N-Acetylcysteine - PsychonautWiki


Summary sheet: 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.

Bioavailability 4%[1]
Threshold 100 mg
Light 400 - 600 mg
Common 600 - 1000 mg
Strong 1000 - 1500 mg
Heavy 1500 mg +
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.[2] 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.[3] It is on the World Health Organization's List of Essential Medicines needed in a basic health system.[4] It is available as a generic medication and is available over the counter in many countries.[5]

N-Acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders.[6] It is 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.[7] 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.


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.


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.[8] 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.[9]

In terms of its psychologically beneficial effects, N-acetylcysteine targets glutaminergic and dopaminergic pathways.[10] 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.[11]

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 ☠.

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

Cognitive effects

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.[18]

This compound can also rarely cause rashes, fever, headache, drowsiness, nose bleeds, low blood pressure, and liver problems.[19]

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.[20]

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 status

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


  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. Acetylcysteine | http://www.drugs.com/monograph/acetylcysteine.html
  3. 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
  4. WHO Model List of Essential Medicines | http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1
  5. 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
  6. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044191/
  7. N-acetylcysteine modulates hallucinogenic 5-HT(2A) receptor agonist-mediated responses: behavioral, molecular, and electrophysiological studies.| https://www.ncbi.nlm.nih.gov/pubmed/24534112
  8. 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
  9. Acetylcysteine (Drugs.com) | http://www.drugs.com/monograph/acetylcysteine.html
  10. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/21118657
  11. 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
  12. Review: could Acetylcysteine cause Bleeding from the nose? | http://www.ehealthme.com/ds/acetylcysteine/bleeding+from+the+nose
  13. 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
  14. 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/
  15. Safety and Tolerability of N-Acetylcysteine in Cocaine-Dependent Individuals (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1513138/
  16. N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/20163391/
  17. Glutamate transmission in addiction (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18675832/
  18. S-Nitrosothiols signal hypoxia-mimetic vascular pathology | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1952618/
  19. Acetylcysteine | http://www.drugs.com/monograph/acetylcysteine.html
  20. 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