The Wrong Doorway

© captainvector | 123rf.com

© captainvector | 123rf.com

Laughing gas or nitrous oxide (N20) has a surprising variety of uses or effects. The World Health Organization lists it as an essential medicine because of its anesthetic and analgesic effects. It’s used as an oxidizer in rockets and motor racing to increase the power output of engines. N20 is also a major greenhouse gas, with a per unit mass impact that is between 265 and 310 times that of carbon dioxide. And it is in the top ten most popular recreational drugs globally.

The English chemist Joseph Priestley discovered nitrous oxide gas in 1772. Priestley is also known for his discovery of oxygen. Humphrey Davy experimented with N20 on himself and others in 1799. He coined the term ‘laughing gas’ after observing its effects on people who inhaled it. Although he reported its analgesic effects in 1800, this property was not tested or used for another 45 years. During that time, it was primarily a ‘party’ or entertainment drug.

A British dentist in 1845 was the first person to demonstrate the anesthetic properties of nitrous oxide. However, it was not widely used in dentistry until 1863. Gardner Quincy Colton and his partners opened a series of dental institutes using laughing gas. Within five years, they had performed a reported 75,000 extractions. A history of reported nitrous oxide users includes: Allen Ginsberg, Samuel Taylor Coleridge, Ken Kesey, Winston Churchill and William James.

In 1882 James published an article titled: “The Subjective Effects of Nitrous Oxide,” in the journal Mind.  He said his use of N20 helped him develop a greater understanding of Hegel’s philosophy and he strongly urged his readers to repeat the experiment. “With me, as with every other person of whom I have heard, the keynote of the experience is the tremendously exciting sense of an intense metaphysical illumination.” Truth was almost blindingly obvious. “The mind sees all logical relations of being with an apparant subtlety and instantaniety to which its normal consciousness offers no parallel.”

But as he “sobered up,” the feeling faded. James was left with a few disjointed words and phrases—like staring at a black cinder left after the fire has gone out. James said he had sheet after sheet of phrases written during intoxication with N20 that to his sober mind seemed to be “meaningless drivel.” The most coherent and articulate sentence that came to him was the following: “There are no differences but differences of degree between different degrees of difference and no difference.”

In his later, seminal work, The Varieties of Religious Experience, James again reflected on the significance of intoxication by alcohol and anesthetics. He said the influence of alcohol over humanity was due to its power to stimulate the mystical faculties of human nature. Sobriety diminishes; drunkenness expands. “The drunken consciousness is one bit of the mystic consciousness and our total opinion of it must find its place in our opinion of that larger whole.”

Nitrous oxide, according to James, stimulated the mystical consciousness to an extraordinary degree. “Depth beyond depth of truth seems revealed to the inhaler.” But that truth fades as the individual sobered up. Nevertheless, a profound sense of meaning persisted. “I know more than one person who is persuaded that in the nitrous oxide trance we have a genuine metaphysical revelation.” He then went on to describe his own previous experiments with N20 described in his 1882 article.

In an article for The Atlantic, “The Nitrous Oxide Philosopher,” Dmitri Tymoczko noted how the experience James had with nitrous oxide remained with him throughout his life. He wrote a second article about it in 1898, “Consciousness Under Nitrous Oxide.” Then in his last essay, completed in 1910, he implied N20 had had an abiding influence on his thinking. Tymoczko thought N20 was a ‘passport’ for James to see religion from the believer’s perspective. “Drugs helped James to understand what religious belief was like from the inside.”

 James’s experiences with nitrous oxide helped to crystallize some of the major tenets of his philosophy. His writings emphasize, for instance, the notion of pluralism, according to which “to the very last, there are various ‘points of view’ which the philosopher must distinguish in discussing the world.” Nitrous oxide had revealed in the most dramatic way possible the existence of alternate points of view.

Tymoczko used William James’s experience with nitrous oxide to argue how drugs can contribute to human well being; sometimes fulfilling an authentic religious need. He reasoned that drugs could allow even the most skeptical people to experience temporary periods of “pleasing falsehood,” dividing their life into periods of sober rationality and “ecstatic religious intoxication”, like William James. “Indeed, this is the real religious significance of drug use, from the Jamesian point of view–that it lets us choose, if only vaguely and temporarily, what to believe.”

He even referenced R. Gordon Wassson, who proposed that religion itself originated with drugs. According to Wasson, religion was a confused reaction to intense experiences provoked by the accidental ingestion of psychoactive plants. There have been examples where religious ritual has been entwined with the use of drugs. Some Native American cultures used psychedelic mushrooms in their rituals; and the Greek cult of Dionysus used wine to provoke visions. But Tymoczko went too far onto the magical mystery tour when he suggested that the use of wine by Christians could be a remnant of similar practices.

The Bible clearly puts the use of bread and wine within the context of a meal; not a mystical psychedelic religious rite. Tymoczko also failed to make a distinction made by James in The Varieties of Religious Experience that separated what James called institutional religion, like Christianity, from personal religion. James defined personal religion as “the feelings, acts, and experiences of [the] individual . . . in their solitude, so far as they apprehend themselves to stand in relation to whatever they may consider the divine.” James was looking at examples of personal religion, not institutional religion in The Varieties of Religious Experience. See “Spiritual, Not Religious Experience” for more on this distinction by James.

So now back to nitrous oxide. The significance of nitrous oxide to William James personally or to his philosophical and other writings has little to tell us about religious experience today. It may resonate with the increased interest in psychedelic drug rituals for therapeutic healing (See “Back to the Future with Psychedelics”). But before walking the path of Timothy Leary and Aldous Huxley, let’s take a look at what modern science tells us about N20—information that wasn’t available to James when he was doing his inhaling.

The Global Drug Survey, annually conducted by Adam Winstock and others, found that nitrous oxide was the seventh most popular drug in the world. More than 7% of the global survey respondents said they had used nitrous oxide in the past year. In the UK, it was used by 23.7% of respondents sometime over the past year. A recent article in the Journal of Psychopharmacology by Kaar et al., Winstock was a coauthor, indicated that the reported lifetime use of nitrous oxide for the UK and US was 38.6% and 29.4% respectively.

Most people using nitrous oxide recreationally do so infrequently without any serious side effects. But there is a subpopulation of heavy users. Quoted in an article for The Fix, Winstock said: “The majority of people who use it don’t use it very often, and only around 3% of heavy users say they have experienced negative health effects.” The Global Drug Survey found nitrous oxide use was associated with hallucinations (27.8%), confusion (23.9%), persistent numbness (4.3%) and accidental injury (1.2%). Accidental injury seems to be dose-dependent—injury is associated with higher numbers of ‘hits’ per session.

The pro-drug website, Erowid, has a ‘vault’ of information on nitrous oxide. Chronic exposure can effect reproduction in women. Immunological problems such as recurrent infections, decreased white blood cell counts and weakness have also been reported. There were also neurological issues with chronic N20 use.

A 1978 article in the British journal Lancet reported that a neurological disorder called myleneuropathy developed in 15 individuals with prolonged exposure to nitrous oxide. R.B. Layzer reported that: “The neurological picture is similar to that of subacute combined degeneration of the spinal cord, and it is possible that nitrous oxide interferes with the action of vitamin B12 in the nervous system.” A 1993 article by Flippo et al. in JAMA Surgery also described the dangers of neurologic degeneration from nitrous oxide. The abstract said:

Five cases (four from the literature and one new case) are presented in which patients unsuspected of having vitamin B12 deficiency developed subacute combined degeneration of the spinal cord following nitrous oxide anesthesia. Patients with vitamin B12 deficiency are exceedingly sensitive to neurologic deterioration following nitrous oxide anesthesia. If unrecognized, the neurologic deterioration becomes irreversible and may result in death.

Happily, some of these issues can be reversed. A 2003 article in the Wisconsin Medical Journal by Waclawik et al. described a case study of an individual who was a chronic nitrous oxide user whose neurological deficit was reversed after administering vitamin B12.

Sporadic use of N20 does not appear to be associated with serious health risks. But chronic exposure is another story. William James may have been influenced by experiences he had with nitrous oxide, just as Sigmund Freud’s use of cocaine shaped his psychoanalytic theories. N20 also fits with the current trend of looking for therapeutic healing or personal insight with psychedelics like LSD, ecstasy and even ayahuasca or ibogaine. But it is better suited as an anesthetic or analgesic in medical procedures; or an oxidizer in rocket engines than it is a doorway to religious experience.


No Laughing Matter

© Ievgen Soloviov | Dreamstime.com

© Ievgen Soloviov | Dreamstime.com

In his famous work, The Varieties of Religious Experience, William James discussed what he said was the ability of nitrous oxide (laughing gas) to produce “mystical consciousness” to an extraordinary degree. “Depth beyond depth of truth seems to be reveled to the inhaler.” But the revelation fades as the gas wears off. What is left seems like nonsense to the awakened mind. But the sense of “a profound meaning” persists. James said he knew more than one person who was persuaded that a genuine metaphysical revelation could come in a nitrous oxide trance. Now, laughing gas is being researched as a treat for depression.

James said he had personally tried nitrous oxide, and even wrote of his experience in print. He said one impression from these experiments stayed with him—that our waking consciousness was but one of several other potential form of consciousness. “No account of the universe in its totality can be final which leave these other forms of consciousness quite disregarded.”  Looking back on his own experiences, he saw them converge towards a kind of insight that he felt had metaphysical significance.

His essay was “Subjective Effects of Nitrous Oxide,” and it appeared in the 1882 volume 7 issue of Mind. It can be found in a few places online. I’ve linked it on the website Erowid, which will also have other references we’ll examine. In his essay, James said that the keynote of nitrous-oxide intoxication was an intense sense of metaphysical illumination that occurred as the altered state of consciousness was wearing off.

The mind sees all logical relations of being with an apparant subtlety and instantaniety to which its normal consciousness offers no parallel; only as sobriety returns, the feeling of insight fades, and one is left staring vacantly at a few disjointed words and phrases, as one stares at a cadaverous-looking snow peak from which sunset glow has just fled, or at a black cinder left by an extinguished brand.

What James saw as the most coherent and articulate of his bursts of insight was this: “There are no differences but differences of degree between different degrees of difference and no difference.” James said there was an initial rapture of emotion in “beholding a process that was infinite” that turned to horror as the individual realized they were caught in an inevitable fate, “with whose magnitude every finite effort is incommensurable and in the light of which whatever happens is indifferent.”

As James himself said in the essay, just as every person’s encounter will vary, the individual’s personal experience with nitrous oxide will vary from time to time. However, he still thought that there still was a common thread running through all those who were intoxicated with nitrous oxide, namely an “intense metaphysical experience.”

A group of researchers, Nagel et al., reported on a pilot study done to assess the potential of nitrous oxide as a rapidly acting treatment for treatment resistant depression (TRD). The theory was based upon the influence of nitrous oxide on the NMDA receptor, which has been “implicated” in the neurobiology of depression. Other NMDA receptor antagonists, such as ketamine, have been shown “to provide a rapid and sustained antidepressant effect” when used at low doses. Given the similar mechanisms of action, the researchers hypothesized that nitrous oxide may also have rapid antidepressant effects on treatment resistant depression. So they designed a study to assess the immediate (2 hours) and sustained (24 hours) antidepressant effects of nitrous oxide in TRD patients.

Patients received either an admixture of up to a maximum of 50% nitrous oxide and 50% oxygen (as the active ingredient) or 50% nitrogen/50% oxygen (as the placebo) for one hour. Outcomes were assessed for each participant at baseline, 2 hours after treatment and 24 hours after treatment. The results indicated a significant improvement in depressive symptoms at 2 and 24 hours. There was also a sustained improvement with some participants for 1 week. Yet there were several limitations noted by the researchers of this study.

The full 60-minute nitrous oxide treatment was only completed by 15 of the 20 patients. The placebo treatment was completed by 20 individuals. The side effects for the treatment group were noted to be mild or moderate (nausea, anxiety, vomiting) and immediately reversible. This suggested an acceptable risk/benefit ratio of nitrous oxide for TRD to the researchers.

Their discussion suggested several limitations of the study. The small sample size meant that the results should be interpreted with caution until the results were replicated in larger populations. They also noted that the euphoric effects of nitrous oxide are hard to mask, so the blinding attempted in the study may not have been adequate. Despite knowing this, the researchers did not try to assess whether or not the participants were aware of their group assignment, “and this limits our conclusions.”

They also pointed out that there could have been a masking effect of depressive symptoms, meaning that: “the depressive symptoms were not really altered, but rather ‘covered up’ by other effects.” They noted where symptom masking has been evident with rapidly acting psychostimulants like cocaine and methylphenidate, “which promote a transient alteration in mood but not a true antidepressant effect.” Their preliminary study concluded there was evidence that nitrous oxide may have rapid and marked antidepressant effects in patients with TRD. They called for further studies that would attempt to determine optimal antidepressant dosing strategies and the risk/benefit of nitrous oxide in a larger and more diverse population of individuals with TRD.

Psychiatrist Sandra Steingard expressed reservations with the promotion of nitrous oxide as a rapid acting treatment for depression. She commented that while she never personally tried nitrous oxide herself, she knew others who did and expected that her mood would undoubtedly have been elevated as theirs was. Her suggestion was the observed “treatment’ effects of nitrous oxide were actually drug effects that would occur with any individual who used it. She proceeded to voice several questions on the use of nitrous oxide, ketamine or stimulants to treat depression. She thought there was a huge potential for harm; possibly greater than the drugs psychiatrist currently prescribed for depression.

What are the long term side effects? How hard is it to stop them?  How do we deal with the corrupting influence of the profit driven forces so powerful in medicine?  Most of these drugs are still studied over weeks and then prescribed for years. With drugs like stimulants, ketamine and nitrous oxide, I have a particular worry because these drugs are known to cause psychosis. Colleagues of mine have told me that they do not see people who become psychotic on stimulants. If they don’t, they are not looking. I am not comfortable assuming when an 18 year old develops psychotic symptoms after several years of treatment with an antidepressant that these two things are not related or that the psychosis was inevitable because the person had a diathesis to Bipolar Disorder. Stimulants are used to create animal models of psychosis because we have known for decades that stimulants can cause a person to become psychotic.

Erowid is the website for an organization that seeks to “provide accurate, specific, and responsible information about how psychoactives are used in the United States and around the world.” So you will find pro and con information on the use and effects of psychoactive substances there. Here are a few of the catalogued articles on problems from nitrous oxide use and abuse: “Asphyxia deaths from the recreational use of nitrous oxide;” “Suicide by nitrous oxide poisoning;” B 12-related medical problems from nitrous oxide: “Nitrous oxide myleopathy in an abuser of whipped cream bulbs [whippets] (nitrous oxide is used in whipped cream cans), “Myleneuropathy after prolonged exposure to nitrous oxide,” and this case report from outside of Erowid of a woman who developed myleopathy.

Below is a quote from a 1991 article on “Health hazards and nitrous oxide” in medical settings. Here is a link to a case report of an individual who suffered paranoid delusions after abusing whippets.

Although N2O was for many years believed to have no toxicity other than that associated with its anesthetic action, bone marrow depression in patients administered N2O for extended periods of time and neurological abnormalities in health care workers who inhaled N2O recreationally have disproved this notion.

Simply put, regardless of the short-term reversals of a depressed mood state, it does not seem that there will be any long-term benefits from the therapeutic use of nitrous oxide (N2O). And there seems to be plenty of concerns with its use. Treating depression with laughing gas is no laughing matter.