Psychopharmacology

DOI 10.1007/s00213-008-1424-0

ORIGINAL INVESTIGATION

Enhancement of suggestibility and imaginative ability

with nitrous oxide
M. G. Whalley & G. B. Brooks

Received: 27 May 2008 / Accepted: 19 November 2008

# Springer-Verlag 2008

Abstract
Rationale Imaginative suggestibility, a trait closely related
to hypnotic suggestibility, is modifiable under some
circumstances. Nitrous oxide (laughing gas) is commonly
used for sedation in dentistry and is reported to be more
effective when combined with appropriate suggestions.
Objective The aim of this study was to determine whether
nitrous oxide inhalation alters imaginative suggestibility
and imagery vividness.
Methods Thirty participants were tested twice in a withinsubjects design, once during inhalation of 25% nitrous
oxide and once during inhalation of air plus oxygen. Before
the study, participants expectancies regarding the effects of
nitrous oxide were assessed. Participants were blinded to
drug administration. During each session, participants were
verbally administered detailed measures of imagination and
suggestibility: the SheehanBetts Quality of Mental Imagery scale and the Stanford Hypnotic Susceptibility Scale
Form C, minus the hypnotic induction.
Results Imaginative suggestibility and imaginative ability
(imagery vividness) were both elevated in the nitrous oxide
condition. This effect was unrelated to participants expectations regarding the effects of the drug.
Conclusions Nitrous oxide increased imaginative suggestibility and imaginative ability. Possible explanations of
these findings are discussed with respect to the effects of Nmethyl-d-aspartate antagonists and to other pharmacological effects upon suggestibility and imagination.

M. G. Whalley (*) : G. B. Brooks

Hypnosis Unit, Department of Psychology,
University College London,
Gower Street,
London WC1E 6BT, UK
e-mail: matwhalley@gmail.com

Keywords Suggestibility . Nitrous oxide . Imagination .

Imaginative ability . Imagery . Hypnosis . Hypnotisability .
Suggestion . Vividness . NMDA

Introduction
Nitrous oxide (laughing gas) inhalation is a form of
conscious sedation and is an analgesic commonly used in
dentistry and also in obstetrics. It has long been noted by
dental practitioners that patients under nitrous oxide
sedation are particularly suggestible and a number of
investigators have noted the clinical advantages of using a
hypnotic voice when administering nitrous oxide (Lippe
1944; Seladin 1947). Bingham (1964) describes a case of
rapid hypnosis by using nitrous oxide and Allen (1972)
notes that during nitrous oxide sedation patients respond
well to suggestions given in a quiet, hypnotic manner.
Hilgard and Hilgard (1975) and Eysenck and Rees (1945)
also informally note that sub-anaesthetic doses of nitrous
oxide will heighten the hypnotic responsiveness of the
patient. If there is a synergistic relationship between nitrous
oxide inhalation and responsiveness to suggestions, then
strategic use of appropriate suggestions for relaxation and
analgesia should enhance the overall clinical effectiveness
of nitrous oxide sedation procedures (Simons et al. 2007).
Suggestibility can also be assessed in the absence of
hypnosis and is termed imaginative suggestibility (Kirsch
and Braffman 2001). Hypnotic inductions are commonly
used to modestly increase suggestibility (Kirsch and
Braffman 2001), and suggestibility can also be modified
by either changing peoples expectations (Vickery and
Kirsch 1991), labeling a situation as hypnotic (Gandhi
and Oakley 2005) or through training (Gorassini and
Spanos 1989). There is disagreement, however, about the

Psychopharmacology

magnitude to which suggestibility can be affected through

training programs (e.g. Benham et al. 1998; Spanos 1986).
One study that has systematically examined the effect
of nitrous oxide upon suggestibility involved 20 volunteers randomly divided into two groups (Barber et al.
1979). One group received nitrous oxide supplemented
with oxygen and the other group received oxygen alone. In
the nitrous oxide group, the dose was increased until a
baseline level giving paraesthesia and generalised warmth
was reached (2040%). When signalled by the anaesthetist,
both groups were read an identical list of suggestions
involving analgesia in one leg, compulsive behaviour
(picking up a pen) and amnesia. The group receiving
nitrous oxide responded to more suggestions, and the
authors report that this effect was unrelated to subsequently
measured hypnotic susceptibility. Unfortunately, it is not
clear whether nitrous oxide was administered throughout
the test session, or just for the period prior to the
suggestions, a detail that could particularly affect scores
on the analgesia item. In addition, the use of a betweensubjects design with a small N of hypnotically unselected
participants increases the likelihood of any effects being
due to uncontrolled pre-existing variations in responsiveness to suggestion.
The primary aim of the present study was to assess
whether nitrous oxide sedation is associated with changes
in suggestibility and imaginative ability, both measured in a
within-subject design using standardised scales. Nonhypnotic imaginative suggestibility, rather than hypnotic
suggestibility, was chosen in order to simplify the experimental procedure and to avoid any complications arising
from participants expectations regarding hypnosis. We
formally assessed participants beliefs about the effects of
nitrous oxide in order to determine whether any increase in
suggestibility was expectancy mediated.

Materials and methods

Participants
Participants in the study were 30 adults recruited from a
dental surgery in Manchester, England. A notice requesting
volunteers for a study of suggestibility and nitrous oxide
was posted in the waiting room and the first 30 participants
who volunteered and met the inclusion criteria were
accepted. Inclusion criteria were that participants should
be aged between 21 and 55 and not have any medical
problem contraindicating the administration of nitrous
oxide. Ethical approval was received from a University
Research Ethics Committee. Thirty participants completed
the study (ten males). Their average age was 40.06
(standard deviation (SD)=12.75).

Measures
All participants completed the SheehanBetts Quality of
Mental Imagery Scale (QMI; Sheehan 1967) and the
suggestions from the Stanford Hypnotic Susceptibility
Scale Form C (SHSS:C; minus the hypnotic induction;
Weitzenhoffer and Hilgard 1962). The QMI is a 35-item
test assessing the vividness of different modalities of mental
imagery (e.g. auditory, olfactory, tactile). It is a shortened
version of Betts (1909) original 150-item questionnaire.
The scale was modified by the authors for verbal
administration, but participants rated each item using the
original seven-point scale (1 = as clear and vivid as the real
thing; 7 = no image present at all, you only know you are
thinking of an object). Testretest reliability for the
SheehanBetts QMI has been found to be 0.75 for females
and 0.72 for males after 2 weeks (Westcott and Rosenstock
1976). Factor analyses of the questionnaire items have
revealed the presence of a large unitary factor corresponding to general vividness of imagery and modality
specific factors (Sheehan 1967; Wagman and Stewart 1974;
White et al. 1974).
The SHSS:C (Weitzenhoffer and Hilgard 1962) is a 12item test, individually administered according to a standardised procedure. The researcher administering the scale
objectively assesses participants responses to each item.
Suggestions on the test are progressively more difficult,
enabling the researcher to terminate the test after the failure
of three consecutive items. The SHSS:C was chosen for a
number of reasons. Firstly, it contains proportionately more
difficult items than other scales (Perry et al. 1992; Bertrand
1989), which is important to minimise any potential ceiling
effects. Secondly, it contains a high proportion of cognitive
items which we theorised might be less affected by
lethargic feelings brought about by nitrous oxide sedation.
As well as removing the hypnotic induction, we made a
number of other modifications to the SHSS:C in order to
increase its suitability for administering to participants
inhaling nitrous oxide. For the age regression item, the
American reference to school grades was omitted and
replaced with the terms junior school and infant school.
The anosmia to ammonia item was omitted to avoid having
to remove nose mask used for administration of the nitrous
oxide. A test of post-hypnotic suggestion modified from the
Stanford Hypnotic Susceptibility Scale Form A (SHSS:A;
Weitzenhoffer and Hilgard 1959) was added to replace the
anosmia item. Post-hypnotic amnesia was assessed by joint
criteria considering both initial amnesia and subsequent
reversibility. Amnesia was scored as present only if the
participants recalled both three or fewer critical items
initially and two or more additional items following the
reversal cue. The instructions for the reversibility test ask
subjects to report all items they remember. These mod-

Psychopharmacology

ifications have been used by other groups (Kihlstrom

2007). For the dream item (where participants are invited
to have a dream), the word hypnosis was replaced by
relaxation. The post-experimental interview was omitted
after the first visit because it was thought that these
questions might have affected the amnesia test for the
second visit. However, after the second visit, these
questions were included and the subject was asked to draw
comparisons between the two visits.
Procedures
Participants made two visits to the dental surgery, with a
gap of approximately 2 weeks. At the first visit, participants
were given information about the study and provided
informed consent. Participants were told that the study
was an investigation of responses to imaginative suggestions, which would produce changes in sensation and
perception. They were told that two sessions would be
involved but that nitrous oxide would only be administered
on one visit. Participants were explicitly told that the study
was not a test of hypnosis.
Half of the participants received the nitrous oxide on the
first visit and half on the second, randomised by a dental
nurse who was blind to the study hypothesis. At the start of
the first session, participants were asked whether they
thought the administration of nitrous oxide would affect
their suggestibility, which direction any effect might be in,
and the extent of this expectation on a scale ranging from
0% to 100%. The mask was then fitted to the participants
nose and they were given instructions to breathe through
the nose. Participants were made aware that breathing
through the mouth would stop the gas from working.
Nitrous oxide was delivered by a McKesson 882 continuous flow machine (McKesson Equipment Company,
Chesterfield, UK). The nose mask was scented in order to
disguise the sweet smell of the nitrous oxide. During the
non-nitrous oxide visit, the mask was placed in position and
the air intake valve left open, with oxygen still delivered at
3 L/min. This gave a mixture of oxygen diluted with air so
that the subject could still feel and hear gas flowing through
the mask. For the nitrous oxide session, the flow rate was
increased slowly until 25% nitrous oxide was being
delivered. The nitrous oxide and oxygen were always
administered by the experimenter (GB).
At both sessions, the SheehanBetts Quality of Mental
Imagery Scale (Sheehan 1967) and the suggestions from the
Stanford Hypnotic Susceptibility Scale Form C (minus the
hypnotic induction) (Weitzenhoffer and Hilgard 1962) were
administered by the same experimenter (GB) who was not
blind to the drug administration condition. For the QMI,
participants were asked to close their eyes to listen to the
description of each item and to imagine it as vividly as

possible, then to open their eyes and rate the item using the
scale. After the final item of the QMI, participants were
asked to open their eyes and the investigator checked that
they were feeling alright.
In the present investigation, the hypnotic induction that
normally precedes the suggestions on the SHSS:C was
omitted, making it a test of imaginative suggestibility
(Kirsch and Braffman 2001). Administration of suggestions
was conducted according to the manual. During the count
down to normal alertness at the end of the SHSS:C, which
was timed to last for 2 min, 100% oxygen was administered. This was to prevent diffusion hypoxia during
emergence since the inhaled air (21% oxygen) is diluted
by the rapid excretion of nitrous oxide, nitrogen being
absorbed only slowly (Cass and Cass 1994).
The QMI was always delivered first because of the
relative complexity of the SHSS:C. During the alerting
phase of the final item of the SHSS:C, the delivery of
nitrous oxide or oxygen was stopped and the participant
was questioned about their memory for items in the test,
followed by the SHSS:C post-experimental interview.
Counterbalanced administration of the tests would have
required restarting delivery of nitrous oxide after this
alerting phase, and it was considered more feasible to
deliver the tests in a single order with nitrous oxide delivery
uninterrupted. At the end of the second session, participants
were asked during which session they thought had received
the nitrous oxide.

Results
Four patients dropped out after completing one session;
they were replaced and their data were not used in the
analysis. Imaginative ability measured by the Sheehan
Betts QMI was greater in the nitrous oxide condition
(85.83, SD = 37.63) than the oxygen alone condition
(111.63, SD=37.77; lower scores on the QMI indicate
higher imaginative ability). Imaginative suggestibility measured by the SHSS:C was greater in the nitrous oxide
condition (7.33, SD=2.80) than the oxygen alone condition
(6.16, SD=2.47).
To test for potential order effects, we included order of
drug administrations as a factor in our analysis (group 1:
first session = drug, second session = no drug; group 2: first
session = no drug, second session = drug). Groups did not
differ with respect to age (t(28)=0.253, p=0.802). A
mixed-model analysis of variance with drug as a withinsubjects factor (nitrous oxide vs. oxygen) and group as a
between-subject factor was conducted for scores on the
SHSS:C and the QMI. For scores on the SHSS:C, there was
no main effect of group (F(1,28)=0.483, p=0.493) and no
drug group interaction (F(1,28)=1.128, p=0.297). For

Psychopharmacology

scores on the SheehanBetts QMI, there was no main effect

of group (F(1,28)=2.075, p=0.161) and no drug group
interaction (F(1,28)=0.806, p=0.377). For scores on the
SHSS:C, there was a main effect of drug (F(1,28)=11.418,
p=0.002, effect size (partial 2)=0.290). For scores on the
QMI, there was a main effect of drug (F(1,28)=42.957,
p<0.001, effect size (partial 2)=0.605).
To see whether nitrous oxide affected certain classes of
suggestion more than others, response rates for each
suggestion were assessed. The percentage pass rates for
each are given in Table 1.
Participants scores on the QMI were broken down by
the modality of each item in order to assess whether any
particular modality was more affected by the administration
of nitrous oxide. Average scores per item are given in Fig. 1
(lower scores equate to higher imagery vividness). Items in
all categories (visual, auditory, touch, movement, taste,
smell, sensation) were significantly more vividly imagined
in the nitrous oxide than in the oxygen condition (by
modality, respectively: t(4)=5.41, p=0.003; t(4)=15.5,
p<0.001; t(4)=5.46, p=0.002; t(4)=6.35, p=0.001; t(4)=
30.45, p<0.001; t(4)=4.18, p=0.007; t(4)=4.9, p=0.004).
Only 11 participants (36.7%) correctly judged which
session they had received nitrous oxide. A binomial test
revealed that this proportion does not differ significantly
from what would be expected by chance (p=0.201) and
indicates that participants were unaware when they were
being administered the nitrous oxide. In order to formally
assess whether changes in suggestibility were affected or
driven by participants expectancy, we examined changes in
suggestibility as a function of participants expectations.
Two participants expected the nitrous oxide to have no
effect upon suggestibility, 19 did not know and nine
participants expected the nitrous oxide to increase suggest-

ibility. The participants who expected an increase were

asked to estimate the size of the effect on a 100-mm visual
analogue scale bounded by the terms no change and large
change. The average magnitude of expected increase was
67.19 (standard deviation 11.27). The correlation between
expected suggestibility change (Dont know responses
assumed to have a magnitude of zero) and actual suggestibility change (difference in scores between the nitrous
oxide and oxygen conditions) was small and non-significant (r=0.039, p=0.838 (two tailed)).
Change scores for imaginative suggestibility and imaginative ability (differences in scores between the nitrous
oxide and oxygen conditions) were calculated by subtracting the oxygen score from the nitrous oxide score. These
two change scores for each participant were then correlated
to determine whether there was an association, revealing a
significant relationship (r=0.511, p=0.004 (two tailed)).
Lower scores on the QMI indicate higher imaginative
ability; thus, there exists a positive relationship between
changes in imaginative ability and changes in imaginative
suggestibility.
In the oxygen-alone condition, scores for imaginative
ability and suggestibility were significantly correlated (r=
0.312, p=0.0465 (one-tailed)). However, in the nitrous
oxide condition, the relationship was non-significant (r=
0.194, p=0.152 (one-tailed)).

Discussion
This investigation demonstrates, for the first time with a
standardised test, that inhalation of 25% nitrous oxide
produces objectively assessed increases in imaginative
suggestibility. Nitrous oxide also increased imaginative

Table 1 Percentage pass rates and Z and p values (Wilcoxon-related samples) for items of the SHSS:C when participants were inhaling either
nitrous oxide or oxygen
SHSS:C item

Item class

Auditory hallucination
Moving hands apart
Post-hypnotic suggestion
Hand lowering
Dream
Taste hallucination
Arm rigidity
Post-hypnotic amnesia
Negative visual hallucination
Age regression
Mosquito hallucination
Arm immobilisation

Cognitive (production)
Motor (inhibition)
Cognitive
Motor (production)
Cognitive
Cognitive
Challenge
Cognitive
Cognitive (inhibition)
Cognitive
Cognitive
Motor (inhibition)

N20 nitrous oxide

*p < 0.05, **p < 0.01

Percentage pass
oxygen

Percentage
pass N20

Difference
(N20oxygen)

6.6
96.6
30
90
56.6
43.3
63.3
40
10
56.6
63.3
53.3

3.3
96.6
33.3
93.3
63.3
50
70
53.3
26.6
73.3
80
80

-3.3
0
3.3
3.3
6.7
6.7
6.7
13.3
16.6
16.7
16.7
26.7

0.277
1
0.333
1
0.577
0.707
1.414
1.155
2.236
2.236
1.89
2.53

p (1-tailed)

0.282
0.5
0.3695
0.1585
0.282
0.24
0.0785
0.124
0.0125*
0.0125*
0.0295*
0.0055**

Psychopharmacology
4

Average Vividness Score Per Item

Fig. 1 Scores on the QMI broken down by modality and drug

administration. Note: Lower
scores indicate higher imaginative ability

3.5

Nitrous Oxide
Oxygen

3
2.5
2
1.5
1
0.5
0

Visual

Auditory

Touch

Movement

Taste

Smell

Sensation

QMI Item Modality

ability, a change strongly correlated with the increase in

suggestibility. The magnitude of the change in suggestibility induced by the inhalation of 25% nitrous oxide
approached 10%. It is difficult to estimate a similar statistic
for the imaginative ability scores because of the non-linear
nature of the QMI scale, although with nitrous oxide
inhalation average item ratings on the QMI improved from
approximating moderately clear and vivid towards very
clear and comparable in vividness to the actual experience.
Increases in imaginative ability under nitrous oxide
sedation were not greater in any particular sensory type,
indicating enhancement across the range of imaginative
modalities. It is difficult to gauge the relative effects of
nitrous oxide inhalation on different types of suggestion
(motor, challenge, cognitive) because of the relative
weighting of the SHSS:C towards cognitive items. The
item demonstrating the single largest effect of nitrous oxide
was the arm immobilisation (motor inhibition) item,
although it is probable that this was due to participants
feeling relaxed and heavy whilst inhaling the gas. Only one
challenge item (arm rigidity) was included and demonstrated a modest increase. The nitrous oxide induced increase in
suggestibility for cognitive items ranged from 3.3% for an
auditory hallucination (friends voice speaking) item to
+16.7% for the mosquito hallucination and age regression
items.
Previous studies have reported modest and uneven
associations between imaginative ability and hypnotic
suggestibility using a variety of measurement instruments
(Sutcliffe et al. 1970; Crawford 1982; Glisky et al. 1995;
for a review see de Groh 1989). The present study is novel
in that it measures suggestibility in the absence of a
hypnotic induction, yet the correlations found here are
within the range found in previous studies, with a
significant relationship demonstrated only in the non-drug
condition.
Alterations in suggestibility are most commonly brought
about by the induction of hypnosis (Kirsch and Braffman

2001) but have also been demonstrated via manipulations

in expectancy (Vickery and Kirsch 1991), labelling a
situation as hypnotic (Gandhi and Oakley 2005) or
undergoing a skills training programme (Gorassini and
Spanos 1989). In order to assess whether the effects of
inhaling nitrous oxide on suggestibility were due to an
expectancy effect, we measured participants expectancies
at the start of the experiment. Only one third of participants
expected the drug to increase suggestibility, with the
majority answering that they did not know. Participants
were not very accurate in identifying when nitrous oxide
was being administered, with just over a third identifying in
which condition they received the drug, further supporting
our conclusion that expectancies did not mediate the
observed effect. Lastly, we did not find expectancies to be
related to the magnitude of changes in suggestibility. These
results indicate the presence of a genuine drug effect upon
suggestibility. Unlike other modifiers of suggestibility such
as response expectancy (Kirsch 1985), the present effect
seems to be independent of participants expectations about
the effect of the drug.
In the absence of an expectancy-mediated effect, it is
interesting to speculate upon possible mechanisms by
which nitrous oxide might mediate changes in suggestibility and imaginative ability. The strong correlation between
changes in suggestibility and imaginative ability could
indicate a drug effect upon a mechanism common to both
of these changes. Nitrous oxide is one of the most widely
used yet least well understood anaesthetic gasses (Franks
and Lieb 1998) and until recently, relatively little was
known about the mechanism of its action. JevtovicTodorovic et al (1998) found that nitrous oxide, like
ketamine, acts as an antagonist at glutamatergic N-methyld-aspartate (NMDA) receptors, which are found throughout
the brain but are densely located in the hippocampus and
cerebral cortex (Morgan et al. 2004). NMDA receptor
antagonists seem to preferentially block NMDA receptors
on inhibitory GABAergic inter-neurons and thus increase

0.54
36
27.5

SSS:A/B Stanford Suggestibility Scale Form A/B, SHSS:A/B Stanford Hypnotic Susceptibility Scale Form A/B, HGSHS Harvard Group Scale of Hypnotic Susceptibility
a
Weitzenhoffer and Sjoberg (1961)
b
Weitzenhoffer and Hilgard (1959)
c
Shor and Orne (1962)

0.06
1.8
1.1
2.56
3.3
2.4
2.5
1.5
1.3
No
No
No
Control (no drug)
Nitrous oxide
Nitrous oxide
Barber et al (1979)

Kelly et al (1978)

Gibson et al (1977)

18
20
20

HGSHSc
Purpose built
Purpose built (excluding
analgesia)

11
5
4

22.6
2.49
4.18
1.69
No

Until quite a bit high, average=

834 mg
NA
2040%
2040%

17

HGSHSc

11

12.7
12.8
0.66
11.75
0.91
0.41
2.16
1.54
0.08
1.41
0.11
0.05
5.5
5.16
3.54
4.75
4.55
5.29
3.33
3.62
3.45
3.33
4.44
5.24
No
No
No
No
Yes
Yes

Mescaline
LSD-25
Psilocybin
Combination
Diazepam
Placebo (nicotinic
acid)
Cannabis
Sjoberg and Hollister
(1965)

5 mg/kg
1.5 mcg/kg
225 mcg/kg
1/3 of each of above
5 mg
50 mg

24
24
24
24
34
37

SSS:A/Ba
SSS:A/Ba
SSS:A/Ba
SSS:A/Ba
SHSS:A/Bb
SHSS:A/Bb

17
17
17
17
12
12

Absolute
Nondrug

Drug

Suggestibility change
Suggestibility

No.
items
Hypnotic
induction?
Suggestibility scale
Number
Dose
Drug
Study

Table 2 Details of previous studies investigating pharmacological manipulation of suggestion

glutamatergic transmission via non-NMDA Glu receptors

(such as -amino-3-hydroxy-5-methyl-4-isoxazole propionate and kainite), which increases excitatory activity
generally.
A brain-wide excitation might explain the present nitrous
oxide induced increase in imagery vividness. The current
consensus is that most of the neural processes that underlie
like-modality perception are also used in imagery (Kosslyn
et al. 2001), and a brain-wide excitation could explain the
increases in vividness observed here across the full range of
imagery modalities. Modality-appropriate sensory activation has also been observed in response to hypnotic
suggestion (e.g. Szechtman et al. 1998; Kosslyn et al.
2000; Derbyshire et al. 2004), although the mechanism by
which suggestions are experienced with an involuntary
quality is thought to be the product of frontally mediated
executive control systems (e.g. Brown and Oakley 2004;
Dienes and Perner 2007). The suggestibility enhancement is
more difficult to explain via a global excitation and it is
useful to consider the effects of other drugs upon
suggestibility.
Little research has investigated the effects of other drugs
upon suggestibility in a controlled manner. Sjoberg and
Hollister (1965) administered lysergic acid diethylamide
(LSD), mescaline and psilocybin separately and in combination to participants and measured imaginative suggestibility before and after drug administration. Gibson et al
(1977) measured the effect of benzodiazepine administration upon hypnotic suggestibility, and Kelly et al (1978)
tested the effect of cannabis intoxication upon the
imaginative suggestibility of participants initially scoring
low to medium on a standardised scale. Details of these
studies and the resulting changes in suggestibility are
given in Table 2. The greatest changes in suggestibility, in
order of decreasing size, are evident after administration of
nitrous oxide, cannabis, LSD, mescaline, combination of
[LSD+mescaline+psilocybin] and diazepam.
Sjoberg and Hollister cautiously interpreted the increases
they observed for LSD, mescaline and psilocybin as a result
of the withdrawal from active reality testing as a result of
drug administration. Despite the advancement of cognitive
models of response to suggestion (e.g. Brown and Oakley
2004; Dienes and Perner 2007), not enough is known about
specific neuroanatomical correlates of such effects to allow
prediction of physiological effects upon suggestion (Ott
2007). The fact that such a wide range of drugs with
varying pharmacological properties have been demonstrated to affect suggestibility argues for a non-specific effect of
drug upon suggestion: It is plausible that feeling sedated,
dissociated, or in an altered state of consciousness with
reality-testing impaired might lead participants to think they
are less in control of their actions and cognitions, in turn
leading to stronger endorsement of suggested effects

Percentage

Psychopharmacology

Psychopharmacology

(c.f. Sjoberg and Hollister 1965). Hilgard (1986) describes

the effect of a hypnotic induction (which increases
suggestibility by similar amounts to the drug effects seen
here) as a manipulation which impairs memory and reduces
reality testing, meaning that response to the stimulation
provided by the hypnotist takes precedence over planned or
self-initiated action, resulting in the voice of the hypnotist
becoming unusually persuasive (cf. Gorasini 2004). Future
studies of the effects of drugs upon suggestibility should
formally assess experiences of dissociation, relaxation,
sedation and alterations in consciousness (Pekala and
Kumar 2007).
Numerous studies have demonstrated powerful euphoric
and dysphoric effects of nitrous oxide administration (for a
review, see Walker and Zacny 2005) and it is therefore
worth briefly considering the possibility of a mediating
effect of emotion upon the present increases in imaginative
ability and suggestibility. Holmes and Matthews (2005)
briefly review the sparse literature on imagery and emotion
and note that despite much theory and speculation, there is
little empirical research. They found that instructions to
imagine aversive events led to greater increases in reported
anxiety than instructions to focus on the verbal meaning of
the same descriptions. Whether anxiety or other emotional
states led to increased vividness of imagery is currently
unresolved, but future studies should closely assess the
subjective effects of drug administration upon affect and
look for interactions with imagery vividness.
There is an important caveat to the aforementioned
results. The present study was single blind; although
participants were unaware of whether they were receiving
the drug, the experimenter who delivered the drug also
administered the tests of imaginative ability and suggestibility. The QMI and SHSS:C were scripted and manualised; nevertheless, it is possible that the observed
differences are due to some degree to demand characteristics and may not solely represent genuine drug effects
(Orne 1962). Such a factor means that the present results
should be considered preliminary and require confirmation
by a double-blind study. The present results raise a number
of other questions for future research. In this study, nitrous
oxide concentration was fixed at 25%, low enough to avoid
causing noticeable side effects, and fixed to avoid having
the experimenter make a necessarily subjective judgment
about how much effect the drug was having (as in Barber et
al. 1979). Since drug concentration in the current study was
fixed at a relatively low 25%, it will be important to
determine whether there is a doseresponse relationship
between drug administration, suggestibility and imaginative
ability. Additionally, we are concerned that the objective
scoring criterion for each suggestibility item used in the
present study may have masked more subtle effects in how
strongly each suggestion was perceived and recommend the

additional use of subjective assessment of response to

suggestion. Similarly, a measure of imaginative ability
using an interval linear scaling might be preferable to the
ordinal responses required by the QMI, and a number of
theoretically derived measures of imagery have recently
been developed (McAvine and Robertson 20062007).
Practically, since the objective of clinicians is to maximise
responsiveness to suggestion, it will be interesting to see
whether nitrous oxide administration plus a hypnotic
induction would increase suggestibility additively. Finally,
since nitrous oxide also has analgesic effects, it will be
interesting to see how these interact with suggestions for
analgesia since many clinicians informally report a synergistic effect between the two (Simons et al. 2007).
Hypnosis in combination with conscious sedation has been
shown to be clinically superior to conscious sedation plus
alternative psychological approaches (Faymonville et al.
1997), and it will be important to test the analgesic
properties of nitrous oxide alone and in combination with
hypnotic suggestion.
Acknowledgements The authors would like to thank David Oakley,
Irving Kirsch, and Celia Morgan for their helpful comments during the
preparation of this manuscript.

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