Current Topics Video Research

Vy’s Papers

Cannabinoid Hyperemesis Syndrome Survey and Genomic Investigation (2022)

  • Genes associated w/ CHS: COMT (catalyzes methalyation for NTs, associated w/ MH issues), TRPV1 (protein encoded by this gene is a capsiacin receptor, related to heat), CYP2C9 (involved in metabolism), DRD2 (dopamine receptor, associated w/ MH issues), ABCA1 (cholesterol pump)

  • n= 99

  • 79.4% of people resumed cannabis use

  • CNR1: Codes for CB1 receptor

    • Not significant in the CHS cohort

  • COMT: Catebolizes dopamine, COMT variants linked to MI and risk taking behavior, SS

    • Intron mutation observed in CHS Ss (57.7% of Ss)

      • Inactivates DA in the PFC

      • Hypoactive COMT: increases rigidity and flexability, continued cannabis use after health reccs to stop

      • Suggests dopamine may be involved in CHS

      • Haloperidol, a dopamine antagonist, can be effective for anti-nausea in CHS patients

  • TRPV1: 71.5% of CHS Ss had this mutation, SS

    • TRPV1 receptor responds to heat, ethanol, and low pH (associated w/ pain responses)

    • Capsaicin and CBD are an agonist/desensitater

    • THC not a ligand (endogenous cannabinoids are)

    • Pain, anxiety, and gut distress all involved

    • Capsaicin treatment may involve this receptor

    • CBD may help given it is also an agonist 

  • CYP2C9: 46.4% prevalence, 60% once PPI meds excluded, SS

    • Part of metabolism for drugs, steroids, vitamins, fatty acids

    • Helps breakdown THC

    • Slow metabolism leads to longer psychoactive exposure

      • THC may accumulate in the brain

  • DRD2: Codes for type 2 DA receptor, 60.7% prevalence, SS

    • Role in fear memories of the limibic system, associated w/ depression and anxiety

  • ABCA1: 67.9% prevalence, SS

    • Affects cholesterol and ATP transportation

    • May increase dementia

    • ABCB1 mutations may increase cannabis dependency

  • CRY1: 78.6% prevalence, NS

    • Involved in the circadian rhythm, mood disorders, and alcoholism

  • Only 28 actually brought back their tests

  • Expalantion: CHS is not functional, it’s a gene-environment interaction disorder

Rare but Relevant: CHS

  • Frequently misdiagosed 

  • THC has anti-emetic properties, hard to identify it as a cause of vomiting

  • Fatalities are rare

  • 98% of CHS patients get relief in hot water

  • Hot bathing not exclusive to CHS, but a key identifier of CHS

  • 0.05% estimated prevalence in 2021

  • Prevalence higher in young chronic users

  • CHS higher in inhaled users vs edibles 

  • More likely to be male, using cannabis for over 5 years, daily users

  • 2014: 21% of CVS patients using cannabis

  • Prodromal, hyperemetic, and recovery stages

    • Prodromal: nausea leads user to take more cannabis

  • No consistent data on time needed for cannabis cessation

  • Potential explanation: hypothalamic thermoregulation

    • High levels of THC stimulate CB1 receptors in the Ht, downregualting the receptor, suppressing THC anti-nausea effects

    • Bathing in hot water redirects blood and reduces vasodialtation in the gut

    • TRPV1 involved 

    • Downregulation of CB1 receptors leads to CHS, increase fear/anxiety, interfere w/ thermoregulation

  • Treatments

    • Fluids, benzos/haloperidol, topical capsican 

    • Cessation of Cannabis use only long term solution

CHS: Genetic Susceptability to toxic exposure

  • Mentions TRPV1 genes

  • Escalating intake of MJ

  • CHS is not a response to toxic intake, continued pattern

  • 2012: 95000 in medical costs before diagnosis

  • Certain scents and CB1 agonists may trigger symptoms after cessation

  • Concerns about pestacides in cannabis

    • Not a likely explanation as the symptoms for acute pesticide ingestions is different than CHS

  • CVS is a part of migrane, manifested w/o the headache

    • CVS pts associated w/ snp on CNR1 gene, absent in CHS suffers

    • CBD may help, low quality control of products

  • ww8r7 t7

Three points:


  • TRPV1 gene

    • Recent research suggests that CHS has a genetic basis. One study found that a heterozygous downstream mutation of the TRPV1 gene is associated with a higher risk of CHS. This gene codes for receptors that deal with pain perception, gut motility, and temperature regulation. Involvement of this gene may explain why capsaicin improves CHS symptoms, as it is a TRPV1 receptor agonist. There is currently no explanation for this association.

  • Haloperidol and DA agonists as treatment, COMT gene

    • Other research suggests that dopamine may be important in CHS. The COMT gene is involved in dopamine metabolism by encoding the production of an important enzyme that breaks down dopamine in the prefrontal cortex. A hypoactive COMT gene mutation may result in less efficient dopamine elimination, leading to cognitive rigidity and risk-taking behavior. This explains the finding that 79.4% of CHS patients resume cannabis use. 

    • Another indication of dopamine’s involvement in CHS is haloperidol’s effectiveness in treating CHS-related nausea. Haloperidol blocks D2 receptors in the brain, decreasing dopamin signalling. 

  • Distinction between CVS and CHS

    • Lastly, a lot of research focuses on differentiating CHS from CVS. This is important because their similar symptom presentation leads to misdiagnosis of CVS, preventing CHS patients from receiving proper treatment and excess medical expenses. 

    • CVS is a part of migraine, THC has anti-nausea effects leading 21% of CVS patients using cannabis

    • CHS is a gene-environment interaction disorder, not a result of acute toxicity 

    • CVS is  genomically different, CNR1 gene mutation only seen in CVS patients