Remembering Molly: Immediate and delayed false memory formation after acute MDMA exposure

This trial (n=60) examined the delayed effects of MDMA (75 mg) on false memory in 60 healthy participants using a basic, associative word list (Deese/Roediger-McDermott (DRM)) paradigm and two applied misinformation tasks using a virtual reality crime, which were administered immediately after the MDMA session and one week later (sober). MDMA increased false memory for related but non-critical lures during the immediate test and decreased false memory for critical lures after a delay. Overall, findings suggest there is no heightened vulnerability to external suggestion in response to MDMA intoxication.

Abstract

“The entactogen 3,4-Methylenedioxymethamphetamine (MDMA) is increasingly being recognized for its therapeutic potential but is also widespread in nightlife settings where it may co-occur with crime. Since previous research detected impaired verbal memory during acute MDMA intoxication, understanding the drug’s ramifications in an applied legal context becomes crucial. We conducted a double-blind, placebo-controlled trial to examine acute and delayed effects of MDMA (75 mg) on false memory in 60 healthy volunteers with a history of MDMA use, using three well-established false memory methods: a basic, associative word list (Deese/Roediger-McDermott (DRM)) paradigm and two applied misinformation tasks using a virtual reality crime. Memory was tested immediately (encoding and retrieval under drug influence) and 1 week later (retrieval when sober). Small MDMA-induced impairments of true memory in the word list task were detected at both time points. MDMA increased false memory for related but non-critical lures during the immediate test and decreased false memory for critical lures after a delay. Episodic memory assessed in the misinformation tasks was not consistently affected. Findings indicate a complex memory profile but no heightened vulnerability to external suggestion in response to MDMA intoxication. Recommendations for future applied legal psychological research include adding measures of recall on top of recognition, using study designs that separate the different memory phases, and potentially testing higher doses. Further research on false memories and suggestibility using imagination procedures can also be relevant for the clinical context.”

Authors: Lilian Kloft, Henry Otgaar, Arjan Blokland, Stefan W. Toennes & Johannes G. Ramaekers

Summary

Abstract

We conducted a double-blind, placebo-controlled trial to examine the acute and delayed effects of MDMA on false memory in 60 healthy volunteers with a history of MDMA use. We found that MDMA increased false memory for related but non-critical lures but decreased false memory for critical lures after a delay.

MDMA is a phenethylamine and a potent indirect monoaminergic agonist, producing stimulant amphetamine-like properties. It has been observed to affect cognition in diverse ways, with some cognitive domains left intact or even improved, while others tend to be impaired.

Evidence that MDMA affects memory functioning comes from two lines of experimentation. Retrospective studies have revealed neurocognitive deficits in MDMA users, but recent well-controlled studies have concluded that light ecstasy use is not associated with clinically deficient verbal memory performance.

Ballard et al. (2012) found that dextroamphetamine increased false memories in a word list task, but MDMA’s effects on memory were specifically mediated by its 5-HT 2A agonism. Thus, MDMA might more closely resemble serotonergic psychedelics when it comes to memory.

Solid and reliable memory functioning is of high relevance to the legal field, especially in court cases where witnesses and suspects are frequently intoxicated. Violence and substance use commonly co-occur in nightlife settings.

Intoxication during a crime, during police interviewing, or both may render an individual particularly susceptible to spontaneous false memories or false memories due to external suggestion. In a recent study, 64 healthy participants received vaporized cannabis and completed three false memory tasks. To date, no research has examined how MDMA impacts false memory production. We conducted a randomized, placebo-controlled study to assess the effects of MDMA on false memory formation.

We tested whether MDMA impaired true memory and false memory by exposing subjects to a virtual reality scenario plus misinformation task.

2.1. Study design

The present study used a 2 by 2 mixed design with Group and Time factors. Participants were matched for age, sex, and education level.

The study was approved by the Medical Ethics Committee of Maastricht University and conducted according to the Declaration of Helsinki and the Medical Research Involving Human Subjects Act.

2.2. Participants

Sixty-one healthy participants with previous MDMA experience were included in the study. All participants were light to moderate users of MDMA and no evidence of long-term structural or functional brain alterations or memory deficits was found.

2.3. Procedures

Subjects were drug-screened (7 days before and 24 h before each test day) and breathalyzed before each testing occasion. All breath alcohol concentration readings showed 0.00 and all pregnancy tests showed a negative result.

Participants received a single dose of MDMA (75 mg) on separate test days, and were tested immediately after ingestion and at a 1-week sober follow-up meeting. MDMA and its metabolite 3,4-methylenedioxyamphetamine (MDA) were analyzed by gas-chromatography coupled to mass spectrometry.

2.4.1. DRM paradigm

In this study, false memory was assessed using the DRM task. Old words were highly associated with the studied words, while new words were less associated with the studied words.

There were two testing phases for each DRM version: one administered immediately after the end of the study phase, and one administered 7 days later. There were 75 words in total, 45 previously presented words, 10 critical lures, and 10 related lures. The delayed version of the Psychovigilance Test consisted of 100 words: 55 presented words, 15 critical lures, 15 related lures, and 15 unrelated words. Participants were instructed to indicate whether they recognized the words from the previous list presentation.

2.4.2. Misinformation paradigm

Participants were exposed to one mock crime scenario per test day in a fully immersive interactive virtual reality environment using the virtual reality headset HTC Vive. Participants experienced a VR scenario in which they were seated on a train witnessing a fight between a man, a police officer and a security guard, or were instructed to steal a purse in a crowded bar. Misinformation was introduced through leading questions at the memory test.

Subjects were instructed to answer with yes or no, to be as truthful as possible, and to guess if they did not know the answer. Interviews consisted of non-leading questions about truly presented details, leading questions about suggested details, and non-leading questions about nonpresented details.

2.5.1. Primary analyses

True memory rates and false memory rates were calculated for the misinformation tasks and DRM, and signal detection parameters were calculated to assess sensitivity and response bias. A correction was applied to true memory rates of 1 and false memory rates of 0.

To test MDMA effects on DRM recognition performance and eyewitness memory performance, two separate 2 (Drug: MDMA vs. placebo) x 4 (Level of association: old words, critical lures, related lures, unrelated words) repeated measures ANOVAs were conducted.

After the effect of Drug/Group was detected, simple main effects were assessed to compare MDMA and placebo at each level of association. Two-tailed t-tests were used for pairwise comparisons of the signal detection parameters.

Equivalence tests were conducted to further explore null findings and to determine equivalence of false memory performance during MDMA and placebo.

2.5.2. Additional analyses

Analyses were conducted to explore whether external factors (i.e. VR telepresence, subjective feeling of being immersed) confounded encoding during the VR experience.

3.1. MDMA concentration levels and subjective intoxication

MDMA and MDA levels were associated with increased ratings of intoxication on all visual analogue scales.

3.2. DRM paradigm

The immediate DRM performance of MDMA and placebo was different for some word categories but not others. MDMA decreased true memory and increased false memory of related lures, but did not affect false memory for critical or unrelated lures.

The level of association effect was still visible for all three false memory rates, but true memory rates were overall lower than false memories for critical lures. MDMA decreased true memory and false memory for critical lures.

3.3.1. Eyewitness scenario

The MDMA and placebo groups performed similarly at the immediate test, but the placebo group showed elevated suggestion-based false memories at the delayed test. Neither sensitivity nor response bias differed statistically between groups.

MDMA decreased false memory for critical lures significantly compared to placebo, with the MDMA group showing more conservative responding at follow-up.

3.3.2. Perpetrator scenario

MDMA-intoxicated individuals showed similar memory performance as their sober counterparts at immediate test, and no significant differences were detected in signal detection parameters.

3.3.4. Additional analyses

MDMA-intoxicated subjects had a higher subjective sense of presence in the VR simulation, but did not affect the findings in the misinformation paradigm.

4. Discussion

This study examined the effects of MDMA on the susceptibility to form false memories. It found that MDMA affected recognition performance in the DRM, but not in the misinformation tasks.

MDMA impaired verbal recognition memory both during acute intoxication and one week later when sober. MDMA also elevated false memories of related lures during acute intoxication, but no other false memory measure was increased by MDMA.

MDMA reduced false memory for critical, thus highly associated lures at the delayed test, whereas true memory impairments were detected. This finding is consistent with the hypothesis that drugs that impair encoding and true memory performance reduce these mechanisms, resulting in reduced associative or gist-based false memory.

Contrary to expectation, no acute MDMA effects on memory were detected in the two misinformation tasks. Intoxicated participants even showed reduced false memories in response to suggestive questions, but only in the eyewitness condition.

MDMA-intoxicated people recognized fewer correct stimuli both when questioned immediately and a week later, but these effects were small and were not found in the misinformation paradigms, where true memory was not affected.

The small and inconsistent memory impairments detected in this study seem to mirror the generally small effect sizes in the MDMA memory literature and may in part reflect its psychostimulant effects.

The present study confirms that MDMA impairs true memory, but small effect sizes and inconsistent results preclude making strong claims about practical relevance. Future research should assess whether MDMA affects recall (instead of recognition) of a forensically relevant event, using study designs that separate different memory phases, and potentially testing higher doses.

Future research could explore whether MDMA’s entactogenic effects translate into people misremembering things they merely imagined, or whether MDMA causes false memories in the context of MDMA-assisted cognitive therapy to treat PTSD.

MDMA seems to have complex effects on memory, with subtler impairments compared to cannabis. Further studies are needed to elucidate the boundary conditions of MDMA-induced memory distortion.

Role of funding

This research was supported by the NWO Research Talent grant. NWO had no further role in study design, data collection, analysis, or interpretation.

Acknowledgements

We thank Dr. Cees van Leeuwen, Dr. Rob van Gassel, Richard Benning, Julia Gros, Kayley van Uden, Rosalie Mourmans, Floor van der Steur, Didi Delsing, Rachel Heutz, Eva van Rosmalen, Elsa Roudot, Beatrice da Rios, Naemi Welter, and Leonie Maatz for their help.