OPEN Foundation

M. Darracq

A Double-Blinded, Randomized, Placebo-Controlled Sub-Dissociative Dose Ketamine Pilot Study in the Treatment of Acute Depression and Suicidality in a Military Emergency Department Setting

Abstract

Background: Rates of completed suicide in the military have increased. Options are limited for acute relief of depression and suicidal ideation. Traditional treatments’ effects take weeks to months. A novel, rapid, therapeutic target has emerged with the N-methyl-D-aspartate antagonist ketamine. Previous studies suggest that a single dose of intravenous (IV) ketamine rapidly alleviates depression and suicidality.

Methods: In this proof of concept study, an active duty convenience sample population presenting to the emergency department (ED) meeting criteria for inpatient psychiatric admission as a result of depression and suicidal thinking were randomized to receive either a subdissociative dose (0.2 mg/kg) of IV ketamine or equivalent volume of normal saline (placebo). Subjects were evaluated for symptoms throughout a 4-hour ED course, at hospital discharge, and 2 weeks postdischarge.

Results: Methodological problems limited analyzable data to 10 subjects. Two of three who received ketamine experienced dramatic decreases in suicidality and hopelessness within 40 minutes. No such improvements were seen in any of seven controls over the 4-hour observation in the ED. At discharge from the hospital, there was no clinically significant difference. No subjects described adverse symptoms.

Conclusion: Despite methodology difficulties noted in this pilot study, there was statistical improvement in intervention group versus controls.

Burger, J., Capobianco, M., Lovern, R., Boche, B., Ross, E., Darracq, M. A., & McLay, R. (2016). A Double-Blinded, Randomized, Placebo-Controlled Sub-Dissociative Dose Ketamine Pilot Study in the Treatment of Acute Depression and Suicidality in a Military Emergency Department Setting. Military Medicine, 181(10), 1195-1199. 10.7205/MILMED-D-15-00431
Link to full text

A Case of 3,4-Dimethoxyamphetamine (3,4-DMA) and 3,4 Methylendioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction

Abstract

BACKGROUND: We present a case of “ecstasy” ingestion revealing 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-dimethoxyamphetamine (3,4-DMA) and absence of cytochrome P450 (CYP)-2D6 MDMA metabolites.

CASE REPORT: A 19-year-old presented following a seizure. Initial vital signs were normal. Laboratories were normal with the exception of sodium 127 mEq/L and urine drugs of abuse screen positive for amphetamines. Twelve hours later, serum sodium was 114 mEq/L and a second seizure occurred. After receiving hypertonic saline (3%), the patient had improvement in mental status and admitted to taking “ecstasy” at a rave prior to her initial presentation. Liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS) of serum and urine revealed MDMA, 3,4-DMA, and the CYP-2B6 MDMA metabolites 3,4-methylendioxyamphetamine (MDA) and 4-hydroxy-3-methoxyamphetamine (HMA). The CYP2D6 metabolites of MDMA, 3,4-dihydromethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), were detected at very low levels.

CONCLUSION: This case highlights the polypharmacy which may exist among users of psychoactive illicit substances and demonstrates that concurrent use of MDMA and 3,4-DMA may predispose patients to severe toxicity. Toxicologists and other healthcare providers should be aware of this potential toxicity.

Darracq, M. A., Thornton, S. L., Minns, A. B., & Gerona, R. R. (2016). A Case of 3, 4-Dimethoxyamphetamine (3, 4-DMA) and 3, 4 Methylendioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction. Journal of Psychoactive Drugs, 1-4. 10.1080/02791072.2016.1225324
Link to full text

Crafting Music for Altered States and Psychedelic Spaces - Online Event - Jan 22nd