The aim of this work is to conduct a randomized, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of cannabidiol (CBD - 300 mg a day) in patients infected with SARS-CoV-2. The specific objectives are to assess whether, in patients with mild and moderate forms of SARS-CoV-2, daily use of CBD 300 mg for fourteen days is capable of: i) decrease viral load; ii) modify inflammatory parameters, such as cytokines, measured from serum; iii) reduce clinical and emotional symptoms through daily clinical evaluation; iv) improve sleep; v) reduce hospitalization and worsen the severity of the disease; v) Monitor the possible adverse effects of CBD use in these patients.
The present study will be a single-center, randomized, parallel, double-blind,
placebo-controlled clinical trial of CBD in patients with mild to moderate SARS-CoV-2
infection. The investigators will use random stratification by minimizing the sample to
stratify all eligible patients according to gender, age, disease severity (mild or moderate)
and presence of comorbidity (controlled diabetes and/or hypertension), followed by random
designation (in a ratio 1: 1) in each stratum to ensure a balanced distribution of disease
severity among treatment groups (CBD plus symptomatic clinical and pharmacological measures)
and control (symptomatic clinical and pharmacological measures and placebo). All patients
will receive the clinical and pharmacological measures standardized by the Brazilian Ministry
of Health's practical guidelines for diagnosis and treatment for mild and moderate cases for
SARS-CoV-2 (https://portalarquivos.saude.gov.br/images/pdf
/2020/April/18/Dirursos-Covid19.pdf). In other words, the following pharmacological measures:
"prescription of drugs for symptom control, if there is no contraindication, with the
possibility of intercalating antipyretic drugs in cases of difficult control of fever. • Oral
antipyretic: 1st option: Paracetamol 500-1000 mg/dose (maximum 3mg / day) • 2nd option:
Dipyrone 500-1000 mg VO (maximum dose in adults 4 grams)", and clinical measures:" Home
isolation by 14 days from the date of onset of symptoms; review every 48 hours, preferably by
phone, providing face-to-face assistance, if necessary; maintain rest, a balanced diet and a
good supply of fluids; isolation from home contacts for 14 days".
Thus, all patients will receive clinical and pharmacological measures of symptoms. Patients
in the investigational treatment group will also receive CBD within 24 hours after
randomization, with a daily dose of 300mg / day (two 150mg doses; 1mL of the formulation) for
14 days. Patients in the placebo group will also receive, within 24 hours after
randomization, 1mL of the same investigational medication vehicle (medium/coconut chain
triglyceride oil - MCT) for 14 days, using a dosing device/syringe indistinguishable from the
CBD medication. Patients, nursing staff, laboratory technicians, doctors who will carry out
the assessments, researchers, and statisticians will be blind to the treatment group and will
not know about the treatment information.
Secretions from the upper respiratory tract, lower respiratory tract, or both, by swab, will
be obtained from each patient in the screening (day -3 to day 1) during treatment and
post-treatment follow-up at the patient's home on days 1, 2, 3, 4, 5, 7, 10, 14, 21, and 28,
to test the viral load and SARS-CoV-2 genotyping. On all these dates, nurses will visit home
to collect swab (only from the oropharynx, to minimize discomfort), blood and will be
evaluated at each visit for vital signs, pulse oximetry, odor test, and treatment guidelines.
Each patient will also receive a digital thermometer to measure the axillary temperature in
case of suspected fever and daily measurement immediately before lunch and dinner.
Drug: Cannabidiol
Already described
Other Name: CBD
Other: PLACEBO
Already described
Other Name: PLB
Inclusion Criteria:
1. Patients of both sexes, older than 18 years of age, with SARS-CoV-2 infection
confirmed in upper or lower respiratory tract secretion, through reverse transcription
followed by polymerase chain reaction (RT- PCR), with mild or moderate manifestations
of Covid-19, who wish to participate, and consent by signing the informed consent form
and not involved in another clinical trial during the study period
2. Pneumonia assessed clinically and / or radiologically will not be mandatory for
inclusion
3. Have a telephone (cellular or landline) that may be available to receive daily calls
throughout the study period.
4. Willingness to voluntarily participate in the study to accept randomization for either
treatment arm.
5. Signing of the approved Free and Informed Consent Form (ICF) by the Research Ethics
Committee (CEP) and CONEP
Exclusion Criteria:
1. Age below 18 years
2. Patients who do not want or can fulfill the necessary home isolation for at least 14
days
3. Chronic clinical conditions, severe or not compensated, such as: insulin-dependent
diabetes (types 1 or 2); uncontrolled hypertension, lung disease such as asthma or
COPD; hematological and liver diseases, chronic kidney disease in advanced stage
(grades 3, 4 and 5), metabolic disorders and immunosuppression
4. Use of any medication with potential interaction with CBD (such as chloroquine,
clobazan, warfarin, or valproic acid) or history of undesirable reactions prior to the
use of this cannabinoid
5. Inability to use oral medication
6. Pregnancy or lactation
7. History of alcohol or drug addiction
8. Smoking in the last three years
9. Marijuana use in the last three months
10. Inability to cooperate with researchers due to cognitive impairment or mental state
11. Patients with severe forms of SARS-CoV-2, (on screening, inclusion or initial visit)
Serviço de Assistência Médica e Social do Pessoal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
Ribeirão Preto, SP, Brazil
Unidade de Pronto Atendimento/UPA - 13 de Maio/Dr. Luis Atílio Losi Viana (UPA Covid)
Ribeirão Preto, São Paulo, Brazil
Jose ALEXANDRE DE S CRIPPA, MD, PhD, Principal Investigator
University of Sao Paulo