"The small trial recruited 28 participants in a crossover design, which is when all the volunteers go through each of the trial’s conditions and their responses are compared to one another (as opposed to two or more distinct groups that either take the drug or placebo). In this case, that meant the volunteers, who had depression for an average of 17.5 years, had three treatment sessions: one where they inhaled a 50% dose of nitrous oxide, another where they inhaled a 25% dose, and one where they inhaled oxygen (the placebo). Afterwards, the volunteers took surveys meant to assess their level of depression.
Ultimately, 24 people participated in at least one treatment session, and 20 took all the treatments. The team found that these volunteers on average experienced a greater improvement in depression symptoms when they took the nitrous oxide at either dose than they did after taking the placebo (based on the primary survey they completed)—an improvement that lasted for up to two weeks. They also found that both doses seemed to provide similar relief, but that people were more likely to experience side-effects like headaches, nausea, and lightheadedness from the larger dose."
https://gizmodo.com/a-little-laughing-gas-can-help-treat-depression-small-1847066477
Nitrous oxide toxicity references
Original here:
https://www.reddit.com/r/NitrousOxide/comments/p5s0o3/nitrous_oxide_toxicity_references/
https://www.erowid.org/chemicals/nitrous/nitrous_info4.shtml
- “It seems likely that in man, in contrast to the rat, exposure of less than 30 minutes will not cause any measurable change in methionine synthase activity. In combination with a wealth of clinical experience, this suggests that there is no special hazard for short exposures to nitrous oxide. There is a variable response to exposures lasting between 30 minutes and 2 h."
- "With respect to repeated exposures to nitrous, be aware that this effect can build up (Nunn gives "intervals of less than 3 days" as a cut-off). "
https://anesthesiageneral.com/nitrous-oxide-metabolism/
- "The administration of folic acid 30 mg twice a day may prevent development of megaloblastic changes due to N,O. Megaloblastic anaemia has been reported among dentists and dental assistants where high concentrations of N20 are used."
https://pubmed.ncbi.nlm.nih.gov/2240633/
- Although an occasional patient may prove highly susceptible to and develop signs of severe vitamin B12 and folic acid deficiency after exposure to N2O, our findings suggest that this is a rare event.
https://pubmed.ncbi.nlm.nih.gov/12751548/
- Toxicity of Nitrous oxide- survey
https://sites.google.com/site/drjoneskids/mthfr/mthfr-nitrous-oxide
- There have been people who have died as a result of being given Dental Nitrous Oxide when they had an undiagnosed Methyltetrafolate Reductase Disorder. In these sad cases, asking a few questions about family history of heart disease or a medical need to take Vitamin B12 and Folic Acid supplements could have prevented these deaths from Nitrous Oxide Side Effects.
https://pubmed.ncbi.nlm.nih.gov/25959209/
- Introduction: The relationship between iron deficiency and vitamin B12 and folate was recognized several decades ago. Combined deficiency is important in clinical practice owing to its relationship with malabsorption syndromes. By contrast, iron deficiency and low levels of serum vitamin B12 with normal metabolic markers were often found mostly in young adults. In this work, vitamin B12/folate changes were investigated during treatment of iron deficiency anaemia (IDA) with pharmacological iron in young adult women.
https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.15348
- Megaloblastic, nonregenerative anemia is a well-known consequence of cobalamin or folate deficiencies in humans but is not recognized in hypocobalaminemic or hypofolatemic dogs. Establishment of relationships between hypocobalaminemia or hypofolatemia and hematologic disease would encourage vitamin B testing, and potentially supplementation, in anemic dogs.
https://pubs.asahq.org/anesthesiology/article/109/1/5/9019/Pharmacogenetics-of-Nitrous-OxideStanding-at-the
- IT has long been known that nitrous oxide in clinically relevant doses and durations shuts down single carbon pathways by virtue of oxidation of the cobalamin cofactor of methionine synthase, the sole occupant at the crossroads of the methylation, transsulfuration, and folate cycles. Surprisingly, the clinical consequences of nitrous oxide–mediated, folate–cobalamin cycle inactivation have not restrained its use in the more...
https://ndnr.com/neurology/folate-cobalamin-depression/
- the enzyme inhibition may cause deficiency in folate and cobalamin
https://www.jocn-journal.com/article/S0967-5868(98)90149-7/pdf90149-7/pdf)
- A 23 year old man presented with a severe posterior column myelopathy related to prolonged nitrous oxide abuse obtained from whipped cream bulbs. The site of pathology was identified by magnetic resonance imaging (MRI) and somatosensory evoked potentials. The mechanism of toxicity involves inactivation of vitamin B12dependent enzymes. Appropriate treatment with methionine and vitamin B12was instituted quickly with good neurological outcome.
https://www.researchgate.net/profile/Chih-Shan-Huang/publication/310612520_Nitrous_Oxide-induced_Subacute_Combined_Degeneration_Presenting_with_Dystonia_and_Pseudoathetosis_A_Case_Report/links/5b5594e1aca27217ffb33601/Nitrous-Oxide-induced-Subacute-Combined-Degeneration-Presenting-with-Dystonia-and-Pseudoathetosis-A-Case-Report.pdf
- AbstractPurpose: Nitrous oxide (N2O) is neurotoxic by interfering with vitamin B12 bioavailability. The clinical picture is indistinguishable to that of subacute combined degeneration (SCD). A movement disorder might occur though it is not a characteristic feature. We report a patient with N2O-induced SCD, exhibiting a combination of different involuntary movements.
- Case Report: A 20-year-old woman presented with one month of progressive unsteady gait, involuntary movements and tingling sensation in a stocking-glove distribution. She had used N2O and ketamine intermittently for recreational purposes for about two years. Neurological examination demonstrated normal cranial nerve functions except for dystonia in the facial muscle and tongue. Her muscle strength was full, but there were bilateral hyperreflexia and extensor plantar response. She exhibited dystonia in four limbs with athetoid movement in fingers and toes, worsened by eye closure. Vibration and proprioception were impaired. Laboratory tests revealed anemia (Hb: 9.9 g/dl) with normal mean corpuscular volume (85.7 fL) and decreased iron level (22 μg/dl) while other results were normal including serum vitamin B12 level (626 pg/ml). Magnetic resonance imaging showed a hyperintense lesion from C1 to C6 level in the posterior column. She was diagnosed as having SCD caused by N2O abuse, presenting with generalized dystonia and pseudoathetosis. The involuntary movements disappeared with vitamin B12 supplementation.
- Conclusion: Movement disorders may be the rare manifestations of SCD associated with N2O abuse. Early recognition of the etiology is vital because it is treatable with vitamin B12 and methionine.
Ultimately, 24 people participated in at least one treatment session, and 20 took all the treatments. The team found that these volunteers on average experienced a greater improvement in depression symptoms when they took the nitrous oxide at either dose than they did after taking the placebo (based on the primary survey they completed)—an improvement that lasted for up to two weeks. They also found that both doses seemed to provide similar relief, but that people were more likely to experience side-effects like headaches, nausea, and lightheadedness from the larger dose."
https://gizmodo.com/a-little-laughing-gas-can-help-treat-depression-small-1847066477
Nitrous oxide toxicity references
Original here:
https://www.reddit.com/r/NitrousOxide/comments/p5s0o3/nitrous_oxide_toxicity_references/
https://www.erowid.org/chemicals/nitrous/nitrous_info4.shtml
- “It seems likely that in man, in contrast to the rat, exposure of less than 30 minutes will not cause any measurable change in methionine synthase activity. In combination with a wealth of clinical experience, this suggests that there is no special hazard for short exposures to nitrous oxide. There is a variable response to exposures lasting between 30 minutes and 2 h."
- "With respect to repeated exposures to nitrous, be aware that this effect can build up (Nunn gives "intervals of less than 3 days" as a cut-off). "
https://anesthesiageneral.com/nitrous-oxide-metabolism/
- "The administration of folic acid 30 mg twice a day may prevent development of megaloblastic changes due to N,O. Megaloblastic anaemia has been reported among dentists and dental assistants where high concentrations of N20 are used."
https://pubmed.ncbi.nlm.nih.gov/2240633/
- Although an occasional patient may prove highly susceptible to and develop signs of severe vitamin B12 and folic acid deficiency after exposure to N2O, our findings suggest that this is a rare event.
https://pubmed.ncbi.nlm.nih.gov/12751548/
- Toxicity of Nitrous oxide- survey
https://sites.google.com/site/drjoneskids/mthfr/mthfr-nitrous-oxide
- There have been people who have died as a result of being given Dental Nitrous Oxide when they had an undiagnosed Methyltetrafolate Reductase Disorder. In these sad cases, asking a few questions about family history of heart disease or a medical need to take Vitamin B12 and Folic Acid supplements could have prevented these deaths from Nitrous Oxide Side Effects.
https://pubmed.ncbi.nlm.nih.gov/25959209/
- Introduction: The relationship between iron deficiency and vitamin B12 and folate was recognized several decades ago. Combined deficiency is important in clinical practice owing to its relationship with malabsorption syndromes. By contrast, iron deficiency and low levels of serum vitamin B12 with normal metabolic markers were often found mostly in young adults. In this work, vitamin B12/folate changes were investigated during treatment of iron deficiency anaemia (IDA) with pharmacological iron in young adult women.
https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.15348
- Megaloblastic, nonregenerative anemia is a well-known consequence of cobalamin or folate deficiencies in humans but is not recognized in hypocobalaminemic or hypofolatemic dogs. Establishment of relationships between hypocobalaminemia or hypofolatemia and hematologic disease would encourage vitamin B testing, and potentially supplementation, in anemic dogs.
https://pubs.asahq.org/anesthesiology/article/109/1/5/9019/Pharmacogenetics-of-Nitrous-OxideStanding-at-the
- IT has long been known that nitrous oxide in clinically relevant doses and durations shuts down single carbon pathways by virtue of oxidation of the cobalamin cofactor of methionine synthase, the sole occupant at the crossroads of the methylation, transsulfuration, and folate cycles. Surprisingly, the clinical consequences of nitrous oxide–mediated, folate–cobalamin cycle inactivation have not restrained its use in the more...
https://ndnr.com/neurology/folate-cobalamin-depression/
- the enzyme inhibition may cause deficiency in folate and cobalamin
https://www.jocn-journal.com/article/S0967-5868(98)90149-7/pdf90149-7/pdf)
- A 23 year old man presented with a severe posterior column myelopathy related to prolonged nitrous oxide abuse obtained from whipped cream bulbs. The site of pathology was identified by magnetic resonance imaging (MRI) and somatosensory evoked potentials. The mechanism of toxicity involves inactivation of vitamin B12dependent enzymes. Appropriate treatment with methionine and vitamin B12was instituted quickly with good neurological outcome.
https://www.researchgate.net/profile/Chih-Shan-Huang/publication/310612520_Nitrous_Oxide-induced_Subacute_Combined_Degeneration_Presenting_with_Dystonia_and_Pseudoathetosis_A_Case_Report/links/5b5594e1aca27217ffb33601/Nitrous-Oxide-induced-Subacute-Combined-Degeneration-Presenting-with-Dystonia-and-Pseudoathetosis-A-Case-Report.pdf
- AbstractPurpose: Nitrous oxide (N2O) is neurotoxic by interfering with vitamin B12 bioavailability. The clinical picture is indistinguishable to that of subacute combined degeneration (SCD). A movement disorder might occur though it is not a characteristic feature. We report a patient with N2O-induced SCD, exhibiting a combination of different involuntary movements.
- Case Report: A 20-year-old woman presented with one month of progressive unsteady gait, involuntary movements and tingling sensation in a stocking-glove distribution. She had used N2O and ketamine intermittently for recreational purposes for about two years. Neurological examination demonstrated normal cranial nerve functions except for dystonia in the facial muscle and tongue. Her muscle strength was full, but there were bilateral hyperreflexia and extensor plantar response. She exhibited dystonia in four limbs with athetoid movement in fingers and toes, worsened by eye closure. Vibration and proprioception were impaired. Laboratory tests revealed anemia (Hb: 9.9 g/dl) with normal mean corpuscular volume (85.7 fL) and decreased iron level (22 μg/dl) while other results were normal including serum vitamin B12 level (626 pg/ml). Magnetic resonance imaging showed a hyperintense lesion from C1 to C6 level in the posterior column. She was diagnosed as having SCD caused by N2O abuse, presenting with generalized dystonia and pseudoathetosis. The involuntary movements disappeared with vitamin B12 supplementation.
- Conclusion: Movement disorders may be the rare manifestations of SCD associated with N2O abuse. Early recognition of the etiology is vital because it is treatable with vitamin B12 and methionine.