348 • NOTES
7. Rick J. Strassman, "Adverse Reactions to Psychedelic Drugs. A Review of the Litera-
ture," Journal of Nervous and Mental Disease 172 (1984): 577-95.
8. Later revelations of CIA involvement in dosing unsuspecting citizens and Army recruits
with LSD and other psychedelics added shame and embarrassment to this already painful
assortment of feelings. See Martin A. Lee and Bruce Shlain, Acid Dreams: The Complete
Social History of LSD, the CIA, the Sixties, and Beyond (New York: Grove Press, 1986);
and Jay Stevens, Storming Heaven: LSD and the American Dream (New York: Grove Press,
1998), for thorough reviews of this remarkable chapter in American domestic national
9. Stanley Schachter and Jerome E. Singer, "Cognitive, Social, and Physiological Determi-
nants of Emotional State," Psychological Review 69 (1962): 379-99.
10. In addition to spawning so many names, psychedelics have inspired quite a following. I
know of no other drugs, except perhaps marijuana, with as many organizations dedicated
to educating about them, and promoting their use. There are dozens of psychedelic orga-
nizations with thousands of dues-paying members. They publish magazines, newsletters,
journals, and Web sites. They organize and sponsor conferences and publish and distrib-
ute books. The late Dr. Freedman from UCLA, an early LSD researcher and a driving
force behind my study, coined the term cultogen, referring to this zeal with which advo-
cates and enemies of their use rushed in with simple, one-sided descriptions of their
effects. Opiate, cocaine, or solvent users don't organize in such an effective manner. What
is so unique about psychedelics that they provoke such evangelical responses?
11. Drugs from other chemical families also may be psychedelic, but only within a narrow
dose range. For example, compounds in the nightshade family of plants, such as jimson-
weed, cause hallucinations and altered thinking processes. However, they do so in the
context of a confused, delirious state, with dangerous disturbances of cardiac function
and temperature control. Oftentimes one remembers little, and serious toxicity, including
death, may result from taking "a little too much." On the other hand, there are no cases of
psychedelic drugs being directly fatal.
Drugs like ketamine ("K" or "special K") and phencyclidine (PCP or "angel dust")
also produce psychedelic effects. However, they first saw use as general anesthetic agents
and cause unconsciousness at higher doses. The "classical" psychedelic drugs such as
LSD or mescaline don't cause general anesthesia.
In addition, ketamine, PCP, and nightshade-based drugs exert their psychoactive ef-
fects through pharmacological mechanisms different from those of LSD, psilocybin, and
DMT. For our purposes I will limit my discussion of "psychedelics" to those with similar
structures and pharmacological properties. For a review of any and all substances with
psychedelic properties, see Peter Stafford, Psychedelics Encyclopedia (Berkeley, CA: Ronin
12. Methyl groups, which consist of a carbon and three hydrogens, are themselves the sim-
plest possible addition to an organic molecule.
13. 5-MeO-DMT is the active ingredient in the secretion from the venom glands of the Sonoran
desert toad, Bufo alvarius. The drug is not obtained by licking these toads, as inaccurate
media reports would have it. Rather, intrepid users catch a toad and painlessly "milk" the
venom onto a glass slide. They release the toad, dry the secretions, and smoke them in a
pipe. See Wade Davis and Andrew T. Weil, "Identity of a New World Psychoactive Toad,"
Ancient Mesoamerican (1988): 51-59.
NOTES • 349
1. Alexander Shulgin and Ann Shulgin, T1HKAL (Berkeley,CA: Transform Press, 1997), 247-84.
2. R. H. F. Manske, "A Synthesis of the Methyl-Tryptamines and Some Derivatives," Cana-
dian Journal of Research 5 (1931): 592-600.
3. 0. Goncalves de Lima, "Observacoes Sobre o Vihno da Jurema Utilazado Pelos Indios
Pancaru de Tacaratu (Pernambuco)," Arquiv. lnst. Pesquisas AgronA (1946): 45-80; and
M. S. Fish, N. M. Johnson, and E. C. Horning, "Piptadenia Alkaloids. Indole Bases of P.
Peregrina (L.) Benth. and Related Species," Journal of the American Chemical Society 77
4. Stephen Szara, "The Social Chemistry of Discovery: The DMT Story," Social Pharmacol-
ogy 3 (1989): 237-48.
5. Stephen Szara, "The Comparison of the Psychotic Effects of Tryptamine Derivatives with
the Effects of Mescaline and LSD-25 in Self-Experiments," in Psychotropic Drugs, edited
by W. Garattini and V. Ghetti. (New York: Elsevier, 1957), 460-67.
6. A. Sai-Halasz, G. Brunecker, and S. Szara, "Dimethyltryptamin: Ein Neues Psychoticum,"
Psychiat. Neurol., Basel 135 (1958): 285-301.
7. A. Sai-Halasz, "The Effect of Antiserotonin on the Experimental Psychosis Induced by
Dimethyltryptamine," Experientia 18 (1962): 137-38.
8. D. E. Rosenberg, Harris Isbell, and E. J. Miner, "Comparison of Placebo, N-Dimethyl-
tryptamine, and 6-Hydroxy-N-Dimethyltryptamine in Man," Psychopharmacology 4 (1963):
9. Jonathan Kaplan, Lewis R. Mandel, Richard Stillman, Robert W. Walker, W. J. A.
Vandenheuvel, J. Christian Gillin, and Richard Jed Wyatt, "Blood and Urine Levels of
N,N-Dimethyltryptamine Following Administration of Psychoactive Dosages to Human
Subjects," Psychopharmacology 38 (1974): 239-45.
10. Timothy Leary, "Programmed Communication During Experiences with DMT," Psyche-
delic Review 8 (1966): 83-95.
11. This uncertainty about DMT effects helped the drug remain relatively obscure until Terence
McKenna began praising it publicly and lavishly in the mid-1980s. More than anyone,
McKenna has raised awareness of DMT, through lectures, books, interviews, and record-
ings, to its present unprecedented level.
12. For an excellent review summarizing the endogenous DMT data, see Steven A. Barker,
John A. Monti, and Samuel T. Christian, "N,N-Dimethyltryptamine: An Endogenous Hal-
lucinogen," International Review of Neurobiology 22 (1981): 83—110.
13. J. Christian Gillin, Jonathan Kaplan, Richard Stillman, and Richard Jed Wyatt, "The
Psychedelic Model of Schizophrenia: The Case of N,N-Dimethyltryptamine," American
Journal of Psychiatry 133 (1976): 203-8.
14. Despite reservations about the DMT theory of schizophrenia, it is worth noting that in the
twenty-five years since scientists abandoned it, there have been no other candidates nearly
as well qualified for this role.
15. In this context, it is a fascinating study in how the winds of public and political opinion
shape the research community's scientific agenda. There now is a flurry of funding for,
350 • NOTES
and publications about, the "ketamine model" of schizophrenia. As discussed previ-
ously, ketamine is an anesthetic drug, low doses of which produce psychedelic effects.
Similar to the "classical" psychedelic drugs, there is overlap between ketamine effects
and schizophrenic symptoms. However, there probably are as many differences and
similarities between schizophrenia and ketamine as there are between schizophrenia
and typical psychedelics.
There are at least two reasons for the current, relatively unimpeded progress in the
ketamine field. Many more rating scales now exist that statistically can compare drug-
induced to schizophrenic states. These provide more objective, mathematical support for
similarities between schizophrenia and ketamine intoxication. This approach may, how-
ever, tend to gloss over the real clinical differences between the two conditions. It was
these real-life differences that caused earlier investigators to reject the utility of compar-
ing typical psychedelic drug effects with symptoms of schizophrenia.
Another, and probably the more important, difference is that ketamine is a "legal"
drug. There are few restrictions limiting its use in human research. Nevertheless, the
recent surge in popularity of recreational ketamine use is tightening monitoring and con-
trols over it. In addition, concerns about worsening schizophrenic symptoms with ketamine,
and the nature of informed consent for these studies, are raising anxiety about psyche-
delic ketamine research in ways similar to older psychedelic studies.
16. Making DMT "from scratch" in the laboratory is not complicated. A reasonably skilled
chemist can produce it with modest effort in several days. The difficulty in making it is
not in the mechanics of doing so, but in obtaining the necessary ingredients, or precur-
sors. Federal drug authorities monitor supplies of these precursors very tightly, and you
need a permit to purchase any that might be turned into a known psychedelic drug.
17. Toshihiro Takahashi, Kazuhiro Takahashi, Tatsuo Ido, Kazuhiko Yanai, Ren Iwata, Kiichi
Ishiwata, and Shigeo Nozoe, "
C-Labelling of Indolealkylamine Alkaloids and the Com-
parative Study of Their Tissue Distributions," International Journal of Applied Radiation
and Isotopes 36 (1985): 965-69; and Kazuhiko Yanai, Tatsuo Ido, Kiichi Ishiwata, Jun
Hatazawa, Toshihiro Takahashi, Ren Iwata, and Taiju Matsuzawa, "In Vivo Kinetics and
Displacement Study of Carbon-11-Labeled Hallucinogen, N,N-[
European Journal of Nuclear Medicine 12 (1986): 141-46.
18. By some unimaginable feat of "pre-literate chemistry," South American natives learned to
combine DMT-containing plants with others possessing anti-MAO compounds, or MAO in-
hibitors. Accompanied by MAO inhibitors, swallowed DMT can withstand enzyme break-
down long enough to enter the bloodstream and exert its psychological effects before MAO
recovers sufficiently to dispose of it. This is the secret by which ayahuasca succeeds in
making DMT orally active. The slower absorption from the stomach and intestines means that
DMT effects in ayahuasca last 4 to 5 hours, rather than just minutes as with injected DMT.
1. Willis W. Harman, Robert H. McKim, Robert E. Mogar, James Fadiman, and Myron J.
Stolaroff, "Psychedelic Agents in Creative Problem-Solving: A Pilot Study," Psychologi-
cal Reports 19 (1966): 211-27.
2. More than twenty years later, in 1995,1 met Dorothy Fadiman at a meeting in Manaus, in
the Brazilian Amazon. When she returned home to California, she sent me her 1970s
video about light, Radiance. The circle finally was complete.
NOTES • 351
3. The Crown or Thousand-Petaled Lotus chakra is not the same as the "third eye." The
latter, located in the middle of the forehead just above and between the eyes, anatomically
corresponds most closely with the pituitary gland.
4. The relationship of cerebrospinal fluid to consciousness recently got a boost from brain
science research. There are very high levels of particular serotonin receptors on the cells
lining the ventricles. It is these lining cells that make cerebrospinal fluid. LSD attaches to
these receptors with extraordinary vigor. Perhaps psychedelics really do alter our conscious-
ness in such powerful ways by controlling production of this unique brain liquid. Descartes
and his followers would certainly get a hearty laugh out of these "modern" discoveries!
5. Rene Descartes, "The Inter-Relation of Soul and Body," in The Way of Philosophy, edited
by P. Wheelright (New York: Odyssey, 1954), 357.
6. We do not know if the opening in the skull, the fontanel, which is located directly above
the infant's pineal, allows enough light in to affect the gland.
7. Aaron B. Lerner, James D. Case, Yoshiyata Takahashi, Teh H. Lee, and Wataru Mori,
"Isolation of Melatonin, the Pineal Gland Factor That Lightens Melanocytes," Journal of
the American Chemical Society 30 (1958): 2587.
8. F. Karsch, E. Bittman, D. Foster, R. Goodman, S. Legan, and J. Robinson, "Neuroendo-
crine Basis of Seasonal Reproduction," Recent Progress in Hormone Research 40 (1984):
9. The pineal gland becomes full of calcium as we age. The calcified gland is an excellent
marker for the mid-line of the brain in skull X-rays and CAT scans. However, little of this
calcium collects in the melatonin-producing cells. While melatonin levels do drop as we
age, this is independent of the level of pineal calcification.
10. Rick J. Strassman, Clifford R. Quails, E. Jonathan Lisansky, and Glenn T. Peake, "El-
evated Rectal Temperature Produced by All-Night Bright Light Is Reversed by Melatonin
Infusion in Men," Journal of Applied Physiology 71 (1991): 2178-82.
Early morning also is when we are most likely to be in dream sleep, and some studies
suggested that large doses of melatonin enhanced dreaming. We were unable to examine
this in our experiments because subjects needed to stay awake with eyes open for light to
suppress melatonin. If melatonin did stimulate dream sleep, we would have expected less
vivid dreams in volunteers whose melatonin production was inhibited. Interestingly, drugs
that suppress nighttime melatonin formation increase, rather than decrease, dreams.
1. While DMT may be involved in both spiritual and psychotic experiences, it is important
to distinguish between them. There is some overlap between spiritual experiences and
psychosis; for example, the thrilling sense of imminence, heightened visual and auditory
perceptions, and a change in the passage of time.
Usually, however, mystical experiences result from a mature and conscious effort toward
obtaining them. The practitioner seeks them out, there is an intellectual and moral context
supporting and encouraging them, and their expression is socially sanctioned and acceptable.
On the other hand, symptoms of schizophrenia most often are unexpected, unwel-
come, and occur in those with prior behavioral and emotional problems. There is little
social support for the experiences, and both the individual and his/her associates wish
they would go away.
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