PMID- 35179622
OWN - NLM
STAT- MEDLINE
DCOM- 20220304
LR  - 20220716
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 239
IP  - 3
DP  - 2022 Mar
TI  - MDMA and memory, addiction, and depression: dose-effect analysis.
PG  - 935-949
LID - 10.1007/s00213-022-06086-9 [doi]
AB  - RATIONALE: +/-3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that 
      shows substantial promise as a psychotherapeutic agent. Still, there is some 
      concern regarding its behavioral toxicity, and its dose-effect relationship is 
      poorly understood. We previously explored the role of dose in the cognitive 
      effects of MDMA in a systematic review of existing literature and found no 
      evidence in animals that MDMA impairs memory at low doses (< 3 mg/kg) but mixed 
      results at high doses (>/= 3 mg/kg). Since this review comprised mostly of 
      single-dose studies and an assortment of methodologies, an empirical dose-ranging 
      study on this topic is warranted. OBJECTIVES: The current study aims to evaluate 
      the conclusion from our systematic review that 3 mg/kg may be the threshold for 
      MDMA-induced amnesia, and to further understand the dose-effect relationship of 
      MDMA on behavioral assays of memory, addiction, and depression. METHODS: We 
      systematically examined the effects of 0.01 to 10 mg/kg MDMA on Pavlovian fear 
      conditioning; behavioral sensitization, conditioned place preference, and 
      conditioned responding; and the Porsolt forced swim test in mice. RESULTS: High 
      doses of MDMA (>/= 3 mg/kg) produced amnesia of fear conditioning memory, some 
      evidence of an addictive potential, and antidepressant effects, while low doses 
      of MDMA (</= 1 mg/kg) had no effect on these behaviors. CONCLUSIONS: The present 
      dose-ranging study provides further evidence that 3 mg/kg is the threshold for 
      MDMA-induced amnesia. These findings, in addition to our systematic review, 
      demonstrate that careful selection of MDMA dose is critical. High doses (>/= 3 
      mg/kg) should likely be avoided due to evidence that they can produce amnesia and 
      addiction. Conversely, there is little evidence to suggest that low doses, which 
      are usually administered in clinical studies (approximately 1-2 mg/kg), will lead 
      to these same adverse effects. Ultra-low doses (< 1 mg/kg) are likely even safer 
      and should be investigated for therapeutic effects in future studies.
CI  - (c) 2022. The Author(s).
FAU - Pantoni, Madeline M
AU  - Pantoni MM
AUID- ORCID: 0000-0001-6572-0162
AD  - Molecular Cognition Laboratory, Department of Psychology, University of 
      California San Diego, La Jolla, CA, USA. maddie.pantoni@gmail.com.
AD  - Translational Psychedelic Research Program, Department of Psychiatry and 
      Behavioral Sciences, University of California San Francisco, CA, San Francisco, 
      USA. maddie.pantoni@gmail.com.
FAU - Kim, Jinah L
AU  - Kim JL
AD  - Molecular Cognition Laboratory, Department of Psychology, University of 
      California San Diego, La Jolla, CA, USA.
FAU - Van Alstyne, Kaitlin R
AU  - Van Alstyne KR
AD  - Molecular Cognition Laboratory, Department of Psychology, University of 
      California San Diego, La Jolla, CA, USA.
FAU - Anagnostaras, Stephan G
AU  - Anagnostaras SG
AD  - Molecular Cognition Laboratory, Department of Psychology, University of 
      California San Diego, La Jolla, CA, USA.
AD  - Molecular Cognition Laboratory, Program in Neurosciences, University of 
      California San Diego, La Jolla, CA, USA.
LA  - eng
PT  - Journal Article
PT  - Review
PT  - Systematic Review
DEP - 20220218
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
EIN - Psychopharmacology (Berl). 2022 Jul;239(7):2369. PMID: 35438305
MH  - Amnesia
MH  - Animals
MH  - Conditioning, Classical
MH  - Depression/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Fear
MH  - Mice
MH  - *N-Methyl-3,4-methylenedioxyamphetamine/adverse effects
PMC - PMC8891111
OTO - NOTNLM
OT  - 3,4-Methylenedioxymethamphetamine
OT  - Addiction
OT  - Behavioral sensitization
OT  - Conditioned place preference
OT  - Depression
OT  - MDMA
OT  - Memory
OT  - Mice
OT  - Pavlovian fear conditioning
OT  - Stimulant
COIS- The authors declare no competing interests.
EDAT- 2022/02/19 06:00
MHDA- 2022/03/05 06:00
PMCR- 2022/02/18
CRDT- 2022/02/18 12:13
PHST- 2021/09/30 00:00 [received]
PHST- 2022/02/07 00:00 [accepted]
PHST- 2022/02/19 06:00 [pubmed]
PHST- 2022/03/05 06:00 [medline]
PHST- 2022/02/18 12:13 [entrez]
PHST- 2022/02/18 00:00 [pmc-release]
AID - 10.1007/s00213-022-06086-9 [pii]
AID - 6086 [pii]
AID - 10.1007/s00213-022-06086-9 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2022 Mar;239(3):935-949. doi: 
      10.1007/s00213-022-06086-9. Epub 2022 Feb 18.