The Autonomic Nervous System (ANS) is a peripheral nervous system division regulating involuntary physiological processes. It comprises two main branches: the Sympathetic Nervous System (SNS) and the Parasympathetic Nervous System (PNS).
Sympathetic Nervous System (SNS)
The SNS is often described as the “fight or flight” system. It prepares the body for high-stress situations by:
- Increasing heart rate and force of contraction
- Dilating bronchi in the lungs
- Dilating pupils
- Increasing blood flow to skeletal muscles
- Decreasing blood flow to the digestive system
- Stimulating glucose release from the liver
- Promoting sweating
- Inhibiting salivation
The SNS uses norepinephrine as its primary neurotransmitter [1].
Parasympathetic Nervous System (PNS)
The PNS is often called the “rest and digest” system. It promotes a state of calm and relaxation by:
- Decreasing heart rate
- Constricting bronchi in the lungs
- Constricting pupils
- Increasing blood flow to the digestive system
- Stimulating salivation and digestion
- Promoting urination and defecation
- Facilitating sexual arousal
The PNS primarily uses acetylcholine as its neurotransmitter [2].
Effects of Therapeutic Ketamine on the SNS and PNS
Ketamine, traditionally used as an anesthetic, has gained attention for its potential therapeutic effects in treating various conditions, including depression and chronic pain. Its impact on the autonomic nervous system is complex and dose-dependent.
Effects on the Sympathetic Nervous System:
- Increased Sympathetic Activity: At lower doses, ketamine stimulates the SNS, increasing heart rate, blood pressure, and cardiac output [3]. This effect is partly due to ketamine inhibiting the reuptake of catecholamines like norepinephrine [4].
- Bronchodilation: Ketamine causes bronchodilation, consistent with sympathetic activation [5].
- Increased Metabolic Rate: Ketamine’s sympathetic stimulation can lead to increased oxygen consumption and CO2 production [6].
Effects on the Parasympathetic Nervous System:
- Salivation: Despite its primarily sympathomimetic effects, ketamine can paradoxically increase salivation, a typically parasympathetic response [7]. This effect may be due to ketamine’s action on various receptors beyond its primary NMDA receptor antagonism.
- Potential Vagal Modulation: Some studies suggest that ketamine might modulate vagal tone, a key component of the PNS. However, this area requires further research [8].
- Bladder Function: Chronic ketamine use has been associated with bladder dysfunction, which may involve both sympathetic and parasympathetic pathways [9].
It’s important to note that ketamine’s effects on the autonomic nervous system can vary based on dosage, route of administration, and individual patient factors. While ketamine generally has a net sympathomimetic effect, its complex pharmacology means it can influence both branches of the ANS in nuanced ways.
The use of ketamine in therapeutic settings is an active area of research, and our understanding of its effects on the autonomic nervous system continues to evolve. Further studies are needed to fully elucidate the mechanisms by which ketamine influences autonomic function and how these effects contribute to its therapeutic potential in various conditions.
[1] https://www.ncbi.nlm.nih.gov/books/NBK539845/
[2] https://www.ncbi.nlm.nih.gov/books/NBK538516/
[3] https://pubmed.ncbi.nlm.nih.gov/25964506/
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258981/
[5] https://www.ncbi.nlm.nih.gov/books/NBK470357/
[6] https://pubmed.ncbi.nlm.nih.gov/15982643/
[7] https://www.ncbi.nlm.nih.gov/books/NBK541087/
[8] https://www.frontiersin.org/articles/10.3389/fneur.2018.00315/full