British Journal of Addiction (1989) 84, 121-123

EDITORIAL

Nitrite Inhalants: promising and

discouraging news
Since the onset of the AIDS epidemic in the early
198O's, a growing body of data suggest that the
volatile nitrites may play an important role in the
pathogenesis of human immunodeficiency virus
(HIV) infection. For example, of the first five
homosexual men with AIDS reported to the U.S.
Centers for Disease Control,' all had used nitrite
inhalants, but only one had abused drugs intravenously, and only two were reported to be
promiscuous. During this same interval, there is
evidence that selected high risk groups for HIV
infection have modified certain behavior so as to
alter their risk profile, and included in this adaptation to the AIDS pandemic appears to be the
restrained use of nitrite inhalants.
Even though this class of agents has received
increased attention because of AIDS, their use has a
long and sordid history. Nitrite inhalants (including
amyl, butyl, and isobutyl nitrite) have been used
since 1867, when amyl nitrite was found to have
clinical utility in the management of coronary
insufficiency.^ Esters of nitrous acid, the nitrites are
highly volatile liquids that have been nicknamed
'poppers' because of the sound made when an amyl
nitrite pearl is crushed. Whereas amyl nitrite is now
a prescription drug in the United States, the butyl
and isobutyl derivatives are marketed as room
odorizers with suggestive trade names such as
'Rush', 'Climax', and 'Heart-on'.
The inhalation of volatile nitrite vapors produces
diffuse relaxation of smooth muscle, thereby causing
an intense vasodilation with fiushing, a fall in blood
pressure, and a refiex tachycardia. The vasodilation
of cerebral vessels appears to trigger an increase in
intracranial pressure which may give rise to the
euphoria and 'rush' reportedly experienced by
users.' Adverse reactions include skin and
tracheobronchial irritation; nausea, headache, and
syncope; true allergic reactions with wheezing and
itching; and the potential for serious bum
injuries.'

Beginning in the late 196O's and into the early

197O's, nitrite inhalant use took two distinct patterns: As a street drug, poppers were used on social
occasions to promote a sense of abandonment,^ or to
produce a euphorigenic rush, an altered state of
consciousness, and even a stimulant-like high.' The
second and more widespread pattern of abuse
appeared to be that associated with overt sexual
activity. Purported to be an aphrodisiac by
heightening libido, other alleged attributes included
prolonging penile erection as well as relaxing rectal
smooth muscle and anal sphincter tone.' None of
these physiologic features have been substantiated;
nevertheless, poppers soon became heavily identified with the male homosexual community, although
both recreational and hard-core drug users often
include poppers in their pharmacologic repetoire of
abuse.
Two recent studies on the nitrite inhalants
conducted at the National Institute on Drug Abuse,
Addiction Research Center (NIDA/ARC) in Baltimore, Maryland report both promising and discouraging news:
The first investigation attempted to discern
whether there has been any change in the use pattern
of nitrites in light of their potential liaison with
AIDS. Two distinct high-risk populations in the
Baltimore-Washington, D.C. metropolitan area
were surveyed, homosexual men and drug abusers.'
Although it was found that the prevalence of current
use in both populations was coincidentally similar,
the predominately heterosexual drug abusing population had not significantly altered their use of
nitrite inhalants during the years studied
(1981-1986). However, the reported use of nitrites
by the male homosexual group had declined appreciably, with the median interval since the drug was
last used being 2 years. In addition, the median
interval since peak use was almost twice as long,
confirming other evidence that certain high risk
behaviors in the homosexual community are being
121

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Editorial

altered, most likely the result of an increased general

awareness of AIDS-related risk.'
Whereas this first investigation confirmed the
promising suspicion that unhealthy behavior can be
modified, the second study confirmed the discouraging precept that this class of chemicals can indeed
have perilous effects on immune system homeostasis.' For some time investigators have been aware
that Kaposi's Sarcoma (KS) has had a higher
occurrence rate in homosexual men with AIDS than
in other population groups with the syndrome.
Other studies have suggested an association between
nitrite abuse and KS*"-" and a possibility that
nitrites may alter T-lymphocytes,'^''' suppress
natural killer cell activity,''' convert amines to
potentially carcinogenic nitrosamines," and otherwise facilitate transmission of HIV."
In the NIDA/ARC investigation, which was orchestrated by Dr Elizabeth M. Dax, a sample of HIVnegative volunteers were exposed to varying doses of
amyl nitrite after first obtaining baseline immune
function testing and informed consent. The results
revealed a significant acute decrease in the absolute
number of peripheral lymphocytes following nitrite
exposure, with a relative increase then being observed by day 7. Additionally, there was a significant
decrease in both T-helper and suppressor cells at
24 h, and by day 7, there was a relative increase in the
circulating number of B lymphocytes.
These results confirm that nitrite inhalation
induces change in the immune system, by initially
suppressing immune function, and this is followed
by a period of non-specific immune stimulation.
This raises the possibility that HIV replication may
be activated as a consequence of this non-specific
and non-directed stimulation; and that in addition to
their other deleterious effects, poppers may facilitate viral replication.
These studies have helped clarify the association
between nitrite inhalant use, immune dysfunction,
and evolving patterns of AIDS expression. For
example, KS is the only manifestation of AIDS to
have shown a decrease since 1981,' and this has
coincided with the decrease in the use of nitrite
inhalants by homosexual men. These trends raise
hope that a greater awareness of AIDS-risk behaviors will result in a greater chance for loosening

the grip that this epidemic has on the world's

population.
W. ROBERT LANGE
JEANNE FRALICH

Addiction Research Center,

National Institute on Drug Abuse,
P.O. Box 5180,
Baltimore, Maryland 21224,
U.S.A.

References
1. CENTERS FOR DISEASE CONTROL (1981)

Kaposi's

Sarcoma and Pneumocystis Pneumonia among

Homosexual MenNew York City and California,
Morbidity and Mortality Weekly Report, 30, pp.
250-252.
2. BRUNTON, T . L . (1867) On the Use of Amyl Nitrite
in Angina Pectoris, Lancet, ii, pp. 1197-1198.
3. HAVERKOS, H . W . & DAUGHTERY, J. (1988) Health

4.

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13.

Hazards of Nitrite Inhalants, The American Journal

of Medicine, 84, pp. 479-482.
SiGELL, L. T. et al. (1978) Popping and Snorting
Volatile Nitrites: A Current Fad for getting High,
American Journal of Psychiatry, 135, pp. 1216-1218.
NiCKERSON, M. et al. (1979) Isobutyl Nitrite and
Related Compounds (San Francisco, California, Pharmex).
LABATAILLE, L . (1975) Amyl Nitrite employed in
Homosexual Relations, Medical Aspects of Human
Sexuality, 19, p. 122.
LANGE, W . R. et al. (1988) Nitrite Inhalants: Patterns
of Abuse in Baltimore and Washington, D . C ,
American Journal of Drug and Alcohol Abuse, 14, pp.
29-39.
LANGE, W . R. et al. (1988) Nitrite inhalants:
contemporary patterns of abuse, in, H. W. HAVERKOS
& J. A. DOUGHERTY (Eds) Health Hazards of Nitrite
Inhalants, NIDA Monograph Series, pp. 86-95.
DAX, E . M . et al. (1988) Effects of nitrites on the
immune system of humans. Ibid, pp. 75-80.
MARMOR, M . et al. (1982) Risk Factors for Kaposi's
Sarcoma in Homosexual Men, Lancet, i, pp.
1083-1087.
HAVERKOS, H . W . et al. (1985) Disease Manifestations amoung Homosexual Men with Acquired Immunodeficiency Syndrome: A Possible Role of Nitrates in Kaposi's Sarcoma, Sexually Transmitted
Diseases, 12, pp. 203-208.
GoEDERT, J. J. et al. (1982) Amyl Nitrite may alter T
Lymphocytes in Homosexual Men, Lancet, i, pp.
412-416.
NEWELL, G . R. et al. (1985) Volatile NitritesUse
and Adverse Effects Related to the Current Epidemic

Editorial
of the Acquired Immune Deficiency Syndrome, The
American Journal of Medicine, 78, pp. 811-816.
14. LOTZOVA, E. et al. (1984) Depression of Murine
Natural Killer Cell Cytotoxicity by Isobutyl Nitrite,
Cancer Immunology Immunotherapy, 17, pp.
130-134.
15. HERSH, E. M . et al. (1983) Effect of the Recreational

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Agent Isobutyl Nitrite on Human Peripheral Blood

Leukocytes and on in Vitro Interferon Production,
Cancer Research, 43, pp. 1365-1371.
16. NEWELL, G . R. et al. (1984) Toxicity, Immunosuppressive Effects and Carcinogenic Potential of Volatile Nitrites: Possible Relationship to Kaposi's Sarcoma, Pharmacotherapy, 4, pp. 284-291.