Other factors, such as chronic stress, genetics, and emotional factors, may influence the risk for CHS.Various pathogenic mechanistic theories attempting to explain symptoms have been put forward:
dose dependent buildup of cannabinoids and related effects of cannabinoid toxicity
the functionality of cannabinoid receptors in the brain and particularly in the hypothalamus (which regulates body temperature and the digestive system)
direct stimulation of cannabinoid receptors in the gut

Cannabinoid buildup theory
Tetrahydrocannabinol (THC) is a fat-soluble cannabinoid that can be deposited into a persons fat stores, accounting for the long elimination half-life of THC. During periods of stress or food deprivation, a persons fat stores can be mobilized (lipolysis) for energy consumption, releasing the previously stored THC back into the blood. The mechanism can be characterized as a "reintoxication effect." Another cannabinoid called cannabigerol acts as an antagonist at cannabinoid(CB1) and serotonin(5HT1A) receptors, antagonizing the anti-emetic effects of cannabidiol that occurs through its effects on serotonin. Diagnosis
The diagnostic criteria for CHS were ill-defined prior to the establishment of the Rome IV criteria of 2016. The criteria specify symptoms which resemble cyclic vomiting syndrome and which occur after long-term cannabis use, but which cease after cannabis use is halted. A retrospective application of these criteria to cases recorded in prior literature suggested that the number of people with CHS had been over-estimated.Various diagnostic frameworks for CHS have been proposed. As of 2015, the modified criteria by Simonetto et al. are the most frequently used. The most important feature is detecting a history of cannabinoid use, the denial of which can delay proper diagnosis.
In February 2007, the American Heart Association warned that with respect to "patients with a prior history of or at high risk for cardiovascular disease... use of COX-2 inhibitors for pain relief should be limited to patients for whom there are no appropriate alternatives, and then, only in the lowest dose and for the shortest duration necessary. "In 2005, a study published in the Annals of Internal Medicine found that cardiovascular effects of COX-2 inhibitors differ, depending on the drug. Other COX-2-selective inhibitors, such as rofecoxib, have significantly higher myocardial infarction rates than celecoxib. In April 2005, after an extensive review of data, the FDA concluded it was likely "that there is a class effect for increased CV risk for all NSAIDs". In a 2006 meta-analysis of randomized control studies, the cerebrovascular events associated with COX-2 inhibitors were examined, but no significant risks were found when compared to nonselective NSAIDs or placebos. Drug interactions
Celecoxib is predominantly metabolized by cytochrome P450 2C9. Caution must be exercised with concomitant use of 2C9 inhibitors, such as fluconazole, which can greatly elevate celecoxib serum levels. If used concomitantly with lithium, celecoxib increases lithium plasma levels. If used concomitantly with warfarin, celecoxib may result in increased risk of bleeding complications. The risk of bleeding and gastric ulcers also increase further when SSRIs are used in combination with celecoxib. The drug may increase the risk of kidney failure with angiotensin-converting enzyme-inhibitors, such as lisinopril, and diuretics, such as hydrochlorothiazide.