Trina's Notes

Today, I’d like to share a compelling case study about a patient I cared for who was grappling with Cannabinoid Hyperemesis Syndrome (CHS). We’ll delve into his presentation, the underlying pathophysiology, and how we managed his condition.

History and Infectious risk

It was around 10 a.m. when Ivan (not his real name), a middle-aged man, was brought into our Emergency Department by his partner. He was in severe distress, experiencing sudden onset of intense abdominal pain, accompanied by relentless nausea and vomiting. Ivan was shaking uncontrollably, sweating profusely, and complained of feeling extremely cold despite his 3 layers of clothing on a 26 degree sunny day.

Ivan had a complex medical history that included a neuroendocrine tumor, Attention Deficit Hyperactivity Disorder (ADHD), anxiety, depression, and habitual cannabis use. He last smoked cannabis about 16 hours before arriving at the hospital. Notably, he had no fever or signs of infection. He lived with his partner, who was well.

Primary assessment:

Airway and Breathing

His airway was clear, but he was slightly tachypnoeic at 24 breaths per minute and could only speak in short sentences. Lung sounds were clear with good air entry on both sides, and his oxygen saturation was 98% on room air.

Circulation

He had strong, regular radial pulses at 88 beats per minute, but his blood pressure was elevated at 165/101 mmHg.

Disability

Ivan was visibly agitated, with wide eyes and constant shaking. He was extremely diaphoretic, with beads of sweat covering his body.

Exposure

Despite a normal tympanic temperature of 36.8°C, he felt intensely cold. His partner had even brought a portable heater, and he was bundled in three heavy blankets. Paradoxically, he was also craving iced water due to extreme thirst, but drinking led to more vomiting.

Fluids in and out

He was extremely thirsty and was trying to drink lots and lots of water. He also had several episodes of diarrhoea.

Glucose

His blood glucose was normal at 6.8 mmol/L.

Focused Abdominal assessment

Abdominal examination revealed a soft, non-tender abdomen with active bowel sounds.

Interventions

We inserted an 18-gauge cannula into his left cubital fossa and started with:

• 100 mcg of Intravenous Fentanyl: Aimed at alleviating his severe pain.
• 8 mg of Intravenous Ondansetron: Intended to control his nausea and vomiting.

Unfortunately, these interventions provided no relief.

Diagnostics

To rule out other potential causes, we conducted several tests:

• Blood Tests: Full blood count, serum electrolytes, liver function tests, and serum lipase—all returned normal results.
• Electrocardiogram (ECG): Showed a normal sinus rhythm.

Re-assessment

Recognizing his history of chronic cannabis use, we considered CHS as a potential diagnosis. We administered:

• 30 mg of Intravenous Ketamine: Known for its analgesic and antiemetic properties.
• Hartmann’s Solution Infusion: To address potential dehydration over a two-hour period.

This approach granted him about 45 minutes of relief before the symptoms re-surged. Subsequent doses included:

• 20 mg of Intravenous Ketamine: Provided another hour of symptom control.
• Additional 30 mg of Intravenous Ketamine: Administered while arranging his transfer to a specialized public hospital where he typically received ketamine infusions during his previous episodes of CHS. 

Understanding CHS: The Culprit Behind Ivan’s Symptoms

So, what was happening with Ivan?

Chronic cannabis use can significantly disrupt the autonomic nervous system through its impact on the endocannabinoid system, which is intricately involved in regulating nausea, vomiting, and body temperature. Overstimulation of cannabinoid receptors leads to:

• Erratic Signaling: Causes intense cycles of vomiting (hyperemesis) and severe abdominal pain.
• Hypothalamic Dysregulation: The hypothalamus, rich in cannabinoid receptors, loses its ability to regulate body temperature effectively. This explains why Ivan experienced severe chills and cold sweats despite having a normal measured temperature.

Effective Management Strategies

Traditional interventions like fentanyl and ondansetron were ineffective because:

• Fentanyl: While it can provide short-term pain relief, it doesn’t address the root cause—endocannabinoid system imbalance.
• Ondansetron: This medication blocks serotonin receptors but doesn’t influence other neurotransmitter systems affected by chronic cannabis use, such as dopamine and glutamate pathways.

Why Ketamine Helped

Ketamine emerged as a more effective treatment due to its multifaceted action:

• NMDA Receptor Antagonist: Blocks NMDA receptors, disrupting pain signal transmission in the brain and spinal cord.
• Antiemetic Properties: Modulates neural pathways involved in nausea and vomiting, although the exact mechanism remains under study.
• Dissociative Effects: Provides a sense of detachment from the body and surroundings, which can alleviate the distress associated with CHS symptoms.

Alternative Therapies

• Capsaicin Ointment: Some studies suggest that applying capsaicin cream to the abdomen can provide relief. Capsaicin activates the transient receptor potential vanilloid-1 (TRPV-1) receptors, creating a sensation of heat that may counteract nausea and vomiting by overactivating these receptors near the endocannabinoid system.
• Haloperidol: Although not traditionally a first-line treatment, haloperidol can provide rapid and effective relief in cases where standard antiemetics fail, hence it has emerged as another potential treatment option for Cannabinoid Hyperemesis Syndrome due to its unique pharmacological properties:
  • Dopamine Blockade: Haloperidol inhibits dopamine D2 receptors in the brain’s chemoreceptor trigger zone (CTZ), significantly reducing nausea and vomiting. Since CHS involves endocannabinoid system dysregulation, which indirectly influences dopamine signaling, haloperidol effectively targets this pathway.
  • Calming Effects: CHS patients often present with anxiety and agitation, symptoms that haloperidol helps mitigate through its sedative properties.
  • Restoring Gut Motility: Chronic cannabis use may lead to abnormal gut motility. By modulating dopamine signaling, haloperidol can help restore balance to the gastrointestinal system.

The Ultimate Solution

The most effective long-term strategy to prevent CHS recurrence is to stop using cannabis entirely.

Ivan’s Outcome

As we awaited the ambulance for his transfer, we encouraged Ivan to stay hydrated as much as possible. Toward the end of my 12-hour shift, he reported feeling hungry and managed to eat two packs of crackers. Feeling noticeably better, Ivan decided to go home instead of transferring to the hospital. He signed a Discharge Against Medical Advice form and left with his partner, appearing much less distressed than upon arrival.

Key Takeaways

This case highlights several critical points:

• Importance of Patient History: Chronic cannabis use can be a key factor in unexplained gastrointestinal symptoms.
• CHS Awareness: Understanding CHS can lead to more effective and timely interventions.
• Holistic Approach: Sometimes, unconventional treatments like ketamine or capsaicin ointment can offer relief when standard therapies fail.
• Patient Education: Informing patients about the risks of chronic cannabis use and encouraging cessation can prevent future episodes.

Cannabinoid Hyperemesis Syndrome is a complex condition that challenges conventional treatment methods. Ivan’s case underscores the necessity for healthcare professionals to consider a patient’s substance use history and to remain open to alternative management strategies. Early recognition and appropriate treatment not only alleviate immediate suffering but also contribute to better long-term outcomes for patients grappling with CHS.

Have you ever looked after a patient who had CHS? How strategies did you take to help alleviate their symptoms?

Here’s the list of papers I used to help me understand CHS and the management strategies that can be used to help these patients:

Abdul, I. M., Jehangir, W., Littlefield, J. M., John, S., & Yousif, A. (2015). Cannabis hyperemesis syndrome: A case report review of treatment. Toxicology Reports, 2, 889–890. https://doi.org/10.1016/j.toxrep.2015.05.015

AGA Clinical Practice Update on Diagnosis and Management of Cannabinoid Hyperemesis Syndrome: Commentary. Rubio-Tapia, A., et al. (2024). Gastroenterology, 166(5), 930-934.e1.

Angulo, M. I. (2024). Cannabinoid Hyperemesis Syndrome. JAMA, 332(17), 1496. https://doi.org/10.1001/jama.2024.9716

Aziz, A., Waheed, T., Oladunjoye, O., Oladunjoye, A., Hanif, M., & Latif, F. (2020). Topical capsaicin for treating cannabinoid hyperemesis syndrome. Case Reports in Gastrointestinal Medicine, 2020, 8868385. https://doi.org/10.1155/2020/8868385

Cue, L., Chu, F., & Cascella, M. (2023). Cannabinoid hyperemesis syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549915/

Perisetti, A., Gajendran, M., Dasari, C. S., Bansal, P., Aziz, M., Inamdar, S., Tharian, B., & Goyal, H. (2020). Cannabis hyperemesis syndrome: An update on the pathophysiology and management. Annals of Gastroenterology, 33(6), 571–578. https://doi.org/10.20524/aog.2020.0528

Valdovinos, E. M., Frazee, B. W., Hailozian, C., Haro, D. A., & Herring, A. A. (2020). A nonopioid, nonbenzodiazepine treatment approach for intractable nausea and vomiting in the emergency department. Journal of Clinical Gastroenterology, 54(4), 327–332. https://doi.org/10.1097/MCG.0000000000001258

Waterson Duncan, R., & Maguire, M. (2017). Capsaicin topical in emergency department treatment of cannabinoid hyperemesis syndrome. The American Journal of Emergency Medicine, 35(12), 1977–1978. https://doi.org/10.1016/j.ajem.2017.06.038

Yang, F., & Zheng, J. (2017). Understand spiciness: Mechanism of TRPV1 channel activation by capsaicin. Protein & Cell, 8(3), 169–177. https://doi.org/10.1007/s13238-016-0353-7