Study to Evaluate the Safety, Tolerability and Efficacy of Cannabidiol (CBD) as a Steroid-sparing Therapy in Chronic Spontaneous Urticaria (CSU) Patients
Study to Evaluate the Safety, Tolerability and Efficacy of Cannabidiol (CBD) as a Steroid-sparing Therapy in Chronic Spontaneous Urticaria (CSU) Patients
Each patient will commence the study with a one month run-in period in which he/she will be
 administered individual patient Standard of Care :anti-histamines and steroids as needed plus
 placebo (olive oil).

 After the run-in period, doses of CBD will be incresed during the first six weeks of the
 study.

 At the conclusion of the six weeks CBD dose escalation segment of the study, if the 300 mg
 CBD dose level is deemed safe for two weeks with standard of care doses of anti-histamines,
 patients will continue receiving 300 mg CBD with Anti-histamines as needed for an additional
 follow-up period of three month.

 Each patient will serve as his/her own control.
Each patient will commence the study with a one month run-in period in which he/she will be
 administered individual patient Standard of Care :anti-histamines and steroids as needed plus
 placebo (olive oil).

 At the end of the one month run-in period, all trial subjects will continue on individual
 Standard of Care plus increasing doses of CBD during the first six weeks of the study. Dosage
 of CBD will start at 25 mg twice daily and will be increased once every 14 days, if no side
 effects are observed, to 50 mg twice a day, 100 mg twice a day and finally to 150 mg twice a
 day CBD respectively. Treatment will be given with food.

 At the conclusion of the six weeks CBD dose escalation segment of the study, if the 300 mg
 CBD dose level is deemed safe for two weeks with standard of care doses of anti-histamines,
 patients will continue receiving 300 mg CBD with Anti-histamines as needed for an additional
 follow-up period of three months. In the case of flare, the patient will be treated with
 higher dose of Anti-histamines and Steroides if needed in addition to CBD. Once the flare has
 been brought under control, then another attempt will be made to discontinue the steroids and
 continue treating with CBD + Anti-histamines only. Each patient will serve as his/her own
 control.

 Laboratory studies will be carried out at the beginning of the study (baseline), and then on
 a monthly basis until the end of the study.

 Adverse events will be continuously assessed throughout the study
Inclusion Criteria:

 -  Patients with active CSU for at least 4 months which was treated with anti-histamines
 as well as at least one course of steroids (ex. Prednisone)

 -  Age ≥18 years

 -  Patients will undergo an ECG and QT parameters will be measured for further analysis.

 -  Female subjects who are postmenopausal (absence of menses for ≥ 2 years confirmed by a
 follicle stimulating hormone test), or who are surgically sterilized may be enrolled.
 Similarly, women of childbearing potential who had a negative pregnancy test at
 screening, who are willing to use two medically acceptable methods of contraception
 for the duration of the study as well as for at least three months after cessation of
 CBD treatment and who are willing to undergo pregnancy testing according to the study
 protocol may be enrolled.

 -  Female subjects who are not breast-feeding and who have no intention to breast-feed
 during the term of the trial and for at least three months after cessation of CBD
 treatment may be enrolled.

 -  Subject able to provide written informed consent

 Exclusion Criteria:

 -  Viral Hepatitis (HAV, HBV, HCV)

 -  HIV

 -  Serious psychiatric or psychological disorders

 -  Other chronic dermatological conditions under active treatment

 -  Active consumption of illicit drugs including cannabis or derivatives for at least
 three months prior to the study

 -  Patients with significant cardiac, respiratory or active malignance disease (except
 Basel Cell Carcinoma) comorbidities.

 -  Any uncontrolled infection at time of registration

 -  Renal comorbidity: eGFR < 30 mL/min/1.73m2 (note: CKD Grade 4 is defined as eGFR 15-29
 mL/min/1.73 m2)

 -  Patient who is taking immunomodulatory medications for other indication

 -  Women of child-bearing potential who intend to become pregnant or who are pregnant or
 breastfeeding