Warning
This is an unofficial archive of PsychonautWiki as of 2025-08-08T03:33:20Z. Content on this page may be outdated, incomplete, or inaccurate. Please refer to the original page for the most up-to-date information.

N-Acetylcysteine

From PsychonautWiki Archive
Jump to navigation Jump to search
Summary sheet: N-Acetylcysteine
N-Acetylcysteine
Chemical Nomenclature
Common names N-Acetylcysteine
Substitutive name (2R)-2-acetamido-3-sulfanylpropanoic acid
Class Membership
Psychoactive class Nootropic
Chemical class Cysteine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



⇣ Oral
Dosage
Bioavailability 4%[1]
Threshold 100 mg
Light 400 - 600 mg
Common 600 - 1000 mg
Strong 1000 - 1500 mg
Heavy 1500 mg +
Duration
Total 3 - 6 hours
Onset 20 - 60 minutes









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Interactions


N-Acetylcysteine (NAC), also known as Acetylcysteine, is a medication that is used to treat paracetamol (acetaminophen) overdose, and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia, bronchitis and cystic fibrosis.[2] It has been used to treat lactobezoar in infants. It can be taken intravenously, by mouth, or inhaled as a mist.[2] Some people use it as a dietary supplement.[3][4]

N-Acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders.[5] It is currently being explored in its effect and relief of a wide variety of cognitive disorders including, but not limited to addiction, autism, obsessive compulsive disorder, grooming disorders, schizophrenia, and bipolar disorder.[6] Acetylcysteine has shown promising results in populations with these disorders and others whom treatment efficacy has previously been limited.

The safe oral dosage of Acetylcysteine appears to range between 300mg and 3000mg daily depending of specific individuals and their underlying condition.

Chemistry

Acetylcysteine is the N-acetyl derivative of the amino acid L-cysteine, and is a precursor in the formation of the antioxidant glutathione in the body. The thiol (sulfhydryl) group confers antioxidant effects and is able to reduce free radicals.

N-acetyl-L-cysteine is soluble in water and alcohol, and practically insoluble in chloroform and ether.[7]

It is a white to white with light yellow cast powder, and has a pKa of 9.5 at 30 °C.[8]

Pharmacology

Pharmacodynamics

Acetylcysteine serves as a prodrug to L-cysteine, a precursor to the biologic antioxidant glutathione. Hence administration of acetylcysteine replenishes glutathione stores.[9]

  • Glutathione, along with oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO), have been found to bind to the glutamate recognition site of the NMDA and AMPA receptors (via their γ-glutamyl moieties), and may be endogenous neuromodulators.[10][11] At millimolar concentrations, they may also modulate the redox state of the NMDA receptor complex.[11] In addition, glutathione has been found to bind to and activate ionotropic receptors that are different from any other excitatory amino acid receptor, and which may constitute glutathione receptors, potentially making it a neurotransmitter.[12] As such, since N-acetylcysteine is a prodrug of glutathione, it may modulate all of the aforementioned receptors as well.
  • Glutathione also modulates the NMDA receptor by acting at the redox site.[13]

L-cysteine also serves as a precursor to cystine, which in turn serves as a substrate for the SLC7A11|cystine-glutamate antiporter on astrocytes; hence there is increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR2/3 receptors, and at higher doses of acetylcysteine, mGluR5.[14][15]

Acetylcysteine also possesses some anti-inflammatory effects possibly via inhibiting NF-κB and modulating cytokine synthesis.

Pharmacokinetics

Acetylcysteine is extensively liver metabolized, CYP450 minimal, urine excretion is 22-30% with a half-life of 5.6 hours in adults and 11 hours in neonates.

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.


Physical effects

Cognitive effects


Toxicity and harm potential

The most commonly reported adverse effects for IV formulations of acetylcysteine are rash, urticaria, and pruritus(itchiness). Up to 18% of patients have been reported to experience anaphylaxis reaction, which are defined as rash, hypotension, wheezing, and/or shortness of breath. Lower rates of anaphylactoid reactions have been reported with slower rates of infusion.

Adverse effects for inhalational formulations of acetylcysteine include nausea, vomiting, stomatitis, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and bronchoconstriction. Although infrequent, bronchospasm has been reported to occur unpredictably in some patients.[22]

Adverse effects for oral formulations of acetylcysteine have been reported to include nausea, vomiting, rash, and fever.[22]

Large doses in a mouse model showed that acetylcysteine could potentially cause damage to the heart and lungs.[23] They found that acetylcysteine was metabolized to S-nitroso-N-acetylcysteine (SNOAC), which increased blood pressure in the lungs and right ventricle of the heart (pulmonary artery hypertension) in mice treated with acetylcysteine. The effect was similar to that observed following a 3-week exposure to an oxygen-deprived environment (chronic hypoxia). The authors also found that SNOAC induced a hypoxia-like response in the gene expression of several important genes both in vitro and in vivo.

The implications of these findings for long-term treatment with acetylcysteine have not yet been investigated. The dose used by Palmer and colleagues was dramatically higher than that used in humans, the equivalent of about 20 grams per day.[23] Nonetheless, positive effects on age-diminished control of respiration (the control of hypoxic ventilatory response) have been observed previously in human subjects at more moderate doses.[24]

Although N-acetylcysteine prevented liver damage when taken before alcohol, when taken four hours after alcohol it made liver damage worse in a dose-dependent fashion.[25]

Addiction and tolerance potential

The chronic use of Acetylcysteine does not seem to cause addiction or psychological dependence. N-Acetylcysteine's positive effects seem to be cumulative overtime.

In most countries, N-Acetylcysteine is widely available in pharmacies, supplements and nootropics stores without prescription.

See also

References

  1. ↑ Olsson, B.; Johansson, M.; Gabrielsson, J.; Bolme, P. (1988). "Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine". European Journal of Clinical Pharmacology. 34 (1): 77–82. doi:10.1007/BF01061422. ISSN 0031-6970. 
  2. ↑ 2.0 2.1 "Acetylcysteine". The American Society of Health-System Pharmacists. Archived from the original on 23 September 2015. Retrieved 22 Aug 2015. 
  3. ↑ Talbott, Shawn M. (2012). A Guide to Understanding Dietary Supplements. Routledge. p. 469. ISBN 9781136805707. Archived from the original on 8 September 2017. 
  4. ↑ "Cysteine". University of Maryland Medical Center. Archived from the original on 1 July 2017. Retrieved 23 June 2017. 
  5. ↑ Dean, O., Giorlando, F., Berk, M. (March 2011). "N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action". Journal of Psychiatry & Neuroscience : JPN. 36 (2): 78–86. doi:10.1503/jpn.100057. ISSN 1180-4882. 
  6. ↑ Lee, M.-Y., Chiang, C.-C., Chiu, H.-Y., Chan, M.-H., Chen, H.-H. (June 2014). "N-acetylcysteine modulates hallucinogenic 5-HT(2A) receptor agonist-mediated responses: behavioral, molecular, and electrophysiological studies". Neuropharmacology. 81: 215–223. doi:10.1016/j.neuropharm.2014.02.006. ISSN 1873-7064. 
  7. ↑ "N-Acetyl-L-cysteine | C5H9NO3S - PubChem". Archived from the original on 16 August 2016. Retrieved 22 July 2016. 
  8. ↑ "N-ACETYL-L-CYSTEINE Product Information" (PDF). Sigma. Sigma-aldrich. Archived from the original (PDF) on 11 June 2014. Retrieved 9 November 2014. 
  9. ↑ "PRODUCT INFORMATION ACETADOTE® CONCENTRATED INJECTION". TGA eBusiness Services. Phebra Pty Ltd. 16 January 2013. Archived from the original (PDF) on 8 September 2017. Retrieved 8 November 2013. 
  10. ↑ Steullet, P.; Neijt, H.C.; Cuénod, M.; Do, K.Q. (2006). "Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: Relevance to schizophrenia". Neuroscience. 137 (3): 807–819. doi:10.1016/j.neuroscience.2005.10.014. ISSN 0306-4522. PMID 16330153. 
  11. ↑ 11.0 11.1 Varga, V.; Jenei, Zs.; Janáky, R.; Saransaari, P.; Oja, S. S. (1997). "Glutathione Is an Endogenous Ligand of Rat Brain N-Methyl-D-Aspartate (NMDA) and 2-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionate (AMPA) Receptors". Neurochemical Research. 22 (9): 1165–1171. doi:10.1023/A:1027377605054. ISSN 0364-3190. PMID 9251108. 
  12. ↑ Oja, S (2000). "Modulation of glutamate receptor functions by glutathione". Neurochemistry International. 37 (2–3): 299–306. doi:10.1016/S0197-0186(00)00031-0. ISSN 0197-0186. PMID 10812215. 
  13. ↑ Lavoie S, Murray MM, Deppen P, Knyazeva MG, Berk M, Boulat O, Bovet P, Bush AI, Conus P, Copolov D, Fornari E, Meuli R, Solida A, Vianin P, Cuénod M, Buclin T, Do KQ (Aug 2008). "Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients". Neuropsychopharmacology. 33 (9): 2187–99. doi:10.1038/sj.npp.1301624 Freely accessible. PMID 18004285. 
  14. ↑ Dodd S, Dean O, Copolov DL, Malhi GS, Berk M (Dec 2008). "N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility". Expert Opinion on Biological Therapy. 8 (12): 1955–62. doi:10.1517/14728220802517901. PMID 18990082. 
  15. ↑ Kupchik YM, Moussawi K, Tang XC, Wang X, Kalivas BC, Kolokithas R, Ogburn KB, Kalivas PW (Jun 2012). "The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine". Biological Psychiatry. 71 (11): 978–86. doi:10.1016/j.biopsych.2011.10.024. PMC 3340445 Freely accessible. PMID 22137594. 
  16. ↑ Acetylcysteine and Bleeding from the nose, a phase IV clinical study of FDA data - eHealthMe 
  17. ↑ Moran, M. M., McFarland, K., Melendez, R. I., Kalivas, P. W., Seamans, J. K. (6 July 2005). "Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking". The Journal of Neuroscience: The Official Journal of the Society for Neuroscience. 25 (27): 6389–6393. doi:10.1523/JNEUROSCI.1007-05.2005. ISSN 1529-2401. 
  18. ↑ Knackstedt, L. A., LaRowe, S., Mardikian, P., Malcolm, R., Upadhyaya, H., Hedden, S., Markou, A., Kalivas, P. W. (15 May 2009). "The Role of Cystine-Glutamate Exchange in Nicotine Dependence in Rats and Humans". Biological psychiatry. 65 (10): 841–845. doi:10.1016/j.biopsych.2008.10.040. ISSN 0006-3223. 
  19. ↑ LaRowe, S. D., Mardikian, P., Malcolm, R., Myrick, H., Kalivas, P., McFarland, K., Saladin, M., McRae, A., Brady, K. (2006). "Safety and Tolerability of N-Acetylcysteine in Cocaine-Dependent Individuals". The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 15 (1): 105–110. doi:10.1080/10550490500419169. ISSN 1055-0496. 
  20. ↑ Gray, K. M., Watson, N. L., Carpenter, M. J., Larowe, S. D. (April 2010). "N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study". The American Journal on Addictions. 19 (2): 187–189. doi:10.1111/j.1521-0391.2009.00027.x. ISSN 1521-0391. 
  21. ↑ Kalivas, P. W., Lalumiere, R. T., Knackstedt, L., Shen, H. (2009). "Glutamate transmission in addiction". Neuropharmacology. 56 Suppl 1: 169–173. doi:10.1016/j.neuropharm.2008.07.011. ISSN 0028-3908. 
  22. ↑ 22.0 22.1 "Mucomyst Package Insert". Archived from the original on 21 April 2014. Retrieved 20 April 2014. 
  23. ↑ 23.0 23.1 Palmer LA, Doctor A, Chhabra P, Sheram ML, Laubach VE, Karlinsey MZ, Forbes MS, Macdonald T, Gaston B (Sep 2007). "S-nitrosothiols signal hypoxia-mimetic vascular pathology". The Journal of Clinical Investigation. 117 (9): 2592–601. doi:10.1172/JCI29444. PMC 1952618 Freely accessible. PMID 17786245. 
  24. ↑ Hildebrandt W, Alexander S, Bärtsch P, Dröge W (Mar 2002). "Effect of N-acetyl-cysteine on the hypoxic ventilatory response and erythropoietin production: linkage between plasma thiol redox state and O(2) chemosensitivity". Blood. 99 (5): 1552–5. doi:10.1182/blood.V99.5.1552 Freely accessible. PMID 11861267. 
  25. ↑ Wang AL, Wang JP, Wang H, Chen YH, Zhao L, Wang LS, Wei W, Xu DX (Mar 2006). "A dual effect of N-acetylcysteine on acute ethanol-induced liver damage in mice". Hepatology Research. 34 (3): 199–206. doi:10.1016/j.hepres.2005.12.005. PMID 16439183. 
Retrieved from "https://psy.st/index.php?title=N-Acetylcysteine&oldid=488703"