DSM-5 Domains

1. Cognitive Systems   – Processes like attention, perception, memory, language, cognitive control. 

2. Arousal/Regulatory Systems    – Sleep, circadian rhythms, arousal, energy balance, stress regulation.

3. Positive Valence Systems   – Responses to positive motivational situations (e.g., reward, anticipation, habit).

4. Negative Valence Systems   – Responses to aversive or stressful situations (e.g., fear, anxiety, loss).

5. Social Processes   – Perception of self and others, social communication, attachment, and affiliation. 

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NOTES

that even a single abbreviated motivational interviewing session can produce meaningful, sustained effects on reducing frequency of adolescent cannabis use [18]. Lastly, de Gee et al. (2014) examined a motivational enhancement intervention consisting of two 60–90 min individual motivational interviewing sessions spaced one week apart. They compared outcomes to an information control session. Although there was no significant difference between groups on frequency outcomes overall, a subgroup analysis found that heavier users receiving the motivational intervention significantly reduced their quantity of cannabis use over the follow-up period [20]. 3.1.3. Retention in Treatment Programs Kaminer et al. (2017) examined an adaptive treatment program for adolescents with cannabis use disorder. Participants initially received motivational and cognitive behavioral therapy (MET/CBT) for 7 weeks. Those who did not achieve abstinence were categorized as poor responders and randomized to receive an additional 10 weeks of either enhanced CBT or the adolescent community reinforcement approach (ACRA). Only 37% of poor responders completed the full 17-week treatment compared to 78% of those who achieved abstinence with initial MET/CBT (good responders) and required no extra treatment. Additionally, 46% of poor responders failed to complete their assigned extra treatment with enhanced CBT or ACRA versus just 22% non-completion among good responders [15]. Stewart et al. (2015) tested an incentivized intervention by comparing motivational interviewing (MI) alone to MI combined with contingency management (CM), which provided financial rewards for progress towards substance use reduction goals. The incentivized MI + CM group showed increased rates of attending additional treatment sessions after completing the research study compared to non-incentivized MI alone [21]. 3.2. Young Age Groups In 11 controlled trials, two assessed pharmacological intervention (vilazodone and topiramate) [30,43], while the others examined non-pharmacological interventions [23–29,31,32] to determine the most effective interventions for cannabis use in young adults. Below, we outline the significant results related to our outcomes of interest. 3.2.1. Abstinence One clinical trial found significant improvements in cannabis abstinence rates in young adults with cannabis use disorders. Mason et al. (2018) tested an automated text messaging intervention called Peer Network Counseling-text (PNC-txt) compared to a no-treatment control in young adults with cannabis use disorder. The PNC-txt program delivered personalized text messages over 4 weeks focused on motivation and peer network relationships to achieve abstinence. PNC-txt recipients had significantly higher rates of negative drug screens indicating cannabis abstinence at all follow-ups versus controls. For example, 80% of PNC-txt participants had negative drug screens at the 4-week follow-up compared to 53% of controls [23]. 3.2.2. Reduced Frequency and Quantity of Cannabis Use In Fischer et al. (2016), study participants were randomized to receive either brief oral or written cannabis interventions (C-O or C-W) focused on health risks and motivational strategies to reduce cannabis use, or parallel general health information control conditions (H-O and H-W). Those receiving the combined C-O plus C-W cannabis interventions significantly reduced their number of days of cannabis use over 3 months, lowering use from 23.79 days at baseline to 22.41 days at follow-up [25]. Moving from oral to computerized delivery of interventions, Riggs et al. (2018) evaluated an eCHECKUP marijuana personal feedback program compared to an attention control condition providing general stress management tips. The eCHECKUP group received detailed personalized feedback on their cannabis use frequency, risks for cannabis use disorder, and tips to reduce use. Over 6 weeks, the eCHECKUP group significantly Brain Sci. 2024, 14, 227 12 of 18 reduced multiple indicators of cannabis use frequency and severity compared to controls, including hours high per week, days high per week, weeks high per month, and weekly use episodes [28]. Transitioning from behavioral to pharmacological interventions, Meisel et al. (2021) examined the opioid antagonist medication topiramate combined with brief motivational and cognitive behavioral therapy (MET-CBT) compared to MET-CBT with placebo. Participants in both groups received only three sessions of MET-CBT, along with either oral topiramate or placebo over 4 weeks. Results found that the topiramate group used significantly fewer grams of cannabis on days they did elect to use over the 6-week trial, exhibiting reduced quantity but not frequency of use. However, the topiramate group did exhibit significantly higher rates of study dropout due to medication side effects [30]. Finally, Macatee et al. (2021) examined an emotional exposure-based distress tolerance training intervention (DTI) compared to a general health education control among young adults with problematic cannabis use and low distress tolerance. Participants received either two 1 h sessions of the computerized DTI program or two 1 h control sessions on sleep/nutrition. Among those with below-average baseline distress tolerance, the DTI group showed significantly greater reductions in their proportion of cannabis use days from pre- to post-treatment, lowering use by 12.2% versus just a 3% reduction in controls [32]. 3.2.3. Retention in Treatment Rigter et al. (2013) compared multidimensional family therapy (MDFT) to individual psychotherapy (IP) for adolescents with cannabis use disorder. MDFT involved two weekly family/parent sessions plus an additional weekly individual session over 5–6 months, focusing on substance use in the family context. Over 12 months, MDFT had significantly higher treatment completion rates than IP (90% vs. 48%) [26]. 3.2.4. Cravings Two trials have demonstrated efficacious interventions for reducing underlying cannabis cravings among young adults. Mason et al. (2018) again examined automated PNC-txt messages versus control and found significantly greater reductions in self-reported craving scores that were sustained over the 3-month follow-up. As previously mentioned, this study also showed the higher abstinence rate following the intervention [23]. Also, Meisel et al. (2021) evaluated craving as a secondary outcome in their pharmacotherapy trial combining MET-CBT with topiramate versus placebo. Cravings were significantly blunted in the topiramate group, but dropout due to medication side effects were high in this group [30]. 

3.3. Older Adults Six clinical trials examined treatment for cannabis use disorder in older adults, with three focusing on pharmacological interventions (lithium, nabiximols, and dronabinol) [33,36,37] and three examining non-pharmacological treatments for this age group. Below, we outline the notable findings from these studies [34,35,38]. 3.3.1. Abstinence Two studies evaluating psychosocial interventions found significant differences in rates of abstinence from cannabis use over time. Walker et al. (2015) compared standard MET/CBT to MET/CBT plus two maintenance check-up (MCU) booster sessions at 1 and 4 months post treatment for adults with cannabis use disorder. Participants received either nine sessions of MET/CBT alone or MET/CBT plus the two MCU boosters. At the 3-month follow-up, those receiving the MCU boosters had significantly higher abstinence rates than standard MET/CBT (36% vs. 13% abstinent, p < 0.05). Abstinence rates remained numerically higher with MCU at 9 months [34]. Lintzeris et al. (2020) examined the cannabinoid medicine nabiximols combined with psychosocial interventions compared to placebo plus psychosocial treatment in 128 adults Brain Sci. 2024, 14, 227 13 of 18 seeking specialized treatment for cannabis dependence. The nabiximols group had significantly higher rates of urine-confirmed abstinence at the 24-week post-treatment follow-up compared to placebo (23% vs. 9%, p = 0.035) [36]. 3.3.2. Reduced Frequency and Quantity of Cannabis Use Lintzeris et al. (2020) demonstrated that nabiximols treatment significantly reduced usage days during the 24-week post-treatment follow-up compared to the placebo group (6.7 fewer use days, p = 0.006). As previously mentioned, the nabiximols group also had significantly higher rates of urine-confirmed abstinence at follow-up, indicating reduced frequency was associated with increased eventual abstinence [36]. 3.3.3. Withdrawal Symptoms A key challenge in treating adult cannabis use disorder is managing distressing physiological and psychological withdrawal symptoms that frequently lead patients to relapse. Johnston et al. (2014) examined the medication lithium carbonate for managing withdrawal symptoms during cannabis cessation among 38 adult inpatients. Participants underwent a 2-week monitored withdrawal program and were randomized to lithium or placebo for days 2–7. Although lithium did not significantly improve total withdrawal severity scores compared to placebo, it did confer selective relief for the withdrawal symptoms of appetite loss, stomach pain/discomfort, and nightmares. Over half rated lithium as helpful [33]. 4. Discussion The use of cannabinoids for recreational and therapeutic purposes has been described for centuries [44]. Cannabis accounts for the third most commonly used substance worldwide, only after alcohol and tobacco [45]. Considering that around 1 in 10 of regular users of cannabis will develop moderate to severe forms of CUD over time, the need for more effective treatments for this condition is pressing [45].

Moreover, the increasing prevalence of cannabis use, CUD, and its complications over the past decade are not negligible, and treatments to date remain insufficient. As of now, there are no FDA-approved medications for this condition, and the off-label use of psychotropic medications has only demonstrated modest to no benefits, particularly for relapse prevention and abstinence [46]. At best, a few psychotropic medications, including cannabinoid agonists, have shown the potential to alleviate cannabis withdrawal symptoms, particularly insomnia, anorexia, and anxiety/restlessness, whereas most placebo-controlled trials for CUD testing a wide range of psychotropic agents have failed to demonstrate benefits for relapse prevention and sustained abstinence [46]. Unfortunately, side effects from these off-label treatments are not insignificant, often limiting compliance and/or resulting in a return to use of cannabis. Moreover, the use of these medications for specific age groups, such as adolescents and older adults, remains unclear, since most studies tend to exclude these specific cohorts from trials. Behavioral and psychosocial interventions remain the main stay treatment for CUD. However, limited access to these evidence-based interventions, engagement, and retention in treatment are often suboptimal, impacting clinical outcomes and overall prognosis. Notably, although some studies have explored correlates of treatment outcomes, the paucity of data on age-specific treatments for CUD in the existing literature remains. Of note, data suggest that SUDs in older adults remain underestimated and largely untreated, in part because this population has traditionally accounted for only a small fraction of the problem [47–49]. The implications of underdiagnosing and undertreating older adults with SUD, including CUD, are particularly concerning, since these individuals are more vulnerable to adverse outcomes associated with drug use [50]. Despite an increasing need for older adult substance use services, facilities with programs designed for older persons remain relatively scarce [51]. In a study of 13,749 responding facilities in the US, only 17.7% had specific programs for older adults [51]. 

Of note, evidence demonstrates that treatments for SUDs are cost-effective and tend to have similar rates of Brain Sci. 2024, 14, 227 14 of 18 recurrence/relapse compared to other chronic illnesses in the older adult population [52]. Moreover, evidence has also shown that older individuals tend to have greater adherence to treatment and clinical outcomes, including days of use and abstinence rates regardless of level of care, compared to younger counterparts [53]. Unfortunately, screening, diagnosis, and treatment of SUDs in older individuals remain suboptimal [54,55]. Expanding substance use services, particularly in primary care settings, would likely be considerably impactful, since primary care providers may play an important role in early detection and delivery of brief interventions, particularly for this particular age group [56,57]. This study underscores the imperative of tailoring cannabis use disorder (CUD) treatment according to age, as developmental stages significantly influence the underlying mechanisms of problematic use and the most effective strategies for behavior change. During adolescence, cannabis use often begins as a social activity driven by peer influence and novelty-seeking behaviors [58]. Still-developing cognitive control networks make it difficult for teens to resist immediate rewards and social pressures. Interventions should provide external reinforcement through rewards or environmental modifications to facilitate positive choices. Approaches boosting internal motivation like motivational interviewing also show promise by activating teens’ emerging self-reflective capacities and goal-setting abilities. As supported by the Stanger et al. randomized trial, interventions incorporating external reinforcement such as contingency management with rewards for abstinence can compensate and scaffold improved decision-making during this critical neurodevelopmental window. Specifically, adding a rewards program reliant on frequent drug testing to standard motivational and cognitive behavioral therapy (MET/CBT) prolonged adolescent cannabis abstinence durations over 12 months more successfully than MET/CBT alone [16]. Additionally, even brief counseling approaches exploring internal motivations and self-efficacy show efficacy for this population. The Mason et al. brief motivational interview session focused on eliciting adolescents’ personal reasons for and confidence in abstaining [18]. By emphasizing emergent introspection and metacognitive capacities, this individualized approach nearly tripled cannabis abstinence rates subsequently. This promising efficacy of brief, norms-based feedback on adolescent and youth cannabis outcomes warrants dedicated investigation into real-world implementation systems that could support almost universal reach across educational, workplace, and clinical settings. All youth could be screened for escalating cannabis use and select individuals offered these minimally demanding but high-impact interventions grounded in where their use diverges from peer averages. Preventing and reversing escalation early in critical neurodevelopmental phases can avert years of morbidity and functioning loss—making optimization and dissemination of these interventions an urgent priority with young populations. Furthermore, for adolescents, involving parents in standard clinic-based treatment significantly improved abstinence outcomes (Stanger 2015), highlighting the vital role of family engagement when targeting youth substance issues [16]. The same emphasis on the role of family engagement was demonstrated in Rigter’s study in young adult age groups, which showed that interventions involving family members significantly impact treatment outcomes [26]. 

These findings highlight the significance of incorporating familybased interventions into substance use treatment programs for both adolescents and young adults. By recognizing and harnessing the influence of family dynamics, clinicians can enhance treatment effectiveness and promote sustainable recovery outcomes across these age groups. Although young adults have greater self-regulation capacities, honing emotional and impulse control skills remains a key developmental task. Interventions should enable value exploration to strengthen evolving self-identity [59]. Similar to adolescents, it seems that building distress tolerance and protective peer communities as well as motivational enhancement and coping skill training serves as a fundamental basis for cannabis use interventions in younger adults. For example, a distress tolerance program focused on emotional exposure significantly reduced cannabis use days among young adults prone to distress intolerance (Macatee et al., 2021) [32]. Brain Sci. 2024, 14, 227 15 of 18 Additionally, the utilization of computerized or mobile programs harnessing technology holds significant appeal for young adults, offering convenient platforms to bolster motivation and facilitate self-monitoring. By integrating young adults’ peer networks, these interventions provide essential accountability and support. For instance, Mason et al. implemented a 4-week automated text messaging program (PNC-txt) aimed at fostering motivation and nurturing positive peer relationships, resulting in notable increases in abstinence rates and reductions in cravings over a 3-month period [23]. Similarly, Riggs et al. demonstrated the effectiveness of a computerized eCHECKUP program, which provided personalized feedback on individual cannabis use patterns alongside tips for reducing use. This intervention yielded significant declines in use frequency and severity [28]. Hence, holistic interventions blending technology-based supports, distress prevention skill building, and positive peer influence optimization demonstrates high promise for reducing cannabis misuse among young adults. In later life, older adults may face higher challenges, such as chronic pain, sleep disturbances, and mental health issues, that may contribute to relapse into entrenched cannabis use. Unlike other age groups, where studies of pharmacological interventions are limited, there seems to be a notable inclination towards medication-based interventions for older adults, perhaps owing to age-related pharmacokinetic changes and medical comorbidities. For example, Lintzeris et al. found that the cannabinoid medicine nabiximols combined with counseling conferred significantly higher abstinence rates and fewer usage days compared to placebo plus counseling. This underscores the potential utility of pharmaceuticals to help stabilize acute cessation in older individuals by alleviating withdrawal and cravings [36]. 

Hence, for older adults, an integrative approach blending medication relief from protracted withdrawal with counseling focused on building psychological resilience and social supports appears most effective. Additionally, extended monitoring and booster sessions prove vital for preventing slips from evolving into full relapse across aging. Walker et al. demonstrated that incorporating brief maintenance check-up sessions into standard psychosocial care improved short-term abstinence rates [34]. Furthermore, there appears to be disproportionately less research conducted in older adult populations compared to adolescents and young adults. Only 6 of the 24 studies majorly focused specifically on those aged 26–65 years old. This may be because cannabis use peaks in young adulthood, so there is greater perceived need to target those age groups. However, with increasing rates of older adults using cannabis regularly, more studies on effective treatments tailored to that population are warranted [42]. Additionally, evidence suggests potential gender differences in treatment response that may inform further personalization of interventions. Walukevich-Dienst et al. evaluated an online personalized feedback program aimed at reducing problems related to cannabis use among college students. Although no overall effects on use frequency were found, genderspecific analyses revealed that women receiving the personalized feedback intervention reported significantly fewer cannabis-related problems at one-month follow-up compared to female controls. However, no differences between intervention and control groups were observed for men. This indicates that web-based personalized normative and risk feedback may confer greater benefits for female versus male young adults regarding problematic use indicators. These preliminary findings highlight the need to better understand variables moderating treatment response—such as biological sex, psychosocial characteristics, and mechanisms maintaining use—that can enable further individualization of interventions by gender and other individual factors [29]. In summary, effective treatment for cannabis use disorder (CUD) necessitates an individualized approach that considers the diverse age groups affected, tailoring interventions to address specific developmental challenges and opportunities across the lifespan. Customized interventions, whether leveraging contingent rewards for adolescents, technological platforms for young adults, or pharmacological adjuncts for older individuals, have shown promise in enhancing outcomes. However, the optimal combination and sequencing of age-specific treatments remain uncertain, highlighting the need for further comparative Brain Sci. 2024, 14, 227 16 of 18 effectiveness research to elucidate the most efficacious approaches. Nonetheless, adopting a personalized, lifespan developmental perspective holds potential to improve upon the modest treatment outcomes observed thus far. 5. Conclusions In conclusion, addressing cannabis use disorder (CUD) demands tailored interventions that acknowledge the unique developmental stages and challenges individuals face across their lifespan. Although interventions such as contingent rewards for adolescents, technology-based platforms for young adults, and pharmacological adjuncts for older individuals show promise, the optimal treatment combination remains uncertain. Further research, particularly comparative effectiveness studies, is imperative to delineate the most efficacious approaches. Although psychosocial interventions offer personalized strategies, age-specific pharmacological recommendations lack adequate evidence. Given the considerable variability among age groups, age-specific treatments need to be further explored. 

Abstract Introduction: Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among adults and older patients have been reported named cannabis hyperemesis syndrome (CHS). CHS is a condition that leads to repeated and severe N/V in long-term users of cannabinoids. Objective: The aim of this study was to outline current treatments for the management of CHS. Methods: A systematic review was conducted using PubMed, Ovid MEDLINE, Cochrane Central, EMBASE, and Google Scholar. Databases were used to search for articles on CHS published from January 2009 to June 2021, yielding 225 results of which 17 were deemed relevant and underwent review by 2 separate reviewers. Results: The duration of cannabis administration ranged between 6 months to 11 years may precipitate symptoms of CHS. The Rome IV diagnostic criteria of CHS require cannabinoid use and persistence of N/V symptoms for at least the past 6 months. Cannabis cessation is noted to be the most successful management, but other treatments also demonstrated symptom relief; these include hot water hydrotherapy, topical capsaicin cream, haloperidol, droperidol, benzodiazepines, propranolol, and aprepitant administration. Conclusion: More research on CHS is needed to enhance knowledge translation, education, and create awareness in the medical community on the side effects of cannabinoids and to propose the best treatment options. 

Introduction Cannabis is the most-used recreational drug worldwide, and its incidence of use continues to grow over time [1]. Approximately 192 million individuals use cannabis in any of its forms at least once a year [2]. Cannabis is a general term that refers to the products derived from the plant genus Cannabis. The active ingredients of plantbased cannabis are known as cannabinoids and include the psychoactive ingredient tetrahydrocannabinol (THC) and cannabidiol [3]. Cannabinoids have become an area of interest for the management of pain, and nausea and vomiting (N/V) [1–3]. Recent research has shown recurrent cases of N/V with distinct pathogenesis associated with chronic cannabis usage, known as cannabis hyperemesis syndrome (CHS) [3]. CHS is the result of ingesting high amounts of cannabis from a botanical or synthetic source [4]. Recreational use of cannabis is most common among individuals aged 18–25 years, where cannabis-induced N/V has a high incidence [5]. The adult population was defined as 18 years and older, with the older adult population defined as 65 years and older. The condition can cause distress for the patient, in addition to repetitive hospitalization, and impacts costs of healthcare [6]. The episodes of extended N/V in CHS may last from a few hours, days, or weeks [7]. The Rome IV criteria defines CHS as stereotypical episodic vomiting, after prolonged excessive cannabis use with symptom onset >6 months, which is relieved by sustained cessation of cannabis [8]. A demonstration of the grading of N/V and the side effects associated with the respective grading can be found in Table 1. Nabilone, sold under the brand name Cesamet©, is a synthetic cannabinoid with therapeutic use as an antiemetic and as an adjunct analgesic for neuropathic pain. Nabilone mimics THC, the primary psychoactive compound found naturally occurring in cannabis. Despite the current acceptance of Nabilone as a treatment option for N/V in patients with CHS, there is a lack of data regarding the side effects of its prolonged use such as accumulation and toxicity, resulting in exacerbation of N/V rather than curing it. Although the exact mechanism of action for cannabinoids are yet to be determined, there are 3 main hypotheses regarding CHS gastrointestinal cannabinoid receptors 1 (CB1), overriding cannabinoid lipid buildup and genetic polymorphisms in the P450 system. Gastrointestinal CB1 receptors reduce gastric emptying causing the N/V seen in CHS [5, 9]. Cannabinoid lipid buildup can also occur as THC is lipid soluble. During stress, fat is broken down leading to the release of large amounts of THC causing CHS symptoms [10, 11]. Further, genetic polymorphisms in the metabolic P450 enzymes lead to a change in the metabolic rate of THC breakdown causing hyper or hyposensitivity [12, 13]. In-depth mechanisms for different CHS hypotheses are presented in Figure 1. Proving the emetic and antiemetic effects of cannabinoids is difficult due to the overlapping nature of the symptoms with other conditions such as cyclic vomiting syndrome, viral gastroenteritis, and bulimia nervosa [14]. Furthermore, it was only categorized as a functional gastrointestinal disease in 2016 [14]. This syndrome produces consequences ranging from volume loss to esophagus rupture [15]. With worldwide increase in cannabinoid use due to legalization, cases of CHS are increasing [16]. Therefore, it is important for clinicians to recognize CHS. Objective The aim of this systematic review was to highlight current management options for CHS as a potential adverse effect of long-term cannabis use in adults and older populations. Methods A systematic review was conducted by 2 independent researchers using PubMed, Ovid MEDLINE, Cochrane Central, EMBASE and Google Scholar. For each study, the keywords “cannabinoid hyperemesis syndrome,” “nausea,” “vomiting,” and “cannabinoids” were utilized in the search. Eligibility assessment was performed by the independent reviewers (H.S. and S.W.) and disagreements were resolved by consensus. A data extraction excel sheet was developed and used to compile and summarize the relevant studies. Inclusion criteria were established in line with the study objective, where relevant articles underwent data extraction and analysis. Inclusion and exclusion criteria can be found in Table 2. The full electronic search history is shown in Figure 2. Inclusion Criteria We included systematic reviews, retrospective cohorts, case reports, and randomized-controlled trials (RCTs), written in the English language; from January 2009 to June 2021 that described the use of cannabinoids and CHS in adult and older populations (18 years and 

Exclusion Criteria The exclusion criteria included studies published outside the time period of January 2009 to June 2021; nonEnglish language articles that had poor translations; articles not assessing cannabinoid use and CHS as the primary focus; adolescent and youth populations under the age of 18 years were excluded. Results Search Results Relevant articles underwent data extraction and analysis where conclusions of this review are drawn from. There were 225 articles identified and screened, and 103 records were excluded based on the title not including the term CHS. 122 Abstracts were then reviewed, and 101 were eliminated due to study design outside of the inclusion criteria (n = 41), not assessing cannabinoid use (n = 10), non-English studies (n = 21), population age <18 years old (n = 27) and articles that had no results (n = 2). Twenty-one full-text articles were then reviewed, and duplicates were excluded (n = 4). Overall, 17 articles met the final inclusion criteria and warranted analysis: case reports or series (n = 9), RCT (n = 2), retrospective cohort studies (n = 2) and systematic reviews (n = 4). The full search strategy and results are presented in Figure 2. Corroborative themes were identified, and the authors responsible for the contributing research were cited appropriately. All additional sources added to the literature search were referenced in the article. The Cochrane Risk of Bias Tool was used to assess the risk of bias in RCTs found in Table 3. An additional version of the tool for assessing the risk of bias in non-randomized studies can be found in Table 4 [17, 18]. Management of CHS The best method to alleviate symptoms in all studies reviewed was the discontinuation of cannabinoid use. In addition, there were 7 management-described options to control N/V induced by cannabis: (i) hot water hydrotherapy; (ii) topical capsaicin; (iii) droperidol; (iv) benzodiazepines; (v) haloperidol; (vi) propranolol; and (vii) aprepitant. The results are summarized in online supplementary Table 1 (for all online suppl. material, see www.karger.com/doi/10.1159/000520417). Hot Water Hydrotherapy Taking hot baths has been shown to provide temporary relief of N/V as THC disrupts thermoregulation [19]. Hot water hydrotherapy is a common self-treatment for patients diagnosed with CHS as it can cause redirection of blood flow from the enteric system to the skin, leading to N/V, combined with the activation of transient receptor potential vanilloid subtype 1 (TRPV1) [19]. Activation of TRPV1 leads to a reduction in the release of substance P, a neuropeptide associated with inflammation and pain, in nerve endings. Over time, the TRPV1 can become unresponsive due to chronic exposure to THC, resulting in pain caused by an increase in substance P [19]. A case report by Portman and Donovan [20] described a 62-year-old man who was on chemotherapy for long-term malignancy and had a history of recurrent N/V, managed with cannabinoids as an antiemetic. However, cannabis use became pro-emetic and resulted in multimer admissions to the ED. Traditional antiemetics and opioids were ineffective; the only effective treatment was immersion in hot water showers and complete cannabinoid aversion [20]. It should be noted that only qualitative evidence presented as a narrative review was found as evidence related to hot water hydrotherapy treatment. Topical Capsaicin Topical capsaicin cream has shown short-term success in patients suffering from CHS [21]. Capsaicin may be similar to hot water hydrotherapy, causing redirection of blood flow from the enteric system to the skin and leading to activation of TRPV1 receptors, reducing substance P [20]. In all studies examined, capsaicin was applied to the abdomen. A novel piloted RCT conducted by Dean et al. [22] examined topical 0.1% capsaicin versus placebo cream applied on the anterior abdominal/pre-umbilical region. The authors reported a 46% reduction in nausea from baseline using the visual analog scale at 60 min from baseline in the capsaicin arm versus 24.9% in the placebo arm [22]. It was concluded that the antiemetic effect of capsaicin was more efficacious at 60 min compared to 30 min measured from the initial administration of capsaicin [22]. Individual case studies have shown improvement in N/V and discharge within hours of admission when patients were administered 0.075% capsaicin on the abdominal region [23]. A retrospective cohort examined 43 patients within the emergency department (ED), patient’s length of stay (LOS) was reduced with variable capsaicin (0.025–0.1%) administered on the abdomen by a median of 22 min, furthermore, patients received fewer additional medications such as opioids if capsaicin was utilized (p = 0.015) [24]. A recent retrospective cohort study revealed that 0.025–0.15% capsaicin cream was associated with a shorter LOS in the ED when administered earlier upon admission (4.83 h vs. 7.09 h, p = 0.01) [25]. A 41-year-old female presented to the ED with severe N/V unresponsive to typical antiemetics such as pantoprazole and morphine [26]. Topical 0.1% capsaicin application 3 times daily on the epigastric region provided dramatic relief of N/V within 24 h with no return to the ED [26]. It should be noted that the case series using capsaicin cream had a small patient sample cohort of only 1–4 patients; as a result, success in larger cohorts may be questioned [23, 26]. The RCT conducted by Dean et al. [22] presented with overall a low risk of bias; however, there were some concerns related to attrition bias, as one individual ended their involvement early. Despite the appropriate statistical methods used in the study conducted by Wagner et al. [24], the subgroup analysis presented a serious risk of bias due to a small sample that may contain unbalanced prognostic factors. Furthermore, in this study, a reduction of opioid and other medications use was reported in conjunction which may confine the results as opioids may lead to N/V, and upon cessation contribute to an effect that is not discernible from other interventions, such as the capsaicin cream [24]. The retrospective cohort conducted by Yusuf et al. [25] had a moderate bias in selecting patients in the ED, as there was selective reporting of patient outcomes, as only the LOS in the ED was measured. Droperidol Droperidol is a short-acting dopamine antagonist that is most commonly used as an antiemetic and antipsychotic agent [26]. A systematic review conducted by Furyk et al. [27] examined the role of droperidol in the management of CHS. It was found that 0.625–2.5 mg of IV droperidol was the only treatment that showed statistically significant (p < 0.05) differences in the visual analog scale compared to placebo in 48 patients [27]. Current evidence has shown droperidol administration for CHS patients results in a shorter LOS in the hospital, decreased necessity of other antiemetics and showed a significant decrease in nausea severity from baseline when compared to a placebo [28]. Lee et al. [28] reviewed 76 cases of which 37 were treated with droperidol, and 39 received no treatment. The median stay in the hospital for the treatment group was significantly lower than that of the no treatment group (6.7 h vs. 13.9 h, p = 0.014) [28]. It should be noted there was serious bias associated with the selection of participants and reporting of results in the retrospective study conducted by Lee et al. [28]. Benzodiazepines A case study which examined clonazepam in treatment-resistant individuals with CHS revealed that 2 doses of 0.5 mg of clonazepam led to rapid cessation of adverse symptoms, complete symptomatic relief and discharge within 24 h after administration [29]. It should be noted that the evidence for benzodiazepine use in CHS is limited, as there was only 1 case study reported with only 4 patients who experienced N/V relief after administration of benzodiazepines [29]. Haloperidol Haloperidol, an antipsychotic has been used in the management of N/V in severe CHS cases [28, 29]. A case reported by Inyat et al. [30] revealed that 1 mg followed by 2 doses of 2 mg of haloperidol relieved N/V in a patient experiencing resistant CHS. The single patient reported complete resolution of refractory N/V and abdominal pain after administration of the above schedule and 1 month follow up revealed no recurrent symptoms [30]. A case series reported by Witsil and Mycyk [31] found 5 mg of haloperidol administered via intravenous (IV) resulted in successful relief of N/V for 4 patients in the ED. A recent RCT conducted by Ruberto et al. [32]examined haloperidol and ondansetron use for CHS. It was found that 0.05 or 0.1 mg/kg of Haldol was superior to ondansetron in decreasing N/V measured with the visual analog scale (p = 0.01) and a shorter ER departure (p = 0.03); however, there were 2 cases of dystonia with the higher dose of haloperidol [32]. A single case report of an 18-year-old woman who presented to the ED with refractory N/V, unwilling to discontinue recreational cannabinoid use agreed to initiate a trial of 5 mg haloperidol daily for 3 weeks [33]. There were no adverse effects reported and there was a complete cessation of N/V for this patient [33]. It should be noted that the majority of evidence found for haloperidol were case studies, which had limited generalizability [30, 31, 33]. However, the RCT by Ruberto et al. [32] was found to have low overall bias, as there was appropriate cohort randomization, allocation concealment, and blinding of participants and outcome assessors without selective reporting of haloperidol used for CHS. Propranolol Richards and Dutzak [34] presented a single case study that examined an extreme case of CHS in the ER who had intractable N/V, abdominal discomfort and who was unresponsive to standard antiemetics. One milligram followed by 1 mg IV injections of propranolol 1 h apart led to rapid termination of N/V and complete resolution of hyperemesis after the second injection [34]. It should be noted there was limited evidence for propranolol use as it was the only case study we found involving a single patient [34]. Aprepitant Aprepitant is a Neurokinin 1 (NK1) receptor antagonist and similarly to capsaicin is involved in the regulation of substance P to alleviate N/V in CHS [35]. A case report described by Parvataneni et al. [35] revealed a 30-year-old female with intermittent N/V who was unresponsive to conventional emetics such as ondansetron. The only treatment the patient responded well to was aprepitant. She was discharged symptom-free 24 h later after the administration of aprepitant [35]. A major limitation of this case report is that the dosage of aprepitant was not described. Discussion Chronic cannabinoid usage can lead to recurrent N/V with distinct pathogenesis, known as CHS. There is a need for awareness among the medical community about what cannabis can and cannot do as CHS can lead to death [36]. Three mechanisms have been proposed for the development of CHS; these are gastrointestinal CB1 overriding, cannabinoid lipid buildup, and genetic polymorphisms in the P450 system. The exact mechanism, however, remains unknown, and it is out of scope for this review to explore it further. Currently, there is no reliable management regime for patients with CHS with the exception of complete cessation of cannabis and response to conventional antiemetics is insufficient. Several treatments have been described to relieve N/V in CHS; however, there are limited controlled data to support management decisions. Topical capsaicin and haloperidol are currently the only treatment with efficacy validated in RCTs [22, 32]. Capsaicin is inexpensive, has shown positive drug-drug interactions with co-administered medications, and has led to decrease opioid requirement/usage, therefore may be feasible for CHS treatment and decrease unnecessary healthcare costs and visits [19, 21–26]. Haloperidol showed improvements in N/V and decreased the LOS in the ED; however, caution should be exercised as it has been shown to cause acute dystonia in higher dosages [30–33]. Other pharmacological interventions, such as droperidol used in the ED for the treatment of CHS, showed accelerated discharge which may help preserve ED resources [27, 28]. Propranolol has also shown relief in N/V for individuals with severe recurrent CHS [34]. Aprepitant was found to rapidly relive N/V in patients resistant to traditional antiemetics [35]. Factors such as persistent stigma, conflicting regulations, research barriers, and scarcity among medicinal cannabinoids, which arises from poor awareness in patients, healthcare professionals, and stakeholders, can hinder the successful integration of cannabinoids in multiple settings [1]. Due to the growing use of cannabinoid integrative medicines, healthcare professionals must be cognizant that N/V in patients undergoing prolonged cannabis treatment may develop cannabinoid toxicity and CHS. N/V induced by cannabinoids may be masked by N/V related to cancer or side effects of chemotherapy drugs [5]. This awareness may help reduce, identify and effectively manage polypharmacy and cannabinoid-related side effects. An example of chronic medicinal cannabis administration is cancer treatment. Cannabis is often used by cancer patients as a self-managing strategy with common routes of administration being concentrated oil capsules, smoking and oromucosal spray [37]. Studies have shown that 1 in 5 patients used cannabis within the preceding 6 months, and 1 in 8 patients used cannabis for at least one cancer-related symptom [38]. Cannabinoids are mostly used in cancer patients to manage symptoms such as chemotherapy-induced N/V, severe pain, muscle spasms, and cachexia [39]. Cannabinoids such as THC and nabilone provided significant (p < 0.01) antiemetic effects for (chemotherapy-induced N/V) compared to placebo; however, cannabinoids were comparable to other antiemetic drugs such as prochlorperazine, domperidone, and alizapride [40, 41]. Side effects were more profound in older patients [42]. Drug interactions between chemotherapy drugs and cannabinoids can lead to undesirable adverse events. For example, cisplatin and paclitaxel can reduce drug clearance, resulting in delayed metabolism of Cesamet leading to toxic levels of THC causing CHS [43]. 

Compulsive hot water bathing can be an important marker for the diagnosis of CHS [5]. Currently, there are high levels of misdiagnosis of CHS. Conditions can overlap or mask CHS including cyclic vomiting syndrome, eating disorders, or drug-seeking behavior [44]. Knowledge of pharmacological treatments for managing CHS may lessen the burden of ED resources with the recurring admission of patients with CHS [20, 23, 25, 28, 31, 33, 35]. Furthermore, indications, contraindications, and drug-drug interaction should be kept in mind and risks versus benefits weighed in older adults with multiple comorbidities while considering the management options. In older populations, benzodiazepines should be used with caution in the management of CHS due to the potential risk of addiction, cognitive impairment, development of delirium, and falls [45]. Haloperidol should also be used with caution in patients with dementia and Parkinson’s disease, as dopamine blockade can dramatically worsen symptoms causing extrapyramidal side effects and incapacitation [46]. Furthermore, propranolol in patients with chronic obstructive pulmonary disease (COPD) and sinus bradycardia should be avoided, as it worsens bronchoconstriction and bradycardia [47]. Awareness in the public and healthcare professionals about the risk of the development of CHS in prolonged cannabis users will help fill existing knowledge gaps. Limitations Only 2 RCTs have investigated topical capsaicin and haloperidol use in patients with CHS [22, 32]. Three retrospective studies were short-term, with small sample sizes, without a standardized reporting of outcomes and subject to the risk of bias found in Tables 3 and 4 [24, 25, 28]. Conclusions made were limited due to the low-quality of available evidence. Additionally, some of the statistically significant studies did not measure symptom relief, instead looked at the reduced LOS in hospitals [23–25, 28, 31]. Furthermore, LOS in the ED was used to measure the stabilization of N/V symptoms; however, it was not a marker of CHS cure. In addition to the lack of controlled studies, most of the articles published on CHS were descriptive case reports [20, 23, 26, 29–31, 33–35]. This anecdotal evidence is important clinically; however, CHS and its management options need to be viewed in the broader context of controlled research. Many different treatments and dosages have been reported among case studies, which may not be generalized to the wider population. It is uncertain whether other adverse effects, rather than N/V, may have arisen from cannabinoid administration. Further Research Due to the global acceptance of medicinal cannabis, further studies should be conducted to fully understand both the beneficial and detrimental effects of cannabinoid drugs, as well as the consequences of its prolonged use and increased concentrations of cannabinoids. RCTs with larger sample sizes and longer follow-ups are warranted. Precise diagnostic criteria for CHS should be postulated where duration and dose of cannabis are predetermined, especially in older adults or patients with renal impairment. Specific genetic variations such as the P450 enzyme polymorphism can also be further evaluated to determine the predisposition for CHS among users. The presented side effects of cannabinoid drugs suggest that further studies are needed to evaluate the safe concentrations of cannabinoid drugs. Furthermore, the data on benzodiazepine use in older populations with CHS are insufficient and based only on case reports; as a result, safe translation of the existent evidence to clinical practice is unclear and requires further investigation [34]. Conclusions With the emergence of cannabis and its widespread usage in various settings, clinicians and users should be more aware of the long-term effects of cannabinoids. CHS is a potential side effect of prolonged cannabis use, causing major distress to consumers. While synthetic cannabinoids have been accepted as one of the main drugs to relieve N/V, their dosage and duration of administration have not been thoroughly investigated long term. This systematic review alerts the possible outcomes of cannabis use and explores the available management options of CHS. The focus of this review is to stress the importance of rapid recognition, diagnosis, and the available treatment options in adults and older populations. Careful consideration is imperative in older individuals where comorbidities and pharmacological interacts can mask or exacerbate CHS. The novel and highlighted unconventional management options for CHS can be solidified as best practice guidelines with future large-scale research initiatives.  

Abstract

This review focuses on Cannabis Hyperemesis Syndrome (CHS) in youth, a condition linked to chronic cannabis use and characterized by cyclic vomiting, abdominal pain, and dehydration. The objectives were to explore CHS progression in youth and its impact on health, and to assess current treatment strategies. There are the three distinct phases of CHS: prodromal, hyperemetic, and recovery. During the prodromal phase, individuals experience early morning nausea and discomfort, often mistakenly alleviated by continued cannabis use. The hyperemetic phase is marked by severe vomiting, dehydration, and complications like electrolyte imbalances, leading to potentially serious health risks. Temporary relief may be experienced through hot showers or baths. In the recovery phase, symptoms gradually resolve, and normal eating and bathing habits return. The review emphasizes the physical and psychological impacts of CHS on youth, highlighting the potential for misdiagnosis and the importance of early intervention. It stresses the need for targeted educational efforts in schools, healthcare settings, and public health campaigns to prevent delayed diagnosis and improve outcomes. Findings underscore the importance of increasing healthcare provider awareness and promoting preventive education. The review also advocates for further research into CHS pathophysiology to improve diagnostic and treatment protocols for young populations.

Keywords: cannabis hyperemesis syndrome; youth; cannabis use; vomiting; dehydration; mental health; treatment; public health; abdominal pain; intervention

1. Introduction

Youth cannabis use is a growing global health issue. In 2021, the global annual prevalence of cannabis use among youth aged 15–16 years was 5.3%, with Europe reporting a higher rate of 11.0% [1]. Meanwhile, in the United States, cannabis use among 19–22-year-olds reached a historic high, with 42.6% reporting use in the past year [2]. Canada also ranks among the highest globally for youth cannabis use [3]. According to the 2024 Canadian Cannabis Survey, 41% of Canadians aged 16–19 reported using cannabis in the past year, with 20% reporting use within the past month and 9% engaging in daily or almost daily use. Usage rates peaked among Canadians aged 20–24, with 48% reporting cannabis use in the past year [4].

A significant concern with youth cannabis use is the increasing potency of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound responsible for the “high” associated with cannabis consumption [5,6,7,8]. THC potency has risen by 400% over the past four decades, increasing from 3% in the 1980s to 15% in 2023, with some strains averaging as high as 30% [9]. Since the brain continues to develop until approximately age 25, THC exposure during this critical period can disrupt neural development, impairing the formation and pruning of neural connections. This disruption can result in long-term cognitive deficits, including difficulties with attention, memory, and learning [10]. Youth cannabis use is also linked to an elevated risk of depression and anxiety [11,12], psychosis and paranoia [13], self-harm [14], and a heightened likelihood of developing cannabis use disorders [15].

A growing concern associated with high-potency cannabis is Cannabis Hyperemesis Syndrome (CHS), a gastrointestinal condition that affects individuals who use cannabis regularly (e.g., daily to weekly) over an extended period (from several months to years). CHS is characterized by severe and persistent vomiting lasting for hours or days, chronic nausea that worsens with cannabis use, abdominal cramping, and temporary symptom relief from hot showers or baths [5,6,8,16,17,18,19,20,21,22,23,24,25,26]. While definitive causation has not been established, emerging evidence suggests that chronic use of high-potency cannabis may be associated with a heightened risk of developing CHS [8]. Younger individuals are also disproportionately affected compared to middle-aged or older adults [6]. CHS was not documented in the literature until 2004 [27], likely due to the limited clinical recognition of the syndrome and a lack of formal case documentation. As a result, many clinicians and cannabis users remain unaware of the condition [28], highlighting the need for increased education and awareness.

A systematic review of 21 studies on CHS diagnosis and management in adolescents, involving a total of 24 patients, revealed that females were more likely than males to present with CHS, and 21% of the patients had a history of anxiety or depression [29]. Although large-scale studies are limited, recent research from Ontario, Canada, highlighted a significant increase in CHS-related emergency department visits among individuals aged 19–24 after the introduction of a legal commercial cannabis market (March 2020–June 2021), with an incident rate ratio of 1.60 (95% confidence interval, 1.19–2.16) [30]. The researchers argued that the commercialization of cannabis markets may have contributed to the rising rates of CHS-related emergency visits [30], a concern that is frequently echoed by others [6,16,21,23,26,31,32].

Given the limited awareness of CHS among both cannabis users and healthcare providers [5,6,26,28,33], this article provides a comprehensive and up-to-date overview of CHS in youth. Building on recent advancements in the literature, it synthesizes the latest evidence on CHS symptoms, diagnostic challenges, and phases of the condition, while also examining its physical and mental health impacts. This review goes further by addressing nutritional considerations, potential misdiagnoses of eating disorders, and the implications of cannabis legalization on youth health. With cannabis use becoming more prevalent and socially accepted, especially among young people, it is critical to raise awareness of CHS and support early intervention, prevention strategies, and clinical education. We hope this expanded scope and recency of evidence will make the paper a useful reference for both clinicians and public health professionals.

2. Materials and Methods

This article is a narrative review that synthesizes the most recent and relevant literature on CHS in youth. The review was guided by a set of predefined thematic areas, including symptomatology and diagnosis, symptom phases, nutritional considerations, physical and mental health impacts, and implications for prevention, education, and public health. These themes were developed in advance and used to guide both the literature search and synthesis process.

An iterative literature search was conducted from October 2024 to March 2025 using PubMed and Google Scholar. Search terms included combinations of keywords such as “Cannabis Hyperemesis Syndrome”, “CHS”, “cyclic vomiting” “adolescents”, “youth”, “cannabis use”, “vomiting”, “prevalence”, “pathophysiology”, “nutrition”, and “treatment”. Additional studies were identified by screening the reference lists of key papers. No restrictions were placed on language, publication date, or geographic location.

Peer-reviewed articles were included if they focused on CHS and addressed at least one of the predefined themes relevant to youth. Eligible studies covered the clinical presentation, diagnosis, symptom progression, treatment and management strategies, prevalence, or public health implications of CHS in adolescents or young adults. Only original research articles were included, such as randomized controlled trials, observational studies, case reports, case series, and qualitative studies. Review articles, expert commentaries, and opinion pieces were excluded to avoid the duplication of findings and maintain focus on primary data sources. Studies were also excluded if they did not focus specifically on CHS or lacked relevance to youth populations.

Articles were screened manually, and relevant data were extracted and synthesized according to thematic relevance. Table 1 provides an overview of the 13 articles included in this review, spanning publications from 2004 to 2024. These articles consisted of 9 case-based studies (6 case reports and 3 case series), 1 randomized controlled trial, 1 longitudinal analysis, 1 repeated cross-sectional study, and 1 qualitative study. Every effort was made to include the most up-to-date and comprehensive literature available up to March 2025.

Table 1. Summary of included studies on cannabis hyperemesis syndrome in youth (N = 13).

A total of 41 peer-reviewed articles were identified through this process. Titles and abstracts were manually screened to assess relevance to CHS in youth, with three articles excluded for lack of relevance. Full-text review was conducted for the remaining 38 articles. Of these, 25 were excluded because they did not present original research data (e.g., narrative reviews, systematic or scoping reviews, expert commentaries). Thirteen original research articles met inclusion criteria and were included in the final synthesis. A modified PRISMA flow diagram is provided in Figure 1 to illustrate this process.

Ijerph 22 00633 g001

Figure 1. Modified PRISMA flow diagram.

3. Symptoms and Diagnosis of Cannabis Hyperemesis Syndrome

CHS is a condition that manifests in individuals who use cannabis frequently over a prolonged period. In their pioneering study, Allen et al. [27] reported on 10 patients from South Australia who experienced cyclical vomiting attributed to chronic cannabis use. The authors noted that 9 out of 10 patients sought relief through multiple hot showers or baths during the acute phase of their illness, and symptoms resolved with cannabis abstinence. While these observations provided an important initial link between chronic cannabis use and cyclical vomiting, the small sample size limited the generalizability of their findings. Additionally, the lack of a control group or randomization underscored the need for larger, more rigorously controlled studies to confirm causality [42].

Since this initial report, cases of CHS have been documented worldwide [6,26], with the first reports emerging from Germany in 2011 [37] and Puerto Rico in 2015 [36]. Emergency department visits for CHS in Canada and the United States have also doubled between 2017 and 2021 [16], highlighting the growing prevalence of this condition as cannabis use becomes more widespread.

The pathophysiology of CHS is complex and is only recently becoming more understood. Paradoxically, while low doses of cannabis can reduce nausea, chronic or high-doses can lead to CHS [11,19]. This is thought to result from disruptions in the endocannabinoid system, the pituitary-adrenal axis, and sympathetic nervous system regulation, with genetic predispositions and stress often playing significant roles [11]. Adolescents are known to experience higher levels of stress than older individuals, a developmental reality that can interact with genetic predispositions to increase the likelihood of adverse health outcomes [43]. Chronic cannabis use may also impair gastric emptying and contribute to symptoms through THC accumulation in fat cells, illustrating the dual anti-emetic and pro-emetic effects of cannabis [11].

A hallmark symptom of CHS is cyclic vomiting, characterized by episodes of severe nausea and vomiting separated by asymptomatic periods lasting weeks or months [6,8,16,18,26,44]. These episodes often include debilitating abdominal pain, and excessive vomiting can lead to dehydration, electrolyte imbalances, and disorientation [6,8,11,16,20,38,44]. A distinctive feature of CHS is the compulsive need for hot showers or baths to relieve symptoms [6,8,16,19,22,23,25,26,32,39]. Compulsive hot bathing is not an anxiety-related behavior but rather a learned response to symptom relief [6,8,26,27,32]. The most effective long-term treatment for CHS, however, is cannabis cessation [5,6,8,11,16,19,26,45]. A systematic review of case reports found that 96.8% of patients who stopped using cannabis experienced complete resolution of symptoms [8]. Symptoms typically resolve within days of stopping cannabis use [6,8], although they can reemerge within 24 h after the last use [16].

What remains unknown about CHS is why some chronic cannabis users develop the condition while others do not, and why symptoms manifest earlier in some individuals than in others [6]. This gap in understanding underscores the need for further research into the condition’s underlying mechanisms and risk factors. However, CHS is now diagnosed under the Rome IV criteria, which includes prolonged and excessive cannabis use, cyclic vomiting, resolution of vomiting episodes following sustained cannabis abstinence, and often, compulsive hot baths or showers for symptom relief [6,21,23,26,46]. This suggests that the diagnosis of CHS relies heavily on recognizing specific symptoms and patterns of patient behavior [6].

A systematic review of 211 CHS cases revealed a typical progression of the condition: the median age of first cannabis use was 16 years, symptoms began at 24 years, and diagnosis was made at 28 years. Among these patients, 71.6% reported daily cannabis use, while only 2.4% used cannabis less than once per week [8]. Importantly, there is no evidence that a single use or experimentation with cannabis can trigger CHS [6].

Despite being considered a rare condition by both clinicians and cannabis users, many cases of CHS remain undiagnosed or misdiagnosed. This is primarily because the symptoms—nausea, abdominal pain, and vomiting—overlap with numerous other medical conditions (e.g., gastroenteritis, peptic ulcer disease, cyclic vomiting syndrome), complicating the diagnostic process [6,8,35]. Addressing this gap in recognition and treatment is critical to improving outcomes for those affected.

While CHS is often underdiagnosed in adults, it is even more frequently overlooked in youth [6,8,18,38]. This is likely due to underreporting of cannabis use and other substances, driven by fear of judgment or stigma [47]. However, research indicates higher rates of CHS among individuals who use other substances [16]. For instance, cannabis use in youth is strongly linked to vaping [48,49], cigarette smoking [48,50], and alcohol consumption [50]. This lack of recognition by clinicians [5,6,28,33] may leave young people unaware that their symptoms are connected to chronic cannabis use. In some cases, youth may mistakenly believe that cannabis can relieve their cyclic vomiting, potentially exacerbating the condition [8].

Diagnosing CHS can thus be a lengthy and expensive process, often involving unnecessary procedures such as computed tomography (CT) scans, magnetic resonance imaging (MRI), gastric emptying tests, and colonoscopies [5,6,8,20,51]. Given these challenges, all youth presenting with cyclic vomiting should be systematically screened for cannabis use and compulsive hot bathing behaviors [8]. For patients who continue to experience CHS despite being informed of the link between their symptoms and cannabis use, referral to addiction specialists, substance use counselors, or rehabilitation programs may be necessary [5,6,45]. This might also suggest that cannabis is more addictive than previously understood.

4. Phases of Cannabis Hyperemesis Syndrome

The symptoms of CHS typically progress through three distinct phases: prodromal, hyperemetic, and recovery. During the prodromal phase, which can last for several months, individuals often experience early morning nausea, fear of vomiting, and abdominal discomfort. Despite these symptoms, they usually continue using cannabis, mistakenly believing it alleviates their nausea [21,26]. They also tend to maintain their usual dietary habits and body weight [21].

The hyperemetic phase is characterized by severe, persistent cyclic vomiting and intense abdominal pain, typically lasting 1–2 days, though it can sometimes extend longer [21,26,52]. This acute phase can lead to dehydration and electrolyte imbalances. Additional symptoms may include hot flashes, sweating, trembling, hypertension [21], weight loss, and difficulty keeping food down without vomiting [26]. It is often during this phase that individuals discover temporary relief from symptoms through very hot showers or baths. However, symptoms quickly return as the water cools or when they leave the hot water [26,27,53].

In the recovery phase, CHS symptoms fully resolve, marked by a return to normal bathing habits, regular eating patterns, and weight gain [21,26]. This phase typically begins within days to weeks of cannabis cessation [21]. One of the main challenges, however, is maintaining cannabis abstinence; symptom recurrence is common in individuals who resume cannabis use, which can perpetuate the cycle of illness [21,26]. While many patients experience complete symptom resolution with sustained abstinence, others may require behavioral support or addiction counseling to prevent relapse [21].

5. The Impact of Cannabis Hyperemesis Syndrome on Physical and Mental Health

Chronic cannabis use can have significant and sometimes severe physical and psychological effects on individuals. While the physical symptoms of CHS can be challenging, the condition also takes a toll on mental health, often intensifying emotional distress.

Frequent vomiting due to CHS may cause the erosion of tooth enamel, potentially leading to tooth loss [16]. Additionally, long-term chronic cannabis use and CHS can result in unintended weight loss, as individuals with the condition often struggle to retain food [6,18,26,38,44]. The condition can also cause severe dehydration and acute kidney injury, sometimes requiring emergency department visits and hospitalization [6,8,16]. In fact, it is common for CHS patients to present frequently to the emergency department and be hospitalized multiple times each year [6]. In rare instances, CHS can lead to death due to electrolyte imbalances resulting from chronic vomiting [6,22,26].

CHS can also negatively affect mental health. The emotional strain caused by frequent vomiting and dehydration can lead to increased anxiety, isolation, and depression, particularly when individuals are unaware that their chronic cannabis use is the underlying cause [21]. Anxiety and depressive symptoms may worsen when healthcare providers are unaware of the cause of the symptoms, especially during repeated visits to the emergency department or long hospital stays without a clear diagnosis. However, more research is needed to determine whether frequent emergency department visits for cannabis-related issues in youth contribute to greater mental health challenges [54].

Importantly, it is possible that some individuals began using cannabis in the first place to cope with pre-existing mental health conditions such as anxiety or depression [3]. In these cases, CHS symptoms may exacerbate, rather than cause, these underlying conditions. This distinction highlights the complex interplay between mental health and cannabis use, where cannabis may both contribute to and be used in response to psychological distress. Additionally, the cognitive impairment linked to CHS [10] could be aggravated by cyclic vomiting and dehydration, as well as the stress of repeated medical interventions.

The physical and psychological impacts of CHS may lead to an increase in substance use. Cannabis may be used as a coping mechanism, despite its potential to worsen CHS symptoms. In a qualitative study of semi-structured interviews with clinicians from California, one clinician noted about adolescents, “I’m seeing more and more who are using daily and who say that they have to in order to cope” [41]. Finally, the stigma surrounding CHS, coupled with the fear of being judged by family, friends, or healthcare providers, may discourage individuals from seeking treatment. This can result in heightened stress and increased feelings of isolation [46].

Furthermore, the negative effects of chronic cannabis use—such as cognitive dysfunction, motivational deficits, and poor academic performance—may intersect with the effects of CHS, compounding functional impairments in youth. For example, both CHS and long-term cannabis use may independently contribute to difficulties with attention, memory, and emotional regulation, potentially making it harder for affected individuals to recover or adhere to treatment recommendations [10,12,29,46].

6. The Importance of Early Intervention and Preventive Education

While there is no overarching acute or long-term evidence-based treatment protocol for CHS [11,26], the San Diego Emergency Medicine Oversight Commission published treatment guidelines in 2018 that recommended rehydration and supportive patient education and counsel to stop the use of cannabis [20]. More recently, the 2024 American Gastroenterology Association Clinical Practice Update recommended a combination of evidence-based psychosocial interventions and pharmacological treatments for management of CHS, although they did not discuss the efficacy of the acute treatments [11]. Regardless, early recognition of CHS is crucial to prevent complications arising from severe dehydration and fluid imbalance [23].

6.1. The Need for Youth-Specific Education

Education on CHS should begin before symptoms develop, particularly in youth who are more likely to use cannabis regularly while lacking awareness of its potential harms. Many CHS patients do not initially believe that cannabis can cause hyperemesis [6], making targeted education efforts in schools, healthcare settings, and public health campaigns essential for prevention. Misconceptions surrounding cannabis use—such as the belief that it is entirely safe or non-addictive—can delay diagnosis and treatment, leading to repeated emergency department visits and unnecessary medical testing [45].

6.2. Early Recognition and Treatment

Patients who go to the emergency department with dehydration caused by CHS usually receive intravenous fluids and antinausea medications [8,16,26,32]. However, conventional antiemetic therapy (e.g., ondansetron) offers little to no relief of symptoms [6,11,19,20,25,26,32]. Some evidence suggests that topical capsaicin (0.1%) cream may decrease nausea when applied to the upper abdomen [5,6,8,11,16,20,24,32,34]. Additionally, acute and short-term use of benzodiazepines (antianxiety medication) and haloperidol (antipsychotic medication) can be useful for some patients [5,8,11,16,20,32], while opioids should be avoided, as they may worsen symptoms and lead to dependence [8,20].

A randomized, triple-blind crossover trial from Ontario, Canada found that a one-time low dose of haloperidol at 0.05 or 0.1 mg/kg (n = 13 subjects) was superior to ondansetron 8 mg (i.e., n = 17 subjects) as a first-line treatment for acute CHS by reducing nausea and abdominal pain, decreasing the need for rescue antiemetics, and allowing earlier discharge from the emergency department [40]. Hospital admission may also resolve CHS by ensuring cannabis cessation during the inpatient stay [6]. However, recommending immediate cessation of cannabis can lead to withdrawal symptoms and a high risk of relapse [16,22,24], which should be carefully discussed with patients.

6.3. The Role of Primary Care and Public Health

Preventative education about CHS should be integrated into discussions about cannabis use in primary care, youth health visits, and school-based health programs. Given that youth may be resistant to quitting cannabis, healthcare providers should approach cessation discussions with harm reduction strategies, including gradual reduction plans, mental health support, and alternative coping mechanisms for those who use cannabis for stress relief or anxiety. Recognizing a patient’s resistance to stopping cannabis even temporarily can also serve as a clinical indicator of chronic cannabis use [6].

6.4. Healthcare and Societal Benefits of Early Intervention

Not only does early intervention spare the individual from unnecessary tests and procedures, but it also saves the healthcare system considerable time and resources [6]. Providing a definitive diagnosis at an early stage may increase the likelihood that young patients will acknowledge the role of cannabis in their symptoms and consider cessation [33,45]. A public health approach that combines early recognition, targeted education, and integrated treatment strategies has the potential to significantly reduce the burden of CHS on both patients and the healthcare system.

By fostering awareness among youth, parents, educators, and healthcare providers, CHS-related emergency visits can be minimized, and individuals struggling with cannabis-related health issues can receive timely and appropriate care.

6.5. Enhancing Disclosure of Cannabis Use in Youth

A significant barrier to the diagnosis and treatment of CHS in youth is the reluctance to disclose cannabis use to healthcare providers, particularly in emergency or clinical settings. This reluctance is often rooted in stigma surrounding cannabis use, fear of judgment, or concerns about legal repercussions [41]. To facilitate disclosure and ensure appropriate care, it is crucial for healthcare providers to create a supportive and non-stigmatizing environment.

One evidence-based recommendation is for providers to receive training on how to approach sensitive topics such as drug use in a non-judgmental manner. This can be achieved through the use of open-ended, neutral questions that avoid accusatory or stigmatizing language. For instance, asking “Have you been using cannabis or other substances recently?” rather than phrasing the question in a way that implies blame or judgment, such as “How much cannabis have you been using?” can help make patients feel more comfortable. This approach has been supported in research on youth substance use [3,10].

Further, medical providers should be educated on the importance of building trust with their patients. When youth feel that their healthcare provider is genuinely concerned about their well-being, they may be more likely to disclose their cannabis use, which in turn aids in the accurate diagnosis and effective treatment of CHS. Building trust and fostering an open dialogue is essential in addressing concerns about cannabis use among youth [12,41].

By fostering an open, empathetic dialogue, providers can not only increase the likelihood of cannabis disclosure but also encourage early intervention and prevention strategies for CHS, ultimately improving both short- and long-term outcomes for young patients [5,29].

7. Nutritional Considerations with Cannabis Hyperemesis Syndrome

When patients are hospitalized with CHS during the hyperemesis phase, treatment typically involves withholding all food and beverages, administering intravenous fluids to manage hydration, and gradually reintroducing clear liquids and food as symptoms improve and tolerance allows [11,24]. For those treated at home, fluids with glucose and electrolytes are recommended between vomiting episodes to stay hydrated [11].

As symptoms improve, patients may benefit from reintroducing bland, easily digestible foods, such as bananas, toast, rice, and broth, while avoiding fatty, spicy, or acidic foods that may trigger nausea. Due to the risk of prolonged vomiting, healthcare providers should monitor for electrolyte imbalances, including hypokalemia (low potassium) and magnesium deficiencies, which may require supplementation [11].

It is possible that CHS is misdiagnosed as an eating disorder because hyperemesis can become mistaken for a self-induced purging behavior [21,26]. Bulimia nervosa, for example, is a common eating disorder among young people and occurs in individuals who have difficulty controlling the quantity of food consumed (i.e., typically consuming more food in a 2 h period than most individuals), followed by purging behaviors [55,56]. This purging behavior after eating a large quantity of food may lead to a false diagnosis of bulimia nervosa when in fact it is really CHS [6]. However, a key distinction is that CHS-related vomiting is involuntary and not motivated by body image concerns, whereas bulimia involves intentional purging [6]. Moreover, about 35% of individuals who have substance use disorder also have an eating disorder [6]. Symptoms such as anorexia, dry heaving, headaches, and stomach pain are characteristic of CHS, but patients with CHS tend to maintain normal eating patterns when symptom-free, which further differentiates it from eating disorders.

8. Discussion

Cannabis Hyperemesis Syndrome (CHS) represents a growing public health concern, particularly due to the increasing use of cannabis among youth, and the liberalization of cannabis laws. Although the condition is becoming more widely recognized, much of the current evidence on CHS remains of low quality, primarily drawn from case reports and case-series [8]. These limitations underscore the need for further high-quality research, including prospective epidemiological studies, adequately powered studies that enhance methodological rigor and study reliability [57], and randomized controlled trials to establish effective treatment protocols. Despite these challenges, it is clear that CHS has a significant impact on both physical and mental health, and its prevalence is likely to rise as cannabis use becomes more widespread.

A critical issue in managing CHS is the need for greater awareness among clinicians (e.g., emergency doctors, gastroenterologists, neurologists, and psychiatrists). Current medical education and training do not sufficiently address CHS, often leading to delays in diagnosis and inappropriate treatments. Educating healthcare providers about the association between chronic cannabis use and CHS is essential for early intervention and effective management [8,21]. Public health campaigns are also necessary to raise awareness among cannabis users, helping them recognize the potential risks of prolonged cannabis consumption and prompting them to seek care when symptoms arise [45].

The pathophysiology of CHS remains poorly understood, and further basic science research is needed to elucidate the underlying mechanisms. Studies exploring the role of the endocannabinoid system, genetic predispositions, and potential biomarkers could significantly improve our understanding of the condition and aid in developing targeted diagnostic and therapeutic strategies [10,19]. Longitudinal research examining genetic factors and biomarkers may help identify individuals at higher risk for CHS and allow for earlier intervention.

The liberalization of cannabis laws has led to a rise in cannabis consumption, especially among youth, which is likely to contribute to an increase in cases of CHS. This highlights the importance of integrating CHS education into public health initiatives, particularly in school-based health programs and primary care settings. Preventative education and harm reduction strategies should be implemented early, addressing both the psychological and physical aspects of cannabis use. Healthcare providers should approach cessation with sensitivity, offering gradual reduction plans and mental health support to help individuals navigate withdrawal and avoid relapse [20]. For a concise overview of key considerations and potential directions for future research and clinical practice regarding CHS, please refer to the Panel Discussion Box 1.

Box 1. Summary of key recommendations and future priorities for addressing Cannabis Hyperemesis Syndrome (CHS) in youth and clinical settings.

Panel Discussion Box: Key Considerations for Cannabis Hyperemesis Syndrome (CHS) Moving Forward

1. Prevention and Early Education for Youth

Targeted Awareness Programs: Launch educational campaigns in schools, healthcare settings, and public health platforms to highlight the risks of chronic cannabis use and CHS.

Parent and Educator Involvement: Engage parents, teachers, and counselors to help recognize CHS symptoms early.

2. Early Recognition and Diagnosis

Screening for CHS: Clinicians should screen youth with cyclic vomiting, abdominal pain, and gastrointestinal issues for CHS.

Diagnostic Challenges and Misdiagnosis: Avoid confusing CHS with eating disorders like bulimia nervosa by differentiating vomiting from self-induced purging.

3. Intervention Strategies for Youth

Treatment of Acute Symptoms: Hospital care should focus on rehydration, electrolyte correction, and supportive care, with pharmacological treatments like haloperidol or benzodiazepines as adjuncts. Long-term treatment requires cannabis cessation.

Support for Withdrawal Symptoms: Monitor and manage withdrawal symptoms (e.g., anxiety), providing counseling to reduce relapse risks.

4. Addressing the Growing Prevalence of CHS

Impact of Legalization: As cannabis becomes more accessible, public health messages should highlight the risks of chronic use, especially for youth.

Public Health Messaging: Utilize campaigns to educate cannabis users about CHS risks.

5. Research Priorities and Future Directions

Pathophysiology of CHS: Urgent need for research into the mechanisms behind CHS.

Epidemiological Studies and RCTs: Conduct prospective studies and randomized controlled trials to better understand CHS prevalence, risk factors, and effective treatments.

6. Building Clinical and Community Support

Training for Healthcare Providers: Train providers to recognize CHS and understand its treatment.

Integration into Substance Use Treatment: Include CHS in substance use treatment frameworks for a comprehensive approach to care.

7. The Role of Policy and Advocacy

Advocacy for Public Health Policy: Advocate for public health policies prioritizing cannabis education to allocate resources for CHS research, treatment, and prevention.

Legislation to Protect Youth: Enforce regulations that limit youth access to cannabis and educate about its long-term risks, including CHS

This narrative review has some limitations. First, much of the existing literature on CHS relies on case reports and observational studies, which may limit the generalizability and reliability of the findings. Second, the pathophysiology of CHS remains poorly understood, with a focus on clinical observations rather than mechanistic research. Lastly, despite efforts to include all relevant studies, the narrative nature of this review means some research may have been overlooked.

9. Conclusions

While CHS is increasingly recognized as a significant public health issue, the quality of current research remains limited, and much work remains to be performed to fully understand and address the condition. Enhancing clinician education, expanding research into CHS pathophysiology, and promoting public health awareness are crucial steps in mitigating the impact of this emerging syndrome. Future longitudinal studies and genetic research will be key to developing more precise diagnostic and treatment strategies, ultimately reducing the burden of CHS on patients and the healthcare system.

Module Overview

The module is organized in two parts. Part 1 addresses Cannabis Use Disorder (CUD) and reviews its diagnostic criteria, epidemiology and burden, risk factors, and evidence-based interventions. Part 2 addresses Cannabinoid Hyperemesis Syndrome (CHS), focusing on clinical presentation, diagnostic criteria, pathophysiology, and management approaches. This module is designed to help clinicians and public health practitioners understand how the increasing accessibility and normalization of cannabis impacts both individual patient care and broader health systems.

Learning Objectives

By the end of this module, participants will be able to analyze the public health and safety implications of CUD across diverse populations; critically evaluate policies and research related to cannabis use disorders; and determine the signs, symptoms, and evidence-based strategies for managing both CUD and CHS.

Required Resources

The module draws on three key systematic reviews: Ghafouri et al. (2024) in Brain Sciences, which reviewed treatments for CUD across the lifespan; Senderovich et al. (2022) in Medical Principles and Practice, which reviewed management options for CHS; and Seabrook et al. (2025) in IJERPH, which examined CHS in youth and its public health implications.

Part 1 – Cannabis Use Disorder (CUD)

Case Study: Adolescent with CUD

A 16-year-old patient presents with daily vaping and edible use. Symptoms include morning irritability, missed school assignments, and ongoing family conflict. The patient demonstrates classic features of CUD: tolerance, withdrawal, craving, role failures, and hazardous use. The intervention was Motivational Enhancement Therapy combined with Cognitive Behavioral Therapy and Contingency Management (both clinic- and home-based). The outcome showed longer abstinence compared to MET/CBT alone, with an odds ratio of 1.16 (95% CI 1.02–1.32). The clinical pearl is that adolescents improve when family engagement and reward systems are included.

Abbreviations from Ghafouri et al., 2024

The review used numerous abbreviations:

• Clinical conditions and diagnoses: CUD (Cannabis Use Disorder), DSM (Diagnostic and Statistical Manual).

• Psychosocial/behavioral approaches: CBT, MI, MET, CM, VBRT, ACRA, TAU, TAUe, MDFT, AMT, PNC, PNC-txt, MCU, DTI, PFI/PNF.

• Pharmacological approaches: CB1 receptor agonists, NAC, topiramate, lithium carbonate, nabiximols, dronabinol.

• Measurement and outcomes: MPS (Marijuana Problems Scale), SIP-D (Short Inventory of Problems—Drug version), LOS (Length of Stay).

• Study design terms: RCT (Randomized Controlled Trial), F/U (Follow-Up).

Case Study: Young Adult with CUD

A 22-year-old patient reports using cannabis 4–6 times daily. Symptoms include poor sleep, depressed mood, and relationship strain. The intervention used was PNC-txt, a four-week text-delivered peer network counseling program. The results were impressive: 80% negative urine screens compared to 53% in the control group, with additional benefits including decreased cravings and reduced cannabis-related problems. The clinical pearl is that peer-oriented, tech-based programs scale effectively for college students and young adults.

Case Discussion: Why These Interventions Work

Contingency Management works by leveraging principles of behavioral economics. Immediate tangible rewards counter the delayed gratification of abstinence, strengthening positive reinforcement of behavior change. This is especially effective in adolescents whose brains are still developing. Text-based interventions are effective through peer norms, low-friction delivery, and timely supportive messaging. They scale easily across large populations, making them practical tools for campus or community-based prevention.

Mapping Cases to DSM-5 Domains

Both cases align with DSM-5 domains for CUD. The adolescent demonstrates impaired control (craving, failed cut-down attempts), social impairment (missed assignments, family conflict), risky use (continued despite consequences), and pharmacological criteria (tolerance and withdrawal). The young adult demonstrates impaired control (multiple daily uses), social impairment (relationship strain), risky use (continued despite mood impact), and withdrawal symptoms (poor sleep). Together, these cases illustrate moderate-to-severe CUD.

DSM-5/DSM-5-TR Criteria for CUD

CUD requires two or more criteria within a 12-month period. Under impaired control: using larger amounts or longer than intended; unsuccessful cut-down attempts; excessive time spent obtaining, using, or recovering; and craving. Under social impairment: role failures, interpersonal problems, and reduced activities. Risky use criteria include use in hazardous situations and continued use despite harm. Pharmacologic criteria include tolerance and withdrawal. Severity is categorized as mild (2–3 criteria), moderate (4–5), and severe (≥6).

CUD Prevalence and Burden

Approximately 1.5% of U.S. adults meet criteria for CUD. More than 35% of high school seniors report cannabis use in the past year. Globally, about 192 million people use cannabis annually. One in ten regular users, one in six adolescent initiators, and up to half of daily users progress to CUD. Cannabis is the third most commonly used psychoactive drug after alcohol and tobacco.

Public Safety and Functional Impact

CUD has multiple public safety implications: impaired driving, increased emergency department visits, and occupational safety risks. Functionally, individuals show decreased academic attainment, reduced productivity, absenteeism, and social isolation. Psychiatric associations include increased risk of depression, anxiety, psychosis (especially with high-potency products), self-harm, and violence among comorbid groups.

Risk Factors for CUD

Potency is a major factor: THC levels have risen 400% since the 1980s, from 3% to 15–30% in modern products, with concentrates reaching 60–90%. Neurodevelopment is also critical, as the prefrontal cortex continues maturing until age 25, making adolescents vulnerable to memory, attention, and executive function impairment. Routes of administration like dabs, high-THC vapes, and edibles pose additional risks. Psychosocial factors include peer influence and risk-taking among youth, and self-medication in adults. Medical comorbidities like chronic pain and insomnia increase exposure. Social determinants such as stress, dispensary density, marketing, and barriers to healthcare influence risk.

Cannabis Withdrawal Profile

Withdrawal begins 24–72 hours after cessation, peaks at one week, and resolves within 1–2 weeks, though some symptoms linger. Common symptoms include irritability, anxiety, poor sleep, appetite loss, restlessness, depressed mood, and cravings.

Screening for CUD

Effective screening uses open-ended, non-stigmatizing questions. Asking about cannabis use context, reasons, and frequency is essential. Importantly, asking about compulsive hot showering can help flag CHS in patients presenting with nausea.

Interventions and Treatments

Psychosocial interventions remain the foundation. Motivational Interviewing builds readiness to change, CBT teaches coping and restructuring, and CM provides incentives, with particularly strong results in adolescents. Family and school programs like parent training and therapy improve abstinence rates.

Digital interventions such as PNC-txt and eCHECKUP scale to young adult populations. PNC-txt achieved 80% abstinence at four weeks versus 53% for controls. eCHECKUP reduced hours/days high per week.

Pharmacologic options are only adjuncts. NAC and gabapentin relieve withdrawal but not relapse. CB1 agonists reduce withdrawal but have side effects. Lithium alleviates certain withdrawal symptoms without improving abstinence. Nabiximols (THC:CBD spray) improved abstinence (23% vs 9% placebo) when combined with counseling. Topiramate reduced grams used per day but caused dropout.

Relapse prevention strategies include trigger planning, sleep normalization, mood care, and building non-using peer networks. Interventions matched to life stage—family plus CM for adolescents, digital peer interventions for young adults, and adjunctive medications for older adults—are most effective.

Part 2 – Cannabinoid Hyperemesis Syndrome (CHS)

Case Study: Young Adult with CHS

A 21-year-old female using daily high-potency flower and concentrates for three years presented with cyclic vomiting and severe abdominal pain. She experienced relief only with very hot showers. She had multiple ED visits, normal labs and imaging, and no response to antiemetics. She met Rome IV criteria for CHS and improved completely after sustained cannabis cessation.

Case Study: Middle-Aged Adult with CHS

A 52-year-old male using cannabis for neuropathic pain had recurrent ED visits for refractory vomiting. Treatment with haloperidol 0.05–0.1 mg/kg IV was superior to ondansetron for nausea and pain, and shortened ED stay. However, dystonia occurred at higher doses. Haloperidol and topical capsaicin have the best trial evidence for CHS; opioids should be avoided.

Diagnostic Features and Course of CHS

Rome IV criteria for CHS include: prolonged, regular cannabis use; cyclical vomiting episodes; symptoms persisting for at least six months; relief with sustained abstinence; and compulsive hot bathing.

CHS progresses through prodromal (nausea, anxiety, continued cannabis), hyperemetic (severe vomiting, dehydration, relief from hot showers), and recovery (symptom resolution with cessation, relapse with reuse) phases.

Epidemiology and Burden

Youth cannabis use is widespread: 42.6% of U.S. young adults and 41% of Canadian youth reported past-year use; 9% reported daily use. In Ontario, ED visits for CHS rose 1.6-fold after retail commercialization. Across North America, CHS ED visits doubled from 2017 to 2021. Females are disproportionately affected, and 21% of adolescents with CHS have anxiety or depression. Misdiagnosis is costly, with patients often undergoing repeated CT/MRI scans, gastric emptying studies, and hospital admissions.

Pathophysiology Hypotheses

The paradox is that cannabis is antiemetic at low doses but pro-emetic in chronic, high-potency use. Possible mechanisms include CB1 receptor dysregulation, THC lipid storage and re-intoxication during stress, and genetic polymorphisms in CYP2C9, CYP2C19, and CYP3A4. TRPV1 activation explains relief from hot showers and capsaicin cream, both of which reduce substance P signaling. Neuro-hormonal dysregulation involving the endocannabinoid system, HPA axis, sympathetic nervous system, and gut hormones also plays a role.

Management

Definitive treatment is cessation, with 96.8% resolution in systematic reviews. Acute care includes hydration and electrolyte correction, avoiding opioids, and patient education. Symptomatic relief may come from hot showers, topical capsaicin (0.1%, reducing nausea 46% vs 25% placebo), or haloperidol (proven superior to ondansetron in the HaVOC RCT). Droperidol, benzodiazepines, propranolol, and aprepitant have only case-level evidence.

Practice Questions

1. Which is NOT a DSM-5 criterion for CUD? (Answer: religious use).

2. Which adolescent therapy prolonged abstinence? (Answer: MET/CBT + CM).

3. Which pharmacologic improved abstinence at 24 weeks? (Answer: Nabiximols).

4. What is PNC-txt? (Answer: text counseling; 80% abstinence vs 53% controls).

5. Which family therapy improved retention? (Answer: MDFT, 90% vs 48% for IP).