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Cannabinoids as Adjunct Treatment for Pancreatic Cancer

Pancreatic Cancer

What is pancreatic cancer?

Cancers that develop within the pancreas fall into two major categories: (1) cancers of the endocrine pancreas (the part that makes insulin) are called “islet cell” or “pancreatic neuroendocrine” cancers and (2) cancers of the exocrine pancreas (the part that makes enzymes). Islet cell cancers are rare and typically grow slowly compared to exocrine pancreatic cancers. Islet cell tumors often release hormones into the bloodstream and are further characterized by the hormones they produce (insulin, glucagon, gastrin, and other hormones). Cancers of the exocrine pancreas develop from the cells that line the system of ducts that deliver enzymes to the small intestine and are called pancreatic adenocarcinomas. Adenocarcinoma of the pancreas comprises ninety five percent of all pancreatic ductal cancers and is the subject of this review.

Cells that line the ducts in the exocrine pancreas divide more rapidly than the tissues that surround them. For reasons that we do not understand, these cells can make a mistake when they divide and an abnormal cell can be made. When an abnormal ductal cell begins to divide in an unregulated way, a growth can form. These changes are called “dysplasia.” Often, dysplastic cells can undergo additional genetic mistakes over time and become even more abnormal. If these dysplastic cells then begin to invade through the walls of the duct from which they arise into the surrounding tissue, a cancer develops.

Pancreatic carcinoma is cancer of the pancreas.

The pancreas is a large organ that is found behind the stomach. It makes and releases enzymes that help the body breakdown proteins (especially fats). It also makes the hormone insulin (and glucagon) that regulate blood sugar levels.
The exact cause is unknown, but pancreatic cancer is more common in smokers and people who are obese. Pancreatic cancer is slightly more common in women than in men. The risk increases with age. A small number of cases are related to genetic syndromes that are passed down through families.

Symptoms

A tumor or cancer in the pancreas may often grow without any symptoms at first. This may mean pancreatic cancer is more advanced when it is first found.

Early symptoms of pancreatic cancer include:
Pain or discomfort in the upper part of the belly or abdomen
Loss of appetite and weight loss
Jaundice (a yellow color in the skin, mucus membranes, or the eyes)
Dark urine and clay-colored stools
Fatigue and weakness
Nausea and vomiting

Other possible symptoms are:

  • Back pain
  • Blood clots
  • Depression
  • Diarrhea
  • Difficulty sleeping
  • Indigestion
Presentation

Pancreatic cancer is sometimes called a “silent killer” because early pancreatic cancer often does not cause symptoms, and the later symptoms are usually nonspecific and varied. Therefore, pancreatic cancer is often not diagnosed until it is advanced.
Most patients with pancreatic cancer experience pain, weight loss, or jaundice.
Pain is present in 80% to 85% of patients with locally advanced or advanced metastatic disease. The pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the back. It may be intermittent and made worse by eating. Weight loss can be profound; it can be associated with anorexia, early satiety, diarrhea, or steatorrhea. Jaundice is often accompanied by pruritus and dark urine. Painful jaundice is present in approximately one-half of patients with locally unresectable disease, while painless jaundice is present in approximately one-half of patients with a potentially resectable and curable lesion.
The initial presentation varies according to location of the cancer. Malignancies in the pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present with steatorrhea, weight loss, and jaundice. The recent onset of atypical diabetes mellitus, a history of recent but unexplained thrombophlebitis (Trousseau sign), or a previous attack of pancreatitis are sometimes noted. Courvoisier sign defines the presence of jaundice and a painlessly distendedgallbladder as strongly indicative of pancreatic cancer, and may be used to distinguish pancreatic cancer from gallstones. Tiredness, irritability and difficulty eating because of pain also exist. Pancreatic cancer is often discovered during the course of the evaluation of aforementioned symptoms.

Pancreatic cancer facts

1. Most pancreatic cancers are adenocarcinomas
2. Few patients diagnosed with pancreatic cancer have identifiable risk factors.
3. Pancreatic cancer is highly lethal.
4. Pancreatic cancer is difficult to diagnose, and the diagnosis is often made late in the disease course. Symptoms include weight loss, back pain, and jaundice.
5. The only curable treatment is surgical removal of all of the cancer.
6. Chemotherapy after surgery can lower the chances of the cancer returning.
7. Chemotherapy for metastatic pancreatic cancer can extend life and improve the quality of life for people with the disease.
8. Patients diagnosed with pancreatic cancer are encouraged to seek out clinical trials to improve pancreatic cancer treatment.

Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for ninety five percent of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a neuroendocrine tumor. The symptoms that lead to diagnosis depend on the location, the size, and the tissue type of the tumor.

Pancreatic cancer is the fourth most common cause of cancer death both in the United States and internationally. Pancreatic cancer often has a poor prognosis: for all stages combined, the (one and five year) relative survival rates are twenty five percent and six percent respectively, while the median survival for locally advanced and for metastatic disease, which collectively represent over eighty percent of individuals, is about ten and six months respectively.

Expectations (prognosis)

Some patients with pancreatic cancer that can be surgically removed are cured. However, in more than eighty percent of patients the tumor has already spread and cannot be completely removed at the time of diagnosis.
Chemotherapy and radiation are often given after surgery to increase the cure rate (this is called adjuvant therapy). For pancreatic cancer that cannot be removed completely with surgery, or cancer that has spread beyond the pancreas, a cure is not possible and the average survival is usually less than one year. Such patients should consider enrolling in a clinical trial (a medical research study to determine the best treatment). Five to ten percent of pancreatic cancer patients have a family history of pancreatic cancer.

“Ninety-five percent of the people diagnosed with this cancer will not be alive in five years”

Complications
  • Blood clots
  • Depression
  • Infections
  • Liver problems
  • Pain
  • Weight loss

Calling your health care provider Call for an appointment with your health care provider if you have:

  • Back pain
  • Unexplained fatigue or weight loss
  • Loss of appetite
  • Persistent abdominal pain
  • Other symptoms of this disorder
Prevention
  • If you smoke, stop smoking.
  • Eat a diet high in fruits, vegetables, and whole grains.
  • Exercise regularly.
Surgery

Treatment of pancreatic cancer depends on the stage of the cancer. The Whipple procedure is the most common surgical treatment for cancers involving the head of the pancreas. This procedure involves removing the pancreatic head and the curve of the duodenum together (pancreato-duodenectomy), making a bypass for food from stomach to jejunum (gastro-jejunostomy) and attaching a loop of jejunum to the cystic duct to drain bile (cholecysto-jejunostomy). It can be performed only if the patient is likely to survive major surgery and if the cancer is localized without invading local structures or metastasizing. It can, therefore, be performed in only the minority of cases.
Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy. Recently, localized cancers of the pancreas have been resected using minimally invasive (laparoscopic) approaches.
After surgery, adjuvant chemotherapy with gemcitabine has been shown in several large randomized studies to significantly increase the 5-year survival (from approximately 10 to 20%), and should be offered if the patient is fit after surgery
Surgery can be performed for palliation, if the malignancy is invading or compressing the duodenum or colon. In that case, bypass surgery might overcome the obstruction and improve quality of life, but it is not intended as a cure.

Chemotherapy

In patients not suitable for resection with curative intent, palliative chemotherapy may be used to improve quality of life and gain a modest survival benefit. Gemcitabine was approved by the United States Food and Drug Administration in 1998, after a clinical trial reported improvements in quality of life and a 5-week improvement in median survival duration in patients with advanced pancreatic cancer. This marked the first FDA approval of a chemotherapy drug primarily for a nonsurvival clinical trial endpoint. Gemcitabine is administered intravenously on a weekly basis.

Prognosis

Exocrine pancreatic cancer (adenocarcinoma and less common variants) typically has a poor prognosis, partly because the cancer usually causes no symptoms early on, leading to locally advanced or metastatic disease at time of diagnosis.
Pancreatic cancer may occasionally result in diabetes. Insulin production is hampered, and it has been suggested the cancer can also prompt the onset of diabetes and vice versa.[65] It can be associated with pain, fatigue, weight loss, jaundice, and weakness. Additional symptoms are discussed above.

For pancreatic cancer:

For all stages combined, the 1-year relative survival rate is 25%, and the 5-year survival is estimated as less than five to six percent.
For local disease, the 5-year survival is approximately 20%.
For locally advanced and for metastatic disease, which collectively represent over 80% to 85-90%of individuals, the median survival is
about 10 and 6 months, respectively. Without active treatment, metastatic pancreatic cancer has a median survival of 3–5 months; complete remission is rare.
Outcomes with pancreatic endocrine tumors, many of which are benign and completely without clinical symptoms, are much better, as are outcomes with symptomatic benign tumors; even with actual pancreatic endocrine cancers, outcomes are rather better, but variable.

In 2010, an estimated 43,000 people in the US were diagnosed with pancreas cancer and almost 37,000 died from the disease; pancreatic cancer has one of the highest fatality rates of all cancers, and is the fourth-highest cancer killer in the US and internationally among both men and women. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for six percent of cancer deaths each year.

Cannabinoids as Adjunct Treatment for Pancreatic Cancer

Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes” and “Delta-9-tetrahydrocannabinol inhibits cell cycle progression in pancreatic cells.

Pancreatic adenocarcinomas are among the most malignant forms of cancer and, therefore, it is of special interest to set new strategies aimed at improving the prognostic of this deadly disease. The present study was undertaken to investigate the action of cannabinoids, a new family of potential antitumoral agents, in pancreatic cancer cells.Despite many years of intensive research, pancreatic cancer remains as the fourth leading cause of cancer death in the United States and the fifth in the Western world overall . Current approved therapies based on the administration of fluorouracil chemoradiation for locally advanced tumors and gemcitabine chemotherapy for metastatic disease have only slightly increased the median survival of affected patients . In the present report, we show that cannabinoids induce apoptosis of pancreatic tumor cell lines in vitro and exert a remarkable growth-inhibiting effect in models of pancreatic cancer in vivo.
Although the pancreatic tumor biopsies and cell lines analyzed expressed both CB1 and CB2 cannabinoid receptors, our findings indicate that the CB2 receptor is the one that plays a major role in the proapoptotic effect of cannabinoids in these cells.

In conclusion, results presented here show that cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells. Cannabinoid treatment increases TRB3 expression and apoptosis in pancreatic tumors but not in normal pancreatic tissue. Intrapancreatic tumors were generated as described in Materials and Methods. Animals were treated with either vehicle or WIN 55,212-2 (1.5 mg/kg for 2 days, 2.25 mg/kg for 2 additional days, and 3.0 mg/kg for 10 additional days; n = 6 for each experimental group). The day after the 14-day treatment, animals were sacrificed, pancreatic tissues containing tumors were fixed, and sections were prepared. A, representative images ( 40) of TUNEL-stained pancreatic tumors. Values in the lower left corner of the bottom images correspond to 12 sections of three dissected tumors for each condition and are expressed as the percentage of TUNEL-positive cells relative to the total number of cells in each section. B, representative images ( 20) of TUNEL-stained pancreas. T, tumor tissue; P, normal pancreatic tissue. C, representative images ( 40) of TRB3-stained pancreatic tumors. Values in the lower left corner of the bottom images correspond to 18 sections of three dissected tumors for each condition and are expressed as the percentage of TRB3-stained area relative to the total area in each section. D, schematic representation of the proposed mechanism of cannabinoid-induced apoptosis on pancreatic tumor cells.

Cancer Research: in vitro and in vivo due to their ability to selectively induce apoptosis of these cells via activation of the p8-ATF-4-TRB3 proapoptotic pathway. These findings may help to set the basis for a new therapeutic approach for the treatment of this deadly disease.

In recent years, there has been increasing interest in cannabinoids as therapeutic drugs for their antineoplastic, anticachectic, and analgesic potential. Growth inhibitory activities of cannabinoids have been demonstrated for various malignancies, including brain, breast, prostate, colorectal, skin and, recently, pancreatic cancer.
Gemcitabine (GEM, 2′,2′-difluorodeoxycytidine) is currently used in advanced pancreatic adenocarcinoma, with a response rate of

Cancers that develop within the pancreas fall into two major categories: (1) cancers of the endocrine pancreas (the part that makes insulin) are called "

Cannabinoids and Pancreatitis

Pancreatitis- inflammation of the pancreas. The pancreas is a gland located behind the stomach. It releases the hormones insulin and glucagon, as well as digestive enzymes that help you digest and absorb food.

Causes

I Acute pancreatitis
II Chronic pancreatitis
III Pancreatic abscess
IV Pancreatic pseudocyst
Symptoms may include:

Abdominal pain
Chills
Clammy skin
Fatty stools
Fever
Mild jaundice
Nausea
Sweating
Weakness
Weight loss
Vomiting

Acute pancreatitis is sudden swelling and inflammation of the pancreas.

Causes, incidence, and risk factors

The pancreas is an organ located behind the stomach that produces chemicals called enzymes, as well as the hormones insulin and glucagon. Most of the time, the enzymes are only active after they reach the small intestine, where they are needed to digest food.
When these enzymes somehow become active inside the pancreas, they eat (and digest) the tissue of the pancreas. This causes swelling, bleeding (hemorrhage), and damage to the pancreas and its blood vessels.
Acute pancreatitis affects men more often than women. Certain diseases, surgeries, and habits make you more likely to develop this condition.
The condition is most often caused by alcoholism and alcohol abuse (70% of cases in the United States). Genetics may be a factor in some cases. Sometimes the cause is not known, however.

Other conditions that have been linked to pancreatitis are:

Autoimmune problems (when the immune system attacks the body)
Blockage of the pancreatic duct or common bile duct, the tubes that drain enzymes from the pancreas
Damage to the ducts or pancreas during surgery
High blood levels of a fat called triglycerides (hypertriglyceridemia)
Injury to the pancreas from an accident

Other causes include:

1. Complications of cystic fibrosis
2. Hemolytic uremic syndrome
3. Hyperparathyroidism
4. Kawasaki disease
5. Reye syndrome
6. Use of certain medications (especially estrogens, corticosteroids, thiazide diuretics, and azathioprine)
7. Viral infections, including mumps, coxsackie B, mycoplasma pneumonia, and campylobacter

Symptoms

The main symptom of pancreatitis is abdominal pain felt in the upper left side or middle of the abdomen.
The pain:

May be worse within minutes after eating or drinking at first, especially if foods have a high fat content
Becomes constant and more severe, lasting for several days
May be worse when lying flat on the back
May spread (radiate) to the back or below the left shoulder blade

People with acute pancreatitis often look ill and have a fever, nausea, vomiting, and sweating.
Other symptoms that may occur with this disease include:

1. Clay-colored stools
2. Gaseous abdominal fullness
3. Hiccups
4. Indigestion
5. Mild yellowing of the skin and whites of the eyes (jaundice)
6. Skin rash or sore (lesion)
7. Swollen abdomen

Treatment

Treatment often requires a stay in the hospital and may involve:

Pain medicines
Fluids given through a vein (IV)
Stopping food or fluid by mouth to limit the activity of the pancreas

Occasionally a tube will be inserted through the nose or mouth to remove the contents of the stomach (nasogastric suctioning). This may be done if vomiting or severe pain do not improve, or if a paralyzed bowel (paralytic ileus) develops. The tube will stay in for 1 – 2 days to 1 – 2 weeks.

Treating the condition that caused the problem can prevent repeated attacks.
In some cases, therapy is needed to:

Drain fluid that has collected in or around the pancreas
Remove gallstones
Relieve blockages of the pancreatic duct

In the most severe cases, surgery is needed to remove dead or infected pancreatic tissue.
Avoid smoking, alcoholic drinks, and fatty foods after the attack has improved.
Expectations (prognosis)
Most cases go away in a week. However, some cases develop into a life-threatening illness.
The death rate is high with:

Hemorrhagic pancreatitis
Liver, heart, or kidney impairment
Necrotizing pancreatitis

Pancreatitis can return. The likelihood of it returning depends on the cause, and how successfully it can be treated.

Complications

Acute kidney failure
Acute respiratory distress syndrome (ARDS)
Buildup of fluid in the abdomen (ascites)
Cysts or abscesses in the pancreas
Heart failure
Low blood pressure

Repeat episodes of acute pancreatitis can lead to chronic pancreatitis.

Chronic pancreatitis is inflammation of the pancreas that does not heal or improve, gets worse over time, and leads to permanent damage.

Causes, incidence, and risk factors

The pancreas is an organ located behind the stomach that produces chemicals (called enzymes) needed to digest food. It also produces the hormones insulin and glucagon.
When inflammation and scarring of the pancreas occur, the organ is no longer able to make the right amount of these enzymes. As a result, your body may be unable to digest fat and other important parts of food.
Damage to the portions of the pancreas that make insulin may lead to diabetes.
The condition is most often caused by alcohol abuse over many years. Repeat episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be a factor in some cases. Sometimes the cause is not known.

Other conditions that have been linked to chronic pancreatitis:
  • Autoimmune problems (when the immune system attacks the body)
  • Blockage of the pancreatic duct or the common bile duct, the tubes that drain enzymes from the pancreas
  • Complications of cystic fibrosis
  • High levels of a fat called triglycerides in the blood (hypertriglyceridemia)
  • Hyperparathyroidism

Use of certain medicationss (especially estrogens, corticosteroids, thiazide diuretics, and azathioprine)
Chronic pancreatitis occurs more often in men than in women. The condition often develops in people ages 30 – 40.

Symptoms
  • Abdominal pain
  • Greatest in the upper abdomen
  • May last from hours to days
  • Eventually may be continuous
  • May get worse from eating or drinking
  • May get worse from drinking alcohol
  • May also be felt in the back
  • Digestive problems
  • Chronic weight loss, even when eating habits and amounts are normal
  • Diarrhea, nausea, and vomiting
  • Fatty or oily stools
  • Pale or clay-colored stools

The symptoms may become more frequent as the condition gets worse. The symptoms may mimic pancreatic cancer. Sitting up and leaning forward may sometimes relieve the abdominal pain of pancreatitis.

Tests for pancreatitis include:
  • Fecal fat test
  • Serum amylase
  • Serum IgG4 (for diagnosing autoimmune pancreatitis)
  • Serum lipase
  • Serum trypsinogen
  • Inflammation or calcium deposits of the pancreas, or changes to the ducts of the pancreas may be seen on:
  • Abdominal CT scan
  • Abdominal ultrasound
  • Endoscopic retrograde cholangiopancreatography (ERCP)
  • Endoscopic ultrasound (EUS)
  • Magnetic resonance cholangiopancreatography (MRCP)

An exploratory laparotomy may be done to confirm the diagnosis, but this is usually done for acute pancreatitis.

Treatment

People with severe pain or who are losing weight may need to stay in the hospital for:

  • Pain medicines
  • Fluids given through a vein (IV)

Stopping food or fluid by mouth to limit the activity of the pancreas, and then slowly starting an oral diet. Inserting a tube through the nose or mouth to remove the contents of the stomach (nasogastric suctioning) may sometimes be done. The tube may stay in for 1 – 2 days, or sometimes for 1 – 2 weeks.

Eating the right diet is important for people with chronic pancreatitis. A nutritionist can help you create the best diet to maintain a healthy weight and receive the correct vitamins and minerals. All patients should be:

  • Drinking plenty of liquids
  • Eating a low-fat diet
  • Eating small, frequent meals (this helps reduce digestive symptoms)
  • Getting enough vitamins and calcium in the diet, or as extra supplements
  • Limiting caffeine

The doctor may prescribe pancreatic enzymes, which you must take with every meal. The enzymes will help you digest food better and gain weight.

Avoid smoking and drinking alcoholic beverages, even if your pancreatitis is mild.

Other treatments may involve:

Pain medicines or a surgical nerve block to relieve pain
Taking insulin to control blood sugar (glucose) levels
Surgery may be recommended if a blockage is found. In severe cases, part or all of the pancreas may be removed.

Expectations (prognosis)

This is a serious disease that may lead to disability and death. You can reduce the risk by avoiding alcohol.

Complications

1. Ascites
2. Blockage (obstruction) of the small intestine or bile ducts
3. Blood clot in the vein of the spleen
4. Fluid collections in the pancreas (pancreatic pseudocysts) that may become infected
5. Poor function of the pancreas
6. Diabetes
7. Fat or other nutrient malabsorption
8. Vitamin malabsorption (most often the fat-soluble vitamins, A, D, E, or K)

Prevention

Determining the cause of acute pancreatitis and treating it quickly may help prevent chronic pancreatitis. Not drinking a lot of alcohol reduces the risk of developing this condition.

A pancreatic abscess is a cavity of pus within the pancreas.

Causes, incidence, and risk factors

Pancreatic abscesses develop in patients with pancreatic pseudocysts that become infected.
Symptoms

1. Abdominal mass
2. Abdominal pain
3. Chills
4. Fever
5. Inability to eat
6. Nausea and vomiting

Signs and tests

Patients with pancreatic abscesses usually have had pancreatitis. However, the complication often takes 7 or more days to develop.

Symptoms usually include:
  • Abdominal pain
  • Fever
Signs of an abscess can be seen on:
  • CT scan
  • MRI of the abdomen
  • Ultrasound
Treatment

It may be possible to drain the abscess through the skin (percutaneous). Surgery to drain the abscess and remove dead tissue is often needed.

Expectations (prognosis)

How the person does depends on how severe the infection is. The death rate from undrained pancreatic abscesses is very high.

Complications

1. Multiple abscesses
2. Sepsis

Prevention

Adequate drainage of a pancreatic pseudocyst may help prevent some cases of pancreatic abscess. However, in many cases the disorder is not preventable.

A pancreatic pseudocyst is a fluid-filled sac in the abdomen, which may also contain tissue from the pancreas, pancreatic enzymes, and blood.

Causes, incidence, and risk factors

The pancreas is an organ located behind the stomach that produces chemicals (called enzymes) needed to digest food. It also produces the hormones insulin and glucagon.
Pancreatic pseudocysts most often develop after an episode of severe, acute pancreatitis. Acute pancreatitis is sudden swelling (inflammation) of the pancreas.
It may also occur after trauma to the abdomen, more often in children.
The cyst happens when the ducts (tubes) in the pancreas are damaged by the inflammation or swelling that occurs during pancreatitis.
A pancreatic pseudocyst may also occur after trauma to the abdomen, and in someone with chronic pancreatitis.

Symptoms

Symptoms can occur within days to months after an attack of pancreatitis, and include:

  • Bloating of the abdomen
  • Constant pain or deep ache in the abdomen, which may also be felt in the back
  • Difficulty eating and digesting food
Treatment

Treatment depends on the size of the pseudocyst and whether it is causing symptoms. Many pseudocysts go away on their own. Those that remain for more than 6 weeks and are larger than 5 cm in diameter often need surgery.

Surgical treatments include:

  • Drainage through the skin (percutaneous) using a needle, usually guided by a CT scan
  • Endoscopic-assisted drainage using an endoscope (a tube containing a camera and a light that is passed down into the stomach)
  • Surgical drainage of the pseudocyst, which involves making a connection between the cyst and the stomach or small intestine. This may be done using a laparoscope.
Expectations (prognosis)

The outcome is generally good with treatment.

Complications

A pancreatic abscess can develop if the pseudocyst becomes infected
The pseudocyst can break open (rupture), which can be a serious complication because shock and excess bleeding (hemorrhage) may develop
The pseudocyst may press down on (compress) nearby organs

Calling your health care provider

Rupture of the pseudocyst is an emergency situation. Go to the emergency room or call the local emergency number (such as 911) if you develop symptoms of bleeding or shock, such as:

  • Fainting
  • Fever and chills
  • Rapid heartbeat
  • Severe abdominal pain
Prevention

The way to prevent pancreatic pseudocysts is by preventing pancreatitis. I f pancreatitis is caused by gallstones, it is usually necessary to remove the gallbladder with surgery (cholecystectomy). When pancreatitis occurs due to alcohol abuse, the patient must stop drinking alcohol to prevent future attacks.

Cannabinoids and Pancreatitis

In humans, acute pancreatitis is associated with up-regulation of ligands as well as receptors of the endocannabinoid system in the pancreas. Furthermore, our results suggest a therapeutic potential for cannabinoids in abolishing pain associated with acute pancreatitis and in partially reducing inflammation and disease pathology in the absence of adverse side effects.
Cannabinoids ameliorate pain and reduce disease pathology in cerulein-induced acute pancreatitis.
In humans, acute pancreatitis is associated with up-regulation of ligands as well as receptors of the endocannabinoid system in the pancreas. Furthermore, our results suggest a therapeutic potential for cannabinoids in abolishing pain associated with acute pancreatitis
The endocannabinoid system is downregulated in chronic pancreatitis and that its augmentation via exogenously administered cannabinoids specifically reduces activation of pancreatic stellate cells. These experiments lay a basis for testing the value of synthetic cannabinoids in the treatment of chronic pancreatitis.

Cannabinoids stop pain and reduce disease pathology in pancreatitis.
Augmentation of the endocannabinoid system via exogenously administered cannabinoid receptor agonists specifically induces a functionally and metabolically quiescent pancreatic stellate cell phenotype and may thus constitute an option to treat inflammation and fibrosis in chronic pancreatitis.

Use medical marijuana as an adjunct treatment for pancreatitis. Use an Indica x Sativa hybrid.

Christoph W Michalski, Tamara Laukert, Danguole Sauliunaite, Pál Pacher, Frank Bergmann, Gastroenterology (2007)
Volume: 132, Issue: 5, Pages: 1968-1978
Michalski CW, Laukert T, Sauliunaite D, Pacher P, Bergmann F, Agarwal N, Su Y, Giese T, Giese NA, Bátkai S, Friess H, Kuner R.
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Kazuhisa Matsuda1), Yukio Mikami1), Kazunori Takeda1), Shoji Fukuyama1), Shinichi Egawa1), Makoto Sunamura1), Ikurou Maruyama2) and Seiki Matsuno1)

1) Division of Gastroenterological Surgery, Tohoku University Graduate School of Medicine
2) Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University Christoph W. Michalski1,2#*, Milena Maier2#, Mert Erkan1#,Danguole Sauliunaite1, Frank Bergmann3, Pal Pacher4,Sandor Batkai4, Nathalia A. Giese2, Thomas Giese5, Helmut Friess1, Jörg Kleeff1
1 Department of Surgery, Technische Universität München, Munich, Germany,2 Department of General Surgery, University of Heidelberg, Heidelberg, Germany, 3 Institute of Pathology, University of Heidelberg, Heidelberg, Germany, 4 Section of Oxidative Stress Tissue Injury, Laboratory of Physiologic Studies, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Maryland, United States of America, 5 Institute of Immunology, University of Heidelberg, Heidelberg, Germany
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Pacher P, Batkai S, Kun
S, Friess H, Kuner R
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Gastroenterology [2007, 132(5):1968-78]
Type: Journal Article, Research Support, Non-U.S. Gov’t, Research Support, N.I.H., Intramural
DOI: 10.1053/j.gastro.2007.02.035
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Pancreatitis- inflammation of the pancreas. The pancreas is a gland located behind the stomach. It releases the hormones insulin and glucagon…