Pre-sleep treatment with galantamine stimulates lucid dreaming: A double-blind, placebo-controlled, crossover study Stephen LaBerge1, Kristen LaMarca1, Benjamin Baird2* 1 Lucidity Institute, Pahoa, HI, United States of America, 2 Wisconsin Institute for Sleep and Consciousness, Department of Psychiatry, University of Wisconsin–Madison, Madison, WI, United States of America * bbaird@wisc.edu a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: LaBerge S, LaMarca K, Baird B (2018) Pre-sleep treatment with galantamine stimulates lucid dreaming: A double-blind, placebo-controlled, crossover study. PLoS ONE 13(8): e0201246. https://doi.org/10.1371/journal.pone.0201246 Editor: Raffaele Ferri, Associazione OASI Maria SS, ITALY Received: December 4, 2017 Accepted: July 11, 2018 Published: August 8, 2018 Copyright: © 2018 LaBerge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All data files are available from the Open Science Framework (OSF) database (DOI 10.17605/OSF.IO/VA3X6). Funding: B.B. was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award F32NS089348 from the NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funder had no role in study design, data collection and analysis, Abstract Lucid dreaming is a remarkable state of consciousness in which one is aware of the fact that one is dreaming while continuing to dream. Based on the strong relationship between physiological activation during rapid eye-movement sleep and lucid dreaming, our pilot research investigated whether enhancing cortical activation via acetylcholinesterease inhibition (AChEI) would increase the frequency of lucid dreams and found AChEI to be a promising method for lucid dream induction. In the current study we sought to quantify the size and reliability of the effect of AChEI on lucid dreaming, dream recall and dream content as well as to test the effectiveness of an integrated lucid dream induction protocol which combined cholinergic stimulation with other methods for lucid dream induction. Participants (N = 121) with high dream recall and an interest in lucid dreaming were randomly assigned counterbalanced orders of 3 doses of galantamine (0, 4 and 8 mg). On 3 consecutive nights, they awoke approximately 4.5 hours after lights out, recalled a dream, ingested the capsules and stayed out of bed for at least 30 minutes. Participants then returned to bed and practiced the Mnemonic Induction of Lucid Dreams technique while returning to sleep. The percentage of participants who reported a lucid dream was significantly increased for both 4 mg (27%, odds ratio = 2.29) and 8 mg doses (42%, odds ratio = 4.46) compared to the active placebo procedure (14%). Galantamine also significantly increased dream recall, sensory vividness and complexity (p<0.05). Dream recall, cognitive clarity, control, positive emotion, vividness and self-reflection were increased during lucid compared to non-lucid dreams (p<0.0001). These results show that galantamine increases the frequency of lucid dreams in a doserelated manner. Furthermore, the integrated method of taking galantamine in the last third of the night with at least 30 minutes of sleep interruption and with an appropriately focused mental set is one of the most effective methods for inducing lucid dreams available today. Introduction During a lucid dream one becomes aware that one is dreaming while continuing to dream. In this remarkable state of consciousness, one can reflect rationally and engage in purposeful, PLOS ONE | https://doi.org/10.1371/journal.pone.0201246 August 8, 2018 1 / 16
decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. volitional actions within the dream. For example, lucid dreamers can recognize that their current sensory experience is a mental construction unrestricted by the usual limits of the waking physical world and often recall details about waking conditions. These details can include autobiographical memories from waking, as well as preset intentions to carry out specific actions in the dream [1, 2]. Awareness of dreaming, and the increased volition and autobiographical memory that often accompany it, occurs while the dreamer remains in unequivocal REM sleep [3], immersed in a dream environment that can appear strikingly realistic. Lucid dreaming presents a unique opportunity for entertainment, exploration and personal growth [4]. Furthermore, the scientific study of lucid dreaming opens novel experimental approaches for studying the psychophysiology of REM sleep that have the potential to expand our understanding of the relationship between consciousness and brain activity [5]. However, while the majority of people report having experienced a lucid dream at least once in their lives, for most people lucid dreams occur very infrequently [6]. Accordingly, the development of reliable methods of inducing lucid dreams is an important focus of research [4, 7–13]. In his dissertation, LaBerge [14] developed one of the first reliable techniques for lucid dream induction based on scientific research, referred to as the Mnemonic Induction of Lucid Dreams (MILD). The purpose of MILD is to increase the frequency of lucid dreams using the intention to remember to do something in the future, a behavior now termed prospective memory. To effectively practice MILD requires good dream recall. One begins by remembering a dream, either from a previous night or, ideally, from which one has just awakened. One then identifies an anomaly within the dream that is characteristic of one’s dreams (called a “dreamsign” [1]). Then, one visualizes returning to the dream, and rehearses recognizing that this anomaly only occurs in dreams, thereby becoming lucid. During this visualization, the practitioner mentally recites, “The next time I’m dreaming I want to remember to recognize that I’m dreaming.” In addition, the technique involves visualizing carrying out a preselected action when one becomes lucid. A meditative focus is required to use MILD effectively. The practitioner repeatedly lets go of distracting thoughts, returning focus on the visualization of recognizing the dreamsign, becoming lucid, and performing the preselected goal, consistently until falling back to sleep. In a case report, LaBerge [7] found that MILD was approximately 800% more effective than autosuggestion for inducing signal-verified lucid dreams in the sleep laboratory. Follow-up studies have confirmed that MILD can increase lucid dream frequency [15]. Another lucid dream induction technique is to use a sensory stimulus as a cue, such as a flashing light applied over the sleeper’s eyes via a sleep mask during REM sleep [8, 10]. Such stimuli are frequently incorporated into an ongoing dream, and with proper mental preparation, individuals can learn to identify the stimulus as a cue and thereby become lucid. Again, prospective memory—the intention to recognize the cue—is required for success with this technique of lucid dream induction. A third approach to lucid dream induction arose from reports that lucid dreaming was more likely after engaging in certain activities during the night, such as meditation, sexual intercourse or reading (e.g., [16, 17]). Given the diversity of these activities, LaBerge [7] suggested that it was not the particular activity but rather the period of alert wakefulness that made lucid dreaming more likely during subsequent sleep. A period of 10–15 minutes of wakefulness was therefore incorporated into the MILD technique [7]. Subsequent studies showed that combining MILD with a longer period of wakefulness of either 30 to 60 minutes late in the sleep cycle was associated with even higher increases in lucid dream frequency in the ensuing sleep period [18]. Consistent with these findings, a recent study found that participants who practiced a combination of MILD and sleep interruption nightly for two weeks demonstrated increased lucid dreaming frequency [19]. PLOS ONE | https://doi.org/10.1371/journal.pone.0201246 August 8, 2018 2 / 16
In earlier research we found that lucid dreams tend to occur during periods of increased physiological activation during REM sleep, and that measures of phasic central nervous system activation, such as increased eye movement density, are associated with lucid dreams [5, 20, 21]. Therefore, increasing physiological activation in REM sleep is another potentially fruitful avenue to explore for stimulating lucidity in dreams. Given the strong evidence that REM sleep is modulated by acetylcholine [22–24] and furthermore that acetylcholinesterease inhibition increases REM sleep phasic activity [25], we tested whether enhancing cortical activation via cholinergic stimulation would increase the frequency of lucid dreaming. In an initial pilot study [26], we evaluated the influence of either 0 mg (placebo), 5 mg, or 10 mg of donepezil (Aricept1), an acetylcholinesterease inhibitor (AChEI), administered at bedtime in a withinsubjects counter-balanced order on three nights in a small group of individuals with prior experience in lucid dreaming. Nine of the ten participants (90%) reported one or more lucid dreams on the experimental nights on donepezil, with only one participant reporting a lucid dream on a placebo night (p<0.01). In the current study we sought to quantify the size and reliability of the effect of AChEIs on lucid dreaming, dream recall and dream content. We evaluated the effect of galantamine, a fast acting AChEI with a mild side effect profile, in a large group of individuals (N = 121) with an interest in lucid dreaming. We tested the effect of galantamine taken during a period of sleep interruption after approximately the third REM cycle. This design allowed us to examine the combined effectiveness of an integrated lucid dream induction protocol, incorporating sleep interruption and the MILD technique together with cholinergic enhancement. Data was collected using a double blind, placebo-controlled, cross-over design across six lucid dreaming training programs. Materials and methods Participants Volunteers were recruited from a high-interest group attending one of six, 8-day training programs on lucid dreaming, titled “Dreaming and Awakening”, presented by the Lucidity Institute. The study was approved by the Lucidity Institute research ethics committee and was conducted in accordance with the Declaration of Helsinki. Participation in the study was voluntary. All participants provided signed informed consent prior to the experiment. Participants’ responses were treated confidentially and anonymously. Exclusion criteria included asthma, taking beta-blockers, severe mental illness or cardiac arrhythmias. However, no exclusions were made for biomedical reasons as no participants presented with any of the exclusionary criteria. The details, study rationale, and possible side effects of cholinergic stimulation, as described above, were explained, including the possibility of unpleasant side effects such as insomnia or nausea. Participants were aware that on at least one of the experiment nights they would be receiving an active dose of an over-the-counter supplement. All workshop participants who met the eligibility criteria and wished to participate in the experiment were included in the study. Extensive piloting of the procedures in previous workshops allowed us to hold all aspects of the protocol constant throughout the entire duration of the study. One hundred twenty nine participants participated in the study. Eight participants were not included in analysis due to not completing at least two nights of the experiment or following instructions, including one participant who discontinued the study due to nausea, and one to avoid the sleep disturbance from completing the nightly procedures. The final group included in the analysis consisted of 121 participants (63 males, 58 females), age 43 ± 12, 19– 75 years [mean ± SD, range]. Participants reported median rates of 1 dream recalled per night and 3–5 lucid dreams recalled per year, similar to pre-experiment estimates of the number of PLOS ONE | https://doi.org/10.1371/journal.pone.0201246 August 8, 2018 3 / 16
lucid dreams recalled in the last six months (median = 2), and most recalled in any 6-month period (median = 3). Ten participants reported no previous lucid dreams. Procedures Participants engaged in an integrated lucid dream induction protocol, which combined sleep interruption and the Mnemonic Induction of Lucid Dreams (MILD) technique together with cholinergic enhancement. As part of the workshop, participants attended lectures about lucid dreaming, which explained what lucid dreams are, reviewed examples of lucid dreams, and provided time for discussion and questions. Participants therefore obtained a thorough conceptual understanding of lucid dreaming during the training workshop before the experiment began. As part of their training in MILD (described above), they learned specific strategies for recognizing cues that they are dreaming [27], prolonging the lucid dream state [28], and responding adaptively to nightmares and sleep paralysis [4]. Participants were instructed on the nightly reporting procedures and the protocol for sleep interruption, which included a modified sleep schedule in which participants interrupted their sleep with a 30-minute period of wakefulness after approximately 4.5 hours of sleep (a rough estimate of 3 REM periods) [see Fig 1 for a schematic diagram of the experimental procedure]. The 30-minute sleep interruption period was selected based on previous research, as noted above, showing that 30 minutes of sleep interruption is more effective than shorter amounts of time [18]. We did not set the sleep interruption period for longer than 30 minutes because it does not lead to further increases in lucid dream frequency. Furthermore, galantamine reaches peak serum concentration (Cmax) approximately 1 hour after oral ingestion [29], and we wanted to align Cmax to occur during the next sleep (and dream) period after allowing participants time to fall back to sleep. Participants practiced MILD while returning to sleep for all awakenings after the sleep interruption period. 94 participants also wore a sleep mask which recorded physiological variables and provided additional memory cues during sleep [8, 10] (see S2 Appendix). Participants who opted to sleep with the mask were required to use it on all three nights of the experiment after the sleep interruption period. Participants used a paperpencil form to track their nightly experiences and time variables, including their lights out time, the time they started the sleep interruption period, the length of the sleep interruption period, the time they ingested the capsules, and their rising time in the morning. Participants were given two nights prior to the experiment to practice the induction and reporting protocol. The experiment was initiated on the fifth night of the workshop. Participants were randomly assigned subject numbers. On each night (A, B, C), they received a coded packet, according to their subject numbers and appropriate night, containing Fig 1. Schematic diagram of experimental procedure. (Note: figure not to scale, timing approximate). A. LO: Lights Out. Sleep for approximately 3 REM cycles. B. DREC: Recall and memorize dream upon awakening to use with MILD procedure at E. C. Ingest galantamine capsules. (All participants received all three doses (0, 4, and 8 mg) in one of 6 counterbalanced orders.) D. Sleep interruption (out of bed for 30 min). Engage in quiet activity with focus on lucid dreaming. (“Wake back to bed") E. Return to sleep practicing MILD using the dream recalled at B. F. Experimental Nap(s). G. REPORT: On awakening, dream recall, content scales, and full reports for lucid dreams. https://doi.org/10.1371/journal.pone.0201246.g001 PLOS ONE | https://doi.org/10.1371/journal.pone.0201246 August 8, 2018 4 / 16
capsules with 0 mg (G0), 4 mg (G4), or 8 mg (G8) of galantamine hydrobromide (Life Enhancement Products Galantamind; S2 Appendix). Numbered packets were arranged to provide a counterbalanced order of doses; however, the participants and experimenters were unaware which dose individuals would be receiving on a particular night (double-blind design). Each night, participants awoke after approximately 4.5 hours of sleep, recalled and memorized a dream, ingested the capsules, and then remained awake for the sleep interruption period while engaged in a quiet wakeful activity of their choice (e.g., reading about lucid dreaming or recording or reviewing their dreams). Participants then returned to bed, practicing MILD until they fell asleep. For all awakenings after the period of sleep interruption, participants completed the report form and recorded the time they woke up and the type of dream. As noted above, lucidity can arise during an ongoing dream (often through the recognition of a cue or an anomaly indicating that one is dreaming) or, less commonly, by maintaining awareness while transitioning directly from the waking state into a dream. These two types of lucid dream onset are referred to respectively as dream-initiated lucid dreams (DILDs) and wake-initiated lucid dreams (WILDs) [15, 20]. On the dream report forms, participants categorized their dream as none (did not recall a dream), non-lucid dream, DILD or WILD. If participants recalled a dream, they rated their extent of dream recall and rated the dream on several dimensions of conscious experience, including sensory vividness, clarity of thinking, negative and positive emotion, bizarreness, complexity, self-reflection, public self-consciousness, and degree of dream control (all on a 0 to 4 scale with 0 = none, 4 = high). Participants also reported "odd somatic sensations", such as strange bodily feelings, paralysis, tingling, vibrations, etc. as well as any perceived side effects (S2 Appendix). For lucid dreams participants wrote a full narrative report of the dream. In the reports, participants were asked to specify the point in the dream report at which they became lucid as well as how they knew they were dreaming (e.g., if it was triggered by a particular event or associated with a specific thought during the dream). Participants also gave a follow-up oral report of all lucid dreams the following morning. Two complementary criteria had to be met in order for a dream report to be classified as lucid. First, the participant himself or herself had to rate their dream as lucid (either a DILD or a WILD). Second, dream reports had to include a reference to the current state as a dream (for example, “It was at this point I knew it was a dream”; “I realized I am dreaming”; “I said aloud, ‘This is a dream.’”). Statistical analysis Linear mixed models were used to account for repeated measures with varied numbers of repeated observations within subjects. The model for evaluating the effect of DOSE (active placebo (G0), galantamine 4 mg (G4), galantamine 8 mg (G8)) on STATE (lucid, non-lucid) used restricted maximum likelihood estimation (REML) and included DOSE and NIGHT (1, 2, 3) as fixed effects and STATE as the outcome variable. The model for responses to the dimensions of consciousness (DIMs) scale used restricted maximum likelihood estimation (REML) and included participant as a random factor, and NIGHT, DOSE, and STATE as fixed effects. As questionnaire responses as well as outcome measures were not normally distributed, we used nonparametric bootstrapping for all significance tests. (We also evaluated the effect of DOSE on STATE using binary logistic regression, for which identical significance thresholds were obtained compared to the bootstrap method). Hypothesis testing of regression coefficients (pairwise tests) from the mixed models was obtained by the following steps: i) constructing a model based on the null hypothesis of no differences between STATE (H0), ii) resampling with replacement the distribution of the response residuals under the null model, reconstructing a PLOS ONE | https://doi.org/10.1371/journal.pone.0201246 August 8, 2018 5 / 16
bootstrap y response vector, and refitting the H1 model to the bootstrap response vectors to generate 10,000 bootstrap estimates of the regression coefficients (ß) under H0, and iii) comparing the observed value of ß against the null bootstrap distribution (two-tailed frequentist p-value). Mixed model construction and mixed model bootstrapping were performed with the lme4 package [30] in the R environment (R Development Core Team, 2006). Mixed model fixed effects were assessed by means of a bootstrap likelihood ratio test on mixed effects models (PBmodcomp in R) specified with maximum likelihood estimation (MLE). We tested 10 DIMs variables for both STATE and DOSE effects (40 total tests); we therefore corrected the type I error rate for these multiple comparisons with the Bonferroni correction (critical α = 0.05/ 40 = 0.0012). Bayesian classification We evaluated the extent to which STATE (lucid, non-lucid) could be classified using a Bayesian classification procedure developed and validated by Allen et al. [31]. We performed a 2-step split-half classification: in the first half, we used binary logistic regression to determine the content variables with the highest predictive value (regression coefficients); in the second half, we then used Bayesian combination of these multiple indicators (predictor variables) to calculate the Bayesian Posterior Probability (BPP) (i.e., the probability that a dream was either lucid or non-lucid given an observed combination of indicators, for example high control and high positive emotionality). The cutpoint for each variable was set at 2 on the 0–4 scale; thus, scores of 0–2 were categorized as low and scores of 3–4 were categorized as high. The BPP is equal to the proportion of dream reports associated with lucid dreams that show the combination of indicators divided by the proportion of all trials (lucid and non-lucid) showing the combination of indicators (1.00 = perfect classification). Results On average, participants reported a total sleep period (lights out to rising time) of 8.1 ± 1.3 [mean ± SD] hours. The sleep interruption period was started on average at 4.54 ± 0.86 [mean ± SD] hours after lights out and lasted 36 ± 18 [mean ± SD] minutes. Lights out to rising time after the sleep interruption period lasted an average of 3.3 ± 1.1 [mean ± SD] hours. In total, 485 dreams were reported: 85 (17%) were DILDs, 32 (7%) were WILDs, and 368 (76%) non-lucid dreams. Lucidity 75 participants (62%) reported one or more lucid dreams during the study—69 (57%) on one or more nights with galantamine and 17 (14%) with the active placebo procedure (including sleep interruption and MILD); 33 (27%) participants with the 4 mg dose, and 51 (42%) participants with the 8 mg dose [Fig 1; Table 1; see S1 Appendix for examples of lucid dreams participants reported during the study]. There was a main effect of galantamine on lucidity [likelihood ratio: 25.54, p<0.001]. Significantly increased incidence of lucid dreaming was observed for both 4 mg (ß = 0.12, p = 0.03, odds ratio = 2.29, 95% CI = 1.19–4.38) and 8 mg doses (ß = 0.28, p<0.0001, odds ratio = 4.46, 95% CI = 2.38–8.35) compared to the active placebo [Fig 2]. The 8 mg dose resulted in significantly higher incidence of lucid dreams compared to the 4 mg dose (ß = 0.16, p = 0.004, odds ratio = 1.94, 95% CI = 1.13–3.33). A dose response analysis confirmed a dose-related response (linear trend) for lucid dreaming probability by galantamine exposure (Mantel-Haenszel χ2 for linear trend = 23.03, p = 0.000001). Compared to the expected frequency of lucid dreams (4%, based on self-reported frequency of lucid dreaming during the 6 months prior to the experiment), lucid dream frequency was PLOS ONE | https://doi.org/10.1371/journal.pone.0201246 August 8, 2018 6 / 16
Table 1. Percent of 121 participants reporting at least one lucid dream in a double-blind, randomized crossover design comparing pre-sleep administration of three doses of Galantamine (0 mg, 4 mg, and 8 mg). Expected Prior6mo 0 mg Observed 4 mg 8 mg 4.3%† 14.1% 27.3% 42.2% [3–6] [8–21] [20–36 [[33–52] - 227% 535% 881% [86–388] [365–737] [667–1110] % (N = 121) % increase † Note: expected percentages based on self-reported frequency of lucid dreaming during the 6 months prior to the experiment. Brackets indicate 95% CI. Significant differences were observed between all 4 conditions (p < 0.05). https://doi.org/10.1371/journal.pone.0201246.t001 approximately three times higher (14%, p = 0.01) for the active placebo procedure (including MILD and sleep interruption). For the combined protocol with 4 mg galantamine, lucid dream frequency was approximately 6 times higher than expected (27%, p<10−5), and approximately 9 times higher than expected for the combined protocol with 8 mg galantamine (42%, p<10−10) [Table 1]. There was no main effect of night on lucidity [likelihood ratio: 1.33, p = 0.52], indicating that participants were not more likely to have a lucid dream on subsequent nights of the experiment independently of other effects. Furthermore, there was no effect of dose order on the likelihood of having a lucid dream (F(1,5) = 0.31, p = 0.90), supporting that consecutive nights were not too close together. Across all dream reports, participants reported a total of 15 DILDs on placebo, 27 DILDs on the 4 mg dose and 43 DILDs on the 8 mg dose, while 3 WILDs were Fig 2. Percent of participants (N = 121) reporting at least one lucid dream (LD) on returning to sleep following ingestion of one of three masked doses of galantamine (0 mg [G0], 4 mg [G4], and 8 mg [G8]) prior to 30–40 minutes out of bed. The baseline estimate (“BASE”, 4%) of lucid dreaming frequency for one night was calculated from the self-reported estimates of how many LDs participants experienced in the previous six months, divided by 180. [95% CI computed by resampling.] Error bars show estimated standard error of the conditional means. Asterisks indicate statistically significant differences between conditions: Ã p<0.05; ÃÃ p<0.01; ÃÃÃ p<0.001. https://doi.org/10.1371/journal.pone.0201246.g002 PLOS ONE | https://doi.org/10.1371/journal.pone.0201246 August 8, 2018 7 / 16
reported on placebo, 10 WILDs on the 4 mg dose and 19 WILDs on the 8 mg dose. Both DILDs (ß = 0.096, p = 0.006) and WILDs (ß = 0.063, p = 0.004) were significantly increased on an active dose of galantamine compared to placebo. Age and gender effects Overall there was no significant association between age and the frequency of lucid dreams reported during the study (ß = -0.003, p = 0.09). Additionally, there was no difference in age between participants who had a lucid dream on an active dose of galantamine and those who did not (t(119) = 1.16, p = 0.25). Older individuals did, however, report overall reduced levels of dream recall (ß = -0.016, p = 0.02). There were no gender differences in lucid dream frequency during the study overall (males = 36, females = 39, t(119) = 1.14, p = 0.26) or on an active dose of galantamine (females: 33 out of 58 participants (56.8%); males: 36 out of 63 participants (57.1%)). Prior experience with lucid dreaming Participants with higher baseline levels of lucid dreams, as estimated by the number of lucid dreams in the last 6 months, were more likely to have lucid dreams during the experiment overall (ß = 0.04, p = 0.0001). Furthermore, individuals who had a lucid dream on an active dose of galantamine reported higher baseline lucid dreaming frequency than those who did not have a lucid dream on the active dose [t(119) = 2.65, p = 0.009]. As noted above, 10 participants reported never experiencing a lucid dream before the experiment. Four of these participants (40%) were able to achieve lucidity during the study, all with the 8 mg dose of galantamine. This was similar to the 42% success rate (47/111) with the same dose for individuals reporting at least one lucid dream prior to the study. No difference in the success rate was observed between individuals who reported a lucid dream prior to the study and those who had never had a lucid dream (χ2 (1,N = 121) = 1.28, p = 0.25). MILD and sleep interruption Participants who practiced MILD for at least 10 minutes (the recommended minimum amount of time) were more likely to have a lucid dream (ß = 0.09, p<0.01, one-tailed). However, the total number of minutes practicing MILD did not predict success in having a lucid dream (ß = 0.003, p = 0.80). Participants were more likely to have a lucid dream if they engaged in at least 30 minutes of sleep interruption (ß = 0.11, p = 0.03, one-tailed; S2 Appendix), confirming the value of sleep interruption for lucid dreaming induction. Dream cognition and recall During lucid compared to non-lucid dreams, participants reported significantly higher sensory vividness, clarity, positive emotion, control, and self-reflection (all p<0.05, Bonferroni corrected; Table 2, Fig 3). Increased complexity and bizarreness and decreased negative emotion were also observed (p<0.05), though these differences did not survive correction for multiple comparisons. Compared to placebo, both 4 mg and 8 mg doses of galantamine significantly increased sensory vividness and environmental complexity (all p<0.05, Bonferroni corrected; Table 3, Fig 3). Increased bizarreness was observed under the 8 mg dose compared to placebo (p<0.05, Bonferroni corrected); 4 mg and 8 mg doses did not significantly differ on any dimension (all p>0.05; Table 3). Dream recall was higher for lucid compared to non-lucid dreams (ß = 0.57, p<0.0001), and was higher under both the 4 mg (ß = 0.43, p<0.0001) and 8 mg (ß = 0.39, p<0.0001) doses compared to placebo. Lucid dreams on an PLOS ONE | https://doi.org/10.1371/journal.pone.0201246 August 8, 2018 8 / 16
Table 2. Dimensions of consciousness (DIM) for lucid and non-lucid dreams. DIM NLD [M (SD)] LD [M (SD)] Beta p-value Recall 2.36 (1.01) 3.03 (0.92) 0.57 <0.0001à Vividness 2.36 (1.08) 3.04 (0.98) 0.61 <0.0001à Clarity 2.00 (1.03) 2.89 (0.96) 0.85 <0.0001à Neg Emotion 1.01 (1.13) 0.87 (1.10) -0.26 0.02 Pos Emotion 1.41 (1.24) 2.63 (1.15) 1.12 <0.0001à Bizarreness 1.62 (1.27) 2.09 (1.37) 0.31 0.01 Complexity 2.04 (1.21) 2.51 (1.14) 0.34 0.002 Control 0.47 (0.84) 2.06 (1.29) 1.61 <0.0001à Self-reflection 1.10 (1.12) 1.48 (1.33) 0.48 <0.0001à PubCons 0.98 (1.12) 1.03 (1.24) 0.06 0.55 Note à denotes significant differences between conditions after correcting for multiple comparisons (Bonferroni correction). NLD = non-lucid dream, LD = lucid dream. https://doi.org/10.1371/journal.pone.0201246.t002 active dose of galantamine did not differ from lucid dreams on the placebo dose for any content dimension (all p>0.05). Prediction/Classification of lucid dreams In half 1 of the dataset, we first used binary logistic regression to predict lucidity from content dimensions of dreams. As shown in S1 Table, the variables with the highest predictive values Fig 3. Responses to dimensions of consciousness (DIMs) questionnaire separated by lucid and non-lucid dreams and galantamine dose (G0 = 0 mg; G4 = 4 mg; G8 = 8 mg). Points and error bars show the mean and standard error of the mean. https://doi.org/10.1371/journal.pone.0201246.g003 PLOS ONE | https://doi.org/10.1371/journal.pone.0201246 August 8, 2018 9 / 16
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