Cannabinoids and Lupus: Exploring Therapeutic Potential

Conor McLeod
Nov 1, 2024
14 min read

Introduction

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease, marked by immune system dysregulation that can cause inflammation across multiple organs. While current treatments focus on reducing immune activity, recent research suggests that cannabinoids, such as CBD (cannabidiol) and CBG (cannabigerol), may have targeted effects that could help manage lupus symptoms and improve quality of life. This article examines how these cannabinoids may interact with key immune pathways in lupus, focusing on mechanisms that contribute to their potential therapeutic effects.

Understanding Lupus Pathophysiology: Where Cannabinoids Might Help

Lupus is characterized by a combination of innate and adaptive immune dysregulation. Specific immune cells like T cells, B cells, and plasmacytoid dendritic cells (pDCs) contribute to chronic inflammation through the production of inflammatory cytokines such as IFN-γ and IL-6 (Robinson et al., 2021; Dörner & Furie, 2019). The endocannabinoid system (ECS), including CB₁ and CB₂ receptors and endogenous cannabinoids like anandamide and 2-arachidonoylglycerol (2-AG), plays an integral role in regulating inflammation and immune response.

Cannabinoids derived from Cannabis sativa can interact with ECS receptors and other immune pathways, potentially providing therapeutic benefits in SLE. Dysregulation of the ECS is increasingly implicated in autoimmune diseases, including lupus (Cristino et al., 2020; Friedman et al., 2019; Navarini et al., 2018; Chiurchiù et al., 2015). Here, we’ll explore the roles of CBG, CBD, CBDA, and CBGA in modulating lupus-related immune pathways.

Cannabigerol (CBG): CBG is a precursor molecule to other cannabinoids, known for its interaction with both CB₁ and CB₂ receptors, as well as with additional non-cannabinoid targets, such as TRP channels and PPAR receptors. Although studies on CBG and lupus are limited, CBG’s known effects suggest multiple mechanisms through which it may alleviate SLE symptoms.
Cannabidiol (CBD): CBD is one of the most extensively studied cannabinoids, with known anti-inflammatory, analgesic, and immunosuppressive properties. While CBD does not have strong affinity for CB₁ or CB₂ receptors, it influences them indirectly through other mechanisms.
Cannabidiolic Acid (CBDA): CBDA is the acidic precursor of CBD, and given CBDA’s effects on COX-2 and TRPV1, it could hypothetically provide dual anti-inflammatory and analgesic benefits in lupus, particularly for pain management and inflammation reduction.
Cannabigerolic Acid (CBGA): CBGA, the precursor to CBG, CBD, and THC, is noted for its broad anti-inflammatory potential. Although direct studies on CBGA and lupus are scarce, its known interactions suggest it may play a role in lupus treatment through cytokine reduction and immunomodulation support.

Modulating Immune Cell Activation through CB₂ Receptor Pathways

The CB₂ receptor, predominantly found on immune cells, plays a crucial role in regulating immune response. Activation of CB₂ reduces inflammation by downregulating pro-inflammatory cytokines and T cell activity, both of which are elevated in lupus.

CBG and CB₂ Receptor Activation: CBG has been shown to activate CB₂ receptors, which are heavily expressed in immune cells like macrophages, T cells, and B cells. CB₂ receptor activation is associated with reduced inflammation by inhibiting cytokine release and T cell activation - critical steps in lupus pathogenesis. Studies have shown that 2-AG, an endogenous cannabinoid with similar CB₂ affinity, can downregulate IFN-γ production in T cells, which plays a significant role in lupus progression (Navarini et al., 2022; Rahaman et al., 2019; Gasperi et al., 2014). CBG could potentially exert similar immunomodulatory effects through CB₂ activation, making it a promising candidate for reducing lupus-related inflammation. This mechanism could potentially alleviate systemic inflammation and organ damage, including that found in the kidneys and skin.
CBD and CB₂ Indirect Modulation: Although CBD doesn’t bind directly to CB₂, it influences CB₂ pathways indirectly, promoting an anti-inflammatory response that could benefit lupus patients by reducing disease activity and inflammatory flare-ups. IFN-γ is a key cytokine in lupus that promotes inflammation and autoantibody production. CBD has been observed to lower IFN-γ production by T cells, potentially reducing lupus disease activity. This effect could complement other immune therapies, allowing patients to reduce their reliance on immunosuppressive drugs (Navarini et al., 2022).
CBGA and CB₂ Indirect Modulation: As a precursor to other cannabinoids, CBGA is thought to exhibit indirect CB₂-mediated effects on immune modulation. Its ability to reduce pro-inflammatory markers in other models suggests it might help in reducing immune overactivity seen in lupus (Sarzi-Puttini et al., 2019).

Patient-Friendly Explanation: Think of the CB₂ receptor as a “dial” on immune cell activity. Cannabinoids like CBG and CBD can turn down the immune response in lupus, potentially easing inflammation and reducing symptom severity.

Inflammatory Cytokine Suppression

Pro-inflammatory cytokines, particularly IFN-γ, IL-6, and TNF-α, are critical drivers of lupus pathology, contributing to symptoms like joint pain, tissue damage, and fatigue. Cannabinoids’ ability to modulate cytokine production makes them attractive as potential treatments for reducing lupus-related inflammation.

CBD and Cytokine Suppression: CBD has shown the ability to suppress IFN-γ, a cytokine that promotes lupus disease activity by activating immune cells that attack healthy tissues. Additionally, CBD can decrease IL-6 and IL-8, cytokines known to cause inflammation and pain, particularly in joints and muscles (Navarini et al., 2022; Selvi et al., 2008).
CBG and PPAR-γ Activation: CBG is known to bind to PPAR-γ, a receptor involved in metabolic regulation and immune modulation. Activation of PPAR-γ has been linked with reduced production of pro-inflammatory cytokines such as IL-6 and TNF-α. Since elevated IL-6 is a hallmark of lupus-related inflammation, CBG’s ability to modulate PPAR-γ activity may provide additional anti-inflammatory effects (Sarzi-Puttini et al., 2019; Rodríguez Mesa et al., 2021).
CBGA and Cytokine Inhibition: CBGA has been shown to inhibit pro-inflammatory cytokines in other models of inflammation, which could translate to benefits for lupus patients experiencing heightened cytokine activity (Sarzi-Puttini et al., 2019; Kotschenreuther et al., 2021).

Patient-Friendly Explanation: Cytokines are like signals that tell the immune system to attack. Cannabinoids help quiet these signals, potentially reducing inflammation and pain in lupus.

T Cell Regulation and Balance of Th17/Treg Cells

Lupus involves an imbalance between pro-inflammatory Th17 cells and anti-inflammatory regulatory T cells (Tregs). The dominance of Th17 cells promotes inflammation, while a lack of Tregs reduces the immune system’s ability to regulate itself. Cannabinoids, particularly CBG and CBD, may help restore this balance.

CBG and Th17 / Treg Management: In lupus, an imbalance in T cell populations, specifically, an increase in pro-inflammatory Th17 cells and a decrease in regulatory T cells (Tregs), exacerbates disease severity. CBG has shown promise in suppressing Th17 cell activation and supporting Treg function. CBG’s interaction with TRP channels may also play a role in T cell regulation and could help restore the T cell balance. By reducing Th17-driven inflammation and promoting Treg balance, CBG could target one of the core immune imbalances in lupus (Kotschenreuther et al., 2021; Almogi-Hazan & Or, 2020).
CBD and T Cell Modulation: CBD is known to influence both Th17 and Treg cells indirectly. By reducing IFN-γ and promoting anti-inflammatory Treg activity, CBD may help alleviate lupus symptoms and reduce autoimmune activity without fully suppressing the immune system (Navarini et al., 2018; Selvi et al., 2008).

Patient-Friendly Explanation: T cells are like managers of the immune system. CBG and CBD help bring back balance between aggressive and calming T cells, which may prevent lupus flares and inflammation.

Oxidative Stress and Organ Protection

Oxidative stress, driven by excess free radicals, plays a significant role in lupus by damaging tissues and contributing to organ failure. Antioxidant properties of cannabinoids may help mitigate this damage, providing protective benefits for organs commonly affected by lupus, like the kidneys and skin.

CBGA and Oxidative Stress: CBGA is recognized for its strong antioxidant properties, which could help counteract the oxidative stress seen in lupus. By neutralizing free radicals, CBGA may protect tissues from further inflammation and damage (Tsokos, 2020). Oxidative stress is a known factor in lupus pathology, contributing to tissue damage and inflammation. CBGA’s antioxidant effects could potentially reduce oxidative damage, offering added protection for organs commonly affected in lupus, such as the kidneys and skin (Tsokos, 2020; Richardson et al., 2008).
CBD and Reactive Oxygen Species: CBD’s antioxidant effects have been observed to protect against oxidative stress in other autoimmune conditions. Although further research is needed in lupus specifically, CBD’s action on ROS (reactive oxygen species) suggests it may help in reducing tissue damage and preserving organ health in lupus patients (Almogi-Hazan & Or, 2020; Chiurchiù et al., 2015).

Patient-Friendly Explanation: Oxidative stress in lupus is like rust that wears down organs over time. Cannabinoids like CBGA and CBD act as “antioxidants,” which may help protect these organs.

Joint and Muscle Pain Management

Pain management in lupus, particularly for joint and muscle pain, remains a significant clinical challenge. TRP (transient receptor potential) channels, especially TRPV1, are involved in pain perception and inflammation. Cannabinoids like CBD and CBDA interact with these channels to produce analgesic effects.

CBD and TRPV1: CBD interacts with TRPV1 receptors, which are involved in pain perception and inflammation. CBD’s activation of TRPV1 can help desensitize pain receptors, potentially providing relief from chronic pain experienced by lupus patients (Katz-Talmor, Katz, et al., 2018).
CBDA and TRPV1 / COX-2: CBDA may act as a TRPV1 agonist, similar to CBD, suggesting it could also have analgesic properties that may benefit patients with chronic pain (Sarzi-Puttini et al., 2019). Although research specific to lupus is limited, CBDA has shown potential in anti-inflammatory modulation through COX-2 inhibition, a pathway commonly targeted by non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief in autoimmune conditions. By blocking COX-2, CBDA could reduce inflammation and pain in lupus, particularly in joint and muscle areas affected by the disease (Almogi-Hazan & Or, 2020; Chiurchiù et al., 2015).

Patient-Friendly Explanation: TRP channels are like “pain sensors.” Cannabinoids can “turn down” these sensors, which may help relieve pain in lupus.

Patient Profile

Patient: Female; 40-50yo
Lupus Diagnosis: 10 years
Symptoms: Chronic open sores, severe pain, inflammation, fatigue, muscle spasms, chronic idiopathic urticaria (hives), and IBS attributed to prior medication use
Medications: Hydroxychloroquine, escitalopram, montelukast, rabeprazole, IBSRELA, Xolair, gradually reducing naltrexone, discontinued muscle relaxants
Cannabinoid Treatment Regimen:
- CBD: One 25mg capsule in the morning
- CBDA: Four 15mg capsules daily (2 in the morning, 2 at night)
- CBG: One 50mg capsule at night
- CBD Balm: Applied to affected areas three times daily

Progress Summary

Over several months, the patient experienced remarkable improvements, including substantial pain reduction, significant healing of open sores on her hands, and improved energy levels, which enabled her to return to regular workouts and her business activities. She attributes these changes to the combination of cannabinoids, particularly CBDA, CBD, and CBG, and has observed improvements in her physical and mental well-being, allowing her to taper off certain medications.

In Her Own Words...

August 26th, 2024 I heard about your product through a friend at yoga. I have open sores from lupus, and I am in pain. Can I buy the product from you?

October 19th, 2024 I have some updates for you. My pain is close to nothing, sometimes I don't have any pain. My hand is almost completely healed… which is amazing after I battled with these sores for 5 to 6 years. It is unbelievable, I have not seen my hand heal this much in six years at all, I tried everything and nothing works. With the Lupus, all my systems got damaged, so I add more illnesses as we go on this journey...The list of medications that I sent you used to be bigger. A long time ago, I decided to quit a bunch of the pills, because what they do is give us all these kinds of pills that don’t work. I tried all the creams in the alphabet with steroids.

I have IBS because of the medicine that they gave me in the beginning. A lot of my illnesses started after I began taking all these chemicals that they pumped me up with. Like day one, diagnosed with lupus, they pump you up with so much medicine and steroids it not even funny. But, because you don’t know anything about it, they’ll take advantage of it, and once you have been in this fight for so many years, you pay attention to what the doctors are doing to you. They want to help, know that, but they don’t always know there are better ways to help. So, to find something made me feel this way that allows me to work out every day. I’m working out every day. Working on my two little businesses, went back to them because they weren’t abandoned… I’m able to do more here at home, more energetic, even my private life is better, if you know what I mean. My hand is almost completely healed. It is a great product for [lupus patients], especially for the pain and for the sores, because every patient with lupus has sores everywhere. We get them in our privates, we get them in the nose, our skin, everywhere. This is the first time I have no sores open in six years.

October 29, 2024 I thought you would like to see this full recovery! I feel so much better but also my mental state is improving tremendously. I’ll keep you updated on my progress. I’m so happy thank you so much, have a blessed day.

Integrating Cannabinoid-Based Therapies into Lupus Treatment

As research advances, cannabinoids like CBG, CBD, CBDA, and CBGA may become valuable additions to lupus treatment by targeting specific pathways related to immune balance, inflammation, oxidative stress, and pain perception. However, given the complexity of lupus and varying patient needs, it is essential to approach cannabinoid treatment on an individualized basis while clinical evidence is still emerging.

Clinicians should balance potential benefits with patient-specific factors such as disease severity, organ involvement, and concurrent medications. Controlled clinical trials are necessary to establish safe dosing guidelines and long-term effects, especially considering mixed findings like CBD’s potential to exacerbate proteinuria in lupus nephritis models (Katz-Talmor, Kivity, et al., 2018).

General Recommendations and Safety Tips

Dosing Adjustments: Begin with the lowest recommended doses, especially for those new to cannabinoids. Gradually increase only if needed and based on tolerance.
Combination Strategy: For patients with multi-symptom involvement, a combination of oral and topical cannabinoids can provide targeted relief.
Monitoring: Patients should track symptom response and consult with their healthcare provider regularly to adjust doses as needed. Consider checking inflammatory markers at baseline and periodically to assess the impact.

Sample Protocols for Lupus Patients Using Cannabinoid Products

Below are suggested protocols that can be adjusted according to patient response and tolerance. Begin with low doses, monitor clinical markers, and assess patient response to cannabinoid therapy as an adjunct to traditional lupus treatments.

NOTE: Cannabinoids should be integrated cautiously alongside traditional lupus medications, with regular monitoring for potential interactions. This information is for educational purposes only and does not constitute medical advice. If you or a loved one have lupus, speak with your medical provider before starting or changing medications.

General Inflammation and Immune Modulation

CBG Oral Capsules: Start with 1 capsule (50mg) daily, ideally taken in the morning with a high-fat meal.
CBD Oral Capsules: Add 1 capsule (25mg) daily in the evening.
Monitoring: Evaluate after two weeks. If well-tolerated, consider increasing to two capsules daily for each capsule.

Severe Inflammation and Organ Protection

CBG Oral Capsules: Start with 1 capsule (50mg), ideally taken in the morning with a high-fat meal. Consider increasing to two doses daily after one week if well-tolerated.
CBGA Oral Capsules: Add 1 capsule (25mg) daily to help counter oxidative stress and protect against organ damage, particularly useful for patients with kidney or skin involvement.
CBDA Oral Capsules: Add 1 capsule (15mg) daily for patients with high levels of inflammation, particularly where COX-2 pathways may be involved. This may also support gastrointestinal comfort in patients sensitive to NSAIDs.
Monitoring: Monitor inflammatory markers before and after starting cannabinoid treatment. Evaluate for two weeks before adding in additional cannabinoids. Consider increasing doses if well-tolerated and patient showing improvement.

Joint and Muscle Pain

CBD Topical Balm: Apply a thin layer to affected joints or muscles, using approximately 1g of balm (20mg CBD) per application. This can be repeated daily as needed.
CBG Topical Balm: For enhanced relief, apply alongside the CBD balm or in alternating applications. CBG’s local anti-inflammatory effects and antibacterial properties may help with pain and skin lesions.
CBD Oral Capsules: Start with 1 capsule (25mg) daily, ideally taken in the evening with a high-fat meal.
CBDA Oral Capsules: Add 1 capsule (15mg) daily in the evening.
Monitoring: Evaluate after two weeks. If well-tolerated, consider increasing to two capsules daily for each capsule. Monitor and evaluate, some patients may need a higher or lower ratio of CBD : CBDA depending on endocannabinoid system needs.

Fatigue and Mood Balance

CBD Oral Capsules: Take 1 capsule (25mg) in the evening with a high-fat meal to help regulate mood and promote relaxation, potentially alleviating stress-related flares.
CBG Oral Capsules: Consider adding 1 capsule (50mg) taken in the morning with a high-fat meal for mild energy support due to CBG’s potential effects on alertness and well-being.
Monitoring: Evaluate after two weeks. If well-tolerated, consider increasing to two capsules daily for each capsule.

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