|Summary sheet: N-Acetylcysteine|
|Substitutive name||(2R)-2-acetamido-3-sulfanylpropanoic acid|
|Routes of Administration|
N-Acetylcysteine (NAC), also known as Acetylcysteine, is a medication that is used to treat paracetamol overdose|paracetamol (acetaminophen) overdose, and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used to treat lactobezoar in infants. It can be taken intravenously, by mouth, or inhaled as a mist. Some people use it as a dietary supplement.
N-Acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders. 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. N-acetylcysteine has shown promising results in populations with these disorders and others whom treatment efficacy has previously been limited.
The safe oral dosage of N-acetylcysteine appears to range between 300mg and 3000mg daily depending of specific individuals and their underlying condition.
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.
It is a white to white with light yellow cast powder, and has a pKa of 9.5 at 30 °C.
- Glutathione, along with oxidized glutathione (GSSG) and S-nitrosoglutathione|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. At millimolar concentrations, they may also modulate the redox state of the NMDA receptor complex. 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. 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.
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.
Acetylcysteine also possesses some anti-inflammatory effects possibly via inhibiting NF-κB and modulating cytokine synthesis.
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.
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 ☠.
- Addiction suppression - N-acetylcysteine's action on glutaminergic and dopaminergic pathways is thought to reverse brain functions which have been disturbed by drug abuse and addiction. This mechanism has been shown to provide relief for those who struggle with compulsive redosing, reward behaviors and psychological cravings, and has been shown to positively reverse nicotine addiction, cocaine addiction, marijuana dependence., and many other compulsive behaviors. Anecdotal reports suggest that one can take this compound over their addictive drug of choice for the purpose of quickly suppressing their cravings.
- Motivation enhancement
- Anxiety suppression
- Focus enhancement
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.
Adverse effects for oral formulations of acetylcysteine have been reported to include nausea, vomiting, rash, and fever.
Large doses in a mouse model showed that acetylcysteine could potentially cause damage to the heart and lungs. They found that acetylcysteine was drug metabolism|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|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. Nonetheless, positive effects on age-diminished control of respiration (the control of respiration|hypoxic ventilatory response) have been observed previously in human subjects at more moderate doses.
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.
Addiction and tolerance potential
The chronic use of N-Acetylcysteine does not seem to cause addiction or psychological dependence. N-Acetylcysteine positive effects seem to be cumulative overtime.
In most countries, N-Acetylcysteine is widely available in pharmacies, supplements and nootropics stores without prescription.
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