Treatment Strategies in CHS
Condition: Cannabis Hyperemesis Syndrome
MeSH terms: Hyperemesis Gravidarum; Syndrome
Study type: Interventional
Phase: Phase 4

Summary: 
      Background:

      In the gastrointestinal (GI) system, the most well-described manifestation of prolonged
      cannabis use is cannabinoid hyperemesis syndrome (CHS). CHS is characterized by severe cyclic
      nausea and vomiting and associated with abdominal pain.Currently, the generally accepted
      management for CHS is complete cannabis abstinence as traditional anti-emetics appear to be
      minimally effective. Preliminary reports from emergency departments suggest that intravenous
      haloperidol, a typical anti- psychotic, provides effective symptomatic relief in CHS.

      Objective:

        1. To learn more about how cannabis use relates to the management of CHS.

        2. To learn if haloperidol is effective in treating the symptoms of CHS.

      Eligibility:

      Alberta residents with ongoing cannabis use, who have completed the baseline study, are ≥ 18
      years and ≤ 65 years, and have gastrointestinal symptomology as measured by GCSI > 2 or
      PAGI-SYM > 2 (upper or lower abdominal pain subscale).

      Design:

      Participants will answer a series of questionnaires online. Study specific questions relating
      to symptoms, cannabis use, and anxiety and depression will be administered. Confirmation of
      cannabis cessation will be assessed with urine creatinine and cannabis metabolite measures.
      Salivary cortisol will be used to asses the stress response.
    

Detailed description: 
      In the gastrointestinal (GI) system, the most well-described manifestation of prolonged
      cannabis use is cannabinoid hyperemesis syndrome (CHS). CHS is characterized by severe cyclic
      nausea and vomiting and associated with abdominal pain.The pathophysiology of CHS is poorly
      understood but may involve alterations gut motility and/or activation of the
      hypothalamic-pituitary-adrenal (HPA) axis.

      Our endogenous endocannabinoid system contains the cannabinoid receptor type I (CB1) and type
      II (CB2), and their ligands, anandamide (AEA) and 2-arachidonylglycerol (2-AG). CB1 receptors
      are widely distributed throughout the central and peripheral nervous system, including the
      myenteric plexus of the GI tract. In humans, oral Δ9-THC (an active cannabis compound)
      reduces gastric emptying and patients with slow transit constipation have increased
      expression of endogenous endocannabinoids and higher CB1 receptor expression. In CHS, chronic
      cannabis use may cause significant activation of peripheral, gut-located CB1.

      The hypothalamic-pituitary- adrenal (HPA) axis, the main neuroendocrine system activated in
      response to stressful stimuli may also be involved in CHS. Activation of centrally located
      CB1 receptors by 2-AG plays a crucial role in down-regulating the HPA axis in recovery from
      stress. Reduction in 2-AG activity within the hypothalamus by stress, leads to reduced
      hypothalamic CB1 receptor activation; this reduced CB1 activation is also observed in
      prolonged cannabis use.

      Currently, the generally accepted management for CHS is complete cannabis abstinence as
      traditional anti-emetics appear to be minimally effective.Preliminary reports from emergency
      departments suggest that intravenous haloperidol, a typical anti- psychotic, provides
      effective symptomatic relief and has become a first-line agent for acute CHS.

      Outcome measures:

      The primary endpoints will look at the correlation between quantitative weekly cannabis use
      and gastrointestinal symptoms at week 8 and the mean change of the GI symptoms from week 8 to
      week 12 during.
    

Intervention name(s): Haloperidol
Intervention type(s): Drug
Intervention description(s): haloperidol intervention
Intervention MeSH terms: Haloperidol; Haloperidol decanoate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment