In this case series, we present 2 cases of MC in male adolescents following recreational vaporized cannabis use.Patient A00 is a 15-year-old boy with a past psychiatric history significant for nonsuicidal self-injurious behavior via cutting, history of childhood trauma, no prior suicide attempts or inpatient hospitalizations, and no known past medical history. He presented to the emergency department with 5 days of aggressive behavior, paranoia, auditory hallucinations, and hyperreligiosity. He endorsed a history of vaping “TKO” marijuana most days of the week for approximately 1 year before presentation and no other substance use. In our ED, his vital signs were notable for tachycardia to 114 beats per minute, temperature of 37.6 Celsius, and hypertension to 171/111 mmHg. Workup in the ED revealed a leukocytosis to 11.2 K/UL, hemoglobin of 15.0 G/DL, hematocrit of 45%, and serum creatine kinase of 408 U/L. Urine drug screen was positive only for cannabis.He experienced episodes of emesis in the ED. Physical examination was notable for mydriasis, psychomotor retardation, and hyperreflexia. His mental status examination was significant for poor eye contact, monotone speech, flat affect, and disorganized thought process. After 2 doses of lorazepam 2mg by mouth and hydralazine 10mg PO, his blood pressure improved to 142/97 mmHg. He was admitted to the general pediatrics service for further workup and management of persistent hypertension and tachycardia. On arrival to the floor, he had a heart rate of 124 beats per minute and a blood pressure of 136/84 mmHg. Urine metanephrines, plasma renin and aldosterone, magnetic resonance image brain without contrast,hydroponic grow tent cerebrospinal fluid studies were all within normal limits. Continuous electroencephalography revealed diffuse low-voltage fast activity but no epileptiform discharges or generalized slowing. Due to ongoing autonomic instability, on hospital day 1, treatment with lorazepam 2mg three times daily as needed for hypertension was started, and he received 4 mg total over 24 hours. On hospital day 2, he reported feeling stiff in his arms and legs and “feeling stuck in his body” and was noted to appear withdrawn with minimal speech output.
The pediatric consultation-liaison psychiatry service was consulted for concern of altered mental status and recent bizarre behavior. On the initial examination by the pediatric consultation-liaison psychiatry service, he was noted to be paranoid with a tangential thought process and significant psychomotor retardation. The initial Bush-Francis Catatonia Rating Scale was 7. He had received lorazepam 2 mg PO x2 the day prior. On serial examinations, he had catalepsy, waxy flexibility, and defificits with attention and calculation. Lorazepam was scheduled 2 mg PO t.i.d. Over the 18-day admission, lorazepam was titrated to 12 mg daily. Psychotic symptoms resolved, though attention deficits persisted. He was discharged to an inpatient psychiatric unit with treatment with lorazepam 11mg per day. He was hospitalized there for 5 days and then discharged on 9 mg daily with instructions to taper over the next 18 days. He re-presented to the ED with catatonia and suicidality 3 weeks later in the context of repeat vaporized cannabis use. He presented with depressed affect but no psychosis.He was transferred to an inpatient psychiatric facility. After discharge, he tapered off of benzodiazepines over 3 months and has remained without symptoms.“Patient B” is a 16-year-old boy with a past psychiatric history significant for attention-deficit/hyperactivity disorder, who was brought to the ED for altered mental status after vaping cannabis. He noted a history of smoking cannabis but reported vaping cannabis the day before ED presentation. Of note, he had been admitted to an outside hospital several months prior for a similar episode of catatonia after reported cannabis use. As per documentation from that hospitalization, catatonic symptoms resolved with lorazepam treatment. On arrival to our ED, he was afebrile but hypertensive to 138/70 mmHg and tachycardiac to 100 beats per minute. Blood work was significant for hemoglobin of 14.8 g/dl , hematocrit of 46.1% , thrombocytosis to 407 K/UL, creatine kinase of 759 U/L, and urine drug screen was positive only for cannabinoids.On physical examination, he was slow to respond to questions and had difficulty following simple commands. He was described as “dazed” and appeared to be responding to internal stimuli; he was too behaviorally dys regulated to meaningfully participate in medical workup or safety assessment, so he was given haloperidol 5 mg IM and lorazepam 2 mg IV, before psychiatric consultation. Four hours after the administration of these medications, he developed writhing motions of his head and neck, thought to be an adverse reaction to haloperidol, which resolved with the administration of diphenhydramine 50 mg PO. Several hours later, he developed rigidity and psychiatry was consulted owing to concern for catatonia. On initial psychiatric evaluation , he scored 8 on the initial Bush-Francis Catatonia Rating Scale .
In light of these findings, a diagnosis of MC was made and treatment with lorazepam 2 mg PO/IV every 6 hours was recommended. He received a total of 6 mg of lorazepam IV in the ED with resolution of his rigidity. Owing to worsening hypertension to 158/68 mmHg, dysregulated behavior, and development of a 2-liter oxygen requirement after lorazepam administration, he was admitted to a medical intensive care unit for continued monitoring and treatment of MC. In the medical intensive care unit, further workup revealed new hyperkalemia to .5.8 mmol/L and uptrending creatine kinase level to 1800 U/L, which were treated with intravenous fluids. Computed tomography of his head without contrast was negative for acute abnormalities. He received 1 additional dose of lorazepam 2 mg IV in the medical intensive care unit , and his rigidity, mutism, staring, hallucinations, and oxygen requirement subsequently resolved. He was transferred to the general pediatrics floor where he was noted to have perseverative speech, intermittent aggression toward staff, and deficits on bedside cognitive testing including poor short-term recall and poor attention. Cardiology was asked to see him to comment on his intermittent hypertension and electrocardiogram changes; a repeat electrocardiogram did not show left ventricular hypertrophy, and an echocardiogram was unremarkable. On hospital day 2, his initial Bush Francis Catatonia Rating Scale was 0 on evaluation by the pediatric consultation-liaison psychiatry service, and scheduled lorazepam was decreased to 2 mg PO t.i.d. On this dose of lorazepam, he remained normotensive and without cognitive deficits or signs of catatonia or psychosis on exam. He was ultimately discharged on hospital day 5 to outpatient psychiatric care.Case reports of substance-induced catatonia in this age group have included catatonia secondary to ecstasy and synthetic cannabis.To the best of our knowledge, the two cases described here represent novel reports of presentations of pediatric MC in the setting of vaporized cannabis use. These cases raise the question if vaporized cannabis use has the potential to be a causative factor in the development of catatonia. Vaping devices facilitate the use of cannabis concentrates, which have been found to have approximately triple the delta-9- tetrahydrocannabinol strength of flower-derived strains.Vaporized cannabis use has been associated with both increased plasma levels of delta-9- tetrahydrocannabinol and subjective drug effects compared with cannabis use via smoking.Highpotency delta-9-tetrahydrocannabinol has been associated with increased negative psychiatric effects such as low mood and anxiety,suggesting the potential for other neuropsychiatric sequelae as well. In these 2 cases, while the completed workup was unrevealing for acute neurologic, infectious, or metabolic precipitants to catatonia, we were limited in our ability to test for all drugs of abuse.
Synthetic cannabinoid and cathinone testing were sent out tests at our institution, and these tests were deferred owing to cost and low likelihood to change management. We considered psychiatric decompensation as the acute precipitants to catatonia in both of these patients. Neither patients endorsed acute emotional distress before presentation, but patient A reported feeling depressed in the setting of ongoing psychosocial stress suggesting the possibility of an affective component as well in this case. It is also unclear from documented history if either patient had a loss of functioning consistent with a prodrome of a primary psychotic disorder before presentation. The acute onset of psychotic symptoms and timeline in relation to cannabis use more strongly suggests psychotic symptoms in both cases were substance-induced, but we cannot exclude the possibility of an underlying vulnerability to a primary psychotic disorder in either patient. In either patient, vaporized cannabis may have lowered the threshold to the development of catatonia given its effects on the gammaaminobutyric acid system. The autonomic instability in the context of catatonic symptoms led us to define these 2 presentations as malignant catatonia. Although the neurobiological underpinnings of catatonia are not well understood,there is evidence supporting alterations in GABA, dopamine, and glutamate in the pathogenesis of this disorder.Clinically, involvement of the GABAergic system in catatonia is suggested by the rapid and often dramatic efficacy of GABA agonists, such benzodiazepines, for the treatment of the syndrome.Exposure to cannabinoid receptor 1 agonists,cheap grow tents such as delta-9-tetrahydrocannabinol, has been associated with disruption of GABAergic-mediated cortical inhibition.Given the importance of cortical GABAergic modulation of feedback loops within mesostriatal and mesocorticolimbic systems,further research is needed to investigate if disturbance in GABA by delta-9-tetrahydrocannabinol may directly precipitate many of the psychomotor symptoms seen in catatonia.Amid the pandemic caused by the novel coronavirus disease , public health measures were enacted in countries around the world to curb the spread of COVID-19. In Canada, wide-scale emergency measures were put in place in March 2020 that severely impacted Canadians’ ability to engage in work, educational, recreational, and social activities. During times of high stress and anxiety, social isolation, and limited out-of-home recreational activities such as those seen during the COVID-19 pandemic, people may increase their use of substances like cannabis . Cannabis is the most widely used psychoactive substance besides alcohol in Canada, and its use can be accompanied by the risk of developing a cannabis use disorder along with numerous short-term and long-term adverse health consequences . Alongside the implementation of COVID-19-related emergency measures, a Statistics Canada survey reported a sharp increase in cannabis sales in March and April 2020 compared with previous months .
Further, a survey of Canadian adults found that among cannabis users, approximately half increased their use of cannabis relative to their pre-pandemic consumption patterns . The widespread use of cannabis and an increase in use during the current COVID-19 pandemic underscores the necessity of understanding the etiology of elevated levels of cannabis use. A key determinant of a substance’s use and misuse is its reinforcing value, which refers to its behavior-strengthening and behaviormaintaining properties . The reinforcing value of a substance has been operationalized as behavioral economic demand, or the relationship between the price of a substance and its consumption. Substance-related demand has been measured in the lab through the use of hypothetical purchase tasks . Purchase tasks have been employed across a number of substances including alcohol, tobacco, and cocaine , and more recently for cannabis . These tasks ask the participant to estimate their consumption of a substance at varying price points . Purchase tasks allow for the characterization of an individual’s pattern of demand via the calculation of several demand indices: four observed indices and one derived index . Intensity refers to unconstrained consumption at zero cost. Omax refers to the peak expenditure, or the maximum total amount of money spent on the substance across price points. Pmax is the price at which this peak expenditure occurs. Breakpoint refers to the cost at which consumption is suppressed to zero. Higher values on each of these indices reflect higher demand for the substance. The derived index, elasticity, refers to the rate at which consumption decreases relative to increases in cost. Latent factor analysis of the Marijuana Purchase Task has revealed that these five indices map onto two underlying dimensions of demand. The first factor is “Amplitude,” which refers to consumption at unrestricted cost and is comprised of one index, intensity. Higher consumption at zero cost reflects higher demand. The second factor, “Persistence,” is comprised of Omax, Pmax, breakpoint, and elasticity, and reflects the individual’s sensitivity to increasing cost . A low sensitivity to increasing cost indicates higher demand. This factor structure aligns with research demonstrating a similar structure for alcohol and tobacco purchase tasks .