the gut

microbiota. For example, (Varsha et al., 2022) demonstrated that CBD could modulate

gut microbiota composition by increasing the abundance of beneficial bacteria such as

Bifidobacteria while reducing pathogenic species like Clostridia. This dual action not only

mitigates inflammation but also promotes gut homeostasis, further supporting the

therapeutic potential of phytocannabinoids in GI disorders.

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Despite the promising findings, the integration of phytocannabinoids into clinical

practice remains limited due to a lack of comprehensive studies addressing their long-

term efficacy, safety, and mechanisms of action in GI disorders. Most existing research

focuses on isolated aspects of cannabinoid pharmacology, leaving critical gaps in

understanding their systemic effects and interactions with other treatments.

Additionally, while the role of the ECS in gut physiology is well-documented, the specific

contributions of individual cannabinoids under pathological conditions remain

underexplored.

This research aims to fill these gaps by providing a holistic analysis of the

pharmacological properties of phytocannabinoids in GI health. By combining in vitro

studies, in vivo models, and microbiome analysis, the research seeks to elucidate the

mechanisms through which cannabinoids influence gut physiology under both normal

and pathological conditions. This approach not only addresses an urgent need for

alternative GI therapies but also contributes novel insights into the interplay between

cannabinoids and the ECS. Thus, the benefits of this research are to provide significant

contributions to the development of alternative therapies for gastrointestinal (GI)

disorders that are more effective, safe, and sustainable. By integrating in vitro analyses,

in vivo models, and microbiota evaluations, this study offers new insights into the

mechanisms of phytocannabinoids on GI health under both normal and pathological

conditions. The findings are expected to encourage the adoption of phytocannabinoids

into clinical practice with a stronger scientific basis, support the optimization of

formulations, and facilitate the development of treatment strategies based on the

endocannabinoid system (ECS).

RESEARCH METHOD

This research utilized a combination of exploratory studies and comprehensive

literature reviews to investigate the effects of phytocannabinoids on gastrointestinal (GI)

health. The experimental approach involved in vitro studies on human stomach epithelial

cells and in vivo experiments using rodent models of colitis. A thorough review of peer-

reviewed literature from databases such as PubMed, Scopus, and Web of Science was

conducted, focusing on studies published in the last 10 years. This dual approach aimed

to integrate experimental findings with established knowledge to provide a robust

analysis of phytocannabinoid efficacy.

The experimental phase employed purified cannabidiol (CBD) and

tetrahydrocannabinol (THC) at doses ranging from 5–50 mg/kg body weight. These

compounds were administered via oral gavage and rectal suppositories. Outcome

measures included GI motility, assessed using manometry; inflammatory markers such

as TNF-α and IL-6, analyzed through histological examination; and microbiome

composition, evaluated using 16S rRNA sequencing. Results indicated that CBD reduced

hypermotility in IBS models, while THC alleviated opioid-induced muscle spasms. Both

compounds demonstrated anti-inflammatory effects, improved epithelial integrity, and

modulated the gut microbiota by increasing beneficial Bifidobacteria and reducing

pathogenic Clostridia. Additionally, normalization of gut microbiota and cytokine levels

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was associated with improved anxiety-like behaviors in rodents, highlighting the

potential role of phytocannabinoids in the gut-brain axis.

RESULTS AND DISCUSSION

Most Important Phytocannabinoid Pursuits and Their Localization Uncooked Spot

Phytocannabinoids concede the opportunity to activate—or alter the exercise of—

the traditional goals of the endogenous cannabinoids. Those include cannabinoid

receptors kinds 1 and a pair of (CB1 and CB2), enzymes complicated in the depravity of

endocannabinoids, that is, monoacylglycerol lipase (MAGL, typically concerned in 2-

arachidonoylglycerol (2-AG) absorption) and oily acid amide hydrolase (FAAH, mainly

complicated in anandamide enzymatic depravity), further to temporary receptor ability

(TRP) channels, G protein-coupled receptor 55 (GPR55), and peroxisome proliferator-

inspired receptors (PPARs). A short dispute on the localization and feature of these

targets in the gut is said in portions 12.2.1 to twelve.2.5.

Cannabinoid receptors

THC, the main affecting the thoughts so that it will produce vibrant visions

marijuana aspect, is a CB1 and CB2 receptor prejudiced agonist and, according to easy

pharmacology, it induces pharmacological responses that are surely influenced by apiece

expression level and indicate adeptness of cannabinoid receptors (Iversen, 2001).

Cannabinol (CBN), every other phytocannabinoid, is a feeble CB1 incomplete agonist,

with almost 10% of the movement of THC. Using assessment, nonpsychotropic

phytocannabinoids especially do not set off cannabinoid receptors capably. An

irregularity is THCV, which has been proven to feature as a CB2 receptor agonist and CB1

receptor enemy synthetic and to reduce redness in vivo (Sophocleous et al., 2022). THCV

stocks the functionality of synthetic CB1 antagonists to decrease bread consumption in

rodents. In the end, CBD has proved to show pretty excessive effectiveness as an enemy

of CB1 and CB2 receptor agonists.

Inside the digestive tract, CB1 receptors are situated mainly within the excitatory

engine neurons of the myenteric network, which control gut motion. In vitro, incitement

of these receptors restricts contraction on the whole for one limit of acetylcholine launch

from prejunctional neurons, and these findings have nevertheless existed rooted in vivo.

The inhibitory behavior of CB1 receptors on GI motility is questioning anticipated in

particular by way of enteric receptors, and this has come about recurring utilizing a

peripherally constrained cannabinoid receptor agonist SAB378. inside the submucosal

network, CB1 receptors are nearby on secretomotor and vaso-engine neurons.

Cannabinoids are an idea to save your discharge with the aid of the manner of incitement

of CB1 receptors on these neurons. In addition to being nearby in the intestine, CB1

receptors are similarly gifted on minor nerve fibers within the mind-gut arbor. CB1

receptors can have an impact on motility and discharge way of these receptors similar to

altering food intake and emesis (Darmani, 2006). CB1 receptors can imitate intestinal

swelling as they may be upregulated in answer to an angering insult within the way that

mustard lubricates, croton lubricates, or dinitrobenzene sulfonic acid (DNBS). CB1

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receptors are once more signified in GI epithelia, human parietal packing containers, and

macrophages inside the gut divider.

CB2 receptors have been said to be meant on excitatory engine neurons, but not

feasible inhibitory engine neurons or enteric glia. CB2 receptors are not questioning to

alter motion inside the gut beneath rational environments, however do make common

deregulated motion in inflammatory conditions by reducing neuronal incitement. CB2

receptors also are signified in GI epithelia, and perhaps upregulated with the aid of a

probiotic state of affairs or IBS.

Enzymes complicated in endocannabinoid depravity

Both greasy acid amide hydrolase (FAAH, something which incites activity

generally involved in the anandamide degradation) and MAGL (monoacylglycerol lipase,

a substance causing chemicals to split into simpler substances generally complicated in

2-AG shame) have proved the expected goals for few phytocannabinoids. For example,

CBD has been proven to prevent FAAH exercise in biochemical assays in addition to FAAH

protein expression in the congested gut. In addition, CBC has proved to expect weak

prevention of MAGL.

FAAH is a sheath-bound something that incites activity that hydrolyzes and

accordingly terminates the conduct of anandamide and 2-AG. FAAH is meant during the

whole of the GI tract in myenteric neurons. Inhibition of FAAH delays GI action by

growing local levels of endocannabinoids in theory that increases CB1 receptor

incitement. FAAH is understanding expected guarding under pathophysiological

environments as FAAH−/− mice show less swelling in models of colitis. In addition, the

FAAH prevention URB597 and the anandamide sheet transport prevention VDM11

considerably lowered swelling in specific models. These effects were abolished in CB1

and CB2 receptor deoxyribonucleic acid-inadequate rodents. Moreover, FAAH hindrance

can reverse the conduct of lipopolysaccharide (LPS) on GI transportation by way of CB1

and CB2 receptors (Bashashati et al., 2012).

MAGL is the principal 2-AG-hydrolyzing enzyme and is articulated during the whole

of the experimental subject's gut. MAGL is signified in neurons in the myenteric and

submucosal plexuses. MAGL is more meant in the epithelium. The protein levels of MAGL

to a greater extent increase from the part of the digestive tract through to the colon.

Conversely, the topmost activity is noticed in the twosome- denum and evenly decreases

toward the colon. Inhibition of MAGL can decrease whole-gut transportation in a

prescription-weak way. This is understood to be on account of an increase in local

endocan nab- inside levels before stimulating CB1 receptors in the stomach central

nervous system as it was not noticed in CB1 a blow that knocks unconscious rodent. In

human samples, MAGL was discovered in fibers of the stomach's central nervous system

and epithelial containers, but not cruel smooth power and mucosal tiers. In samples from

cases with ulcerative colitis, an increase of MAGL verbalization in the colonic epithelium

was noticed, suggesting an increase of 2-AG change dur- insult the redness. 2-AG can

likewise be guarding in the stomach, because the MAGL inhibitor JZL184 obviated

diclofenac-inferred about the stomach bleeding. This securing effect is a concept to

become functional raised stomach levels of 2-AG that likely induce a CB1 receptor-

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arbitrated restriction of the raised release of about the stomach interleukin (IL)-1β, IL-

10, IL-6, carcinoma fatality determinant (TNF)-α and granulocyte community-exciting

factor (Kinsey et al., 2011).

G protein-connected receptor 55

There have been various reports that the GPR55 deoxyribonucleic acid is present

inside the GI area, even though to date, skilled have been no localization studies to decide

if this verbalization is neuronal, powerful, or mucosal. The nonconforming cannabinoid

O-1602 restricts neurogenic shortenings in the rodent colon by way of GPR555; these

findings were habitual utilizing CB1 and CB2 a blow that knocks unconscious tissues as

controls. Although the belongings were mainly pre-junctional, few were postjunctional at

extreme concentrations, and belongings on calcium flow have been excluded. GPR55

performs expected upregulated (at deoxyribonucleic acid and protein level) by redness

in the stomach and abdomen, part of the digestive tract, and colon in a LPS model of

infection of blood; the upregulation of GPR55 was reversed by CBD and O-1602. CBD is

thinking expected an enemy at GPR55, when in fact O-1602 is an agonist. The authors

gamble that GPR55 may support raw spot and that CBD wielded allure antagonistic-

angering effect by being a part of a GPR55 enemy.

Transient receptor potential channels

TRP channels play a main part in GI motility, GI perception, and GI disorders. In

addition, CB1 receptors and TRPV1 channels are colocalized in basic affecting animate

nerve organs imbalance raw spot, and the endocannabinoid, anandamide, can turn on

two together these pharmacological aims. Certain phytocannabinoids can too activate

TRP channels. De Petrocellis and coworkers have stated that CBD, CBG, CBGV, and THCV

excite and dull human TRPV1, and likewise that most phytocannabinoids mobilize and

dull TRPV2. These channels are articulated on instinctive afferents and epithelial cells:

TRPV1 is a concept to has a duty in instinctive chemoception, mechanoception, and

nociception. However, the function of TRPV2 in the gut is still obscure.

Both tentatively and in the hospital, phytocannabinoids may be administered as

standardized marijuana extracts improved accompanying particular phytocannabinoids.

Such an extract is usually.

Dubbed “decorated with flowers drug element” (BDS). CBG BDS (i.e., marijuana

patterned extract improved in CBG) and THCV BDS (that is, cannabis patterned extract

improved in THCV) are powerful informer TRPM8 antagonists (De Petrocellis et al.,

2011). The implications concerning this are unsettled as this channel, situated on

instinctive afferents, is activated by chilling or menthol. However, menthol conduct in the

gut is stated as expected TRPM8 independent accordingly the physiologic function

concerning this channel in the GI area is obscure.

CBC, CBD, THCV, and CBN are TRPA1 agonists and desensitizers (De Petrocellis et

al., 2011). The TRPA1 channel is stimulated by spicy compounds in the way that mustard

lubricates and is articulated in instinctive afferents. This channel provides

mechanosensation and is an idea to play a role in spar container incitement and the

managing of 5-hydroxytryptamine release in enterochromaffin cells (De Petrocellis et al.,

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2011). The TRPA1 channel can show a main pharmacological mark for cannabinoids in

the gut.

A current paper stated that the plant cannabinoid CBC influences TRPV1, TRPV3,

and TRPV4 verbalization in the GI tract that had happened raised by an angering insult

(De Petrocellis et al., 2011). A further research found that CBC normalized croton

lubricate-inferred hypermotility in vivo, and discounted electrically and acetylcholine-

inferred shortenings. These actions were not interceded by cannabinoid receptors or

TRPA1 channels. These data signify that CBC can modify TRP channel verbalization under

instigative environments but does not perform to communicate directly accompanying

aforementioned channels (not completely in action/contractility studies).

Peroxisome proliferator-activated receptors

Endogenous, artificial, and plant-derivative cannabinoids are popular to switch on

PPARs, kin of nuclear receptors including three isoforms—α, β, and γ—that manage

container differentiation, absorption, and invulnerable function. Anandamide and oleoyl

ethanolamide (a fundamental parallel of anandamide) may switch on PPARα, which is

meant by neurons in the myenteric and submucosal plexuses during the whole of the GI

lot. Furthermore, anandamide 2-AG, and ajulemic acid, a structural parallel of THC,

extract antagonistic-angering effects by way of PPARγ incitement. Among the

phytocannabinoids, THC and CBD are famous for stimulating PPARγ (O’Sullivan and

Kendall 2010). CBD has been shown to strive antiproliferative belongings in colorectal

abnormal growth in animate being containers with a system including, not completely

incompletely, PPARγ incitement. Similarly, CBD has existed raise to weaken the

verbalization of S100β and an inducible nitric group of chemical elements synthase

(iNOS) proteins in intestinal biopsies of ulcerative colitis inmates in a PPARγ-adversary

delicate manner.

Pharmacological conduct

Gastric acid discharge and gastroprotection

Cannabinoids decrease acid results in rodents by way of CB1 receptor activation.

The home of operation is on vagal radiating from a central point pathways to the about

the stomach covering layer and not possible parietal containers because CB1 receptor

incitement results in a decline in acid discharge persuaded by 2-deoxy-D-glucose and

pentagastrin (that increases acid discharge through the release of acetylcholine), but not

by histamine, that straightforwardly activates H2 receptors on parietal containers. In

agreement with the stomach antisecretory operation, CB1 receptor incitement by

cannabinoids is guarding in animal models in which the stomach ulcers have happened

persuaded by:

1) Anesthetic

2) Water immersion and limitation stress

3) Cold/restraint stress. Similarly, FAAH inhibitors likewise show gastroprotective

belongings, while CB1 receptor antagonists two together increase acid results in

artificial and annoy experiment- tally induced stomachic lesions.

4) Studies on plant-derivative cannabinoids were first performed before the finding of

cannabinoid receptors. A severe situation accompanying a Cannabis sativa extract

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affected the injury pattern and occurrence of ulcerations guide limitation-induced

stomach ulcerations in rats. THC created a marked decline in stomachic abscess

establishment in the pylorus-ligated rat test. This decline was more evident following

position or time subcutaneously than the oral presidency. THC diminished stomachic

juice book, while free and total stomach acid content was not reduced. In an in vitro

research , THC did not change situated acid production in rats but acted to inhibit

stomachic acid discharge inferred by histamine, that is suggestive of a direct operation

of THC on parietal containers that is to say most likely not interfered by CB1 receptors

(visualize former in this place section). Nevertheless, the completely current finding

of CB1 receptors on human parietal containers points to class dissimilarities and plans

that further studies are needed to completely demonstrate the way of operation of THC

in the control of GI acid secretion.

Lower esophageal sphincter

The lower esophageal sphincter (LES) is a specific, automatic, round, smooth

influence located at the base of the neck that admits the passing of a swallowed tablet and

forbids the decline of the stomach contents into the neck. Defects in LES entertainment

can bring about gastro-esophageal regression disease (GERD). CB1 receptor incitement

has proven to inhibit temporary LES relaxations in dogs and ferrets, the effect is

associated, not completely in the dog, accompanying the hindrance of a burning

sensation. Central and minor vagal methods are involved in these working changes.

Similarly, in active enlists, THC (10 mg and 20 mg) both shy the increase in temporary

LES relaxations stimulated by food ingestion, and weakened willing taking into the throat

as well as basic LES pressure. After consumption of 20 mg THC, half of the matter

experienced sickness in the stomach, and disgorging chief to the untimely termination of

the research . Other side belongings were hypotension, heart attack, and cerebral

belongings. Intriguingly, a fake pill-regulated, double-blind, randomized, crossover

research explained that the CB1 receptor foe, rimonabant, inhibited the food-inferred

increase in temporary LES entertainment, increased postprandial LES pressure chief to a

lower number of burning sensation occurrences, and increased the event of distal

esophageal peristaltic waves.

Gastrointestinal action

Cannabinoid receptor agonists have been shown to humiliate stomachic, limited

stomach, and colonic motility two together in unique pieces and in in vivo studies in

rodents. The effect is largely on account of CB1 receptor incitement, even though CB2

receptors may be complicated in a few pathophysiologic states (visualize sections 12.3.5–

12.3.8). In vitro, cannabinoids take action with prejunctional CB1 receptors to defeat

smooth influence contractility and peristalsis in different regions of the experimental

subject GI lot. Several cannabinoid receptor agonists have shown extreme effectiveness

as inhibitors of electrically persuaded shortenings in several stomach private

developments, containing human ones. Notably, the plant cannabinoids THC and CBN.

Has proved to defeat electrically evoked shortenings in the experimental subject

and rat part of the digestive tract. The system by which- cannabinoid receptor incitement

reduces contractility is mainly connected with the decline of acetylcholine release from

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myenteric sleeplessness. Conversely, cannabinoid receptor antagonists/opposite

agonists have been shown to increase electrically induced shortenings in unique

experimental subject intestinal segments and to quicken stomachic draining and stomach

action in vivo.

The capability of plant cannabinoids to reduce stomach action was earlier famous

before the finding of cannabinoid receptors. In 1972, Dewey and colleagues were the first

to report that THC diminished the rate of transition of black food near the mouse part of

the digestive tract. These verdicts were habitual in other studies. In each of these early

experiments, THC was executed intraperitoneally or subcutaneously and it was found

expected six to ten periods were less powerful than morphine in restricting the transit.

However, when executed intravenously, THC was equipotent accompanying opiate.

Interestingly, THC antagonized (at depressed doses, that is, 0.25 mg/kg) or potentiated

(at a higher quantity, that is, 1 mg/kg) the depreciated action persuaded by prostaglandin

E2 in mice.

In a total research , Shook and Bruks granted that THC and CBN delayed the rate of

gastric consumption and limited stomach transportation when introduced intravenously

in mice and rats. Whereas THC evenly shy about stomach purging and limited intestinal

transportation, CBN had only the slightest belongings on stomachic emptying. THC

presented better hindrance about the stomach exhausting and small stomach

transportation than abundant bowel transportation, indicating relative discrimination

for the more having a common boundary portion of the gut. When THC was introduced

intracerebroventricularly, it shy transit, but only at doses that were still alive when

introduced intravenously, meaning that it was acting at a peripheral ground. In the more

current age, accompanying the availability of discriminating receptor antagonists,

different investigators have proved that the inhibitory belongings of THC and CBN on GI

action are mediated by cannabinoid receptor incitement. Specifically, intraperitoneally

administered CBN reduces the transition of black in the rodent part of the digestive tract

and increases the moment of truth of expulsion of a droplet introduced in the rodent

colon in a CB1 foe-impressionable way. Similarly, the CB1 receptor adversary rimonabant

counteracted the enduring decrease in rat intragastric pressure and pyloric contractility

induced by intravenously executed THC. The effect of THC on the stomach action was

abolished by reciprocal vagotomy at the intervening cervical level and by

hexamethonium, but not by representative sample of the cervical sleep-inducer cord

suggesting that this phytocannabinoid produces allure inhibitory belongings on the

stomach somewhat by pursuing the back vagal complex of the hindbrain to modulate

vagal (parasympathetic) efflux to about the stomach smooth influence.

Recently, the non-psychotropic phytocannabinoids CBD and CBC have been

evaluated as modern- emulators of stomach action, two together in isolated stomach

sectors and in in vivo studies on transportation. Neither compound changed the stomach

motility of administrative rodents in vivo, but two together of bureaucracy did standard

action following the presidency of an instigative insult. In the unique mouse entrails, CBD

weakened acetylcholine- and KCl-inferred shortenings, suggesting a nonspecific

antispasmodic effect. In the unchanging fabric, CBC suggested of choice shortened

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electrically induced shortenings—rather than acetylcholine-persuaded shortenings—by

a means involving neuronal N-type Ca2+ channels.

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Intestinal fluid discharge

An able fluid discharge is necessary for the normal enactment of gut essences ahead

of the bowel. In the colon, fluid is involved, restricting water content; a failure to consume

water or some position of overdone secretion leads to dysentery. Studies on private

stomach sectors have proved that activation of CB1 receptors concede the possibility

produce an antisecretory effect through a neuronal system including the hindrance of

neurotransmitter(s) release from submucosal plexus neurons and foreign basic afferents

In vivo, cannabinoid receppile agonists reduce stomach hypersecretion persuaded by

cholera poison in rodent.

The effect of plant-derived cannabinoids on stomach water and electrolyte

transport has not been exhaustively judged. Early studies showed that THC reinforced

net water assimilation in the informer part of the digestive tract, and this effect was not

guided by a reduced content of prostaglandin E2-like material.

Visceral perception

Experimental evidence suggests that CB1 or CB2 receptor incitement restricts

instinctive sensitivity and pain in rodents. The CB1 receptor-intervened anodyne effect

guides the downregulation of TRPV1, as long as CB2 receptor agonist inhibition of

instinctive pain reactions performs expected on account of inhibition of the algesic

answers to bradykinin. Booker and associates evaluated the antinociceptive effect of any

of the plant-derived cannabinoids in the tart acid elongated test, an experimental subject

instinctive pain model. It was evident that THC and CBN exerted a CB1 foe-delicate, but

not a CB2 enemy-delicate antinociceptive effect at doses inferior to those necessary to

produce locomotor abolition. Also, compatible with accompanying allure CB1 receptor

antagonistic possessions, THCV had no effect when executed uniquely, but acted correctly

with the antinociceptive effect of THC. A premature report granted that two together a

vulgar marijuana extract, and THC, CBN, but not CBD, presented an important anesthetic

effect in the tart acid extended test, with THC being as alive as a drug.

Intestinal redness

Animal studies have proved that cannabinoids, via CB1 or CB2 receptor incitement,

in addition to by way of promotion of endocannabinoid levels, effectively weaken redness

in traditional modernels of angering bowel disease (IBD). Conversely, exploratory

swelling is exacerbated in CB1 or CB2 receptor a striking person or thing rodent or in

rodent discussed accompanying CB1 or CB2 receptor. In the gut of cases accompanying

IBD, adjusting changes of the endogenous cannabinoid scheme (for instance, changes in

cannabinoid receptors and/or in endocannabinoid levels happening from modifications

of an individual or more of the enzymes complicated in endocannabinoid biosynthesis or

degradation) have been noticed.

Concerning plant-derived cannabinoids, THC, CBD, CBC, and CBG have confirmed

expected offspring- official in exploratory models of IBD. Jamontt and associates showed

that THC discounted signs of damage, redness, and working commotion in the

trinitrobenzene sulfonic acid (TNBS) informer model of IBD. THC also enhanced the

function of cholinergic motoneurons, while sulfasalazine (a standard situation for IBD)

acted dismayed any securing effect on TNBS-inferred changes in action. THC still restored

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the raised permeability inferred by ethylenediaminetetraacetic acid (EDTA) in stomach

epithelial containers.

The first manifestation of an advantageous action of CBD in stomach redness was

given by Borrelli and associates, who displayed that this phytocannabinoid, likely

intraperitoneally, diminished the degree of stomach redness created by intracolonic

administration of dinitrobenzene sulfonic acid (DNBS) in rodent. The securing effect of

CBD was guide downregulation of iNOS (but not cyclooxygenase-2) verbalization and

modulation of cytokine (IL- 1β and IL-10) levels since it acted not include interference

accompanying endocannabinoid inactivation machines to a degree FAAH inhibition. The

advantageous effect of CBD in rodents has currently been rooted by Schicho and Storr,

who professed that not only intraperitoneal administration but again intrarectal

situation accompanying CBD led to a meaningful bettering of affliction limits, have

provided evidence that intrarectal transmittal of cannabidiol can show a useful healing

presidency route for the situation of colonic inflammation. Finally, CBD was confirmed

advantageous in the TNBS model of colitis in rats accompanying allure dose–action

friendship showing a bell-formed pattern for the plurality of limits investigated. CBD not

only lowered swelling, but likewise lowered the incidence of working disorders; also,

CBD acted additively or synergistically accompanying THC to weaken redness and to

protect against cholinergic irritation.

Experiments on unique stomach cells have habitual the advantageous effect of CBD

against angering insults. In colorectal carcinoma (Caco-2) containers, CBD obviated

oxidative stress, which may be affiliated with the fundamental determinants chief to

mucosal protection in vivo. Also, CBD was smart to fix the increased permeability inferred

by EDTA or cytokine in the Caco-2 container civilization model of intestinal permeability.

The effect was awake a cannabinoid CB1 receptor adversary, but not to CB2 receptor,

TRPV1, PPARγ, or PPARα antagonists. Finally, in stomach segments acquired from

rodents accompanying LPS-induced stomach swelling, CBD was established to counteract

sensitivity about the stomach gliosis, an effect guided by a large reduction in the astroglial

indicating neurotrophin S100β. Similarly, CBD weakened the expression of S100β and

iNOS proteins in cruel examination samples acquired from patients accompanying

ulcerative colitis.

Recently, CBG and CBC have been proven to exert deterrent and healing effects in

the DNBS rodent model of colitis. Both CBC and CBG shortened the colon burden/colon

length percentage (a natural and trustworthy gravestone of intestinal inflammation),

myeloperoxidase endeavor, and stomach permeability in DNBS-medicated mice. More in-

depth studies revealed that the advantageous effect of CBG was guide modulation of

cytokine (IL-1β, IL-10, and interferon-γ) levels and downregulation of iNOS (but not

cyclooxygenase-2) verbalization. In stomach epithelial containers, CBG obviated reactive

oxygen variety result, which may help to illustrate the securing effect concerning this

phytocannabinoid that has been noticed in vivo.

Motility dysfunctions in the congested gut

Changes in the inside cannabinoid structure during redness can change and/or

contribute to action changes that happen in IBD patients. The experimental evidence

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implies that revolving around- insult on the instigative insult, both CB1 and CB2 receptor

incitement concede the possibility of decreased hypermotility guide gut redness. Thus,

stomach swelling persuaded by croton oil is from the division of the covering layer and a

combination of lymphocytes into the substitute mucosa, and specific changes are guide

curtailed anandamide and palmitoylethanolamide levels, in addition to accompanying

upregulation of cannabinoid CB1 receptors and TRPA1 channels. Motility in the Croton

lubricate model of ileitis may be weakened by an effect that was associated with the

downregulation of phospho-Akt and upregulation of caspase-3. Studies on colorectal

abnormal growth in animate being containers submitted that CBD shielded DNA damage

induced by an oxidative insult and exerted antiproliferative belongings through

diversified methods, containing difficulty of CB1 receptors, TRPV1, and PPARγ.

The decay of marijuana elements leads to the establishment of the matching

quinones, which have manifested expected cytotoxic powers. The quinone of CBD, chosen

HU-331, exerts antiangiogenic and proapoptotic features and prevents topoisomerase II.

Unlike added quinones, it is not cardiotoxic and does not induce the establishment of free

radicals. An approximate in vivo research in rodents has proved HU-331 is expected less

toxic and more direct than doxorubicin in a without clothes, covering rodent HT-29 colon

malignant growth model.

Several drugs including CB1 and CB2 receptor agonists. CBN, CBD, and CBC have

been judged for their capability to alter the action changes that guide the stomach

swelling induced by spoken Croton lubricate presidency, as itemized in division 3.7.

Like other cannabinoid receptor agonists, CBN (a prejudiced cannabinoid CB1

receptor agonist) lowered stomach action two together in control and Croton lubricate-

considered mammals, affecting better inhibitory activity in unhealthy states.

Interestingly, this inhibitory effect was followed not only by a leftward shift in the in vivo

record dose-response curve of CBN but also by an increase in the capacity of its maximum

effect. The artificial agonist CP55940, which has higher CB1 productiveness than CBN,

has shown an effectiveness increase but the current situation is in allure maximal effect.

The reduced doses of CBN that are wanted to humble action during stomach

inflammation are of interest in the light of likely healing requests of aforementioned a

compound in IBD.

More recently, the non-psychotropic phytocannabinoids CBD and CBC have been

judged in the Croton lubricate model of stomach hypermotility. Although neither CBD nor

CBC alters stomach motility in administrative rodents, two together of bureaucracy do

normalize stomach action in congested rodents. The inhibitory effect of CBD includes CB1

receptors by way of promotion of endocannabinoid levels at these receptors inferred by

FAAH inhibition, that is agreeing accompanies the strength concerning this

phytocannabinoid to reduce FAAH verbalization in the congested—but not in the

normal—rodent gut. On the other hand, the inhibitory effect of CBC did not include

cannabinoid receptors or TRPA1 channels. In vitro, two together CBC and CBD applied

spasmolytic conduct in ilea from control and croton-lubricate-treated mammals. More

exhaustive studies on CBC displayed that this phytocannabinoid changed the ex vivo

verbalization of several TRP channels, to a degree TRPA1, TRPV1, TRPV3, and TRPV4,

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raw spot of croton lubricate-discussed rodent (De Petrocellis et al., 2011). Overall, the in

vivo talent of two together CBC and CBD to make universal action in the inflamed gut,

outside delaying the rate of transportation in active animals, is of potential dispassionate

interest because now secondhand antidiarrheal powers are often guided constipating

belongings.

Finally, Lin and associates establish that CBD normalized hypomotility and

instigative responses in the LPS rodent model of poisonous ileus. The feasibility that CBD

acts as an integral anti-angering power in this place model of stomach dysfunction cannot

be rejected.

Colon tumor

Cannabinoids bring to bear antiproliferative, antimetastatic, and proapoptotic

conduct in colorectal carcinoma epithelial containers. In experimental in vivo models of

a colon tumor, cannabinoid agonists may be guarding in different stages of colon

malignancy progression either straightforwardly, through the incitement of CB1 or CB2

receptors, or obliquely, through the height of endocan-cannabinoid levels by way of FAAH

inhibition. Their antitumor conduct can be mediated by either CB1 or CB2 receptor

incitement. The means of CB1-interceded apoptosis includes inhibition of two together

the RAS–MAPK/ ERK and PI3K–Akt endurance indicating cascades and downregulation

of the antiapoptotic determinant survivin. The proapoptotic lipid ceramide may be

involved in two together CB1- and CB2-interfered antitumor belongings.

Recently, the phytocannabinoid CBD has been judged for its likely chemopreventive

effect in a rodent model of colon malignancy inferred apiece carcinogenic power

azoxymethane (AOM). CBD efficiently decreased AOM-persuaded preneoplastic lesions,

polyps, and tumors in the colon, an

Clinical studies

Gastrointestinal action, instinctive sensation, and IBS

Visceral sensitivity to extension and changed GI motility are thought to play a main

part in the pathophysiology of irritable bowel disease (IBS). Both instinctive perception

and GI motility have judged cruel volunteers following in position or time the THC

presidency. Thus, nine male and four female cannabis consumers withstood the stomach

emptying studies that secondhand radiolabeled reliable cooking as a gravestone, after

they had taken THC (at a lot of 10 mg/m2 of carcass surface area) or fake pill. Gastric

consumption afterward THC was slower than following in position or time fake pill fully

subjects. However, no equating was raised between plasma THC levels and the delay in

stomachic unloading. The authors decided that THC, at a dose that can hamper

destructive agent-persuaded nausea and disgorging, considerably slowed gastric

discharging of dependable foodstuff in humans. The inhibitory effect of THC on stomachic

unloading has been rooted again by Esfandyari and associates, in a randomized, double-

blind research performed accompanying 30 athletic signs up who had taken THC (5 mg

doubly moment of truth) or placebo. Gastric clearing was calculated noninvasively. An

overall delay of stomachic emptying accompanying THC distinguished from standard

drugs was observed, the effect being more evident in women than in men.

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In an additional randomized, double-blind trial, Esfandyari and associates

evaluated colonic compli- ance, motility, color, and perception in 52 suggests who had

taken a alone dosage of 7.5 mg THC. An overall significant increase in colonic agreement,

an inexact effect on entertainment in fasting colonic pitch, hindrance of postprandial

colonic pitch, and inhibition of abstaining and postprandial phasic pressure was noticed.

Collectively, the results show that THC relaxes the colon and reduces postprandial colonic

action and volume in persons.

More recently, Wong and associates distinguished the belongings of THC (5 mg)

with those of standard drugs on colonic action and feeling in patients accompanying IBS,

and again administered a pharmacogenetic analysis that investigated the influence of

ancestral alternative in the CB1 receptor, FAAH, and MAGL on the strength of THC to alter

dysentery and colonic transportation in IBS accompanying diarrhea sufferers. In all

subjects (35 with IBS accompanying muscle spasm, 35 accompanying IBS with flux, and

5 accompanying change-dating IBS) THC did not change feeling or color but decreased

the abstaining next abandoned colonic motility index distinguished accompanying

standarddrugs, and increased colonic agreement. The belongings of THC were excellent

in patients accompanying IBS accompanying loose bowels or with rotating IBS. FAAH and

CNR1 variants affected the effect of THC on colonic action. In an after research , the alike

authors raise that THC (2.5 and 5 mg) did not affect gut transit in IBS inmates

accompanying flux, although a situation-by-genotype effect was noticed, bywhich THC

preferentially deferred colonic transportation in inmates accompanying the CNR1

rs806378 CT/TT genotypes (Wong et al. 2012)

Finally,Klooker and associates judged the effect of THC on sensitivity in ten IBS

subjects and 12 active came forward. THC did not change the criterion stomach

perception to extension distinguished to fake pill either in volunteers or in IBS cases.

Similarly, following in position or time bowed stimulation there were no important

dissimilarities between fake pill and THC in neurological thresholds of discom-

stronghold.

In conclusion, studies in persons plan that THC can affect the stomach escaping and

colonic action in healthy and/or IBS inmates, specifically in a subgroup of IBS with

dysentery victims, established a specific historical difference in the CB1 receptor. Further

studies of cannabinoid pharmacogenetics manage to identify a subspace of IBS

accompanying loose bowels inmates in which cannabinoid cures concede the possibility

solve. Conversely, THC does not seem to influence instinctive ideas in humans, a result

that portrays the significance of doing translational studies when fact-finding a likely

clinical use of a cannabinoid.

Inflammatory bowel disease

Some IBD victims anecdotally report that they can acquire remedy by smoking pot.

Recently, three studies, showing the advantageous effects of marijuana use in persons,

appear to confirm the aforementioned reports.

Naftali and associates conducted a retrospective practical research testing ailment

activity, use of medication, and need for medical procedure before and following in

position or time marijuana use in 30 Crohn’s disease (CD) sufferers (26 men). Of the 30

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victims, 21 improved considerably afterward situation with marijuana. The need for the

additional drug was significantly discounted and the number of victims needing

enucleation decreased along with marijuana use.

Lal and colleagues judged marijuana use in 291 IBD sufferers, who achieved an

inquiry concerning current and previous marijuana use. About 50% of these IBD victims,

specifically those with a record of intestinal incision, chronic intestinal pain, and/or an

inferior growth, reported life or current marijuana use. Patients the one had used

marijuana were more likely than nonusers to express an interest in performing in a

supposed therapeutic trial of marijuana for IBD. Collectively specific results show that

cannabis use for syndrome relaxation is ordinary in patients accompanying IBD.

Finally, a ship prospective research including 13 cases accompanying long-standing

IBD determined either situation accompanying inhaled cannabis (cigarettes) revised

kind of growth, reduced ailment venture, and advanced weight gain in IBD cases. After 3

months’ situation, sufferers reported bettering usually well-being perception, public

functioning, talent to work, pain, and concavity. Cannabis more advanced burden gain

and induced a rise in material bulk index.

CONCLUSION

The conclusions of this study suggest that phytocannabinoids, particularly CBD and

THC, show significant potential as therapeutic agents for gastrointestinal (GI) health by

modulating motility, reducing inflammation, and influencing the gut microbiome.

Emerging evidence supports their integration into treatment strategies for GI disorders

such as IBS, IBD, and colorectal malignancies. Future research should focus on optimizing

formulations, evaluating long-term safety and efficacy, and exploring their synergistic

potential with other therapies to enhance clinical applications.

Although preliminary clinical data are promising, challenges remain in balancing

the benefits of cannabinoids with potential adverse effects, such as those linked to CB1

receptor activation. Emphasis should be placed on non-psychoactive cannabinoids, which

offer therapeutic potential with fewer side effects. This research contributes to a growing

understanding of phytocannabinoids, paving the way for their broader and safer

application in managing GI disorders.

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Rehan Haider, Geetha Kumari Das, Zameer Ahmed, Sambreen Zameer (2025)

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AJHS - Asian Journal of Healthy and Science

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