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Keywords Lysergic acid diethylamide (LSD) was synthesized in 1938 and its psychoactive
LSD; Psychopharmacology; Pharmacology;
effects discovered in 1943. It was used during the 1950s and 1960s as an ex-
Pharmacokinetics; Mechanism of action;
perimental drug in psychiatric research for producing so-called “experimental
Hallucinogen; Psychedelic.
psychosis” by altering neurotransmitter system and in psychotherapeutic pro-
Correspondence cedures (“psycholytic” and “psychedelic” therapy). From the mid 1960s, it
Torsten Passie, Department of Clinical became an illegal drug of abuse with widespread use that continues today.
Psychiatry and Psychotherapy, Hannover With the entry of new methods of research and better study oversight, scien-
Medical School, Carl-Neuberg-Str. 1, D-30625 tific interest in LSD has resumed for brain research and experimental treat-
Hannover, Germany.
ments. Due to the lack of any comprehensive review since the 1950s and
Tel.: 0049-511-1235699 12;
the widely dispersed experimental literature, the present review focuses on
Fax: 0049-511-1235699 12;
E-mail: dr.passie@gmx.de all aspects of the pharmacology and psychopharmacology of LSD. A thor-
ough search of the experimental literature regarding the pharmacology of LSD
was performed and the extracted results are given in this review. (Psycho-)
pharmacological research on LSD was extensive and produced nearly 10,000
doi: 10.1111/j.1755-5949.2008.00059.x scientific papers. The pharmacology of LSD is complex and its mechanisms of
action are still not completely understood. LSD is physiologically well tolerated
and psychological reactions can be controlled in a medically supervised setting,
but complications may easily result from uncontrolled use by layman. Actu-
ally there is new interest in LSD as an experimental tool for elucidating neu-
ral mechanisms of (states of) consciousness and there are recently discovered
treatment options with LSD in cluster headache and with the terminally ill.
interest is increasing for using LSD in brain research, choactive properties. D-LSD crystallizes from benzene in
treatment of cluster headache [12], and as an aid in the pointed prisms. It is water-soluble and its melting point
psychotherapeutic treatment of the terminally ill [13,14]. is 83◦ C. LSD is usually stabilized in solution as its tartrate
Though no physical damage results from the use of salt. The molar mass is 323.42 g/mol.
LSD, many psychiatric complications have been reported, A great number of homologs and analogs of LSD has
with a peak occurring at the end of the 1960s [15,16]. Al- been studied [20–23]. These derivatives consist of varia-
though the dosage appears mostly unchanged since the tions of substituents on the amide group, sometimes ac-
1970s [16], the number of complications has probably companied by substituents on the indolic pyrrole ring.
declined since the late 1960s and early 1970s because Except for derivates substituted at the N-6 [24], no other
today there may be better-informed users, better mental derivate has shown a potency comparable to that of LSD
preparation and attention to surrounding conditions, and [25].
reduction in dosage weight (although one report claims
LSD dosage has remained fairly constant since the 1970
[16]). Pharmacology of LSD
Due to the widely dispersed (across time and lan- Psychological Effects
guages) experimental literature concerning the pharma-
cological properties of LSD, old and new data are together A moderate dose (75–150 μg p.o.) of LSD will signif-
reviewed here. It should be noted that the characteriza- icantly alter state of consciousness. This alteration is
tion of the complex effects on the human psyche are not characterized by a stimulation of affect (mostly expe-
the focus of this review [17–19]. rienced as euphoria), enhanced capacity for introspec-
tion, and altered psychological functioning in the direc-
tion of Freudian primary processes, known otherwise as
Chemistry hypnagogic experience and dreams [26]. Especially note-
LSD is a semisynthetic substance derived from lysergic worthy are perceptual changes such as illusions, pseudo-
acid as found in the parasitic rye fungus C. purpurea. The hallucinations, synesthesias, and alterations of thinking
molecule consists of an indole system with a tetracyclic and time experience. Changes of body-image and ego-
ring (C 20 H 25 ON 3 ) (see Figure 1). function also often occur [27,28].
Carbons 5 and 8 are asymmetric: therefore, four iso- The acute psychological effects of LSD last between 6
meric, optically-active LSD isomers are possible and and 10 h, depending on the dose applied.
known. These are d- and l-LSD and d- and l-isolysergic The minimal recognizable dose of LSD in humans is
acid diethylamide. Only the d-LSD isomer has psy- about 25 μg p.o. [29,30]. The “optimum” dosage for a
typical fully unfolded LSD reaction is estimated to be in
the range of 100–200 μg [18,29,31].
Traumatic experiences (called “bad trips”) can have
long-lasting effects on LSD users, including mood swings
and rarely flashback phenomena [15]. It should be noted,
however, that these generally take place in uncontrolled
conditions. Conversely, it has been shown that under
controlled and supportive conditions, the LSD experience
may have lasting positive effects on attitude and person-
ality [32].
Table 2 Blood pressure and heart rate changes during acute effects of moderate doses of LSD
Parameter Sokoloff et al. [75], (n = 13, 120 μg i.v.) DiMascio et al. [67], (n = 6, 1μg/kg p.o.) Kornetsky [35], (n = 10, 100 μg p.o.)
Arterial blood pressure (mmHg) +5, SD 2.9 +12% (syst.) +13 (SD unknown)
+10% (diast.)
Heart rate (beats per min) +15 SD 7 +18% +19 (SD unknown)
SD = standard deviation.
Figure 2 Course of clinical effects of LSD p.o. compared to the hallucinogen psilocybin (modified from Leuner [61]; identical with results of Hoch [88]).
hepatic tests applied. Examination of urinary constituents els [86]. Rinkel et al. [87] found a significant increase of
has also failed to reveal any abnormality (data summary 17-ketosteroid excretion (single-blind, n = 100, 0.5 μg/kg
in Hollister [69]). LSD p.o.).
Another finding (consistent with the presence of psy-
chological stress) is the mobilization of free fatty acids af-
ter ingestion of LSD (1–1.5 μg/kg p.o.) [79]. Pharmacokinetics
Resorption
Changes in Sleep-Waking Cycle and Dreaming After p.o. ingestion, LSD is completely absorbed in the
digestive tract [22,52]. After 100–250 μg LSD p.o., psy-
Low doses of LSD (n = 12, 6–40 μg p.o.) immediately chological and sympathomimetic effects persist for 30–45
applied before or 1 h after sleep onset lead (in a dose- min, reaching their peak after 1.5–2.5 h (see Figure 2)
dependent manner) to a prolongation of the first or sec- [18,88].
ond rapid eye movement (REM) periods by 30–240% and Upshall and Wailling [89] demonstrated that with a
a shortening of following periods. Eye movements dur- large meal, plasma concentrations of orally ingested LSD
ing these periods are less numerous. Total REM sleep is were half as much as on an empty stomach. When a
prolonged. No qualitative changes in sleep as measured smaller meal was eaten, plasma levels were somewhere
on EEG have been found [80]. Torda [81] infused LSD between. It was concluded that the amount of the meal,
(n = 2, 5 μg i.v./hour) after the start of the third REM as well as the pH of the stomach and duodenum, will in-
period and found that the beginning of the fourth REM fluence the absorption of LSD.
period began after 10–15 min, instead of the usual 40– Clinical data about different modes of application are
60 min. Theta activity was decreased in this study. Sleep shown in Table 5.
deprivation prior to LSD application leads to more intense
psychological reactions [82,83].
Table 5 Clinical pharmacokinetics of LSD with different modes of appli-
cation (data from Hoch [88]) (number of subjects not reported)
Endocrinological Changes
Mode of Dose (μg) Onset of Peak effect Total
LSD significantly lowers resting plasma prolactin levels
application symptoms (min) (h)∗ duration (h)∗
in male rats (0.05 and 0.2 mg/kg) [84]. No changes
were found for luteinizing hormone (LH) and follicle- Per os 100–250 30–45 1.0–2.5 9–12
stimulating hormone (FSH) (100 or 500 μg/kg LSD i.p.), Intramuscular 100–250 15–20 1.0 9–10
Intravenous 40–180 3–5 1.0 9–10
even with long time regimes [85].
Intraspinal 20–60 <1 1.0 9–10
In humans, LSD increases serum growth hormone with
a peak at 120 min. but does not alter serum prolactin lev- ∗
Hours after application of LSD.
Figure 5 LSD-levels in plasma (———) and liver (- - - - -) after 0.2 mg/kg LSD i.v. in monkeys (Macaca mulatta) (from Axelrod et al. [97]).
in the expired air as 14 CO 2 . Guinea pigs (1 mg/kg i.p.) ex- excretion of [14 C]-LSD occurred in both the rat and
creted 40% in feces, 28% in urine, and 18% as expired guinea pig [103].
14
CO 2 . Rhesus monkeys (0.15 mg/kg i.m.) eliminated Determination of urinary concentrations of LSD fol-
23% in the feces and 39% in the urine. Extensive binary lowing a single dose of the drug (200 μg p.o.) in humans
Figure 6 Course of plasma levels of LSD after 2 μg/kg i.v. in humans (modified from Aghajanian and Bing [102]).
shows that the rate of excretion of LSD reaches a max- The practical (forensic) detection limits are as low as 0.1
imum approximately 4–6 h after administration [108]. and 0.25 ng/mL for LSD and N-desmethyl-LSD, respec-
The elimination half-life for LSD is 3.6 h. LSD and its tively.
metabolites are reported to be detectable in the urine for The average time for determination of LSD in blood
as long as 4 days after ingestion [108]. Using a radioim- specimens is estimated to be 6–12 h and 2–4 days in urine
munoassay (RIA) screening test (cut-off at 0.1 ng/mL) specimens [109,111,115]. In most LSD-positive urine
the detection limit for 100 μg LSD p.o. is usually around samples the metabolite, 2-oxo-3-hydroxy-LSD, is present
30 h. Each doubling of the initial amount will add about at higher concentrations than LSD and can be detected af-
5 h [109]. LSD or its cross-reactive metabolites were ter LSD ingestion for a longer time than LSD itself [116].
detectable for periods of 34–120 h at concentrations of Determination of LSD in hair specimens is now avail-
2–28 μg/L in urine (n = 7, 300 μg LSD p.o.) [110]. able even for low and single time dosing but not for LSD
metabolites [117,118].
Table 10 Psychotic reactions, suicide attempts and suicides during psycholytic therapy with LSD
Study Patients (n) Sessions Suicide attempts Suicides Prolonged psychotic reactions
distributed in different areas of the brain. The highest sults critically in this way: “It is possible that the action of
concentrations were found in the pituitary and pineal lysergic acid is associated with changes in cerebral circu-
glands with concentrations seven to eight times higher as lation or metabolism, but in areas representing so small
in the cortex. Structures of the limbic system (hippocam- a fraction of the total brain that the effects are obscured
pus, amygdala, fornix, and septal region) contained two in measurements in the brain as a whole. Alternatively,
to three times more LSD than cortical structures. LSD it may be that in a heterogeneous organ like the brain,
compared to cortical regions was two to five times more many of those parts are functionally inversely or recip-
concentrated in the visual and auditory areas, hypotha- rocally related, changes in the net metabolic rate of the
lamus, extrapyramidal system, and thalamus. The brain brain remains unchanged” (p. 475).
stem contained LSD concentrations similar to the cor-
tex. LSD was equally distributed between white and gray
Neurophysiological Actions
matter.
Forrer and Goldner [68] and Hertle et al. [120] described
a dose-dependent hyperreflexia and a mild ataxia as the
Effects on Cerebral Circulation
major neurological effects of LSD.
Cerebral circulation and metabolism have been inves- The EEG shows mild and little specific signs of activa-
tigated in humans only by Sokoloff et al [75]. At the tion after LSD ingestion. Most common is an increase in
height of LSD-effects (n = 13, 120 μg i.v.), the gen- α mean frequency [121–123]. Other researchers describe
eral cerebral blood flow (measured with the nitrous ox- a progressive desynchronization due to a quantitative
ide method), cerebral vascular resistance, cerebral oxy- decrement of the slow component after LSD [124,125].
gen consumption, and glucose utilization were not sig- Goldstein et al. [126] reported a decrease of EEG variabil-
nificantly changed. Sokoloff et al. [74] summed their re- ity of 33% after LSD (0.3–1.0 μg/kg p.o.). Goldstein and
Stoltzfus [127] analyzed human EEG amplitude levels in brainstem and up into the brain. It has been suggested
right and left occipital areas and found that in most sub- that neurons in this brain region may inhibit sensation,
jects the normal pattern of lateralization was reversed by thus protecting the brain from sensory overload. The fact
LSD. that the LC and the RN innervate virtually every part of
the brain shows that serotonin can activate large portions
of the brain from a relatively small area of origination
Neurometabolic Effects
[146].
No studies about the neurometabolic actions of LSD have In general, 5-HT may be seen as a mainly inhibitory
been completed. However, there are neurometabolic transmitter; thus, when its activity is decreased, the next
studies published for related hallucinogens like psilo- neuron in the chain is freed from inhibition and be-
cybin [129,130], dimethyltryptamine (DMT) [131], and comes more active. This view is limited by the fact that
mescaline [132]. There are many incongruencies regard- a few 5-HT receptors are excitatory ion channels (5-HT 3 )
ing the results of the different studies, which limit the and some subtypes may have excitatory effects depend-
plausibility of hypotheses developed to explain neuro- ing upon the G protein coupling within specific neurons.
functional alterations during hallucinogen effects [133]. Since serotonergic systems appear to be intimately in-
Only the major and congruent results will be mentioned volved in the control of sensation, sleep, attention, and
here. The major hallucinogens appear to activate the mood, it may be possible to explain the actions of LSD and
right hemisphere, influence thalamic functioning, and in- other hallucinogens by their disinhibition of these critical
crease metabolism in paralimbic structures and in the systems [146].
frontal cortex. Because most of these metabolic changes LSD acts as a 5-HT autoreceptor agonist on 5-HT 1A re-
are also found in persons during psychological stress ceptors in the LC, the RN, and the cortex. It inhibits fir-
[134,135], it is not easy to distinguish which alterations ing and serotonin release of these cells. It also acts as a
are primary substance-induced and which are due to partial agonist on the postsynaptic 5-HT 1A site. LSD has
secondary (compensatory) psychophysical processes in- high affinity for other 5-HT 1 subtypes 5-HT 1B , 5-HT 1D ,
duced by general psychosocial stress during hallucino- and 5-HT 1E . Effects of LSD on 5-HT 2C , 5-HT 5A , 5-HT 6 ,
gen intoxication under experimental conditions. In re- and 5-HT 7 receptors [e.g., 147–149] are described, but
gard to global brain metabolism, some investigators found their significance remains uncertain. However, the hal-
an increased metabolism [130,132], but others found no lucinogenic effect of LSD has been linked to its affin-
change [129,136]. ity for the 5-HT 2 receptor where it acts as a 5-HT 2
agonist, as this property is shared by hallucinogens of
the phenethylamine group (mescaline, 2,5-dimethoxy-4-
iodoamphetamine, etc.) and the indolamine group (psilo-
Interactions with Receptors
cybin, DMT). A strong correlation was described between
The complex receptor interactions of LSD are a significant psychoactive doses of these hallucinogens and their re-
topic of experimental work and speculation about LSD’s spective potency at the 5-HT 2 receptor [150–151]. Most
working mechanisms. The predominant hypothesis on data indicate a specific 5-HT 2A mechanism, although a
how indole hallucinogens affect serotonin (5-HT) is sum- 5-HT 2C effect cannot be ruled out.
marized as follows: LSD acts to preferentially inhibit sero- LSD is probably best called a mixed 5-HT 2 /5-HT 1 re-
tonergic cell firing while sparing postsynaptic seroton- ceptor partial agonist. Today it is believed that LSD is a
ergic receptors from upregulation/downregulation. This partial agonist at 5-HT 2A receptors [e.g.,152,153], espe-
preference is shared in a somewhat limited fashion by cially those expressed on neocortical pyramidal cells. Ac-
non-indole hallucinogens. Nonhallucinogenic analogs of tivation of 5-HT 2A also leads to increased cortical gluta-
LSD show no such preference. mate levels [154,155] probably mediated by thalamic af-
Serotonin (5-hydroxytryptamine; 5-HT) is produced ferents [25]. However, this increase in glutamate release
by a small number of neurons (1000s) that each inner- can lead to an alteration in corticocortical and corticosub-
vate as many as 500,000 other neurons. For the most cortical transmission. LSD’s dual effect on 5-HT 2 (stim-
part, these neurons originate in the raphe nuclei (RN) ulatory) and 5-HT 1 (inhibitory) can explain how it may
of the midbrain. One major target of these is the lo- appear as an antagonist because it can modulate its own
cus coeruleus (LC), which controls the release of nore- effect.
pinephrine, which regulates the sympathetic nervous sys- In a recent study, Gonzalez-Maeso et al. [156] com-
tem. The LC also has neurons that extend into the cere- pared 2-HT 2A agonists with and without hallucinogenic
bellum, thalamus, hypothalamus, cerebral cortex, and activity in mice. It was found that these types of ago-
hippocampus. The RN extends its projections into the nists differ in regard to the G-protein activiation induced,
especially those of the pertussis toxin-sensitive het- may point to a possible mechanism for the development
erotrimeric G i/o and G a/11 proteins and their coactivation. of acute tolerance to LSD.
Using mice modified to genetically express 5-HT 2A recep- Pretreatment with BOL-148, a nonhallucinogenic con-
tors only in the cortex, it was shown that these recep- gener of LSD with serotonin antagonist properties like
tors were sufficient to produce hallucinogenic effects (as LSD, [166] will not block the effects of LSD [167,168].
indicated by hallucinogen-specific head twitch response) But other derivates of LSD, such as UML-491 and MLD-
with identical firing rates of pyramidal neurons as with- 41, are able to induce cross-tolerance if applied in the
out this manipulation. This may imply that the hallucino- days prior to LSD [167].
genic effects are mainly mediated by cortico-cortical neu- There is partial cross-tolerance (depending on whether
ral circuits rather than by thalamo-cortical circuits as pro- LSD is given first or second) among LSD, mescaline,
posed earlier by some scientists [133]. and psilocybin [168–170]. The most complete cross-
Nichols and Sanders-Bush [157] first described an LSD- tolerance is to mescaline in LSD-tolerant subjects. One
mediated increase in gene expression, which Nichols et study suggested that one-way cross-tolerance from LSD
al. [158] found to be due to activation of 5-HT 2A recep- to DMT does not occur [171]. Studies with -9-
tors. tetrahydrocannabiol (THC) in subjects tolerant to LSD
There is also evidence that LSD interacts with did not demonstrate a cross-tolerance between these
dopaminergic systems. In comparison to other hallucino- drugs [172,173]. There is no cross-tolerance between
gens, LSD interacts agonistically and antagonistically with LSD and amphetamine [169]. See Wyatt et al. [174]
central dopamine D 1 und D 2 -receptors [159,160]. It is and Hintzen [50] for a complete review of tolerance and
not established how these changes are involved in psy- cross-tolerance studies with LSD.
choactive effects of LSD, but studies with the related, but
more selective 5-HT 2A hallucinogen psilocybin demon-
Interactions of LSD with Other Substances
strated an increased release of dopamine, as evidenced
by a 20% decrease of [11 C]raclopride binding after psilo- Various studies have evaluated drug–drug interactions
cybin in human subjects [161]. with LSD. Early clinical studies focussed primarily on
Marona-Lewicka et al. [162] discovered receptor acti- LSD interactions with neuroleptics, especially chlorpro-
vation by LSD to be time-dependent. LSD in rats 15–30 mazine (CPZ). CPZ has proven to be an incomplete an-
min prior to testing in a discriminative stimulus task leads tagonist of LSD. When CPZ is given simultaneously with
to 5-HT 2A activation, while after 90 min D 2 -receptors LSD to humans in small doses (below 0.4 mg/kg), it pro-
may mediate major parts of LSD reactions. These data duces no changes in LSD’s effects [175]. At higher doses
suggest an interaction between dopamine and serotonin (0.7 mg/kg) of CPZ, LSD-induced side effects, such as
receptors and might be a possible explanation for the nausea, vomiting, dizziness, reduction in motor activity,
enormous range of effects LSD engenders in humans. and/or anxiety, have been reported to diminish or disap-
pear [176]. CPZ did not appreciably alter the production
of hallucinations or delusions, but associated unpleasant
Tolerance
feelings were reduced or eliminated [177].
Tolerance is defined as a decrease in responsiveness to As mentioned, sedative-hypnotics like diazepam (5mg
a drug after repeated administration. Tolerance to the p.o./i.m.) are often used in the emergency room set-
effects of LSD occurs in humans and animals. Toler- ting for acute presentations of LSD intoxication to help
ance to autonomic and psychological effects of LSD oc- reduce panic and anxiety [178,179]. Chronic adminis-
curs in humans after a few moderate daily doses of LSD tration of selective serotonin reuptake inhibitors (SSRIs)
[42,163,164]. Abramson et al. [163] gave 5–100 μg LSD as well as monoamine oxidase inhibitor (MAOI) antide-
p.o. for 3–6 days to healthy volunteers. After 2–3 days, pressants are reported to diminish LSD effects [180]. An
a solid tolerance developed as demonstrated in psycho- explanation may be that chronic application of antide-
logical and physiological tests. After tolerance to LSD is pressants decrease 5-HT2-receptor expression in several
achieved and placebo instead of LSD is given for the next brain regions [181]. In turn, one could predict that re-
3 days, the typical LSD effects will finally reoccur on the absorption of 5-HT 2A receptors will not be complete after
fourth day [42]. single predosing with an SSRI or MAOIs; in such circum-
A recent animal experiment with rats (130 μg/kg LSD stances, the risk for serotonin syndrome may be height-
i.v. for 5 consecutive days), who were previously trained ened. Lithium and some tricyclic antidepressants have
to discriminate LSD from saline, indicated a decrease in 5- also been reported to increase the effects of LSD [180].
HT 2A receptor signaling caused by a reduction of 5-HT 2A It has to be mentioned that LSD in combination with
receptor density [165]. This reduction in receptor density lithium drastically increases LSD reactions and can lead
to temporary comatose states as suggested by anecdotal main unclear. LSD is physiologically well tolerated and
medical reports [182]. there is no evidence for long-lasting effects on brain and
other parts of the human organism. The above review
Psychiatric Complications of pharmacology, psychopharmacology, related preclini-
cal research, as well as basic studies with human subjects
Many reports exist about psychiatric complications fol-
are gleaned from research that was for the most part con-
lowing LSD ingestion outside the research setting. The
ducted in the 1950s and 1960s during an era that held
most common unpleasant reaction is an episode of anx-
great promise for LSD and related hallucinogens. Hope
iety or panic (with severe, terrifying thoughts and feel-
was placed in these substances for new treatments for
ings, fear of losing control, fear of insanity or death,
psychiatric conditions and discoveries that would “un-
and despair)—the “bad trip” [15]. Other complicated
lock the mysteries” of the mind. And hallucinogen re-
reactions may include temporary paranoid ideation and,
search did indeed lead to the discovery of serotonin, brain
as after-effects in the days following a LSD experience,
second-messenger systems, and a variety of other re-
temporary depressive mood swings and/or increase of
search techniques such as prepulse inhibition and the use
psychic instability [17,61].
of animals for detection of activation of specific subrecep-
Crucially, there is a lack of evidence that other compli-
tors. The research of LSD faded after these advancements
cations will routinely occur or persist in healthy persons
and also because the clinical promises failed to be realized
taking LSD in a familiar surrounding. Cohen [8], Malle-
while illicit use of hallucinogens pressured governments
son [9], and Gasser [11] observed approximately 10,000
into taking police action against such use. Government
patients safely treated with LSD as a psycholytic agent.
funding of research dried up, as well, and a generation of
Indeed, past clinical studies with LSD were completed re-
scientists moved on to other topics. Today, LSD and other
porting very few if any complications (cf. Table 1).
hallucinogens are once again being evaluated for spe-
An extensive number of individuals participated in LSD
cific purposes, such as for treatment of cluster headache
research, with Passie [2] estimating some 10,000 patients
and as tools in therapy for working with those suffering
participating in research of the 1950s and 1960s. The in-
from anxiety provoking end-of-life issues and for post-
cidence of psychotic reactions, suicide attempts, and sui-
traumatic stress disorder. As these new studies move for-
cides during treatment with LSD, as noted in Table 1,
ward, it is hoped that this present paper will be a roadmap
appears comparable to the rate of complications during
for also securing the data missing from our knowledge of
conventional psychotherapy.
the pharmacology of LSD.
“Flashbacks” are characterized in the WHO Interna-
tional Classification of Diseases, Version 10 (ICD-10) as
of an episodic nature with a very short duration (sec-
onds or minutes) and by their replication of elements of Conflict of Interest
previous drug-related experiences. These reexperiences The authors have no conflict of interest.
of previous drug experiences occur mainly following in-
tense negative experiences with hallucinogens, but can
sometimes also be self-induced by will for positive re- References
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