Exacerbation of Psychosis Triggered by a Synthetic Cannabinoid in a 70-Year-Old Woman with Parkinson Disease

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PRACTICE | CASES MENTAL HEALTH CPD

Exacerbation of psychosis triggered by a synthetic cannabinoid in a 70-year-old woman with Parkinson disease

Sean J. Udow MD, Maria Eliza Freitas MD, Susan H. Fox MB ChB PhD, Anthony E. Lang MD

n Cite as: CMAJ 2018 January 15;190:E50-2. doi: 10.1503/cmaj.170361

sychosis developed in a 70-year-old woman with a 12-year history of Parkinson disease after she ingested KEY POINTS nabilone, a synthetic cannabinoid. The patient had • Evidence for the therapeutic use of medical marijuana and Pchronic and painful dystonia in both feet that occurred as her cannabinoid derivatives in patients with Parkinson disease is medications were wearing off; this was resistant to management heterogenous and of low quality. with frequent and multiple antiparkinsonian medications. She • Cannabinoids may precipitate psychosis, even in patients was advised by a friend with Parkinson disease to try medical without a psychiatric history. marijuana for the dystonia. Her family physician prescribed nabi- • Patients with Parkinson disease have an inherent risk of lone, and the patient took two doses (1 mg) that resulted in psychosis and cognitive impairment, and may be more intrusive visual hallucinations, panic and paranoia within hours. susceptible to the psychomimetic and cognitive effects of cannabinoids. Despite stopping treatment with nabilone after the two doses, the patient’s psychosis worsened over the next three weeks. She had delusions that her neighbours were engaged in illegal and dangerous activities. be her daughter — into her neighbour’s shed. She became so agi- Before the ingestion of nabilone, the patient had had occa- tated that she broke into the shed. A video taken at home by her sional nonintrusive visual hallucinations for many years; insight daughter shows generalized dyskinesia, pressured and tangen- was preserved. Although she had mild cognitive concerns, these tial speech, and delusions (a video [Appendix 1], is available at did not interfere with her daily function, and she lived indepen- www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.170361/-/DC1.) dently at home with her husband. She had scored 27 out of 30 on Because of the patient’s acute psychosis, we admitted her to the Montreal Cognitive Assessment (www.mocatest.org/) hospital the following day. Our goal was to rapidly stop treat- two months before taking nabilone, with points lost for visuospa- ment with the dopamine agonist in a monitored setting, to con- tial and executive function. sider adding clozapine if this did not improve her psychosis and The patient had no other active concurrent medical problems to provide in-hospital support to our patients’ family members, and had made no changes to her other medications, which who were overburdened with her care. included levodopa–carbidopa (1000/250 mg per day), entaca- On admission, a general medical workup was unremarkable. pone (1000 mg per day), pramipexole (4.5 mg per day) and aman- We tapered and stopped pramipexole, but the patient’s psychosis tadine (300 mg per day). persisted. We started clozapine, which resulted in symptomatic She was assessed and managed as an outpatient by her pri- orthostatic hypotension that required the addition of fludrocorti- mary specialists in Parkinson disease. On repeat Montreal Cogni- sone. Over two weeks, the dyskinesias subsided, but her nonmotor tive Assessment testing three weeks after using nabilone, the symptoms of wearing off persisted. We added controlled-release patient scored 23 out of 30, losing points for attention, abstrac- levodopa–carbidopa at bedtime and reduced the dose interval to tion, delayed recall and orientation. Despite ending treatment every 2.5 hours. Eventually, the patient’s psychosis diminished, with amantadine, which has been associated with psychosis, the and we discharged her to home with levodopa–carbidopa patient’s delusions and visual hallucinations persisted. Quetiap- (1000/250 mg/d), entacapone (1000 mg/d), controlled-release ine (12.5 mg) was added at bedtime, and her evening dose of levodopa–carbidopa (100/25 mg/d), fludrocortisone (0.1 mg in the pramipexole was reduced (from 1.5 to 0.75 mg). morning) and clozapine (37.5 mg at bedtime). Despite these adjustments, the patient’s psychosis worsened. Three months after discharge, the patient’s visual hallucina- About two months after first ingesting nabilone, the patient tions and delusions were still present but less severe despite reported seeing two figures drag a body — whom she believed to taking clozapine (12.5 mg in the morning and 50 mg at bedtime).

5 E51 6 3 The use of The use of 4 4,5,12 Neurological effects Neurological ISSUE 2 ISSUE | There is evidence that use of cannabis can precipitate or exac- Synthetic oral cannabinoids (nabilone, dronabinol and Synthetic oral cannabinoids (nabilone, dronabinol and Impairment of short-term memory* short-term of Impairment attention* of Impairment functioning* executive of Impairment visual perception* of Impairment attack panic Anxiety,* Depression* Suicidal ideation Hallucination* Fatigue* Drowsiness* motivation* Low thinking) (e.g., paranoid Psychosis* of intoxication Feelings driving* Impaired weakness Increased state “Zombie”-like Psychosis* or bipolar disorder Development of schizophrenia or addiction* Dependence hemorrhage or brain Stroke erbate psychosis even in patients without a relevant psychiatric tetranabinex/nabidiolex) are licensed in Canada for selected and nausea of management the including conditions, medical neurologic symptoms such as pain and spasticity. cannabinoids to manage motor symptoms in Parkinson disease including tremor, bradykinesia and dyskinesia, as well as other movement disorders, is not well-supported by current evidence, which is heterogenous, of low quality and often observational. Nevertheless, because many motor and nonmotor symptoms of nonmotor symptoms motor and many because Nevertheless, med- to responsive poorly or incompletely are disease Parkinson ical and surgical treatments, patients desperate for relief have begun to turn to medical marijuana and cannabinoids, often encouraged by the belief that marijuana is a “natural remedy” and by the positive anecdotes of peers or videos on the Internet. Unfortunately, patients and their families are often unaware of the potential adverse effects of marijuana and cannabinoids. disease or it may be due to exogenous triggers, such as medical disease or it may be due to exogenous triggers, drugs. illnesses (notably infections) and dopaminergic VOLUME 190 VOLUME | Acute effects Acute Cognition: • • • • Mood: • • • Psychiatric/behavioural: • • • • • • Psychomotor: • • • effects permanent Potential • • • •

2 JANUARY 15, 2018 JANUARY | CMAJ 1 Nonneurological effects Nonneurological Psychosis in Parkinson disease — its timing in relation to dis- Increased heart rate heart Increased blood pressure* Decreased Fainting* (risk of infection) Suppression inflammation Increased fetus harm to Potential in men fertility Decreased milk breast into Passes Nausea (vomiting) syndrome Cannabis hyperemesis Bronchitis, asthma, cough asthma, Bronchitis, risk of lung cancer Increased attack Heart Stroke Vasculitis *People with Parkinson disease and parkinsonism commonly experience these symptoms even before using cannabinoids and, therefore, may be more susceptible to these adverse effects. these adverse to susceptible may be more and, therefore, cannabinoids using even before these symptoms experience commonly and parkinsonism disease with Parkinson *People Inhaled cannabinoids and oral cannabinoids and oral Inhaled cannabinoids Cardiovascular: • • • Immune system: • • Reproduction: • • • Gastrointestinal: • • Box 1: Information for patients on the adverse effects of cannabinoid use for Parkinson disease and parkinsonism and Parkinson disease for cannabinoid use of effects on the adverse patients for 1: Information Box variable amounts combine that orally taken extracts cannabis marijuana and cannabinoids (inhaled of the effect about evidence is conflicting There progressive atrophy, system (e.g., multiple and parkinsonism disease of Parkinson on symptoms and cannabidiol) of Δ9-tetrahydrocannabinol (involuntary) dyskinetic or drug-induced in tremor of improvement some claims are there example, For syndrome). corticobasal palsy, supranuclear may that effects adverse have all cannabinoids claims. Furthermore, support these to scientific evidence good is little there However, movements. the lack of in cannabinoids, and their families of our patients interest the widespread Owing to disease. people with Parkinson to be detrimental of possible adverse ignoring the wide array people are that concern our and symptoms, controlling in effective are these agents that evidence good cannabinoids. of effects health of the adverse a list we provide patients, in most benefits the potential outweigh we believe largely which effects, Inhaled marijuana Respiratory: • • Cardiovascular: • • • or esophagus throat cavity, of the oral of cancers risk increased Possible ease progress and severity of symptoms — exists on a spectrum.

This case illustrates the potential for the synthetic cannabinoid, nabilone, to trigger psychosis in a susceptible patient. The psychomimetic action of even single doses of nabilone are well described, as are the extended effects of a single dose because of the long half-life of active metabolites. Discussion We arranged for home care to help with evening medications. evening medications. We arranged for home care to help with scored 26 out of 30 on She had no new cognitive concerns and the Montreal Cognitive Assessment, which was reassuring of onset the with coincides often psychosis worsening because dementia from Parkinson disease. Patients may have well-formed visual hallucinations with insight into these experiences, but in more severe psychosis, insight can hallucinations. may act in response to their be lost and patients Delusional beliefs may also crystalize around the experiences. Psychosis may occur as part of the natural history of Parkinson PRACTICE disease progression. hypotension, whichmaybedetrimentaltobothcognitionand patients withParkinsondiseasecommonlyhaveorthostatic Use ofcannabiscanalsoloweruprightbloodpressure,and choactive, itsmechanismofactionissimilartothatTHC. also contains THC and cannabidiol. Although potentially less psy- is a mixture of cannabinoids, primarily cannabinol, butit Nabilone E52 glutamate and dopamine neurotransmission, amongothers. ciated with,variableriskofpsychosis,includinginteractionwith areimplicated,andpossiblyasso- ated bycannabinoidreceptor 1 history. with Parkinsondisease. antipsychotic effect,butthesestudiesdidnotincludeparticipants receptors. Somestudieshavesuggestedthatcannabidiolhasan however, cannabidiolactsasafunctionalantagonistatthese endocannabinoid receptors(cannabinoidreceptortypes1and2); to be the most psychoactive, all cannabinoids bind to the same pounds isolated from the cannabis plant.Although THC is thought cannabidiol andcannabinol,arepharmacologicallyactivecom- paranoid delusionalstatewithgeneralizeddyskinesia,andpres- established andthenspiraloutofcontrol.Theassociationher clear trigger that caused her psychotic symptoms to become the developmentofpsychosis,ingestionnabilonewas ous psychiatricsymptomsmayhaveprovidedapredispositionto patient’s Parkinsondisease,antiparkinsoniandrugsandprevi- progressively worseningpsychoticsymptoms.Althoughthe Even aftershestoppedtakingnabilone,continuedtohave she had anxiety, hallucinations without insight and paranoia. nabilone. Sheusedthisdrugonlytwice,butoneachoccasion Her symptomswerestableformanyyears,untilsheingested whichisnotuncommon. hallucinations withpreservedinsight — cause distractibilityandexecutivedysfunctioninsomeusers. function, iscommoninParkinsondisease,andcannabinoidscan nitive impairment,intheformofexecutiveandattentionaldys- and nonneurologicadverseeffectscausedbycannabisuse.Cog- these patients aresusceptible to many ofthe possible neurologic weigh thebenefitsinpatientswithParkinsondisease,because Biogen, Bristol–MyersSquibb,Corticobasal ceived personalfeesfromAbbVie, Acorda, Medicine PracticePlan. the UniversityHealthNetworkDepartment of Western HospitalFoundation;andsalary from of Health,ParkinsonCanadaand Toronto for Parkinson’sResearch,NationalInstitutes funding fromtheMichaelJ.FoxFoundation American AcademyofNeurology;research Disorder Society, CHDI Foundation and the the International Parkinson and Movement Orion, Sunovion and Zambon; honoraria from tannia, C2N,Cynapsus,Eisai,KyowaKirin, Avanir Pharmaceuticals,BiotieTherapies,Bri- consultant feesandresearchfrundingfrom Competing interests:SusanFoxhasreceived Our patient had symptoms of mild parkinsonian psychosis — Our patienthadsymptomsofmildparkinsonianpsychosis — We suggestthatthepotentialrisksofusecannabisout- 7 Cannabinoids,includingΔ 11 8 Anthony Langhasre- Inaddition,othermechanismsnotmedi- 9-tetrahydrocannabinol (THC), 9-tetrahydrocannabinol (THC), CMAJ Neurology, DepartmentofInternal Medicine Health Network,Toronto,Ont.;Section of Lang), TorontoWesternHospital, University Parkinson’s Disease(Udow,Freitas, Fox, Clinic, andtheEdmondJ.SafraProgram in and GloriaShulmanMovement Disorders University ofToronto,Ont.;Morton ment ofMedicine(Udow,Freitas,Fox,Lang), Affiliations: DivisionofNeurology,Depart- The authorshaveobtainedpatientconsent. This articlehasbeenpeerreviewed. were declared. submitted work.Noothercompetinginterests din, Sunovion and Sun Pharma, outside the Solutions, Medichem,Medtronic,Merck,Pala- | JANUARY 15, 2018 10 4,7 9

| VOLUME 190 11. 10. 12. References with theuseofcannabinoids(Box 1). clinic populationofthepotentialadverseeffectsthatcanoccur state mayhavecontributedtoherpsychosis. sured andtangentialspeechsuggestthatahyperdopaminergic 2. 9. 7. 6. 4. 1. 8. 5. 3.

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