How to Take Care of Adolescents and Young Adults with Cannabnoid Hyperemesis Syndrome

Posted on June 16, 2026 by gutsandgrowth

A recent blog post summarized the recent Rome V recommendations which include useful tips for the diagnosis and management of Cannabinoid Hyperemesis Syndrome (Reference article: R Rosen et al. Gastroenterol 2026; 170: 1347-1366. Open Access! Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction).

A practice management article by Nguyen et al (The Journal of Pediatrics, 2026; 291: 114966. Management of Cannabinoid Hyperemesis Syndrome in Adolescents and Young Adults) provides a lot of granular detail on how to improve outcomes.

Clinical manifestations:

“Recurrent vomiting that is not attributable to another disorder and in the context of cannabis use should raise concerns for cannabinoid hyperemesis syndrome (CHS). CHS typically presents with three phases. The prodromal phase is characterized by abdominal discomfort and early morning, episodic nausea on at least 1 day per week. This prodrome
may precede acute vomiting by months or years. The emetogenic phase is characterized by sudden-onset, severe vomiting and abdominal pain episodes. Symptoms start within
24 hours of last cannabis use, last typically for 24-48 hours, and may persist for up to 7-10 days. Abdominal pain is usually described as cramping in nature, radiating diffusely from
the epigastrium or umbilicus. Patients often report symptom improvement with hot showers or baths. Acute nausea and vomiting gradually abate if patients abstain from cannabis, allowing transition from the acute emetogenic phase to the recovery phase and normalization of eating patterns. Symptoms typically recur with re-exposure to
cannabis.”
“CHS is a separate disorder from CVS. It is critical that medical providers avoid providing CHS and CVS as interchangeable diagnoses to patients and families. Inconsistent
diagnoses may erode families’ trust in the health care system by giving the impression that providers have not yet settled on an etiology. Furthermore, patients experiencing CHS
who learn more about CVS outside the formal medical setting may gather that prophylactic medications are the mainstay of episode prevention, rather than cannabis cessation and abstinence.”

Evaluation:

“Bloodwork should include a comprehensive metabolic panel with liver function testing, complete blood count with differential, lipase, urinalysis, and a qualitative urine pregnancy test in a person capable of pregnancy.”
“An electrocardiogram is indicated if a patient has received multiple antiemetics, has an electrolyte abnormality, or is severely malnourished.”
“Abdominal imaging is most helpful to evaluate for suspected structural pathology.”
“A quantitative urine THC level may be helpful for longterm management of adolescents and young adults…A small study in adolescent patients suggests that urine THC levels >100 ng/mL are associated with cannabinoid hyperemesis syndrome….The test may be clinically useful to demonstrate significant marijuana exposure for patients who do not think their use is sufficient to cause their symptoms”

Management:

“Inpatient management can be conceptualized as having two phases. During the first 24 hours, patients require aggressive, proactive management. The goal isto break the vomiting
cycle.”
“Our group’s practice is to select a single antiemetic with evidence in CHS treatment and to schedule this medication at the lowest therapeutic dose for vomiting relief at an interval that prevents recurrence of vomiting. An additional medication may be used as needed for breakthrough symptoms.”
“We typically use olanzapine or haloperidol as the initial agent. We recommend avoiding the use of multiple unscheduled antiemetics ordered “as needed” for nausea and vomiting. This approach risks drug interactions and QTc prolongation.” Typical antiemetics like ondansetron and prochloroperazine are usually ineffective for CHS.
“Regular application of capsaicin cream during the acute phase can decrease the need for oral medications by reducing or eliminating nausea and modestly reducing abdominal pain…We use capsaicin 0.1% cream in our clinical setting.”
“In the second phase of treatment, as the emetogenic phase abates and the patient can sustain oral nutrition, providers should focus on transitioning to a safe outpatient antiemetic
plan.”
“Patients with pre-existing inherited or acquired long QTc should be treated with caution…When a prolonged QTc is identified, providers should consider using topical capsaicin and medications less likely to increase QTc, including lorazepam and aprepitant.”

**These medications, when used for CHS, would be considered “off label.”
**The use of lorazepam and aprepitant have only been report in case studies for CHS.
**Aprepitant can be administered intravenously as a one-time dose.
**Benzodiazepines should be limited to first 24-48 hours due to risk of addcition.

Malnutrition Often Associated with Chronic Cannabis Use:

Despite its perception as causing the ‘munchies,’ “chronic cannabis use is an underrecognized cause of weight loss and malnutrition. The insidious morning nausea and
abdominal pain of the CHS prodrome can contribute to gradual weight loss, and a rapid weight drop may occur with vomiting episodes.”
“Potential medical complications of significant malnutrition include bradycardia, hypotension, hypothermia, orthostatic lightheadedness or presyncopal/syncopal episodes, cold intolerance, fatigue, worsening mood and anxiety, and change in menses…increases risks of superior mesenteric artery syndrome and the refeeding syndrome.”

Outpatient Management of CHS:

“Long-term management of CHS prioritizes cannabis abstinence, reestablishment of normal eating, and return to full daily function, including consistent participation in school
and/or employment.”
“Indications for CHS prophylactic medication are extrapolated from existing literature in
adults with CVS. Prophylaxis should be considered if exacerbations occur more frequently than once a month and last for over 2 days in an adolescent…Amitriptyline, a tricyclic antidepressant, is the first line agent for CHS prophylaxis…Nortriptyline, which is less sedating than amitriptyline, has also shown success in children and adults with CVS.” The authors discussed typical dosing of amitriptyline and nortriptyline (starting at 10-25 mg and titrating up to 1 to 1.5 mg/kg at bedtime [max 75 mg to 100 m])
“We continue the tricyclic antidepressant until hyperemesis exacerbations have been suppressed and the patient has maintained cannabis abstinence for 6-12 months, then slowly taper prophylaxis.”
“CHS is definitively treated with complete cessation and long-term abstinence from marijuana use for weeks to months. Focused treatment of concurrent cannabis use disorder is critical to recovery. We note that patients who intend to abstain from cannabis often struggle for 2-4 weeks after cessation due to withdrawal symptoms.”

My take: This article offers a lot of practical advice for CHS.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Two Games and Vulnerabilities with Generic Drugs

Posted on June 15, 2026 by gutsandgrowth

For those of you who like online games, there are two that I recently discovered that are quick and fun. Currently, both games are free.

MapTap.gg Daily geography game. Each day, the game asks you to identify 5 locations on a realistic unmarked 3D globe. The closer your guess, the higher your score. Each day there are short vignettes and facts.
Anno-Game Daily history game. Each day, the game asks you to determine the year of 5 important historical events. The closer your guess, the higher your score.

K Schulman, AL Kellermann. NEJM 2026;394:1669-1672. Substandard Generic Drugs — Threats to Patient Safety and National Security

An excerpt:

Generic drugs account for more than 90% of prescriptions filled in the United States. The first paragraph on the home page of the Office of Generic Drugs at the Food and Drug Administration (FDA) asserts that “FDA-approved generic drugs have the same high quality, strength, purity and stability as brand-name drugs.” On the strength of this assurance, America’s doctors, pharmacists, and patients assume that every version of a generic drug is equally safe. But this proposition is now being seriously challenged...

Between 2009 and 2019, the availability of generic medicines saved U.S. patients $2.2 trillion, according to the FDA.

Over time, intense price competition drove most production of generic drugs and ingredients offshore to countries with low labor costs and lax regulatory controls. Once that shift occurred, relentless pressure to minimize costs led some manufacturers to compromise on quality. Rapid globalization also outstripped the FDA’s capacity to monitor manufacturers. In 2022, the Government Accountability Office reported that 61% of foreign plants had not been inspected by the FDA in the preceding 5 years.¹

When FDA inspectors finally reach these plants, some find glaring problems…More than 60% of generic-drug shortages are attributable to quality concerns, according to the FDA…

A private-sector laboratory detected high levels of nitrosamines (known carcinogens) in drugs made by several FDA-approved manufacturers, prompting recalls of metformin, angiotensin-receptor blockers, angiotensin-converting–enzyme inhibitors, prazosin, and ranitidine. More recently, independent tests of generic methylphenidate found nitrosamine levels above the FDA’s safety threshold in 7 of 15 immediate-release products…²

Recently, a team of U.S. and South Korean researchers with access to FDA data determined that significantly more serious adverse event reports were linked to generic drugs manufactured in India than to equivalent drugs manufactured in the United States…⁴

In 2008, a total of 238 deaths in the United States were linked to adulterated Chinese heparin. When the FDA toughened its approach to quality assessment of foreign manufacturers, shortages of more than 200 medications followed. This crisis prompted the FDA to prioritize minimizing drug shortages over ensuring safety…

There is a better way to assure the safety of generic drugs. In 1994, the European Medicines Agency (EMA), for example, established a proactive approach involving risk-based surveillance in addition to systematic planned and ad hoc testing of generic drugs both on the market and during routine inspections of manufacturers (in contrast, the FDA does not routinely test generic-drug products themselves, either on the market or during quality inspections of manufacturing plants). EMA testing relies on a network of official medicines control laboratories (OMCLs) that operate in accordance with International Organization for Standardization (ISO) accreditation standards for testing and calibration laboratories. At any point in a drug’s life cycle, an OMCL can pull samples for product testing...

The U.S. government should oversee an effort to rebuild America’s capacity to manufacture generic drugs, combining investment in private manufacturing with incentives for purchasing U.S.-made products under the Medicare and Medicaid programs. Currently, the United States is vulnerable to an embargo of essential drugs or the materials required to make them. A recent evaluation for the Department of Health and Human Services found that 87% of sites that make active pharmaceutical ingredients (APIs) and 63% of sites that produce finished dosage forms were located overseas…

My take (borrowed from the authors): Most generic drugs are safe, but a troubling minority are not…The United States already tests a wide range of consumer products. We should also test our generic drugs.

Related blog posts:

How Much Exercise is Needed for Optimal Cardiovascular Protection?

Posted on June 14, 2026 by gutsandgrowth

Liang Z, Du S, Zhao S, et al. British Journal of Sports Medicine Published Online First: 19 May 2026. doi: 10.1136/bjsports-2025-111351. Open Access! Joint non-linear dose–response associations of device-measured physical activity and cardiorespiratory fitness with cardiovascular disease: a cohort and Mendelian randomisation study

Methods: This accelerometer-based prospective cohort study using the UK Biobank analyzed 17,088 participants. There were 1233 incident cardiovascular disease events which occurred over a median follow-up of 7.85 years.

Key findings:

“Meeting the 150 min/week guideline yielded a modest ~8%–9% risk reduction across fitness levels, whereas achieving a >30% risk reduction required threefold to fourfold higher volumes (~560–610 min/week)”
“Approximately 11.6% of participants, 1980 of 17,088, achieved at least 560 min per week, indicating that although such volumes are attainable, they represent a high behavioural threshold for most individuals”
Limitations: the cohort is likely healthier and fitter than the general population, reflecting a healthy volunteer bias

My take: More moderate-to-vigorous physical activity (MVPA) is associated with better outcomes. Current recommendations of 150 min/week offer benefits but more time is associated with optimal cardiovascular protection.

Related blog posts:

Comparative Safety of Advanced Therapies for Ulcerative Colitis

Posted on June 12, 2026 by gutsandgrowth

D Ahuja et al. Am J Gastroenterol 2026;121:1192–1201. Comparative Safety of Advanced Therapies in Patients With Ulcerative Colitis: An Administrative Claims-Based Study

Methods: Using an administrative claims database (OptumLabs Data Warehouse) with a ‘real-world’ cohort, the authors identified 9,430 patients with UC treated with TNF antagonists (n = 4,111), anti-integrins (n = 3,165), anti-ILs (n = 1,342), JAK inhibitors (n = 701), or sphingosine-1 phosphate receptor modulators (n = 111), followed over median 27 months.

Key findings:

Overall, the risk of serious infections was higher with infliximab than with the other therapies. The incidence of VTE in patients with UC was very low and comparable across all advanced therapies, including JAK inhibitors. Also, the incidence of MACE in patients with UC was
very low and comparable across all advanced therapies, including anti-ILs and JAK inhibitors.

From the discussion: “In a recent network meta-analysis and corresponding clinical guidelines on the management of moderate-to-severe UC, upadacitinib was ranked as having the highest efficacy for induction ofremission compared with all other agents (2,14). However, safety concerns with JAK inhibitors were raised in the pivotal ORAL Surveillance trial (15). In this noninferiority trial, tofacitinib, particularly at higher doses, was associated with a higher risk of serious and opportunistic infections, VTE, and MACE, compared with TNF antagonistsi n patients with rheumatoid arthritis. Following this, the US Food and Drug Administration changed JAK inhibitors’ labeling across all indications, restricting its use in patients with previous failure or intolerance to TNF antagonists…the ORAL Surveillance trial focused on older patients aged 50 years or older with rheumatoid arthritis and at least one cardiovascular risk factor…

[In this study, the] lack of an apparent increase in the risk of JAK inhibitors compared with other medications may be related to superior disease control achieved with JAK inhibitors or reverse causality where patients at high risk of MACE and/or VTE events are not prescribed JAK inhibitors.”

My take: This study provides additional reassurance that newer advanced therapies have similar or better safety than infliximab.

Related blog posts:

Don’t Rush to Judge Risankizumab Effectiveness for Ulcerative Colitis

Posted on June 11, 2026 by gutsandgrowth

R Panaccione et al. Clin Gastroenterol Hepatol 2026; 24: 1424-1433. Open Access! Impact of Extended Risankizumab Treatment in Patients With Ulcerative Colitis Who Did Not Respond to Induction Treatment

Methods:

In the AbbVie-funded phase 3 INSPIRE induction study, 209 initial nonresponders to 12 weeks of 1200 mg intravenous (IV) risankizumab induction were rerandomized to receive 12 weeks of additional 1200 mg risankizumab (weeks 12, 16, and 20) or 180 mg or 360 mg subcutaneous [SC] risankizumab (weeks 12 and 20) in a double-blind fashion
Then, the delayed responders continued to receive blinded risankizumab at their assigned dose in the phase 3 COMMAND maintenance study

Clinical response per adapted Mayo Score (AMS): decrease from baseline ≥2 points and ≥30% from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1
Clinical remission per AMS: SFS ≤1 and not greater than baseline, RBS = 0, and endoscopic subscore ≤1 without the evidence of friability

Key findings:

Initial nonresponders (1200 mg IV [n = 68], 180 mg SC [n = 71], or 360 mg SC [n = 70]) had week 24 clinical response rates of 50%, 56.3%, and 57.1%, respectively
Patients also achieved clinical remission, histologic endoscopic mucosal improvement (8.8%, 12.7%, and 15.7% for both endpoints), endoscopic improvement (17.6%, 18.3%, and 24.3%), and endoscopic remission (1.5%, 8.5%, and 5.7%)

My take: A longer trial of risankizumab is often needed to know with certainty if it will work for ulcerative colitis. More than half of initial nonresponders acquire a clinical response with extended therapy. A similar pattern was noted for risankizumab with Crohn’s disease.

The Spectrum of Esophageal Inflammatory Diseases

Posted on June 10, 2026 by gutsandgrowth

L Bertin et al. Clin Gastroenterol Hepatol 2026; 24: 1220-1231. Open Access! Beyond Eosinophils: Redefining the Spectrum of Esophageal Inflammatory Diseases Through an Immune-Centric Paradigm

This narrative article reviews the four distinct variants that exist beyond classical EoE: EoE-like esophagitis (histologic EoE features with <15 eosinophils/hpf), lymphocytic esophagitis (LyE) (≥30 lymphocytes/hpf), nonspecific esophagitis (NsE) (mixed inflammatory infiltrates), and mast cell esophagitis (elevated intraepithelial mast cells).

Key points:

Differential diagnosis: “Esophageal eosinophilia is not pathognomonic for EoE or EoE-like esophagitis. Alternative causes include GERD, achalasia and other esophageal motility disorders, infectious esophagitis, drug hypersensitivity reactions, connective tissue disorders (systemic sclerosis and dermatomyositis), hypereosinophilic syndrome, graft-versus-host disease, and Crohn’s disease with esophageal involvement.”
“EIDs [esophageal inflammatory diseases] manifest with overlapping yet distinct clinical and endoscopic features.⁴⁹ Dysphagia remains the most consistent symptom across the spectrum, although its prevalence varies significantly”
“EoE-like esophagitis shows interleukin-13 pathway overlap with classical EoE and may progress to EoE (62.2% by 6 years)”
“LyE treatment remains largely empirical, with PPIs showing variable efficacy (24%–86% improvement),⁵³ with a recent multicenter study showing it achieved even lower histological (13% vs 48%) and symptomatic improvement (6.7% vs 43%).⁵⁹ As a second-line therapy, topical steroids should be considered.⁶⁰“
“NsE lacks consensus management strategies, with empiric approaches based on presenting symptoms typically employed.¹⁶“
“McE treatment evidence derives primarily from case reports showing response to combinations targeting mast cell activity.”

My take: Esophageal inflammatory disorders besides EoE are uncommon in the pediatric age group. This article provides a useful review and guidance.

Normalizing Diet with Dupilumab Therapy

Posted on June 9, 2026 by gutsandgrowth

N Wolfest et al. Clin Gastroenterol Hepatol 2026; 24: 1271-1279. Open Access! Efficacy of Dupilumab on Facilitated Food Reintroduction in Eosinophilic Esophagitis

Methods: This open-label pilot study — patients who demonstrated disease control in the dupilumab run-in stage were able to continue into the food reintroduction stage for a total of 52 weeks. Reintroduction of trigger foods occurred at months 3, 6, and 9, while continuing on dupilumab treatment. Symptoms, histology, endoscopy, and esophageal diameter were compared prior to and following every phase of food reintroduction to month 12. All patients had previously failed trigger food reintroduction on their current EoE medication.

Key findings:

Dupilumab effectiveness: At month 3 of the dupilumab run-in stage, 17 of 19 evaluable patients (89%) per protocol had a PEC (peak eosinophil count) of <6 eos/hpf. One patient had a PEC of 6 eos/hpf but was permitted to proceed to the food reintroduction stage.

Food reintroduction:

Reintroduction of an EoE trigger food was successful in 86% of instances (54/63), as defined by a PEC <6 eos/hpf and no symptoms
At month 6, 75% of patients (12/16) successfully reintroduced an EoE trigger food, and, as portion size was increased or additional trigger foods were added, 93% (13/14) and 79% (11/14) successfully introduced EoE trigger foods at months 9 and 12, respectively
By the end of the study, 5 patients successfully achieved unrestricted serving sizes of an EoE trigger food without worsening esophageal biopsies
The mean PEC did not significantly change following food reintroduction at month 6 (5.3 [SD, 8.9]), month 9 (1.3 [SD, 2.8]), or month 12 (2.6 [SD, 4.5]) (see Figures below)

My take (borrowed in part from authors): For most newly-diagnosed patients, the majority prefer medical therapy over dietary restricitons. In those currently managed with dietary restrictions, “dupilumab treatment may provide a safe method for patients with EoE to gradually taper elimination diets for some trigger foods.”

Related blog posts:

Real-life Study of Ustekinumab for Pediatric Crohn’s Disease (REALITI Study)

Posted on June 8, 2026 by gutsandgrowth

SJ Steiner et al. J Pediatr Gastroenterol Nutr. 2026;82:1242–1250. Open Access! Effectiveness and safety of ustekinumab in pediatric Crohn’s disease: Results of the REALITI study

This retrospective study used prospectively-collected data from the ImproveCareNow (ICN) registry for pediatric patients. Overall, 479 patients with CD were treated with ustekinumab, 348 pediatric patients and 131 young adults; most were biologic-exposed (pediatric, 98.9%; young adult, 95.4%).

Key findings:

At week 52, clinical remission was achieved by 47.3% (125/264) of pediatric patients and 44.8% (39/87) of young adults, and CF (corticosteroid-free) clinical remission by 41.3% (109/264) and 39.1% (34/87), respectively
At Week 52 (observed case), among patients with moderately-to-severely active CD, clinical remission was achieved by 36.9% (41/111) of pediatric patients and 34.3% (12/35) of young adults, and CF clinical remission by 31.5% (35/111) and 28.6% (10/35), respectively.
Ustekinumab was well tolerated, with no new safety signals identified; however, a majority (89.4%) of the pediatric patients were 12–17 years old and most (76.5%) weighed ≥40 kg. Thus, further evaluations of ustekinumab in younger pediatric patients with CD and in those weighing <40 kg are still needed.

Observed case analysis of clinical effectiveness endpoints at Week 52 in (A) all patients with CD treated with ustekinumab, and (B) patients with moderately-to-severely active CD treated with ustekinumab.

My take: Studies indicate that newer selective IL-23 agents like risanizumab outperform ustekinumab. However, ustekinumab has FDA approval* for patients 2 years and older. In addition, there are several generic versions of ustekinumab which are less expensive than the newer agents. As such, I anticipate it will continue to be used.

Related blog posts:

*There has been recent approval recent of Stelara (ustekinumab) for the treatment of pediatric patients 2 years and older with moderately to severely active Crohn’s disease. Here’s a link: Johnson & Johnson (JNJ) Gains FDA Approval for Pediatric Crohn’s Disease Treatment

Cheaper Generic Ozempic (semaglutide) Is Coming Soon — But Not for Americans

Posted on June 7, 2026 by gutsandgrowth

NBC News 5/13/26: Cheaper Generic Ozempic (semaglutide) Is Coming Soon — But Not for Americans

An excerpt:

Outside the U.S., approved generic versions of semaglutide are beginning to hit the market. India and Canada recently approved their first generic versions of Ozempic, and countries including China, Brazil and South Africa are expected to soon follow…The U.S., however, remains on a very different timeline.

Evergreening

The standard length of a drug patent in the U.S. is 20 years from the filing date. Novo Nordisk first applied for a U.S. patent on semaglutide in 2006. Due to patent extensions, approved generic versions of semaglutide aren’t expected in the U.S. until at least the end of 2031…

Drugmakers often file additional, secondary patents — a tactic known as evergreening — to extend their monopoly on their product and delay generics. The additional patents can include new doses, formulations or delivery devices…

Novo Nordisk has filed at least 49 semaglutide patents…

Drugmakers’ use of the patent system has delayed cheaper competition and kept prices high for patients.

My take: This is a bad deal for U.S. There is no good reason why patients in the U.S. need to be paying 5-10 times as much for semaglutide as patients in Europe.

Related blog post: “Gaming” U.S. Patent System by Big Pharma

This Day in Gastroenterology History

Posted on June 6, 2026 by gutsandgrowth

From a previous blog post (538: Gut Science Week):

One of the major leaps forward in gut science began with an accidental shooting at a trading post on June 6, 1822. A fur trader named Alexis St. Martin took a bullet in the abdomen, leaving him with a hole ripped through his muscle, bone and internal organs…

His doctor, William Beaumont, could literally tie a bit of food on a string, shove it into St. Martin’s stomach through the hole, and pull it back out again. Using this one weird trick, Beaumont extracted samples of the man’s gastric juices. Over eight years and more than 200 awkwardly invasive experiments, St. Martin and Beaumont gave humanity its first real understanding of how digestion works.