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.
The use of hot water showers in the emergency department setting has been advocated in situations where topical capsaicin cream is unavailable, though the same precautions to hot water use (dehydration, burn injury) are required.The use of antipsychotics, such as haloperidol and olanzapine, have provided complete relief of symptoms in case-reports. The evidence for the use of benzodiazepines, such as lorazepam, has shown mixed results. Other drug treatments that have been tried, with unclear efficacy, include neurokinin-1 receptor antagonists, first-generation antihistamines (e.g. diphenhydramine), 5-HT3 receptor antagonists (e.g. ondansetron), and non-antipsychotic antidopaminergics (e.g. metoclopramide).Acetaminophen has shown some benefit in case reports for alleviating headaches associated with CHS. Opioids can provide some relief of abdominal pain, but their use is discouraged due to the risk of worsening nausea and vomiting. Epidemiology
As of 2017 a French pharmacovigilance program for drug users had received reports of 29 cases of CHS. At the time there were 113 case described in the international medical literature. CHS incidence is likely to have been substantially under-reported.In the United States, an analysis of data from the National Emergency Department Sample between 2006 and 2013 found an increase in emergency room attendees with vomiting who also had cannabis use disorder, to a rate of approximately 13 per 100,000 attendees. It is possible this rise, of around 5+1⁄2 times, may be affected by sampling bias, as initial awareness of CHS prompted more diligent questioning and recording of when such ER attendees were also cannabis users.The number of people affected was unclear as of 2015.