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Hum[ Psychopharmacol[ Clin[ Exp[ 04\ 448Ð454 "1999#

Hallucinogenic Drugs Attenuate the Subjective

Response to Alcohol in Humans
Department of Psycholo`y\ McGill University\ Montreal\ Canada

This study investigated possible interactions between alcohol and hallucinogens in 11 lysergic acid diethylamide
"LSD# and:or psilocybin users through retrospective structured interviews[ Of those who had used LSD with alcohol\
75=6 per cent reported a complete blockade of subjective alcohol e}ects\ while the remaining cases reported a
diminished response[ In addition\ 59 per cent of respondents who had used alcohol and psilocybin together reported
a partial antagonism of subjective alcohol e}ects[ T!test analyses revealed that LSD|s antagonism of alcohol e}ects
were signi_cantly greater than those associated with psilocybin[ It is proposed that LSD|s e}ect on alcohol intoxication
may involve interactions with various serotonergic and:or dopaminergic receptor systems[ Copyright Þ 1999 John
Wiley + Sons\ Ltd[

KEY WORDS * lysergic acid diethylamide^ alcohol^ psilocybin^ hallucinogens^ serotonin^ dopamine

INTRODUCTION partial agonist at dopamine "DA# receptors "Watts

The therapeutic use of lysergic acid diethylamide et al[\ 0884^ Giacomelli et al[\ 0887#\ and mid!brain
"LSD# has been studied extensively as a possible DA transmission has been implicated in several of
adjunct to psychotherapy for the treatment of alcohol|s reinforcing properties "e[g[ Koob et al[\
alcoholism "e[g[ Abraham et al[\ 0885^ Mangini\ 0887#[ Given the fact that LSD is known to a}ect
0887#[ Such studies have produced inconsistent neural systems implicated in ethanol intake\
results and this area of research was abandoned in reinforcement\ and discriminative stimulus\ one
the early 0869s due to concerns over LSD|s safety might expect the subjective human response to etha!
"Mangini\ 0887#[ Despite the fact that several clini! nol to be altered by LSD administration[ Inter!
cal trials were conducted over a 14!year period\ the estingly\ a recent study of the drug taking patterns
e}ects of the combined use of alcohol and LSD of adolescent drinkers suggests that the simul!
were never elucidated[ Nevertheless\ the phar! taneous use of alcohol and hallucinogens is quite
macological pro_les of these two substances suggest common\ with 05 per cent of the sample reporting
the possibility of a clinically signi_cant interaction[ combining alcohol with hallucinogens on at least
For example\ LSD binds with high a.nity at both one occasion "Martin et al[\ 0885#[ The current
4!HT0 and 4!HT1 receptors "e[g[ Peroutka\ 0883#\ investigation presents systematically collected
and drugs that act on either of these receptor sub! information from individuals who have reported
types have been shown to alter both ethanol intake using ethanol with LSD and:or psychotic mush!
and discriminative stimulus e}ects in rats "Szeliga rooms\ a related hallucinogenic drug[
and Grant\ 0887^ Kostowski and Bienkowski\
0888#[ Furthermore\ LSD is thought to act as a
Participants for this retrospective self!report study
 Correspondence to] S[ P[ Barrett\ Department of Psychology\
McGill University\ 0194 Dr[ Pen_eld Avenue\ Montreal\ QC\ were recruited through the {snowball| method of
Canada H2A 0B0[ Tel] 403!871!4902[ Fax] 403!287!3785[ E! sampling[ This sampling method has been widely
mail] barrettÝego[psych[mcgill[ca used to study hidden or clandestine populations

Copyright Þ 1999 John Wiley + Sons\ Ltd[


"Jackson\ 0886#\ and requires the researcher to RESULTS

make an initial set of contacts and to ask these Nineteen males and three females were interviewed
contacts to introduce him:her to potential par! for the present study[ The participants ranged in
ticipants[ In the present study four contacts whose age from 07 to 17 years "M  12=62\ SD  1=75#[
past hallucinogenic use was known a priori were Most participants reported extensive past use of
used to recruit subjects[ Potential participants were hallucinogens\ with 62 per cent of subjects reporting
contacted either in person or by telephone and were 19 or more lifetime uses of LSD and 62 per cent
asked if they would answer some questions about reporting 19 or more lifetime uses of psilocybin[
their alcohol and drug use for a scienti_c study[ Drug interaction e}ects were not analysed for four
Of the 14 individuals contacted\ three declined to subjects who reported that they had never used
participate\ leaving a _nal sample of 11 subjects[ intoxicating levels of alcohol in combination with
Structured interviews were conducted orally and either LSD or psilocybin and for one participant
recorded via audio!tape[ Participants were assured who provided inconsistent\ and thus uncodable\
of their anonymity and informed that their audio! responses to interview questions[ Only partial
taped responses would remain strictly con_dential[ e}ects were analysed for two subjects who reported
The interview consisted of a series of standardized never having used intoxicating levels of alcohol with
open!ended questions designed to elicit information LSD\ and for two subjects who reported never hav!
about the participant|s previous experiences with ing used intoxicating levels of alcohol with psilo!
alcohol\ LSD\ and psilocybic mushrooms when cybin[
used alone or in combination[ In order to avoid any Pearson correlation coe.cients were calculated
possible investigator in~uence\ all questions about in order to determine the inter!rater reliabilities for
possible alcohol:hallucinogenic interactions were the coding of the interviews[ These analyses
always phrased as follows] have you ever used alco! revealed a very high concordance between raters
hol while under the in~uence of LSD "magic mush! for both LSDÐalcohol interactions "r  9=874\
rooms# or LSD "magic mushrooms# while under p ³ 9=990# and psilocybinÐalcohol interactions
the in~uence of alcohol< Did you notice any di}er! "r  9=760\ p ³ 9=990#[ An analysis of the interview
ence in the e}ect of either the alcohol or the LSD ratings revealed a striking antagonism of subjective
"magic mushrooms# when you used the two to! alcohol e}ects when it was used in combination
gether< What was the nature of the di}erence< Can with LSD "see Table 0#[ Speci_cally\ 75=6 per cent
you give me a speci_c example about a time when of the sample reported experiencing a complete
this happened< In order for a report to be con! blockade of subjective alcohol e}ects\ while the
sidered usable\ the subject had to have used at least remainder reported a diminished e}ect[ No di}er!
the minimum dose required to detect the subjective ences in subjective LSD e}ects were associated with
e}ects of each drug when used alone[ alcohol use in any of the subjects[ There was also a
Reported drug interaction e}ects were rated by weaker tendency for subjects to report a diminished
the principal investigator and by an independent e}ect of alcohol when used in conjunction with
rater who was blind to the study|s hypotheses[ Dis! psilocybic mushrooms\ with 59 per cent of the sam!
crepancies in the coding were resolved by having a ple noting a diminished e}ect\ 23 per cent reporting
second independent rater score any interviews in no change and 5=6 per cent reporting an enhanced
question[ Using a _ve!point Likert scale "0com! e}ect[ The majority of the sample "79 per cent# also
pletely blocked\ 1somewhat diminished\ 2neu! reported no change in psilocybin|s e}ects when it
tral\ 3somewhat enhanced\ 4strongly was used with alcohol[ However\ two subjects
enhanced#\ the raters _rst scored the reported e}ect reported a diminished e}ect\ and one subject
of alcohol when it was taken with LSD[ Using the reported an enhanced e}ect of psilocybin when used
same Likert scale\ the raters then coded the reported in combination with alcohol[ In addition\ one par!
e}ect of LSD when it was taken in conjunction with ticipant voluntarily reported experiencing a ple!
alcohol[ Ratings of reported e}ects of alcohol and asant synergistic e}ect when taking psilocybin with
psilocybin when the two drugs were used in com! alcohol\ while another participant reported having
bination were assessed in the same manner[ Raters a very unpleasant synergistic e}ect[
were instructed to eliminate cases in which inter! In order to compare the e}ects of LSD and psi!
viewer bias was present[ A complete transcript of locybin on the subjective response to alcohol\ a
all interviews is available from the authors upon paired samples t!test was performed[ This analysis
request[ revealed that LSD|s antagonism of the alcohol

Copyright Þ 1999 John Wiley + Sons\ Ltd[ Hum[ Psychopharmacol[ Clin[ Exp[ 04\ 448Ð454 "1999#

Table 0[ Subjective e}ects associated with concurrent use of alcohol and hallucinogens

Id Age Sex Estimated Estimated Concurrent use of Concurrent use of alcohol and
lifetime lifetime alcohol and LSD psilocybin
use of LSD use of psilocybin
Subjective Subjective Subjective Subjective
alcohol LSD alcohol psilocybin
e}ects e}ects e}ects e}ects

A 10 M 099Ð049 49Ð099 blocked no change no change no change

B 15 M 19 19 blocked no change no change no change
C 10 M 49 39Ð49 Ð Ð diminished diminished
G 14 M 59Ð89 59Ð89 blocked no change diminished no change
H 16 F 59Ð64 29Ð24 blocked no change Ð Ð
I 17 M 29Ð49 19Ð29 blocked no change diminished no change
J 13 M 14 49 blocked no change no change no change
K 17 M 09Ð14 09Ð14 blocked no change diminished no change
L 14 M 24 49 diminished no change diminished no change
M 13 M 39 49 blocked no change no change no change
P 13 M ×49 29Ð39 Ð Ð diminished no change
R 13 F 29 1 blocked no change Ð Ð
S 12 F 2 29 blocked no change no change diminished
T 13 M 14 29 blocked no change enhanced enhanced
U 15 M 199Ð299 49 blocked no change diminished no change
V 17 M 14 49 blocked no change diminished no change
W 11 M 04 29Ð24 diminished no change diminished no change

e}ect is signi_cantly greater than that associated to H\ LSDÐalcohol interactions work two ways[
with psilocybin t"01#  4=630\ p ³ 9=990[ {The _rst example would be if I were to use LSD
and then drink\ I wouldn|t feel any of the e}ects of
alcohol until after the e}ects of the LSD had worn
REPRESENTATIVE SUBJECTIVE REPORTS o} [ [ [ and if I were to take LSD once I was already
subjectively feeling drunk\ the alcohol e}ects would
LSDÐalcohol interactions go away after taking the LSD[|
G\ a 14!year!old male\ reported extensive experi! T\ a 13!year!old male\ reported using LSD on
ence with LSD\ using it on 59Ð89 separate 14 occasions[ T reported that there were several
occasions[ Typically\ G can begin to discern the occasions where he consumed an intoxicating dose
e}ects of alcohol after four drinks and it takes of alcohol "more than six drinks# while under the
approximately seven or eight drinks for G to in~uence of LSD[ According to T\ {You can|t get
become signi_cantly intoxicated[ According to G\ drunk when you are on LSD [ [ [ One time I drank
{When I was on LSD I found that no matter what about 07 beers\ a half bottle of Bailey|s and a
quantity of alcohol I consumed on the high\ I did Mickey of vodka on two hits of acid and I didn|t
not notice any of the e}ects of the alcohol|[ G feel anything from the booze [ [ [ it was just a normal
recalled one speci_c occasion when he drank LSD high[|
approximately 01 beers over the course of an eve!
ning after ingesting LSD] {[ [ [ at that point\ I didn|t
notice the e}ects of the alcohol at all[ I was not PsilocybinÐalcohol interactions
drunk\ nothing[ I just felt a little bloated[| B\ a 15!year!old male\ has used psilocybic mush!
H\ a 16!year!old female\ reported extensive rooms on 19 separate occasions[ When using alco!
experience with LSD\ using it on between 59 and hol concurrently with psilocybic mushrooms\ B
64 separate occasions[ She reported using an intoxi! claims that {I could feel a combination of both[ It is
cating dose of alcohol "more than seven drinks# in not like LSD where the alcohol e}ects are blocked[
combination with LSD {several| times[ According Sometimes one would be stronger than the other\

Copyright Þ 1999 John Wiley + Sons\ Ltd[ Hum[ Psychopharmacol[ Clin[ Exp[ 04\ 448Ð454 "1999#

but that would just depend on how much I took of partially diminished alcohol e}ects\ a full 39 per
each|[ cent of psilocybin users failed to report any anta!
L\ a 14!year!old male\ has used psilocybic mush! gonizing e}ect[ Because very little is known about
rooms on 49 separate occasions[ According to L\ the pharmacological actions of psilocybin\ and the
when using psilocybin with a normally intoxicating precise nature of the interaction between psilocybin
dose of alcohol "more than four drinks#\ {[ [ [ it pro! and alcohol was not clearly revealed by the present
duces a more mellow buzz[ The alcohol e}ect was data\ the remainder of the discussion will focus
deadened|[ When asked to compare this experience primarily on _ndings concerning the concurrent
with that of LSD\ {I could feel the alcohol more for administration of LSD and alcohol[
sure on mushrooms|[ Prior to commencing a discussion of hypo!
V\ a 17!year!old male\ reported 49 previous uses thesized means by which LSD could attenuate sub!
of psilocybic mushrooms\ including several jective alcohol e}ects\ it would seem appropriate to
occasions where he consumed a normally intoxi! address some possible limitations of the present
cating dose of alcohol "more than six drinks#[ study[ The _rst issue concerns whether or not study
According to V\ when using alcohol and psilocybic participants could reliably recount their experiences
mushrooms together] {You can tell that you|ve with the concurrent use of alcohol and hal!
drunk alcohol when on mushrooms\ but there lucinogenic drugs[ There are several indications
would be less of an e}ect [ [ [ you could feel it more that memory is not signi_cantly impaired by the
than when on LSD|[ administration of hallucinogens[ For example\
there are numerous reports that LSD experiences
can be accurately and vividly recalled "e[g[
DISCUSSION Hofmann\ 0879^ Abraham et al[\ 0885# suggesting
The present data indicate that the subjective that LSD intoxication has a negligible impact on
response to ethanol is strongly attenuated by the memory storage and retrieval[ The accuracy of rec!
administration of LSD[ Of the 04 LSD users who ollections reported by subjects in the present study
reported concurrent use of alcohol\ 02 reported a is further supported by the fact that most of these
complete blockade of alcohol|s subjective e}ects\ participants had extensive past hallucinogenic use
while the remaining two cases reported experi! and reported having used hallucinogens and alco!
encing a virtual elimination of subjective alcohol hol in combination on several occasions[ Thus\ par!
e}ects when the drug was combined with LSD[ The ticipants| responses to questions concerning
_nding that LSD|s antagonism of alcohol|s e}ects alcoholÐhallucinogen interaction e}ects were based
reportedly occurred irrespective of whether the sub! on numerous experiences rather than a single event
ject had consumed LSD prior to drinking or the and compared to their own extensive experience
LSD was ingested when already intoxicated further with hallucinogenic drugs alone or in combination[
supports the conjecture that LSD|s e}ect on the A second consideration concerns whether par!
subjective response to alcohol may be due to a direct ticipants| recollections of alcohol e}ects were sim!
pharmacological interaction[ In contrast to LSD\ ply overwhelmed by the hallucinogenic properties
the use of psilocybic mushrooms failed to fully anta! of LSD and:or psilocybin[ The observation that
gonize the subjective e}ects of alcohol[ Although participants were able to reliably distinguish
nine of the 04 psilocybin users reported a dimin! between LSD and psilocybin in terms of each drug|s
ished response to alcohol\ no participants reported e}ect on the subjective alcohol experience when
that the administration of psilocybin completely taken concurrently argues against this possibility[
blocked the subjective e}ects of alcohol[ Of the In addition\ participants were highly consistent in
remaining six participants\ _ve reported that psi! their reporting concerning both the nature and
locybin had no impact on their subjective response strength of alcoholÐdrug interactions\ despite their
to alcohol\ while the _nal subject stated that psi! di}erential drug histories and being blind to the
locybin actually enhanced the subjective e}ects of study|s hypotheses[ Finally\ the amount of alcohol
alcohol "i[e[ caused an increase in the subjective reportedly consumed by some participants while
sense of intoxication#[ Thus\ although some par! under the in~uence of LSD argues against the possi!
ticipants reported a tendency for psilocybin to bility that alcohol e}ects were simply overwhelmed
weaken the subjective e}ects of alcohol\ this e}ect by hallucinogen intoxication[ For example\ par!
was not as pronounced as that associated with LSD^ ticipant M described an occasion on which he had
while 099 per cent of LSD users reported at least 13 drinks following the use of LSD and T recalled

Copyright Þ 1999 John Wiley + Sons\ Ltd[ Hum[ Psychopharmacol[ Clin[ Exp[ 04\ 448Ð454 "1999#

drinking 07 beers\ a half bottle of liqueur and 02 interferes with alcohol|s discriminative stimulus
ounces of vodka while in a state of LSD intoxi! properties "Maurel et al[\ 0887#[ In their review
cation[ article\ Kostowski and Bienkowski "0888# refer to
While both the consistency and magnitude of such _ndings\ and conclude that serotonergic
reports of LSD|s e}ect on alcohol intoxication neurotransmission plays a key role in the formation
attest to its reliability\ it is important to note that of the ethanol cue\ and that this cue is primarily
in any retrospective study certain issues of potential mediated through 4!HT0B and 4!HT1C receptors[
bias may arise[ Because subjects were not randomly Unfortunately\ the precise nature of LSD|s
selected it remains possible that their experiences action at 4!HT0B remains unknown "Peroutka\
are not characteristic of all hallucinogenic drug 0883#[ The present discussion will therefore focus
users[ However\ this possibility was minimized by on the actions of LSD at 4!HT1C receptors[ LSD
the fact that participants were recruited from four displays partial agonist e}ects at 4!HT1C receptor
di}erent {communities| of drug users through snow! sites "Glennon\ 0889^ Fiorella et al[\ 0884^ Egan et
ball sampling[ It should also be noted that several al[\ 0887#[ Thus\ although LSD displays high a.n!
additional steps were taken to avoid possible inter! ity\ its agonist actions at 4!HT1C are of low e.cacy[
viewer bias[ First\ questions used for queries about Because LSD is a partial agonist at 4!HT1C recep!
potential drug interactions were standardized and tors\ the precise nature of its e}ect at these sites will
neutrally worded[ Second\ three di}erent inter! depend on available 4!HT concentrations and on
viewers were used and all interviews were blindly the presence of other 4!HT agonists and:or antag!
rated[ Finally\ raters were instructed to eliminate onists "Glennon\ 0889^ see also Bonson et al[\ 0885#[
cases were interviewer bias was present[ At low 4!HT concentrations and:or in the absence
The present data are consistent with the notion of another agonist\ LSD behaves as a low!e.cacy 4!
that there is a direct\ pharmacological interaction HT1C agonist\ achieving approximately 29 per cent
between LSD and alcohol[ Although the current maximal excitation "Marek and Aghajanian\ 0885^
methodology did not directly examine either of Egan et al[\ 0887#[ In the presence of a high e.cacy
these drugs| pharmacological e}ects\ LSD is known agonist "i[e[ at higher 4!HT concentrations#\ LSD
to act at various serotonergic and dopaminergic exerts its own maximal e}ect while suppressing the
receptor types "e[g[ Peroutka\ 0883^ Watts et al[\ receptor|s responsiveness to the other agonist\
0884# implicated in ethanol reinforcement "e[g[ thereby blocking the other agonist from achieving
Koob et al[\ 0887# and discriminative stimulus "e[g[ maximal excitation[ Under such conditions\ LSD
Kostowski and Bienkowski\ 0888#[ This raises the may thus appear to function as an antagonist[
possibility that LSD|s e}ect on the subjective LSD|s partial agonist actions are consistent with
response to alcohol may involve an action at one the hypothesis that LSD may prevent the level of
or more of these systems[ 4!HT1C excitation required for the alcohol cue to
LSD exerts e}ects at several 4!HT receptor sub! be subjectively experienced\ and this mechanism
types\ displaying a.nity for 4!HT0A\ 4!HT0B\ 4! may underlie the _ndings of the present study[
HT0D\ 4!HT0E\ 4!HT1A\ 4!HT1C\ 4!HT4A\ 4!HT4B\ 4! The hypothesis that LSD attenuates the ethanol
HT5\ and 4!HT6 "Peroutka\ 0883^ Bonson et al[\ cue in humans through such serotonergic mech!
0885#[ With respect to LSD|s multiple 4!HT anisms is consistent with the present observation
actions\ activity at 4!HT1C and:or 4!HT0B receptors that this e}ect was diminished or absent following
would seem to represent the best candidates for the administration of psilocybin[ Although LSD
LSD|s attenuation of subjective alcohol e}ects\ as and psilocybin are considered similar in terms of
these are the only 4!HT receptor subtypes that have subjective e}ects\ they di}er with regard to ser!
been directly implicated in the formation of the otonergic pharmacological properties[ For exam!
ethanol cue "Maurel et al[\ 0887^ Wilson et al[\ 0887^ ple\ LSD is known to bind to various 4!HT sites
Kostowski and Bienkowski\ 0888#[ Mixed 4! with a greater a.nity than psilocybin "Glennon
HT0B:1C receptor agonists completely generalize to et al[\ 0874^ McKenna et al[\ 0889#[ Furthermore\
the ethanol cue in rats "Kostowski and Bienkowski\ psilocybin is currently believed to act as a full agon!
0888^ Maurel et al[\ 0887^ Szeliga and Grant\ 0887#\ ist at 4!HT1 receptors "Vollenweider et al[\ 0887#\
and are known to produce ethanol!like responses whereas LSD acts as a partial agonist at these sites[
in humans "Kostowski and Bienkowski\ 0888#[ Evi! If\ as hypothesized\ LSD exerts an e}ect on the
dence also suggests that the blockade of 4!HT0B alcohol cue via suppression of the requisite 4!HT1
and 4!HT1C receptors\ alone or in combination\ response\ then one might expect psilocybin to fail

Copyright Þ 1999 John Wiley + Sons\ Ltd[ Hum[ Psychopharmacol[ Clin[ Exp[ 04\ 448Ð454 "1999#

to fully attenuate the subjective e}ects of alcohol[ or alcohol[ Indeed\ without a fuller characterization
Aside from its actions at 4HT receptors\ LSD of each of these drugs| e}ects\ interpretation of the
has also been demonstrated to exert partial agonist present results must remain largely speculative[
e}ects at dopamine D0 "Watts et al[\ 0884# and Despite the fact that the present analysis is unable
D1 "Giacomelli et al[\ 0887# receptors[ Midbrain to fully elucidate the mechanisms governing alco!
dopaminergic activity is thought to be critical for holÐhallucinogen interactions\ the present _ndings
the reinforcement of ethanol administration "e[g[ are highly relevant for several reasons[ First\ this
Koob et al[\ 0887#[ Although DA transmission is is\ to the best of the authors| knowledge\ the _rst
implicated in ethanol reinforcement\ there is cur! documentation of a recreational drug eliminating
rently only limited evidence to suggest that DA subjective alcohol e}ects in humans[ Further explo!
transmission substantially contributes to ethanol|s ration of the interaction between LSD and alcohol
subjective e}ects[ Blocking DA neurotransmission revealed by the present _ndings may ultimately
with preferential DA receptor antagonists does not enhance our understanding of the mechanisms that
appear to a}ect either the discriminative stimulus mediate the subjective e}ects of ethanol[ Second\
e}ects of alcohol in rats "Kostowski and Bien! evidence suggests that alcohol is often co!admin!
kowski\ 0888# or the subjective e}ects of alcohol in istered with hallucinogenic drugs "Martin et al[\
humans "Litten\ 0885#[ Although dopamine antag! 0885#[ Given the amounts of alcohol reportedly
onists fail to signi_cantly alter subjective ethanol consumed by some participants in the present study
e}ects\ there is nevertheless some indication that while under the in~uence of LSD and the illustrated
dopamine agonists may attenuate aspects of the potential for LSD to attenuate alcohol e}ects\ this
ethanol cue[ For example\ amphetamine\ a potent practice may pose signi_cant health risks[ Third\
DA receptor agonist\ has been reported to anta! this analysis demonstrates that\ despite the fact that
gonize ethanol e}ects in rats "Schechter\ 0863# and similarity between LSD and psilocybin has been
cocaine administration has been shown to attenuate assumed by some researchers "e[g[ Strassman\
the sedative e}ects of alcohol in humans "e[g[ Foltin 0881#\ there is likely some discordance in the phar!
et al[\ 0882#[ Such evidence suggests that LSD|s macological e}ects of these two hallucinogens[
blockade of subjective alcohol e}ects may relate to Finally\ this study illustrates a distinctive and e}ec!
its agonist activity at DA receptors[ Unlike LSD\ tive approach for delineating drugÐalcohol inter!
psilocybin does not display an a.nity for DA recep! actions in humans[
tors\ although there is some evidence that it may
increase DA transmission indirectly through ser!
otonergic mechanisms "e[g[ Vollenweider et al[\
0888#[ Nevertheless\ the di}erential a.nity of LSD
and psilocybin for DA receptors may help to Abraham HD\ Aldridge AM\ Gogia P[ 0885[ The psy!
explain reported di}erences in the e}ects of LSD chopharmacology of hallucinogens[ Neuropsycho!
and psilocybin on the subjective response to alco! pharmacolo`y 03] 174Ð187[
hol[ Bonson KR\ Buckholtz JW\ Murphy DL[ 0885[ Chronic
administration of serotonergic antidepressants atten!
In summary\ the subjective e}ects of alcohol are
uates the subjective e}ects of LSD in humans[ Neu!
antagonized by LSD and\ to a lesser extent\ by ropsychopharmacolo`y 03] 314Ð325[
psilocybin[ Although it is proposed that these Egan CT\ Herrick!Davis CT\ Miller K\ Glennon RA\
e}ects may be at least partly mediated by ser! Teitler M[ 0887[ Agonist activity of LSD and lisuride
otonergic and:or dopaminergic mechanisms\ at cloned 4!HT1A and 4!HT1C receptors[ Psy!
actions at either of these systems are likely to in~u! chopharmacol 025] 398Ð303[
ence a variety of physiological and neurochemical Fiorella D\ Rabin RA\ Winter JC[ 0884[ Role of 4!HT1A
processes and the interdependence among these and 4!HT1C receptors in the stimulus e}ects of hal!
should not be underestimated[ It should also be lucinogenic drugs II] reassessment of LSD false posi!
emphasized that the pharmacological pro_les of tives[ Psychopharmacolo`y 010] 246Ð252[
Foltin RW\ Fichman MW\ Pippen PA\ Kelly TH[ 0882[
alcohol and hallucinogens remain incompletely
Behavioral e}ects of cocaine alone and in combination
understood and more research is needed in order to with ethanol or marijuana in humans[ Dru` Alcohol
fully understand the precise nature of the inter! Depend 21] 82Ð095[
actions among these drugs[ This point is par! Giacomelli S\ Palmery M\ Romanelli L\ Cheng CY\ Sil!
ticularly relevant in the case of psilocybin\ which vestrini B[ 0887[ Lysergic acid diethylamide "LSD# is a
has not been examined as extensively as either LSD partial agonist of D1 dopaminergic receptors and it

Copyright Þ 1999 John Wiley + Sons\ Ltd[ Hum[ Psychopharmacol[ Clin[ Exp[ 04\ 448Ð454 "1999#

potentiates dopamine!mediated prolactin secretion in McKenna DJ\ Repke DB\ Lo L\ Peroutka SJ[ 0889[
lactotrophs in vitro[ Life Sci 52] 104Ð111[ Di}erential interactions of indolealkylamines with 4!
Glennon RA[ 0889[ Do classical hallucinogens act as 4! hydroxytryptamine receptor subtypes[ Neuropharma!
HT1 agonists or antagonists< Neuropsychopharma! colo`y 18] 082Ð087[
colo`y 2] 498Ð406[ Peroutka SJ[ 0883[ 4!Hydroxytryptamine receptor inter!
Glennon RA\ Titeler M\ McKenney JD[ 0874[ Evidence actions of D!lysergic acid diethylamide[ In 49 Years of
for 4!HT1 involvement in the mechanism of action of LSD] Current Status and Perspectives of Hallucino`ens\
hallucinogenic agents[ Life Sci 24] 1494Ð1400[ Plescher A\ Ladewig D "eds#[ Parthenon] New York^
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Hill] New York[ Schechter MD[ 0863[ E}ects of propranolol\ d!amphet!
Jackson W[ 0886[ Methods] Doin` Social Research[ Pren! amine and ca}eine on ethanol as a discriminative cue[
tice Hall] Scarborough[ Eur J Pharmacol 18] 41Ð46[
Koob GF\ Roberts AJ\ Schultes G\ Parsons LH\ Heyser Strassman RJ[ 0881[ Human hallucinogen interactions
CJ\ Hyytia P\ Merlo!Pich E\ Weiss F[ 0887[ Neuro! with drugs a}ecting serotonergic neurotransmission[
circuitry targets in ethanol reward and dependence[ Neuropsychopharmacolo`y 6] 130Ð132[
Alcohol Clin Exp Res 11] 2Ð8[ Szeliga KT\ Grant KA[ 0887[ Analysis of the 4!HT1
Kostowski W\ Bienkowski P[ 0888[ Discriminative stimu! receptor ligands dimethoxy!3!indophenyl!1!amino!
lus e}ects of ethanol] neuropharmacological charac! propane and ketanserin in ethanol discriminations[
terization[ Alcohol 06] 52Ð79[
Alcohol Clin Exp Res 11] 535Ð540[
Litten RZ[ 0885[ Pharmacotherapies for alcohol prob!
Vollenweider FX\ Vollenweider!Scherpenhuyzen MFI\
lems] a review of research with focus on development
Babler A\ Vogel H\ Hell D[ 0887[ Psilocybin induces
since 0880[ Alcohol Clin Exp Res 19] 748Ð765[
Mangini M[ 0887[ Treatment of alcoholism using psy! schizophrenia!like psychosis in humans via a sero!
chedelic drugs] a review of the program of research[ J tonin!1 agonist action[ NeuroReport 8] 2786Ð2891[
Psychoactive Dru`s 29] 270Ð307[ Vollenweider FX\ Vontobel P\ Hell D\ Leenders KL[
Marek GJ\ Aghajanian GK[ 0885[ LSD and the phene! 0888[ 4!HT modulation of dopamine release in basal
thylamine hallucinogen DOI are potent partial agon! ganglia in psilocybin!induced psychosis in man * a
ists at 4!HT1A receptors on interneurons in rat piriform PET study with ð00CŁraclopride[ Neuropsycho!
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Copyright Þ 1999 John Wiley + Sons\ Ltd[ Hum[ Psychopharmacol[ Clin[ Exp[ 04\ 448Ð454 "1999#