Amyl Nitrite and The EEG: A Pilot Study
Thomas P. Lowry, M.D.
Journal of Psychedelic Drugs Vol. 11(3) Jul-Sep, 1979

Amyl nitrite has been used since at least 1930, as a psychedelic drug. Amyl (and the related isobutyl nitrite) is now used chiefly to enhance sexual activities, but is also used to make disco dancing a more vivid experience.

Amyl nitrite is a yellowish, volatile; flammable liquid, which decomposes when, exposed to air and light. It is a prescription drug, sold in 0.3 ml gauze-wrapped crushable glass ampules. The "pop", when crushed, yields the slang names of "popper", "Popsey" and "snapper".

Amyl nitrite was first used medically over a century ago Brunton 1867) to treat the chest pains of angina pectoris and has been widely studied (Cash & Dunston 1894). The basic pharmacological action of nitrite is to relax smooth muscle. The relaxant action is nonspecific; it affects all smooth muscles whatever the innervation. Nitrite is a physiological antagonist of norepinephrine, acetylcholine and histamine. The most prominent actions of nitrite are cardiovascular. Inhalation of amyl nitrite produces a dramatic vasodilation over the face, neck and upper shoulders, with warmth and redness; there is a rapid fall in systemic and pulmonary vascular resistance and a precipitous drop in systemic arterial pressure. Reflex venoconstriction and tachycardia follow, and cardiac output rises rapidly because of decreased systemic resistance and increased venous return. The net result is decreased intraventricular pressure, lessened cardiac work and diminished oxygen demand, which accounts for the relief of anginal chest pain with nitrites. However, some patients with severe narrowing of the coronary vessels may have transient ischemia of the heart muscle after taking amyl nitrite, since the effects of decreased coronary artery perfusion pressure may outweigh the value of decreased heart workload (Kerber & Harrison 1972).

Little study has been made of the pharmacology of butyl nitrite. Parker (1979) has shown amyl and butyl nitrite to be very similar in their effects on blood pressure and heart rate.

The toxicology of the volatile nitrites has been studied in some detail (Lowry 1979). Surveys of 249 nitrite users, 47 forensic pathologists and 605 emergency room physicians have shown no deaths; transient vascular headache seems the common symptom. Eli Lilly, who has made amyl nitrite since 1913, has no report of injury in its files. Twenty men who have averaged four "poppers" a day for seven years have normal lung function (Swenson 1979). All types of inhalants (of which the nitrites are a small subgroup) constitute only 0.4 percent of reported drug abuse (DAWN 1977).

Dewey et al. (1973) studied acute toxicology in animals. The lethal dose of amyl nitrite was the equivalent of 13 "Poppers" given intravenously to a normal-sized man. A small dog inhaled 26 "poppers" in 13 minutes; transient incoordination, incontinence and vomiting developed, but the symptoms cleared in eight minutes.

Several authors have expressed concern that the nitrites would precipitate glaucoma, but this fear seems unfounded (Whitworth & Grant 1964). There have been published inferences of deaths with the volatile nitrites (Louria 1970) but these have no documented basis (Louria 1979).

The mechanisms of the psychedelic effects of the volatile nitrites are of principal concern in this pilot study. The phenomenological experiences of users seem consistent from one report to the next (Cohen 1978); McLenegan 1977; Everett 1975; Gay 1975). Users report that sexual experiences seem exalted, intense and prolonged, with frequent perception of a visual yellow spot, surrounded by purple. The change in mental perception may be the result of decreased blood pressure and cerebral anoxia (as suggested by several authors), but this seems unlikely, since sexual users report strong psychedelic effects even when the user is lying on his or her back, with legs up in the air, which would facilitate the return of venous blood from the legs and the maintenance of cerebral blood pressure.

The major electrical wave patterns of interest to us in this study are alpha (8-13 cycles per second {cps}) and beta (14-30 cps). Alpha is most prominent in the posterior areas of the scalp or cortex. Alpha is present particularly during relaxation when the eyes are closed and is attenuated during attention, especially visual. Beta rhythm includes the faster frequencies and tends to be a low-voltage pattern, widespread in distribution, but seen most often in the central regions. Alpha waves tend to disappear when the eyes are opened, but this is not true for all persons. Alpha waves are seen profusely in meditation; beta waves are associated with alertness and mental work such as computation. 

METHOD 

The five subjects were Caucasian adults who had recently passed stringent physical examinations. All had had social experience with amyl nitrite and were interested, informed volunteers. The eight-channel EEG used the standard 10-20 system of recording; the subjects reclined on an easy chair with feet level with the torso. After a baseline EEG, each subject used a nasal inhaler to take a deep breath of a newly opened 0.3 ml ampule of amyl nitrite, which occluding the unused nostril. The deep breath was held 10 seconds and then normal breathing was resumed. EEG recordings were made for 10 minutes after the inhalation.

RESULTS 

• 1. Twenty-six-year-old female flight instructor. Pre-inhalation record showed symmetrical 11 cps alpha with episodes of drowsiness and mild beta activity. Pre-inhalation hyperventilation produced minor slow-wave buildup of no significance. After inhalation, beta waves replaced the alpha for 140 seconds, followed by return to normal alpha activity.
• 2. Thirty-on-year-old male fireman. Pre-inhalation pattern of eight cps alpha, with episodes of drowsiness and six-seven cps waves. Hyperventilation produced no change. After inhalation, there was low-voltage fast desynchronization (beta waves) with return of alpha in 50 seconds and complete recovery of alpha in 140 seconds. Postrecovery alpha seemed "improved" compared with the pre-inhalation pattern.
• 3. Forty-six-year-old female teacher. Resting record showed strong nine cps alpha, especially over the occipital area, disappearing with eye opening. Mild runs of drowsiness. With inhalation, beta replaces alpha. First alpha return is seen after 200 seconds, with full return by 300 seconds.
• 4. Thirty-on-year-old male helicopter pilot. The resting record was a well-organized nine cps alpha over most of the cortex. There are scattered episodes of drowsiness. There is no change with inhalation of amyl nitrite.
• 5. Forty-six-year-old male physician. Resting pattern is low-voltage eight-ten cps alpha waves. With inhalation, there is a small (10 microvolt) increase in amplitude; otherwise, there is no change.

DISCUSSION

Our search of the literature showed only one previous study of EEG and amyl nitrite, which was done by Hans Berger, the inventor of the EEG, in 1929. Berger had his son sniff amyl nitrite to demonstrate that the electrical waves recorded from the scalp were from the cortex, not from the dilated scalp vessels. Berger found no change in the EEG pattern with amyl nitrite.

While our pilot study shows no pathological changes, additional studies should be done if only because of the very wide usage of amyl and butyl nitrite in the last few years. Techniques such as EEG frequency analysis and evoked potential and radioactive isotope studies of cerebral circulation might clarify the central nervous system effects of the volatile nitrites, which give their psychedelic qualities.