external

rts of endogenoushyltryptamines in

n

otoxpo, wThhegdaou

MS) (Tables 13, references ). Indeed, the review of the dimethylated-tryptamines (DMTs) increasing visibility within[75]

ReviewDrug Testingand Analysis

Accepted: 3 January 2012 Published online in Wiley Online Library55-year history of the development ofmethodology for the analysisof these compounds shows how closely it has paralleled the evolu-tion of analytical technology itself, with each researcher seekingmore specic and sensitive techniques.

A renewed interest in these compounds as naturallyoccurring substances in humans has occurred, in part, dueto DMTs recent characterization as an endogenous substratefor the ubiquitous sigma 1 receptor[70] and for its possibleaction at trace amine receptors.[71] In both cases, the rolesof DMT and the receptors themselves in regulating someaspect(s) of human physiology are poorly understood. Given

medical, non-medical, religious and/or recreational contextsreinforce the importance of determining their endogenousrole.

This review addresses several fundamental issues regardingthese three endogenous psychedelics. For example, are DMT,

* Correspondence to: Steven A. Barker, Department of Comparative BiomedicalSciences, School of Veterinary Medicine, Louisiana State University, BatonRouge, LA 70806, USA. E-mail: [email protected] activity have been reported as endogenoussubstances in humans. These compounds, all metabolites oftryptophan, 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 humancerebrospinal uid (CSF), urine, and/or blood utilizing eitherpaper and/or thin layer chromatography (TLC), direct ultravio-let (UV) or uorescence (Fl) measurements, gas chromatog-raphy (GC) using various sensors (nitrogen-phosphorousdetector (NPD); electron capture detector (ECD); massspectrometry detector (MSD)), high-performance liquidchromatography (HPLC) using UV and/or Fl detection, HPLC-radioimmunoassay, HPLC-electrochemical detection, andliquid chromatography-tandem mass spectrometry (LC-MS/

[169]

the role of these compounds in humans awaits furtherresearch, much of which awaits the development of adequateanalytical methodology.

Interest in DMT has also increased because of theburgeoning use and popularity of the religious sacrament aya-huasca which contains DMT and several harmala alkaloids,which serve to make DMT orally active. Ayahuasca tourismin South America and the establishment of syncretic churchesusing ayahuasca as a sacrament[73,74] have stimulated researchinto the mechanisms of its effects and its possible use as atherapeutic.[75] The resumption of human research character-izing DMTs psychopharmacology[7684] and the ongoing useof pure DMT for therapeutic and recreational purposes havealso focused interest on this and related psychedelics. TheA critical review of repopsychedelic N, N-dimethumans: 19552010Steven A. Barker,a* Ethan H. McIlhen

Three indole alkaloids that possess differing degrees of psychsubstances in humans; N,N-dimethyltryptamine (DMT), 5-hydrhave undertaken a critical review of 69 published studies recompounds in human body uids. In reviewing this literaturedetermination of the presence of DMT, MDMT, and HDMT.conducted from 1955 to 2010, summarizing the ndings for tuid. A critique of the data is offered that addresses the strenThe review also discusses the shortcomings of the existingovercome. Suggestions for the future directions of endogenWiley & Sons, Ltd.

Keywords: dimethyltryptamine; psychedelic; endogenous

Introduction

Three indole alkaloids that possess differing degrees of psychotropic/

Received: 7 December 2011 Revised: 3 January 2012

(wileyonlinelibrary.com) DOI 10.1002/dta.422their known psychedelic effects, there remains an interest intheir possible role in naturally occurring altered states ofconsciousness, such as psychosis, dreams, creativity and imag-ination, religious phenomena, and even near-death

Drug Test. Analysis (2012)ya and Rick Strassmanb

ropic/psychedelic activity have been reported as endogenousy-DMT (bufotenine, HDMT), and 5-methoxy-DMT (MDMT). Werting the detection or detection and quantitation of thesee address the methods applied and the criteria used in thee review provides a historical perspective of the researchindividual compounds in blood, urine, and/or cerebrospinal

ths and weaknesses of the methods and approaches to date.ta in light of more recent ndings and how these may bes psychedelics research are offered. Copyright 2012 John

experiences.[72] Although the vast majority of research intothe presence of these compounds sought their role in mentalillness, no denitive conclusions yet exist. A determination ofa School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA,USA

b School of Medicine, University of New Mexico, Albuquerque, and CottonwoodResearch Foundation, Taos, New Mexico, USA

Copyright 2012 John Wiley & Sons, Ltd.

The search for endogenous psychedelics soon followedthe discovery of the psychedelic effects of mescaline and

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

Drug Testingand AnalysisHDMT, and/or MDMT truly present in humans?[85] Earlycriticisms of reports of endogenous psychedelics weredirected at the fact that rather non-specic chemical testswere being applied, double-blind analyses were not alwaysbeing performed, and dietary or medication sources werenot always adequately ruled out as responsible for the identi-cations.[2,12] Further, it was claimed that possible artifactsproduced from the extraction solvents and conditions ofanalysis may have led to misidentication of the DMTs insome early studies[20] and, more recently, that the use ofhalogenated solvents in the analysis may have affected theirdetection.[86] Biological factors that may have affected thedetectabilty of these compounds in the periphery were alsoacknowledged, which included their rapid metabolism.[87,88]

Finally, there have been concerns that the studies searchingfor their presence and an association with specic clinicaldisorders have failed to understand and fully characterize

[8891]

Figure 1. Structures of the compounds discussed.their metabolism or monitor their metabolites.To address these issues, we have undertaken a critical

review of 69 published studies reporting the detection ordetection and quantitation of these compounds in humanbody uids. In reviewing this literature, we address themethods applied and the criteria used in the determinationof the presence of DMT, MDMT, and HDMT. We begin withthe original report of the presence of bufotenin (HDMT) inhuman urine in 1955 using paper chromatography[1] andend with the most recent report concerning the presence ofbufotenin (HDMT) in human urine using LC-MS/MS.[69]

We will be addressing the following questions: How validwere early studies regarding the presence and/or quantitiesof these compounds in human cerebrospinal uid (CSF),blood and/or urine? Were the analytical methodologiesand the identication criteria adequate? Are they truly there?When present, are they of dietary origin? When and where inthe human body are they produced? Can we inuence theirdetection in biological samples by pharmacologically inhibit-ing their metabolism by monoamine oxidase (MAO)? Howdoes turnover rate and metabolism of these substancesinuence their detectabilty? Have the precursors and/or meta-bolites of these compounds been adequately monitored? Is

wileyonlinelibrary.com/journal/dta Copyright 20lysergic acid diethylamide (LSD) in humans. Observations ofthese effects gave rise to hypotheses that they were relatedto the symptomology observed in a heterogeneous group ofmental disorders, especially psychoses either mania orschizophrenia.[92] It was proposed that schizophrenics may

[93]monitoring these compounds in biological samples such asCSF, blood and/or urine the best, or even most practicalway to determine their role? What will such data tell us aboutthe function of these compounds? Where does the researchon endogenous psychedelics go from here?

Historical perspectivebiochemically produce similar compounds as schizotoxins.A search for mescaline-like compounds proved unreward-ing,[94] but in studies examining urine samples for serotonin-like compounds, researchers reported in 1955[1] and 1956,[2]

the presence of 5-hydroxy-N,N-DMT (HDMT, bufotenin) inhumans. Subsequently, Axelrod[95] reported the presence ofan enzyme capable of N-methylating indole-ethylamines andproducing DMTs. Following these reports, attention began tofocus in earnest on the possible endogenous formation ofthe indole-ethylamine psychedelics. During the next 50 years,many studies reported nding DMT, HDMT, and/or MDMT inhuman CSF, urine, and/or blood. Most of these studies soughtdifferences in levels between controls and psychiatric,especially psychotic, patients. Some studies claimed higherconcentrations and signicant differences in levels betweenthe groups; some reported not nding the compounds at allin either patients or controls.

It is of interest to note that in its original conception, theschizotoxin hypothesis proposed that the formation of anendogenous psychedelic schizotoxin would be an aberrationof metabolism and that normals would not form suchcompounds.[92] However, numerous studies subsequentlyreported nding one or more of these compounds in controls

12 John Wiley & Sons, Ltd. Drug Test. Analysis (2012)

Table

1.

Review

of69

studiesregardingen

dog

enous

psych

edelicsshowingtheyear,referen

ce,compoundsan

alyzed

,typ

eofsample

andmethod

ofextraction.A

cronym

san

dab

breviations;IV,intra-

venous;HNMT,

5-hyd

roxy-N-m

ethyltryp

tamine;

ext,extraction;v

ol,vo

lume;

w/w

o,w

ithorwithou

t;evap

,evaporate;p

pt,precipitate;

sat.,

saturated;T

LC,thin-la

yerch

romatography;

cent,centrifu

ge;

TFAA,triuoro-acetican

hyd

ride;

SPE,

solid

-phaseextraction;LC,liquid

chromatography.

Year

Author

CompoundsAnalyzed

Collection

ExtractionMethod

1955

Bumpus

andPa

ge[1]

HNMT,HDMT

24-hou

rurine10

mlp

ortions,HCl;urease

Evap

,Acetone,

evap

,MeO

H,e

vap,A

lO3co

lumn

1956

Rodnight[2

]HNMT,HDMT

24-hou

rurine;

7512

0mle

xtracted

Zeo-Karb

226resin,EtOH/acetone

ppt,evap

1961

Fischer

etal.[3

]HDMT

1Lofurine

NaH

CO3sat.,

butanol,evap

,acetone

1961

Fischer

etal.[4

]HDMT

1Lofurine

NaO

HpH9,

butanol,e

vap,acetone

1961

Feldsteinet

al.[5

]HDMT

8hoururines;IV/oral1

4Cserotonin

(130

mg)

notdescribed

1962

Perryet

al.[6

]HDMT,co

njugate

24-36hoururine;

extvo

l500

mgcreatinine;

AmberliteCG-120

,CG-50;

ethan

ol-a

cetoneppt

w/w

ohyd

rolysis

1963

Bruneet

al.[7

]HDMT;DMT

24hoururine

pH10

,ethyl

ether

ext,evap

,acetone

1963

Perry[8]

HDMT;DMT

24or48

hoururine;

extvo

l500

mgcreatinine

AmberliteCG-120

,CG-50;

ethan

ol-a

cetoneppt

1963

Sprince

etal.[9

]DMT,

HDMT

24hoururine

pH10

,ethyl

ether-butanoneext,evap

,acetone

1963

Perryan

dSchroed

er[10]

HDMT

24-36hoururine;extvo

l250

35

0mgcreatinine

AmberliteCG-120

,CG-50;

ethan

ol-a

cetoneppt

1965

Fran

zenan

dGross

[11]

DMT,

HDMT

bloodan

durine(24hour)

Extensive

multi-stepextraction,p

ptan

dclean-up

1965

Sieg

el[12]

HDMT

freshurine,

100ml

pH10

,ethyl

ether

ext,evap

,acetone

1965

Nishim

ura

andGjessing[13]

HDMT

freshurinevo

l500

1,00

0mgcreatinine

Dowex

50,A

mberliteCG50

,

1965

Takesadaet

al.[1

4]

HDMT

24hoururine

Ext,Dowex

50co

lumn,aluminaco

lumn

1966

Rungeet

al.[1

5]

HDMT

1Lofurine

pH8

9,butanole

xt,acetoneppt,aceton

e

1966

Perryet

al.[1

6]

DMT,

HDMT

48hoururine

Dowex

50W,A

mberliteCG-50;

HClh

ydrolysis

1966

Heller[1

7]

HDMT

1Lofurine

NaH

CO3sat.,

butanol,evap

,acetone

1967

Fischer

andSp

atz[18]

HDMT

100mlfresh

urine

NaC

O3,

ether

ext,evap

,acetone

1967

Kakim

oto

etal.[1

9]

DMT,

HDMT

24hoururine;

vol6

00mgcreatininean

alyzed

Ext,Dowex

50co

lumn,aluminaco

lumn

1967

Tanim

ukai[2

0]

HNMT,HDMT,NMT,DMT,MDMT

24hoururine;

1/4thusedin

assay

Dowex

50W

X2;

w/w

oHClh

ydrolysis

1967

Tanim

ukaie

tal.[2

1]

HDMT

24hoururine;1/3rd

usedin

assay

cation

exch

angeresin;w

/woHCLhyd

rolysis

1967

Tanim

ukaie

tal.[2

2]

HDMT

24hoururine;

1/4thusedin

assay

Dowex

50W

X2;

HClh

ydrolysis

1967

Acebal

andSp

atz[23]

HDMT

100mlu

rine

NaC

O3,

ether

ext,evap

,acetone

1968

Faurbye

andPind[24]

HDMT

24hoururine,

hyd

rolyzedat

pH1.6

columnch

romatog

raphy,sublim

ation,p

aper/TLC

1969

Sireixan

dMarini[2

5]

HDMT

100mlfresh

urine

NaC

O3,

ether

ext,evap

,acetone

1969

Spatzet

al.[2

6]

HDMT

50mlfresh

urine;

100mlfresh

urine

pH10

NaO

H,ethylacetate;diazo-reage

ntor

TLC

1970

Fischer

andSp

atz[27]

HDMT

50mlfresh

urine;

acid

hyd

rolysis

pH10

NaO

H,e

thyl

acetate;

diazo-reagen

tan

dTLC

1970

Saaved

raan

dUdab

e[28]

HDMT

50mlfresh

urine;

acid

hyd

rolysis

pH10

NaO

H,e

thyl

acetate;

diazo-reagen

tan

dTLC

1970

Tanim

ukaie

tal.[2

9]

HNMT,HDMT,DMT,

MDMT

24hoururine;

1/4thusedin

assay

Dowex

50W

X2;

HClh

ydrolysis

1970

Helleret

al.[3

0]

DMT,

MDMT,

HDMT

fastingblood,o

xalate

tube;

acid

hyd

rolyzed

Dow

ex50;H

Clextan

dethylacetateatpH10.2

1971

Narsimhacharie

tal.[3

1]

DMT,

MDMT,

HDMT

24hoururine;

75%

usedin

assay

Dow

ex50;H

Clextan


1971

Narasim

hacharie

tal.[3

2]

NMT,

DMT,MDMT

fastingblood,o

xalate

tube

Dow

ex50;H

Clextan

dethylacetate

atpH10.2

1971

Fischer

etal.[3

3]

HDMT,glucu

ronide

50mlm

orningurine;

w/w

oglucuronidase

Liquid-Liquid

ext;w/w

oglucuronidasetreatm

ent

1972

Him

wichet

al.[3

4]

HDMT,DMT,

MDMT

24hoururine

Dow

ex50;H

Clextan


1972

Narasim

hacharie

tal.[3

5]

HDMT,DMT,

MDMT

24hoururine

Fran

zenan

dGross;H

Cle

xtethyl

acetateat

pH10

.2

1973

Walkeret

al.[3

6]

DMT

plasm

a;DMTstab

lefor60

daysat

6deg

rees

CHCLextacid

pHwithCHCl3,p

H9,

extCHCl3,e

vap

Reports of endogenous psychedelic N, N-dimethyltryptamines in humans

Drug Testingand Analysis

Drug Test. Analysis (2012) Copyright 2012 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/dta

Table

1.

(Con

tinue

d)

Year

Author

CompoundsAnalyzed

Collection

ExtractionMethod

1973

Wyatt

etal.[3

7]

DMT

plasm

aHCLextacid

pHwithCHCl3,p

H9,

extCHCl3,e

vap

1973

Narasim

hacharia

ndHim

wich[38]

DMT,HDMT

24-hou

rurine

Dow

ex50;H

Clextan


1974

Lipinskie

tal.[3

9]

DMT

plasm

aseparated

bycentrifu

gation

HCLextacid

pHwithCHCl3,p

H9,

extCHCl3,e

vap

1974

Bidder

etal.[4

0]

DMT

Hep

arinised

plasm

aorwhole

blood;2

4hrurine

HCLextacid

pHwithCHCl3,p

H9,

extCHCl3,e

vap

1974

Narasim

hacharie

tal.[4

1]

HDMT,DMT,MDMT

24hoururine

Dow

ex50;H

Clextan


1975

Carpen

teret

al.[4

2]

DMT,HDMT

24hoururine,

90%

usedin

assay

Dowex

50;H

Cle

xtan

dethyl

acetateat

pH10

.2

1975

Christianet

al.[4

3]

DMT,MDMT

Cereb

rospinaluid

Dep

roteinization,liquid-liquid

ext,CH2C

l2

1975

Narasim

hacharia

ndHim

wich[44]

DMT,HDMT

24hoururine,

80%

usedin

assay

Dowex

50;H

Cle

xtan

dethyl

acetateat

pH10

.2

1976

Angrist

etal.[4

5]

DMT

non-fastingblood;h

eparin;1

0mla

ssayed

HCLextacid

pHwithCHCl3,p

H9,

extCHCl3,e

vap

1976

Rodnightet

al.[4

6]

DMT

24-hou

rurine

Dowex

50;H

Cle

xtan

dethyl

acetateat

pH10

.2

1976

Murray

andOon[47]

DMT

24-hou

rurine

Dowex

50;H

Cle

xtan

dethyl

acetateat

pH10

.2

1976

Huszka

etal.[4

8]

HDMT,DMT,MDMT

24hoururine;

1/3rd

usedin

assay

Dowex

50W

X2;

HClh

ydrolysis

1977

Cottrellet

al.[4

9]

HDMT

24hoururine

HCLextacid

pHwithCHCl3,p

H11

,ext

CHCl3,e

vap

1977

Oonet

al.[5

0]

DMT,NMT

24-hou

rurine;

50%

used;

50%concen

trated

andextractedwith

toluen

e

DMT,NMTstab

le90

daysat1

5C

puried

byTLC,d

erivatized

withTFAA

1977

Oonan

dRo

dnight[5

1]

DMT,NMT

24-hou

rurine;

50%

usedin

assay

50%

concentrated

andextractedwithtoluen

e

puried

byTLC,d

erivatized

withTFAA

1978

Ricebergan

dVan

Vunakis[52]

DMT,HDMT,MDMT

24hoururine;

300mlu

sedin

assay

Urine(pH10

.5)extwithCHCl3

50mlw

holeblood;p

lasm

aWhole

bloodlysed,p

rotein

ppt.withHClO4

extractedtw

icewithch

loroform

1978

Corbettet

al.[5

3]

DMT,MDMT

Cereb

rospinaluid

Dep

roteinization,Liquid-Liquid

ext,CH2C

l2

1979

Walkeret

al.[5

4]

DMT

10mlw

holeblood;arteriala

ndvenous

HCLextacid

pHwithCHCl3,p

H9,

extCHCl3,e

vap

1979

Murray

etal.[5

5]

DMT,NMT

24-hou

rurine;

50%

usedin

assay

acidied

withHCl

50%concen

trated

andextractedwith

toluen

e

puried

byTLC,d

erivatized

withTFAA

1979

Checkley

etal.[5

6]

DMT

24hoururine;

50%

usedin

assay

acidied

withHCl

50%concentrated

andextractedwith

toluen

e

puried

byTLC,d

erivatized

withTFAA

1979

Raisan

enan

dKarkkainen

[57]

DMT,HDMT

150mlm

orningurinesamples

pH11

,XADresin,e

thyl

acetateelution,e

vap,T

LC

1979

Smythieset

al.[5

8]

DMT,MDMT

Cereb

rospinaluid

Dep


ext,CH2C

l2

1980

Checkley

etal.[5

9]

DMT

Serial

24hoururine;

longitudinal

study

acidied

withHCl

50%concentrated

andextractedwith

toluen

e

puried

byTLC,d

erivatized

withTFAA

1983

Ueb

elhacket

al.[6

0]

DMT,MDMT

Cereb

rospinaluid

Dep


ext,CH2C

l2

1983

Sitaram

etal.[6

1]

HDMT

12hrspecim

ens(8pm-8am

);20

0mla

ssayed

ionpairextCHCl3,LC-silica

columnpurication

1984

Raisan

enet

al.[6

2]

HDMT

notstated

pH11

,XADresin,e

thyl

acetateelution,e

vap,T

LC

1988

Karkkainen

etal.[6

3]

HDMT

morningurinesamples

pH11

,XADresin,e

thyl

acetateelution,e

vap,T

LC



wileyonlinelibrary.com/journal/dta Copyright 2012 John Wiley & Sons, Ltd. Drug Test. Analysis (2012)

Table

1.

(Con

tinue

d)

Year

Author

CompoundsAnalyzed

Collection

ExtractionMethod

1992

Karkkainen

andRa

isan

en[64]

HDMT

individual

urinesamples;

pH11

,XADresin,e

thyl

acetateelution,e

vap,T

LC

w/w

onialamidetreatm

ent

1995

Karkkainen

etal.[6

5]

HDMT

morningurinesamples;50

10

0ml

pH11

,XADresin,e

thyl

acetateelution,e

vap,T

LC

1995

Takedaet

al.[6

6]

HDMT,HNMT

morningurinesamples

centrifu

gation,d

irectinjectionof80

mlofurine

2001

Forsstrom

etal.[6

7]

DMT,

MDMT,

HDMT,

NMT

morningan

dafternoonurines;5

mla

ssayed

urinecentrifu

ged

andextonOasisSP

Ecartridge

2005

Karkkainen

etal.[6

8]

DMT,

HDMT

urine(5ml),

plasm

aorserum

(1ml),

stool;

urinecentan

dextonOasisHLB

cartridge;

tissues

(0.5-1.5g)

Prep

LCforblood

2010

Eman

ueleet

al.[6

9]

HDMT

random

urinesamples

urinecentan

dextonOasisHLB

cartridge

Table

2.

Review

of69

studiesregardingen

dog

enouspsych

edelicsshow

ingtheyear,referen

ce,compoundsan

alyzed

,detectionmethod

s,lim

itsofdetection(LOD)an

dco

nrm

ationcriteria.A

cronym

san

dab

breviations;HNMT,5-hyd

roxy-N-m

ethyltryp

tamine;

TLC,thin-la

yerch

romatography;2-D,twodim

ension

al;G

C-FID,g

asch

romatog

raphy-am

eionizationdetector;derive,derivative;HFB

I,hep

ta-

uoro-butyryl-imidazole;IS,internalstan

dard;H

PLC,h

ighperform

ance

liquid

chromatography;ESI,electrosprayionization;M

S,massspectrometry;N

D,n

otdetermined

;RT,retentiontime;UV,u

ltraviolet;

TI,total

ion;m

/z,m

ass-to-chargeratio;C

I,ch

emical

ionization;IA,immunoa

ssay;M

RM,m

ultiple

reaction

mon

itoring.

Year

Author

Compounds

Analyzed

DetectionMethods

LimitofDetection

Conrm

ationCriteria

1955

Bumpus

andPa

ge[1]

HNMT,

HDMT

pap

erch

romatography(1

system

),co

lorreaction

,bioassay

ND

Rfan

dco

lor(1

system

)

1956

Rodnight[2

]HNMT,

HDMT

pap

erch

romatography(3

system

s),colorreaction,b

ioassay

>5mg

/24

hourforHDMT

Rfan

dco

lor(3

system

s)

1961

Fischer

etal.[3

]HDMT

pap

erch

romatography(1

system

)ND

Rfan

dco

lor(1

system

)

1961

Fischer

etal.[4

]HDMT

pap

erch

romatography(1

system

)ND

Rfan

dco

lor(1

system

)

1961

Feldsteinet

al.[5

]HDMT

pap

erch

romatographyan

dau

to-rad

iographs

ND

Rfandcolor(1

system

),radioactivespot

1962

Perryet

al.[6

]HDMT,

conjugate

pap

erch

romatography(2-D),co

lorreaction

ND

Rfan

dco

lor(2-D)

1963

Bruneet

al.[7

]HDMT;

DMT

pap

erch


lorreaction

20ng/m

lRf

andco

lor(2-D)

1963

Perry[8]

HDMT;

DMT

2-Dpap

erch

romatog

raphy,co

lorreaction

ND

Rfan

dco

lor(2-D)

1963

Sprince

etal.[9

]DMT,HDMT

2-Dpap

erch

romatog

raphy,co

lorreaction

ND

Rfan

dco

lor(2-D)

1963

Perryan

dSchroed

er[10]

HDMT

pap

erch

romatography(3

system

s)ND

Rfan

dco

lor(3

system

s)

1965

Fran

zenan

dGross

[11]

DMT,HDMT

Fluorescen

ce2ng/m

lFluoresence

read

ing

1965

Sieg

el[12]

HDMT

TLC(1

system

),co

lorreaction

0.1mg

/100

ml

Rfan

dco

lor(1

system

)

1965

Nishim

ura

and

Gjessing[13]

HDMT

TLC(2-D),co

lorreaction

ND

Rfan

dco

lor(2-D)

1965

Takesadaet

al.[1

4]

HDMT

pap

erch

romatography,co

lorreaction

20mg

/24hour

Rfan

dco

lor




Table

2.

(Con

tinue

d)

Year

Author

Com

pounds

Analyzed

DetectionMethods

LimitofDetection

Conrm

ationCriteria

1966

Rungeet

al.[1

5]

HDMT

pap

erch

romatography,co

lorreaction

ND

Rfan

dco

lor(2-D)

1966

Perryet

al.[1

6]

DMT,HDMT

pap

erch


lorreaction

2mg

/24hrforDMTan

dHDMT

Rfan

dco

lor(2-D)

1966

Heller[1

7]

HDMT

pap

erch


lorreaction

ND

Rfan

dco

lor(2-D)

1967

Fischer

andSp

atz[18]

HDMT

pap

erch


lorreaction

ND

Rfan

dco

lor(2-D)

1967

Kakim

oto

etal.[1

9]

DMT,HDMT

pap

erch

romatography(3

system

s),colorreaction

10mg

/24hour

Rfan

dco

lor(3

system

s)

1967

Tanim

ukai[2

0]

HNMT,HDMT,NMT,

DMT,

pap

eran

dTLC(2-D);co

lorreaction

;GC-FID

ofHDMT

5ng/m

lHDMT;1ng/m

lothers

Rfan

dco

lor(2-D

pap

er,TLC

)

MDMT

1967

Tanim

ukaie

tal.[2

1]

HDMT

pap

erch

romatography,TLC(2-D),co

lorreaction;G

C-FID

>0.1mg

/24hour

Rfan

dco

lor(2-D);GC-RT

1967

Tanim

ukaie

tal.[2

2]

HDMT

pap

eran

dTLC(2-D);co

lorreaction

;GC-FID

ofHDMT

ND

Rfan

dco

lor(2-D

pap

er,TLC

);GC-RT

1967

Acebal

andSp

atz[23]

HDMT

pap

erch


lorreaction

ND

Rfan

dco

lor(2-D)

1968

Faurbye

andPind[24]

HDMT

pap

erch

romatographyan

dTLC,colorreaction

>0.7mg

/24hour

Rfandcolor(pap

erand2-DTLC)

1969

Sireixan

dMarini[2

5]

HDMT

UV;p

aper

chromatography,co

lorreaction

ND

Rfan

dco

lor(2-D)

1969

Spatzet

al.[2

6]

HDMT

UVofdiazo-deriv;p

aper

chromatography,co

lorreaction

ND

UV;R

fan

dco

lor

1970

Fischer

andSp

atz[27]

HDMT

UV;T

LC,colorreaction

ND

UV;R

fan

dco

lor

1970

Saaved

raan

dUdab

e[28]HDMT

UV;T

LC,colorreaction

ND

UV;R

fan

dco

lor

1970

Tanim

ukaie

tal.[2

9]

HNMT,HDMT,DMT,

MDMT

pap

eran

dTLC(2-D);co

lorreaction

;GC-FID

ofHDMT

ND

Rfandcolor(2-D

pap

er,TLC

);GC-RT

1970

Helleret

al.[3

0]

DMT,MDMT,HDMT

GC-FID,T

LC,andSp

ectrouorometry

2ng/m

lGC-RTan

dTLCorspectrouorometer

1971

Narsimhacharie

tal.[3

1]

DMT,MDMT,HDMT

TLCan

dGC-FID,veried

withspectrouorometer

5mg

/mlp

er24

hourforDMT

TLCan

dGC-FID,spectrouorometer

1971

Narasim

hacharie

tal.[3

2]NMT,DMT,

MDMT

TLCan

dGC-FID,veried


2ng/m

lTLCan

d/orGC-FID,spectrouorometer

1971

Fischer

etal.[3

3]

HDMT,glucu

ronide

UV;p

aper

chromatography,co

lorreaction

ND

UV;R

fan

dco

lor

1972

Him

wichet

al.[3

4]

HDMT,DMT,MDMT

TLC(3

system

s),colorreaction

;veried

with

spectrouorometer

ND

Rf,coloran

duoresence

1972

Narasim

hacharie

tal.[3

5]HDMT,DMT,DMT

pap

eran

dTLC(2-D);co

lorreaction

;GC-FID

0.05

mg/24hou

rRf

andco

lor(2-D);GC-RT

1973

Walkeret

al.[3

6]

DMT

GC-M

S;2ft.SE-30

glasscapillarycolumn,DMT-d2

IS,TMSderiv

0.5ng/m

l;m/z

202/20

4,26

0/26

2GC-RT,

twoionsan

dratio

1973

Wyatt

etal.[3

7]

DMT

GC-M

S;2ft.SE-30


IS,TMSderiv

0.5-1.8ng

/ml;m/z202/204,260/262

GC-RT,tw

oions

andratio

1973

Narasim

hacharia

nd

Him

wich[38]

DMT,HDMT

TLCDACAan

dOPT

sprayoncellu

lose

andsilica;GC/M

S,

58m/z

only

5ng/m

lHDMT;1ng/m

lDMT

Rfan

dco

lor(2-D);GC-RT;GC/M

S58

mz

TIspectrum

match

withDMTstan

dard

1974

Lipinskie

tal.[3

9]

DMT

GC-M

S;2ft.SE-30


IS,TMSderiv

0.5ng/m

lGC-RT,tw

oions

andratio

1974

Bidder

etal.[4

0]

DMT

GC-M

S;2ft.SE-30


IS,TMSderiv

bloo

d0.05-2ng

/ml;urine0.07-

0.2ng

/ml

GC-RT,tw

oions

andratio

1974

Narasim

hacharie

tal.[4

1]HDMT,DMT,MDMT

TLCDACAan

dOPT

sprayoncellu

lose

andsilica;GC/M

S,

58m/z

only

5ng/m

lHDMT;1ng/m

lDMT

Rfan

dco

lor(2-D);GC-RT;GC/M

S58

mz

TIspectrum

match

withDMT,HDMT

1975

Carpen

teret

al.[4

2]

DMT,HDMT

TLCDACAan

dOPT

sprayoncellu

lose

andsilica;GC/M

S,

58m/z

only

5ng/m

lHDMT;1ng/m

lDMT

Rfan

dco

lor(2-D);GC-RT;GC/M

S58

mz

1975

Christianet

al.[4

3]

DMT,MDMT

GC-ECD;p

ackedco

lumn

DMT10

pg/m

l;MDMT5pg/m

lRT

1975

Narasim

hacharia

nd

Him

wich[44]

DMT,HDMT

TLCDACAan

dOPT

sprayoncellu

lose

andsilica;GC/M

S,

58m/z

only

5ng/m

lHDMT;1ng/m

lDMT

Rfan

dco

lor(2-D);GC-RT;GC/M

S58

mz




Table

2.

(Con

tinue

d)

Year

Author

Compounds

Analyzed

DetectionMethods

LimitofDetection

Conrm

ationCriteria

1976

Angrist

etal.[4

5]

DMT

GC-M

S;2ft.SE-30

glasscapillary

column,DMT-d2IS,TMSderiv

0.05

ng/m

lRT

,twoionsan

dratio

1976

Rodnightet

al.[4

6]

DMT

GC-FID,TLC

oncellu

lose;G

C/M

S2patients

andpooled

(10)

extract

0.5mg

/24h

our

Rfan

dco

lor;GC-RT;match

ingTI

MS

1976

Murray

andOon[47]

DMT

GC-FID,TLC

oncellu

lose;G

C/M

S2patients

andpooled

(10)

extract

20ng/24h

our

Rfan

dco

lor;GC-RT;GC-M

S

1976

Huszka

etal.[4

8]

HDMT,

DMT,MDMT

TLCan

dGC-FID,veried


4ng/m

lTLCan

dGC-FID,spectrouorometer

1977

Cottrellet

al.[4

9]

HDMT

HFB

Iderivatives,G

C-ECD

0.01

ng/m

lper

12hr

RTan

duoresence

spectrum

1984

Raisan

enet

al.[6

2]

HDMT

TMSderivatives;G

C/M

S,multiple

iondetection

0.1-0.15

ng/m

lDMT;0.25-0.3ng

/ml

HDMT

RT,m

olecularionsorfrag

men

ts

1988

Karkkainen

etal.[6

3]

HDMT

TMSderivatives;G

C/M

S,multiple

iondetection

0.1-0.15

ng/m

lDMT;0.25-0.3ng

/ml

HDMT

RT,m

olecularionsorfrag

men

ts

1992

Karkkainen

and

Raisan

en[64]

HDMT

TMSderivatives;G

C/M

S,multiple

iondetection

0.1-0.15

ng/m

lDMT;0.25-0.3ng

/ml

HDMT

RT,m

olecularionsorfrag

men

ts

1995

Karkkainen

etal.[6

5]

HDMT

TMSderivatives;G

C/M

S,multiple

iondetection

0.1-0.15

ng/m

lDMT;0.25-0.3ng

/ml

HDMT

RT,m

olecularionsorfrag

men

ts

1995

Takedaet

al.[6

6]

HDMT,

HNMT

3-D-HPL

C-electroch

emical

detection

50pg/m

lRT

andelectroche

micalrespon

se

2001

Forsstrom

etal.[6

7]

DMT,MDMT,HDMT,

NMT

HPL

C/ESI-M

S-MS

0.35

ng/m

lHDMT;0.1ng/m

lDMT

RT,P

seudomolecularion,M

RM

0.1ng/m

lMDMT;0.05

ng/m

lNMT

2005

Karkkainen

etal.[6

8]

DMT,HDMT

HPL

C/ESI-M

S/MS

0.3ng/m

lHDMT;0.2ng/m

lDMT

RT,P

seudomolecularion,M

RM

2010

Eman

ueleet

al.[6

9]

HDMT

HPL

C/ESI-M

S/MS

ND

RT,P

seudomolecularion,M

RM




Table3.

Review

of6

9studiesregardingen

dog

enous

psych

edelicsshowingtheyear,referen

ce,compoun

dsan

alyzed

,thesubjects(patientsan

dco

ntrols),theresultspositive

orneg

ativeoutofthetotal

(i.e.4/12

)an

dtheco

ncentrationsoftheco

mpoundsobserved

.Acronym

san

dab

breviations;HNMT,5-hyd

roxy-N-m

ethyltryp

tamine;med

s,med

ications;MAOI,monoam

ineoxidaseinhibitor;ad

min,ad-

ministration;sch

izo,sch

izophrenia;n

eg,n

egative;

ND,n

otdetected;N

A,n

otap

plicab

le;p

sych

iat,psych

iatric;sig

dif,

signicantdifferen

ce;

Year

Author

Compounds

Analyzed

Subjects

Positive/Neg

ative

Con

centration

1955

Bumpus

andPa

ge[1]

HNMT,

HDMT

4healthyad

ults

pooled

sample;5

-HNMT,HDMT

ND

1956

Rodnight[2

]HNMT,

HDMT

11healthyad

ults

noHNMTorHDMTdetected

ND

1961

Fischer

etal.[3

]HDMT

5acute

schizophrenics,4co

ntrols

5/5schizophrenicsHDMT,4co

ntrolsneg

400ng/m

l

1961

Fischer

etal.[4

]HDMT

15schizophrenics,10

controls

14/15HDMT;0/10

HDMT

ND

1961

Feldsteinet

al.[5

]HDMT

15schizophrenics,10

controls;n

omed

sfor2wee

ksnoHDMTdetected

ND

1962

Perryet

al.[6

]HDMT,

conjugate

20co

ntrolchild

ren;6

received

MAOIp

hen

iprazine

(3)ornialamide(3)

1/20

HDMT;

4/6HDMTfollo

wingMAOI

0.3mg

/10

0mgcreatinine;

0.5-2.2mg

/100

mg

creatininewithMAOI

3onaplant-free

dietduringad

min

ofneo

mycin

to

reduce

intestinalora

1963

Bruneet

al.[7

]HDMT;

DMT

5schizophrenics;3men

tally

de

cien

tpatients;M

AOI

isocarboxazidplusbetaine

9of17

urinesamples;0/3;

MAOI

increasedschizosymptoms

20-30mg

/24hourHDMT;DMT

neg

ativein

allsam

ples

1963

Perry[8]

HDMT;

DMT

18juvenilepsychotics;Someon

plant-freediet

andMAOI

noDMTdetected;2

positive

forHDMT

afterMAOI

30ng/100

mgcreatinine

1963

Sprince

etal.[9

]DMT,HDMT

4schizophrenics,2psych

oneu

rotics;M

AOI

tran

ylcypromine,

methioneortryp

tophan

noDMTorHDMTdetected

NA

1963

Perryan

dSchroed

er[10]

HDMT

7co

ntrola

nd2psych

oticch

ildren;1

controlo

n

plant-free

diet;2co

ntrolsreceived

MAOI

1/2psych

otics

HDMT;2/2co

ntrols

receivingMAOI

NA

1965

Fran

zenan

dGross

[11]

DMT,HDMT

blood37

controls;u

rine46

controls

11/37bloodDMT;37

/37urineDMT

8-55

ng/m

l;42

.98+/

8.6mg

/24hou

r

12/37bloodHDMT;

46/46urineHDMT

1-40

ng/m

l;62

.8+/

7.2mg

/24hour

1965

Sieg

el[12]

HDMT

5norm

als,21

schizophrenics

noHDMTdetected

NA

1965

Nishim

ura

andGjessing[13]

HDMT

2periodiccatitonia

patients;strictdietary

control;

phen

elzineMAOI

noHDMTdetected

NA

1965

Takesadaet

al.[1

4]

HDMT

7schizophrenics,8co

ntrols;n

omed

s30

days

noHDMTdetected

NA

1966

Rungeet

al.[1

5]

HDMT

22schizophrenicsnomed

s;14

schizophrenicson

med

s,17

controls;n

omed

s60

days

noHDMTdetected

ND

1966

Perryet

al.[1

6]

DMT,HDMT

12maleschizophrenics,7maleco

ntrols;M

AOI

phen

elzinead

ministered;

noHDMTorDMTdetected

NA

nomed

sfor6weeks;noplantsor

cheese

indiet

1966

Heller[1

7]

HDMT

11schizoph

renics,4

controls;10schizoph

renics,4

controls

received

MAOI

10/11HDMT,0/4HDMT;10

/10HDMT,

0/4HDMT

ND

1967

Fischer

andSp

atz[18]

HDMT

95schizophrenicsw/o

treatm

ent,43

withtreatm

ent;

102co

ntrols

71/95HDMT,16

/43HDMT;0/10

2HDMT

ND

1967

Kakim

oto

etal.[1

9]

DMT,HDMT

8schizophrenicfemales;treated

withmethionine

andisocarboxazide(M

AOI)

noHNMT,NMT,HDMTorDMT

detected

NA




Table

3.

(Con

tinue

d)

Year

Author

Com

pounds

Analyzed

Subjects

Positive/Neg

ative

Concentration

1967

Tanim

ukai[2

0]

HNMT,HDMT,

NMT,

DMT,

4malech

ronicschizophrenics;MAOItranylcypromine;

speciald

iet;nomed

s

46wee

ks

4/10

0samplesHDMT;

3/10

0

conjugated

ND

MDMT

DMTan

dMDMTobserved

insomesamples

1967

Tanim

ukaie

tal.[2

1]

HDMT

6maleschizoph

renics,4

malemen

tally

defective

patients;speciald

iet;no

med

s7weeks

HDMT;co

njugated

inall1

0,

free

in7/10

>1mg

/24hour

1967

Tanim

ukaie

tal.[2

2]

HDMT

4schizophrenics,MAOItranylcypromine,

cysteinead

min;speciald

iet

1/4free

HDMT,

3/4co

nj;MAO

4/4free

,3/4

conj

HDMT4

10mg

/24hou

r

1967

Acebal

andSp

atz[23]

HDMT

10schizophrenics;7co

ntrols;p

atients

administeredtriuperidol

7/10

HDMT,0/10

aftertriuperidol;

0/7HDMT

ND

1968

Faurbye

andPind[24]

HDMT

7schizophrenics,5co

ntrols

6/7schizophrenics,3/5co

ntrols

schizophrenics0

3.7mg

/24hou

r;

controls0

7.5mg

/24hour

1969

Sireixan

dMarini[2

5]

HDMT

20schizophrenics,20

non

-sch

izophrenics,

20co

ntrols;speciald

iets

19/20HDMT,

19/20HDMT,18

/20

schizophrenicmeanof15

5ng/m

l,

non

-21

ng/m

l,co

ntrols29

ng/m

l;

nodietary

effects

1969

Spatzet

al.[2

6]

HDMT

65schizophrenics,73

controls

65/65schizophrenics,73

/73co

ntrols

65/65mean17

2ng/m

l;73

/73mean

36ng/m

l

1970

Fischer

andSp

atz[27]

HDMT

67co

ntrols,1

1ep

ilepsy,9

dep

ression,

8psycho

pathic,86no

n-treatedschizophren

ics

67/67normals,11

/11ep

ilepsy,

9/9dep

ression

norm

1289

ng/m

l,ep

ilepsy

2667

ng/m

l,dep

ress

1242

ng/m

l,psych

o20

54

ng/m

l,

45treatedschizophrenics

8/8psych

opathic,8

6/86

,45/45

schizophrenics

schizo17

/8612

96

ng/m

l,69

/86

100

375ng/m

l,33

/4510

10

0ng/m

l,

12/4510

121

2ng/m

l

1970

Saaved

raan

dUdab

e[28]

HDMT

4co

ntrols,2

5psych

iatricpatients,1

1non

-

treatedschizo,4

treated,4

hysteria

allp

ositive

norm

17+/

2.7ng/m

l,psych

iat

24+/

2.8ng/m

l,schizountreated

160+

/22

.7,

treated35

+/

10ng/m

l,hysteria

69+/

9ng/m

l

1970

Tanim

ukaie

tal.[2

9]

HNMT,HDMT,

DMT,

MDMT

4schizophrenics,MAOItranylcypromine,

methionineorcysteinead

min;speciald

iet

4/4HDMT,3/4MNMT,3/4DMT,

2/4MDMT

HDMT4

10mg

/24hou

r

1970

Helleret

al.[3

0]

DMT,MDMT,

HDMT

5acuteschizophren

ics,9chronicschizophren

ics,

2no

rmals,1dep

ressive

5/5DMT,5/5MDMT,2/5HDMT;

0/12

forothers

NA

1971

Narsimhacharie

tal.[3

1]

DMT,MDMT,

HDMT

2schizophrenics,6co

ntrols;M

AOI

tran

ylcypromine,

cysteinead

min.

2schiziphrenicspositive;6

controls

neg

ative

10-40mg

/ml

1971

Narasim

hacharie

tal.[3

2]

NMT,DMT,

MDMT

22acuteschizoph

renics,20no

n-schizophren

ics

15/22DMTan

d/orMDMT,2/22

HDMT;

2/20

positive

2ng/m

l

1971

Fischer

etal.[3

3]

HDMT,glucuron

ide

4each,con

trol,acute

andchronicscizop

hren

ics

allp

ositive

controls(Freeortotal)63

+/

14.3

or93

+/

21ng/m

l;ch

ronic

91+/

21.6

or18

8+/

16ng/m

l;




Table

3.

(Con

tinue

d)

Year

Author

Compounds

Analyzed

Subjects

Positive/Neg

ative

Concentration

acute200+

/47.5or

289+

/78

ng/m

l

1972

Him

wichet

al.[3

4]

HDMT,DMT,

MDMT

6au

tistics,6co

ntrols;speciald

iets

6co

ntrolsneg

forall;5/6au

tistics

positive

forHDMT

50

0ng/24hr;12

/20>

500ng/24hr;

1/19>50

0ng/24hr

1979

Raisan

enan

d

Karkkainen

[57]

DMT,HDMT

26co

ntrols

allD

MTan

dHDMTpositive

DMTmean96

ng/g

creatinine;

HDMT

mean95

0ng/g

creatinine

1979

Smythieset

al.[5

8]

DMT,MDMT

11patients

undergoinglumbar

puncture

11/11DMT;1/11

MDMT

DMTrangefrom

external

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