Cannabinoids are a class of diverse chemical compounds that acts on cannabinoid receptors in cells, altering neurotransmitter release in the brain. They are commonly associated with and found in marijuana. There are also similar compounds within the human body.
They have many effects on our body, specifically as it relates to the cannabinoid system within the body. For example, cannabinoids can provide anti-cancer effects such as anti-inflammatory properties, antioxidants, apoptosis, anti-viral protections, and immune system boosters.
It’s time to bring Cannabis out of the closet.
Long associated with hippie stoners and rebellious teenagers, cannabis (also known as marijuana, weed, dope, ganja, green, Mary Jane and many other synonyms) is increasingly understood to be an effective tool in the management of cancer-related symptoms caused by treatment or the cancer itself.
In one recent survey of cancer patients at a large comprehensive cancer center (Seattle Cancer Care Alliance) within a state with medically and recreationally legalized Cannabis found that 24% of patients reported active use. The authors noted use for cancer-related symptoms (i.e. pain, nausea, appetite, stress, depression, insomnia) in 75% of active Cannabis users (REF) They also reported that 74% of the patients surveyed wanted to learn about Cannabis from their health care providers, but they were unable to glean enough information from them.
A 2018 national survey of oncologists found that 80% of them had discussions regarding medical marijuana with patients, and 78% reported that these conversations were more frequently initiated by patients and their families. Unfortunately, less than 30% of the surveyed oncologists felt knowledgeable enough about medical marijuana to make recommendations. Nevertheless, their beliefs on its benefits were generally very supportive (REF):
- 67% believed medical marijuana to be helpful for alleviating pain when used together with standard therapies
- Most believed that it poses a lower risk than opioids for overdose death (75%) and addiction (52%)
- 65% viewed it as equally or more effective than standard treatments for poor appetite and extreme weight loss
Unfortunately, many decades of legal prohibition have attached such a stigma to this botanical compound that it still feels daring to discuss it in polite company – including in medical circles. Nonetheless, more and more cancer specialists – especially in the field of integrative oncology – are paying close attention to the emerging research on Cannabis, and increasingly offering it to their patients.
What is Cannabis?
Cannabis has two species, hemp (legal, as it contains no more than 0.3% THC) and marijuana (federally illegal, as it contains more than 0.3% THC).
Despite powerful evidence pointing to its medical efficacy, marijuana is classified in the U.S. as a controlled substance with an “increased potential for abuse and no known medical use” (Schedule 1). By federal law, possessing marijuana is illegal in the U.S.. However, 33 states (listed here) and the District of Columbia permit its use for certain medical conditions with a physicians’ prescription, and a growing number of states permit its use for recreational purposes, too.
Patient advocacy groups are pressuring the government to loosen marijuana legislation and make it accessible to people nationwide for medical purposes.
The Cannabis plant contains over 400 chemical compounds, including so-called cannabinoids, the molecules that exert most of the pharmacological activity of the plant. There are more than 60 cannabinoids, the best-studied of which are delta-9-tetrahydrocannabinol (delta-9-THC), cannabidiol (CBD), cannabinol (CBN), and tetrahydrocannabivarin (THCV). The main psychoactive consitituent of Cannabis is delta-9-THC, often simply referred to as THC. In 1986, a synthetic delta-9-THC was FDA approved (dronabinol or Marinol) for the treatment of chemotherapy-associated nausea and vomiting. In 1992, it was approved for poor appetite and weight loss in patients with HIV.
The second most prevalent of the active compounds of marijuana is cannabidiol or CBD, however most CBD is derived from the federally legal hemp plant. Unlike THC, CBD does not cause a “high.” In fact, CBD inhibits the psychoactive effects of THC.
The strongest evidence for CBD’s effectiveness is in the treatment of rare seizure syndromes (Dravet and Lennox-Gastaut), which led to the 2018 U.S. FDA approval of a Cannabis-derived CBD extract (Epidiolex). Currently, most people use hemp-derived CBD which they obtain legally through websites or CBD retailers. CBD is commonly used to address anxiety, insomnia and chronic pain conditions (i.e. inflammatory, neuropathic), although there is a lack of high-quality clinical studies supporting these indications.
Amazing: Our bodies are programmed for cannabinoids
Perhaps the most exciting area of cannabinoid research involves the discovery of the human body’s own endocannabinoid system. Incredibly, our bodies make their own cannabis-like chemicals that interact with and stimulate cannabinoid receptors on our cells. The 2 main endocannabinoids are 2-arachidonylglycerol (2-AG) and anandamide. Anandamide (as does THC) binds and stimulates CB1 receptors, and 2-AG binds and stimulates CB2 receptors. While CBD does not bind to either of these receptors, it causes a change in the CB1 receptor that impairs the ability of anandamide and THC to bind to it. CBD directly interacts with opioid, dopamine and serotonin receptors, which likely explains the broad effects of this compound.
Studies continue to uncover the numerous functions of our endocannabinoid system. The functions in bold have anticancer implications:
- Anti-inflammatory activity
- Antioxidant activity
- Inhibiting tumor cell growth and promoting cancer cells’ self-destruction (apoptosis)
- Inhibiting blood vessel growth to tumors (anti-angiogenesis)
- Antiviral activity
- Involved in learning and nervous system plasticity
- Pain processing
- Neuroprotective effects
- Visual perception
- Immune system modulation
Cancer Patient Recommendations
As a general rule, Dr. Lawenda usually recommends administration that is determined by the kind of relief or outcome a patient hopes to receive.
Chronic Pain. Since chronic pain is a constant, taking a long-acting administration method makes more sense. Edibles often last four to 10 hours, which would provide a steady state of cannabinoids to help alleviate the pain.
Immediate Relief. Since breakthrough pain, nausea, and other acute symptoms occur quickly but less frequently, sublingual and vaporized products provide much quicker relief and last approximately 30 minutes to two hours.
In most cases, cancer patients seem to respond best with a CBD-to-THC ratio of 1:1. Although many patients feel this is too potent to start, it may be worthwhile to build up tolerances with a 4:1 ratio for two weeks, 2:1 ratio for two weeks, and then a 1:1 ratio.
When Should I Use Both A Long-Acting and Short-Acting Product?
I often recommend that patients have both an edible (long-acting and slow onset product) and a sublingual tincture or vape (both are short-acting and rapid onset products) handy when using cannabinoids to manage chronic side effects, such as pain.
How much should you use?
Unfortunately, there is no way to know how much of any cannabinoid product is right for each person and condition. This has to be determined by trial and error. The rule of thumb is to start with the smallest dose and slowly increase the amount until your reach the desired effect or until you have undesired side effects. Cannabis can have a biphasic effect, where at lower doses it can have one effect, but provide the opposite at a higher dose. For example:
- Low dose (energizing effects) vs. high dose (sedating effects)
- Low dose (superior pain reduction effects) vs. high dose (less pain reduction effects)
- Low dose (reduces anxiety/stress) vs. high dose (increases anxiety and paranoia)
The Various Routes of Administration:
Cannabinoids can be swallowed (e.g., oils, baked products, butters, teas, liquid sprays and tinctures, gum, beer, candies, etc.), inhaled (smoking or vaporizing), used topically on the skin (creams, oils, lotions, patches) or by suppositories (rectal or vaginal).
The route of administration will dictate the onset of action and the duration of effects.
- The fastest onset and shortest duration of effects comes from sublingual (tinctures, oils) and inhalational (smoking or vaporizing) routes
- 1-15 minute onset
- 30 minutes to 2 hour effects
- The slowest onset and longest duration of effects comes from edible products, suppositories and topical products
- 30 minutes to 2 hour onset
- 4-10 hour effects (certain topical patches may have a longer duration)
Full Spectrum vs Isolates
“Full spectrum” products have a wide-range of cannabinoids and terpenes (organic compounds in Cannabis and all plants that are responsible for their aroma, flavor and possess their own pharmacologic properties). The combination of these compounds often leads to synergistic effects (also known as “entourage effects”), which may improve the desired effectiveness of the cannabinoid product.
“Isolates,” on the other hand, include only “pure” compounds (i.e. CBD or THC) and no detectable levels of other cannabinoids or terpenes. “Broad spectrum” products are those that contain almost everything in the full spectrum extract, but some of the compounds have been removed (i.e. THC, CBD, etc.)
Dr. Lawenda recommends that his patients stick with full spectrum products, as these are less processed and contain most of the naturally occurring compounds in the marijuana or hemp plant (which takes advantage of the entourage effect).
When purchasing marijuana or hemp plant extracts, Dr. Lawenda recommends looking at the label for those that are produced with either ethanol alcohol or supercritical CO2 extraction, as these are considered the cleanest (least toxic).
Many of my patients use CBD-rich hemp tinctures. Unfortunately, most of these products have a very low bioavailability. A new type of product formulation has been recently developed, called “nano-encapsulation.” This process significantly increases the bioavailability, such that you can absorb 20-times greater the amount of CBD per drop of tincture than you would otherwise. Since nano-encapsulated tinctures are water soluble, they can be added to drinks and maintain their high bioavailability.
Medical Indications for Cannabis and Cannabinoids:
The individual states that have legal medical marijuana programs allow patients to be enrolled when they are diagnosed with a medical condition that is recognized by that state for which Cannabis or cannabinoids have potential efficacy. These conditions vary state-by-state. While many conditions are listed as potential indications, the quality of the supporting data is often not high-quality. For example, in the state of Washington these are the listed conditions for eligibility in their medical program (REF):
- Cancer, human immunodeficiency virus (HIV), multiple sclerosis, epilepsy or other seizure disorder, or spasticity disorders.
- Intractable pain, limited for the purpose of this chapter to mean pain unrelieved by standard medical treatments and medications.
- Glaucoma, either acute or chronic, limited for the purpose of this chapter to mean increased intraocular pressure unrelieved by standard treatments and medications.
- Crohn’s disease with debilitating symptoms unrelieved by standard treatments or medications.
- Hepatitis C with debilitating nausea or intractable pain unrelieved by standard treatments or medications.
- Diseases, including anorexia, which result in nausea, vomiting, wasting, appetite loss, cramping, seizures, muscle spasms, or spasticity, when these symptoms are unrelieved by standard treatments or medications.
- Chronic renal failure requiring hemodialysis.
- Posttraumatic stress disorder.
- Traumatic brain injury.
Dr. Lawenda often recommends a trial of Cannabis or cannabinoid extract as an optional non-pharmacologic therapy to help his patients better manage 5 common symptoms:
- Nausea
- Diminished appetite (and associated weight loss)
- Pain
- Sleeping difficulties
- Psycho-emotional distress (i.e. anxiety, stress and depression)
When these symptoms are severe, they may make it difficult for patients to continue their treatment without interruption, and this can diminish treatment effectiveness. This is where many patients find that Cannabis and cannabinoid extracts can be of great help. If these symptoms were treated pharmacologically, your doctor would need to prescribe 5 different drugs to manage all of them. Instead, in many cases, cannabinoids can address all five symptoms. Furthermore, they can be significantly less expensive than many pharmaceuticals and have fewer untoward side effects.
Combining pharmaceuticals along with other botanical compounds, various evidence-based complementary therapies and cannabinoids is usually safe, but Dr. Lawenda strongly emphasizes that this should only be done after getting approval to do so by your oncology health care providers. Dangerous interactions are theoretically possible when combining cannabinoids with other pharmaceuticals, so it’s essential to check for these. Dr. Lawenda uses online drug interaction checkers:
Another one of my favorites is the WebMD Drug Interaction Checker
Another beneficial outcome reported by many patients is that they often report that they are able to decrease their use (frequency, quantity, dose) of drugs for pain, anxiety, sleeping problems and nausea when they use cannabinoids. This can help patients by reducing the side effects or risks of these drugs, such as opioids (e.g., nausea, sluggishness, constipation or a dependency on opioids).
Cannabis as an anticancer agent?
To date, there are no high-quality clinical studies in humans that show whether cannabis or any of the cannabinoids are able to improve cancer-treatment outcomes (i.e. slower progression of the disease, longer survival, lower risk of recurrence). There are suggestions of potential clinical benefit (longer survival) based on very small reports:
- CBD and brain tumors
- Cannabis extract (Nabiximols/Sativex, a Cannabis extract with a 1:1 ratio of THC:CBD) and gliobastoma multiforme brain tumors
There are, however, many interesting pre-clinical studies (studying cancer cells in test tubes and animal studies) that demonstrate the anticancer activity of cannabinoids.
According to the U.S. National Cancer Institute (REF), studies in rodents have shown that cannabinoids may inhibit tumor growth by causing cell death, stopping cell growth and blocking the development of blood vessels needed by tumors to grow. Laboratory and animal studies have also shown that cannabinoids may be able to kill cancer cells while protecting normal cells.
Preclinical studies have shown that cannabinoids have been found to inhibit the growth of various cancer cell lines, including breast carcinoma, prostate carcinoma, colorectal carcinoma, gastric adenocarcinoma, skin carcinoma, leukemia cells, neuroblastoma, lung carcinoma, uterus carcinoma, thyroid epithelioma, pancreatic adenocarcinoma, cervical carcinoma, oral cancer, biliary tract cancer (cholangiocarcinoma) and lymphoma.
While these reports are exciting, it is important to keep in mind that many seemingly amazing outcomes have been reported in countless pre-clinical studies of promising potential therapies that failed to deliver the desired outcomes when conducted in human studies. More research is needed before we can say with more clarity if cannabinoids are an effective anticancer therapy in humans.
Is it safe to smoke marijuana?
Research indicates that habitual use of marijuana in adults does not appear to lead to abnormalities in lung function, nor does it increase the risks of chronic obstructive lung disease, or either lung or upper airway cancer. It is associated with increased symptoms of chronic bronchitis, but the symptoms disappear upon marijuana smoking cessation.
That said, we recommend that you vaporize dried Cannabis flower rather than smoking, which comes with a long list of toxins and carcinogens that are produced when herbs and tobacco are burned. Filters and water pipes (i.e., bongs, hookahs, etc.) remove only a fraction of these dangerous molecules, so are best avoided as well.
An electric vaporizer is a safer inhalational option. Instead of burning the plant material, vaporizers heat it to a temperature that does not cause combustion. Depending on the vaporizer, it typically takes between 5-60 seconds of heating before vapor is produced. Since vapor is produced at lower temperatures than it takes to burn the plant material, essentially none of the toxic chemicals are produced.
There are also vaporizers that use liquid Cannabis concentrates or solid resin concentrates, which heat these products to a temperature that causes their vaporization. Inhaling this vapor could potentially be dangerous, as hospitals across the U.S. have reported thousands of cases of individuals who have developed lung injury or died resulting from the use of these products. At the time of writing this section, the U.S. FDA warns consumers to stop using THC vaping products (REF). This risk has not been seen with the use of dried Cannabis vaporizers nor with smoking Cannabis.
How safe are cannabinoids?
When used correctly, they are very safe – especially compared to many prescription drugs.
According to a 1995 review prepared for the World Health Organization, “there are no recorded cases of overdose fatalities attributed to Cannabis, and the estimated lethal dose for humans extrapolated from animal studies is so high that it cannot be achieved by … users.” Indeed, pharmacologic studies indicate that a human would need to eat 1,500 pounds of Cannabis within 15 minutes to achieve lethal levels of cannabinoids!
In 2008, investigators at McGill University and the University of British Columbia reviewed 23 clinical investigations of medical cannabinoid drugs (typically oral THC or liquid cannabis extracts) and eight observational studies conducted between 1966 and 2007. Investigators “did not find a higher incidence rate of serious adverse events associated with medical cannabinoid use” compared to non-using controls over these four decades.
That said, cannabinoids are active drugs with potential risks and side-effects. These may include rapid heartbeat, low blood pressure, muscle relaxation, bloodshot eyes, slowed digestion and movement of food by the stomach and intestines, dizziness, depression, hallucinations and paranoia. Even CBD has potential side effects, including nausea, fatigue and irritability.
Cannabis and its extracts (although not CBD) may be addictive. Symptoms of withdrawal may include restlessness, hot flashes, nausea and cramping (rare). If you think you are becoming addicted to Cannabis, talk to your doctor about ways to wean yourself off it.
Dr. Lawenda’s 90-Minute Cannabinoids Talk
You will come away from this talk knowing much more about:
- History of medical cannabinoids
- Federal and state laws (with specifics on WA state)
- Driving under the influence
- Medical vs. recreational programs, types of cannabis products (edibles, tinctures, oils, flower, etc.)
- How they are used
- Time to effect
- Duration of effects
- How to determine the best dose for you
- Assess if there are medication-cannabinoid interactions
- The basics of the endocannabinoid system
- Types of cannabinoids (THC, CBD)
- Terpenes
- Synergistic/entourage effects of cannabinoids and terpenes
- Uses/indications
- Anticancer effects
- Finding clinical trials
