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Can Cannabinoids Help Lupus and Other Diseases?

Yale Medicine doctor investigates whether a synthetically created molecule that mimics the properties and effects of CBD could treat diseases.

Lupus is an inflammatory disease that causes the body’s immune system to attack its own tissues, affecting internal organs, which can start to deteriorate. One doctor is looking for a cure using a synthetically created molecule that mimics the properties and effects of CBD.

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A lupus diagnosis can be devastating. The disease causes the body’s immune system to attack its own tissues and can affect internal organs—including the brain, heart, and lungs—which can start to deteriorate. Lupus flare-ups can leave patients so fatigued and in pain that they’re unable to do the simplest of things, such as walk, cook, or read. Many can’t go outdoors without layers of sunscreen, because the disease can make them extremely susceptible to sunburn.

Lupus affects approximately 240,000 people in the United States, and yet at present doctors neither know the exact cause nor have a cure. Instead, current treatments focus on improving quality of life by controlling symptoms and minimizing flare-ups to reduce risk of organ damage.

“The landscape for treatment of lupus is a bit bleak,” says Fotios Koumpouras, MD, a rheumatologist and director of the Lupus Program at Yale Medicine. “A multitude of drugs have failed in the last 10 to 15 years. Most of the drugs we use are being repurposed from other conditions and are not unique to lupus. Many of them can’t be used during pregnancy, which is a problem because lupus mostly affects young women. All of these issues create the impetus to find new and more effective therapies.”

This is why he’s exploring a candidate for a new lupus treatment option: a molecule with a cannabinoid template structure that binds to cannabinoid receptors, the same receptors involved in the chemicals found in the marijuana plant.

What is CBD?

CBD is a form of cannabinoid called “cannabidiol.” Cannabinoids are a type of chemical that binds to CB1 and CB2 receptors found throughout the body. CB1 receptors are mostly located in the nervous system, connective tissues, gonads, glands, and organs; CB2 receptors are primarily found in the immune system, along with the spleen, liver, heart, kidneys, bones, blood vessels, lymph cells, endocrine glands, and reproductive organs. (Collectively this is called the endocannabinoid system.)

What these cannabinoids do when they bind to the receptors depends on which receptor is activated, and thus can produce effects ranging from the firing of neurotransmitters (the chemical messengers sent from the brain to the rest of the body) that alter mood, to reducing inflammation and promoting digestion.

So, our bodies have their own endocannabinoid system, but cannabinoids can also be found in nature, most abundantly in the marijuana plant. The two most well-known types of cannabinoids in the marijuana plant are THC (tetrahydrocannabinol) and CBD (cannabidiol). THC binds to both the CB1 and CB2 receptors, but the CB1 receptor seems to be responsible for many of the well-known psychoactive effects of marijuana, such as euphoria, increased heart rate, slower reaction times, and red eyes. CB2 receptor binding results in the production of a series of proteins that reduce inflammation. (These proteins are called “resolvins” because they appear to resolve inflammation.) The pharmacology of CBD at cannabinoid receptors is complex and highly variable, but CBD has been shown to activate the endocannabinoid system.

Fotios Koumpouras, MD, is researching a synthetically created cannabinoid molecule that binds preferentially to CB2 receptors (called Lenabasum) to see if it can help ease pain and inflammation in patients with lupus.

Credit: Robert A. Lisak

Dr. Koumpouras learned from a colleague of ajulemic acid, a side-chain analog of Δ8-THC-11-oic acid, which was designed as a potent therapeutic agent free of the psychotropic adverse effects typical of most cannabinoids. This molecule may help relieve pain and reduce inflammation in systemic lupus erythematosus (SLE), the most common type of lupus. “Reducing inflammation is crucial for patients with lupus because it is what causes the buildup of scar tissue in vital organs that can eventually lead to their deterioration and malfunction,” he says. This cannabinoid molecule was already in study for other diseases, including systemic sclerosis and dermatomyositis.

In 2018, Dr. Koumpouras joined a multi-site randomized clinical trial that aims to recruit 100 participants to examine whether a drug using a synthetically created cannabinoid molecule that binds preferentially to CB2 receptors (called Lenabasum) can help ease pain and inflammation in patients with lupus. Participants will receive Lenabasum or a placebo for almost three months and will continue to be monitored for pain and inflammation levels, as well as lupus disease activity. The study is ongoing, but Dr. Koumpouras anticipates that it will wrap up by early next year.

From “miracle drug” to medicine?

Dr. Koumpouras’ excitement over the new drug comes at a time when products containing CBD have flooded supermarkets, labeled with claims that they treat everything from back pain to insomnia. Although CBD is not yet approved by the FDA, the hype around it stems from the popularity of the marijuana plant it is derived from.

But whether CBD actually provides those benefits in a significant way remains to be seen. Only a few studies—small ones—have definitively proven the effectiveness of medicines that involve the endocannabinoid system. To date, the only FDA-approved medication containing CBD is Epidiolex, a medication used to treat two rare forms of severe epilepsy—Lennox-Gastaut syndrome and Dravet syndrome, both which begin mostly in infancy and early childhood. In a group of three clinical trials, Epidiolex seemed to reduce the number of seizures significantly. And yet, Vinita Knight, MD, a Yale Medicine pediatric neurologist, says her patients who take Epidiolex have had mixed results. Some have had reductions in seizures and others haven’t shown much improvement. “We’re not seeing as much success as what’s been reported on Facebook and Twitter,” she says, but adds that so far it has only been prescribed for children with the most debilitating and difficult-to-treat seizures. In addition, some researchers believe that CBD works most effectively in combination with other cannabinoids and compounds found in the marijuana plant, in what is known as the “entourage effect.” Thus, it would be less effective as an isolated chemical in pill form, but that, too, remains unproven.

But these questions are why Dr. Koumpouras is focusing on a compound that, until recently, few have studied.

His research is one of many new studies at Yale and elsewhere looking at the endocannabinoid system and molecules related to CBD action for use in treating everything from Crohn’s disease to psoriatic arthritis, and he hopes that this new data will be used to help paint a more complete picture about the chemical for future treatment options.

“The more data the better,” he says. “The more we’re able to make informed decisions.”

Yale Medicine doctor investigates whether a synthetically created molecule that mimics properties and effects of CBD could treat diseases.

Can cannabis help with lupus? Patients recommend it, but research is lacking

Lupus is an autoimmune disease of inflammation. It can affect joints, skin, and even vital organs such as the brain and heart as the immune system attacks tissues and organs in the body. Symptoms of the disease can vary, and people experience them at different rates or severity. Some of the most common include:

  • Fatigue
  • Fever
  • Joint pain
  • Stiffness and swelling
  • Chest pain
  • Difficulty breathing
  • Headaches
  • Distinctive facial rash

The most common form of lupus is systemic lupus erythematosus (SLE) which affects multiple organs in the body.

We know that cannabis is widely used to relieve inflammation, so it makes sense that it would bring relief to those with lupus. But can it do more? How far can cannabis go as a treatment for lupus, and should it be discussed with your doctor? Let’s take a look at the current research.

Living with lupus

The cause of lupus can be genetic, environmental, or a combination of both. A predisposition to the disease can lead to the possibility of it being triggered by things such as sunlight, infections, or certain medications such as ones for blood pressure, anti-seizure, and antibiotics. Most experience their first symptoms between the ages of 15 and 45.

According to a LupusCorner survey, 83% of the 381 people who reported using cannabis said they would recommend it to others. The same survey reports that 96% of people did not discuss cannabis with their doctor.

But lupus can be far more than just inflammation. The kidneys are the most at risk, with kidney failure being a leading cause of death associated with lupus. The brain and central nervous system can also be affected, creating side effects such as confusion, dizziness, headaches, behavior changes, vision issues, strokes, or seizures. Lupus can also cause anemia, blood clotting, and issues with the lungs, heart, and bones. Risk of heart attacks, cardiovascular disease, bone tissue death, as well as pneumonia and difficulty breathing increase. Lupus also lends itself to complications during pregnancy, and increases the risk of infections and possibly cancer.

With treatment, remission and controlling the disease is possible, but there is currently no cure. Currently, those diagnosed with lupus can look to prescription medications for relief, but many are also looking to cannabis.

So far, there’s very little research that explores cannabis as a treatment for lupus. But there are a few relevant studies, and even more anecdotal evidence.

Although they do not address lupus specifically, there are several studies that examine cannabis’ effect on inflammation. As for studies directly related to cannabis for lupus? There’s currently no such noteworthy research.

According to a LupusCorner survey, 83% of the 381 people who reported using cannabis said they would recommend it to others. The same survey reports that 96% of people did not discuss cannabis with their doctor. This lack of physician involvement, along with the lack of research on the topic, means that people with lupus are pursuing cannabis as alternative medicine on their own accord or at the referral of friends.

Using cannabis for lupus

Brianna Smith, 27, was diagnosed with lupus nephritis at the age of 25. It took four months of severe symptoms—such as nausea, mouth sores, extreme joint pain, and headaches—before she received her diagnosis, and the trials did not stop with identifying the disease. She describes her lupus as “out of control,” and was hospitalized twice during this time.

“Cannabis helped me out significantly with my pain and on an emotional level. I hit a real slump in the beginning stages of my diagnosis, and cannabis would make those periods feel okay.”

Brianna Smith, lupus fighter

“It got scary when I started experiencing neurological issues,” Smith said. “That’s when I began to use CBD oil. At this point in time I was only using oil [and not smoking] due to a lot of internal inflammation. I was unsure about whether or not smoking was okay for me. To this day, it’s still a question that I’m too afraid to ask my doctor.”

Smith lives in Texas, and thus medicates with cannabis without the guidance of a physician due to strict cannabis laws . She uses cannabis in conjunction with her prescribed medication to help curb their side effects.

In the beginning, she was on high doses of an immunosuppressant, a steroid, and another medication traditionally used to treat malaria. In addition, she was receiving a low dose of chemotherapy. She was suffering from a slew of side effects including extreme nausea, stomach pain, and headaches. She was prescribed more medicine for these symptoms, but in time was able to reduce her prescription intake by using cannabis instead.

“Lupus patients take a lot of different toxic medications,” Smith said. “Cannabis helped significantly in alleviating the negative side effects of some of the medications.”

Today, Smith says she is healthy and “pretty much back to living a normal life.” In addition to cannabis, she also credits diet and exercise as her “saving grace.” She expresses gratitude for the ways in which cannabis helped her cope.

“Cannabis helped me out significantly with my pain and on an emotional level. I hit a real slump in the beginning stages of my diagnosis, and cannabis would make those periods feel okay at the moment. Of course, I would deal with these issues once I had the energy to cope,” Smith said.

Smith isn’t alone in her experience—not by a long shot. While writing this article, many people with lupus came forward wanting to talk about their experience with cannabis.

Another lupus fighter, Melissa Tompkins, was diagnosed at 26 years old. She’s now 32 and continues on the road to recovery. She suffered kidney failure and was put on dialysis and six months of chemotherapy. She had been using cannabis recreationally for years prior, but after her diagnosis and treatment, that relationship with cannabis changed; she found it medicinally useful for combating nausea, anxiety, insomnia, and that it helped with “relaxation, when you are super worried and tense.”

“I don’t think I could deal with coming to dialysis three times a week if I wasn’t stoned,” says Tompkins, “[It] helps with the anxiety of sitting there wondering if I’m going to live another week or not.” Tompkins is currently waiting to be put on the list for a kidney transplant.

Talking to your doctor about cannabis for lupus

When it comes to speaking with your physician regarding using cannabis for lupus, patients will have to decide their own comfort level when broaching the topic. Do you trust your doctor? Do you feel comfortable speaking with them frankly?

If deciding to take the plunge, patients can start with questions such as, “Would you be willing to research how cannabis may be able to help my symptoms?” It’s advisable to stick to the word “cannabis” and avoid terms like “marijuana” or “weed” when speaking with your doctor.

As for Smith’s question about a preferred method of delivery? Dr. Dustin Sulak , an expert in medical cannabis, noted, “Lupus is easily exacerbated by stress and sleep disturbance, two things that often improve with cannabis use in any delivery method. I’ve seen several patients with lupus use inhaled cannabis effectively, but the ideal method is usually oromucosal delivery [such as a tincture or lozenges] for baseline treatment, and inhaled for breakthrough symptoms.”

Lupus, like most autoimmune diseases, is characterized not simply by one symptom, but many. Some are serious, like kidney failure, others are demoralizing, such as hair loss—but for many of the symptoms that affect daily quality of life, such as inflammation , anxiety , nausea , headaches , pain , and insomnia , cannabis may be able to help.

Despite so many people using cannabis for lupus, research and guidance from doctors remains in short supply. ]]>