3,4-Methylenedioxymethamphetamine (MDMA) impairs cognitive function during withdrawal via activation of the arachidonic acid cascade in the hippocampus.
Yoko Nawata, Tsuyoshi Nishioku, Tsuneyuki Yamamoto, Taku Yamaguchi
Drug and Alcohol Dependence April 1, 2024 DOI: 10.1016/j.drugalcdep.2024.111139 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | MDMA diclofenac |
| Dose | 10 mg/kg, i.p., once daily for 7 days |
| Duration | 7-day repeated administration, withdrawal assessed on day 1 |
| Topics | MDMA |
| Keywords | Cognitive impairment Cyclooxygenase Prostaglandin e2 Drug research Memory disorders Psychopharmacology Cognitive science |
| Citations | 2 |
| Key points | Activation of the arachidonic acid cascade in the hippocampus is likely involved in recognition memory impairment during MDMA withdrawal, and co-administration of a cyclooxygenase inhibitor prevents this impairment. |
Abstract
The recreational drug ±3,4-methylenedioxymethamphetamine (MDMA; also known as "ecstasy") has unusual subjective prosocial and empathogenic effects, and has exhibited potential as an adjunct to psychotherapy in recent years. However, there has been some concern regarding possible neuropsychiatric symptoms, such as cognitive impairment and dependence, emerging after abstinence. Therefore, this study aimed to evaluate the mechanism underlying cognitive impairment during MDMA withdrawal. To achieve this, we focused on the arachidonic acid cascade, which is related to addiction to some abusive drugs. A novel object recognition task was used to investigate cognitive function in mice. Furthermore, we quantified prostaglandin E2 during MDMA withdrawal. The recognition index significantly decreased during withdrawal after repeated administration of MDMA (10mg/kg, i.p., once daily for 7 days), but not following co-administration of diclofenac (10mg/kg, i.p.), a cyclooxygenase inhibitor. On day 1, following repeated MDMA treatment, prostaglandin E2 content significantly increased in the hippocampus but not in the prefrontal cortex and striatum. Our findings indicate that activation of the arachidonic acid cascade at least in the hippocampus is likely involved in the development of recognition memory impairment during MDMA withdrawal. Therefore, co-use of cyclooxygenase inhibitors with MDMA may reduce concerns regarding MDMA-induced impairment of recognition memory.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 13
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- MDMA enhances emotional empathy and prosocial behavior Social Cognitive and Affective Neuroscience October 4, 2013
- Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. The Lancet Psychiatry April 5, 2016
- 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning Translational Psychiatry September 15, 2015
- The effects of MDMA on socio-emotional processing: Does MDMA differ from other stimulants? Journal of Psychopharmacology August 26, 2016
and 8 more in the library