Cannabidiol (CBD) Consumption and Perceived Impact on Extrahepatic Symptoms in Patients with Autoimmune Hepatitis
Utilization and safety of cannabidiol (CBD) in patients with autoimmune hepatitis (AIH) are currently unknown. We aimed to identify the frequency of CBD use, impact on symptoms, and safety profile.
An invitation to complete a CBD-specific questionnaire was posted every other day to well-established autoimmune hepatitis Facebook communities (combined membership of 2600 individuals) during a 10-day study period. Age ≥ 18 years and an AIH diagnosis by a physician were the eligibility criteria for participation in the survey.
In total, 371 AIH patients (median age 49 years, 32% reported advanced fibrosis) completed the questionnaire. Respondents were 91% women, 89% Caucasian, and 89% from North America. Ninety-three (25%) respondents were ever CBD users, with 55 of them (15% of the survey responders) identified as current users. Among ever users, 45.7% reported their treating doctors were aware of their CBD use. The most common reason cited for CBD use was pain (68%), poor sleep (62%), and fatigue (38%). Most respondents using CBD for these symptoms reported a significant improvement in pain (82%), sleep (87%), and fatigue (61%). In ever CBD users, 17.3% were able to stop a prescription medication because of CBD use: pain medication (47%), immunosuppression (24%), and sleep aids (12%). Side effects attributed to CBD use were reported in 3% of CBD users, yet there were no reported emergency department visits or hospitalizations.
CBD use was not uncommon in patients with AIH, and its use was associated with reports of improvement in extrahepatic symptoms.
Autoimmune hepatitis (AIH) is a chronic liver disorder in which clinical presentation can vary widely from non-specific extrahepatic symptoms to fulminant hepatic failure . Immunosuppressive therapy is the mainstay of treatment for AIH  and has been associated with improvement in symptoms, liver biochemistries, and histologic inflammation . Unfortunately, impairment of emotional and mental health is prevalent in AIH and can diminish the health-related quality of life in these patients [4, 5]. The etiology of this phenomenon remains unclear, yet may be linked to common AIH symptoms such as pain, fatigue, and sleep disturbances [6, 7].
Complementary and alternative medical strategies have become a popular approach for patients with chronic diseases  and often are utilized to target pain, anxiety, and depression . Cannabidiol (CBD), one of the more than 110 different cannabinoids that have been isolated by researchers from Cannabis Sativa plant, is more commonly known as marijuana. However, CBD does not cause intoxication or euphoria (the “high”) that comes from tetrahydrocannabinol (THC), the psychoactive cannabinoid. CBD has received lot of recent attention after Food & Drug Administration’s (FDA) approval of purified CBD, Epidiolex, as treatment for two rare forms of epilepsy . Utilization of CBD outside this indication for a variety of symptoms such as pain, glaucoma, anxiety has had mixed reviews and is not recognized by the FDA as an ailment that CBD can treat [11, 12]. Furthermore, there is a shift in legal status after the 2018 Farm Bill allowing for expanded cultivation of industrial hemp and permission for the transfer of hemp-derived products across state lines for commercial or other purposes. Removal of hemp-derived products from Schedule 1 status has led to an explosion of CBD-related products to be available legally in some states. However, adding CBD, regardless of its extraction source, to food, beverages, and dietary supplements, is currently not permitted by the FDA.
Research in a rare disease is challenging due to limited access to patients. However, patients with rare disease are increasingly colocated virtually online through social media outlets such as Facebook, Instagram or through traditional Web sites that promote peer-to-peer connections (www.patientslikeme.com) or nonprofit organizations dedicated to their disease . Our group in the past has successfully leveraged social media to conduct research in online cohorts of autoimmune hepatitis by deploying surveys that even included confirmation of diagnosis by procuring medical records and biosamples [14, 15]. In the current study, we aimed to identify the frequency of CBD use in AIH patients and assess the impact on symptoms and safety profile using two large AIH-specific social media groups.
We conducted a cross-sectional survey study using AIH social media communities on Facebook (www.facebook.com): Autoimmune Hepatitis Research Network and Autoimmune Hepatitis Association. We have previously described this approach for collecting patient-reported disease attributes  as well as recruitment to an ongoing AIH biorepository at Indiana University . At the time of the survey, the combined membership of these online communities was over 2600. An online invitation to participate in a research study collecting information on CBD use was posted on these groups every other day for 10 days (October 2018). The survey included a link directed to an IRB-approved Redcap database for data collection.
The questionnaire was composed of 33 questions (Supplementary Table 1) assessing participant demographics, AIH disease characteristics, history of and current CBD use, and adverse effects. Participants were required to be aged ≥ 18 years and have previously received a diagnosis of AIH from a medical doctor.
Survey data were analyzed using SPSS 25 software. Continuous variables were summarized as median and the 25th and 75th percentiles, and p values were obtained with the Wilcoxon rank-sum test.
A total of 371 participants with AIH completed the questionnaire during the study period. The group was predominantly female (91.4%) and Caucasian (88.9%) and had a median age of 49 years at survey completion (Table 1). The median age of AIH diagnosis was 42 years. Of the 319 patients who reported having liver biopsy completed, 34.5% had early fibrosis, 32.1% had advanced fibrosis, and 34% did not know the stage of fibrosis reported on most recent biopsy.
Immunosuppressant Therapy for AIH
At the time of the survey, 88.1% of patients were on immunosuppressive medications: 35.2% on prednisone, 12.4% on budesonide, 52.3% on azathioprine (AZA), 6.5% on 6-mercaptopurine (6-MP), 13.2% on mycophenolate mofetil (MMF), 4.6% on tacrolimus, 0.8% on sirolimus, 1.1% on cyclosporine (CSA), and 12.4% on ursodeoxycholic acid (UDCA). In total, 198 participants (53.4%) were on at least on one immunosuppressant, and 129 (34.8%) were on more than one. There were 118 participants (31.8%) on two immunosuppressants, 10 (2.7%) on three, and 1 (0.3%) on four. Among participants taking more than two immunosuppressants, 99 (76.7%) were taking a combination of steroid and a thiopurine (AZA or 6-MP), 25 (19.3%) a combination of steroid and MMF. Only 12 patients were taking more than one immunosuppressant beyond steroids: 4 (33.3%) on tacrolimus and MMF, 4 (33.3%) on tacrolimus and AZA, 1 (8.3%) tacrolimus and AZA and sirolimus, 2 (16.7%) CSA and AZA, and 1 (8.3%) CSA and MMF.
There were 44 participants (11.9%) not on immunosuppression at the time of the survey, of these, and 35 (79.5%) had been treated previously with immunosuppression. Among all participants, former immunosuppression regimens had included prednisone (224, 60.4%), budesonide (56, 15.1%), AZA (117, 31.5%), 6-MP 14 (3.8%), MMF 32 (8.6%), tacrolimus 10 (2.7%), sirolimus 2 (0.5%), and CSA 9 (2.4%).
In total, 93 (25.1%) patients reported they had ever used CBD for the treatment of AIH or its perceived symptoms (Fig. 1). Ever CBD users were similar to never CBD users; however, ever users tended to be female (p < 0.09) and have lower household incomes (p < 0.07) (Table 2). Ever CBD users were also more likely not to be taking any other therapy for the treatment of AIH (12.9% vs. 6%, p = 0.035). In total, 278 (74.9%) participants reported they never used CBD because of high cost (18.3%) or they never heard of it (17.6%), but also worried about positive drug screening (10.4%), local laws (9.7%), side effects (4.7%), effectiveness (3.2%), and moral or religious issues (3.2%). Knowledge about CBD use was attributed to information from social media (78.5%), family/friends (69.9%), other patients (24.7%), doctors (20.4%), and other media (19.4%).
Survey completion and CBD use among AIH patients
Among ever CBD users, 55 (59%) were current users for the treatment of AIH and 38 (41%) were prior users. Among ever users, 45.7% reported their treating doctors were aware of their CBD use at the time of use. The most frequent AIH symptoms treated by participants with CBD were poor sleep (66.7%), pain (66.7%), fatigue (44.1%), “liver inflammation” (29%), and itch (10.8%). Survey participants reported CBD used resulted in significant improvement in sleep (54/59, 93%), pain (55/63, 87.3%), fatigue (25/38, 65.8%), “liver inflammation” (27/32, 84.4%), and itch (7/8, 87.5%). Seventeen (18.3%) ever CBD users reported they were able to stop or reduce a prescription medication because of CBD use. Drug classes reduced or stopped included pain (11/17; 5 narcotics, 4 NSAIDs, two other), immunosuppressants (4/17; 3 steroids, 1 AZA), anxiolytics (3/17; 2 lorazepam, one diazepam), antidepressants (1/17; sertraline), and sedatives (1/17; zolpidem).
CBD was administered most frequently via sublingual drops (55.9%), oral capsule (32.3%), inhalation (28%), and topically (12.9%). Only a minority of participants reported characteristics of CBD dose (29%). Among reported dosing information, the median dose was 20 mg (5 mg, 200 mg), the median daily frequency was 1 (1, 2), and total daily dose was 25.5 mg (4.8 mg, 87.5 mg). The median duration of CBD use among current CBD users was 3.5 months (1, 6) and was significantly more than prior CBD users (1 month (1, 3), p = 0.007). The most common cause for stopping CBD was cost (50%), worry about positive drug test (10.5%), side effects (10.5%), ineffective (7.9%), the doctor advised against CBD (7.9%), and change in the law (7.1%). There was no difference in the various demographics and medication usage between ever CBD users in either of the histology groups (Table 3).
Serious side effects attributed to CBD therapy were reported by three participants (3.2%) and included: hunger (1), dry mouth (1), red eyes (1), euphoria (1), and itchiness (1). Two participants reported side effects were significant enough to seek their doctor’s advice, but there were no emergency room visits or hospitalizations reported.
CBD has been used to treat various symptoms in the gastroenterology field with variable outcomes [17,18,19,20], yet its use among patients with chronic liver disease remains unknown . In the current study, we observed that 25% of study participants reported ever CBD use directed at the most frequent AIH-related extrahepatic symptoms: pain, sleep, and fatigue. Females and those with lower household incomes were more likely to have used CBD, yet many patients reported their treating doctor was unaware of their use. A majority of ever CBD users saw significant improvement in targeted symptoms with CBD use and very few experienced severe side effects.
The FDA, when supported by rigorous scientific research, has endorsed medical use of marijuana-derived products as drugs for the treatment of disease. Extrapolating the approval of a purified CBD derived from marijuana for a seizure disorder to hemp-derived use of CBD to treat a variety of symptoms can be serious, unproven, risky, and dangerous. Furthermore, in the Epidiolex-treated patients in the clinical trials, sleepiness, sedation, and lethargy; elevated liver enzymes; decreased appetite; diarrhea; rash; fatigue, malaise and weakness, insomnia, sleep disorder, and poor quality sleep; and infections were reported. Therefore, the CBD use among the patients with AIH as evidenced by the survey respondents is concerning. The usage varied equally among the age groups and liver fibrosis staging suggesting no rationale or vulnerability of specific demographics or disease phenotype from illegal marketing. Depending on the percentage of THC in a product and frequency of use, a positive urine drug screen for cannabinoids is possible. This observation could pose a significant hindrance for patients undergoing liver transplant evaluation for end-stage liver disease associated with AIH.
CBD, a potent inhibitor of CYP3A4 and CYP2C19, can target a variety of channels and receptors including human TRP and voltage-gated channels, serotonin receptors 5-HT1A and 5-HT2A, and G-coupled protein and adenosine receptors . Data on drug interactions in human subjects taking CBD are scarce; however, we hypothesize that there is risk of altered pharmacokinetics in CBD or concurrently administered drugs undergoing metabolism via these CYP systems. The steroid drug class and calcineurin inhibitors , metabolized via CYP3A4, are of significant concern given 177 patients (47.7%) of study respondents reported current use of either prednisone or budesonide and 21 patients (5.7%) reported use of either tacrolimus or cyclosporine. The relative infrequency that patients did not report CBD use to their treating doctors (45.7%) and product variability across manufacturers [23, 24], dose , and route  of administration could further expand this risk.
No published data encapsulate CBD use across populations, yet the frequency of CBD use reported in our study is similar to that observed among adults with liver disease in the USA using other complementary and alternative medicines . Health-related quality of life in AIH is significantly reduced [27, 28]; thus, the use of CBD by patients to mitigate symptoms attributed to AIH outside the liver is not surprising. A majority of patients reported significant improvement in AIH-related indications for use (pain, poor sleep, fatigue, and itch) which included very few serious side effects. Other data about the improvement in these symptoms and safety profiles within other CBD-treated populations are unavailable, but our observations are congruent with a meta-analysis that assessed all cannabinoids for medical use .
We readily admit the possible limitation of patient-reported disease and CBD use data in this study. Historically, we have shown that AIH patients participating in similar research approaches exhibit excellent diagnosis agreement when compared to their medical records  as well as similar demographics and disease attributes . However, we also believe there are tremendous benefits to treating physicians and patients allowed by rapid recruitment and dissemination of research regarding emerging and popular healthcare trends . Furthermore, the anonymity offered through social media may allow for unbiased answers for a sensitive topic such as CBD use. CBD has been recently showing up in everything from beauty creams and bath bombs to vape pens, seltzer, and snacks; thus, our survey may underestimate total CBD use among patients. Furthermore, attribution of all reported extrahepatic symptom improvement to CBD use in our study is inappropriate, as we did not collect other interventions or exposures (marijuana, other over the counter supplements, meditation, etc.) that may have been completed concurrently with CBD.
In summary, CBD use in our online cohort was common and associated with a significant improvement in AIH-related symptoms and side effects of immunosuppressant medications. The overall positive therapeutic benefits from this study as well as the observation of few serious side effects would be supportive of future trials (possibly with cannabinoids) aimed at improving health-related quality of life in AIH patients. Strict regulation of product formulation and dose and well as further examination of CBD pharmacokinetics would help alleviate safety concerns in patients taking a wide variety of pharmaceuticals.
Heneghan MA, Yeoman AD, Verma S, et al. Autoimmune hepatitis. Lancet. 2013;382:1433–1444.
Cbd oil hemp vs canabias for auto immune
Cannabidiol (CBD) is a naturally occurring compound found in the resinous flower of cannabis, and it is one of more than a hundred cannabinoids found in Cannabis sativa, a plant more well-known colloquially as “marijuana” or hemp. CBD is closely related to tetrahydrocannabinol (THC), which is the psychoactive component of the plant, yet it is safe, non-addictive. Marijuana/ cannabis has been used as a pain reliever for over 5000 years!
So what is the “buzz” all about? CBD is a non-intoxicating component of the cannabis plant thought to have enormous therapeutic POTENTIAL. CBD has been studied in numerous conditions from autoimmune diseases to skin disease to GI disorders, and it may provide relief for chronic pain, anxiety, inflammation, depression and PTSD. CBD works by mimicking and augmenting the effects of the compounds in our bodies called “endocannabinoids”, and as the endocannabinoid system is dysregulated in nearly all pathological conditions, it must stand to reason that modulating endocannabinoid system activity should have therapeutic potential in almost all diseases affecting humans.
Does CBD work? Show me the data!!
The data on the efficacy of CBD is fair at best and mostly inconclusive. A 2015 meta-analysis that appeared in JAMA (link: “Cannabinoids for Medical Use”) found moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. Patients had improvements in their symptoms, but meaningful statistical significance was lacking. A 2019 meta-analysis from the Cochrane Library (link: “Cannabis-based medicines for chronic neuropathic pain in adults”) stated that there was no high‐quality evidence for the efficacy of any cannabis‐based product including herbal cannabis (marijuana) in any condition with chronic neuropathic pain.
So in the absence of any real substantive data, there are only 3 things you can tell patients with certainty about CBD oil. One, if they are going to try CBD oil, they should purchase a product that is 100% CBD oil. Many products bought in gas stations or natural food stores are likely “cut” with coconut oil and flavorings. Patients should look for a “full spectrum” CBD oil, which means the oil contains a “full spectrum” or all of the naturally occurring cannabinoids and terpenes of the cannabis plant; it is thought (but not proven) that all of the cannabinoids work synergistically to improve efficacy. A “pure” CBD oil extract is devoid of these additional cannabinoids as they have been burned off due to the higher temperatures used to produce “pure” CBD oil.
Two, hemp oil is not the same as CBD oil. Many products (particularly the creams) may call themselves “hemp cream” but patients should look for CBD on the label if one even exists. If the ingredients are hard to decipher, patients should not buy that product!
Three is dosing. For most conditions, patients should take 24 mg of CBD twice a day for the first month, and then 24 mg once a day for the following months. If taken for sleep, then once at night is appropriate. 24mg is about 10 drops of high quality (“full spectrum”) CBD oil “sloshed” under the tongue.
Two final words of caution: CBD products are like the wild west. It is buyer beware. If patients are willing to try them, then they should put themselves into the best product possible. Lastly, both coumadin and CBD are metabolized the hepatic P450 system, and CBD can compete with coumadin metabolism at the receptor level thus decreasing coumadin metabolism. Patients taking both coumadin and CBD should have their levels checked and medication adjusted if necessary.
What You Need to Know about CBD Oil in Colorado
Cannabidiol (CBD) oil has recently gained popularity nationwide due to reported therapeutic effects for both common ailments and severe illness. CBD is not psychoactive and does not get users “high,” so many Americans have embraced it.
Despite these benefits, CBD is not yet legal in all 50 states. Worse, new legislation passed in December 2016 made CBD and other marijuana extracts federally illegal.
What does this mean for Coloradans?
Fortunately, CBD oil is derived from cannabis. Since Colorado enjoys some of the most progressive cannabis laws in the country, CBD is fully legal here.
Below we’re going to cover CBD oil basics, the health benefits of CBD oil, the legality of CBD oil, and how to find quality CBD oil in Colorado.
What Exactly Is CBD Oil?
The cannabis plant contains over 100 bioactive compounds, collectively known as cannabinoids. Among the cannabinoids, the best-known compounds are tetrahydrocannabinol (THC) and cannabidiol (CBD).
THC is psychoactive, and has euphoric effects that get users “high.” However, THC alone is not as effective as whole-plant extracts in treating most health conditions that can be alleviated by cannabis. This suggests that other cannabinoids may be responsible for the therapeutic effects of marijuana.
CBD, as mentioned above, is not psychoactive, and does not give users high. Further, CBD has been found to be as effective as whole-plant extracts at treating a variety of illnesses, suggesting that CBD is responsible for many of marijuana’s therapeutic effects.
Because many modern marijuana strains have been selectively bred to produce high levels of THC and relatively low levels of CBD, you may find more therapeutic benefit from CBD oil, or from high-CBD marijuana strains.
How Can CBD Oil Benefit Coloradans
CBD oil is a potent anti-inflammatory, and has been used successfully to treat a wide variety of inflammatory diseases such as autoimmune disease, arthritis, diabetes, diabetic complications, and acne.
CBD oil also has beneficial effects in mental health disorders such as anxiety, depression, insomnia, and psychosis. Moreover, it is not addictive, unlike many pharmaceuticals used to treat psychiatric conditions, such as benzodiazepines.
Some studies suggest that CBD oil may have anti-cancer effects, although these studies need to be further verified. However, it is well-accepted that CBD oil reduces symptoms related to cancer, and side effects related to cancer treatment such as nausea and vomiting. CBD oil also alleviates muscle wasting.
Additionally, CBD oil activates the brain’s endocannabinoid system and other signaling pathways that are related to neuroprotection. It has been used to successfully treat neurodegenerative disease and other neurological disorders such as epilepsy.
Finally, many users report that CBD oil is an effective remedy for common ailments such as insomnia and moderate pain.
Hemp versus Marijuana-Derived CBD Oil
CBD oil can be derived from the marijuana plant, or from the hemp plant, which is closely related to marijuana but does not produce THC. Although the composition of hemp versus marijuana-derived CBD oil is theoretically the same, the legality of CBD oil differs based on the source.
Fortunately, in Colorado that doesn’t matter because recreational marijuana is legal, meaning that both hemp and marijuana-derived CBD oil are fully legal. However, in most states only hemp-derived CBD oil is legal. It is something to remember if you buy in Colorado and plan to travel to other states.
Importantly, hemp is an industrial crop, and is cultivated to produce products such as fibers. Therefore, hemp is not as well-regulated as marijuana, which is intended for human consumption.
As you can probably tell from all of this, the legality of CBD oil is complex. Moreover, the production of CBD oil is often not regulated, meaning that consumers may not be getting actual CBD oil, and that commercially available CBD oil preparations could potentially contain dangerous contaminants.
How to Find Quality CBD Oil in Colorado
Since Colorado has legalized recreational marijuana purchased from licensed dispensaries, you may obtain CBD oil legally in the state of Colorado, regardless of the source. However, getting high-quality CBD oil here is not as easy as you might think.
Generally speaking, it’s best to obtain CBD oil from a dispensary. Hemp-derived CBD oil available in smoke shops and gas stations is not as well-regulated as the marijuana-derived oil sold in dispensaries. Moreover, dispensaries are required to test each batch of products sold, meaning that you’ll know exactly how much CBD you’re getting, and be able to verify that the product contains no psychoactive THC.
Not all dispensaries carry CBD-only products, however, as the psychoactive THC products tend to be more popular. You’ll therefore need to do some research to identify which dispensaries carry CBD products. Further, availability may vary from day to day, so you’re best off calling or checking the website for updated availability before you go.
About the Author:
Denver-based criminal defense and DUI attorney Jacob E. Martinez is a knowledgeable and experienced litigator with a record of success providing innovative solutions to clients facing criminal charges of any severity. Mr. Martinez has been designated a Top 100 Trial Lawyer by the National Trial Lawyers and has been awarded both the Avvo Client’s Choice Award and Avvo Top Attorney designation, evidencing his reputation for his exemplary criminal and DUI defense work and high moral standards.