Substance Abuse Catatonia and Cannabis ...

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Catatonia and Cannabis Withdrawal: a case report a

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Mathieu Caudron M.D. , Benjamin Rolland M.D. PhD , Sylvie Deheul M.D. , Pierre Alexis efg

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Geoffroy M.D. , Pierre Thomas M.D. PhD & Ali Amad M.D. PhD a

Pôle de psychiatrie, Univ Lille Nord de France, CHRU de Lille, F-59000 Lille, France

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Addiction Consultation-Liaison Service, Department of Addiction Medicine, University Hospital of Lille, France c

Department of Pharmacology, INSERM U1171, University of Lille, France

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Department of Addictovigilance, University Hospital of Lille, France

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Inserm, U1144, Paris, F-75006, France

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Université Paris Descartes, UMR-S 1144, Paris, F-75006, France & Université Paris Diderot, UMR-S 1144, Paris, F-75013, France g

AP-HP, GH Saint-Louis - Lariboisière - Fernand Widal, Pôle Neurosciences, 75475 Paris Cedex 10, France Accepted author version posted online: 06 Aug 2015.

To cite this article: Mathieu Caudron M.D., Benjamin Rolland M.D. PhD, Sylvie Deheul M.D., Pierre Alexis Geoffroy M.D., Pierre Thomas M.D. PhD & Ali Amad M.D. PhD (2015): Catatonia and Cannabis Withdrawal: a case report, Substance Abuse, DOI: 10.1080/08897077.2015.1052869 To link to this article: http://dx.doi.org/10.1080/08897077.2015.1052869

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ACCEPTED MANUSCRIPT Catatonia and Cannabis Withdrawal: a case report

Mathieu CAUDRON1 M.D., Benjamin ROLLAND2,3 M.D. PhD, Sylvie DEHEUL4 M.D., Pierre Alexis GEOFFROY5,6,7 M.D., Pierre THOMAS1 M.D. PhD, Ali AMAD1 M.D. PhD


1) Pôle de psychiatrie, Univ Lille Nord de France, CHRU de Lille, F-59000 Lille, France 2) Addiction Consultation-Liaison Service, Department of Addiction Medicine, University Hospital of Lille, France 3) Department of Pharmacology, INSERM U1171, University of Lille, France 4) Department of Addictovigilance, University Hospital of Lille, France 5) Inserm, U1144, Paris, F-75006, France 6) Université Paris Descartes, UMR-S 1144, Paris, F-75006, France & Université Paris Diderot, UMR-S 1144, Paris, F-75013, France 7) AP-HP, GH Saint-Louis - Lariboisière - Fernand Widal, Pôle Neurosciences, 75475 Paris Cedex 10, France.

Correspondence should be addressed to Ali Amad, MD, PhD, Unité d'Hospitalisation, Spécialement Aménagée (UHSA) Lille-Seclin, Chemin du bois de l'hôpital, 59113 SECLIN, France. Email : [email protected]

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ACCEPTED MANUSCRIPT ABSTRACT. Background: Catatonia is a severe motor syndrome found in approximately 10% of all acute psychiatric hospital admissions. It can occur in various psychiatric diseases. We report the first case report of catatonia during cannabis withdrawal. Case presentation: Mr. A, a 32-year-old man, reported to have daily smoked approximately 20 grams of cannabis since aged 11 years. Mr. A was incarcerated and was reported three weeks later to the medical department


for having completely ceased talking and eating. At admission in our department, the patient presented with classical catatonia symptoms (Bush-Francis Catatonia Rating Scale (BFCRS) score = 39/69). All laboratory results and brain MRI were normal. Six weeks after his admission and treatments by lorazepam and memantine, his BFCRS score was 0/69. Discussion: This single-case study highlights the previously under-reported emergence of physical and motor symptoms following cannabis withdrawal. Pathophysiological aspects of abrupt cannabis cessation contributing to GABA/glutamate balance dysregulation and to catatonia are discussed.

Keywords: Cannabis withdrawal, catatonia, gaba/glutamate balance

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ACCEPTED MANUSCRIPT INTRODUCTION

Catatonia is a severe motor syndrome found in approximately 10% of all acute psychiatric hospital admissions1. It can occur in various psychiatric diseases, including mood disorders and schizophrenia, as well as substance intoxication/withdrawals and other medical conditions1,2.


This is the first published case report of catatonia during cannabis withdrawal.

CASE DESCRIPTION

Mr. A was a 32-year-old man incarcerated for interrupting a chase related to a drug trafficking. His medical history showed evidence of mild intellectual disability (IQ = 67) and a polyneuropathy at the age of sixteen, which affected his cranial nerves. Full recovery was obtained with corticosteroid therapy. Family and general practitioner (GP) reports showed no personal or family psychiatric history, nor notable personal medical history. Mr. A. reported to have daily smoked approximately 20 grams of cannabis (resin and marijuana), since aged 11 years. During three previous incarcerations for drug trafficking, he reported using far lower amounts, without any complications. Due to religious and cultural beliefs, Mr. A never consumed alcohol or other illicit drugs, confirmed by his GP and family. Mr. A's family described his behavior as normal on the day before his imprisonment. Both the GP and the psychiatrist who examined him on his arrival in jail did not report any medical symptoms. During his current incarceration the patient was unable to obtain cannabis due to a lack of money. Three weeks later the patient was reported to the medical department, having

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ACCEPTED MANUSCRIPT completely ceased talking and eating for several days, as well as having set his coat on fire, without any skin damage thanks to intervention of the prison staff. The patient was then transferred from jail to the emergency medical department due to confusion and mutism. Blood tests were normal and after examination, the psychiatrist decided on compulsory admission to our forensic psychiatry department.


At admission the patient presented with classical catatonia symptoms, including apathy, mutism, disorientation in time and space, psychomotor agitation, catalepsy, waxy flexibility, impulsivity, ‘mitgehen’ (movement in any direction in response to a very light finger pressure), plastic hypertonia and cogwheel. On the Bush-Francis Catatonia Rating Scale3 (BFCRS) the patient scored 39/69, suggesting a diagnosis of catatonia. No psychotic symptoms, including delusions or disorganization were evident. Due to catatonic symptomatology, we attempted a zolpidem test4, but the patient refused any oral treatment. We then decided to administer 1 mg of clonazepam by intramuscular injection, which allowed for treatment with oral lorazepam, starting at 10mg per day5. By gradually increasing the lorazepam dose, his symptomatology improved. At 25 mg per day, the improvement in his catatonic symptoms stagnated. We then added oral memantine5, starting at 5 mg per day, which further decreased his catatonic symptomatology. During this hospitalization, and given the patient’s history, many examinations were performed. All laboratory results were normal, including: toxicological analyses (cannabis, amphetamines, cocaine, opiates/opioids), full blood count, electrolyte panel, liver function panel, coagulation panel, serum protein electrophoresis, C reactive protein, fibrinogen, blood glucose, thyroid function tests, B9 vitamin, albumin, hepatitis panel, angiotensin converting enzyme, salivary

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ACCEPTED MANUSCRIPT gland biopsy, HIV and syphilis. The involvement of autoimmune and paraneoplastic processes were also excluded by the analysis of a variety of factors, including: homocystein, anti-nuclear antibodies, anti-transglutaminase antibodies, antineutrophil cytoplasmic antibodies and onconeural antibodies, which were all negative. The tuberculin skin test and quantiferon level were also negative. Vitamin B12 and iron levels were normal. Brain MRI showed two minor non-


specific lesions in the white matter of the left periventricular and insular areas. Six weeks after his admission, his BFCRS score was 0/69. After a period of consolidation, his medication was decreased to lorazepam 1.5 mg/week, with no symptom re-emergence. Mr. A left the hospital on his release from jail, with treatment continued in a psychiatry outpatient department.

DISCUSSION

To our knowledge, this is the first reported case of cannabis withdrawal-induced catatonia. Laboratory and imagery investigations were within normal limits and excluded delirium, toxicological, neurological, systemic and paraneoplastic causes of his catatonic symptoms. We hypothesize that the patient experienced catatonia following sudden heavy cannabis use cessation. According to the WHO-UMC Causality Assessment6, derived from clinicalpharmacological aspects of the case history, the causality between cannabis cessation and catatonia was "probable", given that the event appeared with reasonable temporal relationship to drug withdrawal and being unlikely to be attributable to disease or other drugs.

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ACCEPTED MANUSCRIPT Physical and motor symptoms are generally lower, compared with other symptoms, after cannabis cessation7 and the relation between cannabis dose and the magnitude of abstinence effects is still being debated8. However, these symptoms are included in the DSM-5 cannabis withdrawal syndrome9. Such physical symptoms occur more frequently from day 5 following cannabis cessation7. However, given Mr. A's initial incarceration, there is no certainty as to the


sequence of symptom emergence, being only reported when clearly visible after at least two weeks incarceration. Pathophysiologically, abrupt cannabis cessation can dysregulate the GABA/glutamate balance, contributing to catatonia. Indeed, chronic consumption of cannabinoids, like Δ9 tetrahydrocannabinol, decreases extracellular glutamate and increases extracellular GABA, as well as enhancing dopamine release in both the striatum and mesolimbic system10. This pattern is reversed by abrupt cannabis cessation, leading to a typical catatonia pattern of GABA-A and dopamine D2 receptor hypoactivity and glutamate NMDA receptor hyperactivity5. Interestingly, GABA-ergic regulating drugs, such as the selective GABA-B agonist, baclofen, show promise in the management of cannabis dependence11. In conclusion, the single-case study detailed here highlights the previously under-reported emergence of physical and motor symptoms following cannabis withdrawal. This case report further highlights how sudden cessation due to incarceration can be extremely dangerous, without appropriate management. This common clinical situation requires careful monitoring and more research on abrupt heavy cannabis cessation is needed in order to improve patient care and management.

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ACCEPTED MANUSCRIPT FUNDING

The authors received no funds for this research. The authors declare no conflicts of interest.


AUTHOR CONTRIBUTIONS

MC and AA managed the case, MC, BR and AA wrote the first draft, SD, PAG and PT were responsible for critical revision of the manuscript. All authors have read and approved the final version of the manuscript.

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