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CNS Spectr. 2006;11(4):262-264

Dr. André is professor of neurology in the Department of Internal Medicine at Federal University of Rio de Janeiro, Brazil. Dr. Jaber-Filho is psychiatrist and medical director of the Jorge Jaber Psychotherapy Clinic in Rio de Janeiro. Mr. Bento and Ms. Damasceno are associate researchers and Dr. Aquino-Neto is professor of chemistry and head of the LABDOP-LADETEC in Department of Organic Chemistry at Federal University of Rio de Janeiro.

Disclosure: The authors do not have an affiliation with or financial interest in any organization that might pose a conflict of interest.

Submitted for publication: August 15, 2005, accepted October 11, 2005.

Please direct all correspondence to: Charles André, MD, PhD, Rua General Venâncio Flores 305/602, CEP 22441-090, Rio de Janeiro, Brasil; Tel/Fax: 55-21-2540-9091; E-mail: andrecmd@unisys.com.br.

Focus Points

• The ingestion of marijuana integrated into cookies may lead to delirium and psychotic behavior.

• Urine analysis under strict methodological criteria may elicit the correct diagnosis even after several days of exposure.

• Symptoms usually improve under adequate pharmacologic treatment and elimination of the drug but complete recovery may take >1 week.

• Continued exposure to marijuana may be associated with a prolonged symptomatic period and make the differential diagnosis of substance induced and primary psychosis difficult.

Abstract

Objective: To describe a case of marijuana-induced delirium and the techniques used to detect psychoactive agents and metabolites in urine.

Methods: A case of delirium following involuntary ingestion of cannabis is described. A urine sample was analyzed applying various chemical procedures, using high-resolution gas chromatography coupled with mass spectrometry technique. 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid was quantified by the methodology for steroids and cannabis.

Results: A 26–year-old man was hospitalized with severe agitation and psychotic behavior 36 hours after suspected involuntary ingestion of cannabis contained in a brigadeiro, a typical Brazilian cookie, consumed during a party. Treatment with neuroleptics resulted in complete regression of the symptoms over 2 weeks. The urine sample revealed marijuana ingestion, demonstrated by the presence of its metabolite, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in high concentration. No other investigated substance was found in the patient’s urine.

Conclusion: Severe delirium can follow oral ingestion of cannabis integrated into homemade cookies.

Introduction

Cannabis sativa is generally consumed via cigarettes or pipes. Users also utilize this drug by oral intake in the form of cakes, teas, and other products. This article describes the case of a patient with suspected involuntary ingestion of a psychoactive agent possibly contained in a typical Brazilian cookie referred for inpatient treatment in order to control agitation and severe psychotic behavior. Treatment with neuroleptics resulted in gradual regression of the symptoms.

A urine sample was examined to identify the agent promoting psychotic symptoms. It was analyzed applying various chemical procedures described herein and using high-resolution gas chromatography coupled with mass spectrometry technique (HRGC/MS).

Methods

Analysis

A urine sample was collected from the patient on the fifth day after the admission (day 7 after symptom onset) and analyzed for the presence of possible xenobiotic substances.

The sample was divided into five aliquots and each was submitted to a different analytical extraction procedure (Table).^2,7 These procedures differ in the extraction type (liquid-liquid partition or solid-phase extraction) and in the organic solvent used; in the pH of the extraction; and in the carrying out or not of an enzymatic hydrolysis step, necessary to transform the drugs that are excreted in urine as conjugates (eg, linked to glucuronic acid or sulphate) in their free form (not-conjugated). The analytical modifications in each extraction procedure facilitate the recovery (removal) of a specific class of drugs from the urine matrix. Each extract was analyzed by HRGC/MS.

The 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) found was identified and quantified by the methodology for steroids and Cannabis, consisting of an enzymatic hydrolysis of the urine with β-glucuronidase from E. coli, liquid-liquid extraction with tert-butylmethylether in an alkaline medium (pH: 9.5) and derivatization with N-methyl-N-(trimethylsilyl)trifluoroacetamide, to generate the bis O-trimethylsilylated (bis-OTMS) derivative.

Results

The urine analysis revealed high urinary concentration (672 ng/mL) of the inactive metabolite of cannabis, THC-COOH,4,7 generated by oxidation of Δ9-tetrahydrocannabinol (ie, THC), its main active principle. Figure shows the chemical structure of this compound and its acidic metabolite.

Total ion chromatogram and fragmentogram (characteristic ions m/z 371, m/z 473 and m/z 488) of the sample submitted to cannabis procedure by HRGC/MS revealed a signal at the characteristic retention time for THC-COOH indicating a possible presence of its bis-OTMS derivative. Confirmation was obtained when the mass spectrum and suitable diagnostic ions relationship of the signal were also comparable with the reference spectrum of THC-COOH-bis-OTMS.

No other substance—amphetamines and related substances (ecstasy, etc), ephedrines, morphine-related substances, cocaine, anabolic steroids—was found in the patient’s urine in any of the methodologies.

Discussion

The diagnosis of delirium related to oral ingestion of marijuana (ICD-10:F12.03) was made in this case, based on a typical clinical course and history and urine data attesting single drug exposure. The high urine concentrations of marijuana after 1 week of symptom onset suggested a more prolonged exposure to the drug than recognized by the patient. No complementary diagnostic tests, such as brain magnetic resonance or electroencephalogram, were performed, since it seemed most unlikely that any acute cerebral lesion, such as a stroke¹¹ or partial complex epilepsy,³ could be responsible for the psychiatric disturbance.

The complex relation between marijuana use and acute and chronic psychosis is the object of intense research.¹ Cannabis consumption seems to increase the risk of developing psychosis in psychosis-free individuals.¹⁰ Acute and severe psychiatric reactions including anxiety and agitation, confusion, paranoia, delusions, or mood disorders lasting hours or days have been reported and seem to be much more common in inexperienced individuals following oral intake of brownies and cookies than after smoking of the drug.⁵ The higher risk after ingestion can be explained by the relatively high blood concentrations of the drug⁹ for longer periods than following smoking. As in the present case, recovery is usually complete with prolonged abstinence.⁶ Patients who persist in the use of the drug, however, may have an increased risk of a prolonged illness.¹²

Conclusion

This study presented the clinical case of a delirious patient severely intoxicated by a psychoactive agent. Analytical results showed high urinary concentrations of THC-COOH, an oxidation product of THC, in the material collected 7 days after the described ingestion, confirming the diagnosis of delirium due to ingestion of marijuana present in a chocolate cookie. Severe substance intoxication delirium can follow oral ingestion of cannabis integrated into homemade cookies. CNS

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