767648
letter2018
JOP0010.1177/0269881118767648Journal of PsychopharmacologyBarker
Letter to the Editor
N,N-dimethyltryptamine facts and myths
Steven A Barker
I write concerning the review article “N,N-dimethyltryptamine
and the pineal gland: Separating fact from myth”, authored by
David E. Nichols and recently published in the Journal of
Psychopharmacology (Nichols, 2018).
It appears the peer review process has failed you.
In his effort to “separate fact from myth”, the reviewers and
Journal failed to note that the author is actually attempting to cre-
ate a myth about N,N-dimethyltryptamine (DMT) all his own.
The author states at the opening:
“This review will essentially focus on whether or not DMT is
produced in the human body. More specifically, is DMT
produced in the human body, and especially by the pineal
gland in physiologically relevant amounts? It seems clear that
DMT can be produced in the body, as well as by the pineal
gland, in extremely tiny amounts (Barker et al., 2012, 2013),
but the more important issue is whether those amounts are
sufficient to affect human physiology”.
However, neither of the two references cited provide any
data as to the concentration of DMT in the brain in general or
the pineal gland specifically. Nonetheless, he is correct that
more than adequate data have been produced in the scientific
literature proving that DMT, a potent hallucinogen, is produced
in vivo.
However, the myth the author wishes to create is that DMT is
produced in the pineal gland “in extremely tiny amounts,” a sci-
entifically meaningless description. His myth is then extrapo-
lated to the conclusion that the role of endogenous DMT is,
therefore, insignificant. The facts are that there has yet to be any
study quantitating DMT in this gland or surrounding brain struc-
tures. Knowing the actual concentration of DMT is a sine qua
non for Nichols’ review and the topics he discussed.
As the corresponding author of the only publication to have
definitively identified DMT in rat pineal gland liquid chromatog-
raphy-mass spectrometry-mass spectrometry (LC/MS/MS) anal-
ysis of the endogenous dimethyltryptamine hallucinogens, their
precursors, and major metabolites in rat pineal gland microdi-
alysate: Barker et al., 2013, which Nichols specifically references
as a source, I think it is important that this newly created myth
and misinformation by Nichols be addressed, corrected and dis-
pelled in order to forestall premature closure of research into
endogenous DMT synthesis and function.
For a number of reasons, we (Barker et al., 2013) did not
attempt quantitation of DMT in the pineal gland itself nor in the
Journal of Psychopharmacology
2018, Vol. 32(7) 820­–822
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dialysates. The analysis was only qualitative, conducted to
determine if DMT could be shown to be present in the pineal
gland of the living rat. Conducting only a qualitative analysis
was due, in part, to the nature of the experiments themselves and
the samples so collected. First, the probe used in these studies
approximates the position of the pineal gland, traversing both
the pineal gland as well as the superficial layers of the occipital
cortex on either side of the gland. Thus, contribution from sur-
rounding areas could not be excluded. Second, the perfusion
dialysis was performed with an artificial cerebrospinal fluid
solution flowing continuously through the perfused area at 2 μL/
min for 2 h (240 µL total). In this study, all sample collections
were performed during daylight hours. The analyses of the per-
fusates were conducted by LC/MS/MS using a 30 µL injection
or only 12.5% of the total perfusate. No extraction or concentra-
tion of the sample was attempted, with analyses occurring by
direct injection.
Therefore, one must then consider these details as well as oth-
ers when assessing the data as to any representation of the
“amount” of DMT: a) perfusion dialysis is a “washing” of the per-
fused area and will only collect “free” analytes; b) the dialysate is
a dilution of the substances present in the washed area; c) the effi-
ciency of recovery of the substances relative to their actual con-
centration in the tissue cannot be known with any certainty,
variations in the placement and size of the probe can also affect
the amount recovered; and d) samples were collected for only 2 h
during the day. This latter point prevents any assessment of the
total amount produced/day or any changes that may occur due to
circadian rhythms (perhaps particularly relevant to measurements
in the pineal gland) or other physiological changes on the relative
amounts of DMT to be found.
Thus, neither Nichols nor anyone else knows the concentrations
of DMT in rat pineal gland, much less that of humans. Accordingly,
it was inappropriate and scientifically unfounded for Nichols to
base his review, dismissing an abundance of previously published
peer-reviewed research in the process, solely on his pretense that
Department of Comparative Biomedical Sciences, School of Veterinary
Medicine, Louisiana State University, Baton Rouge, USA
Corresponding author:
Department of Comparative Biomedical Sciences, School of Veterinary
Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
Email: sbarke1@lsu.edu
Barker
DMT is only produced “in extremely tiny amounts”. The only exist-
ing published data regarding DMT’s presence in pineal gland does
not, as described, lend itself to such a determination. Indeed,
Nichols stated in his presentation that he is basing his opinion solely
on the fact that a very sensitive technique (LC/MS/MS) was used
and is either ignoring or unaware of the factors affecting such meas-
urements or estimations as outlined in the points outlined above.
It is unfortunate that the Journal of Psychopharmacology
published what constitutes a far-from-rigorous critique, moti-
vated, it would appear, by opposition to ideas and opinions
expressed in a documentary movie, a popular book, and various
blogs and websites. It is certainly not based on actual published
science. In so doing, Nichols appears determined to discourage
legitimate, rigorous scientific research into the biosynthesis and
function of DMT, an endogenous psychedelic substance.
No one yet knows what DMT is doing in the brain or what
physiological role it may or may not perform. We remain curious
as to why a known hallucinogen is present in the brain. Only
hypothesis-driven, objective, open-minded research will deter-
mine what is fact and what is myth, something Nichols’ opinion-
piece does not accomplish.
References
Barker SA, McIlhenny EH and Strassman R (2012) A critical review
of reports of endogenous psychedelic N,N-dimethyltryptamines in
humans: 1955–2010. Drug Test Anal 4: 617–635.
Barker SA, Borjigin J, Lomnicka I, et al. (2013) LC/MS/MS analysis of
the endogenous dimethyltryptamine hallucinogens, their precursors,
and major metabolites in rat pineal gland microdialysate. Biomed
Chromatogr 27: 1690–1700.
Nichols DE (2018) N,N-dimethyltryptamine and the pineal gland: Sepa-
rating fact from myth. J Psychopharmacol 32: 30–36.
Author’s reply
David E Nichols
Chemical Biology and Medicinal Chemistry, University of North Carolina
at Chapel Hill, USA
Corresponding author:
David E Nichols, Chemical Biology and Medicinal Chemistry, University
of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Genetic
Medicine Building, Chapel Hill, NC 27599-7360, USA.
Email: drdave@purdue.edu
This reply is a response to the letter recently sent to this Journal
by Dr Steven Barker concerning my review in this Journal enti-
tled “N,N-dimethyltryptamine and the pineal gland: Separating
fact from myth” (Nichols, 2018).
Dr Barker suggests that I am attempting to “create a myth” all
my own. The relevant definition of myth is: a widely held but
false belief or idea. Dr Barker states that my motivation appears
to be opposition to ideas and opinions expressed in a “documen-
tary movie, a popular book, and various blogs and websites.”
Indeed, those media outlets generally reinforce the myth that
DMT is secreted from the pineal gland to produce altered states
of consciousness, and I specifically wished to point out that this
821
myth needs to be exposed. However, I fail to see how I am
attempting to create a new myth. Does my critiquing a documen-
tary movie, a popular book, and various blogs and websites
equate to me attempting to create a new myth?
Dr Barker’s central attack on my review seems to stem from the
fact that no quantitative data exist for amounts of DMT produced
by the pineal gland. Thus, he argues, I have no basis for saying that
amounts of DMT produced in the body are not physiologically rel-
evant. It is true that no one has so far quantified the amount of
DMT produced by the pineal gland. However, it seems generally
agreed that the principle function of the pineal gland is the produc-
tion of melatonin. As I pointed out in my original article, measured
daily secretion of melatonin by the human pineal was found to be
between 21.6 μg (women) and 35.7 μg (men). I noted in my review
that it seems very improbable that in some situations the pineal
gland would ramp up acute DMT production to amounts approach-
ing 25 mg, when it normally can produce only about 1/1000th that
amount of melatonin. Given the approximate weight of the pineal
of < 200 mg, that would mean the pineal would have to produce
one-eighth of its weight in DMT in a very few minutes, given that
metabolism would constantly be breaking down the DMT that was
produced. That 25 mg amount, which is suggested by Gallimore
and Strassman’s (2016) calculations, must be given by intravenous
administration to produce a typical DMT intoxication.
In Dr Barker’s excellent and comprehensive 2012 review
(Barker et al., 2012), he cites quantitative DMT data from many
other laboratory studies. In that regard, looking at Table 3, and as
summarized at the bottom of page 629, in studies that tested for the
presence of DMT in the blood, the summary reads: “the concentra-
tions of DMT in blood ranged from 51 pg/mL (HPLC-
radioimmunoassay) to 55 ng/mL (direct fluorescence assay of
extracts).” According to Gallimore and Strassman (2016), a 100
ng/mL concentration “at the effective site” would produce a psy-
choactive effect. These reported blood DMT concentrations do not
correlate with any behavioral measure, and they are below the con-
centrations that might be expected to have a physiological effect. If
all of the studies summarized in that review article have similarly
low measured concentrations, on what basis would one conclude
that DMT was produced in anything other than tiny amounts?
Dr Barker also accuses me of being unaware of or ignoring
factors involved in microdialysis measurements. In my own labo-
ratory, we employed microdialysis to measure serotonin, dopa-
mine and norepinephrine, and created standard curves to allow
estimation of amounts of analytes. It is certainly possible to
quantify amounts of analytes in microdialysis studies, and it is
puzzling why, if that is a crucial factor in resolving a decades-old
controversy, Dr Barker, an expert who also has worked in this
field for decades, has not done so.
Dr Barker further argues that I have dismissed “an abundance
of previously published peer-reviewed research” in reaching my
conclusion that DMT is produced in only tiny amounts. I am not
aware of any previously published research, abundant or other-
wise, that indicates that DMT is produced in other than tiny
amounts.
Contrary to Dr Barker’s assertion, I am not “determined to dis-
courage legitimate, rigorous scientific research into the biosynthe-
sis and function of DMT…” To the contrary, I would love to see a
study that actually quantifies the absolute amounts of DMT pro-
duced by the pineal, or present in the blood, over a 24 h period. I am
willing to be proved wrong, but please, do the experiment!