Unique Effects of Sedatives, Dissociatives, Psychedelics, Stimulants, and Cannabinoids on Episodic Memory: A Review and Reanalysis of Acute Drug Effects on Recollection, Familiarity, and Metamemory

This preprint (2022) assessed the effects of different psychoactive drugs on episodic memory and cognition by reanalysing episodic memory confidence data from 10 previously published datasets. Sedatives, dissociatives, psychedelics, stimulants, and cannabinoids had unique patterns of effects on these mnemonic processes dependent on which phase of memory while all drugs at encoding, except stimulants impaired recollection, and sedatives, dissociatives, and cannabinoids at encoding impaired familiarity. Psychedelics at encoding tended to enhance familiarity and did not impact metamemory.

Abstract

“Despite distinct classes of psychoactive drugs producing putatively unique states of consciousness, there is surprising overlap in terms of their effects on episodic memory and cognition more generally. Episodic memory is supported by multiple subprocesses that have been mostly overlooked in psychopharmacology and could differentiate drug classes. Here, we reanalyzed episodic memory confidence data from 10 previously published datasets (28 drug conditions total) using signal detection models to estimate 2 conscious states involved in episodic memory and 1 consciously-controlled metacognitive process of memory: the retrieval of specific details from one’s past (recollection), noetic recognition in the absence of retrieved details (familiarity), and accurate introspection of memory decisions (metamemory). We observed that sedatives, dissociatives, psychedelics, stimulants, and cannabinoids had unique patterns of effects on these mnemonic processes dependent on which phase of memory (encoding, consolidation, or retrieval) was targeted. All drugs at encoding except stimulants impaired recollection, and sedatives, dissociatives, and cannabinoids at encoding impaired familiarity. The effects of sedatives on metamemory were mixed, whereas dissociatives and cannabinoids at encoding tended to enhance metamemory. Surprisingly, psychedelics at encoding tended to enhance familiarity and did not impact metamemory. Stimulants at encoding and retrieval enhanced metamemory, but at consolidation, they impaired metamemory. Together, these findings may have relevance to mechanisms underlying unique subjective phenomena under different drug classes, such as blackouts from sedatives or deja vu from psychedelics. This study provides a framework for interrogating drug effects within a domain of cognition beyond the global impairments on task performance typically reported in psychopharmacology.”

Authors: Manoj Doss, Jason Samaha, Frederick S. Barrett, Roland Griffiths, Harriet de Wit, David Gallo & Joshua Koen

Summary

Research

The author/funder of this preprint (Manoj K. Doss, 5510 Nathan Shock Drive, Baltimore, MD 21224 ORCID: 0000-0003-2939-2518) has granted bioRxiv a license to display the preprint in perpetuity.

The author/funder of this preprint (MDEA = 3,4-methylenedioxyethylamphetamine, NMDA = N-methyl-d-aspartate, PAM = positive allosteric modulator, ROC = receiver operator characteristic, THC = D9-tetrahydrocannabinol) has granted bioRxiv a license to display the preprint in perpetuity.

We reanalyzed episodic memory confidence data from 10 previously published datasets (28 drug conditions total) using signal detection models to estimate 2 conscious states involved in episodic memory and 1 consciously-controlled metacognitive process of memory. Sedatives, dissociatives, psychedelics, stimulants, and cannabinoids had unique patterns of effects on memory processes, depending on which phase of memory was targeted. Sedatives impaired recollection, while dissociatives and cannabinoids impaired familiarity.

This systematic review and reanalysis of several datasets indicates that different drugs can have idiosyncratic effects on episodic memory, and provides a framework for future work to differentiate the effects of psychoactive drugs within a domain of cognition.

Acute drug effects on episodic memory include sedatives, dissociatives, psychedelics, stimulants, catecholamine transporter inhibitors, cannabinoids, and psilocybin. The preprint is made available under a CC-BY-NC-ND 4.0 International license, and the copyright holder is the author/funder.

This preprint discusses the effects of MDMA, Dextroamphetamine, THC, and other drugs on episodic memory. It also discusses the degree of receptor distribution, which may determine drug effects on familiarity, and the dual process model of memory.

Several classes of psychoactive drugs are found to impair episodic memory, have little impact on post-encoding stabilization of memories, and increase false memories when remembering memories. Finally, most drugs impair metacognition. Although non-episodic memory has been extensively investigated in psychopharmacology, episodic memory is underexplored in terms of its utility to understanding addictive behaviors.

This preprint is made available under aCC-BY-NC-ND 4.0 International license and is not certified by peer review. Understanding how drugs impact episodic memory may be crucial for developing novel therapeutics. For example, the sedative midazolam impairs the encoding of contextual information, whereas the cannabinoid -9-tetrahydrocannabinol spares context reinstatement effects on memory. Computational modeling can be used to estimate the contribution of different mnemonic subprocesses to performance on a memory task, and can be more sensitive to drug effects than standard measures of cognition that do not differentiate key mnemonic subprocesses.

We utilized two computational models of memory confidence to explore unique patterns of drug effects on recollection, familiarity, and metamemory. We found that these processes may support distinct aspects of consciousness and be selective targets of different psychoactive drugs. We introduce recollection, familiarity, and metamemory, and then use the dual process signal detection (DPSD) model and the meta-d’ model to analyze 10 datasets with 28 different drug manipulations. We conclude with a discussion of novel drug effects and guidance for future work.

This preprint is available under a CC-BY-NC-ND 4.0 International license and was not certified by peer review.

Recent neurocognitive models have explored the interactions between mnemonic representations and metacognitive operations that contribute to conscious experience. Measuring the effects of drugs on recollection, familiarity, and metamemory may allow us to capture idiosyncratic “altered states of consciousness”. Recollection and familiarity are two qualitatively distinct processes that contribute to memory performance. Recollection is associated with a subjective reliving of an experience, while familiarity is a feeling of knowing that a stimulus has been experienced.

12 unique acute drug effects on episodic memory evidence. Recollection and familiarity are thought to be supported by sensory hierarchies and semantic memory stores, with perirhinal cortex supporting this function. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Acute drug effects on episodic memory are unique in that familiarity can lead to intrusions in memory that may no longer be relevant, whereas recollection can be used to update memories with new associations. Acute drug effects on episodic memory include impairment of recollection, enhancement of mental imagery, and a greater tendency to misattribute familiar objects to having visited the location.

Multiple mechanisms of false memory induction may be driven by some drugs under certain conditions. We focus on retrospective metamemory here. Metamemory is the degree to which confidence tracks performance, and one’s confidence in one’s memory can be influenced by how well they understand their own memory system and their resulting expectations. Poor metamemory can result in memory distortions.

There has been increased interest in metacognitive processes in psychiatry, and treatments aimed at improving metacognition may have some success in improving psychiatric illnesses. However, enhancing dopaminergic signaling in healthy participants can impair metamemory. Patients with cocaine addiction and opioid addiction who are receiving methadone maintenance treatment had impaired perceptual metacognition, but their retrospective metamemory was not impaired.

This preprint is made available under aCC-BY-NC-ND 4.0 International license and was not certified by peer review. Anxiety and depression are associated with better perceptual metacognition, but compulsion and intrusive thoughts are associated with worse perceptual metacognition. An impairment in metamemory may underlie obsessive checking even if memory is intact, and prolonged use of cognitively impairing drugs may contribute to the belief that one has poor memory. Episodic memory paradigms contain an encoding phase followed by a retrieval phase. Most work in psychopharmacology administers a drug prior to the encoding phase.

Acute drug effects on episodic memory are typically made to ensure that participants are paying attention and that the “depth of processing” is held constant across experimental conditions. This minimizes differences in cognitive operations that could spontaneously vary across experimental conditions. After encoding, a delay period is sometimes implemented to allow memories to stabilize or “consolidate”. Pharmacological manipulations of consolidation may be able to retroactively enhance or impair recently encoded memories, but this is time-dependent.

Acute drug effects on episodic memory enhancements with stress can drastically differ from pre-encoding effects. Free recall is the most common test of memory for verbal stimuli in psychopharmacology, and recognition memory tests are another common way to assess memory.

Recognition memory tests can lead to different conclusions about memory relative to recall tests, and may be able to shed light on multiple mnemonic processes to which recall tests may be less sensitive.

There are four outcomes of a recognition test: a hit, a false alarm, a miss, and a correction rejection. The hit rate and false alarm rate are the main measures of recognition memory accuracy. At least two processes, namely recollection and familiarity, support accurate responding on recognition memory tests. The process dissociation procedure is a method that puts recollection and familiarity in opposition to each other and allows to quantify the contribution of recollection and familiarity more readily.

Acute drug effects on episodic memory can be estimated using the probabilities of accepting stimuli from encoding on either memory test. Another method is the remember/know procedure, which asks participants to report subjective experiences of recollection and familiarity. The “know” response is an underestimate of familiarity because it measures familiarity in the absence of recollection. One last method for dissociating recollection and familiarity is to have participants report their confidence in their old/new recognition decisions. This confidence data can be analyzed with signal detection theory to estimate different mnemonic processes.

Different signal detection models have been developed to tease apart influences on memory confidence, including recollection and familiarity, but rarely direct comparisons between dual process and metacognitive signal detection models have been conducted within the same study. Signal detection theory states that when making a recognition memory decision or any other decision, an observer must determine whether a stimulus has actually been observed in the context of an inherently noisy system. The response bias can vary from one individual to another.

The author/funder of this preprint has granted bioRxiv a license to display the preprint in perpetuity. Reversing the contingencies in the above example would lead to a more conservative response bias, where targets are labelled only a few stimuli as targets. Signal detection theory attempts to identify the distance between two Gaussian distributions of internal evidence corresponding to two different mental states (memory or no memory for a given stimulus) while accounting for an individual’s response criterion. ROC curves suggest that the signal and noise distributions are not equal in variance.

The author/funder of this preprint (which was not certified by peer review) has granted bioRxiv a license to display the preprint in perpetuity. Multiple levels of response bias can be obtained by having participants report their confidence in their old/new recognition decisions. Animals can also show different levels of response bias by varying the reward for correct trials or the difficulty to respond. A large body of work has shown that ROC curves from recognition tasks that tap episodic memory are typically asymmetrical, suggesting that there are at least two processes that influence confidence judgements in old/new memory decisions.

Acute drug effects on episodic memory are controversial. Data are made available for further analyses under other frameworks. A dual process signal detection model (DPSD) was proposed to explain why mnemonic ROC curves were asymmetrical, and that familiarity is a continuous signal detection process. Yonelinas (1994, 1999) proposed a model where recognition memory decisions are determined by a mixture of a high-threshold process and an equal-variance signal detection process. The parameters for recollection and familiarity typically converge with those from other non-signal detection methods.

This preprint discusses the effects of acute drugs on episodic memory. It is made available under a CC-BY-NC-ND 4.0 International license, and has not been certified by peer review. The rank order correlation gamma is an imperfect measure of metamemory because it correlates with memory performance, and it can be influenced by nonspecific response biases. However, signal detection theory can handle these problems.

Acute drug effects on episodic memory are available under a CC-BY-NC-ND 4.0 International license. Type 2 signal detection models plot the proportion of correct responses against the proportion of incorrect responses, regardless of whether the test stimulus is old or new at different response criteria. Type 2 ROC curves can be used to compute a discrimination score that quantifies how far the curve is from the chance diagonal. However, the area under the type 2 ROC curve is affected by type 1 d’ and criterion, and therefore does not control for type 1 difficulty. One can generate type 2 ROC curves for given type 1 decisions and type 2 ROC curves for given type 1 decisions. The author/funder of this preprint has granted bioRxiv a license to display the preprint in perpetuity.

A drug’s acute effects on episodic memory can be measured by its effect on the type 2 ROC curve alone, or by dividing it by the observed type 1 ROC curve. We briefly review what is currently known about the effects of different classes of drugs on episodic memory, and then apply the DPSD and meta-d’ models to the acquired datasets.

The author/funder of this preprint (which was not certified by peer review) grants bioRxiv a license to display the preprint in perpetuity.

With careful manipulations, such as separating encoding and retrieval phases with a 24 hour delay, certain drug effects can be attributed to different phases. For instance, pre-encoding sedatives can impair discrimination between targets and lures on a recognition memory test, but not false alarm rates. Drug effects at encoding or consolidation may have less impact on metamemory than effects at retrieval.

Metamemory is impacted by drug effects during encoding or consolidation. The author/funder has granted bioRxiv a license to display the preprint in perpetuity.

29 Unique acute drug effects on episodic memory are possible, but it is unclear how they would affect confidence judgements. Sedatives are drugs that facilitate activity at the GABAA receptor, specifically GABAA positive allosteric modulators (PAMs). Alcohol, benzodiazepines, and non-benzodiazepine hypnotics are particularly sedating and appear to have strikingly similar effects on episodic memory, suggesting that most of these mnemonic effects can be accounted for by GABAA facilitation.

We discuss acute drug effects on episodic memory, but do not discuss retrieval effects. Sedatives are particularly well-known for their amnestic effects, though these effects are only present when these drugs are administered prior to memory encoding. Sedatives impair both recollection and familiarity, and alcohol impairs both recollection and familiarity. GABAA PAMs at encoding also impair memory, which may explain why sedatives can cause “blackouts”. Several studies have found that sedatives impair metamemory, though not always. However, all of these studies used gamma, which is susceptible to response bias confounds and memory accuracy scaling.

Sedatives decrease memory accuracy when administered at encoding, but enhance memory if administered immediately post-encoding (i.e., during consolidation). This effect has been found in multiple groups, with different sedatives, on different stimuli, and across various delays between encoding and retrieval. Several studies have shown that sedatives enhance slow waves and sleep spindles, processes important for memory consolidation, and that sedatives prevent the encoding of new information that would normally interfere with information previously encoded in a drug-free state.

Acute drug effects on episodic memory are associated with larger memory enhancements of zolpidem at consolidation on recollection-based memory, though this effect is mostly only apparent for neutral and not emotionally positive or negative stimuli. Dissociative hallucinogens are drugs that antagonize the N-methyl-D-aspartate (NMDA) receptor. Although the effects of dissociatives are likely not mediated solely by NMDA antagonism, the similar dissociative state evoked by dissociatives and other NMDA antagonists suggests that NMDA antagonism is a primary mechanism of action.

Dissociative drugs have little impact on memory accuracy at retrieval, and have some evidence of diminished metamemory. They have strong amnestic effects when administered prior to encoding like sedatives. Dissociatives at encoding impair recollection and familiarity, but it is less clear if familiarity is also impacted. It is also unclear whether these dissociatives at encoding impact metamemory.

34 studies have found acute drug effects on episodic memory of metamemory with higher doses of dextromethorphan. The most recent study did not find any impact of ketamine at encoding on metamemory. Psychedelics have a range of effects on perception, particularly vision, and appear to facilitate or distort semantic processing, which may be responsible for the sense that some experiences are endowed with highly significant meaning. Although some use the term “psychedelic” to refer to other hallucinogens, we reserve the term here for drugs with serotonin 2A (5-HT2A) agonism. Moreover, co-administration of a 5-HT2A antagonist attenuates the subjective effects of psilocybin, LSD, and DMT.

The isolated R-enantiomer of 3,4-methylenedioxyethylamphetamine (MDMA) appears to produce psychedelic effects distinct from the S-enantiomer, and for these reasons, we group MDMA with psychedelics. MDMA’s effects on episodic memory resemble those of psychedelics, and may be particularly familiarity-based. Studies have consistently found that MDMA impairs free recall, even though typical stimulants can enhance memory encoding. Moreover, this impairment can be abolished with 5-HT2A antagonism.

Acute drug effects on episodic memory include impaired recollection and enhanced familiarity, though these effects are only found for emotional (negative and positive) but not neutral stimuli. Psychedelic users anecdotally report that these drugs give a better understanding of one’s mind, but psychedelics have not been tested on any measure of metacognition. MDMA numerically impaired recollection but not familiarity, but did not appear to impact recollection measured from the remember/know procedure.

The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. Stimulants are drugs that inhibit catecholamine transporters, such as amphetamine, methamphetamine, cocaine, methylphenidate, and cathinones. Amphetamine and methylphenidate are prescribed for ADHD, and methamphetamine is still a prescribed drug for obesity despite its high abuse potential. Stimulants at encoding can enhance recollection-based memory, but the benefit is inconsistent and can be canceled out by impaired sleep.

Stimulants at encoding may enhance memory via dopamine-dependent replay, though the effects of stimulants at consolidation have not been tested. It is unclear what effects stimulants at consolidation have on recollection, familiarity, or metamemory. Most studies on the effects of stimulants at retrieval are in the context of state-dependent learning. One study found dextroamphetamine to increase false memories, but another study did not replicate this effect.

Studies of state-dependency are mixed, with some finding that stimulants at retrieval can reduce recollection-based memory, while others finding no such evidence. Cannabinoids (e.g., THC) are compounds in cannabis that act on the cannabinoid 1 receptor (CB1). They have subjective and perceptual effects that can mimic psychotic symptoms, and are sometimes labeled as hallucinogens. We focus on encoding and retrieval effects of cannabinoids, and note that one study found no impact of THC at consolidation on free recall. However, THC administered during encoding might not impact recognition.

THC at encoding may impair metamemory, though the measure used to assess this is likely to suffer from the same problems as gamma. THC at retrieval increases false memories as measured by increased high confidence false alarms on a cued recollection test and false recognition with “remember” and “know” responses on a recognition test. This effect may be reflected in an impairment of metamemory, though it may simply be a criterion shift in signal detection models.

This preprint is available under a CC-BY-NC-ND 4.0 International license and was not certified by peer review.

Analytic Methods

We re-analyzed data from 10 double-blind, placebo-controlled drug administration studies to determine the effects of a variety of drug classes on recollection, familiarity, and metamemory. We used the ROC Toolbox for Matlab to estimate recollection and familiarity.

Table I

Some datasets contained as few as 36 trials per drug condition, which makes it difficult to estimate single subject parameters. We performed a bootstrapping procedure to generate distributions of recollection and familiarity parameters, and discussed recurring trends, especially those that may be unique to a class of drugs. We used meta-d’ Matlab functions to estimate metamemory from the meta-d’ model. A type 1 d’ can be interpolated from this type 2 ROC curve assuming a metacognitively ideal observer.

We performed bootstrapping experiments using identical random samples of participants and compared each drug condition to the placebo condition of a given dataset. The results show that there are 44 unique acute drug effects on episodic memory. Alcohol impaired recollection and familiarity, though these effects were mostly only apparent for negative and positive stimuli, and were supported by a reanalysis of remember/know data from several studies with GABAA PAM manipulations at encoding that had previously failed to use the independence correction.

45 unique acute drug effects on episodic memory impairments on verbal recognition tests using gamma were found. However, gamma is problematic as a measure of metacognition, and longer delays between encoding and retrieval may attenuate metamemory impairments. Alcohol and other GABAA modulators at encoding are known to impair memory, but GABAA modulators administered immediately post-encoding (i.e., at consolidation) enhance memory. It is unclear what the effects of alcohol at consolidation will be on metamemory.

A double-blind, between-subjects design was used in which 59 young adults were randomized to one of 3 demographically similar groups: placebo, encoding, or consolidation. Alcohol and placebo were administered orally via gelatin. Participants consumed gelatin for the first session and completed an encoding phase of a cued recollection task. The second session consisted of a cued recollection test, and participants were only permitted to listen to music without lyrics during the first two hours. This preprint is made available under aCC-BY-NC-ND 4.0 International license and was not certified by peer review.

Participants were presented with 240 labels and asked whether they had seen a picture of each label. The results are displayed in Figure IIa-c. Alcohol impaired recollection and familiarity, and impaired metamemory, but the effect was driven by beverage stimuli, which have more overlapping conceptual and perceptual features than negative, neutral, and positive stimuli. Alcohol’s enhancement of consolidation was only trending for recollection and negligible for familiarity.

Acute drug effects on episodic memory include impaired recollection, familiarity, and metamemory, though the metamemory impairment may have been due to idiosyncratic stimuli. Alcohol at consolidation enhanced recollection but had no impact on familiarity or metamemory.

Zolpidem, a GABAA PAM, impairs memory on verbal free recall tests, as well as metamemory on verbal recognition tests measured with gamma. Although the complex design of the current dataset has several potential confounds, it also has many advantages, such as allowing for the assessment of multiple memory tests within a session and allowing for the potential development of tolerance to zolpidem between these sessions.

This preprint is available under a CC-BY-NC-ND 4.0 International license and was not certified by peer review. In a double-blind, within-subjects design, 15 young adults took zolpidem nightly for 22 to 30 days before each of 4 sessions that contained 4 verbal memory tests. They used a single response, hybrid old/new six-point confidence scale to indicate whether each word was previously presented. Participants took a capsule, went to sleep for 30 minutes, and were woken up 80 minutes later to take a second memory test. After the second memory test, they went back to sleep for another 210 to 270 minutes.

The author/funder of this preprint (which was not certified by peer review) has granted bioRxiv a license to display the preprint in perpetuity. We separately compared both zolpidem sessions to both placebo sessions for each memory test at a given timepoint, producing four contrasts. Three of the four contrasts found zolpidem to impair recollection at encoding, and memory retrieval occurred shortly after encoding. Zolpidem impaired familiarity in all contrasts (first placebo vs. first zolpidem, first placebo vs. second zolpidem: familiarity, second placebo vs. second zolpidem: familiarity, third placebo vs. third zolpidem: familiarity). Acute drug effects on episodic memory is available under aCC-BY-NC-ND 4.0 International license.

None of the contrasts found zolpidem to impair metamemory, though the distributions were extremely wide.

This preprint is made available under aCC-BY-NC-ND 4.0 International license, and the author/funder has granted bioRxiv a license to display the preprint in perpetuity.

zolpidem had unique acute effects on episodic memory, with memory retrieval occurring 270 minutes post-encoding with sleep between these phases. All contrasts found zolpidem to impair recollection and familiarity, but none found zolpidem to impair metamemory. Zolpidem did not impair memory for the order of events or the order of the events themselves. The current analysis of triazolam and ketamine at encoding suggests that triazolam should impair recollection, familiarity, and perhaps metamemory, while ketamine should impair recognition and not metamemory.

Ketamine at encoding would be expected to impair recollection with possible impairments on familiarity and metamemory. 20 young to middle-aged adults were orally administered a capsule followed 75 minutes later by an intramuscular infusion. They then completed a verbal memory test and a free recall test followed by a recognition test.

Figure IVa-c display the distributions of parameter estimates from the DPSD and meta-d’ models for the triazolam conditions. Triazolam impaired recollection but not familiarity or metamemory.

Triazolam impaired recollection and familiarity, but had no impact on metamemory. Ketamine enhanced metamemory with increasing doses, though in other datasets higher doses of dissociatives tended to impair familiarity.

Ketamine impaired recollection but not familiarity or metamemory, and the higher dose of ketamine enhanced metamemory. The dissociative dextromethorphan at encoding had a similar effect on recollection but not familiarity or metamemory. A dataset from (Carter, Reissig, et al., 2013) was used to compare the effects of triazolam and dextromethorphan on encoding. It was found that triazolam impaired free recall, recognition, and metamemory measured with gamma, while dextromethorphan left familiarity and metamemory relatively intact.

62 participants (27.5-years-old, range = 20-40, 9 males) were administered placebo, triazolam, or dextromethorphan orally for up to 11 sessions. The maximum tolerable dose of dextromethorphan was 300 mg/70 kg, and analyses were limited to the first three doses. At 120 minutes post-capsule ingestion, triazolam impaired recollection and familiarity, but not free recall. There was a trend for triazolam to impair recognition memory at 320 minutes post-capsule ingestion.

Acute drug effects on episodic memory include impairments of recollection and familiarity, and enhancements of metamemory. Triazolam at encoding enhances metamemory, but the distribution of metamemory estimates is abnormally wide.

Triazolam impaired recollection and familiarity and had a trend for enhancement of metamemory, though this enhancement did not replicate for any other sedative manipulation. Dextromethorphan had no impact on metamemory.

Dextromethorphan impaired recollection but not familiarity, and numerically but non-significantly increased metamemory, similar to the previous analysis with ketamine. However, 300 mg/70 kg of dextromethorphan decreased both recollection and familiarity, but not metamemory. The dataset from the current analysis comes from (Barrett et al., 2018). The DPSD analysis found that dextromethorphan impaired recollection and familiarity compared to placebo, but the effects on metamemory are unclear.

Psilocybin at encoding impaired free recall and recollection at the two higher doses, but did not impact familiarity. However, there were numerical enhancements in recollection at the higher doses, which is peculiar, as most impairments of recollection in the previous analyses were accompanied by familiarity impairments. A double-blind, within-subjects design was used in which 20 young to middle-aged adults were orally administered a capsule containing placebo, a moderately high dose of dextromethorphan, a moderate dose of psilocybin, a moderately high dose of psilocybin, and a high dose of psilocybin prior to encoding stimuli.

Dextromethorphan impaired recollection (M = .18, SD = .07, CI = [.06, .32], p = .002) after encoding, but not after a free recall test.

The effects of dextromethorphan at encoding on familiarity were not significant, but dextromethorphan at encoding enhanced metamemory similar to the numerical increases in the previous analyses with ketamine and 100 mg/70 kg of dextromethorphan at encoding.

Dextromethorphan impaired recollection and familiarity, psilocybin enhanced metamemory, and ketamine impaired recollection and familiarity. Psilocybin had no impact on metamemory.

Psilocybin impairs episodic memory at doses of 10 mg/70 kg, 20 mg/70 kg, and 30 mg/70 kg, but enhances familiarity at doses of 20 mg/70 kg and 30 mg/70 kg. There is no evidence that psychedelics impact metamemory. MDMA impairs recollection but enhances familiarity estimates, though only for emotional stimuli. Given that MDMA activates the 5-HT2A receptor, it is possible that MDMA at encoding could have similar effects as stimulants such as dextroamphetamine and available under aCC-BY-NC-ND 4.0 International license.

According to the analyses of stimulant data below, MDMA’s mnemonic effects more closely resemble a psychedelic. MDMA at retrieval did not significantly impact recollection or familiarity, but there was some evidence for MDMA to increase high confidence false alarms. This study used a double-blind, between-subjects design in which 60 young adults were randomized to one of three groups: placebo, encoding, or retrieval. Doses of MDMA were administered orally via capsules.

This preprint is available under aCC-BY-NC-ND 4.0 International license and was not certified by peer review. Participants were presented with 180 labels and were asked to indicate on a five-point scale how much they would like to see a picture of each label. After the encoding phase, they remained in the lab for three and a half hours and completed the retrieval phase. MDMA at encoding impaired recollection, but increased familiarity, and did not significantly impact metamemory. MDMA at retrieval did not impact recollection, familiarity, or available under aCC-BY-NC-ND 4.0 International license.

There was no evidence for a psychedelic enhancement of the awareness of mnemonic processes. The preprint is made available under aCC-BY-NC-ND 4.0 International license.

Figure VII

MDMA impaired recollection and enhanced familiarity, particularly for emotional stimuli, but had no impact on metamemory. MDMA at retrieval had no impact on recollection, familiarity, or metamemory, again not exhibiting the stimulant effects observed in Study 7.

The dataset from the current analysis comes from (Weafer et al., 2014), and shows that dextroamphetamine increases synaptic monoamines, but does not activate 5-HT2A receptors. However, other studies have found that dextroamphetamine and methylphenidate at encoding improve memory on recollection-based tasks. Dextroamphetamine at retrieval has been found to increase recall intrusions and false recognition, but the original study did not find evidence for an increase in false alarms.

There are state-dependent effects of stimulants on episodic memory that are greater than encoding enhancements alone. However, other studies have found no evidence for enhancements when a stimulant is given during both encoding and retrieval on recollection-based tasks. A double-blind, between-subjects design was used in which 59 young adults were randomized to one of four demographically similar groups: placebo, encoding, retrieval, or both encoding and retrieval. Participants completed a 144-trial cued recollection task after consuming the first capsule.

Acute drug effects on episodic memory were studied using a cued recollection task. Participants were presented with a negative, neutral, or positive label and were asked whether they had seen a picture of that label. Dextroamphetamine at encoding did not impact recollection, familiarity, or metamemory, but enhanced familiarity and metamemory at retrieval.

There was a trend for a familiarity enhancement and a robust metamemory enhancement in the retrieval group, but not in the encoding group. The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. The metamemory enhancement was numerically greater in the “both” group than the retrieval group, suggestive of a state-dependent effect.

Dextroamphetamine at encoding had no impact on recollection, familiarity, or metamemory, but enhanced familiarity and metamemory at retrieval. Dextroamphetamine at both encoding and retrieval enhanced metamemory more than either encoding or retrieval alone.

Dextromethamphetamine was not found to impact memory on a picture recognition test, but it caused poor sleep in several participants. It is unclear whether dextromethamphetamine at consolidation will impact recollection, familiarity, or metamemory. A double-blind, mixed within- and between-subjects design was used in which 60 young adults were randomized to one of 2 demographically similar groups: encoding (N = 29, 14 males) or consolidation (N = 31, 15 males).

84 unique acute drug effects on episodic memory were studied. The encoding group received each drug manipulation prior to encoding stimuli, and the consolidation group received each drug manipulation immediately post-encoding. Participants completed a 60-trial picture recognition task, during which they rated the picture’s valence and arousal. During the retrieval phase, they indicated whether they had previously seen the picture (yes/no), followed by a confidence rating on a 9-point scale and valence and arousal ratings, resulting in an 18-point scale.

The author/funder of this preprint (which was not certified by peer review) has granted bioRxiv a license to display the preprint in perpetuity. The 10 mg dose did not impact recollection, but the 20 mg dose did enhance familiarity.

Dextromethamphetamine at encoding had no impact on recollection or familiarity, but the lower dose enhanced metamemory. Dextromethamphetamine at consolidation had no impact on recollection or familiarity, but both doses impaired metamemory.

Dextromethamphetamine had no impact on recollection or familiarity, but impaired metamemory. This is in sharp contrast to the previous findings that found stimulants at encoding, retrieval, or both encoding and retrieval to enhance metamemory. The effects of THC on encoding were studied, and it was found that THC impairs recollection. The dataset from the current analysis comes from (Doss, Weafer, et al., 2020), and it is made available under aCC-BY-NC-ND 4.0 International license.

THC at encoding was not found to modulate context reinstatement, but did modulate false memory in a post hoc analysis. This suggests that THC may have less of an impact on recollection compared to other drugs and perhaps even spare familiarity. A double-blind, within-subjects design was used in which 24 young adults received a capsule containing placebo and THC (15 mg) approximately 155 minutes prior to encoding stimuli in 2 separate experimental arms.

Participants were presented with object-scene pairings, but the object could be the original object, a similar object, or a completely new object. They were to decide whether the object (but not the scene) was “old”, “similar”, or “new” and then rate their confidence on a five-point scale.

THC impaired recollection and familiarity, but enhanced metamemory. The copyright holder for this preprint (which is made bioRxiv preprint doi: https://doi.org/10.1101/2022.05.20.492842; this version posted May 24, 2022) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Study 10 found that THC at retrieval increased false alarms, including high confidence false alarms, and hit rates were unaffected. However, this may not actually be an impairment in recollection, as others have found no impairment of THC at retrieval on verbal free recall. A double-blind, within-subjects design was used in which 23 young adults received a capsule containing placebo and THC (15 mg) prior to the retrieval phase (sober encoding). During the first session of each arm, participants completed a 120-trial cued recollection task.

Participants were given acute drug effects on episodic memory and then completed a cued recollection task. They were presented with labels and asked whether they had seen a picture of them. The effect of THC on recollection appears to be bimodal, with a peak shifted leftward from the placebo distribution but also a single peak at 0. There is no significant impact of THC on familiarity or metamemory. This preprint is available under a CC-BY-NC-ND 4.0 International license and was not certified by peer review.

Figure XI

The effects of -9-tetrahydrocannabinol at retrieval were to impair recollection, though this was strictly due to an increase in false alarms, suggesting a false memory effect that is not captured in the dual process signal detection model.

Different psychoactive drugs produce unique patterns of effects on episodic memory. Sedatives, dissociatives, and cannabinoids at encoding consistently impaired recollection and familiarity at higher doses, while psychedelics at encoding enhanced familiarity but had no effect on metamemory.

Table II

Psychoactive drugs can enhance or impair memory. A trending effect indicates a mixed finding, and an asterisk indicates potentially inappropriate modeling of a false memory effect.

98 unique acute drug effects on episodic memory were identified across datasets. These effects ranged from small physiological effects to large physiological effects and difficulties in overall functioning. Across studies, we observed modulation of the same processes within a drug class without any reliable nonlinearities, yet there were stark deviations between drug classes. These idiosyncratic patterns of impairments and enhancements could be useful in the prediction of different drug use and abuse.

We discuss similarities and differences between the mnemonic effects of different drugs classes and highlight particularly novel and interesting findings. We also discuss the implications of these findings for psychedelic research and the use of drugs to understand the mind. Familiarity appears to arise from the activity of brain areas such as the occipitotemporal and anterior temporal cortices, and may be more robust to drug manipulations than recollection.

The author/funder of this preprint (which was not certified by peer review) has granted bioRxiv a license to display the preprint in perpetuity. Sedatives, dissociatives, and cannabinoids impair recollection and familiarity, but there are subjective differences in these amnestic states. Although CB1 receptors are typically inhibitory, there are excitatory CB1 receptors in entorhinal cortex, which may enhance signaling to the hippocampus and provide a buffer against complete amnestic episodes. Alternatively, activating 5-HT2A receptors on inhibitory interneurons may impair recollection by shunting information flow to the hippocampus.

Psychedelics impair recollection, which is associated with autonoetic consciousness, while sparing familiarity, which is associated with noetic consciousness. This may lead to unique downstream effects or states of consciousness. Some evidence suggests that sedatives preserve semantic and perceptual processing, whereas dissociatives and THC may impair and enhance semantic activation, respectively. Moreover, even within sedatives, there may be idiosyncratic perceptual effects that differentially impact processes supporting familiarity.

The author/funder of this preprint (which was not certified by peer review) has granted bioRxiv a license to display the preprint in perpetuity. Metamemory, measured with metacognitive efficiency, appeared to be more robust to modulation than observed with previous measures of metamemory, specifically, gamma. The findings reported here and prior findings using gamma to measure metamemory may be because gamma does not consider response bias or overall levels of performance. Sedatives at encoding impair memory accuracy but not metamemory, and dissociatives at encoding do not consistently impair metamemory.

We found inconsistent enhancements in episodic memory when dissociatives were administered at encoding. It is possible that these enhancements were not always apparent or significant because memory was tested on the same day as drug administration. A recent study found that ketamine impairs metamemory at retrieval, but THC enhances metamemory 48 hours after encoding, despite impairments of both recollection and familiarity. Although impairments in memory are also observed in schizophrenia, the effects of THC and ketamine on metamemory are not “hallucinogen-general”, as metamemory was unaffected by psychedelics, thereby questioning the validity of psychedelic effects on memory.

Stimulants inconsistently enhanced memory, but consistently impacted metamemory, a finding that diverges from metacognitive measures correlated with overall performance. This finding may explain why stimulants are used by healthy college students studying for exams despite minimal cognitive enhancements in non-clinical populations. Dextromethamphetamine at consolidation impaired metamemory, but the recollection estimates were zero, similar to patients with medial temporal lobe amnesia and false memory manipulations.

This preprint is available under a CC-BY-NC-ND 4.0 International license, and its copyright holder is the author/funder. Low doses of haloperidol, which enhance dopaminergic transmission via antagonism of presynaptic dopamine 2 autoreceptors, were found to impair metamemory when administered at retrieval. Moreover, haloperidol increased striatal activity during memory retrieval and enhanced both recollection and familiarity. It is unclear how a drug administered at encoding or consolidation can modulate retrospective metamemory decisions, though it is possible that impairment of certain memories could differentiate them more compared to the case in which one has an abundance of memories.

Acute drug effects on episodic memory consolidation can make memories more confusable, and suspecting one had a drug onboard during encoding could impact confidence judgements made on a subsequent day (while sober), possibly making one more cautious, which might improve metamemory independent from actual memory effects. Psychedelic effects on memory support dual process models of memory, whereby psilocybin and MDMA impair recollection while sparing or even enhancing familiarity. This finding is consistent with previous findings that psychedelics enhance familiarity-like memory when administered at consolidation.

MDMA, a synthetic psychedelic, enhanced familiarity and impairing recollection by releasing the neurohormone oxytocin, but did not consistently enhance recollection or enhance familiarity. This suggests that the 5-HT2A agonism of MDMA’s R-enantiomer may underlie the similar pattern of mnemonic effects as psilocybin. Although dual process models fit well to the data, recollection and familiarity tend to correlate. Evolution may have placed constraints on when these processes can completely dissociate, and an enhancement or preservation of familiarity along with a concurrent impairment in recollection may not necessarily be an overall enhancement per se.

Déjà vu, premonition, and presque vu are illusory phenomena associated with conditions of high familiarity and low recollection. Users of psychedelics report having insights, but it is unknown whether these insights are tangibly realized in a reliable or frequent fashion. It is worth noting that stimulation of the right anterior temporal lobe facilitates insight problem-solving. Certain types of information may be more readily processed during psychedelic experiences, such as familiarity-based memory, whereas recollection-based memory may be associated with scenes, context, and novel bindings of disparate information.

The anterior temporal lobe is involved in familiarity-based memory and face processing, and may be a possible functional locus for illusory social events. 5-HT2A agonism may alter the style of information processing such that mnemonic heuristics become less efficiently encoded and global matching based on conceptual and perceptual fluency is facilitated. This would explain why some work has found psychedelics to enhance semantic and low-level visual processing.

This review and reanalysis contains many gaps in our knowledge of drug effects, and was not certified by peer review. It is made bioRxiv preprint doi: https://doi:10.1101/2022.05.20.492842.

Acute drug effects on episodic memory have been studied in 110 studies, most of which used verbal vs. pictorial stimuli, recognition vs. cued recollection memory tests, 6-point vs. 10-point confidence scales. Some findings are generalizable, but others require further replications. Although most datasets analyzed here did not contain a manipulation of consolidation or retrieval, more in-depth analyses may be able to identify drug effects on memory that were otherwise missed. Finally, state-dependent drug effects are not always reliable, and deeper analyses may reveal which mnemonic processes are in fact modulated.

There are many different acute drug effects on episodic memory supported by familiarity and/or recollection, and potential distortions in cognitive and metacognitive processes during retrieval. Another interesting prospect for future work is how these drugs impact other metacognitive processes such as prospective metamemory. This report highlights the utility of implementing confidence in tests of episodic memory to identify unique properties of different drugs, and recommends the use of non-standard episodic memory available under aCC-BY-NC-ND 4.0 International license.

The copyright holder for this preprint (which was not certified by peer review) has granted bioRxiv a license to display the preprint in perpetuity. The preprint discusses drug effects on context-dependent memory. Although this report focused on episodic memory, many areas of cognition have progressed far beyond the standardized paradigms and analyses implemented in most clinical work. Other potentially interesting areas of study could be visual perception and attention.

This preprint is dedicated to Boru Doss who provided invaluable support and passed during the writing of this manuscript. It is made available under aCC-BY-NC-ND 4.0 International license.

Author Contributions

The author/funder of this preprint (who has granted bioRxiv a license to display the preprint in perpetuity) is Doss, Samaha, Barrett, Griffiths, de Wit.

Acute drug effects on episodic memory include impairment of visual working memory performance, and Déjà vu experiences in patients with schizophrenia. Aghajanian GK, Marek GJ, Aly M, and Yonelinas AP (2012) found that serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells, and Ames F (1958) found that cannabis sativa causes model psychoses. Amphetamine increases errors during episodic memory retrieval and THC preferentially modulates emotional memory in humans. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Acute drug effects on episodic memory include effects of methamphetamine on emotional memory formation, effects of psilocybin and dextromethorphan on cognition, and effects of ketamine on resting-state network-specific breakdown of functional connectivity in volunteers. Brainerd CJ, Gomes CFA, Moran R, Broyd SJ, van Hell HH, Beale C, Yücel M, and Solowij J (2016) reviewed the effects of cannabinoids on human cognition, and Bruce KR, Pihl RO, and Bustamante JA discussed state dependent learning in humans.

Acute drug effects on episodic memory include psilocybin, MDMA, Wall MB, Erritzoe D, Kaelen M, Ferguson B, De Meer I, Tanner M, Bloomfield M, Williams TM, Bolstridge M, Stewart L, Morgan CJ, Newbould RD, Feilding A, Curran HV, and Nutt DJ. Carter LP, Kleykamp BA, Griffiths RR, Mintzer MZ, and Reissig CJ (2013) investigated the cognitive effects of ketamine and dextromethorphan in healthy volunteers, and Carter OL, Pettigrew JD, Wallis GM, Hasler F, and Vollenweider FX (2004) investigated the relationship between attention, working memory, and serotonin receptors. The feeling of knowing was measured in patients with schizophrenia and is available under a CC-BY-NC-ND 4.0 International license.

Acute drug effects on episodic memory include familiarity from the configuration of objects in 3-dimensional space and its relation to déjà vu, and effects of dopamine on memory retrieval performance but impairs metacognition. Damian RI, Simonton DK, Das RK, Tamman A, Nikolova V, Freeman TP, Bisby JA, Lazzarino AI, Kamboj SK, David AS, Bedford N, Wiffen B, Gilleen J, and Davis AK are the authors/funders of this preprint, which is made available under aCC-BY-NC-ND 4.0 International license.

A Randomized Clinical Trial of 119 Unique Acute Drug Effects on Episodic Memory Disorder found that memantine pretreatment improved memory and mood during MDMA intoxication. Diana RA, Yonelinas AP, Ranganath C, Doss MK, Bluestone MR, and Gallo DA (2007) proposed a three-component model of imaging recollection. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

120 Unique acute drug effects on episodic memory have been reported. These include impairment of encoding and consolidation of both recollection and familiarity in episodic memory by alcohol and pharmacologically similar sedatives. This preprint was not certified by peer review, and the author/funder grants bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.

121 unique acute drug effects on episodic memory have been described, including effects of schizophrenia, ketamine and cannabis, evidence of overlapping memory deficits, and effects of associations and aging on illusory recollection. Gardiner JM (2001), Geyer M, and Vollenweider F (2008), Goldstein RZ, Craig AD (Bud), Bechara A, Garavan H, Childress AR, Paulus MP, and Volkow ND (2009), Griffiths RR, Hurwitz ES, Davis AK, Johnson MW, and Jesse R (2019), and others have made this preprint available.

Acute drug effects on episodic memory include mystical-type experiences, false insights, post-learning hippocampal dynamics, preferential retention of rewarding events, metacognitive beliefs in addictive behaviours, and effects of oxytocin on recognition memory for own-race and other-race faces in women and men. Ketamine was used to study memory and conscious awareness in healthy volunteers. Individual differences in psychotic effects of ketamine are predicted by brain function measured under placebo.

Acute drug effects on episodic memory include impairment of specific memory processes by sub-psychotic doses of ketamine, and implications for pharmacological modelling of core symptoms of schizophrenia. Research shows that ketamine can impair working memory, but not maintenance. Ingram KM, Mickes L, Wixted JT, and Bacon E (2006) found that lorazepam can impair complete and partial information retrieval and monitoring accuracy. Jacoby LL (1991), Janak PH, Martinez JL (1992), Jarosz AF, Colflesh GJH, and Wiley J (2012), Kaestner EJ, Wixted JT, and Mednick SC (2013), Kamboj SK, and Curran HV (2006) are authors of this preprint.

124 unique acute drug effects on episodic memory have been reported, including effects of zolpidem extended-release, triazolam, and alcohol on cognitive performance and sleep in healthy volunteers, and effects of alcohol and other drugs on false memory and suggestibility. The author(s) of this preprint (who have not been certified by peer review) grants bioRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint (who have not been certified by peer review) is the author/funder.

Koen, JD, and Yonelinas AP (2013) Still no evidence for the encoding variability hypothesis; Kometer, M, and Vollenweider FX (2016) Serotonergic hallucinogen-induced visual perceptual alterations; Koob, GF, and Volkow ND (2016) Neurobiology of addiction. Kostic B, Booth SE, Cleary AM, and Krivanek JA (2015) found that reporting the presque vu state signals the near retrieval of a source analogy. Kuypers K, Torre R, Farre M, Pujadas M, and Ramaekers J (2013) found that inhibition of MDMA induced increase in cortisol does not prevent acute impairment of verbal memory.

There are 126 unique acute drug effects on episodic memory, including differences in pattern separation related transfer functions in human CA3/dentate and CA1, and a reduction in memory formation during sleep through triple phase-locking of cortical, thalamic, and hippocampal rhythms. Anosognosia for memory impairment in addiction: insights from neuroimaging and neuropsychological assessment of metamemory. Le Berre A-P, LeDoux JE, Lau H, and Lehrer DS, and Libby LA, Yonelinas AP, Ranganath C, and Ragland JD (2013) are the authors/funders of this preprint.

Acute drug effects on episodic memory include enhancement of declarative memory consolidation by methylphenidate. Lofwall MR, Griffiths RR, Mintzer MZ (2006), Mackie K (2005), Maniscalco B, and Lau H (2012), and Fleming SM, and Frith CD (2014) studied the cognitive and subjective acute dose effects of intramuscular ketamine in healthy adults. Psychedelics recruit multiple cellular types and produce complex transcriptional responses within the brain. McDonough IM, Wong JT, and Gallo DA (2013) tested the compensation and dysfunction accounts for age-related differences in prefrontal cortex activity during retrieval monitoring.

The author/funder of this preprint (which was not certified by peer review) has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Triazolam and scopolamine have dose-dependent effects on metamemory, and individual differences in brain structure may contribute to metacognitive impairment in active cocaine use disorder.

This preprint is by Moritz S, Klein JP, Lysaker PH, and Mehl S and is made available under a CC-BY-NC-ND 4.0 International license.

Patients with obsessive-compulsive disorder (OCD) have comparable performance to healthy controls for verbal and nonverbal memory accuracy and confidence. Moritz S, Woodward TS, Jelinek L, and Klinge R (2008) discussed memory and metamemory in schizophrenia. Muetzelfeldt L, Kamboj SK, Rees H, Taylor J, Morgan CJA, and Curran HV (2008) discussed phenomenological aspects of ketamine use. A complementary-learning-systems approach to memory modeling was used in the study of compulsivity, and metacognitive impairments extend perceptual decision making weaknesses in compulsivity. The study was not certified by peer review.

Acute drug effects on episodic memory include context maintenance and retrieval, hierarchical single- and dual-process models of recognition memory, and changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness. Ranganath C, Ritchey M, Reder LM, Victoria LW, Manelis A, Oates JM, Dutcher JM, Bates JT, Cook S, Aizenstein HJ, Quinlan J, and Gyulai F (2018) reported that tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information.

Acute drug effects on episodic memory include impairment in recognition memory, altered dopamine release, and decreased resting-state network connectivity in amphetamine users and healthy controls. Scofield MD, Heinsbroek JA, Gipson CD, Kupchik YM, Spencer S, Smith ACW, Roberts-Wolfe D, and Kalivas PW (2016) found that the nucleus accumbens is important for addiction across drug classes and that the optimism bias is present in children receiving methylphenidate.

This preprint discusses the acute drug effects on episodic memory, and how these effects differ from long-term effects. It is made available under a CC-BY-NC-ND 4.0 International license, and was not certified by peer review. Spitzer M, Franke B, Walter H, Buechler J, Wunderlich AP, Schwab M, Kovar K-A, Hermle L, and Grön G (2001) found that N-ethyl-3,4-methylenedioxyamphetamine increased activation of indirect semantic associations in humans. This preprint describes the effects of oxazepam and lorazepam on implicit and explicit memory, and how these effects may be influenced by time course. It is made available under a CC-BY-NC-ND 4.0 International license.

Ayahuasca inhibits alpha oscillations through serotonin-2A receptor activation, which underlies the visual effects of ayahuasca in humans. Repeated checking causes memory distrust, and blockade of 5-HT2 receptor selectively prevents MDMA-induced verbal memory impairment. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Anterior temporal face patches are involved in cognitive flexibility and are disrupted in psychotic illness. Atypical endocannabinoid signaling initiates a new form of memory-related plasticity at a cortical input to the hippocampus, and the copyright holder has granted bioRxiv a license to display the preprint in perpetuity.

Acute drug effects on episodic memory include familiarity being related to conceptual implicit memory, alcohol being related to emotional memory, and ethanol being related to temporal fractal properties of the brain. A case report of persistent psychogenic déjà vu is made available on bioRxiv, and it is made available under a CC-BY-NC-ND 4.0 International license. It is made available by the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Wixted JT, Wong JT, Cramer SJ, Gallo DA, Yaden DB, Johnson MW, Griffiths RR, Doss MK, Garcia-Romeu A, Nayak S, Gukasyan N, Mathur BN, Barrett FS, and Yaden DB (2017) investigated the noetic quality of memories. Yonelinas AP (2001), Aly M, Wang W-C, and Koen JD (2002), Yonelinas AP (1994), Yonelinas AP (1999), Yonelinas AP (2012), and Jacoby LL (2012) discuss the process-dissociation approach to recognition memory. Yonelinas AP, Kroll NEA, Dobbins I, Lazzara M, Knight RT, and Parks CM (2007) reviewed the use of receiver operating characteristics (ROCs) in recognition memory and how they are used in neuroscience.

This work was supported by the National Institute on Drug Abuse and the National Institute on Aging. It is made available under a CC-BY-NC-ND 4.0 International license.

The authors of this preprint have no competing interests to declare. It was not certified by peer review, and is made available under a CC-BY-NC-ND 4.0 International license.