Lupus Therapies - What's The Evidence for Cannabis?
Our last blog post for National Lupus Awareness month talks prescriptions, cannabis and clinical trials.
There is currently no cure for Lupus, but as our guests this month shared, many people living with Lupus take medications to manage the symptoms of the disease and its flares. Every person responds to therapy differently - as our last guest put it, "we are all clinical trials with an N of 1" - and many people try several different combinations and doses throughout their treatment.
We'll start by talking about the prescription therapies, then go into what the evidence says for cannabis, and then finish with what the clinical trial progress has been for a synthetic cannabinoid and the disease.
Current Prescription Therapies
Lupus is caused by an over-active immune system, so while the medications below all act through different mechanisms, the goal is to reduce inflammation and dampen the immune system to lessen the damage it can cause to joints, tissues, and organs. All of these therapies have been used and studied in Lupus patients, but only one drug, Benlysta, is currently FDA-approved for Lupus.
This class of drugs has gotten a lot of attention in the context of the COVID-19 outbreak, and it is important to recognize that many people living with Lupus rely on these drugs. The Johns Hopkins Lupus Center even calls these drugs "lupus life insurance". The way these drugs work against Lupus is unknown, but it is likely mediated by long term suppression of immune molecules known as T-cells and cytokines (1). Examples of these drugs are hydroxychloroquine and chloroquine.
Steroids are a standby treatment for many conditions that involve a hyperactive immune system. Patients may take lower doses in tablet form daily if they have mild symptoms, or may take large doses of intravenous steroids called 'pulses'. Some patients may also use steroid creams or ointments on their skin to calm rashes caused by Lupus. Prednisone is a commonly used steroid for people with Lupus and many other inflammatory conditions.
The name of this class of drugs loosely translates to 'cell-killing' and that is what these drugs do. These are the types of drugs also used to kill cancer cells and prevent transplant rejection. Because of their toxicity and side effects they are usually reserved for cases where Lupus has attacked the kidneys (2). This class of drugs includes azathioprine, cyclophosphamide, and mycophenolate.
'Biologic' is an umbrella term used for drugs that are made of molecules, called antibodies, specifically targeted to stick to particular cells or proteins in the body. In the case of Lupus, the drugs target immune molecules, bind to them, and block over-active immune system activity. These drugs are injections given as intravenous infusions or under-the-skin injections. There are two biologic drugs used for Lupus - Rituxan and Benlytsa. Rituxan is an older drug (approved in 1997) and is used in a board rage of conditions including rheumatoid arthritis and various forms of cancer (3).
Like we mentioned at the top of this post, all of the treatments so far have been studied and shown efficacy in treating Lupus, but only one drug - Benlysta - actually went through clinical trials to receive an FDA indication specially for Lupus (4).
Cannabis and Lupus - Current State
The National Lupus Foundation's position on the use of cannabis in Lupus short and sweet - we need more research in this area, and anyone considering using cannabis to treat their Lupus symptoms should first discuss it with their doctor. I couldn't agree more. You can read the full statement here.
Many state medical programs, including Oregon, have avenues for people living with Lupus to qualify for a medical card. For example, Oregon's program lists chronic pain, a common symptom of Lupus, as a qualifying condition for the Oregon Medical Marijuana Program. We have more information on how to get an OMMP card for our readers in Oregon here.
Lupus is a disease caused by an over-active immune system, and studies in mice and other animal models have shown that cannabinoids have an impact on molecules of the immune system. A 2016 review paper that analyzed dozens of experimental mouse models concluded there was ... "credence to the medicinal uses of delta-9-THC that relate to dampening immune function" (5).
Studies of cannabis use in humans, however, involve many more factors than controlled laboratory environments. Studies of actual cannabis use in Lupus patients are scarce, and not all are positive. A 5-year observational study by the University of New Mexico did not find that cannabis use improved pain or Lupus severity in a group of 276 patients (6).
Larger 'real world' studies of cannabis use are even more complex, often rely on self-reported information or do not involve true control groups. These studies, however, can still shed light on the impact cannabis has on common symptoms associated with Lupus. The Minnesota Department of Health, for example, collects self-reported data from all patients in its medical cannabis program. Their October 2019 report shows that of patients who used cannabis for intractable pain, 10.5% of patients showed significant sustained improvement in their pain and 22.8% showed significant and sustained improvement in fatigue (7).
Cannabis and Lupus - Clinical Trials
Anyone interested in clinical trial activity for Lupus or potentially enrolling in a clinical trial can visit clinicaltrials.gov and enter 'Lupus' in the condition search bar to see all active, enrolling and completed clinical trials. When one filters to Lupus clinical trials with the term 'cannabis' you find a much-talked about investigational drug JBT-101, or lenabasum.
Lenabasum is a synthetic cannabinoid that binds to the CB2 receptors of our endocannabinoid system, which are found in a variety of tissues in the periphery of our bodies, including immune cells, muscle cells, and cells lining our organs. When lenabasum binds the CB2 receptor it actives processes that resolve inflammation, prevent fibrosis (hardening of tissues), and reduce the production of proteins involved in inflammatory responses.
Because of its broad effects on the immune system, lenabasum is being studied in a variety of auto-immune conditions including Lupus, Dermatomytosis, Systemic Sclerosis, and Cystic Fibrosis (8). The study of lenabasum for Lupus involves about 100 patients and is expected to conclude December 2020 (9).
Lenabasum is a synthetic cannabinoid, and the results of the study won't be a direct comparison to cannabis products obtained through medical cannabis programs, especially full spectrum products that contain a variety of potentially active plant molecules in addition to cannabinoids. However, the results of the clinical trials of lenabasum for any indication will give researchers insight into how modifying the endocannabinoid system impacts diseases caused by over active immune systems.
1) Hahn BH. Management of systemic lupus erythematosus. In: Ruddy S, Harris ED, Sledge CB, eds. Kelley's Textbook of Rheumatology, 6th ed.
2) Balow JE, Boumpas DT, Austin HA III. New prospects for treatment of lupus nephritis. Semin Nephrol 2000; 20:32-39