Caja PDF

Comparta fácilmente sus documentos PDF con sus contactos, la web y las redes sociales.

Compartir un archivo PDF Gestor de archivos Caja de instrumento Buscar PDF Ayuda Contáctenos



Endogenous DMT Review 2012 .pdf



Nombre del archivo original: Endogenous DMT Review_2012.pdf

Este documento en formato PDF 1.6 fue generado por pdftk 1.44 - www.pdftk.com / itext-paulo-155 (itextpdf.sf.net-lowagie.com), y fue enviado en caja-pdf.es el 24/09/2013 a las 11:16, desde la dirección IP 92.56.x.x. La página de descarga de documentos ha sido vista 2386 veces.
Tamaño del archivo: 918 KB (26 páginas).
Privacidad: archivo público




Descargar el documento PDF









Vista previa del documento


Journal Code
D T A

Article ID
Dispatch: 30.01.12
4 2 2 No. of Pages: 19

CE:
ME:

Drug Testing
and Analysis

Review
Received: 7 December 2011

Revised: 3 January 2012

Accepted: 3 January 2012

Published online in Wiley Online Library

(wileyonlinelibrary.com) DOI 10.1002/dta.422

A critical review of reports of endogenous
psychedelic N, N-dimethyltryptamines in
humans: 1955–2010
Steven A. Barker,a* Ethan H. McIlhennya and Rick Strassmanb
Three indole alkaloids that possess differing degrees of psychotropic/psychedelic activity have been reported as endogenous
substances in humans; N,N-dimethyltryptamine (DMT), 5-hydroxy-DMT (bufotenine, HDMT), and 5-methoxy-DMT (MDMT). We
have undertaken a critical review of 69 published studies reporting the detection or detection and quantitation of these
compounds in human body fluids. In reviewing this literature, we address the methods applied and the criteria used in the
determination of the presence of DMT, MDMT, and HDMT. The review provides a historical perspective of the research
conducted from 1955 to 2010, summarizing the findings for the individual compounds in blood, urine, and/or cerebrospinal
fluid. A critique of the data is offered that addresses the strengths and weaknesses of the methods and approaches to date.
The review also discusses the shortcomings of the existing data in light of more recent findings and how these may be
overcome. Suggestions for the future directions of endogenous psychedelics research are offered. Copyright © 2012 John
Wiley & Sons, Ltd.
Keywords: dimethyltryptamine; psychedelic; endogenous

Introduction
Three indole alkaloids that possess differing degrees of psychotropic/
psychedelic activity have been reported as endogenous
substances in humans. These compounds, all metabolites of
tryptophan, are N,N-dimethyltryptamine (DMT, 1, Figure 1),
5-hydroxy-DMT (bufotenine, HDMT, 2), and 5-methoxy-DMT
(MDMT, 3). Their presence has been reported in human
cerebrospinal fluid (CSF), urine, and/or blood utilizing either
paper and/or thin layer chromatography (TLC), direct ultraviolet (UV) or fluorescence (Fl) measurements, gas chromatography (GC) using various sensors (nitrogen-phosphorous
detector (NPD); electron capture detector (ECD); mass
spectrometry detector (MSD)), high-performance liquid
chromatography (HPLC) using UV and/or Fl detection, HPLCradioimmunoassay, HPLC-electrochemical detection, and
liquid chromatography-tandem mass spectrometry (LC-MS/
MS) (Tables 1–3, references[1–69]). Indeed, the review of the
55-year history of the development of methodology for the analysis
of these compounds shows how closely it has paralleled the evolution of analytical technology itself, with each researcher seeking
more specific and sensitive techniques.
A renewed interest in these compounds as naturally
occurring substances in humans has occurred, in part, due
to DMT’s recent characterization as an endogenous substrate
for the ubiquitous sigma 1 receptor[70] and for its possible
action at trace amine receptors.[71] In both cases, the roles
of DMT and the receptors themselves in regulating some
aspect(s) of human physiology are poorly understood. Given
their known psychedelic effects, there remains an interest in
their possible role in naturally occurring altered states of
consciousness, such as psychosis, dreams, creativity and imagination, religious phenomena, and even near-death

Drug Test. Analysis (2012)

experiences.[72] Although the vast majority of research into
the presence of these compounds sought their role in mental
illness, no definitive conclusions yet exist. A determination of
the role of these compounds in humans awaits further
research, much of which awaits the development of adequate
analytical methodology.
Interest in DMT has also increased because of the
burgeoning use and popularity of the religious sacrament ayahuasca which contains DMT and several harmala alkaloids,
which serve to make DMT orally active. Ayahuasca tourism
in South America and the establishment of syncretic churches
using ayahuasca as a sacrament[73,74] have stimulated research
into the mechanisms of its effects and its possible use as a
therapeutic.[75] The resumption of human research characterizing DMT’s psychopharmacology[76–84] and the ongoing use
of pure DMT for therapeutic and recreational purposes have
also focused interest on this and related psychedelics. The
dimethylated-tryptamines (DMTs) increasing visibility within
medical, non-medical, religious and/or recreational contexts[75]
reinforce the importance of determining their endogenous
role.
This review addresses several fundamental issues regarding
these three endogenous psychedelics. For example, are DMT,

* Correspondence to: Steven A. Barker, Department of Comparative Biomedical
Sciences, School of Veterinary Medicine, Louisiana State University, Baton
Rouge, LA 70806, USA. E-mail: sbarker@vetmed.lsu.edu
a School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA,
USA
b School of Medicine, University of New Mexico, Albuquerque, and Cottonwood
Research Foundation, Taos, New Mexico, USA

Copyright © 2012 John Wiley & Sons, Ltd.

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

1

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
F1 35
36
37
38
39
40
41
42
43
44
45
46
T1T2 T347
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Drug Testing
and Analysis

2

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

S. A. Barker, E. H. McIlhenny and R. Strassman

Figure 1. Structures of the compounds discussed.

HDMT, and/or MDMT truly present in humans?[85] Early
criticisms of reports of endogenous psychedelics were
directed at the fact that rather non-specific chemical tests
were being applied, double-blind analyses were not always
being performed, and dietary or medication sources were
not always adequately ruled out as responsible for the identifications.[2,12] Further, it was claimed that possible artifacts
produced from the extraction solvents and conditions of
analysis may have led to misidentification of the DMTs in
some early studies[20] and, more recently, that the use of
halogenated solvents in the analysis may have affected their
detection.[86] Biological factors that may have affected the
detectabilty of these compounds in the periphery were also
acknowledged, which included their rapid metabolism.[87,88]
Finally, there have been concerns that the studies searching
for their presence and an association with specific clinical
disorders have failed to understand and fully characterize
their metabolism or monitor their metabolites.[88–91]
To address these issues, we have undertaken a critical
review of 69 published studies reporting the detection or
detection and quantitation of these compounds in human
body fluids. In reviewing this literature, we address the
methods applied and the criteria used in the determination
of the presence of DMT, MDMT, and HDMT. We begin with
the original report of the presence of bufotenin (HDMT) in
human urine in 1955 using paper chromatography[1] and
end with the most recent report concerning the presence of
bufotenin (HDMT) in human urine using LC-MS/MS.[69]
We will be addressing the following questions: How valid
were early studies regarding the presence and/or quantities
of these compounds in human cerebrospinal fluid (CSF),
blood and/or urine? Were the analytical methodologies
and the identification criteria adequate? Are they truly there?
When present, are they of dietary origin? When and where in
the human body are they produced? Can we influence their
detection in biological samples by pharmacologically inhibiting their metabolism by monoamine oxidase (MAO)? How
does turnover rate and metabolism of these substances
influence their detectabilty? Have the precursors and/or metabolites of these compounds been adequately monitored? Is

wileyonlinelibrary.com/journal/dta

monitoring these compounds in biological samples such as
CSF, blood and/or urine the best, or even most practical
way to determine their role? What will such data tell us about
the function of these compounds? Where does the research
on endogenous psychedelics go from here?

Historical perspective
The search for endogenous psychedelics soon followed
the discovery of the psychedelic effects of mescaline and
lysergic acid diethylamide (LSD) in humans. Observations of
these effects gave rise to hypotheses that they were related
to the symptomology observed in a heterogeneous group of
mental disorders, especially psychoses – either mania or
schizophrenia.[92] It was proposed that schizophrenics may
biochemically produce similar compounds as ‘schizotoxins’.[93]
A search for mescaline-like compounds proved unrewarding,[94] but in studies examining urine samples for serotoninlike compounds, researchers reported in 1955[1] and 1956,[2]
the presence of 5-hydroxy-N,N-DMT (HDMT, bufotenin) in
humans. Subsequently, Axelrod[95] reported the presence of
an enzyme capable of N-methylating indole-ethylamines and
producing DMTs. Following these reports, attention began to
focus in earnest on the possible endogenous formation of
the indole-ethylamine psychedelics. During the next 50 years,
many studies reported finding DMT, HDMT, and/or MDMT in
human CSF, urine, and/or blood. Most of these studies sought
differences in levels between controls and psychiatric,
especially psychotic, patients. Some studies claimed higher
concentrations and significant differences in levels between
the groups; some reported not finding the compounds at all
in either patients or controls.
It is of interest to note that in its original conception, the
schizotoxin hypothesis proposed that the formation of an
endogenous psychedelic schizotoxin would be an aberration
of metabolism and that ‘normals’ would not form such
compounds.[92] However, numerous studies subsequently
reported finding one or more of these compounds in controls

Copyright © 2012 John Wiley & Sons, Ltd.

Drug Test. Analysis (2012)

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Bumpus and Page
Rodnight[2]
Fischer et al.[3]
Fischer et al.[4]
Feldstein et al.[5]
Perry et al.[6]

Brune et al.[7]
Perry[8]
Sprince et al.[9]
Perry and Schroeder[10]
Franzen and Gross[11]
Siegel[12]
Nishimura and Gjessing[13]
Takesada et al.[14]
Runge et al.[15]
Perry et al.[16]
Heller[17]
Fischer and Spatz[18]
Kakimoto et al.[19]
Tanimukai[20]
Tanimukai et al.[21]
Tanimukai et al.[22]
Acebal and Spatz[23]
Faurbye and Pind[24]
Sireix and Marini[25]
Spatz et al.[26]
Fischer and Spatz[27]
Saavedra and Udabe[28]
Tanimukai et al.[29]
Heller et al.[30]
Narsimhachari et al.[31]
Narasimhachari et al.[32]
Fischer et al.[33]
Himwich et al.[34]
Narasimhachari et al.[35]
Walker et al.[36]

1963
1963
1963
1963
1965
1965
1965
1965
1966
1966
1966
1967
1967
1967
1967
1967
1967
1968
1969
1969
1970
1970
1970
1970
1971
1971
1971
1972
1972
1973

[1]

Author

1955
1956
1961
1961
1961
1962

Year

Drug Test. Analysis (2012)
HDMT; DMT
HDMT; DMT
DMT, HDMT
HDMT
DMT, HDMT
HDMT
HDMT
HDMT
HDMT
DMT, HDMT
HDMT
HDMT
DMT, HDMT
HNMT, HDMT, NMT, DMT, MDMT
HDMT
HDMT
HDMT
HDMT
HDMT
HDMT
HDMT
HDMT
HNMT, HDMT, DMT, MDMT
DMT, MDMT, HDMT
DMT, MDMT, HDMT
NMT, DMT, MDMT
HDMT, glucuronide
HDMT, DMT, MDMT
HDMT, DMT, MDMT
DMT

HNMT, HDMT
HNMT, HDMT
HDMT
HDMT
HDMT
HDMT, conjugate

Compounds Analyzed
24-hour urine 10 ml portions, HCl; urease
24-hour urine; 75–120 ml extracted
1 L of urine
1 L of urine
8 hour urines; IV/oral 14 C serotonin (130 mg)
24-36 hour urine; ext vol 500 mg creatinine;
w/wo hydrolysis
24 hour urine
24 or 48 hour urine; ext vol 500 mg creatinine
24 hour urine
24-36 hour urine; ext vol 250–350 mg creatinine
blood and urine (24 hour)
fresh urine, 100 ml
fresh urine vol 500–1,000 mg creatinine
24 hour urine
1 L of urine
48 hour urine
1 L of urine
100 ml fresh urine
24 hour urine; vol 600 mg creatinine analyzed
24 hour urine; 1/4th used in assay
24 hour urine;1/3 rd used in assay
24 hour urine; 1/4th used in assay
100 ml urine
24 hour urine, hydrolyzed at pH1.6
100 ml fresh urine
50 ml fresh urine; 100 ml fresh urine
50 ml fresh urine; acid hydrolysis
50 ml fresh urine; acid hydrolysis
24 hour urine; 1/4th used in assay
fasting blood, oxalate tube; acid hydrolyzed
24 hour urine; 75% used in assay
fasting blood, oxalate tube
50 ml morning urine; w/wo glucuronidase
24 hour urine
24 hour urine
plasma; DMT stable for 60 days at 6 degrees C

Collection

pH 10, ethyl ether ext, evap, acetone
Amberlite CG-120, CG-50; ethanol-acetone ppt
pH 10, ethyl ether-butanone ext, evap, acetone
Amberlite CG-120, CG-50; ethanol-acetone ppt
Extensive multi-step extraction, ppt and clean-up
pH 10, ethyl ether ext, evap, acetone
Dowex 50, Amberlite CG 50,
Ext, Dowex 50 column, alumina column
pH 8–9, butanol ext, acetone ppt, acetone
Dowex 50 W, Amberlite CG-50; HCl hydrolysis
NaHCO3 sat., butanol, evap, acetone
NaCO3, ether ext, evap, acetone
Ext, Dowex 50 column, alumina column
Dowex 50 W X2; w/wo HCl hydrolysis
cation exchange resin; w/wo HCL hydrolysis
Dowex 50 W X2; HCl hydrolysis
NaCO3, ether ext, evap, acetone
column chromatography, sublimation, paper/TLC
NaCO3, ether ext, evap, acetone
pH 10 NaOH, ethyl acetate; diazo-reagent or TLC
pH 10 NaOH, ethyl acetate; diazo-reagent and TLC
pH 10 NaOH, ethyl acetate; diazo-reagent and TLC
Dowex 50 W X2; HCl hydrolysis
Dowex 50; HCl ext and ethyl acetate at pH 10.2
Dowex 50; HCl ext and ethyl acetate at pH 10.2
Dowex 50; HCl ext and ethyl acetate at pH 10.2
Liquid-Liquid ext; w/wo glucuronidase treatment
Dowex 50; HCl ext and ethyl acetate at pH 10.2
Franzen and Gross; HCl ext ethyl acetate at pH 10.2
HCL ext acid pH with CHCl3, pH 9, ext CHCl3, evap

Evap, Acetone, evap, MeOH, evap, AlO3 column
Zeo-Karb 226 resin, EtOH/acetone ppt, evap
NaHCO3 sat., butanol, evap, acetone
NaOH pH 9, butanol, evap, acetone
not described
Amberlite CG-120, CG-50; ethanol-acetone ppt

Extraction Method

Table 1. Review of 69 studies regarding endogenous psychedelics showing the year, reference, compounds analyzed, type of sample and method of extraction. Acronyms and abbreviations; IV, intravenous; HNMT, 5-hydroxy-N-methyltryptamine; ext, extraction; vol, volume; w/wo, with or without; evap, evaporate; ppt, precipitate; sat., saturated; TLC, thin-layer chromatography; cent, centrifuge;
TFAA, trifluoro-acetic anhydride; SPE, solid-phase extraction; LC, liquid chromatography.

Reports of endogenous psychedelic N, N-dimethyltryptamines in humans

Copyright © 2012 John Wiley & Sons, Ltd.

Drug Testing
and Analysis

wileyonlinelibrary.com/journal/dta

3

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

4

wileyonlinelibrary.com/journal/dta

Copyright © 2012 John Wiley & Sons, Ltd.
DMT, MDMT
DMT
DMT, NMT

DMT

DMT, HDMT
DMT, MDMT
DMT

Riceberg and Van Vunakis[52]

Corbett et al.[53]
Walker et al.[54]
Murray et al.[55]

Checkley et al.[56]

Raisanen and Karkkainen[57]
Smythies et al.[58]
Checkley et al.[59]

1978

1978
1979
1979

1979

1979
1979
1980

DMT, MDMT
HDMT
HDMT
HDMT

DMT, HDMT, MDMT

Oon and Rodnight[51]

1977

Uebelhack et al.[60]
Sitaram et al.[61]
Raisanen et al.[62]
Karkkainen et al.[63]

DMT, NMT

Wyatt et al.[37]
Narasimhachari and Himwich[38]
Lipinski et al.[39]
Bidder et al.[40]
Narasimhachari et al.[41]
Carpenter et al.[42]
Christian et al.[43]
Narasimhachari and Himwich[44]
Angrist et al.[45]
Rodnight et al.[46]
Murray and Oon[47]
Huszka et al.[48]
Cottrell et al.[49]
Oon et al.[50]

1973
1973
1974
1974
1974
1975
1975
1975
1976
1976
1976
1976
1977
1977

1983
1983
1984
1988

DMT
DMT, HDMT
DMT
DMT
HDMT, DMT, MDMT
DMT, HDMT
DMT, MDMT
DMT, HDMT
DMT
DMT
DMT
HDMT, DMT, MDMT
HDMT
DMT, NMT

Author

Year

Compounds Analyzed

Cerebrospinal fluid
12 hr specimens (8 pm-8 am); 200 ml assayed
not stated
morning urine samples

150 ml morning urine samples
Cerebrospinal fluid
Serial 24 hour urine; longitudinal study

24 hour urine; 50% used in assay

Cerebrospinal fluid
10 ml whole blood; arterial and venous
24-hour urine; 50% used in assay

24 hour urine; 300 ml used in assay
50 ml whole blood; plasma

plasma
24-hour urine
plasma separated by centrifugation
Heparinised plasma or whole blood; 24 hr urine
24 hour urine
24 hour urine, 90% used in assay
Cerebrospinal fluid
24 hour urine, 80% used in assay
non-fasting blood; heparin; 10 ml assayed
24-hour urine
24-hour urine
24 hour urine; 1/3 rd used in assay
24 hour urine
24-hour urine; 50% used;
DMT, NMT stable 90 days at 15 C
24-hour urine; 50% used in assay

Collection

HCL ext acid pH with CHCl3, pH 9, ext CHCl3, evap
Dowex 50; HCl ext and ethyl acetate at pH 10.2
HCL ext acid pH with CHCl3, pH 9, ext CHCl3, evap
HCL ext acid pH with CHCl3, pH 9, ext CHCl3, evap
Dowex 50; HCl ext and ethyl acetate at pH 10.2
Dowex 50; HCl ext and ethyl acetate at pH 10.2
Deproteinization, liquid-liquid ext, CH2Cl2
Dowex 50; HCl ext and ethyl acetate at pH 10.2
HCL ext acid pH with CHCl3, pH 9, ext CHCl3, evap
Dowex 50; HCl ext and ethyl acetate at pH 10.2
Dowex 50; HCl ext and ethyl acetate at pH 10.2
Dowex 50 W X2; HCl hydrolysis
HCL ext acid pH with CHCl3, pH 11, ext CHCl3, evap
50% concentrated and extracted with toluene
purified by TLC, derivatized with TFAA
50% concentrated and extracted with toluene
purified by TLC, derivatized with TFAA
Urine (pH 10.5) ext with CHCl3
Whole blood lysed, protein ppt. with HClO4
extracted twice with chloroform
Deproteinization, Liquid-Liquid ext, CH2Cl2
HCL ext acid pH with CHCl3, pH 9, ext CHCl3, evap
acidified with HCl
50% concentrated and extracted with toluene
purified by TLC, derivatized with TFAA
acidified with HCl
50% concentrated and extracted with toluene
purified by TLC, derivatized with TFAA
pH 11, XAD resin, ethyl acetate elution, evap, TLC
Deproteinization, liquid-liquid ext, CH2Cl2
acidified with HCl
50% concentrated and extracted with toluene
purified by TLC, derivatized with TFAA
Deproteinization, liquid-liquid ext, CH2Cl2
ion pair ext CHCl3, LC-silica column purification
pH11, XAD resin, ethyl acetate elution, evap, TLC
pH11, XAD resin, ethyl acetate elution, evap, TLC

Extraction Method

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Table 1. (Continued)

Drug Testing
and Analysis
S. A. Barker, E. H. McIlhenny and R. Strassman

Drug Test. Analysis (2012)

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

Drug Test. Analysis (2012)
HDMT
HDMT, HNMT
DMT, MDMT, HDMT, NMT
DMT, HDMT
HDMT

Karkkainen et al.[65]
Takeda et al.[66]
Forsstrom et al.[67]
Karkkainen et al.[68]

Emanuele et al.[69]

1995
1995
2001
2005

2010

individual urine samples;
w /wo nialamide treatment
morning urine samples; 50–100 ml
morning urine samples
morning and afternoon urines; 5 ml assayed
urine (5 ml), plasma or serum (1 ml), stool;
tissues (0.5-1.5 g)
random urine samples

Collection

pH11, XAD resin, ethyl acetate elution, evap, TLC
centrifugation, direct injection of 80 ml of urine
urine centrifuged and ext on Oasis SPE cartridge
urine cent and ext on Oasis HLB cartridge;
Prep LC for blood
urine cent and ext on Oasis HLB cartridge

pH11, XAD resin, ethyl acetate elution, evap, TLC

Extraction Method

Copyright © 2012 John Wiley & Sons, Ltd.
paper chromatography, color reaction

HDMT

1965

paper chromatography (1 system), color reaction, bioassay
paper chromatography (3 systems), color reaction, bioassay
paper chromatography (1 system)
paper chromatography (1 system)
paper chromatography and auto-radiographs
paper chromatography (2-D), color reaction
paper chromatography (2-D), color reaction
2-D paper chromatography, color reaction
2-D paper chromatography, color reaction
paper chromatography (3 systems)
Fluorescence
TLC (1 system), color reaction
TLC (2-D), color reaction

HNMT, HDMT
HNMT, HDMT
HDMT
HDMT
HDMT
HDMT, conjugate
HDMT; DMT
HDMT; DMT
DMT, HDMT
HDMT
DMT, HDMT
HDMT
HDMT

Bumpus and Page[1]
Rodnight[2]
Fischer et al.[3]
Fischer et al.[4]
Feldstein et al.[5]
Perry et al.[6]
Brune et al.[7]
Perry[8]
Sprince et al.[9]
Perry and Schroeder[10]
Franzen and Gross[11]
Siegel[12]
Nishimura and
Gjessing[13]
Takesada et al.[14]

1955
1956
1961
1961
1961
1962
1963
1963
1963
1963
1965
1965
1965

Detection Methods

Compounds
Analyzed

Author

Year

Rf and color (1 system)
Rf and color (3 systems)
Rf and color (1 system)
Rf and color (1 system)
Rf and color (1 system), radioactive spot
Rf and color (2-D)
Rf and color (2-D)
Rf and color (2-D)
Rf and color (2-D)
Rf and color (3 systems)
Fluoresence reading
Rf and color (1 system)
Rf and color (2-D)
Rf and color

20 mg/24 hour

Confirmation Criteria

ND
>5 mg/ 24 hour for HDMT
ND
ND
ND
ND
20 ng/ml
ND
ND
ND
2 ng/ml
0.1 mg/100 ml
ND

Limit of Detection

Table 2. Review of 69 studies regarding endogenous psychedelics showing the year, reference, compounds analyzed, detection methods, limits of detection (LOD) and confirmation criteria. Acronyms
and abbreviations; HNMT, 5-hydroxy-N-methyltryptamine; TLC, thin-layer chromatography; 2-D, two dimensional; GC-FID, gas chromatography-flame ionization detector; derive, derivative; HFBI, heptafluoro-butyryl-imidazole; IS, internal standard; HPLC, high performance liquid chromatography; ESI, electrospray ionization; MS, mass spectrometry; ND, not determined; RT, retention time; UV, ultraviolet;
TI, total ion; m/z, mass-to-charge ratio; CI, chemical ionization; IA, immunoassay; MRM, multiple reaction monitoring.

HDMT

Karkkainen and Raisanen[64]

Compounds Analyzed

1992

Year

Author

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Table 1. (Continued)

Reports of endogenous psychedelic N, N-dimethyltryptamines in humans

Drug Testing
and Analysis

wileyonlinelibrary.com/journal/dta

5

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

6

wileyonlinelibrary.com/journal/dta
TLC DACA and OPT spray on cellulose and silica; GC/MS,
58 m/z only
TLC DACA and OPT spray on cellulose and silica; GC/MS,
58 m/z only
GC-ECD; packed column
TLC DACA and OPT spray on cellulose and silica; GC/MS,
58 m/z only

HDMT, DMT, DMT
DMT
DMT
DMT, HDMT

DMT
DMT

DMT, MDMT
DMT, HDMT

Narasimhachari et al.[35]
Walker et al.[36]
Wyatt et al.[37]
Narasimhachari and
Himwich[38]

Lipinski et al.[39]
Bidder et al.[40]

Narasimhachari et al.[41] HDMT, DMT, MDMT

DMT, HDMT

Heller et al.[30]
Narsimhachari et al.[31]
Narasimhachari et al.[32]
Fischer et al.[33]
Himwich et al.[34]

Carpenter et al.[42]

Christian et al.[43]
Narasimhachari and
Himwich[44]

1970
1971
1971
1971
1972

1972
1973
1973
1973

1974
1974

Copyright © 2012 John Wiley & Sons, Ltd.

1974

1975

1975
1975

GC-MS; 2 ft. SE-30 glass capillary column, DMT-d2 IS, TMS deriv
GC-MS; 2 ft. SE-30 glass capillary column, DMT-d2 IS, TMS deriv

GC-FID, TLC, and Spectrofluorometry
TLC and GC-FID, verified with spectrofluorometer
TLC and GC-FID, verified with spectrofluorometer
UV; paper chromatography, color reaction
TLC (3 systems), color reaction; verified with
spectrofluorometer
paper and TLC (2-D); color reaction; GC-FID
GC-MS; 2 ft. SE-30 glass capillary column, DMT-d2 IS, TMS deriv
GC-MS; 2 ft. SE-30 glass capillary column, DMT-d2 IS, TMS deriv
TLC DACA and OPT spray on cellulose and silica; GC/MS,
58 m/z only

paper chromatography, TLC (2-D), color reaction; GC-FID
paper and TLC (2-D); color reaction; GC-FID of HDMT
paper chromatography (2-D), color reaction
paper chromatography and TLC, color reaction
UV; paper chromatography, color reaction
UV of diazo-deriv; paper chromatography, color reaction
UV; TLC, color reaction
UV; TLC, color reaction
paper and TLC (2-D); color reaction; GC-FID of HDMT

Tanimukai et al.[21]
Tanimukai et al.[22]
Acebal and Spatz[23]
Faurbye and Pind[24]
Sireix and Marini[25]
Spatz et al.[26]
Fischer and Spatz[27]
Saavedra and Udabe[28]
Tanimukai et al.[29]

paper chromatography, color reaction
paper chromatography (2-D), color reaction
paper chromatography (2-D), color reaction
paper chromatography (2-D), color reaction
paper chromatography (3 systems), color reaction
paper and TLC (2-D); color reaction; GC-FID of HDMT

1967
1967
1967
1968
1969
1969
1970
1970
1970

HDMT
DMT, HDMT
HDMT
HDMT
DMT, HDMT
HNMT, HDMT, NMT,
DMT,
MDMT
HDMT
HDMT
HDMT
HDMT
HDMT
HDMT
HDMT
HDMT
HNMT, HDMT, DMT,
MDMT
DMT, MDMT, HDMT
DMT, MDMT, HDMT
NMT, DMT, MDMT
HDMT, glucuronide
HDMT, DMT, MDMT

Detection Methods

Runge et al.[15]
Perry et al.[16]
Heller[17]
Fischer and Spatz[18]
Kakimoto et al.[19]
Tanimukai[20]

Author

1966
1966
1966
1967
1967
1967

Year

Compounds
Analyzed

DMT 10 pg/ml; MDMT 5 pg/ml
5 ng/ml HDMT; 1 ng/ml DMT

5 ng/ml HDMT; 1 ng/ml DMT

RT
Rf and color (2-D); GC-RT; GC/MS 58 mz

TI spectrum match with DMT, HDMT
Rf and color (2-D); GC-RT; GC/MS 58 mz

Rf and color (2-D); GC-RT; GC/MS 58 mz

TI spectrum match with DMT standard
GC-RT, two ions and ratio
GC-RT, two ions and ratio

Rf and color (2-D); GC-RT
GC-RT, two ions and ratio
GC-RT, two ions and ratio
Rf and color (2-D); GC-RT; GC/MS 58 mz

0.05 mg/24 hour
0.5 ng/ml; m/z 202/204, 260/262
0.5 - 1.8 ng/ml; m/z 202/204, 260/262
5 ng/ml HDMT; 1 ng/ml DMT

0.5 ng/ml
blood 0.05-2 ng/ml; urine 0.070.2 ng/ml
5 ng/ml HDMT; 1 ng/ml DMT

GC-RT and TLC or spectrofluorometer
TLC and GC-FID, spectrofluorometer
TLC and/or GC-FID, spectrofluorometer
UV; Rf and color
Rf, color and fluoresence

Rf and color (2-D); GC-RT
Rf and color (2-D paper, TLC); GC-RT
Rf and color (2-D)
Rf and color (paper and 2-D TLC)
Rf and color (2-D)
UV; Rf and color
UV; Rf and color
UV; Rf and color
Rf and color (2-D paper, TLC); GC-RT

>0.1 mg/24 hour
ND
ND
>0.7 mg/24 hour
ND
ND
ND
ND
ND
2 ng/ml
5 mg/ml per 24hour for DMT
2 ng/ml
ND
ND

Rf and color (2-D)
Rf and color (2-D)
Rf and color (2-D)
Rf and color (2-D)
Rf and color (3 systems)
Rf and color (2-D paper, TLC)

Confirmation Criteria

ND
2 mg/24 hr for DMT and HDMT
ND
ND
10 mg/24 hour
5 ng/ml HDMT; 1 ng/ml others

Limit of Detection

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Table 2. (Continued)

Drug Testing
and Analysis
S. A. Barker, E. H. McIlhenny and R. Strassman

Drug Test. Analysis (2012)

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

Drug Test. Analysis (2012)

Copyright © 2012 John Wiley & Sons, Ltd.
GC/MS selected ion monitoring; d4-DMT, d4-MDMT IS
GC with nitrogen-sensitive detector
GC-FID
HPLC/fluoresence spectrum
TMS derivatives; GC/MS, multiple ion detection
TMS derivatives; GC/MS, multiple ion detection
TMS derivatives; GC/MS, multiple ion detection
TMS derivatives; GC/MS, multiple ion detection

DMT, NMT

DMT, HDMT, MDMT

DMT, MDMT
DMT

DMT, NMT

DMT
DMT, HDMT

DMT, MDMT
DMT
DMT, MDMT
HDMT
HDMT

HDMT

HDMT

HDMT

HDMT, HNMT
DMT, MDMT, HDMT,
NMT

DMT, HDMT
HDMT

Oon and Rodnight[51]

Riceberg and Van
Vunakis[52]

Corbett et al.[53]
Walker et al.[54]

Murray et al.[55]

Checkley et al.[56]
Raisanen and
Karkkainen[57]
Smythies et al.[58]
Checkley et al.[59]
Uebelhack et al.[60]
Sitaram et al.[61]
Raisanen et al.[62]

Karkkainen et al.[63]

Karkkainen and
Raisanen[64]
Karkkainen et al.[65]

Takeda et al.[66]
Forsstrom et al.[67]

Karkkainen et al.[68]
Emanuele et al.[69]

1977

1978

1978
1979

1979

1979
1979

1988

1992

1995
2001

2005
2010

1995

1979
1980
1983
1983
1984

GC-ECD; HFBI derivative
GC/MS, Selective Ion Monitoring capillary column gas
chromatography
GC-NPD,TLC on cellulose; GC/MS 2 patients and pooled
(10) extract
GC with nitrogen-sensitive detector
TMS derivatives; GC/MS, multiple ion detection

HDMT, DMT, MDMT
HDMT
DMT, NMT

Huszka et al.[48]
Cottrell et al.[49]
Oon et al.[50]

1976
1977
1977

HPLC/ESI-MS/MS
HPLC/ESI-MS/MS

3-D-HPLC-electrochemical detection
HPLC/ESI-MS-MS

Radioimmunoassay and HPLC (RIA-HPLC)

GC/NPD;GC/MS

DMT

Murray and Oon[47]

1976

GC-MS; 2 ft. SE-30 glass capillary column, DMT-d2 IS, TMS deriv
GC-FID,TLC on cellulose; GC/MS 2 patients and pooled
(10) extract
GC-FID,TLC on cellulose; GC/MS 2 patients and pooled
(10) extract
TLC and GC-FID, verified with spectrofluorometer
HFBI derivatives, GC-ECD
GC/NPD;GC/MS

DMT
DMT

Detection Methods

Angrist et al.[45]
Rodnight et al.[46]

Author

1976
1976

Year

Compounds
Analyzed

RT; MS of selected samples
GC/MS RT, m/z 58 only

15fmol/ml DMT
DMT 10 pg/ml; MDMT 5 pg/ml
10 pg/ml whole blood

RT and electrochemical response
RT, Pseudo molecular ion, MRM

RT, Pseudo molecular ion, MRM
RT, Pseudo molecular ion, MRM

0.1 ng/ml MDMT; 0.05 ng/ml NMT
0.3 ng/ml HDMT; 0.2 ng/ml DMT
ND

RT, molecular ions or fragments

RT, molecular ions or fragments

RT, molecular ions or fragments

RT, ion fragments, ratios
RT
RT
RT and fluoresence spectrum
RT, molecular ions or fragments

RT
RT, molecular ions or fragments

20 ng/24hour DMT; 50 ng/24
hour NMT
0.5 mg/ml per 24hour
0.1-0.15 ng/ml DMT; 0.25-0.3 ng/ml
HDMT
70 pg/ml DMT, MDMT
0.5 mg/ml per 24hour
ND
>0.01 ng/ml per 12 hr
0.1-0.15 ng/ml DMT; 0.25-0.3 ng/ml
HDMT
0.1-0.15 ng/ml DMT; 0.25-0.3 ng/ml
HDMT
0.1-0.15 ng/ml DMT; 0.25-0.3 ng/ml
HDMT
0.1-0.15 ng/ml DMT; 0.25-0.3 ng/ml
HDMT
50 pg/ml
0.35 ng/ml HDMT; 0.1 ng/ml DMT

RT; MS of selected samples

RT; CI MS confirmation
HPLC RT and IA response

TLC and GC-FID, spectrofluorometer
RT
RT; CI MS confirmation

Rf and color; GC-RT; GC-MS

RT, two ions and ratio
Rf and color; GC-RT; matching TI MS

Confirmation Criteria

4 ng/ml
<1 nmol/24 hour
20 ng/24hour for DMT; 50 ng/ml
NMT
50 ng/24hour for NMT
20 ng/24hour for DMT (30 ng/L)
50 ng/24hour for NMT
5fmol/ml HDMT or MDMT,

20 ng /24hour

0.05 ng/ml
0.5 mg/24hour

Limit of Detection

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Table 2. (Continued)

Reports of endogenous psychedelic N, N-dimethyltryptamines in humans

Drug Testing
and Analysis

wileyonlinelibrary.com/journal/dta

7

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

8

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

wileyonlinelibrary.com/journal/dta

Bumpus and Page[1]
Rodnight[2]
Fischer et al.[3]
Fischer et al.[4]
Feldstein et al.[5]
Perry et al.[6]

Author

Copyright © 2012 John Wiley & Sons, Ltd.

HDMT
HDMT

HDMT
HDMT

DMT, HDMT

HDMT

1965 Siegel[12]
1965 Nishimura and Gjessing[13]

1965 Takesada et al.[14]
1966 Runge et al.[15]

1966 Perry et al.[16]

1966 Heller[17]

DMT, HDMT

DMT, HDMT

1965 Franzen and Gross[11]

1967 Kakimoto et al.[19]

HDMT

1963 Perry and Schroeder[10]

HDMT

DMT, HDMT

1963 Sprince et al.[9]

1967 Fischer and Spatz[18]

HDMT; DMT

HDMT; DMT

HNMT, HDMT
HNMT, HDMT
HDMT
HDMT
HDMT
HDMT, conjugate

Compounds
Analyzed

1963 Perry[8]

1963 Brune et al.[7]

1955
1956
1961
1961
1961
1962

Year

5 normals, 21 schizophrenics
2 periodic catitonia patients; strict dietary control;
phenelzine MAOI
7 schizophrenics, 8 controls; no meds 30 days
22 schizophrenics no meds; 14 schizophrenics on
meds, 17 controls; no meds 60 days
12 male schizophrenics, 7 male controls; MAOI
phenelzine administered;
no meds for 6 weeks; no plants or cheese in diet
11 schizophrenics, 4 controls; 10 schizophrenics, 4 controls
received MAOI
95 schizophrenics w/o treatment, 43 with treatment;
102 controls
8 schizophrenic females; treated with methionine
and isocarboxazide (MAOI)

4 schizophrenics, 2 psychoneurotics; MAOI
tranylcypromine, methione or tryptophan
7 control and 2 psychotic children; 1 control on
plant-free diet; 2 controls received MAOI
blood 37 controls; urine 46 controls

3 on a plant-free diet during admin of neomycin to
reduce intestinal flora
5 schizophrenics; 3 mentally deficient patients; MAOI
isocarboxazid plus betaine
18 juvenile psychotics; Some on plant-free diet and MAOI

4 healthy adults
11 healthy adults
5 acute schizophrenics, 4 controls
15 schizophrenics, 10 controls
15 schizophrenics, 10 controls; no meds for 2 weeks
20 control children; 6 received MAOI pheniprazine
(3) or nialamide (3)

Subjects

no HNMT, NMT, HDMT or DMT
detected

10/11 HDMT, 0/4 HDMT; 10/10 HDMT,
0/4 HDMT
71/95 HDMT, 16/43 HDMT; 0/102 HDMT

no HDMT or DMT detected

no HDMT detected
no HDMT detected

1/2 psychotics HDMT; 2/2 controls
receiving MAOI
11/37 blood DMT;37/37 urine DMT
12/37 blood HDMT; 46/46 urine HDMT
no HDMT detected
no HDMT detected

9 of 17 urine samples; 0/3; MAOI
increased schizo symptoms
no DMT detected; 2 positive for HDMT
after MAOI
no DMT or HDMT detected

pooled sample; 5-HNMT, HDMT
no HNMT or HDMT detected
5/5 schizophrenics HDMT, 4 controls neg
14/15 HDMT; 0/10 HDMT
no HDMT detected
1/20 HDMT; 4/6 HDMT following MAOI

Positive/Negative

NA

ND

ND

NA

NA
ND

8-55 ng/ml; 42.98 +/ 8.6 mg/24 hour
1-40 ng/ml; 62.8 +/ 7.2 mg/24 hour
NA
NA

NA

NA

20-30 mg/24 hour HDMT; DMT
negative in all samples
30 ng/100 mg creatinine

ND
ND
400 ng/ml
ND
ND
0.3 mg/ 100 mg creatinine;
0.5-2.2 mg/100 mg
creatinine with MAOI

Concentration

Table 3. Review of 69 studies regarding endogenous psychedelics showing the year, reference, compounds analyzed, the subjects (patients and controls), the results positive or negative out of the total
(i.e. 4/12) and the concentrations of the compounds observed. Acronyms and abbreviations; HNMT, 5-hydroxy-N-methyltryptamine; meds, medications; MAOI, monoamine oxidase inhibitor; admin, administration; schizo, schizophrenia; neg, negative; ND, not detected; NA, not applicable; psychiat, psychiatric; sig dif, significant difference;

Drug Testing
and Analysis
S. A. Barker, E. H. McIlhenny and R. Strassman

Drug Test. Analysis (2012)

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

Author

Drug Test. Analysis (2012)

Copyright © 2012 John Wiley & Sons, Ltd.

Narasimhachari et al.[32]

Fischer et al.[33]

1971

1971

HDMT

Saavedra and Udabe[28]

1970

Narsimhachari et al.[31]

HDMT

Fischer and Spatz[27]

1970

1971

HDMT

Spatz et al.[26]

1969

Heller et al.[30]

HDMT

Sireix and Marini[25]

1969

1970

HDMT

Faurbye and Pind[24]

1968

HNMT, HDMT,
DMT, MDMT
DMT, MDMT,
HDMT
DMT, MDMT,
HDMT
NMT, DMT,
MDMT
HDMT, glucuronide

HDMT

Acebal and Spatz[23]

1967

Tanimukai et al.[29]

HDMT

Tanimukai et al.[22]

1967

1970

HDMT

Tanimukai et al.[21]

MDMT

HNMT, HDMT,
NMT, DMT,

1967

1967 Tanimukai[20]

Year

Compounds
Analyzed

4 each, control, acute and chronic scizophrenics

4 schizophrenics, MAOI tranylcypromine,
methionine or cysteine admin; special diet
5 acute schizophrenics, 9 chronic schizophrenics,
2 normals, 1 depressive
2 schizophrenics, 6 controls; MAOI
tranylcypromine, cysteine admin.
22 acute schizophrenics, 20 non-schizophrenics

4/4 HDMT, 3/4 MNMT, 3/4 DMT,
2/4 MDMT
5/5 DMT, 5/5 MDMT, 2/5 HDMT;
0/12 for others
2 schiziphrenics positive; 6 controls
negative
15/22 DMT and/or MDMT, 2/22 HDMT;
2/20 positive
all positive

all positive

8/8 psychopathic, 86/86, 45/45
schizophrenics

45 treated schizophrenics

4 controls, 25 psychiatric patients, 11 nontreated schizo, 4 treated, 4 hysteria

67/67 normals, 11/11 epilepsy,
9/9 depression

65/65 schizophrenics, 73/73 controls

19/20 HDMT, 19/20 HDMT, 18/20

DMT and MDMT observed
in some samples
HDMT; conjugated in all 10,
free in 7/10
1/4 free HDMT, 3/4 conj; MAO
4/4 free, 3/4 conj
7/10 HDMT, 0/10 after trifluperidol;
0/7 HDMT
6/7 schizophrenics, 3/5 controls

4/100 samples HDMT; 3/100
conjugated

Positive/Negative

67 controls, 11 epilepsy, 9 depression,
8 psychopathic, 86 non-treated schizophrenics

65 schizophrenics, 73 controls

20 schizophrenics, 20 non-schizophrenics,
20 controls; special diets

6 male schizophrenics, 4 male mentally defective
patients; special diet; no meds 7 weeks
4 schizophrenics, MAOI tranylcypromine,
cysteine admin; special diet
10 schizophrenics; 7 controls; patients
administered trifluperidol
7 schizophrenics, 5 controls

4 male chronic schizophrenics; MAOI tranylcypromine;
special diet; no meds
4–6 weeks

Subjects

controls (Free or total) 63+/ 14.3
or 93+/ 21 ng/ml; chronic
91+/ 21.6 or 188+/ 16 ng/ml;

2 ng/ml

10-40 mg/ml

NA

schizophrenics 0–3.7 mg/24 hour;
controls 0–7.5 mg/24 hour
schizophrenic mean of 155 ng/ml,
non- 21 ng/ml, controls 29 ng/ml;
no dietary effects
65/65 mean 172 ng/ml; 73/73 mean
36 ng/ml
norm 12–89 ng/ml, epilepsy
26–67 ng/ml, depress
12–42 ng/ml, psycho 20–54 ng/ml,
schizo 17/86 12–96 ng/ml, 69/86
100–375 ng/ml, 33/45 10–100 ng/ml,
12/45 101–212 ng/ml
norm 17+/ 2.7 ng/ml, psychiat
24 +/ 2.8 ng/ml, schizo untreated
160+/ 22.7,
treated 35+/ 10 ng/ml, hysteria
69+/ 9 ng/ml
HDMT 4–10 mg/24 hour

ND

HDMT 4–10 mg/24 hour

>1 mg/24 hour

ND

Concentration

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Table 3. (Continued)

Reports of endogenous psychedelic N, N-dimethyltryptamines in humans

Drug Testing
and Analysis

wileyonlinelibrary.com/journal/dta

9

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

10

wileyonlinelibrary.com/journal/dta

HDMT, DMT,
MDMT
HDMT

DMT, NMT

DMT, NMT

Huszka et al.[48]

Cottrell et al.[49]

Oon et al.[50]

Oon and Rodnight[51]

Riceberg and Van
Vunakis[52]

1976
1976
1976

1976

1977

Copyright © 2012 John Wiley & Sons, Ltd.

1977

1977

1978

DMT, HDMT,
MDMT

6 controls

69 patients, 24 normal

19 normal

20 psychiatric patients; 2 controls

7 schizophrenics, special diet; MAOI phenelzine

4/4 DMT, 2/4 MDMT, 4/4 HDMT,
whole blood

3/4 DMT, 1/4 MDMT, 3/4HDMT, plasma

No diurnal variation, no dietary source
69/69 DMT; 17/24 DMT

15/20 HDMT; 0/2 HDMT; no DMT or
MDMT detected
19/19 DMT; 19/19 NMT

No HDMT, DMT, MDMT detected

13/23 DMT; 7/17 DMT
37/122 DMT; 1/20 DMT
23/54 DMT; 1/14 DMT

23 psychiatric patients, 17 controls
122 psyciatric patients; 20 controls
54 psychiatric patients, 14 controls; 1 patient
strict diet, 2 patients on neomycin

Christian et al.[43]
Narasimhachari and
Himwich[44]
Angrist et al.[45]
Rodnight et al.[46]
Murray and Oon[47]

1975
1975

DMT
DMT
DMT

Carpenter et al.[42]

1975

positive for DMT, MDMT
24/47 HDMT, 10/47 DMT; 14/46 HDMT

Narasimhachari et al.[41]

1974

2/11 acute schizo DMT
2/38 blood DMT; 1/44 urine psychotic
patients
6/6 HDMT;3/6 DMT; 0/6 MDMT

1 control cerebrospinal fluid
47 infantile autism, 46 controls

Lipinski et al.[39]
Bidder et al.[40]

1974
1974

3/6 DMT, 6/6 HDMT

DMT, MDMT
DMT, HDMT

HDMT, DMT,
MDMT
DMT, HDMT

Narasimhachari and
Himwich[38]

1973

6 controls neg for all; 5/6 autistics
positive for HDMT
4/6 schizo DMT, HDMT; 7/7 controls
negative;
6/45 DMT
1/11 DMT; 1/29 DMT

Positive/Negative

4/26 DMT, 6/26 5-HDMT; 4/10 DMT,
8/10 HDMT

DMT
DMT

Walker et al.[36]
Wyatt et al.[37]

1973
1973

6 chronic schizophrenics, 7 controls; special
diets, restricted meds
45 controls
11 controls, 29 psychiatric patients; no meds
for 30 days
6 chronic schizophrenics

6 autistics, 6 controls; special diets

Subjects

7 control
6 chronic schizo, 11 acute schizo, 11 hepatic coma
34 with acute psychotic illness, 3 with non
psychotic illness, 1 control
6 chronic schizophrenics highly restricted diet,
no drug administration 4 weeks
26 acute schizophrenics; 10 controls; no meds
for 3 weeks

DMT, HDMT

Narasimhachari et al.[35]

1972

HDMT, DMT,
MDMT
HDMT, DMT,
MDMT
DMT
DMT

Himwich et al.[34]

Author

1972

Year

Compounds
Analyzed
78 ng/ml

DMT range 0.1-4.5 mg/ 24 hr; DMT
range 0.1-0.5 mg/ 24 hr
HDMT 0.25-0.38pmol/ml, MDMT
0.09pmol/ml, DMT 0.77-3.69pmol/ml
HDMT 0.11-2.64pmol/ml, MDMT
0.7-2.89pmol/ml, DMT 0.27-14pmol/ml

DMT range 20–2500 ng/24 hour; NMT
range 121–3000 ng/24 hour

1-120 nmol HDMT/24 hour

0.05-0.79 ng/ml; 0.06-0.22 ng/ml
>500 ng/24 hour
DMT > 500 ng/24 hour, Mean range
226–1,717 ng/ 24 hour; control
228 ng/ 24 hour
NA

HDMT mean 1.67 mg/24 hr schizo,
1.73 mg/24 hr controls; DMT not
quantitated
ND
ND

(1) 6, (1) 1.8
(1) 2.5 ng/ml, (1) 4.6 ng/ml;
0.76 ng/ml
1-3 mg/24 hour; <1 mg/24 hour

HDMT 1–3 mg/24 hour;
DMT 1 mg/24 hour

<5 mg/ 24 hour DMT; 3–5 mg/ 24 hour
HDMT; 0/6, 0/7 for MDMT
1-2 ng/ml
1.0 ng/ml; 10.6 ng/ml

acute 200+/ 47.5 or 289+/
<3-5 mg/24 hour

Concentration

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Table 3. (Continued)

Drug Testing
and Analysis
S. A. Barker, E. H. McIlhenny and R. Strassman

Drug Test. Analysis (2012)

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

Drug Test. Analysis (2012)

DMT, NMT

DMT

Murray et al.[55]

Checkley et al.[56]

1979

1979

Copyright © 2012 John Wiley & Sons, Ltd.

DMT, MDMT

HDMT
HDMT

HDMT

Uebelhack et al.[60]

Sitaram et al.[61]
Raisanen et al.[62]

Karkkainen et al.[63]

Karkkainen and
Raisanen[64]

1979
1980

1983

1983
1984

1988

1992

HDMT
HDMT, HNMT

DMT, MDMT,
HDMT, NMT

Karkkainen et al.[65]
Takeda et al.[66]

Forsstrom et al.[67]

1995
1995

2001

HDMT

DMT, MDMT
DMT

Raisanen and
Karkkainen[57]
Smythies et al.[58]
Checkley et al.[59]

DMT, HDMT

DMT

Walker et al.[54]

1979

1979

DMT, MDMT

Corbett et al.[53]

Author

1978

Year

Compounds
Analyzed

7/23 HDMT, 3/23 DMT, 7/23 NMT
14/29 HDMT, 0/29 DMT, 13/29 NMT
2/13 HDMT, 2/13 DMT, 2/13 NMT

29 psychiatric patients
13 internal medicine patients

112/112 HDMT
89/140 HDMT, 46/140 HNMT;
2/200 HDMT

1/1 before; HDMT greatly increased
after MAOI

75/75 HDMT; 51/51 HDMT

11/11 DMT; 1/11 MDMT
2/5 DMT
2/5 DMT
14/14 DMT, 12/14 MDMT; 12/12 DMT,
10/12 MDMT
5/8 HDMT
48/48 HDMT; 23/23 HDMT

all DMT and HDMT positive

all DMT positive

74/74 DMT; 19/19 DMT

17/57 DMT, 14/57 MDMT; 9/41 DMT,
2/41 MDMT
6/9 DMT

2/6 DMT, 2/6 MDMT, 6/6 HDMT, urine

Positive/Negative

23 surgical patients;

112 male violent offenders
140 psychiatric and non-psychiatric patients;
200 controls

1 healthy male; with and without MAOI nialamide

75 psychiatric patients; 51 controls

8 healthy adults
48 male violent offenders; 23 controls

11 patients undergoing lumbar puncture
5 schizophrenics
4 manic-depressives
14 schizophrenics; 12 controls

26 controls

74 psychiatric patients; 19 controls; no meds
for 2 weeks
18 schizophrenics;20 patients with liver disease;
19 controls

9 schizophrenics

57 psychiatric patients; 41 controls

Subjects

arterial range 24–118 pg/ml; venous
range 18–103 pg/ml; no sig dif
between two sources
DMT range 0.1-4.5 mg/ 24 hr; DMT
range 0.1-0.5 mg/ 24 hr
10/18 >500 ng/24 hr; 12/20 >
500 ng/24 hr;
1/19 >500 ng/24 hr
DMT mean 96 ng/g creatinine; HDMT
mean 950 ng/g creatinine
DMT range from <0.12-100.4 ng/ml;
~1-3 mg/ml, ~1-2 mg/ml
~0.5-1 mg/ml, ~0.5-3 mg/ml
Sum DMT + MDMT; 1,404.3+/ 481 ng/ml
patients; 234.4+/ 213.6 ng/ml controls
0.02-7.8 nmol/12 hour
range 0.15-103 nmol/g creatinine;
1.23-14.1 nmol/g creatinine
range 0.05-96.3 nmol/g creatinine;
0.29-23.2 nmol/g creatinine; MAOI
407 nmol/ g creat
range 0.002-1.785 nmol/ mmol
creatinine; 0.06-16.6 nmol/mmol
creatinine MAOI
no diurnal variation observed;
bufotenin excretion was
intermittent
range 0.01-17.1 nmol/mol creatinine
range 2.5-288 ng/ mg creatinine,
HNMT 2.0-102 ng/mg; mean
10.9 ng/mg creatinine
HDMT 0.43-33.57 mg/l, DMT
0.16-.28 mg/l, NMT 0.12-.29 mg/l
HDMT 0.81-24.9 mg/l, NMT
0.05-0.25 mg/l
HDMT 0.48-7.2 mg/l, DMT 0.42-.54 mg/l,
NMT 0.05-0.13 mg/l

HDMT 1.1-10.3 nmol/ml, MDMT
1.3-8.7 nmol/ml, DMT 9.1-13.1 nmol/ml
ND

Concentration

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Table 3. (Continued)

Reports of endogenous psychedelic N, N-dimethyltryptamines in humans

Drug Testing
and Analysis

wileyonlinelibrary.com/journal/dta

11

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

3.3+/ 0.49 ng/ml; 4.39+/ 0.43 ng/ml;
1.53+/ 0.30 ng/ml
HDMT
Emanuele et al.[69]

15 autistic spectrum disorder; 15 schizophrenics;
18 controls

13/13 controls stool samples HDMT,
1/13 DMT
15/15 HDMT; 15/15 HDMT; 18/18 HDMT

NA
<0.05-9.1 ng/ml; NA (Kidney tissue
15 pg/g HDMT and DMT,
14 pg/g DMT in lung)
1.0-180 ng/g HDMT; 0.13 ng/g DMT
0/137 plasma or serum DMT, HDMT
9/9 urine controls HDMT; 0/9 DMT
DMT, HDMT
Karkkainen et al.[68]

137 hospital patients; 9 control

Positive/Negative
Compounds
Analyzed

as well as patients. Despite many such efforts, a definitive link
has yet to be demonstrated between the blood and/or urine
levels of these compounds and any psychiatric diagnosis.[85,93]
The earliest studies (1950s–1960s) in the search for endogenous psychedelics applied the technology available at the
time. These were mainly paper and thin-layer chromatography
(TLC) using different reagents as visualization (colour development) sprays, as well as comparing Rf values with spotted
standards as the criteria for identification. In 1967, thin-layer
spots were isolated and derivatized in an attempt to confirm
their identification by gas–liquid-chromatography (GC) using
a flame-ionization detector (FID).[21] In this case, Rf values
from TLC and relative retention time (Rt) from GC that were
consistent with known standards served as the confirmation
criteria. Subsequent studies applied this technology utilizing
other detectors, such as nitrogen-phosphorous, electron
capture and, eventually, mass spectrometry (MS). In many of
these studies, the sole criterion for identification was retention time compared to a reference standard. However, in the
case of the early MS data, the presence of a single major
fragment ion[38] (m/z 58) or one or two minor ions,[39] served
as additional confirmation. Liquid chromatography with UV
and fluorescence detection was also applied, with the
collected peaks being confirmed by GC-MS in some cases.
As the analytical technology evolved, so too did the methods
applied to detect and measure the compounds of interest,
with resultant gains in sensitivity, specificity, and validity.
The most recent methods have applied LC-MS/MS technologies in combination with more stringent confirmation
criteria.[67–69] These criteria are based on specific protonated
molecules, fragment ions and their ratios to one another,
and on relative retention times. However, as the criteria have
become more exacting and the specificity of the methodology
has improved, detection of the endogenous psychedelics
appears to have become less frequent and, where detection
has occurred, at significantly lower concentrations than
originally reported.
Tables 1–3 are a compilation of 69 studies directed towards
detecting or detecting and quantitating the three indole
psychedelics – DMT, HDMT, and MDMT – in human (patient
and/or control) CSF, blood, and/or urine. The entries for each
study were taken from copies of the original publications. In
some cases, the published studies neglected to address the
relevant analytical issues reviewed.

Author

Subjects

S. A. Barker, E. H. McIlhenny and R. Strassman



HDMT: urine

Study review

wileyonlinelibrary.com/journal/dta

2010

2005


Year

Table 3. (Continued)

12

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Concentration

Drug Testing
and Analysis

Sixty-nine studies were reviewed. Other studies that exist
were either not accessible through current abstract search
engines, were sufficiently obscure as not to be abstracted, or
were not available in a translated form for inclusion in this
analysis. Articles were obtained through SciFinder (Chem
Abstracts Selects; https://scifinder.cas.org) and PubMed
(http://www.ncbi.nlm.nih.gov/pubmed/) database searches.

Fifty-one studies examined urine samples for HDMT (27
assayed urine for HDMT only). Taking into account the
presence of the 5-hydroxyl group on HDMT, 7 studies specifically addressed the issue of the excretion of HDMT as a

Copyright © 2012 John Wiley & Sons, Ltd.

Drug Test. Analysis (2012)

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

Reports of endogenous psychedelic N, N-dimethyltryptamines in humans
conjugate by using hydrolysis with HCl or enzyme treatment.
From these studies we know that approximately 50% of the
total HDMT is excreted as a glucuronide conjugate. The
remaining 44 studies did not conduct hydrolysis or enzyme
treatment and thus did not determine the total amount of
HDMT excreted but rather free HDMT alone.
• Urine samples from 1912 individuals were assayed; 1249
patients (predominantly diagnosed with schizophrenia)
and 663 controls. Among patients, 886 were positive for
HDMT (71%) and 363 were negative. Among controls, 363
were positive for HDMT (55%) and 300 were negative.
Thus, 1249 individuals were positive (65%) and 663 were
negative. Most of the urine samples were obtained from
24-h collections with varying quantities of the total collection being used for analysis. However, many other studies
only used morning or random samples, while a few used
8- or 12-h collections. Varying amounts of urine were used
in the assays, based on volume or total mg creatinine. The
range of extraction techniques is shown in Table 1 and the
analytical approaches employed are shown in Table 2. One
study examined and failed to find a diurnal variation in
urine concentrations of HDMT,[50] while another reported
that HDMT excretion did not vary diurnally but rather
was intermittent.[64] Several studies examined dietary
influences on detection of HDMT but none established a
dietary source (Table 3).
• Concentrations of HDMT were usually reported as mg/24 h
while other studies reported concentrations as mg/g or
mg/mg creatinine, nmol or pmol/ml or per 24 h, and
ng/ml or mg/L. Using the most common methods of reporting, these studies demonstrated concentrations ranging
from 1 to 62.8 mg/24 h, and from 0.48 to 218 ng/ml.





DMT: blood



HDMT: blood
• Of the 69 studies, 4 examined blood for the presence of
HDMT.
• Blood samples from 240 individuals were examined: 166
patients and 74 controls. Plasma, serum, and whole blood
were used. A single study provided 146 of these total
samples[67]; it used a limit of detection of 0.3 ng/ml and a
1.0 ml sample of plasma or serum for analyses. For all of the
studies combined, 4 patients were positive for HDMT (2.4%)
and 162 were negative. Eighteen controls were positive for
HDMT (24%) and 56 were negative. Thus, a total of 22
individuals were positive for HDMT (9%) in blood and 218
were negative. One study reported higher concentrations of
HDMT were obtained from extraction of whole blood
compared to serum.[52]
• When concentrations were reported (rather than simply
present or not present) the concentrations of HDMT in
blood ranged from 22 pg/ml (HPLC-radioimmunoassay)[52] to
40 ng/ml (direct fluorescence assay of extracts).[11]






• None of the 69 studies examined CSF for HDMT.

• Of the 69 studies, 29 examined urine for DMT.

Drug Test. Analysis (2012)

Of the 69 studies, 11 examined blood for DMT.
Blood samples from 417 individuals were examined for the
presence of DMT: 300 patients and 117 controls. Blood
samples used were plasma, serum and/or whole blood.
Among patients, 44 were positive (15%) and 256 were
negative. A single study is responsible for 137 of these
negative samples[68]; the authors – who used a 1.0 ml
sample of plasma or serum – reported a limit of detection
of 0.2 ng DMT/ml. Among controls, 28 were positive (24%)
and 89 were negative. Thus, a total of 72 individuals were
positive for DMT (17%) in blood and 345 were negative.
The range of extraction methods used is shown in Table 1
and analytical approaches employed are shown in Table 2.
One study demonstrated that higher concentrations of
DMT were found by extracting whole blood rather than
using plasma.[52] One study demonstrated that there was
no difference in DMT blood levels between venous and
arterial blood.[54] One study reported that DMT concentrations were stable in plasma when stored for 60 days at
6 C[36] (Table 3).
When concentrations were reported (rather than simply
present or not present), the concentrations of DMT in
blood ranged from 51 pg/ml (HPLC-radioimmunoassay)[52]
to 55 ng/ml (direct fluorescence assay of extracts).[11]

DMT: cerebrospinal fluid

HDMT: cerebrospinal fluid

DMT: urine

Urine samples from 861 individuals were examined: 635
patients and 226 controls. Among patients, 276 were
positive for DMT (43%) and 359 were negative. Among
controls, 145 were positive (64%) and 81 were negative.
Thus, a total of 421 individuals were positive for DMT
(49%) in urine and 440 were negative. Most of the urine
samples were 24-h collections and analytical samples
varied in volume. However, many also used morning or
random samples, while a few used 8- or 12-h collections.
Various amounts of the urine were used in the assays,
based on a set volume of urine or that containing a predetermined amount of creatinine. The range of extraction
techniques is shown in Table 1 and analytical approaches
employed are shown in Table 2. Several studies examined
dietary influences on detection of DMT and were uniformly
negative (Table 3). One study reported that DMT and NMT
(N-methyltryptamine; 4, Figure 1) concentrations in urine
were stable when stored at 15 C for up to 90 days.[50]
Concentrations of DMT were usually reported as mg/24 h while
others used mg/g or mg/mg creatinine, nmol/ml or pmol/ml
nmol/24 h, pmol/24 h, ng/ml or mg/L, etc. Concentrations
ranged from 0.02 to 42.98 +/ 8.6 (SD) mg/24 h, and from
0.16 to19 ng/ml.



Of the 69 studies, 4 examined CSF for DMT.
CSF samples from 136 individuals were examined for the
presence of DMT: 82 patients and 54 controls. Among
patients, 34 were positive for DMT (41%) and 48 were
negative. Among controls, 22 were positive (41%) and 32
were negative. Thus, 56 individuals were positive (41%)
and 80 were negative.
Concentrations of DMT in CSF ranged from 0.12 to100 ng/ml
(Table 3).

Copyright © 2012 John Wiley & Sons, Ltd.

wileyonlinelibrary.com/journal/dta

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

13

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Drug Testing
and Analysis

Drug Testing
and Analysis

14

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

S. A. Barker, E. H. McIlhenny and R. Strassman

MDMT: urine
• Of the 69 studies, 9 examined urine for the presence of MDMT.
• Urine samples from 113 individuals were examined: 94
patients and 19 controls. A single study was responsible for
65 of these samples.[67] Combining all studies, two patients
were positive for MDMT in urine (2%) and 92 were negative.
Two controls were positive (10.5%) and 17 were negative.
• The concentrations of MDMT in urine ranged from 0.3 to
1.3 ng/ml (HPLC-radioimmunoassay).[52]
MDMT: blood
• Of the 69 studies, 2 examined blood for the presence of
MDMT.
• Blood samples from 39 individuals were examined: 36 patients
and 3 controls. Among patients, 20 were positive (51%) and 16
were negative. None of the 3 controls was positive for MDMT
(Table 3).
• A single estimate of 2.0 ng/ml was reported by one study
(HPLC-radioimmunoassay).[52]
MDMT: cerebrospinal fluid
• Of the 69 studies, 4 examined CSF for MDMT.
• CSF samples from 136 individuals were assayed: 83 patients
and 53 controls. Among patients, 28 were positive (34%) and
55 were negative. Among controls, 12 were positive (23%)
and 41 were negative. Thus, a total of 40 individuals were
positive (29%) and 96 were negative.
• Only one study reported concentrations of MDMT in CSF, in
which case the mean combined concentrations of DMT and
MDMT were approximately 1400 ng/ml for patients and
230 ng/ml for controls with quite large standard deviations
(GC-FID).[60]
The above does not address the analytical methods’
sensitivity and specificity, and assumes that all of the data
as collected and reported are accurate, either in their detection or non-detection of the target analyte(s) or the concentrations observed. However, this is almost certainly not the
case. As can be seen from Table 2, almost every study
conducted between 1955 and 1972 used paper or TLC for
detection, quantitation, and confirmation of one or more of
these compounds. Several studies used multiple chromatographic conditions and detection reagents in attempting to
‘confirm’ their results. It is well-known, however, that paper
chromatography is limited in specificity and sensitivity in that
spots tend to be diffused and the mobility of the compounds
of interest is influenced by the presence of other components
and salts. TLC is somewhat better but is also susceptible to
these same factors in addition to many other variables such
as humidity. Other studies used 2-D chromatographic conditions and very sensitive and moderately specific detection
reagents. Nevertheless, the criteria for detection relied on Rf
values and colour reactions relative to standards (Table 2).
There were no data regarding the structure of the detected
compounds. Much of the literature acknowledged their limitations and qualified results by referring to the compounds
detected as, for example, ‘bufotenin-like’.[4,7,15]
In many studies, large volumes of urine were extracted and
concentrated (Table 1), resulting in a final extract less than
optimal for such analysis. For example, in order to precipitate

wileyonlinelibrary.com/journal/dta

salts and other compounds, acetone was often used in the
final steps of sample purification. However, Tanimukai
demonstrated that acetone forms adducts with primary
amines co-extracted in the process leading to formation of
compounds that behaved similarly to bufotenin, for example,
on paper or TLC.[20] Although there do not seem to be any
published replications of Tanimukai’s findings, they did
lead to modification of many of the extraction procedures
that were subsequently designed to fractionate tertiary from
primary amines (Table 1).
As can be seen from Table 1, the extraction methods
employed were predominantly classical liquid-liquid extractions with appropriate pH adjustments or the use of ion
exchange resins or packings. The earliest studies, and
especially those extracting large volumes of urine, often used
a combination of methods in sequence in an attempt to
obtain an adequately purified and appropriate extract for
paper or TLC analysis. Almost none of these studies reported
analyte recoveries, however. The most recent methods have
all employed ion exchange solid-phase extraction for the
isolation of the target compounds from urine.[67–69]
In addition to methodological complications, misidentifications of compounds may also have occurred because both
paper and TLC using colour reagents require a somewhat
subjective interpretation. For example, Rodnight[2] and Siegel
et al.[12] proposed that the substance detected by Bumpus
and Paige[1] was tryptamine and not HDMT. Another
potential problem, involving co-injection of extracted indoleethylamines in GC analyses using the solvent methylene
chloride, was addressed by Brandt et al.[86] These authors
showed that the compounds of interest react with methylene
chloride under such conditions, forming quaternary salts and
analytical artifacts.
Some early studies used more than one method for their
analyses, increasing the likelihood that their identifications
were accurate; for example, combining TLC and GC with
packed column technology. However, the resolving power of
packed column technology is low and individual ‘peaks’ were
often broad humps, sometimes several minutes wide. Subsequent studies using capillary chromatography have consistently demonstrated that some peaks observed using packed
columns were often a composite of several compounds. In
addition, the flame ionization detector that many studies used
also lacked specificity. Although these approaches used two
different technologies, the technologies themselves were relatively non-specific and yielded equivocal results.
Some investigators added, or used exclusively, GC with ECD
or NP detectors. While these detectors added sensitivity – and
in the case of NPD a degree of specificity – they continued to
rely on Rt and detector response as their identification criteria.
No structural data were generated. Other research teams used
ultraviolet spectrometry and/or spectrofluorometry to detect
and quantify the relevant compounds in extracted samples,
either directly or after thin-layer or paper chromatography
purification. However, the non-specificity of these methods
also did not provide data regarding structural identity. For
example, Siegel[12] demonstrated that the fluorescence
method used by Franzen and Gross[11] did not actually
measure a maxima from HDMT but instead the tail of the
fluorescence spectrum of another compound. These findings
bring into question studies that applied these and similar
methods.

Copyright © 2012 John Wiley & Sons, Ltd.

Drug Test. Analysis (2012)

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

Reports of endogenous psychedelic N, N-dimethyltryptamines in humans
Inconsistent findings in previous research suggest that
sensitivity was also an issue. Data concerning extraction
efficiency and recovery, limits of detection, specificity, reproducibility, storage stability, the use of double blind and replicate
analyses, and other variables that are now basic requirements
in assay research are lacking either altogether or in part in earlier
studies. At best, some early papers point to other references for
some of these data. However, we found direct comparisons of
methods in either positive or negative studies difficult to
conduct.
The first applications of mass spectrometry to the detection
and quantitation of putative endogenous psychedelics in
man occurred in 1973. Walker et al.[36] and Wyatt et al.[37]
employed an isotope dilution method monitoring two ions to
detect and quantitate DMT in blood. Soon thereafter,
Narasimhachari and Himwich used GC-MS with single ion monitoring (m/z 58) to detect DMT from urine extracts.[38] These latter
authors also extracted sufficient material, using TLC for clean-up,
to obtain a total ion mass spectrum of the detected substance,
and demonstrated its identity with authentic DMT. These data
were the first methodologically credible regarding DMT’s
presence in humans. Subsequent studies by these and other
authors applied different MS capabilities for the detection,
quantitation, and unequivocal confirmation of DMT and HDMT
in humans. In 1974, Narasimhachari et al., providing a matching
total ion spectrum of an extracted compound, reported the
unequivocal identification of HDMT from human urine.[41] In
1976, Rodnight et al.,[46] using similar methods, published a
matching total ion spectrum for DMT in human urine. Other MS
techniques matched the retention time and protonated molecule
ions (chemical ionization MS) for DMT and HDMT in urine.[50,51]
Additional studies detected, quantified, and confirmed the
identity of DMT, NMT, and HDMT in human blood and urine using
selected ion monitoring (SIM) of multiple fragment ions (Table 2). It
is important to note that MDMT has yet to be unequivocally
detected by any MS-based method in blood or urine. However,
there are two reports of its presence in CSF using GC-MS/SIM.[53,58]
Continual improvement in MS technologies has greatly
enhanced detection, sensitivity, and specificity of analytic
studies searching for these compounds; for example, capillary
chromatography for GC, and more advanced LC-mass spectrometers. This being the case, it is encouraging to note that all studies
since 1973 using MS methodology have confirmed the presence
of one or more of these compounds in human body fluids
(Table 2). The most recent methods utilize LC-MS/MS which
afford analyses and confirmation by several additional chemical
processes; LC separation and matching of Rt, molecular ion
matching, and fragment ion presence and ratio matching. This
technique also allows for the detection of these compounds in
the pg/ml range while providing unequivocal mass spectrometric
confirmation of structural identity.
Thus, while many early studies lacked today’s more definitive technology, it is likely that many have been confirmed
by later MS-based studies. On the other hand, most early
studies that reported rather high concentrations on these
compounds were most likely in error.

Discussion and conclusions
The answer to the question, ‘Are the tryptamine psychedelic
substances DMT, HDMT and MDMT present in the human body?’

Drug Test. Analysis (2012)

is most likely yes. We believe that the preponderance of the mass
spectral evidence proves, to a scientific certainty, that DMT and
HDMT are indeed endogenous and can be measured in human
body fluids. The evidence is less compelling for MDMT where
the only two MS-based positive studies – in CSF – were
performed by the same research group. There is no mass spectral
data on detection of MDMT in blood or urine. Thus, further
studies are necessary to determine whether MDMT exists in
humans. Similarly, there are no data on the possible presence
of HDMT in CSF. This too requires examination.
With respect to the paucity of data regarding endogenous
MDMT, it should also be noted that HDMT is both a metabolite
of and precursor for MDMT. The relationship of these two
compounds may help explain why HDMT is so much more
frequently detected than MDMT. Future studies will help
explicate this relationship.
As to the question, ‘Were the analytical methodologies and the
criteria for compound identification adequate?’, the answer is less
certain. Undoubtedly, some studies misidentified the target
compounds or, at the minimum, greatly overestimated their
concentrations.
Are they of dietary origin? Many early studies attempted to
determine if diet or gut bacteria were responsible for positive
results. Sterilization of the gut with antibiotics or feeding subjects
special diets had no effect on these studies’ results. In addition,
no evidence suggested that medication(s) played a role. More
recently, however, Karkkainen et al.[68] isolated significant quantities of HDMT from stool samples, and hypothesized that HDMT
may be synthesized by cells of the intestinal epithelium or the
kidney, but not by gut flora.
When are these compounds produced? The very small numbers of studies that have looked for diurnal, circadian, or ultradian
variations in levels of DMT or HDMT in humans have been
negative. This may be due, in part, to too infrequent sampling
times and inadequate assay methodologies. However, one longitudinal study and one assessing diurnal rhythms of DMT in
human urine suggest that measurable concentrations occur only
intermittently.[50] The same is apparently true for HDMT.[64] There
are no comparable data available for MDMT. The two DMT
studies cited were conducted in urine only and such analyses
are probably best conducted in blood. They do stand, however,
as examples of one of the possible further complications in
understanding the source, role and function of these compounds.
Where in the human body are they synthesized? The tissue
source or sources of these compounds in humans remains
unknown and, that being the case, we should not assume that
monitoring blood, urine, or CSF will answer this question. DMT
synthesis has been proposed to occur in adrenal and lung, where
high levels of the enzyme responsible for its synthesis – indole-Nmethyltransferase (INMT) – have been reported.[96,97] While these
studies did not demonstrate high INMT levels in brain, the active
transport of DMT across the blood–brain barrier[98] suggests that
peripheral synthesis may nevertheless affect central function. In
addition, the mapping of INMT sites thus far has been based
solely on INMT mRNA studies which only establish where active
enzyme translation is occurring. However, recent studies by Cozzi
et al.,[99] using a fluorescent antibody to INMT and confocal
microscopy, have identified INMT in spinal cord, brain, retina,
and pineal, and suggest the possibility of applying other
powerful molecular biology tools and methods for mapping the
location and characterizing the regulation of the endogenous
psychedelic pathway. Their findings suggest that INMT may be

Copyright © 2012 John Wiley & Sons, Ltd.

wileyonlinelibrary.com/journal/dta

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

15

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Drug Testing
and Analysis

Drug Testing
and Analysis

16

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

S. A. Barker, E. H. McIlhenny and R. Strassman

an inducible enzyme. These molecular biological approaches, in
combination with advances in assay methodology, may help
finally characterize the biochemistry and physiology of these
compounds in humans.
The next questions – Can we influence the detection of
endogenous psychedelics in humans by pre-treatment with
MAO inhibitors? How does the turnover rate and metabolism
of these substances influence their detectabilty? Have the
precursors and/or metabolites of these compounds been
adequately monitored? – require synthesizing several parallel
lines of evidence. In humans, only a very small percentage
of exogenously administered DMT is excreted in urine as the
parent compound.[88] This is also true for HDMT[100] and
MDMT.[101] Despite this fact, every cited study monitored,
without exception, only the parent compounds themselves
in the various biological fluids examined. These compounds
all have a very short half-life – a few minutes – and blood
levels are undetectable in less than an hour after administration. This rapid metabolism is due to their being excellent
substrates for MAO-A. This enzyme’s action on the
psychedelic tryptamines results in the formation of their
corresponding indoleacetic acids, which are indistinguishable
from these same acids resulting from other better-known
sources, such as tryptamine and serotonin. Several studies
attempted to maximize detection of these substances by
treating subjects with MAO inhibitors such as tranylcypromine
and phenelzine (Table 3). In most cases, this did result in
higher concentrations of the target compounds. Nevertheless,
even with significant MAO inhibition, the concentrations of
parent compounds remained quite small. This observation
has, perhaps, a ready explanation: the other metabolic
pathways for DMT, MDMT, and HDMT.
Recognition and understanding of these compounds’
pathways for degradation may afford an approach to circumventing the low concentrations of the parent compounds
observed even after MAO inhibition. Sitaram et al.[89–91] have
shown that, in MAO-inhibited rats, metabolism of these
psychoactive tryptamines is shifted away from MAO-A and
indoleacetic acid formation to the N-oxidase and the respective N-oxides. However, no studies have yet pre-treated
humans with MAO inhibitors and measured the parent
compounds and their corresponding N-oxides. The advantage
of such a study is that the N-oxide, as opposed to the indoleacetic acid, retains the original structure of the parent
molecule, permitting a cumulative association. As a proof of
concept, we, have measured blood and urine levels of DMT
and its N-oxide (5, Figure 1) in humans administered a
botanical preparation of DMT and MAO-A inhibiting harmala
alkaloids – the Amazonian brew ayahuasca.[102,103] Concentrations of the N-oxide of DMT in these subjects were 3–4 times
greater in blood, and 20 times greater in urine, than DMT
itself. Therefore, monitoring the N-oxide metabolites rather
than the parent compounds alone in MAO-inhibited
humans may provide a substantial advantage in detecting
and quantitating the endogenous psychedelic compounds.
Several of the studies reviewed did examine samples for
the corresponding NMT, which is both a precursor for and a
metabolite of the three endogenous psychedelics (NMT,
HNMT, MNMT). However, in humans administered ayahuasca
NMT was only intermittently detected in blood and urine
and concentrations were quite low (pg/ml).[102,103] This
also may be the result of a shift in metabolism of DMT to

wileyonlinelibrary.com/journal/dta

the N-oxide after MAO inhibition and suggests that monitoring NMT in vivo may not be necessary or possible. Nonetheless, several of the reviewed studies suggested that the
corresponding NMT was detected (Table 3). That data must
now also be in question.
DMT-N-oxide is neither a substrate for MAO-A nor for
N-demethylases. Since similar metabolic pathways exist for
HDMT and MDMT, we suggest that MAO inhibition in humans
will enhance detection and quantitation of these compounds
in the periphery, especially if the N-oxide metabolites are
monitored.
Thus, we can respond to the questions ‘Is monitoring these
compounds in biological samples such as CSF, blood and/or
urine the best, or even most practical way to determine their
activity?’ and ‘What will such data tell us about the possible
normal function of these compounds in humans?’ Data
regarding their peripheral dynamics – concentrations, circadian variation, and metabolism – as assessed by rigorous
analytic methods applied to biological samples represent the
most accessible approach to beginning to determine their
possible role in human psychophysiology and should be
pursued.
Our last question is ‘Where does the research on endogenous psychedelics go from here?’ One avenue for future
studies concerns the endogenous nature of MDMT. This
review has illustrated the convincing evidence that DMT and
HDMT are endogenous in humans. However, MDMT has not
been reported in human blood or urine but is apparently
present in CSF. However, CSF has not been examined for
the presence of HDMT. We propose that future studies of
CSF, blood (including whole blood where higher concentrations may be observed) and urine monitor all three compounds and their N-oxides using superior, fully validated mass
spectrometric methodology. Pretreatment of study subjects
with an MAO inhibitor should optimize results and may prove
critical to such studies. A technical issue regarding HDMT
analysis also must be considered in future studies. Assays for
this compound should include an enzyme hydrolysis step to
free conjugates that may be formed from both the parent
compound and its N-oxide.
Another area for future research concerns assay sensitivity.
We believe it is necessary to improve sensitivity of assays of
the parent compounds to 1.0 pg/ml or less. Given the possible
intermittent presence of these compounds in the periphery,
blood and urine analyses may require more frequent
sampling and longer collection times.
The search for endogenous psychedelic tryptamines should
also turn towards other human tissues than blood, urine and
CSF; that is, solid organs such as adrenal, brain, lung, pineal,
retina, and other tissues in which INMT activity has been
noted using molecular biology tools. The combination of
assaying relevant compounds with cell and molecular biology
approaches will provide the most detailed possible assessment of the location(s) of synthesis and, ultimately, the role
of these compounds in human physiology.
For example, mapping of INMT and its presence within
certain cell types and locations should reveal its intracellular
distribution and possible associations with various receptors.
The introduction of an INMT knockout mouse to the research
effort could greatly assist in understanding the role of this
enzyme and, by inference, the endogenous psychedelics. With
these tools in hand, the research that can be conducted may

Copyright © 2012 John Wiley & Sons, Ltd.

Drug Test. Analysis (2012)

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

Reports of endogenous psychedelic N, N-dimethyltryptamines in humans

Q1

finally provide us an answer to the question: ‘Why do humans
produce endogenous psychedelics?’ The research thus far is
limited but there are many possibilities awaiting further
inquiry.

References
[1] F.M. Bumpus, I.H. Page. Serotonin and its methylated derivatives in
human urine. J. Biol. Chem. 1955, 212, 111.
[2] R. Rodnight. Separation and characterization of urinary indoles
resembling 5-hydroxytryptamine and tryptamine. Biochem. 1956,
64, 621.
[3] E. Fischer, F.A. Vazquez, T.A. Fernandez, L. Liskowski. Bufotenin in
human urine. Lancet 1961, 1, 890.
[4] E. Fischer, T.A. Fernandez Lagravere, A.J. Vazquez, A.O. Di Stefano. A
bufotenin-like substance in the urine of schizophrenics. J. Nerv.
Ment. Dis. 1961, 133, 441.
[5] A. Feldstein, H. Hoagland, H. Freeman. Radioactive serotonin in
relation to schizophrenia. Arch. Gen. Psychiatr. 1961, 5, 54.
[6] T.L. Perry, K.N.F. Shaw, D. Walker, D. Redlich. Urinary excretion of
amines in normal children. Pediatrics 1962, 30, 576.
[7] G.G. Brune, H.H. Hohl, H.E. Himwich. Urinary excretion of bufoteninlike substance in psychotic patients. J. Neuropsychiatry1963, 4, 14.
[8] T.L. Perry. N-Methylmetanephrine: Excretion by juvenile psychotics.
Science 1963, 139, 587.
[9] H. Sprince, C.M. Parker, D. Jameson, F. Alexander. Urinary indoles in
schizophrenic and psychoneurotic patients after administration of
tranylcypromine (Parnate) and methionine or tryptophan. J. Nerv.
Ment. Dis. 1963, 137, 246.
[10] T.L. Perry, W.A. Schroeder. The occurrence of amines in human
urine: Determination by combined ion exchange and paper
chromatography. J. Chromatogr. 1963, 12, 358.
[11] F. Franzen, H. Gross. Tryptamine, N,N-dimethyltryptamine, N,Ndimethyl-5-hydroxytryptamine and 5-methoxytryptamine in human blood and urine. Nature 1965, 206, 1052.
[12] M. Siegel. A sensitive method for the detection of N,Ndimethylserotonin (bufotenin) in urine; Failure to demonstrate
its presence in the urine of schizophrenic and normal subjects.
J. Psychiatr. Res. 1965, 3, 205.
[13] T. Nishimura, L.R. Gjessing. Failure to detect 3,4-dimethoxyphenylethylamine and bufotenine in the urine from a case of
periodic catatonia. Nature 1965, 206, 963.
[14] M. Takesada, E. Miyamoto, Y. Kakimoto, I. Sano, Z. Kaneko. Phenolic
and indole amines in the urine of schizophrenics. Nature 1965, 207,
1199.
[15] T.M. Runge, F.Y. Lara, N. Thurman, J.W. Keyes, S.H. Hoerster Jr.
Search for a bufotenin-like substance in the urine of
schizophrenics. J. Nerv. Ment. Dis. 1966, 142, 470.
[16] T.L. Perry, S. Hansen, L. MacDougall, C.J. Schwarz. Urinary amines in
chronic schizophrenia. Nature 1966, 212, 146.
[17] B. Heller. Influence of treatment with an amine oxidase inhibitor on
the excretion of bufotenin and the clinical symptoms in chronic
schizophrenic patients. Int. J. Neuropsychiat. 1966, 2, 193.
[18] E. Fischer, H. Spatz. Determination of bufotenin in the urine of
schizophrenics. Int. J. Neuropsychiat. 1967, 3, 226.
[19] Y. Kakimoto, I. Sano, A. Kanazawa, T. Tsujio, Z. Kaneko. Metabolic
effects of methionine in schizophrenic patients pretreated with a
monoamine oxidase inhibitor. Nature 1967, 216, 1110.
[20] H. Tanimukai. Modifications of paper and thin layer chromatographic methods to increase the sensitivity for detecting Nmethylated indolamines in urine. J. Chromatogr. 1967, 30, 155.
[21] H. Tanimukai, R. Ginther, J. Spaide, H.E. Himwich. Psychotomimetic
indole compound in the urine of schizophrenics and mentally
defective patients. Nature 1967, 216, 490.
[22] H. Tanimukai, R. Ginther, J. Spaide, J.R. Bueno, H.E. Himwich.
Occurrence of bufotenin (5-hydroxy-N,N-dimethyltryptamine) in
urine of schizophrenic patients. Life Sci. 1967, 6, 1697.
[23] E.M. Acebal, H. Spatz. Effect of trifluperidol (R 2498) on the urinary
elimination of bufotenin in schizophrenia. Int. J. Neuropsychiat.
1967, 3, 472.
[24] A. Faurbye, K. Pind. Occurrence of bufotenin in the urine of
schizophrenic patients and normal persons. Nature 1968, 220, 489.
[25] D.W. Sireix, F.A. Marini. Studies on the elimination of bufotenin in
urine. Behav. Neuropsychiatry 1969, 1, 29.

Drug Test. Analysis (2012)

[26] H. Spatz, D.W. Sireix, F.A. Marini, E. Fischer, A. Bonhour, E.M. Acebal.
Laboratory and animal studies on the chemistry of bufotenin.
Quantitative determination on bufotenin in human urine. Behav.
Neuropsychiatry 1969, 1, 25.
[27] E. Fischer, H. Spatz. Studies on urinary elimination of bufotenin-like
substances in schizophrenia. Biol. Psychiat. 1970, 2, 235.
[28] J.M. Saavedra, U. Udabe. Quantitative assay of bufotenine in
psychiatric outpatients. Psychosom. 1970, 11, 90.
[29] H. Tanimukai, R. Ginther, J. Spaide, J.R. Bueno, H.E. Himwich.
Detection of psychotomimetic N, N-dimethylated indoleamines
in the urine of four schizophrenic patients. Br. J. Psychiatr.
1970, 117, 421.
[30] B. Heller, N. Narasimhachari, J. Spaide, L. Haskovec, H.E. Himwich.
N-Dimethylated indoleamines in blood of acute schizophrenics.
Experientia 1970, 26, 503.
[31] N. Narasimhachari, B. Heller, J. Spaide, L. Haskovec, M. Fujimori,
K. Tabushi, H.E. Himwich. Urinary studies of schizophrenics and
controls. Biol. Psychiat. 1971, 3, 9.
[32] N. Narasimhachari, B. Heller, J. Spaide, L. Haskovec, H. Meltzer,
M. Strahilevitz, H.E. Himwich. N,N-Dimethylated indoleamines in
blood. Biol. Psychiat. 1971, 3, 21.
[33] E. Fischer, H. Spatz, T. Fledel. Bufotenin like substances in form of
glucuronide in schizophrenic and normal urines. Psychosom.
1971, 12, 278.
[34] H.E. Himwich, R.L. Jenkins, M. Fujimori, N. Narasimhachari,
M. Ebersole. A biochemical study of early infantile autism. J. Autism
Child. Schizophr. 1972, 2, 114.
[35] N. Narasimhachari, J. Avalos, M. Fujimori, H.E. Himwich. Studies of
drug free schizophrenics and controls. Biol. Psychiat. 1972, 5, 311.
[36] R.W. Walker, H.S. Ahn, G. Albers-Schonberg, L.R. Mandel, W.J.
Vandenheuvel. Gas chromatographic-mass spectrometric isotope
dilution assay for N,N-dimethyltryptamine in human plasma.
Biochem. Med. 1973, 8, 105.
[37] R.J. Wyatt, L.R. Mandel, H.S. Ahn, R.W. Walker, W.J. Vanden Heuvel.
Gas chromatographic-mass spectrometric isotope dilution determination of N,N-dimethyltryptamine concentrations in normals and
psychiatric patients. Psychopharmacol. 1973, 31, 265.
[38] N. Narasimhachari, H.E. Himwich. Gas chromatographic-mass
spectrometric identification of N, N-dimethyltryptamine in urine
samples from drug-free chronic schizophrenic patients and its
quantitation by the technique of single (selective) ion monitoring.
Biochem. Biophys. Res. Commun. 1973, 55, 1064.
[39] J.F. Lipinski, L.R. Mandel, H.S. Ahn, W.J. Vanden Heuvel, R.W. Walker.
Blood dimethyltryptamine concentrations in psychotic disorders.
Biol. Psychiat. 1974, 9, 89.
[40] T.G. Bidder, L.R. Mandel, H.S. Ahn, W.J. VandenHeuvel, R.W. Walker.
Letter: Blood and urinary dimethyltryptamine in acute psychotic
disorders. Lancet 1974, 1, 165.
[41] N. Narasimhachari, P. Baumann, H.S. Pak, W.T. Carpenter, A.F.
Zocchi, L. Hokanson, M. Fujimori, H.E. Himwich. Gas chromatographic-mass spectrometric identification of urinary bufotenin
and dimethyltryptamine in drug-free chronic schizophrenic
patients. Biol. Psychiat. 1974, 8, 293.
[42] W.T. Carpenter Jr, E.B. Fink, N. Narasimhachari, H.E. Himwich. A test
of the transmethylation hypothesis in acute schizophrenic patients.
Am. J. Psychiatr. 1975, 132, 1067.
[43] S.T. Christian, F. Benington, R.D. Morin, L. Corbett. Gas–liquid
chromatographic separation and identification of biologically
important indolealkylamines from human cerebrospinal fluid.
Biochem. Med. 1975, 14, 191.
[44] N. Narasimhachari, H.E. Himwich. Biochemical studies in early
infantile autism. Biol. Psychiat. 1975, 10, 425.
[45] B. Angrist, S. Gershon, G. Sathananthan, R.W. Walker, B.
Lopez-Ramos, L.R. Mandel, W.J. Vandenheuvel. Dimethyltryptamine
levels in blood of schizophrenic patients and control subjects.
Psychopharmacol. 1976, 47, 29.
[46] R. Rodnight, R.M. Murray, M.C. Oon, I.F. Brockington, P. Nicholls,
J.L. Birley. Urinary dimethyltryptamine and psychiatric symptomatology and classification. Psychol. Med. 1976, 6, 649.
[47] R.M. Murray, M.C. Oon. The excretion of dimethyltryptamine in
psychiatric patients. Proc. Royal Soc. Med. 1976, 69, 831.
[48] L. Huszka, D.H. Zabek, J.W. Doust. Urinary excretion of N,
N-dimethylated tryptamines in chronic schizophrenia. A review of
the present status of the hypothesis. Can. Psychiatr. Assoc. J.
1976, 21, 541.

Copyright © 2012 John Wiley & Sons, Ltd.

wileyonlinelibrary.com/journal/dta

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105Q2
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

17

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Drug Testing
and Analysis

Drug Testing
and Analysis

18

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
Q3 42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

S. A. Barker, E. H. McIlhenny and R. Strassman

[49] A.C. Cottrell, M.F. McLeod, W.R. McLeod. A bufotenin-like substance in the urine of schizophrenics. Am. J. Psychiatr. 1977,
134, 322.
[50] M.C. Oon, R.M. Murray, R. Rodnight, M.P. Murphy, J.L. Birley.
Factors affecting the urinary excretion of endogenously formed
dimethyltryptamine in normal human subjects. Psychopharmacology 1977, 54, 171.
[51] M.C. Oon, R. Rodnight. A gas chromatographic procedure for determining N, N-dimethyltryptamine and N-monomethyltryptamine in
urine using a nitrogen detector. Biochem. Med. 1977, 18, 410.
[52] L.J. Riceberg, H.V. Vunakis. Determination of N,N-dimethylindolealkylamines in plasma, blood and urine extracts by radioimmunoassay and high pressure liquid chromatography. J.
Pharmacol. Exp. Ther. 1978, 206, 158.
[53] L. Corbett, S.T. Christian, R.D. Morin, F. Benington, J.R. Smythies.
Hallucinogenic N-methylated indolealkylamines in the cerebrospinal fluid of psychiatric control populations. Br. J. Psychiatr. 1978,
132, 139.
[54] R.W. Walker, L.R. Mandel, J.E. Kleinman, J.C. Gillin, R.J. Wyatt, W.J.
Vandenheuvel. Improved selective ion monitoring massspectrometric assay for the determination of N,N-dimethyltryptamine
in human blood utilizing capillary column gas chromatography. J.
Chromatogr. 1979, 162, 539.
[55] R.M. Murray, M.C. Oon, R. Rodnight, J.L. Birley, A. Smith.
Increased excretion of dimethyltryptamine and certain features
of psychosis: a possible association. Arch. Gen. Psychiatr. 1979,
36, 644.
[56] S.A. Checkley, M.C.H. Oon, R. Rodnight, M.P. Murphy, R.S. Williams, J.
L.T. Birley. Urinary excretion of dimethyltryptamine in liver disease.
Am. J. Psychiatr. 1979, 136, 439.
[57] M. Raisanen, J. Karkkainen. Mass fragmentographic quantification
of urinary N,N-dimethyltryptamine and bufotenine. J. Chromatogr.
1979, 162, 579.
[58] J.R. Smythies, R.D. Morin, G.B. Brown. Identification of
dimethyltryptamine and O-methylbufotenin in human cerebrospinal fluid by combined gas chromatography/mass spectrometry. Biol. Psychiat. 1979, 14, 549.
[59] S.A. Checkley, R.M. Murray, M.C. Oon, R. Rodnight, J.L. Birley. A
longitudinal study of urinary excretion of N,N,-dimethyltryptamine
in psychotic patients. Br. J. Psychiat. 1980, 137, 236.
[60] R. Uebelhack, L. Franke, K. Seidel. Methylierte und nichtmethylierte
indolamine in zisternalen liquor bei akuten endoenen psychosen.
Biomed. Biochim. Acta 1983, 42, 1343.
[61] B.R. Sitaram, G.L. Blackman, W.R. McLeod, G.N. Vaughan. The
ion-pair extraction, purification, and liquid chromatographic
analysis of indolealkylamines in human urine. Anal. Biochem.
1983, 128, 11.
[62] M.J. Raisanen, M. Virkkunen, M.O. Huttunen, B. Furman, J.
Karkkainen. Increased urinary excretion of bufotenin by violent
offenders with paranoid symptoms and family violence. Lancet
1984, 2, 700.
[63] J. Karkkainen, M. Raisanen, H. Naukkarinen, J. Spoov, R. Rimon.
Urinary excretion of free bufotenin by psychiatric patients. Biol.
Psychiat. 1988, 24, 441.
[64] J. Karkkainen, M. Raisanen. Nialamide, an MAO inhibitor, increases
urinary excretion of endogenously produced bufotenin in man.
Biol. Psychiat. 1992, 32, 1042.
[65] J. Karkkainen, M. Raisanen, M.O. Huttunen, E. Kallio, H. Naukkarinen,
M. Virkkunen. Urinary excretion of bufotenin (N,N-dimethyl-5hydroxytryptamine) is increased in suspicious violent offenders: A
confirmatory study. Psychiatr. Res. 1995, 58, 145.
[66] N. Takeda, R. Ikeda, K. Ohba, M. Kondo. Bufotenine reconsidered as
a diagnostic indicator of psychiatric disorders. Neuroreport 1995, 6,
2378.
[67] T. Forsstrom, J. Tuominen, J. Karkkainen. Determination of
potentially hallucinogenic N-dimethylated indoleamines in
human urine by HPLC/ESI-MS-MS. Scand. J. Clin. Lab. Invest.
2001, 61, 547.
[68] J. Karkkainen, T. Forsstrom, J. Tornaeus, K. Wahala, P. Kiuru, A.
Honkanen, U.H. Stenman, U. Turpeinen, A. Hesso. Potentially
hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine
and dimethyltryptamine in blood and tissues. Scand. J. Clin. Lab.
Inv. 2005, 65, 189.
[69] E. Emanuele, R. Colombo, V. Martinelli, N. Brondino, M. Marini, M.
Boso, F. Barale, P. Politi. Elevated urine levels of bufotenine in

wileyonlinelibrary.com/journal/dta

[70]
[71]

[72]
[73]
[74]
[75]
[76]
[77]
[78]

[79]
[80]
[81]

[82]

[83]

[84]

[85]
[86]

[87]
[88]
[89]

[90]

[91]

patients with autistic spectrum disorders and schizophrenia. Neuro
Endocrinol. Lett. 2010, 31, 117.
M.J.D. Fontanilla, A.R. Hajipour, N.V. Cozzi, M.B. Jackson, A.E. Ruoho.
The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous
sigma-1 receptor regulator. Science 2009, 323, 934.
T.-P. Su, T. Hayashi, D.B. Vaupel. When the endogenous
hallucinogenic trace amine N,N-Dimethyltryptamine meets the
sigma-1 receptor. Sci. Signal. 2009, 2. DOI: 10.1126/
scisignal.261pe12.
R. Strassman. DMT: The Spirit Molecule: A Doctor’s Revolutionary
Research into the Biology of Near-Death and Mystical Experiences.
Park Street Press, Rochester, Vermont, USA, 2001.
M. Winkelman. Drug tourism or spiritual healing? Ayahuasca
seekers in Amazonia. J. Psychoactive Drugs 2005, 37, 209.
K.W. Tupper. The globalization of ayahuasca: Harm reduction or
benefit maximization? Int. J. Drug Policy 2008, 19, 297.
D.J. McKenna. Clinical investigations of the therapeutic potential of
ayahuasca: Rationale and regulatory challenges. Pharmacol.
Therapeut. 2004, 102, 111.
R.J. Strassman. Human hallucinogenic drug research in the United
States: A present-day case history and review of the process. J.
Psychoactive Drugs 1991, 23, 29.
R.J. Strassman, C.R. Qualls. Dose–response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and
cardiovascular effects. Arch. Gen. Psychiatr. 1994, 51, 85.
R.J. Strassman, C.R. Qualls, E.H. Uhlenhuth, R. Kellner. Dose–
response study of N,N-dimethyltryptamine in humans. II. Subjective
effects and preliminary results of a new rating scale. Arch. Gen.
Psychiatr. 1994, 51, 98.
R.J. Strassman, C.R. Qualls, L.M. Berg. Differential tolerance to biological and subjective effects of four closely spaced doses of N,Ndimethyltryptamine in humans. Biol. Psychiat. 1996, 39, 784.
R.J. Strassman. Human psychopharmacology of N,N-dimethyltryptamine. Behav. Brain Res. 1996, 73, 121.
E. Gouzoulis-Mayfrank, K. Heekeren, A. Neukirch, M. Stoll, C.
Stock, M. Obradovic, K.A. Kovar. Psychological effects of
(S)-ketamine and N,N-dimethyltryptamine (DMT): A double-blind,
cross-over study in healthy volunteers. Pharmacopsychiatry 2005,
38, 301.
J. Daumann, D. Wagner, K. Heekeren, A. Neukirch, C.M. Thiel, E.
Gouzoulis-Mayfrank. Neuronal correlates of visual and auditory
alertness in the DMT and ketamine model of psychosis. J.
Psychopharmacol. 2010, 24, 1515.
J. Riba, M. Valle, G. Urbano, M. Yritia, A. Morte, M.J. Barbanoj. Human
pharmacology of ayahuasca: Subjective and cardiovascular effects,
monoamine metabolite excretion, and pharmacokinetics. J.
Pharmacol. Exp. Ther. 2003, 306, 73.
J. Riba, P. Anderer, F. Jane, B. Saletu, M.J. Barbanoj. Effects of
the South American psychoactive beverage ayahuasca on regional
brain electrical activity in humans: A functional neuroimaging
study using low-resolution electromagnetic tomography. Neuropsychobiology 2004, 50, 89.
S. Szara. DMT at fifty. Neuropsychopharmacol. Hungar. 2007,
9, 201.
S.D. Brandt, C.P. Martins, S. Freeman, N. Dempster, P.G. Riby, J.
Gartz, J.F. Alder. Halogenated solvent interactions with N,Ndimethyltryptamine: formation of quaternary ammonium salts
and their artificially induced rearrangements during analysis.
Forensic Sci. Int. 2008, 178, 162.
S.A. Barker, J.A. Monti, S.T. Christian. Metabolism of the
hallucinogen N,N-dimethyltryptamine in rat brain homogenates.
Biochem. Pharmacol. 1980, 29, 1049.
S.A. Barker, J.A. Monti, S.T. Christian. N, N-dimethyltryptamine: An
endogenous hallucinogen. Int. Rev. Neurobiol. 1981, 22, 83.
B.R. Sitaram, L. Lockett, G.L. Blackman, W.R. McLeod. Urinary
excretion of 5-methoxy-N,N-dimethyltryptamine, N,N-dimethyltryptamine and their N-oxides in the rat. Biochem. Pharmacol.
1987, 36, 2235.
B.R. Sitaram, L. Lockett, R. Talomsin, G.L. Blackman, W.R. McLeod.
In vivo metabolism of 5-methoxy-N,N-dimethyltryptamine and N,
N-dimethyltryptamine in the rat. Biochem. Pharmacol. 1987, 36,
1509.
B.R. Sitaram, W.R. McLeod. Observations on the metabolism of the
psychotomimetic indolealkylamines: Implications for future clinical
studies. Biol. Psychiat. 1990, 28, 841.

Copyright © 2012 John Wiley & Sons, Ltd.

Drug Test. Analysis (2012)

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

Drug Testing
and Analysis

Reports of endogenous psychedelic N, N-dimethyltryptamines in humans
[92] H. Osmond, J. Smythies. Schizophrenia: A new approach. Br. J.
Psychiat. 1952, 98, 309.
[93] J.C. Gillin, J. Kaplan, R. Stillman, R.J. Wyatt. The psychedelic model of
schizophrenia: The case of N,N-dimethyltryptamine. Am. J.
Psychiatr. 1976, 133, 203.
[94] J.C. Gillin, R.J. Wyatt. Evidence for and against the involvement of N,Ndimethyl- tryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine
(5-MeO-DMT) in schizophrenia. Psychopharmacol. Bull. 1976, 12, 12.
[95] J. Axelrod. Enzymatic formation of psychotomimetic metabolites
from normally occurring compounds. Science 1961, 134, 343.
[96] M.A. Thompson, R.M. Weinshilboum. Rabbit lung indolethylamine
N-methyltransferase. cDNA and gene cloning and characterization.
J. Biol. Chem. 1998, 273, 34502.
[97] M.A. Thompson, E. Moon, U.J. Kim, J. Xu, M.J. Siciliano, R.M. Weinshilboum. Human indolethylamine N-methyltransferase: cDNA
cloning and expression, gene cloning, and chromosomal localization. Genomics 1999, 61, 285.
[98] N.V. Cozzi, A. Gopalakrishnan, L.L. Anderson, J.T. Feih, A.T. Shulgin,
P.F. Daley, A.E. Ruoho. Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin

Drug Test. Analysis (2012)

[99]
[100]
[101]

[102]

[103]

uptake transporter and the vesicle monoamine transporter. J.
Neural Transm. 2009, 116, 1591.
N.V. Cozzi, T.A. Mavlyutov, M.A. Thompson, A.E. Ruoho. Indolethylamine N- methyltransferase expression in primate nervous tissue.
Soc. Neurosci. Abs. 2011, 37, 840.19.
E. Sanders-Bush, J.A. Oates, M.T. Bush. Metabolism of bufotenine-2’14C in human volunteers. Life Sci. 1976, 19, 1407.
X.-L. Jiang, H.-W. Shen, J.C. Winter, A.-M. Yu. Psychedelic 5-methoxy-N,N-dimethyltryptamine: Metabolism, pharmacokinetics, prug
interactions, and pharmacological actions. Curr. Drug Metabol.
2010, 11, 659.
E.H. McIlhenny, J. Riba, M.J. Barbanoj, R. Strassman, S.A. Barker.
Methodology for determining major constituents of ayahuasca
and their metabolites in blood. Biomed. Chromatogr. 2011. DOI:
10.1002/bmc.1657
E.H. McIlhenny, J. Riba, M.J. Barbanoj, R. Strassman, S.A.
Barker. Methodology for and the determination of the major
constituents and metabolites of the Amazonian botanical
medicine ayahuasca in human urine. Biomed. Chromatogr.
2011, 25, 970.

Copyright © 2012 John Wiley & Sons, Ltd.

wileyonlinelibrary.com/journal/dta

66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130

19

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65

Review
A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans:
1955–2010
Steven A. Barker, Ethan H. McIlhenny and Rick Strassman

Three indole alkaloids that possess differing degrees of psychotropic/psychedelic activity have been reported as endogenous substances in humans; N,N-dimethyltryptamine (DMT), 5-hydroxy-DMT (bufotenine, HDMT) and 5-methoxy-DMT
(MDMT). We have undertaken a critical review of 69 published studies reporting the detection or detection and quantitation of these compounds in human body fluids. In reviewing this literature, we address the methods applied and the
criteria used in the determination of the presence of DMT, MDMT, and HDMT.

Author Query Form
Journal: Drug Testing and Analysis
Article: dta_422
Dear Author,
During the copyediting of your paper, the following queries arose. Please respond to these by annotating your proofs with the
necessary changes/additions.
• If you intend to annotate your proof electronically, please refer to the E-annotation guidelines.
• If you intend to annotate your proof by means of hard-copy mark-up, please refer to the proof mark-up symbols guidelines. If
manually writing corrections on your proof and returning it by fax, do not write too close to the edge of the paper. Please
remember that illegible mark-ups may delay publication.
Whether you opt for hard-copy or electronic annotation of your proofs, we recommend that you provide additional clarification
of answers to queries by entering your answers on the query sheet, in addition to the text mark-up.

Query No.

Query

Remark

Q1

AUTHOR: Please check volume number.

277

Q2

AUTHOR: Please check volume number.

303

Q3

AUTHOR: Please check volume number.

324

USING e-ANNOTATION TOOLS FOR ELECTRONIC PROOF CORRECTION
Required software to e-Annotate PDFs: Adobe Acrobat Professional or Adobe Reader (version 8.0 or
above). (Note that this document uses screenshots from Adobe Reader X)
The latest version of Acrobat Reader can be downloaded for free at: http://get.adobe.com/reader/
Once you have Acrobat Reader open on your computer, click on the Comment tab at the right of the toolbar:

This will open up a panel down the right side of the document. The majority of
tools you will use for annotating your proof will be in the Annotations section,
pictured opposite. We’ve picked out some of these tools below:

1. Replace (Ins) Tool – for replacing text.

2. Strikethrough (Del) Tool – for deleting text.

Strikes a line through text and opens up a text
box where replacement text can be entered.
How to use it

Strikes a red line through text that is to be
deleted.
How to use it



Highlight a word or sentence.



Highlight a word or sentence.



Click on the Replace (Ins) icon in the Annotations
section.



Click on the Strikethrough (Del) icon in the
Annotations section.



Type the replacement text into the blue box that
appears.

3. Add note to text Tool – for highlighting a section
to be changed to bold or italic.

4. Add sticky note Tool – for making notes at
specific points in the text.

Highlights text in yellow and opens up a text
box where comments can be entered.
How to use it

Marks a point in the proof where a comment
needs to be highlighted.
How to use it



Highlight the relevant section of text.





Click on the Add note to text icon in the
Annotations section.

Click on the Add sticky note icon in the
Annotations section.



Click at the point in the proof where the comment
should be inserted.



Type the comment into the yellow box that
appears.



Type instruction on what should be changed
regarding the text into the yellow box that
appears.

USING e-ANNOTATION TOOLS FOR ELECTRONIC PROOF CORRECTION

5. Attach File Tool – for inserting large amounts of
text or replacement figures.

6. Add stamp Tool – for approving a proof if no
corrections are required.

Inserts an icon linking to the attached file in the
appropriate pace in the text.
How to use it

Inserts a selected stamp onto an appropriate
place in the proof.
How to use it



Click on the Attach File icon in the Annotations
section.



Click on the Add stamp icon in the Annotations
section.



Click on the proof to where you’d like the attached
file to be linked.





Select the file to be attached from your computer
or network.

Select the stamp you want to use. (The Approved
stamp is usually available directly in the menu that
appears).



Click on the proof where you’d like the stamp to
appear. (Where a proof is to be approved as it is,
this would normally be on the first page).



Select the colour and type of icon that will appear
in the proof. Click OK.

7. Drawing Markups Tools – for drawing shapes, lines and freeform
annotations on proofs and commenting on these marks.
Allows shapes, lines and freeform annotations to be drawn on proofs and for
comment to be made on these marks..

How to use it


Click on one of the shapes in the Drawing
Markups section.



Click on the proof at the relevant point and
draw the selected shape with the cursor.



To add a comment to the drawn shape,
move the cursor over the shape until an
arrowhead appears.



Double click on the shape and type any
text in the red box that appears.

For further information on how to annotate proofs, click on the Help menu to reveal a list of further options:

WILEY AUTHOR DISCOUNT CLUB
We would like to show our appreciation to you, a highly valued contributor to Wiley’s
publications, by offering a unique 25% discount off the published price of any of our
books*.

O

O

The Database Group (Author Club)
John Wiley & Sons Ltd
The Atrium
Southern Gate
Chichester
PO19 8SQ
UK
Alternatively, you can register online at www.wileyeurope.com/go/authordiscount
Please pass on details of this offer to any co-authors or fellow contributors.

FS

All you need to do is apply for the Wiley Author Discount Card by completing the
attached form and returning it to us at the following address:

PR

After registering you will receive your Wiley Author Discount Card with a special promotion
code, which you will need to quote whenever you order books direct from us.
The quickest way to order your books from us is via our European website at:

EC

TE

Key benefits to using the site and ordering online include:
Real-time SECURE on-line ordering
Easy catalogue browsing
Dedicated Author resource centre
Opportunity to sign up for subject-orientated e-mail alerts

D

http://www.wileyeurope.com

Alternatively, you can order direct through Customer Services at:
cs-books@wiley.co.uk, or call +44 (0)1243 843294, fax +44 (0)1243 843303

O
R

R

So take advantage of this great offer and return your completed form today.

N

C

Yours sincerely,

U

Verity Leaver
Group Marketing Manager
author@wiley.co.uk

*TERMS AND CONDITIONS
This offer is exclusive to Wiley Authors, Editors, Contributors and Editorial Board Members in acquiring books for their personal use.
There must be no resale through any channel. The offer is subject to stock availability and cannot be applied retrospectively. This
entitlement cannot be used in conjunction with any other special offer. Wiley reserves the right to amend the terms of the offer at any
time.

REGISTRATION FORM

For Wiley Author Club Discount Card

Accounting
Public
Corporate

[]
[]
[]

Architecture

[]

Business/Management

[]

Chemistry
Analytical
Industrial/Safety
Organic
Inorganic
Polymer
Spectroscopy

[
[
[
[
[
[
[

]
]
]
]
]
]
]

Computer Science
Database/Data Warehouse
Internet Business
Networking
Programming/Software
Development
Object Technology

[
[
[
[
[

Encyclopedia/Reference
Business/Finance
Life Sciences
Medical Sciences
Physical Sciences
Technology

[
[
[
[
[
[

]
]
]
]
]
]

Engineering
Civil
Communications Technology
Electronic
Environmental
Industrial
Mechanical

[
[
[
[
[
[
[

]
]
]
]
]
]
]

Earth & Environmental Science

[]

Hospitality

[]

Finance/Investing
Economics
Institutional
Personal Finance

[
[
[
[

]
]
]
]

Genetics
Bioinformatics/
Computational Biology
Proteomics
Genomics
Gene Mapping
Clinical Genetics

[]
[]

Life Science

[]

U

Non-Profit

]
]
]
]
]
]
]
]
]

[]

O

[]

O

PR

D

TE

EC
R

]
]
]
]

O
R
[
[
[
[
[
[
[
[
[

C

N

Medical Science
Cardiovascular
Diabetes
Endocrinology
Imaging
Obstetrics/Gynaecology
Oncology
Pharmacology
Psychiatry

[
[
[
[

]
]
]
]
]

FS

To enjoy your 25% discount, tell us your areas of interest and you will receive relevant catalogues or leaflets
from which to select your books. Please indicate your specific subject areas below.

Landscape Architecture

[]

Mathematics
Statistics

[]
[]

Manufacturing
[]
Materials Science
Psychology
Clinical
Forensic
Social & Personality
Health & Sport
Cognitive
Organizational
Developmental & Special Ed
Child Welfare
Self-Help

[
[
[
[
[
[
[
[
[
[
[

]
]
]
]
]
]
]
]
]
]
]

Physics/Physical Science

[]

Please complete the next page /

I confirm that I am (*delete where not applicable):
a Wiley Book Author/Editor/Contributor* of the following book(s):
ISBN:
ISBN:
a Wiley Journal Editor/Contributor/Editorial Board Member* of the following journal(s):

SIGNATURE: ……………………………………………………………………………………

Date: ………………………………………

PLEASE COMPLETE THE FOLLOWING DETAILS IN BLOCK CAPITALS:
TITLE: (e.g. Mr, Mrs, Dr) …………………… FULL NAME: …………………………………………………………………………….…
..…………………………………………………………………………………………………………………

FS

JOB TITLE (or Occupation):

DEPARTMENT: ……………………………………………………………………………………………………………………………………………..

O

COMPANY/INSTITUTION: ……………………………………………………………………………………………………………………………

O

ADDRESS: ……………………………………………………………………………………………………………………………………………………

PR

………………………………………………………………………………………………………………………………………………………………………
TOWN/CITY: …………………………………………………………………………………………………………………………………………………
COUNTY/STATE: ………………………………………………………………………………………………………………………………………….

D

COUNTRY: …………………………………………………………………………………………………………………………………………………….

TE

POSTCODE/ZIP CODE: …………………………………………………………………………………………………………………………………
DAYTIME TEL: ………………………………………………………………………………………………………………………………………………

EC

FAX: ………………………………………………………………………………………………………………………………………………………………

R

E-MAIL: …………………………………………………………………………………………………………………………………………………………

O
R

YOUR PERSONAL DATA
We, John Wiley & Sons Ltd, will use the information you have provided to fulfil your request. In addition, we would like to:
Use your information to keep you informed by post of titles and offers of interest to you and available from us or other
Wiley Group companies worldwide, and may supply your details to members of the Wiley Group for this purpose.
[ ] Please tick the box if you do NOT wish to receive this information

2.

Share your information with other carefully selected companies so that they may contact you by post with details of
titles and offers that may be of interest to you.
[ ] Please tick the box if you do NOT wish to receive this information.

N

C

1.

U

E-MAIL ALERTING SERVICE
We also offer an alerting service to our author base via e-mail, with regular special offers and competitions. If you DO wish to
receive these, please opt in by ticking the box [ ].
If, at any time, you wish to stop receiving information, please contact the Database Group (databasegroup@wiley.co.uk) at John Wiley & Sons Ltd,
The Atrium, Southern Gate, Chichester, PO19 8SQ, UK.

TERMS & CONDITIONS
This offer is exclusive to Wiley Authors, Editors, Contributors and Editorial Board Members in acquiring books for their personal use. There should
be no resale through any channel. The offer is subject to stock availability and may not be applied retrospectively. This entitlement cannot be used
in conjunction with any other special offer. Wiley reserves the right to vary the terms of the offer at any time.

PLEASE RETURN THIS FORM TO:
Database Group (Author Club), John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, PO19 8SQ, UK author@wiley.co.uk
Fax: +44 (0)1243 770154


Documentos relacionados


Documento PDF endogenous dmt review 2012
Documento PDF frances garrett religion medicine and the human embryo in tibet
Documento PDF mc doughall jhon treating multiple sclerosis with diet fact or fraud
Documento PDF manuel nevera furgo
Documento PDF de angelo et al 2010 jwm track identification
Documento PDF seralini et al 2012


Palabras claves relacionadas