Why Cannabinoid Hyperemesis Syndrome Happens And What To Do About It

Cannabinoid Hyperemesis Syndrome (CHS) is a syndrome of cyclic episodes of nausea, vomiting, and abdominal pain associated with chronic cannabis usage. R R

In this post, we will discuss the pathology of CHS and how to treat it. 

Cannabinoid Hyperemesis Syndrome (CHS) may involve toxic metabolites from the cannabis plant or progressive high exposure to the ligand may lead to down-regulation of cannabinoid receptors and loss of the endocannabinoid anti-emetic pathway.

As a regulator of the gut-brain axis, endocannabinoid receptors in the hypothalamus can become dysregulated from overactivity of cannabinoid ingestion (everything from terpenes, marijuana, synthetic analogues, and supplementary/dietary cannabinoids) or stress (HPA-dysfunction). 

Another problem comes from being able to excrete cannabinoids (genetic problem in liver transforming enzymes/detox), thus cannabinoids stay in the system for longer.

Features of cannabinoid hyperemesis syndrome: R

• Current, heavy cannabis use

• Abdominal pain, epigastric or periumbilical

• Recurrent episodes of severe nausea and intractable vomiting

• Compulsive bathing with symptom relief

• Resolution of symptoms with cannabis cessation

• Failure of standard antiemetics to resolve nausea and vomiting

CHS is divided into 3 phases: R

1. Prodrome - nausea, anorexia, and vague abdominal discomfort

2. Hyperemesis - bouts of emesis and diffuse abdominal pain that can last for hours

3. Recovery - resolution of all symptoms

1. Stress And Loss of CB1 Activity

Stress (cortisol) increases CNR1 thus increasing CB1 receptors in the hypothalamus, leading to lower activity. R

This lower activity allows TRPV1 receptors to be more sensitive (thus decreasing pain threshold). R

CB1 activity is important as it reduce intestinal 5-HT release and increases GABA. R

Stress also increases FAAH and MAGL, which lowers the amount of anandamide (endocannabinoid). R

2. Toxins And Detox Phases

Other toxins may be sprayed or grown with marijuana.

For example, neem oil is used to preserve marijuana and the ingredient Azadirachtin has shown to be toxic (overdose essentially) causing symptoms similar to CHS. R R

3. Other Genetic Problems

Mutations in 5HT1R, CNR1, TRPV1, or GPR55 may cause problems with regulation of CB receptors and endocannabinoids. R R

Stop Cannabis Consumption

In thousands of studies, cannabis cessation has shown to be very effective in stopping CHS. R R

If you must get high, most studies have shown CHS does not happen in those that take purely THC. R

If stopping cannabis use doesn't help CHS, then cyclic vomiting syndrome (CVS) should be considered (see pic below). R

Avoid Stress And Fasting

Stress causes HPA-axis dysfunction which can contribute to development and persistence of CHS. R

Stress and fasting may overwhelm the endocannabinoid system and cause CHS. R

Heat

Heat works on TRPV1 receptors and can help with CHS. R

Some ways to activate heat:

• Capsaicin (topically put all over) R R R

  • Shift in TRPV1 temperature activation threshold

  • “Desensitization” or “defunctionalization” of nociceptors

  • TRPV1 and CB1 polymorphisms and down-regulation

  • Restoration of DNIC imbalance

  • Depletion/inhibition of substance P, neurokinin A

  • Stimulation of somatostatin

  • Stimulation of PACAP

  • Depletion/inhibition of CGRP

  • Inhibition of histamine, acetylcholine, and serotonin

  • Restoration of CB1/TRPV1 balance

• Hot Shower/Bath (>43
  ºC) - good during phase 2 R

  • Cutaneous thermoceptor and TRPV1 activation

  • Reversal of hypothalamic cannabinoid-induced hypothermia

  • Decreased HPA-axis and sympathetic nervous system activation

  • Restoration of DNIC balance

  • “Cutaneous steal” syndrome

  • Stimulation of somatostatin

  • Stimulation of PACAP

  • Depletion/inhibition of CGRP

  • Restoration of CB1/TRPV1 balance

Drugs:

• Benzodiazepines R R

• Haloperidol R

• Intravenous fluids (due to dehydration) R

• Proton pump inhibitors (for pain if reflux) R

• Tricyclic antidepressants R

Pathways:

• CB1 agonists R

• Dopamine antagonists (such as phenothiazines and butyrophenones) R

• FAAH inhibition R

• H1 receptor antagonists R

• Neurokinin-1 receptor antagonists R

• 5-HT3 antagonists R

Possible Mechanisms: R

• 
  Stimulation of CRH production in the hypothalamus

• Increased monoamine production in the cortex, limbic system, and medulla

• Stimulation of tyrosine and tryptophan hydroxylase

• Inhibition of monoamine oxidase

• Inhibition of GABA, acetylcholine, and glutamate

• CB1 receptor down-regulation, desensitization, and internalization

• Genetic variations in cytochrome P-450 cannabinoid metabolism

• Lipolysis and excess cannabinoid release from fasting and/or stress

• Cannabinoid enhancement of SCN circadian HPA axis and SNS

• Decreased dopamine and GABA activity and catatonia from abrupt cannabis withdrawal

• Increased dopamine and GABA inhibition and anxiety/psychosis from excessive cannabis use

• DAT and COMT gene polymorphisms increase psychotomimetic effects and memory impairment

• b-blocker control of SNS-induced CNS and peripheral catecholamine release

• Hot water hydrotherapy mitigation of SNS activation

• Classical forms of CHS can exist with bradycardia, and pain can be relieved by cold temperature. R