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Cannabinoid compounds may inhibit growth of colon cancer cells

Medical marijuana has gained attention in recent years for its potential to relieve pain and short-term anxiety and depression. Now, Penn State College of Medicine researchers say some cannabinoid compounds may actually inhibit the growth of colon cancer cells in the lab.

The researchers tested the effects of synthetic cannabinoid compounds on colon cancer cells in an experiment in test tubes. While the compounds most commonly associated with cannabis — THC and CBD — showed little to no effect, 10 other compounds were effective at inhibiting cancer cell growth.

Kent Vrana, chair of the Department of Pharmacology at Penn State College of Medicine, said the study — recently published in Cannabis and Cannabinoid Research — helped identify compounds that could be tested further to understand their anti-cancer properties.

“Now that we’ve identified the compounds that we think have this activity, we can take these compounds and start trying to alter them to make them more potent against cancer cells,” Vrana said. “And then eventually, we can explore the potential for using these compounds to develop drugs for treating cancer.”

Colorectal cancer is one of the most common cancers diagnosed in the United States, according to the National Cancer Institute, with an estimated 140,250 newly diagnosed cases and 50,630 deaths in 2018. While medical cannabis has largely been used in recent years for palliative care, the researchers said some previous studies suggested that certain cannabinoid compounds may have the potential to inhibit or prevent the growth of tumors.

To explore how effective cannabinoids were at reducing the viability of colon cancer cells specifically, the researchers tested how 370 different synthetic cannabinoid compounds affected seven types of human colon cancer cells.

“There are many different ways cells can become cancerous,” Vrana said. “Each of the seven cells we tested had a different cause or mutation that led to the cancer, even though they were all colon cells. We didn’t want to test these compounds on just one mutation or pathway to cancer.”

The researchers incubated the cancer cells in a lab for eight hours before treating them with the cannabinoid compounds for 48 hours. Any compounds that showed signs of reducing the viability of one kind of cancer cell was then used to treat all seven kinds of cells.

After further screening and analysis, the researchers identified 10 compounds that inhibited the growth of almost all seven types of colon cancer types tested. But while the researchers were able to identify these compounds, Vrana said they are still unsure about how exactly the compounds worked to reduce the viability of the cancer cells.

“The 10 compounds we found to be effective fall into three classes, so they’re similar to each other but with small changes,” Vrana said. “We know how one of them works, which is by inhibiting the division of cells in general. We also found that the most potent and effective compounds don’t seem to work through traditional marijuana receptors, although we’re not sure of the exact mechanism yet.”

Vrana said certain types of cells, like skin and colon cells, are more susceptible to cancers because they divide very frequently: “Every time a cell divides, there’s the chance that it will mutate and keep dividing when it shouldn’t, which is how cancers can start. So if we block that signal that’s telling cancer cells to continue to divide, that could be a way to stop that cancer.”

Vrana said that because the other compounds did not seem to be working through traditional cannabinoid signaling pathways, future research will focus on better understanding how the compounds interact with cancer cells and whether researchers can make the compounds more potent and effective.

Medical marijuana has gained attention in recent years for its potential to relieve pain and short-term anxiety and depression. Now, researchers say some cannabinoid compounds may actually inhibit the growth of colon cancer cells in the lab.

Marijuana and Cancer

Marijuana is the name given to the dried buds and leaves of varieties of the Cannabis sativa plant, which can grow wild in warm and tropical climates throughout the world and be cultivated commercially. It goes by many names, including pot, grass, cannabis, weed, hemp, hash, marihuana, ganja, and dozens of others.

Marijuana has been used in herbal remedies for centuries. Scientists have identified many biologically active components in marijuana. These are called cannabinoids. The two best studied components are the chemicals delta-9-tetrahydrocannabinol (often referred to as THC), and cannabidiol (CBD). Other cannabinoids are being studied.

At this time, the US Drug Enforcement Administration (DEA) lists marijuana and its cannabinoids as Schedule I controlled substances. This means that they cannot legally be prescribed, possessed, or sold under federal law. Whole or crude marijuana (including marijuana oil or hemp oil) is not approved by the US Food and Drug Administration (FDA) for any medical use. But the use of marijuana to treat some medical conditions is legal under state laws in many states.

Dronabinol, a pharmaceutical form of THC, and a man-made cannabinoid drug called nabilone are approved by the FDA to treat some conditions.

Marijuana

Different compounds in marijuana have different actions in the human body. For example, delta-9-tetrahydrocannabinol (THC) seems to cause the “high” reported by marijuana users, and also can help relieve pain and nausea, reduce inflammation, and can act as an antioxidant. Cannabidiol (CBD) can help treat seizures, can reduce anxiety and paranoia, and can counteract the “high” caused by THC.

Different cultivars (strains or types) and even different crops of marijuana plants can have varying amounts of these and other active compounds. This means that marijuana can have different effects based on the strain used.

The effects of marijuana also vary depending on how marijuana compounds enter the body. The most common ways to use marijuana are in food (edible marijuana) and by smoking or vaping it (inhaled marijuana):

  • Edible marijuana: When taken by mouth, such as when it’s used in cooking oils, drinks (beer, tea, vodka, soda), baked goods (biscuits, brownies, cookies), and candy, the THC is absorbed poorly and can take hours to be absorbed. Once it’s absorbed, it’s processed by the liver, which produces a second psychoactive compound (a substance that acts on the brain and changes mood or consciousness) that affects the brain differently than THC. It’s important to know that the amount of THC in foods that have had marijuana added to them is often unknown and getting to much THC might cause symptoms of overdose.
  • Inhaled marijuana: When marijuana is smoked or vaporized, THC enters the bloodstream and goes to the brain quickly. The second psychoactive compound is produced in small amounts, and so has less effect. The effects of inhaled marijuana fade faster than marijuana taken by mouth.

How can marijuana affect symptoms of cancer?

A number of small studies of smoked marijuana found that it can be helpful in treating nausea and vomiting from cancer chemotherapy.

A few studies have found that inhaled (smoked or vaporized) marijuana can be helpful treatment of neuropathic pain (pain caused by damaged nerves).

Smoked marijuana has also helped improve food intake in HIV patients in studies.

There are no studies in people of the effects of marijuana oil or hemp oil.

Studies have long shown that people who took marijuana extracts in clinical trials tended to need less pain medicine.

More recently, scientists reported that THC and other cannabinoids such as CBD slow growth and/or cause death in certain types of cancer cells growing in lab dishes. Some animal studies also suggest certain cannabinoids may slow growth and reduce spread of some forms of cancer.

There have been some early clinical trials of cannabinoids in treating cancer in humans and more studies are planned. While the studies so far have shown that cannabinoids can be safe in treating cancer, they do not show that they help control or cure the disease.

Relying on marijuana alone as treatment while avoiding or delaying conventional medical care for cancer may have serious health consequences.

Possible harms of marijuana

Marijuana can also pose some harms to users. While the most common effect of marijuana is a feeling of euphoria (“high”), it also can lower the user’s control over movement, cause disorientation, and sometimes cause unpleasant thoughts or feelings of anxiety and paranoia.

Smoked marijuana delivers THC and other cannabinoids to the body, but it also delivers harmful substances to users and those close by, including many of the same substances found in tobacco smoke.

Because marijuana plants come in different strains with different levels of active compounds, it can make each user’s experience very hard to predict. The effects can also differ based on how deeply and for how long the user inhales. Likewise, the effects of ingesting marijuana orally can vary between people. Also, some chronic users can develop an unhealthy dependence on marijuana.

Cannabinoid drugs

There are 2 chemically pure drugs based on marijuana compounds that have been approved in the US for medical use.

  • Dronabinol (Marinol®) is a gelatin capsule containing delta-9-tetrahydrocannabinol (THC) that’s approved by the US Food and Drug Administration (FDA) to treat nausea and vomiting caused by cancer chemotherapy as well as weight loss and poor appetite in patients with AIDS.
  • Nabilone (Cesamet®) is a synthetic cannabinoid that acts much like THC. It can be taken by mouth to treat nausea and vomiting caused by cancer chemotherapy when other drugs have not worked.

Nabiximols is a cannabinoid drug still under study in the US. It’s a mouth spray made up of a whole-plant extract with THC and cannabidiol (CBD) in an almost one to one mix. It’s available in Canada and parts of Europe to treat pain linked to cancer, as well as muscle spasms and pain from multiple sclerosis (MS). It’s not approved in the US at this time, but it’s being tested in clinical trials to see if it can help a number of conditions.

How can cannabinoid drugs affect symptoms of cancer?

Based on a number of studies, dronabinol can be helpful for reducing nausea and vomiting linked to chemotherapy.

Dronabinol has also been found to help improve food intake and prevent weight loss in patients with HIV. In studies of cancer patients, though, it wasn’t better than placebo or another drug (megestrol acetate).

Nabiximols has shown promise for helping people with cancer pain that’s unrelieved by strong pain medicines, but it hasn’t been found to be helpful in every study done. Research is still being done on this drug.

Side effects of cannabinoid drugs

Like many other drugs, the prescription cannabinoids, dronabinol and nabilone, can cause side effects and complications.

Some people have trouble with increased heart rate, decreased blood pressure (especially when standing up), dizziness or lightheadedness, and fainting. These drugs can cause drowsiness as well as mood changes or a feeling of being “high” that some people find uncomfortable. They can also worsen depression, mania, or other mental illness. Some patients taking nabilone in studies reported hallucinations. The drugs may increase some effects of sedatives, sleeping pills, or alcohol, such as sleepiness and poor coordination. Patients have also reported problems with dry mouth and trouble with recent memory.

Older patients may have more problems with side effects and are usually started on lower doses.

People who have had emotional illnesses, paranoia, or hallucinations may find their symptoms are worse when taking cannabinoid drugs.

Talk to your doctor about what you should expect when taking one of these drugs. It’s a good idea to have someone with you when you first start taking one of these drugs and after any dose changes.

What does the American Cancer Society say about the use of marijuana in people with cancer?

The American Cancer Society supports the need for more scientific research on cannabinoids for cancer patients, and recognizes the need for better and more effective therapies that can overcome the often debilitating side effects of cancer and its treatment. The Society also believes that the classification of marijuana as a Schedule I controlled substance by the US Drug Enforcement Administration imposes numerous conditions on researchers and deters scientific study of cannabinoids. Federal officials should examine options consistent with federal law for enabling more scientific study on marijuana.

Medical decisions about pain and symptom management should be made between the patient and his or her doctor, balancing evidence of benefit and harm to the patient, the patient’s preferences and values, and any laws and regulations that may apply.

The American Cancer Society Cancer Action Network (ACS CAN), the Society’s advocacy affiliate, has not taken a position on legalization of marijuana for medical purposes because of the need for more scientific research on marijuana’s potential benefits and harms. However, ACS CAN opposes the smoking or vaping of marijuana and other cannabinoids in public places because the carcinogens in marijuana smoke pose numerous health hazards to the patient and others in the patient’s presence.

Learn how marijuana and drugs derived from the marijuana plant can affect cancer-related symptoms.