What medications are used to treat Gastrointestinal (GI) symptoms in patients with cannabinoid (CBD) use disorder?

From the Guidelines

For patients with GI symptoms due to cannabinoid use, the most effective approach is to cease cannabis use for at least 6 months, as this leads to resolution of symptoms, and for acute management, topical capsaicin, benzodiazepines, haloperidol, promethazine, olanzapine, and ondansetron can be used, with tricyclic antidepressants like amitriptyline being the mainstay for long-term management. When considering medication for GI symptoms in these patients, it's crucial to prioritize those that have shown efficacy in managing symptoms without worsening the condition or leading to addiction.

• Topical capsaicin (0.1%) cream can be applied to improve symptoms by activating transient receptor potential vanilloid type 1 receptors, as noted in the 2024 study by 1.
• Benzodiazepines, haloperidol, promethazine, olanzapine, and ondansetron are supported by evidence for acute and short-term care, according to 1.
• For long-term management, counseling for marijuana cessation and tricyclic antidepressants, such as amitriptyline, starting at 25 mg and titrating up to 75-100 mg at bedtime, are recommended, as per 1. It's also important to avoid opioids due to their potential to worsen nausea and the high risk of addiction, as cautioned in 1. In the emergency department setting, the approach differs, focusing on immediate evaluation for life-threatening conditions, but in outpatient settings, after ruling out structural issues, differential diagnoses should include conditions like rumination syndrome, gastroparesis, and functional chronic nausea and vomiting syndrome, as outlined in 1.

From the Research

Medications for GI Symptoms in Patients with Cannabinoid Use

• The medications used to treat GI symptoms in patients with cannabinoid use include:
  • Tricyclic antidepressants (TCAs) and lorazepam, which have been discussed as effective long- and short-term treatments for cannabinoid hyperemesis syndrome (CHS) 2
  • Ondansetron, promethazine, diphenhydramine, and opioids, which have been mentioned as potential treatments, but their efficacy is not well established 2
  • Antiepileptics such as zonisamide and levetiracetam, which have been reported as effective in some cases 2
  • Benzodiazepines, haloperidol, and capsaicin, which have been reported as helpful in acute treatment 2
  • Metoclopramide, which has been reported as effective in some cases 2
  • Haloperidol, which has been shown to be superior to ondansetron in a randomized controlled trial for the acute treatment of cannabis-associated hyperemesis 3
• It's worth noting that hot showers and baths have been cited as universally effective in relieving symptoms of CHS 2, 4

GI Symptoms and Cannabinoid Use

• Cannabinoid use has been associated with various GI symptoms, including:
  • Nausea and vomiting, which are common symptoms of CHS 2, 4
  • Abdominal pain, which is reported by most patients with CHS 4
  • Cyclic vomiting syndrome, which can be caused by cannabinoid use 5
  • Gastrointestinal dysmotility, which can be associated with cannabinoid mechanisms 6

Therapeutic Potential of Cannabinoids

• Cannabinoids have been shown to have therapeutic potential for various GI and liver diseases, including:
  • Reducing gastrointestinal, pancreatic, or hepatic inflammation 5
  • Treating motility, pain, and functional disorders 5
  • However, randomized trials are needed to clarify their effects in patients, and potential adverse effects on the central nervous system or the developing fetus must be considered 5