Background/Aims: Little research effort has so far been dedicated to the analysis of the hypothalamic-pituitary-adrenal axis of aetiologically differing subgroups of patients with panic disorder (PD). The current study aimed at a deeper understanding of the cortisol stress response in cannabis-induced PD (CIPD) patients. Methods: Matched groups of 7 PD patients (mean age ± SD: 32.95 ± 9.04 years), 7 CIPD patients (31.94 ± 8.40 years), and 7 healthy controls (HC) (31.13 ± 8.57 years) were included in the study. The Trier Social Stress Test (TSST) was used for stress induction. Salivary cortisol samples were collected and panic- and depression-related questionnaires were applied. Results: A stress response to the TSST was found in 28.6% of PD patients, in 51.1% of CIPD patients, and in 100% of HC subjects. Statistical analyses revealed a cortisol hyporesponsiveness in PD and CIPD patients. While cortisol values of PD patients and HC participants differed significantly, CIPD patients’ cortisol courses balanced between those of PD patients and HC subjects. Conclusions: Current findings show a distinctive pattern of the stress-induced cortisol reaction in CIPD patients, which is markedly different from the hormonal response in PD patients as well as HC subjects. Previous findings of cortisol hyporesponsiveness in PD patients compared to HC subjects were confirmed.

1.
American Psychiatric Association
.
Diagnostic and statistical manual of mental disorders
, fourth edition (DSM-IV-TR). Washington, DC: American Psychiatric Association. At risk for panic disorder. Biol Psychiatry.
2004
;57:1485-1492.
2.
Jacobi
F
,
Höfler
M
,
Strehle
J
,
Mack
S
,
Gerschler
A
,
Scholl
L
, et al
.
Psychische Störungen in der Allgemeinbevölkerung : Studie zur Gesundheit Erwachsener in Deutschland und ihr Zusatzmodul Psychische Gesundheit (DEGS1-MH)
.
Nervenarzt
.
2014
Jan
;
85
(
1
):
77
87
.
[PubMed]
0028-2804
3.
Wittchen
HU
,
Jacobi
F
.
Angststörungen
.
Berlin
:
Gesundheitsberichterstattung des Bundes
;
2004
.
4.
Zvolensky
MJ
,
Lewinsohn
P
,
Bernstein
A
,
Schmidt
NB
,
Buckner
JD
,
Seeley
J
, et al
.
Prospective associations between cannabis use, abuse, and dependence and panic attacks and disorder
.
J Psychiatr Res
.
2008
Oct
;
42
(
12
):
1017
23
.
[PubMed]
0022-3956
5.
Abelson
JL
,
Khan
S
,
Liberzon
I
,
Young
EA
.
HPA axis activity in patients with panic disorder: review and synthesis of four studies
.
Depress Anxiety
.
2007
;
24
(
1
):
66
76
.
[PubMed]
1091-4269
6.
Coryell
W
,
Noyes
R
Jr
,
Schlechte
J
.
The significance of HPA axis disturbance in panic disorder
.
Biol Psychiatry
.
1989
Apr
;
25
(
8
):
989
1002
.
[PubMed]
0006-3223
7.
Petrowski
K
,
Wintermann
GB
,
Joraschky
P
,
Siepmann
M
.
HPA Axis Activity under Psychosocial Stress in Patients with Acute and Remitted Panic Disorder
.
Ger J Psychiatry
.
2011
;
14
:
72
9
.1433-1055
8.
Petrowski
K
,
Herold
U
,
Joraschky
P
,
Wittchen
HU
,
Kirschbaum
C
.
A striking pattern of cortisol non-responsiveness to psychosocial stress in patients with panic disorder with concurrent normal cortisol awakening responses
.
Psychoneuroendocrinology
.
2010
a
Apr
;
35
(
3
):
414
21
.
[PubMed]
0306-4530
9.
Petrowski
K
,
Wintermann
GB
,
Schaarschmidt
M
,
Bornstein
SR
,
Kirschbaum
C
.
Blunted salivary and plasma cortisol response in patients with panic disorder under psychosocial stress
.
Int J Psychophysiol
.
2013
Apr
;
88
(
1
):
35
9
.
[PubMed]
0167-8760
10.
van Duinen
MA
,
Schruers
KR
,
Jaegers
E
,
Maes
M
,
Griez
EJ
.
Salivary cortisol in panic: are males more vulnerable
.
Neuro Endocrinol Lett
.
2004
Oct
;
25
(
5
):
386
90
.
[PubMed]
0172-780X
11.
Stephens
MA
,
Wand
G
.
Stress and the HPA axis: role of glucocorticoids in alcohol dependence
.
Alcohol Res
.
2012
;
34
(
4
):
468
83
.
[PubMed]
2168-3492
12.
Stinson
FS
,
Ruan
WJ
,
Pickering
R
,
Grant
BF
.
Cannabis use disorders in the USA: prevalence, correlates and co-morbidity
.
Psychol Med
.
2006
Oct
;
36
(
10
):
1447
60
.
[PubMed]
0033-2917
13.
King
GR
,
Ernst
T
,
Deng
W
,
Stenger
A
,
Gonzales
RM
,
Nakama
H
, et al
.
Altered brain activation during visuomotor integration in chronic active cannabis users: relationship to cortisol levels
.
J Neurosci
.
2011
Dec
;
31
(
49
):
17923
31
.
[PubMed]
0270-6474
14.
Ranganathan
M
,
Braley
G
,
Pittman
B
,
Cooper
T
,
Perry
E
,
Krystal
J
, et al
.
The effects of cannabinoids on serum cortisol and prolactin in humans
.
Psychopharmacology (Berl)
.
2009
May
;
203
(
4
):
737
44
.
[PubMed]
0033-3158
15.
van Leeuwen
AP
,
Creemers
HE
,
Greaves-Lord
K
,
Verhulst
FC
,
Ormel
J
,
Huizink
AC
.
Hypothalamic-pituitary-adrenal axis reactivity to social stress and adolescent cannabis use: the TRAILS study
.
Addiction
.
2011
Aug
;
106
(
8
):
1484
92
.
[PubMed]
0965-2140
16.
Petrowski
K
,
Wichmann
S
,
Kirschbaum
C
.
Stress-induced pro- and anti-inflammatory cytokine concentrations in panic disorder patients
.
Psychoneuroendocrinology
.
2018
Aug
;
94
:
31
7
.
[PubMed]
0306-4530
17.
Brown
TT
,
Dobs
AS
.
Endocrine effects of marijuana
.
J Clin Pharmacol
.
2002
Nov
;
42
S1
:
90S
6S
.
[PubMed]
0091-2700
18.
Wittchen
HU
,
Zaudig
M
,
Fydrich
T
. SKID Strukturiertes Klinisches Interview für DSM-IV Achse I und II Handanweisung.
SKID Strukturiertes Klinisches Interview für DSM-IV Achse I und II Handanweisung
.
Göttingen
:
Hogrefe
;
1997
.
19.
Kirschbaum
C
,
Pirke
KM
,
Hellhammer
DH
.
The ‘Trier Social Stress Test’—a tool for investigating psychobiological stress responses in a laboratory setting
.
Neuropsychobiology
.
1993
;
28
(
1-2
):
76
81
.
[PubMed]
0302-282X
20.
Bandelow
B
.
Assessing the efficacy of treatments for panic disorder and agoraphobia. II. The Panic and Agoraphobia Scale
.
Int Clin Psychopharmacol
.
1995
Jun
;
10
(
2
):
73
81
.
[PubMed]
0268-1315
21.
Derogatis
L
.
SCL-90-R: Administration, scoring and Procedures Manual-I for the R (evised)
.
Baltimore
:
Version
;
1977
.
22.
Geiser
F
,
Imbierowicz
K
,
Conrad
R
,
Schilling
G
,
Liedtke
R
.
[Differences between patients classified as “recovered” or “improved” and “unchanged” or “deteriorated” in a psychotherapy outcome study]
.
Z Psychosom Med Psychother
.
2001
;
47
(
3
):
250
61
.
[PubMed]
1438-3608
23.
Chambless
DL
,
Caputo
GC
,
Bright
P
,
Gallagher
R
.
Assessment of fear of fear in agoraphobics: the body sensations questionnaire and the agoraphobic cognitions questionnaire
.
J Consult Clin Psychol
.
1984
Dec
;
52
(
6
):
1090
7
.
[PubMed]
0022-006X
24.
Chambless
DL
,
Caputo
GC
,
Jasin
SE
,
Gracely
EJ
,
Williams
C
.
The mobility inventory for agoraphobia
.
Behav Res Ther
.
1985
;
23
(
1
):
35
44
.
[PubMed]
0005-7967
25.
Foley
P
,
Kirschbaum
C
.
Human hypothalamus-pituitary-adrenal axis responses to acute psychosocial stress in laboratory settings
.
Neurosci Biobehav Rev
.
2010
Sep
;
35
(
1
):
91
6
.
[PubMed]
0149-7634
26.
Harris
DS
,
Reus
VI
,
Wolkowitz
OM
,
Mendelson
JE
,
Jones
RT
.
Repeated psychological stress testing in stimulant-dependent patients
.
Prog Neuropsychopharmacol Biol Psychiatry
.
2005
Jun
;
29
(
5
):
669
77
.
[PubMed]
0278-5846
27.
Gaab
J
.
PASA - Primary appraisal secondary appraisal
.
Verhaltenstherapie
.
2009
;
19
(
2
):
114
5
. 1016-6262
28.
Miller
R
,
Plessow
F
,
Kirschbaum
C
,
Stalder
T
.
Classification criteria for distinguishing cortisol responders from nonresponders to psychosocial stress: evaluation of salivary cortisol pulse detection in panel designs
.
Psychosom Med
.
2013
Nov-Dec
;
75
(
9
):
832
40
.
[PubMed]
0033-3174
29.
Hoehn
T
,
Braune
S
,
Scheibe
G
,
Albus
M
.
Physiological, biochemical and subjective parameters in anxiety patients with panic disorder during stress exposure as compared with healthy controls
.
Eur Arch Psychiatry Clin Neurosci
.
1997
;
247
(
5
):
264
74
.
[PubMed]
0940-1334
30.
Armario
A
.
Activation of the hypothalamic-pituitary-adrenal axis by addictive drugs: different pathways, common outcome
.
Trends Pharmacol Sci
.
2010
Jul
;
31
(
7
):
318
25
.
[PubMed]
0165-6147
31.
Leyton
M
,
Bélanger
C
,
Martial
J
,
Beaulieu
S
,
Corin
E
,
Pecknold
J
, et al;
N.M.K. Ng Ying Kin
.
Cardiovascular, neuroendocrine, and monoaminergic responses to psychological stressors: possible differences between remitted panic disorder patients and healthy controls
.
Biol Psychiatry
.
1996
Sep
;
40
(
5
):
353
60
.
[PubMed]
0006-3223
32.
Sinha
SS
,
Coplan
JD
,
Pine
DS
,
Martinez
JA
,
Klein
DF
,
Gorman
JM
.
Panic induced by carbon dioxide inhalation and lack of hypothalamic-pituitary-adrenal axis activation
.
Psychiatry Res
.
1999
May
;
86
(
2
):
93
8
.
[PubMed]
0165-1781
33.
King
A
,
Munisamy
G
,
de Wit
H
,
Lin
S
.
Attenuated cortisol response to alcohol in heavy social drinkers
.
Int J Psychophysiol
.
2006
Mar
;
59
(
3
):
203
9
.
[PubMed]
0167-8760
34.
Zhang
GF
,
Ren
YP
,
Sheng
LX
,
Chi
Y
,
Du
WJ
,
Guo
S
, et al
.
Dysfunction of the hypothalamic-pituitary-adrenal axis in opioid dependent subjects: effects of acute and protracted abstinence
.
Am J Drug Alcohol Abuse
.
2008
;
34
(
6
):
760
8
.
[PubMed]
0095-2990
35.
Block
RI
,
Farinpour
R
,
Schlechte
JA
.
Effects of chronic marijuana use on testosterone, luteinizing hormone, follicle stimulating hormone, prolactin and cortisol in men and women
.
Drug Alcohol Depend
.
1991
Aug
;
28
(
2
):
121
8
.
[PubMed]
0376-8716
36.
Cone
EJ
,
Johnson
RE
,
Moore
JD
,
Roache
JD
.
Acute effects of smoking marijuana on hormones, subjective effects and performance in male human subjects
.
Pharmacol Biochem Behav
.
1986
Jun
;
24
(
6
):
1749
54
.
[PubMed]
0091-3057
37.
Wichmann
S
,
Kirschbaum
C
,
Lorenz
T
,
Petrowski
K
.
Effects of the cortisol stress response on the psychotherapy outcome of panic disorder patients
.
Psychoneuroendocrinology
.
2017
Mar
;
77
:
9
17
.
[PubMed]
0306-4530
38.
Pariante
CM
,
Lightman
SL
.
The HPA axis in major depression: classical theories and new developments
.
Trends Neurosci
.
2008
Sep
;
31
(
9
):
464
8
.
[PubMed]
0166-2236
39.
Stetler
C
,
Miller
GE
.
Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research
.
Psychosom Med
.
2011
Feb-Mar
;
73
(
2
):
114
26
.
[PubMed]
0033-3174
40.
Burke
HM
,
Davis
MC
,
Otte
C
,
Mohr
DC
.
Depression and cortisol responses to psychological stress: a meta-analysis
.
Psychoneuroendocrinology
.
2005
Oct
;
30
(
9
):
846
56
.
[PubMed]
0306-4530
41.
Kirschbaum
C
,
Kudielka
BM
,
Gaab
J
,
Schommer
NC
,
Hellhammer
DH
.
Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis
.
Psychosom Med
.
1999
Mar-Apr
;
61
(
2
):
154
62
.
[PubMed]
0033-3174
You do not currently have access to this content.