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.
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].
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.
Viral hepatitis B (HBV) and hepatitis C (HCV) pose a major health problem globally and if untreated, both viruses lead to severe liver damage resulting in liver cirrhosis and cancer. While HBV has a vaccine, HCV has none at the moment. The risk of drug resistance, combined with the high cost of current therapies, makes it a necessity for cost-effective therapeutics to be discovered and developed. The recent surge in interest in Medical Cannabis has led to interest in evaluating and validating the therapeutic potentials of Cannabis and its metabolites against various diseases including viruses. Preliminary screening of cannabidiol (CBD) revealed that CBD is active against HCV but not against HBV in vitro. CBD inhibited HCV replication by 86.4% at a single concentration of 10 μM with EC50 of 3.163 μM in a dose-response assay. These findings suggest that CBD could be further developed and used therapeutically against HCV.
Conflict of interest statement
Summary: Cannabidiol exhibited in vitro activity against viral hepatitis C. Abbreviations Used: CB2: Cannabis receptor 2, CBD: Cannabidiol, DNA: Deoxyribonucleic acid, HBV: Hepatitis B virus, HCV: Hepatitis C virus, HIV/AIDS: Human immunodeficiency virus/acquired immune deficiency syndrome, HSC: Hepatic stellate cells, MTS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, PCR: Polymerase chain reaction.
Keywords: Cannabis; cannabidiol; hemp; hepatitis B; hepatitis C.
The anti-HBV assay was performed as previously described[17,18] with modifications to use in real time quantitative polymerase chain reaction (PCR) (TaqMan) to measure extracellular HBV DNA copy number associated with virions released from HepG2 2.2.15 cells. The HepG2 2.2.15 cell line is a stable cell line producing high levels of the wild-type ayw1 strain of HBV. Antiviral compounds blocking any later step of viral replication such as transcription, translation, pregenome encapsidation, reverse transcription, particle assembly, and release can be identified and characterized using this cell line.
The bioactivity of CBD against HBV and HCV is shown in Tables Tables1 1 and and2. 2 . CBD inhibited HCV replication by 86.4% at a single concentration of 10 µM. The compound was not active against the HBV virus in vitro but exhibited a significant cytotoxicity against HepG2 2.2.15 cells which were used to culture the virus. In the HCV assay, CBD inhibited the virus with minimal toxicity against the Huh7.5 cells that were used to culture the virus. Lamivudine and interferon alpha were used as positive controls against HBV and HCV, respectively, and they significantly inhibited viral replication at the single-dose assay. CBD was found to exhibit a dose-dependent inhibition of the HCV virus in the dose-response assay [ Table 2 ].
Chemical structure of cannabidiol
Anti-hepatitis C assay
Abbreviations Used: CB2: Cannabis receptor 2, CBD: Cannabidiol, DNA: Deoxyribonucleic acid, HBV: Hepatitis B virus, HCV: Hepatitis C virus, HIV/AIDS: Human immunodeficiency virus/acquired immune deficiency syndrome, HSC: Hepatic stellate cells, MTS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, PCR: Polymerase chain reaction
In brief, HepG2 2.2.15 cells are plated in 96-well microtiter plates. Only the interior wells were utilized to reduce “edge effects” observed during cell culture; the exterior wells were filled with complete medium to help minimize sample evaporation. After incubation with 5% CO2 atmosphere at 37°C for 16–24 h, the confluent monolayer of HepG2 2.2.15 cells was washed and the medium was replaced with complete medium containing test compounds at a single concentration of 10 µM. Three days later, the culture medium was replaced with fresh medium and test compounds at a single concentration of 10 µM. Six days following the initial administration of the test compounds, the cell culture supernatant was collected, treated with pronase and DNAse, and then used in a real-time quantitative TaqMan PCR assay. Antiviral activity was determined by calculating the reduction in HBV DNA levels compared to untreated virus control samples. Compound cytotoxicity was determined using MTS (CellTiter 96 Reagent, Promega) to measure cell viability as described above.
RESULTS AND DISCUSSIONS
Experiments were carried out in duplicate, and results were given as the mean of the two experiments. The data in all the experiments were analyzed using Microsoft Excel.
Viral hepatitis is caused by a group of viruses divided into five types (A, B, C, D, and E), and they are primarily known to attach to the liver. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most dangerous and prevalent of the five virus types.[2,3] Chronic cases of HBV as well as HCV are among the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC) in the world. HBV and HCV infections are also implicated in the development of other diseases including lymphoma, diabetes, and atherosclerosis.[5,6] HBV is the most prevalent type worldwide and the leading cause of HCC in some countries, especially in Asia. Despite the fact that great strides have been made in the treatment and prevention of HBV and HCV, the global burden remains a major health problem. There is as such a great need to continue to search for new molecules with activity against hepatitis viruses.