Nitrous oxide “Whippit” abuse presenting with cobalamin responsive psychosis

Abstract

Introduction: Nitrous oxide is a commonly abused inhalant drug. It is known to precipitate vitamin B12 deficiency when used chronically and acutely, especially in people having marginal vitamin B12 reserve.Case report: We are presenting a case of nitrous oxide "whippit" abuse in a thirty-three-year-old male with bizarre behavior and delusions. The patient had low normal levels of vitamin B12 (202 pg/ml), but he had markedly high methylmalonyl CoA (1078 nmol/L) and homocysteine (48.4 mcmol/L). Treatment with intramuscular cobalamin led to a resolution of his psychosis.Discussion: This case report highlights the need to consider vitamin B12 deficiency in patients who arrive at a hospital with psychiatric manifestations and who report having a history of nitrous oxide exposure or abuse in the recent or remote past. A review of the literature on the neuropsychological manifestations of vitamin B12 deficiency is provided.

Subacute combined degeneration of the spinal cord in a patient abusing nitrous oxide and self-medicating with cyanocobalamin

“…6 When abused chronically and in high volume, nitrous oxide has been associated with myelopathy related to vitamin B 12 deficiency, a disorder in which patients commonly have paresthesia, ataxia, and loss of position and vibration senses. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Other cases have also demonstrated the manifestation of myelopathy from acute nitrous oxide exposure via anesthesia in patients with underlying vitamin B 12 deficiency. [21][22][23][24][25][26] The spinal cord abnormality caused by vitamin B 12 deficiency, often seen on magnetic resonance imaging (MRI) as an irregular demyelination of white matter, is known diagnostically as subacute combined degeneration (SCD).…”

Nitrous Oxide (N2O)-Induced Acute Psychosis

“…N 2 O inactivates vitamin B 12 via an irreversible oxidation of the cobalt core from the monovalent to the trivalent state. 3 Inhibition of the methylmalonyl-coenzyme A mutase enzyme leads to an accumulation of methylmalonate and propionate; these compounds appear to provide an atypical source of substrate for fatty acid synthesis, leading to the integration of aberrant fatty acids into the myelin sheath. In the second pathway, impediment of methionine and ultimately S-adenosyl methionine synthesis precludes the methylation of myelin sheath phospholipids, thereby diminishing myelin formation.…”

“…1 When individuals with a borderline vitamin B 12 reserve abuse N 2 O acutely or chronically, cobalamin deficiency may be precipitated. 3 Some people may remain completely asymptomatic, but others may present with the more well-known neurological and/or hematological manifestations. These findings are listed in the Table, and are beyond the scope of this report.…”

“…Less commonly documented are the psychiatric sequelae, with only a handful of cases described in the medical literature. 1,3,5,6 These may occur in the absence of hematological and/or neurological abnormalities. Personality changes, mood disorders (depression, hypomania), paranoid psychosis with visual and auditory hallucinations ("megaloblastic madness"), and violent behavior have all been depicted.…”

“…Personality changes, mood disorders (depression, hypomania), paranoid psychosis with visual and auditory hallucinations ("megaloblastic madness"), and violent behavior have all been depicted. 1,3,5,6 Total serum vitamin B 12 level is one of the standard laboratory investigations ordered to assess for cobalamin deficiency. Holotranscobalamin is a more sensitive test for vitamin B 12 deficiency that is now commercially available.…”