CBD Oil For Autoimmune Diseases

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Are you looking for hemp-derived CBD products that may help with autoimmune diseases? Here are some of the best CBD oils to improve your quality of life. The tale of Cannabis sativa is as old as time

Compare the best CBD Oil for Autoimmune Diseases in 2022

Each bottle of the 750mg CBD oil tincture contains 25mg of CBD per dropper full. The oil is peppermint flavor to mask any unpleasant tastes related to CBD.

2. NuLeaf Naturals 900mg Full Spectrum Hemp CBD Oil
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No other flavors

Approximately 300 drops total

Overview

Natural remedy for various illnesses. NuLeaf Naturals’ CBD oil is a whole-plant extract containing a full spectrum of naturally occurring synergistic cannabinoids and terpenes.

3. Spruce 2400mg Lab Grade CBD Oil
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No artificial flavoring or colors

No THC-free option

Made from 100% organic and natural ingredients

Overview

The largest bottle of CBD oil that Spruce offers contains 2,400mg of CBD. This is full-spectrum CBD oil, which is the maximum possible potency. Each high potency dropper full contains 80mg of CBD. There are no flavorings in it, which allows for the most CBD to fit in the 30ml bottle.

4. Avida Full Spectrum CBD Oil Tincture 500mg
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Light Spearmint flavor

No other flavor

Non-THC, Non-detected in drug test

Overview

Avida Extracts Full Spectrum CBD oil is the latest iteration of the brand’s advanced Avida CORE Spectrum technology. They use a proprietary full spectrum blend, resulting in the highest naturally occurring Phyto-cannabinoids and Terpenes with THC (<0.3) to support your health.

5. cbdMD CBD Oil Tincture Natural 1500mg
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Various delicious flavors to choose from

cbdMD uses MCT as its carrier oil so individuals who are allergic with coconuts should consider other brand options

Has vegan, organic, and gluten-free ingredients

Free shipping for this particular product within USA

World-class customer service team

Overview

cbdMD’s CBD oil tinctures are made using only CBD sourced from medical hemp and MCT oil as a carrier oil. Tinctures are offered in orange, mint, natural, and berry flavors. Safe for daily use, the oil tinctures are packaged with a built-in rubber dropper to adjust CBD dosage easily. The packaging is made to be easy to transport and discreet to use.

6. CBDistillery THC Free CBD Oil Tinctures
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60-Day Satisfaction Guarantee

Dropper is a bit shaky

Oil extracted from aerial plant parts of US grown industrial hemp

Sourced from non-GMO industrial hemp grown in the USA through natural farming practices

Overview

CBDistillery’s Isolate CBD Oil Tinctures harness the power of pure CBD. CBD Isolate Oil Tinctures include 0.0% THC. When you use CBDistillery CBD Isolate Oil Tinctures, you can be assured you’re using the highest quality CBD on the market.

7. NuLeaf Naturals 300mg Full Spectrum Hemp CBD Oil
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No other flavors

A bit pricey compared to competitors

Approximately 100 drops total

Overview

This is one of several concentrations from NuLeaf Naturals. As the lowest concentration, it is the company’s best option for those new to CBD oil. The product is lab-tested and fully organic. It is full-spectrum, so it contains THC in small quantities.

8. cbdMD CBD Oil Tincture Natural 750mg
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Vegan and Gluten free

Does not ship internationally

Has a third-party lab test

Wide variety of CBD strengths and sizes

Overview

A 750mg bottle of cbdMD’s Broad Spectrum Oil Tincture does not contain THC. It also has a fairly wide flavor range which is perfect for those who prefer other taste. Vegan consumers are considered since cbdMD offers Vegan products. Aside from all of that, another reason why people love cbdMD is because it’s free from harmful chemicals.

9. Hemp Bombs 750mg CBD Oil
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Wide variety of flavors

Incomplete information about the product

Lab test results are complete

Does not ship to all international countries

30-day money-back guarantee

Overview

Hemp Bombs offer CBD Oil Tinctures that come in a 30ml bottle containing 750mg of CBD. They provide a wide range of flavors perfect for those that have a knack for sweets. Consumers can safely intake this because it’s free of chemicals and pesticides. Hemp Bombs also offer a 20% off on products upon subscription.

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How CBD Helps With Autoimmune Diseases

Cannabidiol (CBD) is a plant-derived cannabinoid . CBD has a structural similarity to tetrahydrocannabinol ( THC ), the primary psychotropic substance in cannabis . THC is responsible for the euphoric high people experience after using marijuana (1) .

Meanwhile, cannabidiol is non-psychoactive and bicyclic, comprising two fused rings in the molecule structure. CBD contains an aromatic ring and terpene , a fragrant compound found in plants (2) .

Moreover, CBD produces biological effects in the central nervous system (CNS). Although the chemical is active in the CNS, it does not create a euphoric effect, unlike THC (3) .

Based on a 2020 review published in Cannabis and Cannabinoid Research, CBD contains anti-inflammatory properties . It is also immune suppressive ( 4) .

A person’s immunity is maintained through numerous cell types, such as myeloid cells, acting together to protect against foreign substances (5) .

Myeloid cells or blood cells comprise the innate immune system , which destroys pathogens or organisms that cause various diseases (6) .

The human immune system is made up of two parts: innate and adaptive (7) .

The purpose of the innate response is to prevent the spread of pathogens throughout your body. It is your body’s first line of defense against germs, whereas the adaptive response explicitly targets the germs that cause the infection (8) .

In an event where there is an insufficient innate reaction, some innate cells can activate the adaptive immune response, composed of T and B cells (9) .

T cells are white blood cells that stimulate B cells. Meanwhile, B cells fight viruses and bacteria by producing antibodies that neutralize pathogens (10) .

According to the researchers, the effect of cannabidiol on immune response can involve innate or adaptive responses. Research authors Nichols and Kaplan suggested CBD may cure autoimmune diseases by directly suppressing various resistant cell types (11) .

Autoimmune diseases occur when your body fails to differentiate your cells from foreign cells. Thus, your immune system mistakenly attacks your healthy tissues (12) .

The endocannabinoid system ( ECS ) plays a vital part in the central nervous system development and the response to endogenous and environmental insults (13) .

The ECS is composed of cannabinoid receptors , namely, CB1 and CB2. Both receptors are found throughout the CNS , in the immune system, and other body organs (14 ) .

The ECS has its chemical messengers called endocannabinoids that interact with CB1 and CB2 receptors (15) .

CB1 receptors have a significant role in motor regulation, memory processing, appetite, mood, sleep, and pain sensation. Meanwhile, CB2 receptors , when activated, stimulate a response that fights inflammation (16) .

CBD indirectly interacts with your ECS , signaling it to produce more of its natural cannabinoids . In addition, it inhibits the enzyme that breaks it down.

This reaction results in more endocannabinoids circulating in your body for a longer duration (17) . Your body uses these endocannabinoids efficiently and returns to homeostasis ( 18 ) .

Homeostasis is your body’s capacity to maintain the stability of different variables, such as water level, acidity, and temperature, in the event of constant environmental disturbance (19) .

Although the existing research on CBD for autoimmune diseases is promising, longitudinal clinical studies are needed to determine CBD’s effectiveness in dealing with autoimmune conditions .

Benefits of Using CBD for Autoimmune Diseases

CBD’s neuroprotective and immunosuppressive mechanisms make it an ideal therapeutic candidate for multiple sclerosis (MS) (20) .

MS is a neurodegenerative autoimmune condition of the central nervous system in which the body’s immune system attacks its tissues (21) .

Multiple sclerosis affects 2.5 million people globally. Usually, the age of onset is 30 years old, and symptoms differ for each individual with the condition , depending on the lesion locations within the CNS (22) .

Animal models of MS often used in a laboratory environment to study multiple sclerosis are Theiler’s murine encephalomyelitis virus (TMEV) and the experimental autoimmune encephalomyelitis model (23 ) .

Research from the British Journal of Pharmacology successfully demonstrated that a 5mg/kg i.p. ( intraperitoneal injection) of CBD administered at the onset of the disease may help the activation of microglia, the resident immune cells of the CNS (24) .

Intraperitoneal injection is the injection of a substance into the body cavity.

Results also showed that CBD administration may attenuate the T cell infiltration into the CNS using the EAE (25 ) .

On the other hand, cannabidiol showed similar effects in the TMEV model in a study from the journal of Neurobiology of Disease (26) .

The researchers demonstrated that 5mg/kg i.p. of CBD administered for the first ten days following the start of the disease may reduce neuroinflammation and clinical condition. They also hypothesized that CBD may help decrease immune cell trafficking signals in the CNS and microglial activation (27 ) .

Despite the promising results of these studies, it is still unclear if the successful outcome with CBD in the animal models of MS can also be observed in MS patients and those with an autoimmune disease .

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CBD at 20mg/kg was also administered to patients with Crohn’s disease , an inflammatory bowel disease. The researchers stated that, while CBD was safe to use, the compound did not improve or worsen the condition (28) .

C annabidiol may reduce intestinal inflammation in other models of human inflammatory bowel disease (29) .

However, further investigation is warranted to determine CBD’s effect on autoimmune diseases .

How Long After Taking CBD Will It Start to Help With an Autoimmune Disease?

Inhaling cannabidiol using vape pens is the fastest method of ingestion to benefit from the effects of CBD (30) . However, vaping may be detrimental to the lungs (31) .

On the other hand, the second quickest way to absorb CBD is through sublingual administration. Taking the compound under the tongue ensures its prompt delivery into the system ( 32 ) .

Research from the Journal of Young Pharmacists stated that fast-dissolving oral films are a popular choice among people taking medical substances .

These films are easy to administer. More importantly, the sudden onset of drug action is possible since they are taken through the sublingual route ( 33) .

B etter compliance from individuals with the condition is also expected when the sublingual method is used.

Taking a sublingual tablet does not require swallowing since it works much faster when absorbed through the lining of the mouth. This method may benefit those people with dysphagia or individuals with swallowing difficulties (34) .

You may use droppers to dispense CBD oil or tinctures straight into your mouth. It commonly takes about 15 to 30 minutes for the compound to take effect (35 ) .

Meanwhile, CBD edibles, such as gummies and capsules, may take longer to work, with some individuals feeling their effects 30 minutes or more after intake (36) .

You may also consider topical CBD products like CBD creams and lotions for your skin.

However, with topicals, you only target specific areas of the body or system. CBD may not take effect quickly because the compound does not reach the bloodstream.

Still, these characteristics make them safer, considering the lack of information on cannabidiol ’s long-term safety (37 ) .

After CBD Starts to Help, How Long Will It Last?

Ingestion methods have varying rates of bioavailability, or the extent a substance or a drug becomes available to its biological destination. In other words, bioavailability is a measure of the rate and fraction of a drug’s initial dose (38) .

A study published in Frontiers Pharmacology reviewed the discrepancy in the pharmacokinetics of cannabidiol . It also examined the lack of data regarding CBD despite its widespread use in humans ( 39) .

A systematic search was done to retrieve all articles about pharmacokinetic data of CBD in humans. Out of the 792 retrieved articles, 24 included pharmacokinetic parameters in humans ( 40 ) .

Pharmacokinetics involves the time course of drug absorption, distribution, metabolism, and excretion (41) .

Results showed that the half-life of CBD is between 1.4 and 10.9 hours after oromucosal spray, two to five days after chronic oral administration, 24 hours after intravenous medications, and 31 hours after smoking ( 42) .

Half-life refers to the time it takes for a drug in the system to be reduced by 50%. After one half-life, a compound’s concentration in the body becomes half of the starting dose.

Results showed that CBD bioavailability after smoking is 31%. However, no other studies have attempted to report the absolute bioavailability of CBD following different routes in humans, despite intravenous formulations being available (43) .

The analysis of properties, such as bioavailability and half-life is critical to future therapeutic success. Robust data from various formulations are required.

Risks and Side Effects of CBD for Autoimmune Diseases

Although studies showed that cannabidiol is relatively safe to consume (44) , there is no evidence linking CBD to specific autoimmune disease medication.

Thus, further studies are needed to determine CBD’s effectiveness on the entire body over long-term consumption.

Below are common side effects of CBD ( 45) :

  • Changes in alertness, such as drowsiness or sleepiness
  • Gastrointestinal distress, such as decreased appetite and diarrhea
  • Changes in mood, such as irritability and agitation

How to Take CBD for Autoimmune Diseases

For autoimmune disorders , you may take CBD oil in consumable forms, such as brownies, gummies , and soft gel capsules.

For a controlled CBD intake, you may choose sublingual administration instead. In this method, you may use a calibrated dropper usually included in CBD tincture products.

Begin by applying a few oil drops under your tongue and leave the oil for a few seconds before swallowing for better absorption.

Some CBD brands also sell CBD topical products. CBD topicals may be in the form of cream, lotion, or transdermal patches.

Research published in the British Journal of Pharmacology showed that transdermal delivery is utilized to produce clinical effects, such as anti-inflammatory activity and local anesthesia, deep within or beneath the skin (46) .

Transdermal drug delivery offers compelling opportunities to address the low bioavailability of several oral drugs and the inconvenience and pain of injections (47) .

A transdermal system is non-invasive, allowing users to self-administer. In addition, transdermal patches may also improve an individual’s compliance.

Since the method is generally inexpensive (48) , it may also be beneficial for those with a limited budget.

Administering topical CBD may be useful for autoimmune conditions that affect the skin. According to a 2021 study , atopic dermatitis (eczema), a chronic skin disorder, is associated with one or more autoimmune diseases (49) .

In addition, a 2018 study showed that CBD exhibited anti-inflammatory properties in an experimental allergic contact dermatitis mode l (50) . Therefore, topical administration of cannabidiol may benefit those with eczema.

Another method of CBD ingestion is vaping . However, note that CBD vapes may worsen lung disorders (51) . When using CBD for the first time, make sure to consult with a licensed physician with a background in cannabidiol use.

Usage Guide

It is crucial to select high-quality CBD products to ensure overall wellness and optimal effectiveness. However, with many brands promising the best CBD products to their customers, you may find it challenging to decide which product to choose.

When choosing the best CBD oil for autoimmune disease , here are some things you need to consider:

  1. Read the ingredient list of the CBD product carefully. If possible, choose organic types or non-genetically modified (non-GMO) ingredients.
  2. Support CBD brands that are transparent about their farming practices. Visit their website and check if it includes information about CBD extraction and testing methods.
  3. Ensure that your CBD products come with certificates of analysis (COAs) and lab test results from third-party laboratories.

A third-party lab test is essential to determine the presence of harmful contaminants, such as residual solvents and pesticides . CBD products must be tested to ascertain their consistency and potency.

CBD Dosage for Autoimmune Disease

There have been no approved U.S. Food and Drug Administration (USFDA) guidelines for CBD dosing specifically for autoimmune diseases .

However, cannabidiol dosage in most clinical studies ranges from 100mg to 800mg ( 52) . If you cannot tolerate 100mg, you may start with a lower amount unless your healthcare provider recommends a specific dosage .

It is highly recommended to speak with a physician experienced in cannabis use before trying CBD oil for autoimmune disease .

Legality of CBD

About 36 states in the United States have legalized medical marijuana. The remaining 14 states have ratified laws permitting the use of CBD extract (53) .

You may travel with CBD but only between states with similar regulations for cannabidiol use.

The U.S. Congress approved the 2018 Farm Bill, legalizing industrial hemp and products obtained from the hemp plant (54) .

According to the FDA, the redefinition of hemp made it distinct from cannabis plants under the Controlled Substance Act (CSA) ( 55) .

The CSA issues the legal basis for the U.S. government’s “war on drugs,” a consolidated law on manufacturing and distributing drugs of all kinds (56) .

The Controlled Substance Act or the Comprehensive Drug Abuse Prevention and Control Act of 1970 created a drug schedule to classify substances into five categories based on the medical use and potential for drug dependence (57) .

Although numerous states have legalized recreational and medical marijuana , marijuana is still considered a Schedule I drug (58) .

However, since hemp is now distinct from marijuana, the change may streamline the process for researchers to study cannabis derivatives that have no more than 0.3% THC by dry weight ( 59 ) .

Cannabis derivatives, including cannabinoids , such as CBD, may advance the development of new drugs from those substances (60) .

Product Frequently
Asked Questions

How can CBD help with autoimmune diseases?

A study in 2020 showed that CBD’s anti-inflammatory and immunosuppressive properties may help with human autoimmunity (61) .

The researchers suggested that the compound may help with autoimmune diseases by directly suppressing different immune cell types (62) .

What evidence or research exists to say that CBD helps with autoimmune diseases?

CBD’s neuroprotective and immunosuppressive properties make it an ideal therapeutic candidate for multiple sclerosis , an autoimmune disease of the central nervous system (63) .

Is there evidence that CBD can make autoimmune diseases worse?

There is no direct link between CBD and worsening autoimmune diseases . However, using cannabidiol may induce side effects , such as drowsiness, diarrhea, and irritability ( 64) .

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Will CBD interact with any current medication I may be taking for autoimmune diseases?

There is no evidence of cannabidiol interacting with a particular autoimmune disease medication. However, there are risks of CBD interacting with other medicines, leading to possible adverse side effects (65) .

Are there other treatments I should consider alongside CBD to help with autoimmune diseases?

You may use CBD topicals, like creams and lotions, alongside massage therapy to relieve chronic pain triggered by autoimmune diseases .

In 2017, a review in Complementary Therapies in Clinical Practice noted the benefits of massage on pain when used for autoimmune diseases , such as (66) :

  • Knee osteoarthritis
  • Rheumatoid arthritis
  • Joint pain
  • Fibromyalgia
  • Diabetes
  • Dermatitis
  • Multiple sclerosis

However, there is a lack of research and clinical trials on massage therapy and autoimmune conditions .

Meanwhile, a study showed that cannabinoids , such as CBD, may be used to manage difficult to treat pain (67) . CBD may help bring about pain relief or alleviate chronic inflammation .

Still, it is best to consult your healthcare provider to avoid a potential reaction, especially if you plan to take CBD or hemp oil with any anti-inflammatory drugs and supplements.

Can I fail a drug test if I use CBD for autoimmune diseases?

Cannabidiol (CBD) is a non-psychoactive and non-intoxicating drug. However, high doses and frequent intake of CBD may result in a positive drug test.

What is the dosage for autoimmune diseases?

There are no official dosage guidelines for CBD. CBD as a medication has not been approved by the U.S. Food and Drug Administration (FDA).

The general rule is to go slow and start low. You may begin with a low CBD potency, gradually increasing the dosage until you get the desired effects.

The World Health Organization (WHO) reported that dosages in most clinical research studies usually range between 100 and 800mg of CBD daily (68) .

How much CBD should I take?

If you are a first-time user and think you cannot tolerate the standard CBD dosage, you may opt for a microdose.

The recommended microdose for cannabidiol is 500mg CBD oil . Note that one drop of 500mg CBD oil contains approximately 2mg of CBD (69) .

How do I choose the best CBD oil for autoimmune diseases?

You may choose CBD isolate , broad-spectrum , or full-spectrum CBD oil. Full-spectrum CBD oil contains all the natural elements of Cannabis sativa plants. Meanwhile, CBD isolate is the pure form of cannabidiol (70) .

Make sure to consult with a physician expert in cannabis use before trying any CBD product.

Also, check a brand’s website and see if there is any product disclaimer . CBD brands need to be transparent with their consumers.

A third-party lab tests all products to determine whether they contain any heavy metals or residual solvents.

Article

Katz D 1,2 , Katz I 1,2 , Shoenfeld Y 1,3*

1 The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, Israel
2 Faculty of Medicine, The Hebrew University of Jerusalem, Israel
3 Incumbent of the Laura Schwarz-kipp chair for research of autoimmune diseases, Sackler Faculty of Medicine, Tel-Aviv University, Israel

Introduction

The tale of Cannabis sativa is as old as time. Through its first days as an herbal remedy, ranging back to 4000 BC and to Emperor Shen Nung’s Rule (2700 BC), to cannabis low point of being banned internationally at 1925 to its recent re-emergence by prof. Mechoulam isolation of the Tetrahydrocannabinol (THC, 1963), Cannabis is slowly gaining its place in medicine 1,2 .

Cannabis sativa, also known as Marijuana has been called many names, yet the variety of names given to Cannabis does not encompass the vast medical opportunities that lie within the cannabis. As of now, 545 ingredients have been identified, of which over 100 classified as unique to Cannabis 3 . The two main and most researched active ingredients are – Tetrahydrocannabinol (THC) which holds a psychoactive properties and on the other hand, Cannabidiol (CBD) which is considered non psychoactive. The components are joined by the two main known endocannabinoids – Ananamide (AEA) and 2-Arachidonoylglycerol (2-AG) (also discovered by prof. Mechoulam and colleagues) 4,5 . The other half of the cannabinoid system (as we know thus far) comprises of CB1 and CB2 receptors, G-protein coupled receptors. The two receptors differ in distribution and function. While the major psychoactive effect of cannabis is attributed to the CB1 receptor and accordingly widely distributed in neurons, while the CB2 receptor has been linked to maintaining homeostasis and commonly appears in cells of the immune system 6,7 .

Cannabis and the Brain Immune System

It is well established that murine microglial cells express both CB1 and CB2 receptors, yet the pattern of receptors expression differs in location as well as in levels of expression. While CB1 receptor is consistently expressed in microglial cells in low levels, CB2 receptor is indetectable in resting state cells and highly expressed in activated microglia 8,9 . The pattern of expression and distribution of CB2 receptor in microglial cell suggest a role in microglial migration, CB2 receptor was found to be expressed heterogeneously throughout murine microglial cells with particularly high density at the leading edges of lamellipodia and microspkies (cellular protrusions that mediate cell migration). Moreover, 2-AG, AEA and abnormal-cannabidiol increase microglial cell migration 10 .

Another aspect of the endocannabinoid system effect on microglial cell is the attenuation of the immune response induced by LPS (Lipopolysaccharide) stimulation, AEA attenuates the immediate release of IL-6 and NO by microglial cell by induction of MPK-1 11 .

A different mechanism of action is suggested by the inhibition of the IL-1 signaling pathway following administration of the synthetic cannabinoid R(+)WIN 55,212-2. Appling R(+)WIN 55,212-2 to astrocytoma cells priori stimulated by IL-1 resulted in dose dependent inhibition of ICAM-1 and VCAM-1 adhesion molecules induction, as well as IL-8 and NFκB. The effect aforementioned is independent from the cannabinoids receptors CB1 and CB2 as suggested by the lack of regulation of CB1 and CB2 antagonist on the immunomodulating effects mentioned above, implying that there is still much to learn in the field of Cannabis and immunomodulation 12 .

Cannabis and the Blood-Brain-Barrier

The blood-brain-barrier (BBB) as well as the blood-spinal cord-barrier (BSCS) and their disturbance is often postulated as a possible mechanism of pathogenesis in neurological autoimmune disease. A possible link of pathogenesis has been suggested in Multiple Sclerosis 13 , Neuromyelitis Optica1 14 , Guillain-Barré Syndrome 15 , Chronic Inflammatory Demyelinating Polyneuropathy 16 and Antiphospholipid Syndrome with neurological involvement 17 .

In murine model of LPS induced vascular and inflammatory changes CBD counteracts the effect of LPS. Mice which received LPS+CBD showed no cerebral vasodilation, no leukocyte migration, reduced TNF-α and COX-2 levels compared to LPS treated mice and more over exhibited reduced dextran extravasation (dextran extravasation is used as a quantification instrument of BBB integrity) 18 .

Similar effect is obtained by administration of Anandamide to TMEV-infected endothelial brain cell. AEA inhibits VCAM-1 induction in vitro, and thus limit leukocyte migration through a transwell filter (coated with collagen type I and fibronectin) model of the BBB. Accordingly, in vivo experiment correlated the result of the in vitro experiments. AEA increased tone (by UCM-707, an AEA uptake inhibitor) inhibited VCAM-1 induced expression, as well as attenuated microglial cell activation 19 .

A role for CB2 receptor was also exemplified by in vivo murine model. Ex vivo CB2-activted leukocytes were injected to LPS treated mice resulting in adhesion reduction of up to 96% using GP1a (CB2 receptor agonist) in comparison with to non GP1a treated mice 20 .

The beneficial effect of cannabinoid also extends to human brain endothelial cells (BMVEC). Using human cells from HIV-1 CNS infected patients and from seronegative controls, a group of researches demonstrated enhanced CB2 receptor expression in HIV infected cells compared to controls. Further investigation of naive human BMVEC revealed that the increased expression of CB2 receptor can also be accomplished separately by IL-1β, TNF-α and LPS. Once induced and activated, CB2 receptor decreased leukocyte adhesion, prevented up regulation of adhesion molecules, promoted 2.2-2.7 increase in tight junction proteins (occludin and claudin-5) and significantly reduced BBB resistance drop induced by LPS 21 .

The coherence of the above mentioned experiments is also exemplified at the genetic level. Human BMVEC isolated from eleptogenic patients were activated using TNF-α to evaluate consequent gene expression. Out of 33 genes that were up regulated by TNF-α, 31 and 32 genes were suppressed using CB2 agonist O-1966 or JWH-133 respectively 22 .

Cannabinoids protective effect goes beyond the BBB and also extends to the BSCB. Pretreatment by JHW-015, a CB2 receptor agonist prevents down regulation of occludin and ZO-1 induced by spinal cord ischemia reperfusion injury (SCII) in murine in vivo model. Moreover, JWH-015 pretreatment reduces BBB leakage (measured by Evans blue) compared to SCII only group 23 .

Cannabis potential ability to protect BBB integrity is of possible great importance, not only in autoimmune neurologic disorders, but in a vast verity of neurological fields as in Alzheimer’s disease and ischemia injury.

Cannabis and Autoimmune Demyelinating Disease

Multiple Sclerosis (MS) is known as the hallmarks of neurological autoimmune disease with prevalence as high as 200:100,000 in some countries in northern Europe 24 .

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MS Patients are characterized by high CSF levels of AEA compared to healthy control. In accordance high levels of AEA were also measured in autoimmune encephalomyelitis (EAE), a murine model of MS. Moreover, increased NAPE-PLD (part of AEA production) activity and reduced FAAH (degrades AEA) activity 25 . CB1 receptor deficient mice exhibit substantial neurodegeneration following EAE induction including higher prevalence of residual paresis and axonal pathology in relation to wild type mice 26 .

CBD treatment of TMEV infected mice induces a wide range of immunomodulatory outcomes. CBD reduce the infiltrate of immune cell to the brain parenchyma and decreased microglial activation. Moreover, CBD treatment has a long lasting effect, an 80 days follow up of the treatment group revealed restoration of both horizontal and vertical motor activities to that of the healthy mice and a correlating reduction in the expression of TNF-α and IL-β1 27 .

MS is positively influenced by a variety of cannabinoids, both natural and synthetic, each demonstrating a different mechanism of action to our knowledge. Among the different cannabinoids we can find Cannabidiol which holds the ability to attenuate a range of neuronal apoptotic pathways 28 , Cannabigerol Quinone which its application on murine neuronal culture results in inhibition of IL-1β, IL-6 and PGE2 release 29 . Also Gp1a, a selective CB2 receptor agonist that modulates EAE development by reducing Th17 differentiation 30 , HU-446 and HU-465 (CBD derivatives) and many more which we won’t elaborate on 31 .

There is scarce evidence regarding clinical use of Cannabis in MS patients. A recent Meta-analysis concluded that cannabinoids (nabilone and nabiximols) were associated with a greater average improvement in spasticity assessed by using numerical rating scale (mean difference, -0.76 [95% CI, -1.38 to -0.14]). Also, the average number of patients who reported an improvement on a global impression of change score was greater using nabiximols rather placebo (OR, 1.44 [95% CI, 1.07-1.94]) 32 . Notably, a new large multi centered blinded study was recently published, in which 489 MS patients participated and received either oral dronabinol (THC) or placebo. The study failed to prove the beneficial outcome of dronabinol use in two main outcomes (time to confirmed EDSS [Extended Disability Status Scale] score progression and change in MSIS-29 [Multiple Sclerosis Impact Scale-29] score). However, while taking into consideration the results of this trail, it is worth mentioning a possible weakness in the trail inclusion criteria. The disease progression in MS as measured by the EDSS scale is not linear, and progression through EDSS 4-5.5 is faster the in EDSS 6-6.6. hus making the EDSS 6+ patient’s population insensitive to treatment during the study period of time, leaving the question of Cannabis medical use in MS patients in need of further research 33,34 . Currently, evidenced based recommendation published in 2014 by the American academy of neurology are: oral cannabis extracts (CBD/THC or CBD alone) are the only products with an A – effective rating, next in line is THC (dronabinol/nabilone) with B rating- probably effective 35 .

Another demyelinating autoimmune disease that shows promise for cannabis treatment is Neuromyelitis Optica (NMO). Plasma levels of 2-AG were found to be elevated in NMO patients compared to healthy patients. Moreover, 2-AG levels were negatively correlated with pain sensitivity, while AEA correlated positively with pain sensitivity 36 .

Multiple Sclerosis and Neuromyelitis Optica are the milestones of medical cannabis implantation in neurologic autoimmune disease, yet only the foundation has been accomplished up to now and further clinical investigation is the core of establishing Cannabis Sativa and its products as a new therapeutic solution.

Cannabis Adverse Effects

Cannabis addiction is one of the main adverse effects of chronic cannabis use, though once considered as only “psychological addiction”, recent evidence revels a physiological ingredient to the addiction 37 . Epidemiological studies indicate that about 9% of adult marijuana users will develop cannabis addiction, while adolescent’s percentages of addiction is as high as 17% 38 .

Another adverse effect of great importance lurking chronic cannabis users is the consequence anatomical changes, a 2013 meta-analysis concluded that chronic cannabis consumption results in reduction of hippocampal grey mater 39 . Accordingly a new research conducted at 2015 demonstrated reduced hippocampus and amygdala volumes 40 .

Acute adverse effects (some may be found beneficial in some indications) include anxiety, dysphoria, psychosis/hallucinations, tachycardia, and stimulation of appetite 39 . Further side effects are listed in table 1.

System Adverse Effect Statistics a References
Neurologic ↓hippocampus & amygdala volumes
↑ Incidence of acute ischemic stroke
Age 15-54
Age 25 -34
Age 45 – 54
Drowsiness
Dizziness
↓Educational performance (adolescents)
Lower IQ
RR 1.13 (1.11-1.15)*
RR 2.26 (2.14 – 2.38)*
RR 1.45 (1.42 – 1.54)*
OR 3.68 (2.24-6.01)*
OR 5.09 (4.10-6.32)*
↓11% (% GCSE† points)*
Linear trend, t test
t: -3.36***
32,40-43
Psychiatric Psychosis Schizophrenia
Anxiety
Depression
OR 1.41 (1.20–1.65)*
OR 1.9 (1.1–3.1)*
OR 1.98 (0.73-5.35)*
OR 1.49 (1.15–1.94)*
32,44,45
Cardiovascular Tachyarrhythmia
Palpitation
Angina
RR 1.5 (1.1–2.1)*
↓ 48% (↓time to, during exercise)**
38,46,47
Pulmonary (cannabis smoking) Chronic Bronchitis symptoms
↑health services for respiratory infections
25%-33% of smokers 46,48
Gastrointestinal Nausea
Diarrhea
Vomiting
Abdominal pain
Constipation
OR 2.08 (1.63-2.65)*
OR 1.65 (1.04-2.62)*
OR 1.67 (1.13-2.47)*
32, 49,50
General Dry mouth OR 3.50 (2.58-4.75)* 38
Cannabis dependence
Withdrawal syndrome
Adults, Adolescents
Anxiety
Insomnia
Appetite disturbance
Depression
Irritability
9%, 17% (percentage of users who will
become addicted)
38
51
Pregnancy Maternal anemia
Decrease birth weight
↑Intensive care unit
pOR 1.36 (1.1 – 1.69)*
pOR 1.77 (1.04 – 3.01)*
pOR 2.02 (1.27 – 3.21)*
52

Table 3: Perfusion analysis from 1H-NMR in 12-month-old female mdx mice.

Reperfusion mean has been calculated during the first 25 minutes after release of ischemia. Wild-type mice, n=6; mdx mice, n=7. **p < 0.01.

(a)The set-up of the tourniquet was sufficient to induce an absence of perfusion in both groups. After release of tourniquet, a rapid and important increase of perfusion was detected and the reperfusion of mdx mice was greater than wild-type mice. A single peak of reperfusion was however observed in mdxmice, when a first rapid and strong peak followed by a second attenuated peak of reperfusion was observed in wild-type animals.
Because the release of ischemia induced movements of the leg, images affected by these movement artifacts, at the moment of ischemia release, were removed from analysis of muscle perfusion.

(b) In the first 5 minutes after ischemic stress release, below a threshold of 250 mL/100 g reperfusion (concerning mostly wt mice), PCr resynthesis rate was dependent on perfusion, an increase in reperfusion leading to a decrease of τPCr. In contrast, above the threshold of 250 mL/100 g reperfusion (concerning mostly mdx mice), PCr resynthesis rate was poorly affected by the increase of post-ischemia reperfusion.

a: Perfusion analysis was performed through from 1H-NMR as described in the Material and Methods section; b: Correlation between reperfusion and PCr resynthesis rate (from 31P-spectroscopy analysis) during the first 300 seconds (5 minutes) after ischemia; n = 6 (wt, a, b); n = 7 (mdx, a, b); τPCr: time of creatine rephosphorylation.

Conclusion

Nowadays Cannabis tends to be considered as a “buzz word”, with global recognition of the potential embodied in medical Cannabis, more and more countries legalize the use of medical cannabis, leaving many physicians overwhelmed due to the rapid changes. In this article we aimed to review the laboratory and clinical evidence regarding Medical Cannabis and neurological autoimmunity diseases.

Unfortunately, lack of clinical data prevents a definitive conclusion. Nonetheless, clinical trials conducted upon MS and NMO patients suggests a future role for medical cannabis in MS and NMO treatment by obtaining relief in patient symptoms. Yet, the trails aforementioned only paves the beginning, much research is yet to be done in order to evaluate the therapeutic effects of cannabis in treating autoimmune neurologic diseases versus.

Unfortunately, lack of clinical data prevents a definitive conclusion. Nonetheless, clinical trials conducted upon MS and NMO patients suggests a future role for medical cannabis in MS and NMO treatment by obtaining relief in patient symptoms. Yet, the trails aforementioned only paves the beginning, much research is yet to be done in order to evaluate the therapeutic effects of cannabis in treating autoimmune neurologic diseases versus.

Another promising aspect is cannabis protective effect on the BBB, having great potential not only in the field of autoimmunity but also in a variety of other pathologies with attributed BBB damage pathogenesis. The field of cannabis immunomodulation and BBB protection is an exciting new medical pathway, but only further research is to say what will be Cannabis sativa place in medical history.

Abbreviations

THC : Tetrahydrocannabiol; CBD : Cannabidiol; AEA : Ananamide; 2-AG : 2-Arachidonoylglcerol; LPS : Lipopolysaccharide; IL-6 : Interleukin 6; NO : Nitric oxide; MPK-1 : Mitogen-activated protein kinase 1; IL-1 : Interleukin 1; ICAM-1 : Intercellular Adhesion Molecule 1; VCAM-1 : vascular cell adhesion molecule 1; IL-8 : Interleukin 8; NFκB : Nuclear factor kappa-light-chain-enhancer of activated B cells; BBB : Blood – brain – barrier; BSCB : Blood – spinal cord – barrier; TNF-α : Tumor necrosis factor α; COX-2 : Cyclooxygenase-2; TMEV : Theiler’s Murine Encephalomyelitis Virus.

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