Psychopharmacology
https://doi.org/10.1007/s00213-021-05991-9
ORIGINAL INVESTIGATION
Low doses of LSD reduce broadband oscillatory power and modulate
event‑related potentials in healthy adults
Conor H. Murray1 · Ilaria Tare1 · Claire M. Perry1 · Michael Malina1 · Royce Lee1 · Harriet de Wit1
Received: 28 May 2021 / Accepted: 20 September 2021
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021
Abstract
Rationale Classical psychedelics, including psilocybin and lysergic acid diethylamide (LSD), are under investigation as
potential therapeutic agents in psychiatry. Whereas most studies utilize relatively high doses, there are also reports of beneficial effects of “microdosing,” or repeated use of very low doses of these drugs. The behavioral and neural effects of these
low doses are not fully understood.
Objectives To examine the effects of LSD (13 μg and 26 μg) versus placebo on resting-state electroencephalography (EEG)
and event-related potential (ERP) responses in healthy adults.
Methods Twenty-two healthy men and women, 18 to 35 years old, participated in 3 EEG sessions in which they received
placebo or LSD (13 μg and 26 μg) under double-blind conditions. During each session, participants completed drug effect
and mood questionnaires at hourly intervals, and physiological measures were recorded. During expected peak drug effect,
EEG recordings were obtained, including resting-state neural oscillations in scalp electrodes over default mode network
(DMN) regions and P300, N170, and P100 ERPs evoked during a visual oddball paradigm.
Results LSD dose-dependently reduced oscillatory power across delta, theta, alpha, beta, and gamma frequency bands during
both eyes closed and eyes open resting conditions. During the oddball task, LSD dose-dependently reduced ERP amplitudes
for P300 and N170 components and increased P100 latency. LSD also produced dose-related increases in positive mood,
elation, energy, and anxiety and increased heart rate and blood pressure. On a measure of altered states of consciousness,
LSD dose-dependently increased Blissful State, but not other indices of perceptual or sensory effects typical of psychedelic
drugs. The subjective effects of the drug were not correlated with the EEG measures.
Conclusions Low doses of LSD produced broadband cortical desynchronization over the DMN during resting state and
reduced P300 and N170 amplitudes, patterns similar to those reported with higher doses of psychedelics. Notably, these
neurophysiological effects raise the possibility that very low doses of LSD may produce subtle behavioral and perhaps
therapeutic effects that do not rely on the full psychedelic experience.
Keywords LSD · EEG · ERP · Psychedelic · Microdose
Introduction
The past decade has seen a resurgence of interest in human
psychedelic research. Several clinical trials for treatment of anorexia, obsessive-compulsive disorder, addictions, and depression have been conducted, using single,
relatively high doses of psilocybin and LSD (Nutt and
* Harriet de Wit
hdew@uchicago.edu
1
Department of Psychiatry and Behavioral Neuroscience,
University of Chicago, 5841 S Maryland Ave MC3077,
Chicago, IL 60637, USA
Carhart-Harris, 2021). However, there have also been
widely publicized anecdotal reports on the beneficial effects
of “microdosing”—a practice of taking repeated, very low
doses of LSD (10–15 μg) every few days to improve mood
and cognition (Fadiman, 2011; Johnstad, 2018; Waldman,
2018; Fadiman and Korb, 2019; Kuypers et al., 2019; Polito
and Stevenson, 2019; Kuypers, 2020). Initial studies indicate
that these low doses of LSD produce detectable, but modest,
effects (Bershad et al., 2019; Yanakieva et al., 2019; Family
et al., 2020; Szigeti et al., 2021). Controlled laboratory studies indicate that single low doses increase ratings of vigor
(Bershad et al., 2019), decrease attentional lapses (Hutten
et al., 2020) and affect time perception (Yanakieva et al.,
13
Vol.:(0123456789)
Psychopharmacology
2019), but have few other effects on mood and do not impair
cognition or proprioception (Family et al., 2020). A “selfblinding” study conducted outside the laboratory detected
modest reductions in anxiety (Szigeti et al., 2021). Yet, even
in the absence of pronounced behavioral effects, it is possible that very low doses LSD subtly change neural function,
which ultimately affects behavior and perhaps contributes to
users’ positive reports. In this study, we examine the neural
signature of low doses of LSD using EEG.
LSD is a partial agonist that acts at serotonin receptors,
with some affinity to dopamine receptors (De Gregorio et al.,
2018). Although LSD and psilocybin bind to several targets
in the brain, their subjective and neurophysiological effects
are thought to be predominantly driven by activation of the
5-HT2a receptor (Quednow et al., 2012; Preller et al., 2018;
Preller et al., 2019). Upon activation, the 5-HT2a receptor
facilitates release of the excitatory neurotransmitter glutamate and enhances overall excitability of cortical networks
(Aghajanian and Marek, 1997; Beique et al., 2007; Nichols,
2016).
Several studies have investigated the effects of psychedelic drugs on functional connectivity in the brain using
functional magnetic resonance imaging (fMRI), most at
relatively high doses. For instance, 100 μg LSD increased
connectivity from the thalamus to cortical regions (Preller
et al., 2019), while both 75 μg LSD and moderate doses
of psilocybin increased measures of global brain connectivity (Lebedev et al., 2015; Tagliazucchi et al., 2016). In
one study, increased “complexity” in connectivity after 75
μg LSD was correlated with subjective effects (Luppi et al.,
2021). Together, resting-state fMRI studies indicate that
classical psychedelic drugs increase functional connectivity across networks while decreasing connectivity within
networks (Carhart-Harris et al., 2012; Carhart-Harris et al.,
2016; Tagliazucchi et al., 2016; Mueller et al., 2017). This
pattern, labeled neural “entropy,” is correlated with psychedelic drug-induced increases in trait openness (Lebedev
et al., 2016). Some authors have suggested that this pattern
represents a dismantling of maladaptive neuropsychological processes that underlies the drugs’ therapeutic effects
(Carhart-Harris and Friston, 2019). Little is known about
these neural effects at very low doses. In one of few such
studies, LSD (13 μg) increased connectivity between the
amygdala and middle frontal gyrus, and this was correlated
with positive mood after the drug (Bershad et al., 2020).
Dampened amygdala responses and connectivity to the frontal lobe have also been observed after 100 μg LSD and psilocybin (Mueller et al., 2017; Grimm et al., 2018). Thus, low
and higher doses of psychedelic drugs may produce similar
effects on connectivity.
Another way to study neural effects of psychedelic
drugs is using EEG or magnetoencephalography (MEG).
This technology provides better temporal resolution than
13
fMRI, but the primary measures are obtained from the
surface of the brain. EEG measures are used to assess
both resting-state oscillations and event-related potentials
(ERPs). Several studies have examined effects of higher
doses of psychedelic drugs on EEG. LSD (75 μg) and
moderate doses of psilocybin reduce broadband cortical
oscillatory power during resting state, particularly within
the posterior cingulate cortex (PCC) (Muthukumaraswamy
et al., 2013; Kometer et al., 2015; Carhart-Harris et al.,
2016). Decreases in oscillatory power, particularly at
lower frequencies, typically indicate greater neural function (Klimesch et al., 2007; Schroeder and Lakatos, 2009;
Buschman et al., 2012). Several researchers have examined associations between EEG measures and behavioral
effects. In one study (Carhart-Harris et al., 2016), LSD
(75 μg) decreased alpha power in the occipital region, and
this was correlated with intensity of visual imagery. The
authors also reported that decreased alpha power in the
PCC was correlated with reports of ego-dissolution. This
is consistent with the fact that the PCC is a major hub of
the default mode network (DMN), a major resting-state
network implicated in self-referential processing (Raichle,
2015). ERPs are waveforms elicited in response to stimuli,
including infrequent or “oddball” audio tones or visual
images. Changes in the amplitudes and latencies of the
components of these waveforms are taken to indicate
changes in neural information processing. Several studies
have examined effects of psychedelic drugs on ERPs. In
one study, psilocybin (0.26 mg/kg) reduced amplitudes
of perceptual (P100) and cognitive (P300) components
during an auditory oddball task (Bravermanova et al.,
2018), and in another study, the same drug reduced N170
responses to fearful, but not happy faces, in healthy subjects (Schmidt et al., 2013). Overall, these EEG findings
are consistent with fMRI findings suggesting that psychedelic drugs increase neural complexity while reducing
event-related neural responses. To our knowledge, however, the effects of very low doses on EEG measures have
not been studied.
Studying the effects of low doses of LSD on neural
function, such as those used in microdosing, is important for several reasons. First, understanding how the drug
alters brain function will help us to understand and study
the possible therapeutic effects of the drug. Second, such
studies will help to understand the relationships between
behavioral or subjective drug effects and the drugs’ effects
on neural systems. Such basic information will help to
guide future drug discovery. Thus, the present study was
designed to examine resting-state EEG and ERP responses
in healthy adults after 13 μg and 26 μg LSD and to examine the relationship between these neural effects and the
drug’s subjective effects.
Psychopharmacology
Methods
Study design
This study used a within-subject, double-blind design to test
effects of low doses of LSD on mood and EEG. Healthy
young adults participated in three 5-h sessions in which
they received, in randomized order, placebo, 13, or 26 μg of
LSD (sublingual). Subjective mood states and cardiovascular measures were recorded before drug administration and
at 60-min intervals after drug administration. During the
time of peak drug effect, 120 to 180 min after drug administration, EEG recordings were obtained to assess broadband
oscillatory activity during resting state and event-related
potential responses to infrequent (oddball) stimuli. The primary outcome measures were broadband oscillatory power
during resting state and event-related potentials (ERP) during an oddball task.
Subjects
Healthy subjects (N = 22, 8 women) 18 to 35 years of age
participated. They were screened for physical and psychiatric health with a physical examination, electrocardiogram,
modified Structural Clinical Interview for DSM-5, and selfreported health and drug-use history. Inclusion criteria were
English fluency, right-handedness, at least a high school education, body mass index of 18 to 32 kg/m2, and at least one
prior use of a classical psychedelic drug (e.g., LSD, psilocybin, N,N-dimethyl-tryptamine [DMT]) or 3,4-methylenediox-ymethamphetamine (MDMA). Exclusion criteria were
a history of psychosis, severe posttraumatic stress disorder
or panic disorder, past-year substance use disorder (except
nicotine), pregnant or nursing, working night shifts, regular
medication aside from birth control, adverse reaction to a
psychedelic drug, or unwillingness to use this type of drug
again. Subjects provided written, informed consent prior to
beginning the study, which was approved by the Institutional
Review Board of the Biological Sciences Division of The
University of Chicago.
Procedure
before and 24 h after each session, from cannabis for 7 days
before and 24 h after each session, and from alcohol for 24
h before and 12 h after each session. They were permitted
to consume their normal amounts of caffeine and nicotine
up to 3 h before sessions. Subjects were instructed to have
a normal night’s sleep and fast for 12 h before the sessions.
To minimize drug-specific expectancies, subjects were told
they might receive a placebo, stimulant, sedative, or hallucinogenic drug.
Experimental sessions
Subjects attended three 5-h sessions from 8 am to 1 pm,
separated by at least 7 days. Compliance to drug abstention
was verified by urinalysis (CLIAwaived Instant Drug Test
Cup, San Diego, CA; amphetamine, cocaine, oxycodone,
THC, PCP, MDMA, opiates, benzodiazepines, barbiturates,
methadone, methamphetamine, buprenorphine) and breath
alcohol testing (Alcosensor III, Intoximeters, St. Louis,
MO). Female subjects provided urine samples for pregnancy
tests and were tested at any phase of the menstrual cycle.
Subjects received a granola bar as a standardized breakfast.
Pre-drug measures of subjective state and cardiovascular
function were obtained, and then LSD (13 or 26 μg, tartrate
solution in water) or placebo (water) was administered sublingually under double-blind conditions. Participants held
the solution under the tongue without swallowing for 60 s,
under observation of the research assistant. Subjective and
cardiovascular measures were taken at 60, 120, 180, and 240
min. EEG recordings began 120 min after drug administration and lasted about 60 min. After the final time point at
240 min, subjects completed end-of-session questionnaires
and were discharged.
Drug
The drug was manufactured by Organix and was prepared
in solution with tartaric acid by the University of Chicago
Investigational Pharmacy. Drug solution (or water) was
administered in a volume of 0.5 mL. The doses were selected
to be below the threshold for hallucinatory effects (Bershad
et al., 2019) and within the range that is used in naturalistic
settings (Polito and Stevenson, 2019).
Drug effect measures
Orientation session
Subjects attended an orientation session to review the protocol, provide informed consent, receive presession instructions, and practice study tasks and questionnaires. They
completed the DASS-21, a 21-item Depression, Anxiety, and
Stress Scale (Lovibond and Lovibond, 1995). They were
instructed to abstain from drugs and medications for 48 h
Mood states and subjective drug effects were assessed before
and at regular intervals after drug administration using the
Drug Effects Questionnaire (DEQ) (Fischman and Foltin, 1991; Morean et al., 2013), the Addiction Research
Center Inventory (ARCI) (Haertzen et al., 1963; Martin
et al., 1971), and Profile of Mood States during each session (POMS) (McNair et al., 1971). The DEQ consists of 5
13
Psychopharmacology
questions assessing subjective drug effects using 100-mm
visual analog scales: Do you feel a drug effect?, Do you
like the drug effect?, Do you feel high?, Do you want more
of what you received?, and Do you dislike the drug effect?
The ARCI consists of 49 true/false questions measuring
typical drug effects: amphetamine-like (ARCI-A; stimulant
effects); benzedrine group (ARCI-BG; energy and intellectual efficiency); morphine-benzedrine group (ARCI-MBG;
euphoric effects); LSD (ARCI-LSD; hallucinogen-like
effects); and pentobarbital-chlorpromazine-alcohol group
(ARCI-PCAG; sedative effects). The POMS consist of 72
mood adjectives rated on a Likert scale from 0 (not at all) to
4 (extremely), divided into 8 subscales, friendliness, anxiety,
elation, anger, fatigue, depression, confusion, and vigor, and
two composite scales: positive mood (elation minus depression) and arousal (vigor plus anxiety minus confusion plus
fatigue). At the end of each session, subjects also completed
an end-of-session drug identification questionnaire and the
5 Dimensions of Altered States of Consciousness (5D-ASC)
questionnaire (Dittrich, 1998). Blood pressure and heart rate
were monitored every 60 min using portable blood pressure
cuffs (Critikon Dinamap Plus; GE Healthcare Technologies,
Waukesha, WI).
EEG measures
EEG acquisition
EEG recordings were collected using a 128 sintered Ag/
AgCl active electrodes (ActiveTwo™ system, BioSemi
B.V., Amsterdam) placed according to equiradial layout on
the head cap. Additional electrodes were placed at reference locations of the mastoids, around the eye to detect eye
blinks, and on the chest to detect EKG artifacts (8 peripheral
electrodes in total). The analog-to-digital box receiving the
electrode leads was battery powered to electrically isolate
participants. EEG data was acquired continuously, amplified,
and digitized using Biosemi ActiveView software. Digitization of electrode placement reflecting actual head shape was
conducted using a Patriot™ Digitizer Stylus (Polhemus Co.,
Colchester VT) and Locator software (Source Signal Imaging, Inc., San Diego CA). The stylus touches each electrode
site until registered by the software (5–10 min total). EEG
recordings occurred in a sound attenuated room, with the
subject sitting comfortably. EEG recordings were high-pass
filtered (1 Hz) and low-pass filtered (60 Hz, −12 dB/octave)
to remove extraneous high and low frequency noise. EEG
and electrooculogram (EOG) signals were processed by
voltage-controlled amplifiers and digitized (16 bit/500 Hz
sampling rate) for storage and analysis. Data was processed
offline based on data stored on computer workstation hard
drives.
13
Resting state
EEG data were continuously recorded, while participants
rested comfortably with eyes closed for 5 min, followed
by eyes open for 5 min with eyes rested on a fixation cross.
Subjects were instructed to minimize excessive blinking
and head movements and remain awake. The primary outcome measure was oscillatory power across five frequency
bands (delta, 1–4 Hz; theta, 4–8 Hz; alpha 8–13 Hz; beta
13–30 Hz; gamma 30–80 Hz). Scalp electrodes chosen for
the analysis (Supp. Fig. 1) were selected to reflect default
mode network hubs (medial prefrontal cortex, posterior
cingulate cortex, left temporoparietal cortex, and right
temporoparietal cortex) observed in simultaneous fMRIEEG studies (Neuner et al., 2014).
Emotional faces oddball task
An oddball task was used to assess event-related potentials (ERP). In the task, subjects viewed frequent happy
faces and infrequent neutral and angry faces in a 3:1 ratio
(Eckman and Friesen, 1976). The neutral and angry faces
depicted the same 2 models and were presented in separate
blocks (i.e., all neutral or all angry) with order counterbalanced across participants. Participants were instructed
to press the left button if they observed a happy face and
the right button if they observed a non-happy face. EEG
data from incorrect trials were discarded. Stimuli were
displayed on a computer screen for 1500 ms, followed by
a blank screen for 1000 ms, followed by a fixation cross
for 1000 ms (Supp. Fig. 2). A total of 320 face stimuli
were presented. Total task length was 15 min. The primary
outcome measures were the amplitudes and latencies of
task-evoked ERPs. For our purposes, the main analysis
was the response to infrequent facial expressions, and in
secondary analyses, we compared the rare neutral to rare
angry faces.
Data analysis
Subjective and cardiovascular effects
Visual inspection of the time course of each measure indicated that the effects of LSD peaked 2–3 h after administration, and the time course was similar for all measures
examined. To reduce the number of analyses, peak change
scores were calculated, subtracting the pre-drug values from
the highest or lowest value in each session. These scores
were analyzed using a one-way repeated measures analysis
of variance (drug dose), with follow-up contrasts to compare
each dose with placebo.
Psychopharmacology
EEG preprocessing
Results
Data were preprocessed using the EEGLAB extension
v2021.0 (Delorme & Makeig, 2004) for MATLAB (Mathworks, Inc.). Data were filtered with a low-pass filter of 1
and a high-pass filter of 60 Hz. Channels and periods of
continuous data containing gross movement artifacts were
selected and removed after manual inspection, and data
were re-referenced to the average reference. Gross movements were defined by interruptions of signal that occurred
across all electrodes in continuous data. Other artifactual
noise, including eye blink, eye movement, muscle, or EKG
related artifacts, were removed after independent component analysis (ICA) based on topography and morphology
of ICA components. After ICA, peripheral electrodes were
removed from analysis. Analysts were blind to drug condition during preprocessing steps to prevent bias during
manual inspection.
Demographic characteristics
Resting‑state analyses
Following ICA and removal of artifactual noise, oscillatory
power in the delta (1–4 Hz), theta (4–8 Hz), alpha (8–13
Hz), beta (13–30 Hz), and gamma (30–80 Hz) bands was
calculated using fast Fourier transform on scalp electrodes
during eyes closed or eyes open resting state. Scalp electrodes chosen for the analysis (Supp. Fig. 1) were selected
to correspond to default mode network hubs as observed in
simultaneous fMRI-EEG studies (Neuner et al., 2014). For
either eyes closed or eyes open, repeated measures analysis
of variance was performed across each of the four default
mode network regions and across the five frequency bands
with dose as within-subject factor.
ERP analyses
Following ICA, data were epoched from −500 to 1000 ms
around stimulus triggers. Trials with incorrect behavioral
responses were discarded. Data files were analyzed using the
EEGLAB Study function with multiple designs. ERP analyses were performed on Pz and PO 10 electrodes, selected a
priori for analysis of the P300 component (parietal (Pz)), and
visual processing components N170 and P100 (right parietooccipital (PO 10)), the latter chosen based on proximity to
the fusiform face gyrus and N170 findings in the literature
(Gao et al., 2019). For each component, peak amplitude
and latency to peak amplitude were extracted and exported
to SPSS software (version 25; SPSS Inc, Chicago, IL) for
statistical analysis. Repeated measures analyses of variance
were performed on either amplitude or latency from each
subject, with dose as within-subject factor.
Most subjects were in their 20s (mean age 25), with some
college education (mean education: 15 years) (Table 1).
Most reported current use of cannabis and alcohol, and their
mean lifetime use of psychedelic drugs was about 11 times.
Drug response measures
LSD (13 and 26 μg) dose-dependently increased subjective (Fig. 1, Supp. Table 1) and cardiovascular measures
(Fig. 2) over the course of the 5-h session. To illustrate
the time course of effects on a representative value, Fig. 1
includes mean values on DEQ Feel Drug for each time
point. Other rating scales and cardiovascular measures
had a similar time course. The time course indicates that
the EEG measures were obtained during the peak time
of the drug effect. LSD significantly increased ratings
on the DEQ Feel Drug (Fig. 1A), Feel High, Like Drug,
and Want More (Supp. Fig. 3). LSD also significantly
Table 1 Demographics and drug use characteristics of the participants in the study
Category
n or mean ± SD (range)
Subjects (male/female)
Age, years
Education, years
Body mass index, kg/m2
Race
Caucasian
African American
Asian
Other/>1 race
DASS-21
Depression
Anxiety
Stress
Current drug use in past month
Cannabis, times/month (n = 17)
Alcohol, drinks/week (n = 20)
Alcohol, drinking days/week
Caffeine, servings/day (n = 18)
Tobacco, times/day (n = 2)
Total lifetime drug use, nonmedical
Psychedelic (n = 22)
MDMA (n = 8)
Stimulant (n = 8)
Opiate (n = 5)
22 (14/8)
25 ± 5 (19–33)
15 ± 1 (14–18)
22.5 ± 2.9 (18–28.9)
18
1
1
2
5.0 ± 3.5 (0–14)
2.6 ± 3.5 (0–15)
5.9 ± 4.2 (0–16)
8.8 ± 8.7 (0–25)
4.7 ± 4.1 (0–17)
2.2 ± 1.5 (0–5)
1.1 ± 1.1 (0–3.5)
0.4 ± 1.8 (0–8.5)
10.9 ± 20.8 (1–100)
1.6 ± 3.9 (0–16)
24.3 ± 106.3 (0–500)
2.8 ± 8.8 (0–30)
13
Psychopharmacology
Fig. 1 Mean (± SEM) subjective effects ratings after placebo (0 μg),
13 and 26 μg LSD. The top left panel shows mean scores on “Feel
Drug” each hour after drug administration (A). Other scales showed
a similar time course. Other panels show mean change from baseline
scores for the Drug Effects Questionnaire (A), Profile of Mood States
(B), and Addiction Research Center Inventory (C). ARCI-LSD:
hallucinogen-like effects; ARCI-A: stimulant effects; ARCI-MBG:
euphoric effects; ARCI-BG: energy and intellectual efficiency. Significant main effects of dose were obtained for all scales shown; the
asterisks show which means differed significantly from placebo using
independent follow-up t-tests (*p < 0.05; **p < 0.01; ***p < 0.001).
increased Elation, Anxiety, and Positive Mood on the
POMS (Fig. 1B), and on the ARCI, it increased measures of LSD-like effects (ARCI-LSD), amphetamine-like
effects (ARCI-A), euphoric effects (ARCI-MBG), and
energy and intellectual efficiency (ARCI-BG) (Fig. 1C,
Supp. Fig. 3). Full time course and peak change from baseline data, including non-significant responses, are shown
in Supp. Fig. 3.
On cardiovascular measures, LSD increased heart rate
and systolic and diastolic blood pressure (Fig. 2) (heart
rate: dose, F1,21 = 5.11, p = 0.035; systolic BP: dose, F1,21
= 8.16, p = 0.009; 26 μg vs. placebo, p = 0.036; diastolic
BP: dose, F1,21 = 4.72, p = 0.041).
EEG recordings
13
During eyes closed resting state, LSD reduced broadband
oscillatory power across four major hubs of the default
mode network (medial prefrontal, posterior cingulate, and
left and right temporoparietal cortices) and five frequency
bands (delta [1–4 Hz], theta [4–8 Hz], alpha [8–13 Hz], beta
[13–30 Hz], and gamma [30–80 Hz]) (Fig. 3A) (dose, F1,420
= 10.39, p = 0.001). A secondary analysis examining power
for each of the four regions (Supp. Fig. 4) indicated that
the effects of LSD were most pronounced with electrodes
over the posterior cingulate cortex (dose, F1,105 = 15.71, p
< 0.001). The drug also reduced broadband power for left
Psychopharmacology
Fig. 2 Mean (± SEM) cardiovascular measures after placebo
(0 μg), 13 and 26 μg LSD. LSD
increased heart rate, systolic
BP, and diastolic BP (repeated
measures ANOVA). The
asterisk indicates significant
difference between placebo and
LSD using follow-up independent t-tests (*p < 0.05).
E) (dose, F1,42 = 11.13, p = 0.002). No significant dose ×
face condition interactions were found for LSD’s effects on
amplitude, latency, or error rate. Across all scalp electrodes,
LSD attenuated electropositive and electronegative potentials associated with the P300 and N170 ERPs, respectively,
as shown in scalp topographies (Fig. 5A, B).
End of session questionnaires
Fig. 3 Effects of LSD (13 and 26 μg) and placebo on oscillatory
power during eyes closed resting state in the default mode network.
Data are expressed as mean ± SEM. The drug decreased power
across all frequency bands (repeated measures ANOVA; main effect
of dose, p < 0.05; no interaction with frequency band). Follow-up
independent t-tests compared each LSD dose to placebo (*p < 0.05).
and right temporoparietal cortices (left: dose, F1,105 = 8.61,
p = 0.004); however, the right temporoparietal cortex was
only marginally affected (right: dose × band, F1,105 = 3.76,
p = 0.055). This pattern of reduced oscillatory power also
extended to the eyes open resting-state condition (Supp.
Fig. 5) (dose, F1,420 = 5.78, p = 0.017). During eyes open,
the drug decreased broadband oscillatory power in the posterior cingulate cortex (dose, F1,105 = 5.96, p = 0.016), in
addition to the medial prefrontal cortex (dose, F1,105 = 8.62,
p = 0.004), but not left or right temporoparietal cortices.
In the oddball task, LSD dose-dependently reduced
error rates (dose, F1,42 = 6.39, p = 0.015) (Supp. Fig. 6)
and decreased amplitudes for the P300 and N170, but not
the P100 ERP (Fig. 4A–D) (P300: dose, F1,42 = 7.52, p =
0.009; N170: dose, F1,42 = 4.87, p = 0.033). LSD increased
the latency of the P100 component without affecting the
latency of the later N170 or P300 components (Fig. 4A,
On the end of session questionnaire (Table 2), most participants correctly guessed “placebo” on placebo sessions
and “hallucinogen” on 26 μg LSD sessions. On 13 μg sessions, guesses were mixed between “placebo,” “sedative,”
and “hallucinogen” responses. On the 5D-ASC, LSD (26
μg only) significantly increased scores on Blissful State and
not any other subscale of the 5D-ASC (Fig. 6) (dose, F1,21 =
5.91, p = 0.024; 26 μg vs. placebo, p = 0.001).
Discussion
This study investigated the subjective and electrophysiological effects of low doses of LSD (13, 26 μg) and placebo
in healthy adults. Using resting-state EEG, we detected
a reduction of oscillatory power across frequency bands
indicative of broadband cortical desynchronization during
rest, both with eyes closed and eyes open. Using a visual
oddball paradigm to assess modulation of ERPs, the drug
decreased the amplitude and increased the latency of evoked
responses to visual stimuli. Subjectively, the drug produced
small increases in measures of energy, positive mood, elation, anxiety, and intellectual efficiency. On a measure of
altered states of consciousness (5D-ASC), it increased the
subscale Blissful State.
The main finding in this analysis was that low doses of
LSD reduced broadband oscillatory power. This finding is
13
Psychopharmacology
Fig. 4 Event-related potentials (ERPs) in response to rare stimuli
in the oddball task (angry and neutral faces). Grand averaged ERP
traces are shown under Pz (used to assess P300) and PO 10 (used to
assess N170 and P100) electrodes. Shaded regions indicate windows
used for peak extraction (P300, 300–700 ms; N170, 160–200 ms;
13
P100, 90–140 ms) (A). Significant mean amplitudes or latencies for
each ERP across subjects plotted (B). Repeated measures ANOVA
showing significant main effects of dose (p < 0.05). No interaction
with faces condition. Follow-up independent t-tests compared each
LSD dose to placebo (*p < 0.05; **p < 0.01; ***p < 0.001).
Psychopharmacology
consistent with reports with larger doses of classical psychedelics, including 75 μg LSD (Riba et al., 2002; Muthukumaraswamy et al., 2013; Kometer et al., 2015; Carhart-Harris
et al., 2016). Findings of broadband cortical desynchronization after administration of a classical psychedelic were
initially detected in an EEG study of dimethyltryptaminecontaining “ayahuasca” capsules (Riba et al., 2002) and
later after moderate intravenous doses of psilocybin, using
MEG (Muthukumaraswamy et al., 2013). The authors of
the MEG-psilocybin study detected decreases in oscillatory power over posterior and frontal associated cortices,
with large decreases in areas of the DMN, including the
posterior cingulate cortex (PCC). They attributed desynchronization in the PCC to increased excitability of deeplayer pyramidal neurons that are rich in 5-HT2a receptors
(Erritzoe et al., 2009). Moderate oral doses of psilocybin
have also been shown to reduce oscillatory power during
EEG from 1.5 to 20 Hz (affecting all frequency bands except
for gamma) within the PCC, anterior cingulate cortex, and
retrosplenial cortex (Kometer et al., 2015). Based on the
inverse relationship between oscillatory power and neural
activity, particularly at lower frequencies (Klimesch et al.,
2007; Schroeder and Lakatos, 2009; Buschman et al., 2012),
the authors suggested their findings indicate a shift in the
resting-state excitation/inhibition balance toward excitation.
LSD (75 μg) also decreased oscillatory power across delta,
alpha, theta, and beta bands and increased “diversity” in
neural signals (Carhart-Harris et al., 2016; Schartner et al.,
2017). Diversity refers to distinct patterns that have been
used to index levels of sedation and sleep (Schartner et al.,
2017). The authors reported that decreases in alpha power in
the occipital lobe correlated with intensity of visual imagery,
while decreases of alpha in the PCC correlated with “egodissolution,” as measured by the 5D-ASC (Carhart-Harris
et al., 2016). An important limitation of our analysis was
that we did not include dipole or distributed source detection of intracranial spectral density, but rather for the sake
of simplicity focused on scalp electrodes over DMN regions
during resting state. Due to the inverse problem of inferring
the source of scalp recorded signals from deeper structures,
our interpretation of the results is limited until further confirmation using either intracranial EEG or source estimations.
LSD reduced neural responses to unexpected stimuli in
the visual oddball paradigm. The drug dose-dependently
reduced amplitudes to both cognitive (P300) and perceptual (N170) ERPs and increased latency to the early perceptual P100 component. Because the oddball task used facial
images as stimuli, these findings raise the possibility that
low doses of LSD affect cognitive and perceptual processing associated with facial recognition, including allocation of attentional resources (P300), structural encoding of
facial configurations (N170), and fast extraction of visual
information (P100) (Posner, 1975; Schmidt et al., 2013).
Notably, the low doses of LSD did not impair behavioral
responses to facial stimuli, but instead improved responses
by reducing error rates. It remains to be determined whether
similar effects would be observed with non-facial stimuli
at low doses. In higher doses, several studies have shown
that LSD and psilocybin affect ERPs as well as facial recognition. Specifically, LSD and psilocybin often reduce
the recognition of negative facial expressions (Rocha et al.,
2019). Psilocybin also reduced N170 amplitudes in response
to fearful, but not happy faces (Schmidt et al., 2013). The
authors noted that N170 amplitudes for fearful faces were
greater than for happy faces under placebo conditions, suggesting that psilocybin induced a shift away from the bias to
fearful faces. Although our study was not designed to assess
changes in recognition of the valence of emotional face processing, LSD did not differentially alter N170 amplitudes
after neutral or angry faces in the present study. Other studies have reported that psilocybin (at relatively high doses)
also reduced amplitudes in P300 ERPs during an auditory
oddball task (Bravermanova et al., 2018), and LSD has been
found to reduce the amplitudes of visual average and photic
evoked responses (Rodin and Luby, 1966; Shagass, 1966).
The findings from this study suggest that even microdoses
of LSD have effects on brain processing of visual stimuli
that parallel that seen with higher doses of LSD and other
psychedelic drugs.
The subjective reports in our study showed that low
doses of LSD increased positive mood and produced some
stimulant-like effects. Specifically, LSD (26 μg) increased
elation, positive mood, and anxiety on the POMS, as well
as amphetamine-like effects on the ARCI. The subjective
reports on stimulant-like effects are consistent with the
known action of LSD at dopamine receptors (Pieri et al.,
1974; Kelly and Iversen, 1975) raising the possibility that
some of these effects are mediated by dopamine rather than
serotonin. However, other studies (Preller et al., 2017) have
shown that the subjective effects of higher doses of LSD
are completely blocked by a 5-HT2a antagonist. Whether
dopamine receptors are engaged at these low doses of LSD
(De Gregorio et al., 2018) remains to be determined. We
also note that most of the participants correctly identified
the 26 μg dose as a “hallucinogen” at the end of the session.
The subjective effects they experienced during the session
presumably led to this identification. However, we recognize that effects experienced early in the session could also
have influenced responses later in the session (i.e., through
“unblinding”). Future analyses examining relationships
between direct subjective effects and drug identifications
may help resolve this issue.
The present findings can also be related to EEG studies with other drugs. D-amphetamine, like classical psychedelics, reduces resting-state neuronal oscillations in delta,
theta, and alpha bands, predominately localized to frontal
13
Psychopharmacology
13
Psychopharmacology
◂Fig. 5 Scalp topographies averaged across subjects for P300 (A),
N170 (B), and P100 (C) event-related potential amplitudes for angry
and neutral conditions in the emotional faces oddball paradigm.
Right: red electrodes indicate electrodes where there were significant
differences between placebo and 26 μg LSD condition (p < 0.05).
in positive mood after LSD (13 μg) was correlated with connectivity between the amygdala and middle frontal gyrus
during resting state. It remains to be determined how fMRI
measures of connectivity and EEG measures of broadband
oscillatory power after low doses of LSD can be reconciled.
Table 2 End of session questionnaire. Number of subjects who
labeled the drug they received as a placebo, hallucinogen, stimulant,
sedative, or opioid
Conclusions
Study session (LSD dose)
Placebo
Hallucinogen
Stimulant
Sedative
Opioid
Placebo
13 μg
26 μg
12
2
2
5
1
6
6
2
5
3
2
13
2
4
1
and central regions (Albrecht et al., 2016). Conversely,
sedative-like drugs such as alcohol or thiagabine (a GABA
reuptake inhibitor) robustly increase delta, theta, and alpha
power (Lansbergen et al., 2011; Muthukumaraswamy
and Liley, 2018). Subanesthetic doses of ketamine, which
enhance cortical excitatory signaling (Gerhard et al., 2020),
also robustly reduce delta, alpha, and beta band power similarly to classical psychedelics (Muthukumaraswamy and
Liley, 2018). Within the greater context of pharmaco-EEG
studies, our findings indicate that low doses of LSD facilitate
cortical neuronal activity.
In the present study, EEG activity (resting state or ERPs)
was not related to subjective or behavioral responses. This
lack of correlation may be due to the limited statistical power
of this study to detect such a relationship. In a previous study
with fMRI (Bershad et al., 2020), we found that the increase
These data add to the literature on classical psychedelics by
describing acute effects of low doses of LSD from a neurophysiological perspective. We found that 13 and 26 μg
doses of LSD have subtle, mostly positive subjective effects
related to mood and cognition and yet produce some of the
same EEG effects reported at higher doses of LSD (75 μg)
and moderate doses of psilocybin. It has been proposed that
classical psychedelics produce therapeutic effects by altering
spontaneous cortical activity, inducing neural entropy that
counters maladaptive neuroplasticity and associated mental
rigidity (Carhart-Harris and Friston, 2019). Although we
did not assess clinical outcome, our findings suggest that
low doses of LSD produce neural effects that are similar
to higher doses, raising the possibility that these low doses
may lead to beneficial outcomes without producing psychedelic states. Future studies are needed to extend these
observations to populations with psychiatric symptoms, and
after repeated doses of the drug, as it is used in microdosing. Future studies should also examine the effects of these
low doses when combined with psychotherapy. If effective,
repeated low doses may provide an alternative model alongside high dosing procedures that have shown therapeutic
benefits when used with additional support and preparation
(Griffiths et al., 2016; Ross et al., 2016).
Fig. 6 Mean scores (± SEM)
on subscales of altered states of
consciousness after placebo, 13
μg LSD, and 26 μg. LSD (26 μg
only) increased scores on Blissful State (ANOVA *p < 0.05).
13
Psychopharmacology
Supplementary Information The online version contains supplementary material available at https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 00213-0​ 21-0​ 5991-9.
Acknowledgements We thank Robin Nusslock for the helpful comments on the manuscript.
Funding This research was supported by the National Institutes of
Health [DA02812]. CHM was supported by the National Institutes of
Health [T32DA043469]. Additional support was received as a pilot
grant from the Department of Psychiatry and Behavioral Neuroscience,
University of Chicago.
Declarations
Conflict of interest The author declare no competing interests.
References
Aghajanian GK, Marek GJ (1997) Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal
cells. Neuropharmacol 36:589–599
Albrecht MA, Roberts G, Price G, Lee J, Iyyalol R, Martin-Iverson
MT (2016) The effects of dexamphetamine on the resting-state
electroencephalogram and functional connectivity. Hum Brain
Mapp 37:570–588
Beique JC, Imad M, Mladenovic L, Gingrich JA, Andrade R (2007)
Mechanism of the 5-hydroxytryptamine 2A receptor-mediated
facilitation of synaptic activity in prefrontal cortex. Proc Natl
Acad Sci U S A 104:9870–9875
Bershad AK, Schepers ST, Bremmer MP, Lee R, de Wit H (2019)
Acute subjective and behavioral effects of microdoses of lysergic
acid diethylamide in healthy human volunteers. Biol Psychiatry
86:792–800
Bershad AK, Preller KH, Lee R, Keedy S, Wren-Jarvis J, Bremmer
MP, de Wit H (2020) Preliminary report on the effects of a low
dose of lsd on resting-state amygdala functional connectivity. Biol
Psychiatry Cogn Neurosci Neuroimaging 5:461–467
Bravermanova A, Viktorinova M, Tyls F, Novak T, Androvicova R,
Korcak J, Horacek J, Balikova M, Griskova-Bulanova I, Danielova D, Vlcek P, Mohr P, Brunovsky M, Koudelka V, Palenicek
T (2018) Psilocybin disrupts sensory and higher order cognitive
processing but not pre-attentive cognitive processing-study on
P300 and mismatch negativity in healthy volunteers. Psychopharmacol (Berl) 235:491–503
Buschman TJ, Denovellis EL, Diogo C, Bullock D, Miller EK (2012)
Synchronous oscillatory neural ensembles for rules in the prefrontal cortex. Neuron 76:838–846
Carhart-Harris RL, Friston KJ (2019) REBUS and the anarchic brain:
toward a unified model of the brain action of psychedelics. Pharmacol Rev 71:316–344
Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P,
Evans J, Feilding A, Wise RG, Nutt DJ (2012) Neural correlates
of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci U S A 109:2138–2143
Carhart-Harris RL et al (2016) Neural correlates of the LSD experience
revealed by multimodal neuroimaging. Proc Natl Acad Sci U S
A 113:4853–4858
Delorme A, Makeig S (2004) EEGLAB: an open source toolbox for
analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods 134:9–21
13
De Gregorio D, Enns JP, Nunez NA, Posa L, Gobbi G (2018) d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens:
mechanism of action and potential therapeutic applications in
mood disorders. Prog Brain Res 242:69–96
Dittrich A (1998) The standardized psychometric assessment of altered
states of consciousness (ASCs) in humans. Pharmacopsychiatry
31(Suppl 2):80–84
Eckman P, Friesen W (1976) Pictures of facial affect. Consorting Psychologies' Press, Palo Alto CA; Folkman S, Chesney M, McKusick L, Ironson G, Johnson DS, Coates TJ (1991) Translating Coping Theory into an Intervention. The Social Context of Coping,
S:239-260.
Erritzoe D, Frokjaer VG, Haugbol S, Marner L, Svarer C, Holst K,
Baaré WF, Rasmussen PM, Madsen J, Paulson OB, Knudsen GM
(2009) Brain serotonin 2A receptor binding: relations to body
mass index, tobacco and alcohol use. Neuroimage 46:23–30
Fadiman J (2011) The psychedelic explorer’s guide: safe, therapeutic,
and sacred journeys: Inner Traditions/Bear.
Fadiman J, Korb S (2019) Might microdosing psychedelics be safe
and beneficial? An Initial Exploration. J Psychoactive Drugs
51:118–122
Family N, Maillet EL, Williams LTJ, Krediet E, Carhart-Harris RL,
Williams TM, Nichols CD, Goble DJ, Raz S (2020) Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose
lysergic acid diethylamide (LSD) in healthy older volunteers.
Psychopharmacol (Berl) 237:841–853
Fischman MW, Foltin RW (1991) Utility of subjective-effects measurements in assessing abuse liability of drugs in humans. Br J Addict
86:1563–1570
Gao C, Conte S, Richards JE, Xie W, Hanayik T (2019) The neural
sources of N170: Understanding timing of activation in faceselective areas. Psychophysiology 56:e13336.
Gerhard DM, Pothula S, Liu RJ, Wu M, Li XY, Girgenti MJ, Taylor
SR, Duman CH, Delpire E, Picciotto M, Wohleb ES, Duman RS
(2020) GABA interneurons are the cellular trigger for ketamine’s
rapid antidepressant actions. J Clin Invest 130:1336–1349
Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA,
Richards BD, Cosimano MP, Klinedinst MA (2016) Psilocybin
produces substantial and sustained decreases in depression and
anxiety in patients with life-threatening cancer: a randomized
double-blind trial. J Psychopharmacol 30:1181–1197
Grimm O, Kraehenmann R, Preller KH, Seifritz E, Vollenweider FX
(2018) Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination. Eur Neuropsychopharmacol 28:691–700
Haertzen CA, Hill HE, Belleville RE (1963) Development of the
Addiction Research Center Inventory (Arci): selection of items
that are sensitive to the effects of various drugs. Psychopharmacologia 4:155–166
Hutten N, Mason NL, Dolder PC, Theunissen EL, Holze F, Liechti ME,
Feilding A, Ramaekers JG, Kuypers KPC (2020) Mood and cognition after administration of low LSD doses in healthy volunteers:
A placebo controlled doseeffect finding study. Eur Neuropsychopharmacol 41:81–91
Johnstad PG (2018) Powerful substances in tiny amounts: an interview study of psychedelic microdosing. Nordisk Alkohol Nark
35:39–51
Kelly PH, Iversen LL (1975) LSD as an agonist at mesolimbic dopamine receptors. Psychopharmacologia 45:221–224
Klimesch W, Sauseng P, Hanslmayr S (2007) EEG alpha oscillations:
the inhibition-timing hypothesis. Brain Res Rev 53:63–88
Kometer M, Pokorny T, Seifritz E, Volleinweider FX (2015) Psilocybin-induced spiritual experiences and insightfulness are associated
with synchronization of neuronal oscillations. Psychopharmacol
(Berl) 232:3663–3676
Psychopharmacology
Kuypers KP, Ng L, Erritzoe D, Knudsen GM, Nichols CD, Nichols DE,
Pani L, Soula A, Nutt D (2019) Microdosing psychedelics: more
questions than answers? An overview and suggestions for future
research. J Psychopharmacol 33:1039–1057
Kuypers KPC (2020) Microdosing with psychedelics: what do we
know? Tijdschr Psychiatr 62:669–676
Lansbergen MM, Dumont GJ, van Gerven JM, Buitelaar JK, Verkes
RJ (2011) Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with
ethanol or THC (delta-9-tetrahydrocannabinol). Psychopharmacol
(Berl) 213:745–756
Lebedev AV, Lovden M, Rosenthal G, Feilding A, Nutt DJ, CarhartHarris RL (2015) Finding the self by losing the self: neural correlates of ego-dissolution under psilocybin. Hum Brain Mapp
36:3137–3153
Lebedev AV, Kaelen M, Lovden M, Nilsson J, Feilding A, Nutt DJ,
Carhart-Harris RL (2016) LSD-induced entropic brain activity predicts subsequent personality change. Hum Brain Mapp
37:3203–3213
Lovibond PF, Lovibond SH (1995) The structure of negative emotional
states: comparison of the depression anxiety stress scales (DASS)
with the beck depression and anxiety inventories. Behav Res Ther
33:335–343
Luppi AI, Carhart-Harris RL, Roseman L, Pappas I, Menon DK,
Stamatakis EA (2021) LSD alters dynamic integration and segregation in the human brain. Neuroimage 227:117653.
Martin WR, Sloan JW, Sapira JD, Jasinski DR (1971) Physiologic,
subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man.
Clin Pharmacol Ther 12:245–258
McNair DM, Lorr M, Droppleman LF (1971) Manual profile of mood
states.
Morean ME, de Wit H, King AC, Sofuoglu M, Rueger SY, O’Malley
SS (2013) The drug effects questionnaire: psychometric support
across three drug types. Psychopharmacol (Berl) 227:177–192
Mueller F, Lenz C, Dolder PC, Harder S, Schmid Y, Lang UE, Liechti
ME, Borgwardt S (2017) Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects. Transl
Psychiatry 7:e1084
Muthukumaraswamy SD, Liley DT (2018) 1/f electrophysiological
spectra in resting and drug-induced states can be explained by
the dynamics of multiple oscillatory relaxation processes. Neuroimage 179:582–595
Muthukumaraswamy SD, Carhart-Harris RL, Moran RJ, Brookes MJ,
Williams TM, Errtizoe D, Sessa B, Papadopoulos A, Bolstridge
M, Singh KD, Feilding A, Friston KJ, Nutt DJ (2013) Broadband
cortical desynchronization underlies the human psychedelic state.
J Neurosci 33:15171–15183
Neuner I, Arrubla J, Werner CJ, Hitz K, Boers F, Kawohl W, Shah
NJ (2014) The default mode network and EEG regional spectral
power: a simultaneous fMRI-EEG study. PLoS One 9:e88214
Nichols DE (2016) Psychedelics. Pharmacol Rev 68:264–355
Nutt D, Carhart-Harris R (2021) The current status of psychedelics in
psychiatry. JAMA Psychiatry 78:121–122
Pieri L, Pieri M, Haefely W (1974) LSD as an agonist of dopamine
receptors in the striatum. Nature 252:586–588
Polito V, Stevenson RJ (2019) A systematic study of microdosing
psychedelics. PLoS One 14:e0211023
Posner MI (1975) Chapter 15 - Psychobiology of attention. In: Handbook of Psychobiology (Gazzaniga MS, Blakemore C, eds), pp
441-480: Academic Press.
Preller KH, Razi A, Zeidman P, Stampfli P, Friston KJ, Vollenweider
FX (2019) Effective connectivity changes in LSD-induced altered
states of consciousness in humans. Proc Natl Acad Sci U S A
116:2743–2748
Preller KH, Herdener M, Pokorny T, Planzer A, Kraehenmann R,
Stampfli P, Liechti ME, Seifritz E, Vollenweider FX (2017) The
fabric of meaning and subjective effects in LSD-induced states
depend on serotonin 2A receptor activation. Curr Biol 27:451–457
Preller KH, Burt JB, Ji JL, Schleifer CH, Adkinson BD, Stampfli P,
Seifritz E, Repovs G, Krystal JH, Murray JD, Vollenweider FX,
Anticevic A (2018) Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor. Elife 7.
Quednow BB, Kometer M, Geyer MA, Vollenweider FX (2012) Psilocybin-induced deficits in automatic and controlled inhibition are
attenuated by ketanserin in healthy human volunteers. Neuropsychopharmacol 37:630–640
Raichle ME (2015) The brain’s default mode network. Annu Rev Neurosci 38:433–447
Riba J, Anderer P, Morte A, Urbano G, Jane F, Saletu B, Barbanoj
MJ (2002) Topographic pharmaco-EEG mapping of the effects of
the South American psychoactive beverage ayahuasca in healthy
volunteers. Br J Clin Pharmacol 53:613–628
Rocha JM, Osorio FL, Crippa JAS, Bouso JC, Rossi GN, Hallak JEC,
Dos Santos RG (2019) Serotonergic hallucinogens and recognition
of facial emotion expressions: a systematic review of the literature. Ther Adv Psychopharmacol 9:2045125319845774
Rodin E, Luby E (1966) Effects of LSD-25 on the EEG and photic
evoked responses. Arch Gen Psychiatry 14:435–441
Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt
BL (2016) Rapid and sustained symptom reduction following
psilocybin treatment for anxiety and depression in patients with
life-threatening cancer: a randomized controlled trial. J Psychopharmacol 30:1165–1180
Schartner MM, Carhart-Harris RL, Barrett AB, Seth AK, Muthukumaraswamy SD (2017) Increased spontaneous MEG signal diversity for psychoactive doses of ketamine. LSD and psilocybin. Sci
Rep 7:46421
Schmidt A, Kometer M, Bachmann R, Seifritz E, Vollenweider F
(2013) The NMDA antagonist ketamine and the 5-HT agonist
psilocybin produce dissociable effects on structural encoding of
emotional face expressions. Psychopharmacol (Berl) 225:227–239
Schroeder CE, Lakatos P (2009) Low-frequency neuronal oscillations
as instruments of sensory selection. Trends Neurosci 32:9–18
Shagass C (1966) Effects of LSD on somatosensory and visual evoked
responses and on the EEG in man. Recent Adv Biol Psychiatry
9:209–227
Szigeti B, Kartner L, Blemings A, Rosas F, Feilding A, Nutt DJ,
Carhart-Harris RL, Erritzoe D (2021) Self-blinding citizen science to explore psychedelic microdosing. Elife 10.
Tagliazucchi E, Roseman L, Kaelen M, Orban C, Muthukumaraswamy
SD, Murphy K, Laufs H, Leech R, McGonigle J, Crossley N, Bullmore E, Williams T, Bolstridge M, Feilding A, Nutt DJ, CarhartHarris R (2016) Increased global functional connectivity correlates with LSD-induced ego dissolution. Curr Biol 26:1043–1050
Waldman A (2018) A really good day: how microdosing made a mega
difference in my mood, my marriage, and my life: Anchor Books.
Yanakieva S, Polychroni N, Family N, Williams LTJ, Luke DP, Terhune
DB (2019) The effects of microdose LSD on time perception: a
randomised, double-blind, placebo-controlled trial. Psychopharmacol (Berl) 236:1159–1170
Publisher's note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
13