Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Education in the Field in the Post-Neuropsychopharmacology Era

Substances with an effect on consciousness
Educational Series 2. Bulletin 8, Chapter 3


          Substances with an effect on consciousness were first synthesized in the mid-18th century. They were “gases,” such as “nitrous oxide” and “ether” which could block consciousness, i.e., awareness of one’s body, self and environment, transiently, when administered in a particular concentration. Development of the necessary technology for the purification and measured administration of these gases, was instrumental to the birth of general anesthesia during the first half of the 19th century (Ban 1969).

            The term anesthesia was coined and introduced by Oliver Wendell Holmes (1809-1894), in 1846 for a drug-induced state characterized by “lack of sensation” (Rice 1859). Under “general anesthesia” there is a loss of ability to perceive pain associated with loss of consciousness for a period covered by amnesia (Stedman 1990).


            Nitrous Oxide is a colorless, non-toxic gas with a faint, sweet odor. It was first developed by Joseph Priestley (1733 -1804), who described the procedure he used for producing it in the second volume of his “Experiments and Observations on Different Kinds of Air,” first published in 1775.  

            To render “gases” accessible for study, James Watt (1736-1819) built a special machine that made the measured administration of “nitrous oxide” possible by “inhalation” (Beddoes and Watt 1794).  

            Humphry Davy (1778-1829) was first to explore the effects of the substance with the employment of Watt’s machine. He noted that nitrous oxide inhalation produced a “thrilling” and “pleasant” feeling of “merriment” and coined the term “laughing gas” to characterize the substance. Davy was also first to recognize the “analgesic” effect of “nitrous oxide” and its potential use in “surgical operations.” 

            Davy presented his observations and findings with “nitrous oxide” in his Researches, Chemical and Philosophical, published in 1800.  Nevertheless, almost half a century passed after Humphrey’s report that Horace Wells (1815 – 1848), in 1844, first demonstrated the “anesthetic” effect of the substance, i.e. insensitivity to pain during dental extraction. Another quarter of a century went by before, in the early 1870s, the use of the substance was generally accepted in “dental anesthesia” (Jacobsohn 1995; Shaw, Kumar and Doods 2011).   

            In the 20th century nitrous oxide found its special place among the “anaesthetics,” e.g., for use in child birth. It was also in the 20th century that explorations of its possible use in the facilitation of “psychological” and “pharmacological” treatments” began (Lecore 1994). In the early years of the 21st century explorations of its use in the pharmacological treatment of psychiatric disorders, e.g., depressions, were intensified (Nagele, Duma, Kopec et al. 2015). It still remains to be seen whether the substance could be used in psychiatric emergencies, e.g., relieving suicidal ideation, in view of its unique prompt euphorizing properties.   

            Ether (diethyl ether) is a white, colourless, volatile, highly inflammable liquid with a powerful characteristic odour and a hot sweetish taste (Encyclopedia Britannica 1969). Wilhelm Godefroy Froben, a German chemist was first, in 1735, to describe the substance and name it (Gibbson 1929).

            Instrumental to the introduction of the substance into medicinal use was William Cullen’s recognition, in 1773, that “ether” was effective only when vaporised. Observations, in the late 1790s with the employment of James Watt’s “machine,” indicated that the effects of the substance were similar to the effects of “nitrous oxide” (Beddoes and Watt 1794; Donovan 1975). Both induced “inhibition” of “nervous activity” when inhaled in high concentration and “disinhibition” of “verbal activity” when inhaled in low.  

            It was Crawford Williamson Long first, in 1842, who used “ether” successfully as an “anesthetic,” but he did not report on his successful induction of “anesthesia” with “ether” for some time (Boland 1950). Nevertheless, the name of William Green Morton (1819-1868) became associated with “ether anesthesia.” Morton used “ether” for “anesthesia” first in 1844 and on September 30, 1846, successfully demonstrated the use of diethyl ether in “general anesthesia” at the Massachusetts General Hospital (Committee of Citizens in Boston 1871). In the years that followed, until well into the first half of the he 20th century, “ethyl ether” remained the he most extensively used substance in “general anesthesia.”

            The possible use of the “disinhibiting” properties of  “ether” (in low concentrations) for the facilitation of psychotherapy was first raised in the 1920s by Schielder and Weissmann (1927). They were also first to employ the substance in “chemically-induced excitatory abreactions.” Yet, almost 20 years passed before, in the mid-1940s, “excitatory abreactions with ether” found their place in psychiatry, in the treatment of “war neurosis.”  Under the influence of “ether forgotten memories are experienced visibly by excitement that raises to a crescendo, followed by silence” (Ban 1969; Palmer 1945; Sargant and Shorvon 1945; Sim 1963).

            Nitrous oxide and ether were among the first substances which could predictably affect mental functioning. By their potential of producing loss of consciousness, a state in which with the blockade of sensorial experiencing one’s reflection of one’s body, self and environment is discontinued, research with these drugs opened the path for studying the relationship between the brain and mental activity.  




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Palmer HA. Abreactive techniques: ether. J Roy Army 84: 86. Med Corp 1945; 84: 86.


Priestley J. Impregnating water with fixed air. London: For J. Johnson; 1772. 


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Rice NP. Trials of public benefactor as illustrated in the discovery of etherization 

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Sargant W, Shorvon HJ. Acute war neuroses. Arch Neurol Psychiat1945; 54: 231


Schielder P, Weissmann H. Atheorisierung Geisteskranken. Ztschr Ges Neurol Psychiat 1927; 11:  779.  


Shaw I, Kumar Ch, Dudds C, editors.  Oxford Textbook of Anaesthesia for Oral and Maxillofacial Surgery. Oxford: Oxford University Press; 2011.


Sim M. Guide to Psychiatry. Edinburgh: Livingstone; 1963.


Stedman TL. Stedman’s Medical Dictionary. 25th edition. Baltimore: Williams & Wilkins; 1982. 


March 8, 2018