N-Acetylcysteine

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Summary sheet: N-Acetylcysteine
N-Acetylcysteine
Molecular structure of N-Acetylcysteine
N-Acetylcysteine.svg
Chemical Nomenclature
Common names N-Acetylcysteine
Substitutive name (2R)-2-acetamido-3-sulfanylpropanoic acid
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 99%
Threshold 100 - 400 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.

N-Acetylcysteine (also known as Acetylcysteine, N-Acetyl-L-cysteine, or commonly as NAC) is a substituted amino acid which is primarily used as a medication for treating acetaminophen (also known as Paracetamol, and the brand-name Tylenol) overdose and to loosen thick mucus in the treatment of cystic fibrosis or chronic obstructive pulmonary disease.[1] Outside of the traditional medical context, it is gaining in popularity as a nootropic substance that produces mild-to-moderate stimulant effects.

This compound was initially patented in 1960 and licensed for use in 1968.[2] It is on the World Health Organization's List of Essential Medicines needed in a basic health system.[3] It is available as a generic medication and is available over the counter in many countries.[4]

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

The recommended safe oral dosage range of N-acetylcysteine ranges between 300mg and 3000mg.

Chemistry

N-Acetylcysteine, or (2R)-2-acetamido-3-sulfanylpropanoic acid, is similar to both L-Cysteine (NAC being but an acetylated form of it) and the glutathione enzyme itself (being the direct precursor to glutathione synthesis). The structure of N-Acetylcysteine is comprised of propanoic acid, a three carbon chain with a carboxyl group (C(=O)OH) on the terminal carbon. This chain is substituted at R3 with a sulfanyl group, and at R2 with an acetamide (CH3CONH2) constituent in dextrorotary conformation. It is structurally related to cysteine, with an additional acetyl group at RN.

Pharmacology

Acetylcysteine serves as a prodrug to L-cysteine. L-cysteine is a precursor to the biologic antioxidant glutathione; thus, administration of acetylcysteine replenishes glutathione stores.[7] This is why N-acetylcysteine is used in the event of a paracetamol overdose. It works by increasing glutathione levels and binding with the toxic breakdown products of paracetamol.[8]

In terms of its psychologically beneficial effects, N-acetylcysteine targets glutaminergic and dopaminergic pathways.[9] This could potentially account for its stimulating properties. It is also thought that provision of additional cysteine (an endogenous amino acid) via N-acetylcysteine supplementation reverses function disturbed with usage of drugs in the pathology of addiction.[10]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include injury or death.

In comparison to other commonly used nootropics, N-acetylcysteine has considerably stronger stimulation and motivation enhancement, but with a greater amount of side effects such as dehydration and nausea. However, unlike other stimulants, this compound does not seem to induce a "crash" or "come down" during the offset of its experience.

Physical effects
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Cognitive effects
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Toxicity and harm potential

N-Acetylcysteine is considered to be safe for most adults when used as a prescription medication although the exact toxic dosage is unknown. However, dosage ranges more than twenty grams over an extended period may adversely affect heart and lung function.[17]

This compound can also rarely cause rashes, fever, headache, drowsiness, nose bleeds, low blood pressure, and liver problems.[18]

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

The chronic use of N-Acetylcysteine does not seem to cause addiction or psychological dependence. This is likely a result of its known mechanisms for reversing drug addiction.[19]

Tolerance to many of the effects of N-Acetylcysteine develops quickly with repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). N-Acetylcysteine does not seem to present a cross-tolerance with other stimulants.

Legal issues

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This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

N-Acetylcysteine is uncontrolled in most countries, and is legally bought and sold in pharmacies and supplement stores without a prescription.

See also

External links

References

  1. Acetylcysteine | http://www.drugs.com/monograph/acetylcysteine.html
  2. Analogue-based Drug Discovery edited by IUPAC, Janos Fischer, C. Robin Ganellin | https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA544#v=onepage&q&f=false
  3. WHO Model List of Essential Medicines | http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1
  4. The Top 100 Drugs e-book: Clinical Pharmacology and Practical Prescribing By Andrew Hitchings, Dagan Lonsdale, Daniel Burrage, Emma Baker | https://books.google.ca/books?id=oeYjAwAAQBAJ&pg=PT44#v=onepage&q&f=false
  5. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044191/
  6. N-acetylcysteine modulates hallucinogenic 5-HT(2A) receptor agonist-mediated responses: behavioral, molecular, and electrophysiological studies.| https://www.ncbi.nlm.nih.gov/pubmed/24534112
  7. ACETADOTE® CONCENTRATED INJECTION Product Information | https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03960-3&d=2016041216114622483
  8. Acetylcysteine (Drugs.com) | http://www.drugs.com/monograph/acetylcysteine.html
  9. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/21118657
  10. Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16000629
  11. Review: could Acetylcysteine cause Bleeding from the nose? | http://www.ehealthme.com/ds/acetylcysteine/bleeding+from+the+nose
  12. Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16000629
  13. The Role of Cystine-Glutamate Exchange in Nicotine Dependence in Rats and Humans (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756612/
  14. Safety and Tolerability of N-Acetylcysteine in Cocaine-Dependent Individuals (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1513138/
  15. N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/20163391/
  16. Glutamate transmission in addiction (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18675832/
  17. S-Nitrosothiols signal hypoxia-mimetic vascular pathology | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1952618/
  18. Acetylcysteine | http://www.drugs.com/monograph/acetylcysteine.html
  19. Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16000629