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.


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


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"


  • 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


  • If you smoke, stop smoking.
  • Eat a diet high in fruits, vegetables, and whole grains.
  • Exercise regularly.


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.


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.


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 < 20%.  The purpose of our work was to improve GEM activity by addition of cannabinoids.  Here, we show that GEM induces both cannabinoid receptor-1 (CB1) and cannabinoid receptor-2 (CB2) receptors by an NF-κB-dependent mechanism and that its association with cannabinoids synergistically inhibits pancreatic adenocarcinoma cell growth and increases reactive oxygen species (ROS) induced by single treatments.   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.

Madrid, Spain: Compounds in cannabis inhibit cancer cell growth in human breast cancer cell lines and in pancreatic tumor cell lines, according to a pair of preclinical trials published in the July issue of the journal of the American Association for Cancer Research.
These findings may contribute to a new therapeutic approach for the treatment of pancreatic cancer," authors concluded.

Cannabinoids Reduce Markers of Inflammation and Fibrosis in Pancreatic Stellate Cells.
In conclusion, we show that the endocannabinoid system is down regulated in chronic pancreatitis and that administered cannabinoids specifically reduces activation of pancreatic stellate cells.  And suppresses pro-inflammatory cytokines.

Cannabinoids Halt Pancreatic Cancer, Breast Cancer Growth, Studies Say

Cannabinoid administration selectively increased apoptosis (programmed cell death) in pancreatic tumor cells while ignoring healthy cells, researchers found. In addition, "cannabinoid treatment inhibited the spreading of pancreatic tumor cells and reduced the growth of tumor cells" in animals.
Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes"


Cannabinoids  make an excellent choice for the adjunct treatment of pancreatic cancer.
Indica x Sativa hybrid (Indica dominant)  (high CBD/THC levels)
Whole plant extracts taken under the tongue 2-4 times daily.


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