Chronic Cannabis Intoxication and Propofol-Induced Salivation: Causes and Considerations
, Carey Ford 1,†, Nazar Hafiz 2, Sudha Pandit 2, Aditya Vyas 2, Samuel Igbinedion 2, James Morris 2, Paul Jordan 2, Qiang Cai 2 and Jonathan Steven Alexander 1,2,3,*Round 1
Reviewer 1 Report
In the proposed article, the authors presented three clinical cases of the use of propofol for anesthesia in patients who used cannabinoids in anamnesis, and described the effect of hypersalivation in these patients. Based on the cases presented, the authors suggest that chronic cannabinoid use leading to higher doses of Propofol during surgical procedures acts synergistically on the salivary glands to provoke excessive intracellular Ca mobilization, thus leading to excessive salivation. This possible mechanism is logical and requires further study.
Despite the logic of the description, a number of points in the article require clarification.
1. When describing clinical cases, data on the duration of taking cannabinoids in anamneses are not given.
2. In all clinical cases, the patients had rather severe clinical diseases. It should be expected that they were taking therapy by medicines, which could also affect the mechanisms of salivation. However, the use of drug therapy is described partly only for the correction of arterial hypertension.
3. I would like to see the data of laboratory studies.
Author Response
We appreciate the reviewer's useful comments that the mechanisms proposed were logical and agree they deserve further study which will improve safety for patients undergoing procedures who may use cannabis products. We would like to respond to the queries made as follows:
Reviewer 1. In the proposed article, the authors presented three clinical cases of the use of propofol for anesthesia in patients who used cannabinoids in anamnesis, and described the effect of hypersalivation in these patients. Based on the cases presented, the authors suggest that chronic cannabinoid use leading to higher doses of Propofol during surgical procedures acts synergistically on the salivary glands to provoke excessive intracellular Ca mobilization, thus leading to excessive salivation. This possible mechanism is logical and requires further study.
Despite the logic of the description, a number of points in the article require clarification.
1. When describing clinical cases, data on the duration of taking cannabinoids in anamneses are not given.
Answer. We would like to clarify, agree and acknowledge that if the duration and level of cannabinoid consumption by these patients were known, it would be extremely helpful and useful in predicting clinical/pharmacological responses. However, our patients using cannabis may not always provide an accurate description of their use and in our clinical experience, many patients will initially not declare cannabinoid use or may minimize their cannabis use. Additionally, cannabis products vary widely in their cannabinoid content. In many cases, patient screening and profiling for cannabinoids can helps to avoid dangerous drug interactions. Additionally, individual metabolism and frequency of use can influence drug metabolism and therefore, we regret that we do not have a highly accurate representation of patient drug levels. This limitation is hopefully now better described and acknowledged in the manuscript.
2. In all clinical cases, the patients had rather severe clinical diseases. It should be expected that they were taking therapy by medicines, which could also affect the mechanisms of salivation. However, the use of drug therapy is described partly only for the correction of arterial hypertension.
Answer. This is a very valid point. We have now provided prescription drugs used by each patient in the current revision and separated these drugs as to whether they are known to influence salivation.
We also note the limitation of the study as follows:
Although there were several other drugs being used by patients, they do not appear to explain the CHAPP phenomenon and are usually agents which provoke xerostomia or have no known effect on salivation. This is a potential limitation of the study and will need to be evaluated in further studies.
3. I would like to see the data of laboratory studies.
Answer. We studied the lab values for these patients for abnormal lab values and have now reported that all normal hospital lab values were reported as normal.
Reviewer 2 Report
The manuscript by A. Derise et al entitled “Synergistic Mechanisms of Cannabis and Propofol-Induced Hypersalivation” is presented for review.
The study highlights mechanistic pathways involved in cannabis and Propofol signaling in a light of evaluation of patients at Louisiana State University Health – Shreveport, LA with cannabis-induced hypersalivation after propofol (CHAPP) symptoms. The Authors report three cases of CHAPP with similar case histories and outcomes, thus raising awareness for the patient treatment going forward with widespread cannabis legalization. It is proposed that chronic cannabinoid use leading to higher doses of Propofol during surgical procedures acts synergistically on the salivary glands to provoke excessive intracellular Ca mobilization, thus leading to excessive salivation and risk of suffocation.
It is this reviewer’s opinion that the paper is very timely and addresses poorly investigated clinical problem (i.e. CHAPP). The suggested potential signaling pathways involved in CHAPP phenomenon are well introduced and may help to develop new pharmacological strategies for patient management going forward with widespread cannabis legalization. Potential caveats/limitations are acknowledged and addressed. In addition, the paper is well-written and was easy to follow.
As such, this reviewer has NO MAJOR concerns.
Minor concerns:
- The manuscript should be checked for minor typographical errors.
Author Response
We appreciate the reviewer's useful comments and provide the revised version of our manuscript.
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
