Disclaimer
Do not use the content of this post as an alternative to personal examination and advice from licensed healthcare providers. Do not begin, delay, or discontinue treatments and/or exercises without licensed medical supervision. This is strictly for educational/informational purposes. Non endorsing and Non instructional
NMDA receport antagonists are substances that block NMDA receptors, which are a type of glutakate receports in the brain important for learning and memory, synaptic plasiticy, pain plasticity, excitatory neuro transmission.
Some well known include, ketamine (girl at my old schools favourite for parties JFL), DXM, nitrous oxide, memantine and phencyclidine
For chronic pain, the go to choice tends to be opioid analgesics, with the addition of other analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and other adjuvant therapies, including tricyclic antidepressants (TCAs), anticonvulsants, and topical anesthetics as necessary.
Opiod resistance and why there is an emerging role of NMDA antagonists
Opioid resistance is defined as unresponsiveness to IV morphine sulfate of at least 100 mg per hour (or equivalent dosing of another opioid), consistently high pain ratings, and unrelieved pain even after the opioid dose is doubled. Opioid resistance has been found in a multitude of disease states including cancer, chronic pain, neuropathy, complex regional pain syndrome, postherpetic neuralgia, and pancreatitis. Neuropathic pain results from injury to peripheral or central nerves and is commonly treated with agents such as TCAs and anticonvulsants. Unfortunately, a majority of patients do not experience significant relief with these agents. In both opioid resistance and neuropathic pain, NMDA antagonists may be an option.
NMDA is a receptor for the excitatory neurotransmitter glutamate, which is released with noxious peripheral stimuli. The activation of NMDA receptors has been associated with hyperalgesia, neuropathic pain, and reduced functionality of opioid receptors. Hyperalgesia and neuropathic pain are a result of increased spinal neuron sensitization, leading to a heightened level of pain. The reduced function of opioid receptors is caused by a decrease in the opioid receptor’s sensitivity. This decreased sensitivity, in turn, translates to opioid tolerance as patients will require higher doses of opioids to achieve the same therapeutic effects. Therefore, NMDA antagonists may have a role in these areas of pain management.
It is important to note the claim it can prevent tolerance to opiods but there is NO EVIDENCE for this claim.
There are several NMDA receptor antagonists available: ketamine, methadone, memantine, amantadine, and dextromethorphan. They each differ in their level of activity on the NMDA receptor. Ketamine is a strong NMDA antagonist, whereas the others are weaker NMDA receptor blockers.
Role in looksmaxxing
-Feeling dissociation from pain after extreme working out
-Allowing excercise to continue while in pain/while injured and needing to recover.
-Possibly reducing anxiety
-Reducing fatigue signals
-Reducing "central sensitization" from chronic pain
-Belief it prevents tolerance to opoids or stimulants (but this has no studies to back it up)
-Tunnel vision interpretated by some as "improved focus"
Possible side effects
Severity and frequency of side effects depend on affinity for the NMDA receptor. In adults, adverse effects of NMDA antagonists are mainly central nervous system side effects including hallucinations, lightheadedness, dizziness, fatigue, headache, out-of-body sensation, nightmares, and sensory changes. Since ketamine is a strong NMDA antagonist, it is less tolerable than the other antagonists due to a higher incidence of side effects, in particular hallucinations and a dissociative mental state. There is also a possible risk for neuro toxicity (see Olney's lesions in this article https://brainstuff.org/blog/what-are-olneys-lesions )
Do not use the content of this post as an alternative to personal examination and advice from licensed healthcare providers. Do not begin, delay, or discontinue treatments and/or exercises without licensed medical supervision. This is strictly for educational/informational purposes. Non endorsing and Non instructional
NMDA receport antagonists are substances that block NMDA receptors, which are a type of glutakate receports in the brain important for learning and memory, synaptic plasiticy, pain plasticity, excitatory neuro transmission.
Some well known include, ketamine (girl at my old schools favourite for parties JFL), DXM, nitrous oxide, memantine and phencyclidine
For chronic pain, the go to choice tends to be opioid analgesics, with the addition of other analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and other adjuvant therapies, including tricyclic antidepressants (TCAs), anticonvulsants, and topical anesthetics as necessary.
Opiod resistance and why there is an emerging role of NMDA antagonists
Opioid resistance is defined as unresponsiveness to IV morphine sulfate of at least 100 mg per hour (or equivalent dosing of another opioid), consistently high pain ratings, and unrelieved pain even after the opioid dose is doubled. Opioid resistance has been found in a multitude of disease states including cancer, chronic pain, neuropathy, complex regional pain syndrome, postherpetic neuralgia, and pancreatitis. Neuropathic pain results from injury to peripheral or central nerves and is commonly treated with agents such as TCAs and anticonvulsants. Unfortunately, a majority of patients do not experience significant relief with these agents. In both opioid resistance and neuropathic pain, NMDA antagonists may be an option.
NMDA is a receptor for the excitatory neurotransmitter glutamate, which is released with noxious peripheral stimuli. The activation of NMDA receptors has been associated with hyperalgesia, neuropathic pain, and reduced functionality of opioid receptors. Hyperalgesia and neuropathic pain are a result of increased spinal neuron sensitization, leading to a heightened level of pain. The reduced function of opioid receptors is caused by a decrease in the opioid receptor’s sensitivity. This decreased sensitivity, in turn, translates to opioid tolerance as patients will require higher doses of opioids to achieve the same therapeutic effects. Therefore, NMDA antagonists may have a role in these areas of pain management.
It is important to note the claim it can prevent tolerance to opiods but there is NO EVIDENCE for this claim.
There are several NMDA receptor antagonists available: ketamine, methadone, memantine, amantadine, and dextromethorphan. They each differ in their level of activity on the NMDA receptor. Ketamine is a strong NMDA antagonist, whereas the others are weaker NMDA receptor blockers.
Role in looksmaxxing
-Feeling dissociation from pain after extreme working out
-Allowing excercise to continue while in pain/while injured and needing to recover.
-Possibly reducing anxiety
-Reducing fatigue signals
-Reducing "central sensitization" from chronic pain
-Belief it prevents tolerance to opoids or stimulants (but this has no studies to back it up)
-Tunnel vision interpretated by some as "improved focus"
Possible side effects
Severity and frequency of side effects depend on affinity for the NMDA receptor. In adults, adverse effects of NMDA antagonists are mainly central nervous system side effects including hallucinations, lightheadedness, dizziness, fatigue, headache, out-of-body sensation, nightmares, and sensory changes. Since ketamine is a strong NMDA antagonist, it is less tolerable than the other antagonists due to a higher incidence of side effects, in particular hallucinations and a dissociative mental state. There is also a possible risk for neuro toxicity (see Olney's lesions in this article https://brainstuff.org/blog/what-are-olneys-lesions )
The clinical trials so far have demonstrated the value of ketamine and methadone in reduction of neuropathic pain and opioid-resistant pain. However, CNS adverse effects are a concern, especially with ketamine. Memantine, amantadine, and dextromethorphan are weaker NMDA antagonists with a safer toxicity profile but have not shown consistent benefit in these pain settings. More studies of NMDA-antagonists are needed to determine their best use in pain management as well as to effectively manage their side effects.
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