Abstract
Non-communicable diseases, such as heart disease and diabetes, require continuous
medication, such as anticoagulants and antihyperglycemic drugs. In addition, due to the policy of using
cannabis for medical purposes, patients hope that using cannabis together with current medications will
alleviate or cure non-communicable diseases. Therefore, there is a chance that non-communicable
drugs and cannabis may interact. When cannabis enters the body, it uses the same drug metabolizing
pathway as anticoagulants or antihyperglycemic drugs. Therefore, if such drugs are given together with
cannabis, there is a chance that they may cause adverse drug reactions or failure of drug therapy.
Conversely, if drugs can use more enzymes or drug metabolizing pathways than cannabis, they may
cause cannabis adverse reactions. This study aimed to study the effects of interactions between
cannabis and non-communicable drugs using a systematic literature review on the use of cannabis
together with non-communicable drugs and a case collection method for patients who used cannabis
together with warfarin or glipizide.
The results of the literature review study found that patients who received warfarin together with
cannabis in the form of smoking or taking it in the form of drugs or products were affected by an
increase in INR from 2.5-3.5 to 4.6-5.2, which is expected to be a result of inhibition of the CYP2C9
enzyme by the main ingredient in cannabis, CBD, which slows down the elimination of warfarin, resulting
in high blood levels of warfarin and causing an increase in INR. In addition, drugs that are likely to be
affected by the use of cannabis or products were found, including 1) Brivaracetam (CBD→CYP2C19
inhibition) → increased blood levels of drugs 2) Tacrolimus (CBD→CYP3A4 inhibition) → increased
blood levels of drugs 3) Everolimus (CBD→CYP3A4 inhibition) → increased blood levels of drugs and
4) Carbamazepine (CBD→CYP3A4 inhibition) → increased blood levels of drugs.
The results of the case report study found that for patients taking warfarin, 3 cases were
collected. All 3 patients had been receiving treatment at the warfarin clinic regularly and consistently.
The INR level was always within the range specified by the doctor. Later, when the patients started
using cannabis or cannabis products in the form of leaf decoction, tea, or sublingual oil for the purpose
of helping them sleep better and relieve stress, most of the time, the INR level was found to be higher,
but there were no abnormal symptoms. When the pharmacist advised them to stop using them and
made an appointment for a follow-up, after stopping the cannabis use, the INR level was found to have
decreased back to the range specified by the doctor. As for the case report for patients taking glipizide,
2 cases were collected. Both patients had been receiving regular treatment for diabetes and were able
to control their blood sugar levels sometimes and sometimes not. After the patients started using
cannabis, either in the form of tea, inhalation, or sublingual oil, for the purpose of treating their disease
or helping them sleep better, relieve stress, or reduce blood sugar levels for 1 month, when they came
for a follow-up, it was found that the FBS blood sugar level did not change much. However, the patients
reported that they often had palpitations, dizziness, sweating, and felt like they were going to faint. After
drinking sweet water, the symptoms would improve. But the blood sugar level at the fingertip was not
measured at the time of the symptoms occurred. Therefore, from the study results, it can be concluded
that when patients use cannabis together with taking chronic non-communicable diseases medications,
there is a chance of an interaction in the pharmacokinetic process, especially the drug metabolism
process. Drugs that have the same metabolism pathway as cannabis are more likely to have an impact
from the interaction, such as warfarin and glipizide. Both of these drugs use the CYP2C9 enzyme
metabolism pathway, which is the same enzyme as the metabolism pathway of cannabis or the active
ingredient in cannabis. Therefore, medical personnel should carefully select drugs, considering the use
of cannabis in patients, and should educate patients who need to use drugs that have the same
metabolism pathway as cannabis that they should avoid using cannabis in order to prevent interactions
from using cannabis together with chronic non-communicable diseases medications.
