The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease

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“In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract.

Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors.

After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS.

The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/27561826

Survey of herbal cannabis (marijuana) use in rheumatology clinic attenders with a rheumatologist confirmed diagnosis.

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“Cannabinoids may hold potential for the management of rheumatic pain.

Arthritis, often self-reported, is commonly cited as the reason for the use of medicinal herbal cannabis (marijuana). We have examined the prevalence of marijuana use among 1000 consecutive rheumatology patients with a rheumatologist-confirmed diagnosis and compared in an exploratory manner the clinical characteristics of medicinal users and nonusers.

Current marijuana use, medicinal or recreational, was reported by 38 patients (3.8%; 95% CI: 2.8-5.2). Ever use of marijuana for medical purposes was reported by 4.3% (95% CI: 3.2-5.7), with 28 (2.8%; 95% CI: 1.9-4.0) reporting current medicinal use. Current medicinal users had a spectrum of rheumatic conditions, with over half diagnosed with osteoarthritis. Medicinal users were younger, more likely unemployed or disabled, and reported poorer global health. Pain report and opioid use was greater for users, but they had similar physician global assessment of disease status compared with nonusers.

Medicinal users were more likely previous recreational users, with approximately 40% reporting concurrent recreational use. Therefore, less than 3% of rheumatology patients reported current use of medicinal marijuana. This low rate of use in patients with a rheumatologist-confirmed diagnosis is in stark contrast to the high rates of severe arthritis frequently reported by medicinal marijuana users, especially in Canada. Familiarity with marijuana as a recreational product may explain use for some as disease status was similar for both groups.”

https://www.ncbi.nlm.nih.gov/pubmed/27842047

Cannabis improves night vision: a case study of dark adaptometry and scotopic sensitivity in kif smokers of the Rif mountains of northern Morocco.

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“Previous reports have documented an improvement in night vision among Jamaican fishermen after ingestion of a crude tincture of herbal cannabis, while two members of this group noted that Moroccan fishermen and mountain dwellers observe an analogous improvement after smoking kif, sifted Cannabis sativa mixed with tobacco (Nicotiana rustica).

Field-testing of night vision has become possible with a portable device, the LKC Technologies Scotopic Sensitivity Tester-1 (SST-1).

This study examines the results of double-blinded graduated THC administration 0-20 mg (as Marinol) versus placebo in one subject on measures of dark adaptometry and scotopic sensitivity.  Analogous field studies were performed in Morocco with the SST-1 in three subjects before and after smoking kif.

In both test situations, improvements in night vision measures were noted after THC or cannabis. It is believed that this effect is dose-dependent and cannabinoid-mediated at the retinal level.

Further testing may assess possible clinical application of these results in retinitis pigmentosa or other conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/15182912

Preparation and Distribution of Cannabis and Cannabis-Derived Dosage Formulations for Investigational and Therapeutic Use in the United States.

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“Cannabis is classified as a schedule I controlled substance by the US Drug Enforcement Agency, meaning that it has no medicinal value. Production is legally restricted to a single supplier at the University of Mississippi, and distribution to researchers is tightly controlled. However, a majority of the population is estimated to believe that cannabis has legitimate medical or recreational value, numerous states have legalized or decriminalized possession to some degree, and the federal government does not strictly enforce its law and is considering rescheduling. The explosive increase in open sale and use of herbal cannabis and its products has occurred with widely variable and in many cases grossly inadequate quality control at all levels-growing, processing, storage, distribution, and use. This paper discusses elements of the analytical and regulatory system that need to be put in place to ensure standardization for the researcher and to reduce the hazards of contamination, overdosing, and underdosing for the end-user.”

http://www.ncbi.nlm.nih.gov/pubmed/27630566

The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease.

Image result for Neurogastroenterol Motil

“In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract.

Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors.

After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS.

Cannabinoid receptors and their endogenous ligands, the endocannabinoids, participate in the regulation of GI motility, secretion, and the maintenance of the epithelial barrier integrity.

In addition, other receptors, such as the transient receptor potential cation channel subfamily V member 1 (TRPV1), the peroxisome proliferator-activated receptor alpha (PPARα) and the G-protein coupled receptor 55 (GPR55), are important participants in the actions of CBs in the gut and critically determine the course of bowel inflammation and colon cancer.

PURPOSE:

The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/27561826

Cannabis in Pain Treatment: Clinical and Research Considerations

“Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse.

Although research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts.

Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care.

Expanded research on cannabis is needed to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications.

This article reviews clinical, research, and policy issues related to herbal cannabis to support clinicians in thoughtfully advising and caring for patients who use cannabis, and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids.

Perspective

Herbal cannabis is increasingly available for clinical use in the United States despite continuing controversies over its efficacy and safety. This article explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it, and identifies needed directions for research.”

http://www.jpain.org/article/S1526-5900%2816%2900543-5/fulltext

“APS Issues New Guidance on Medical Marijuana for Pain”  http://www.medscape.com/viewarticle/863396

Cannabis in Pain Treatment: Clinical & Research Considerations.

“Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse. While research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts. Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care. Expanded research on cannabis is needed both to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications. This paper reviews clinical, research and policy issues related to herbal cannabis in order to support clinicians in thoughtfully advising and caring for patients who use cannabis and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids.

PERSPECTIVE:

Herbal cannabis is increasingly available for clinical use in the U.S despite continuing controversies over its efficacy and safety. This paper explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it and to identify needed directions for research.”

http://www.ncbi.nlm.nih.gov/pubmed/26961090

Cannabinoids: Medical implications.

“Herbal cannabis has been used for thousands of years for medical purposes.

With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored.

While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy.

While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards.

Where medical cannabis is legal, patients typically see a physician who “certifies” that a benefit may result.

Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis.

Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.

Key messages The medical disorders with the current best evidence that supports a benefit for cannabinoid use are the following: multiple sclerosis patient-reported symptoms of spasticity (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis central pain or painful spasms (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis bladder frequency (nabiximols), and chronic cancer pain/neuropathic pain (nabiximols and smoked THC).

Participating physicians should be knowledgeable about cannabinoids, closely look at the risk/benefit ratio, and consider certain important criteria in selecting a patient, such as: age, severity, and nature of the medical disorder, prior or current serious psychiatric or substance use disorder, failure of standard medical therapy as well as failure of an approved cannabinoid, serious underlying cardiac/pulmonary disease, agreement to follow-up visits, and acceptance of the detailed explanation of potential adverse risks.

The normal human endocannabinoid system is important in the understanding of such issues as normal physiology, cannabis use disorder, and the development of medications that may act as agonists or antagonists to CB1 and CB2.

By understanding the endocannabinoid system, it may be possible to enhance the beneficial effects of cannabinoid-related medication, while reducing the harmful effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26912385

The endocannabinoid system: potential for reducing cardiometabolic risk.

“The endocannabinoid system (ECS) affects multiple metabolic pathways in the brain and other organs. The transmembrane CB receptors were cloned in the early 1990s, followed shortly thereafter by the discovery of endogenous ligands, now known as endocannabinoids.

Three general types of cannabimimetic compounds have been described: herbal CBs, which occur uniquely in the cannabis plant (Cannabis sativa); endogenous CBs (or endocannabinoids), which are produced in the brain and peripheral tissues; and synthetic CBs, which are functionally similar compounds synthesized in the laboratory.

Obesity is associated with increased risk for insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease, atherogenic dyslipidemia, and cardiovascular disease. Recent studies indicate that the body protects itself from weight loss by lowering energy expenditure. Both energy consumption and energy expenditure are regulated by hormones from a number of organs that act on the brain, as well as neural signals emanating from the brain itself.

Lifestyle modification is the initial intervention for obesity, with emphasis on reducing calorie intake and increasing physical activity; pharmacotherapy may be indicated for certain cardiovascular and metabolic risk factors.

This review focuses on the link between the biology of the cannabinoid receptor type 1 (CB1 receptor) system and body-weight regulation, as well as clinical data from studies of the first CB1 receptor antagonist…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905146/

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS).

“Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic noncancer pain.

The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among subjects with chronic noncancer pain.

A standardized herbal cannabis product (12.5% THC) was dispensed to eligible subjects for a one-year period; controls were subjects with chronic pain from the same clinics who were not cannabis users.

The primary outcome consisted of serious adverse events (SAEs) and non-serious adverse events (AEs). Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver and endocrine function.

Secondary efficacy parameters included pain and other symptoms, mood, and quality of life.

Two hundred and sixteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 215 controls (chronic pain but no current cannabis use) from seven clinics across Canada. The median daily cannabis dose was 2.5g/d.

There was no difference in risk of SAEs between groups.

Medical cannabis users were at increased risk of non-serious AEs; most were mild to moderate. There were no differences in secondary safety assessments.

Quality-controlled herbal cannabis, when used by cannabis-experienced patients as part of a monitored treatment program over one year, appears to have a reasonable safety profile.

This study evaluated the safety of cannabis use by patients with chronic pain over one year. The study found that there was a higher rate of adverse events among cannabis users compared to controls but not for serious adverse events at an average dose of 2.5g herbal cannabis per day.”

http://www.ncbi.nlm.nih.gov/pubmed/26385201

http://www.thctotalhealthcare.com/category/pain-2/