Learn the ins and outs of safe nitrous oxide exploration.

When used alone nitrous oxide can be somewhat fun and a generally pleasant experience, but when combined with mushrooms, LSD, or similar psychedelics, it becomes a dissociative stargate par excellence. Taking a few hits of nitrous during the peak of a psychedelic experience can bring time nearly to a standstill and reveal inner cycles of the manifesting universe. I'm sure many readers know precisely what I'm talking about as this seems to be a relatively popular practice among psychedelic connoisseurs. Nitrous oxide can also be very useful for shifting gears during a trip and breaking up repetitive thought loops. All in all nitrous is a unique tool with many possible applications for the psychedelic explorer.

Having recently acquired a taste for nitrous along with a plentiful supply, I thought it would be wise to do some research before partaking in its pleasures. I was quite familiar with the stories of dentists and habitual users experiencing nerve damage due to vitamin B12 deficiencies caused by the gas, but I really wasn't up to speed on the physiological mechanics involved nor the exact usage parameters.

With the desire to repeat my experiences and experiment further with nitrous, I set out to answer a few key questions. How often and for how long can I enjoy the gas without causing any major physical imbalance? What are the pharmacological mechanics of its actions and what are the possible repercussions? Are there any adjuncts or supplements that can be used to lessen the detrimental aspects of the gas? In this article I will present some pertinent data points uncovered from the medical literature that will allow readers to form a more educated opinion.

So let's get right down to business and dig into the dark side of nitrous oxide. It's well known that prolonged exposure to nitrous oxide can cause adverse effects in the blood, nervous, and reproductive systems of humans. Pernicious anemia may become evident along with signs of impaired nerve function such as numbness, tingling and burning sensations in the extremities. Depression and impaired mental function may also occur. Other symptoms can include paleness, fatigue, shortness of breath, diarrhea, and heart and nervous system disorders. One of the most serious side effects of nitrous is that it can interfere with DNA synthesis. This effect has been observed with nitrous oxide exposures of as little as a 2 hours (Amos RJ. 1982; Nunn JF. 1986).

The various side effects and nerve degeneration caused by excessive use of nitrous are very similar to what is seen with vitamin B12 deficiencies. This is because nitrous oxide effectively disrupts the metabolic pathway of vitamin B12 in the body. To understand the mechanics of this process, one first has to know a little about the metabolic pathway. Once absorbed into the body vitamin B12 gets actively bound to the enzyme methionine synthase. The combination compound B12+methionine synthase is the bioavailable form of vitamin B12 that gets utilized by the body for the various metabolic processes. It has been shown that nitrous oxide irreversibly oxidizes and inactivates the essential enzyme methionine synthase, and thus changes the existing B12+methionine synthase in the body to an unusable form. Once the existing B12+methionine synthase has been deactivated, physical balance can only be restored by absorption of new vitamin B12 and the synthesis of new methionine synthase in the body. Physical balance can't be restored by simply supplementing with additional vitamin B12 because it will not become bioavailable unless the body has enough methionine synthase enzyme to activate it. Just how much of the enzyme gets knocked out is dependent on length and concentration of the nitrous oxide exposure as well as individual sensitivity.

To more fully define the exact rate of methionine synthase inactivation, a group of scientists performed a study (Royston & Nunn 1988) on 20 human volunteers who were already scheduled to undergo abdominal surgery. The study required taking 800mg biopsies of the patient's liver at various times during a nitrous oxide exposure. It's interesting to note that most of the research in this field had been previously performed on rodents, and the results of the animal testing could be quite misleading if one tries to extrapolate the data to humans. Rodents are far more sensitive to the enzyme inactivation effects of nitrous. In rats half of their total methionine synthase was inactivated after a 5.4 minute exposure with a 70% nitrous oxide 30% oxygen mixture. Humans proved to be much more resilient, with the average inactivation half time being 46 minutes. There was considerable variation and personal sensitivity noted in the rate of enzyme inactivation in the patients tested. Some normal enzyme values were found with nitrous exposures up to 75 minutes, while one subject was overly sensitive with an abnormally low value appearing after a 40 minute exposure. This makes it somewhat difficult to predict the exact rate of inactivation and provide a precise estimation of the effects. However it gives us a pretty good indication that single exposures of less than 25 minutes are most likely harmless and probably not inactivating enough methionine synthase to cause a problem. This is certainly not the case with repeated exposures however, and care must be taken to avoid a cumulative effect. There is anecdotal evidence that even very short exposures of 5-10 minutes can cause imbalances if repeated on regular basis.

Another interesting study (Christensen & Guttormsen 1994) can shed some light on how often one should partake in nitrous oxide as well as provide a good strategy for harm reduction through dietary supplementation. In vitro data suggested that supplying additional methionine to cells decreased the initial rate of methionine synthase inactivation caused by nitrous oxide. Methionine is a common amino acid that can be found in your local health food store. Christensen's study was designed to classify the inactivation and recovery rates of methionine synthase in normal test subjects and compare it with those who received an oral pre-load dose of methionine (100mg/kg) two hours prior to the nitrous oxide exposure. Test subjects all received significant exposures of 75-230 minutes using the standard 70% nitrous oxide 30% oxygen mixture. In the control group of normal test subjects, enzyme recovery was characterized by an initial rapid phase of enzyme resynthesis lasting for 2-3 days which then slowed down and only gradually increased over the next week. The enzyme measurements were well below the preoperative levels for more than 8 days after the exposure. Methionine pre-loading didn't affect the rate and extent of enzyme inactivation, however it did significantly enhance the recovery rate. In patients who received the methionine pre-load, enzyme levels were equal to, and in some cases even exceeded the preoperative level within 5-7 days after the exposure. These results suggest that it would be wise to consume copious amounts (4-8g depending on your body weight) of methionine, vitamin B12 and folinic acid prior to a heavy nitrous session in order to assist the body and shorten the recovery process. This data also suggests that there should be at least a 1-2 week interval between nitrous sessions to allow for complete enzyme recovery.

I would highly recommend that experimenters go to the extra effort and acquire a tank of pure oxygen to mix with their nitrous. Using oxygen mixtures provides a much nicer overall effect and will prevent the possibility of hypoxia (decreased oxygen content in the blood and body tissues). It should be noted that unless the gas is administered with 20% oxygen hypoxia can be induced. In order to achieve a substantial effect from nitrous a 50% or greater concentration must be inhaled. If you were to inhale a mix 50% nitrous and 50% regular air you would still only be receiving 10% oxygen which is not enough. Hypoxia can be quite a serious condition and in some cases may cause irreversible brain damage. Be sure to provide your body all the oxygen it needs while you surf along carefree in hyperspace! I recommend using no less than 30% oxygen for the nitrous mix. Oxygen can be easily and cheaply obtained from your local specialty gas company. After speaking with a gas company manager I learned that the only difference between the medical grade oxygen and the oxygen used for welding applications is the tank and the price tag. Both are filled from the same pure oxygen tank at the supplier. There is a slight possibility of contamination with a used welding tank, however this can easily be avoided by purchasing a new tank and only filling it with pure oxygen.

Users should also bone up on all the nitrous oxide basics as this article is not meant to be a comprehensive, all inclusive review. More information can be found in the Erowid nitrous oxide vault and the Lycaeum nitrous oxide archives.

Just say N2O !

References:

Royston BD, Nunn JF, Weinbren HK, Royston D, Cormack RS. Division of Anesthesia, Clinical Research Centre, Harrow, U.K. "Rate of inactivation of human and rodent hepatic methionine synthase by nitrous oxide." Anesthesiology 1988 Feb;68(2):213-6.

Christensen B, Guttormsen AB, Schneede J, Riedel B, Refsum H, Svardal A, Ueland PM. Department of Clinical Biology, Bergen, Norway. "Preoperative methionine loading enhances restoration of the cobalamin-dependent enzyme methionine synthase after nitrous oxide anesthesia." Anesthesiology 1994 May;80(5):1046-56.

Amos RJ, Amess JAL, Hinds CJ, Mollin DL. "Incidence and pathogenesis of acute megaloblastic bone marrow change in patients receiving intensive care." Lancet 2:835-839, 1982.

Nunn JF., Chanarin I, Tanner AG, Owen ERTC. "Megaloblastic bone marrow changes after repeated nitrous oxide anaesthesia. Reversal with folinic acid" Br J Anaesth 58:1469-1470, 1986.