Cannabis is one of the most commonly abused drugs worldwide. Over the past decade, marijuana has remained the most commonly used illicit substance with close to 50% of high school seniors admitting use at some time[1
]. It is estimated that each year 2.6 million individuals in the USA become new users and most are younger than 19 years of age[6
The long-term and short-term toxicity of cannabis abuse is associated with pathological and behavioural effects. However, cannabis has also been suggested to have therapeutic properties with anticonvulsive, analgesic, antianxiety and anti-emetic activities. Cannabis has also been used to treat anorexia in patients with acquired immunodeficiency syndrome[3–5
]. The actions of cannabis are mediated by specific cannabinoid receptors. The first of the cannabinoid receptors-CB-1-was identified in 1990 and this finding revolutionized the study of cannabinoid biology. Since then, a multitude of roles for the endogenous cannabinoid system has been proposed. A large number of endogenous cannabinoid neurotransmitters or endocannabinoids have been identified, and the CB-1 and CB-2 cannabinoid receptors have been characterized[7
]. The CB-1 receptors exert a neuromodulatory role in the central nervous system and enteric plexus[8
]. Cannabinoid type 2 receptors have an immunomodulatory effect and are located on tissues such as microglia[5
]. The presence of other receptors, transporters, and enzymes responsible for the synthesis or metabolism of endocannabinoids are being recognised at an extraordinary pace. Cannabinoids have a wide variety of effects on the body systems and physiologic states (Table ) due to their actions on the receptors as well as direct toxic effects.
Table 1 Harmful effects of cannabinoids on body systems[1,6,7]
The anti-emetic effect of cannabinoids is largely mediated by CB-1 receptors in the brain and the intestinal tract, although some of their effect may also be receptor-independent. However, in this report, we were presented with the paradoxical effect of hyperemesis in a susceptible chronic cannabis abuser. Such a paradoxical response has previously only been demonstrated following acute toxicity to an intravenous injection of crude marijuana extract[9
]. Proposed mechanisms of cannabinoid hyperemesis include toxicity due to marijuana’s long half-life, fat solubility, delayed gastric emptying, and thermoregulatory and autonomic disequilibrium via
the limbic system[10
]. Cannabinoids are known to impair peristalsis in a dose-dependent manner[11,12
], which can theoretically override the centrally mediated anti-emetic effects, thus leading to hyperemesis. It is not known why the hyperemesis syndrome surfaces after several years of cannabis abuse. The effects of cannabinoids on the functions of the thermoregulatory and autonomic mechanisms of the brain can lead to behavioural changes[10
]. Such effects might be the underlying mechanism for the compulsive hot bathing behaviour. There is also a supposition that the syndrome could represent a type of cyclic vomiting. Cyclic vomiting syndrome (CVS) in adults is now very well recognized, and it has been proposed that marijuana contributes to CVS[13
]. However, unlike the other forms of CVS, patients with cannabinoid hyperemesis are not likely to have a history of migraine or other psychosocial stressors and the peculiar behaviour of hot showers is unique to this syndrome.
Based on the published research and case reports[10,14–16
], we propose the set of clinical characteristics for the diagnosis of cannabinoid hyperemesis syndrome shown in Table . Allen et al[10
] first noted this condition in a group of nineteen patients from Australia with chronic cannabis abuse and cyclical vomiting illness. An earlier case report by de Moore et al[17
] described a chronic cannabis abuser with psychogenic vomiting, which was complicated by spontaneous pneumomediastinum. Subsequent reports have identified similar clinical presentations[7–9,18
]. Given the high prevalence of chronic cannabis abuse worldwide and the paucity of reports in the literature, clinicians need to be more attentive to the clinical features of this underrecognised condition.
Clinical diagnosis of cannabinoid hyperemesis