red22
Bluelighter
- Joined
- Nov 23, 2009
- Messages
- 1,200
Immediate Effects of Opioids on Mood Receptors
- Opioids bind to mu-opioid receptors in the brain, leading to the release of dopamine in the reward pathway. This creates euphoria and relief from pain or distress.
- With prolonged use, the brain adapts by reducing the sensitivity and/or number of opioid receptors (downregulation) and altering dopamine signaling. This contributes to tolerance (needing more of the drug for the same effect) and dependence (experiencing withdrawal symptoms without the drug).
Short-Term Recovery After Opioid Use
- After discontinuing opioids, individuals experience withdrawal symptoms, which include both physical and psychological distress (e.g., anxiety, depression, irritability). These symptoms are part of acute withdrawal and typically resolve within a few days to weeks.
- However, even after the acute withdrawal phase, people may experience protracted withdrawal symptoms (lasting weeks to months), such as mood disturbances, anhedonia (inability to feel pleasure), and dysphoria (intense dissatisfaction). This period is sometimes referred to as post-acute withdrawal syndrome (PAWS).
Long-Term Effects on Mood and Recovery
- Neuroplasticity: Chronic opioid use can induce long-lasting changes in brain structure and function, particularly in areas like the prefrontal cortex, amygdala, and reward circuits. These changes can lead to long-term difficulties in mood regulation, stress response, and decision-making.
- Full Recovery Potential: While many people can recover from the mood-related effects of opioid use over time, recovery is not always complete or rapid. Studies suggest:
- Partial Reversal: The brain's opioid receptors and dopamine system show some degree of plasticity and recovery with sustained abstinence, but the process can take months or even years, depending on the duration and intensity of use.
- Lasting Vulnerability: Some individuals may experience lingering deficits in mood regulation, anhedonia, or a heightened risk of relapse due to lasting changes in the brain's reward and stress systems.
Research Evidence
- Animal Studies: Long-term opioid exposure leads to persistent changes in receptor density, dopamine signaling, and stress responses, even after prolonged abstinence.
- Human Studies: Brain imaging studies in former opioid users show altered activity in the reward and stress circuits, which may take over a year to normalize. However, the extent of recovery varies widely among individuals.
- Clinical Observations: Some people fully recover and regain normal mood regulation, while others continue to experience depression or anxiety, which might require therapeutic interventions.
Factors Affecting Recovery
1. Duration and Intensity of Use: Longer and heavier opioid use is associated with greater neurochemical and structural changes.
2. Individual Differences: Genetics, pre-existing mental health conditions, and environmental factors play a role in recovery outcomes.
3. Supportive Interventions: Evidence-based treatments, such as medication-assisted therapy (e.g., buprenorphine, methadone), psychotherapy, and lifestyle modifications, can improve recovery and mood stabilization.
Conclusion
While most individuals recover significantly from the mood-related receptor changes caused by opioid use, the timeline and degree of recovery depend on many factors. In some cases, there may be lasting impacts on the brain's reward and stress systems, but with the right interventions and sustained abstinence, full or near-full recovery is possible for many people.
(ChatGPT)
reddit post:
So I’m often reassured that opioids cannot cause neuronal death with the exception of an overdose (hypoxia). Googling opioid neurotoxicity usually brings up sources that seem to talk about how opioids can impair cognition but don’t seem to actually be talking about brain damage but rather a temporary disregulation (as you would expect with any recreational drug)
Recently I’ve come across some studies that do discuss opioids going further than just disregulation, possibly causing excitotoxicity. Below are some quotes I’ve extracted (they get more vague and less relevant as they go on but probably still worth including)
“Exogenous opioids alter the homeostatic environment of the CNS by inducing immunological signaling events that limit the analgesic properties of opioids (12). Immunological events such as the release of proinflammatory cytokines and chemokines via activation of toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK) are linked to opioid tolerance, which is known as opioid-induced hyperalgesia (OIH). Astrocytes, under prolonged stress from persistent opioid use, lose their ability to adequately remove excess glutamate from neuronal synapses (13). When combined with inhibition of gamma-aminobutyric acid (GABA), the resulting imbalance leads to excitotoxity and in prolonged cases, degradation of neurons (14). Such events increase pain sensitivity and reduce the neuroprotective capacity of glial cells, leaving the CNS vulnerable to acute extracellular changes with the potential to alter physiological and behavioral components in individuals with opioid use disorder.”
“The process by which opioids induce excitotoxicity via modulation of astrocytes has two components: inhibition of gamma-aminobutyric acid (GABA)-mediated neurotransmission and downregulation of glutamate transporters. “
https://www.sciencedirect.com/science/article/pii/S2772392522000220
“The phenomenon is probably associated with the downregulation of opioid receptors and excessive activation of NMDA, N-metyl-D-aspartate receptors. “
https://journals.viamedica.pl/palliative_medicine_in_practice/article/download/PMPI.2021.0013/64327
“Psychostimulants, alcohol, and opioids all decrease expression of GLT-1, an astrocyte-specific glutamate transporter that clears glutamate from the synapse (Smith et al., 2015).”
https://onlinelibrary.wiley.com/doi/10.1111/ejn.14163
It seems to me that the consensus from the general drug community that opioids don’t cause neuronal degradation/death except in hypoxic scenarios is wrong and as someone that has been worried about causing any further neurotoxicity/excitotoxicity with their drug use this is quite alarming as I considered opioids to be “safe” in this regard so long as I’m careful with my dose. A great many people who abuse opioids also regularly abuse benzodiazepines leading to further downregulation of GABA, and some use stimulants regularly or in combination with opioids, further compounding excitotoxicity.
Do opioids cause neuronal degradation/death via excitotoxicity? CantinaMan, Aug 12, 2023, reddit
Identification and management of opioid-induced neurotoxicity in older adults. Godwin, B., Frank, C., Molnar, F., Dyks, D., & Akter, R. (2022). Canadian family physician Medecin de famille canadien, 68(4), 269–270. DOI: 10.46747/cfp.6804269
This book is about fentanyl: The Memory Thief: The Secrets Behind How We Remember—A Medical Mystery. Lauren Aguirre, 2021, Pegasus Books, ISBN: 9781643136523
Sometimes, it’s not the discovery that’s hard – it’s convincing others that you’re right. The Memory Thief chronicles an investigation into a rare and devastating amnesia first identified in a cluster of fentanyl overdose survivors. When a handful of doctors embark on a quest to find out exactly what happened to these marginalized victims, they encounter indifference and skepticism from the medical establishment.
But after many blind alleys and occasional strokes of good luck, they go on to prove that opioids can damage the hippocampus, a tiny brain region responsible for forming new memories. This discovery may have implications for millions of people around the world.
Through the prism of this fascinating story, Aguirre recounts the obstacles researchers so often confront when new ideas bump up against conventional wisdom. She explains the elegant tricks scientists use to tease out the fundamental mechanisms of memory. And finally, she reveals why researchers now believe that a treatment for Alzheimer’s is within reach.
FINALIST FOR THE 2022 PEN/E.O. WILSON LITERARY SCIENCE WRITING AWARD
"Aguirre writes clearly, concisely, and often cinematically. The book succeeds in providing an accessible yet substantive look at memory science and offering glimpses of the often-challenging process of biomedical investigation.”— Science
Certainly LSD, which was for a time considered in the Western world,
above all in the United States, to be the number-one inebriant, has
relinquished this leading role to other inebriants such as hashish and the habituating, even physically destructive drugs like heroin and amphetamine. The last-mentioned drugs represent an alarming sociological and public health problem today.
Albert Hofmann. LSD: My Problem Child (1979, 1980), ISBN: 9780070293250. 5. From Remedy to Inebriant / Sandoz Stops LSD Distribution
- Opioids bind to mu-opioid receptors in the brain, leading to the release of dopamine in the reward pathway. This creates euphoria and relief from pain or distress.
- With prolonged use, the brain adapts by reducing the sensitivity and/or number of opioid receptors (downregulation) and altering dopamine signaling. This contributes to tolerance (needing more of the drug for the same effect) and dependence (experiencing withdrawal symptoms without the drug).
Short-Term Recovery After Opioid Use
- After discontinuing opioids, individuals experience withdrawal symptoms, which include both physical and psychological distress (e.g., anxiety, depression, irritability). These symptoms are part of acute withdrawal and typically resolve within a few days to weeks.
- However, even after the acute withdrawal phase, people may experience protracted withdrawal symptoms (lasting weeks to months), such as mood disturbances, anhedonia (inability to feel pleasure), and dysphoria (intense dissatisfaction). This period is sometimes referred to as post-acute withdrawal syndrome (PAWS).
Long-Term Effects on Mood and Recovery
- Neuroplasticity: Chronic opioid use can induce long-lasting changes in brain structure and function, particularly in areas like the prefrontal cortex, amygdala, and reward circuits. These changes can lead to long-term difficulties in mood regulation, stress response, and decision-making.
- Full Recovery Potential: While many people can recover from the mood-related effects of opioid use over time, recovery is not always complete or rapid. Studies suggest:
- Partial Reversal: The brain's opioid receptors and dopamine system show some degree of plasticity and recovery with sustained abstinence, but the process can take months or even years, depending on the duration and intensity of use.
- Lasting Vulnerability: Some individuals may experience lingering deficits in mood regulation, anhedonia, or a heightened risk of relapse due to lasting changes in the brain's reward and stress systems.
Research Evidence
- Animal Studies: Long-term opioid exposure leads to persistent changes in receptor density, dopamine signaling, and stress responses, even after prolonged abstinence.
- Human Studies: Brain imaging studies in former opioid users show altered activity in the reward and stress circuits, which may take over a year to normalize. However, the extent of recovery varies widely among individuals.
- Clinical Observations: Some people fully recover and regain normal mood regulation, while others continue to experience depression or anxiety, which might require therapeutic interventions.
Factors Affecting Recovery
1. Duration and Intensity of Use: Longer and heavier opioid use is associated with greater neurochemical and structural changes.
2. Individual Differences: Genetics, pre-existing mental health conditions, and environmental factors play a role in recovery outcomes.
3. Supportive Interventions: Evidence-based treatments, such as medication-assisted therapy (e.g., buprenorphine, methadone), psychotherapy, and lifestyle modifications, can improve recovery and mood stabilization.
Conclusion
While most individuals recover significantly from the mood-related receptor changes caused by opioid use, the timeline and degree of recovery depend on many factors. In some cases, there may be lasting impacts on the brain's reward and stress systems, but with the right interventions and sustained abstinence, full or near-full recovery is possible for many people.
(ChatGPT)
reddit post:
So I’m often reassured that opioids cannot cause neuronal death with the exception of an overdose (hypoxia). Googling opioid neurotoxicity usually brings up sources that seem to talk about how opioids can impair cognition but don’t seem to actually be talking about brain damage but rather a temporary disregulation (as you would expect with any recreational drug)
Recently I’ve come across some studies that do discuss opioids going further than just disregulation, possibly causing excitotoxicity. Below are some quotes I’ve extracted (they get more vague and less relevant as they go on but probably still worth including)
“Exogenous opioids alter the homeostatic environment of the CNS by inducing immunological signaling events that limit the analgesic properties of opioids (12). Immunological events such as the release of proinflammatory cytokines and chemokines via activation of toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK) are linked to opioid tolerance, which is known as opioid-induced hyperalgesia (OIH). Astrocytes, under prolonged stress from persistent opioid use, lose their ability to adequately remove excess glutamate from neuronal synapses (13). When combined with inhibition of gamma-aminobutyric acid (GABA), the resulting imbalance leads to excitotoxity and in prolonged cases, degradation of neurons (14). Such events increase pain sensitivity and reduce the neuroprotective capacity of glial cells, leaving the CNS vulnerable to acute extracellular changes with the potential to alter physiological and behavioral components in individuals with opioid use disorder.”
“The process by which opioids induce excitotoxicity via modulation of astrocytes has two components: inhibition of gamma-aminobutyric acid (GABA)-mediated neurotransmission and downregulation of glutamate transporters. “
https://www.sciencedirect.com/science/article/pii/S2772392522000220
“The phenomenon is probably associated with the downregulation of opioid receptors and excessive activation of NMDA, N-metyl-D-aspartate receptors. “
https://journals.viamedica.pl/palliative_medicine_in_practice/article/download/PMPI.2021.0013/64327
“Psychostimulants, alcohol, and opioids all decrease expression of GLT-1, an astrocyte-specific glutamate transporter that clears glutamate from the synapse (Smith et al., 2015).”
https://onlinelibrary.wiley.com/doi/10.1111/ejn.14163
It seems to me that the consensus from the general drug community that opioids don’t cause neuronal degradation/death except in hypoxic scenarios is wrong and as someone that has been worried about causing any further neurotoxicity/excitotoxicity with their drug use this is quite alarming as I considered opioids to be “safe” in this regard so long as I’m careful with my dose. A great many people who abuse opioids also regularly abuse benzodiazepines leading to further downregulation of GABA, and some use stimulants regularly or in combination with opioids, further compounding excitotoxicity.
Do opioids cause neuronal degradation/death via excitotoxicity? CantinaMan, Aug 12, 2023, reddit
Identification and management of opioid-induced neurotoxicity in older adults. Godwin, B., Frank, C., Molnar, F., Dyks, D., & Akter, R. (2022). Canadian family physician Medecin de famille canadien, 68(4), 269–270. DOI: 10.46747/cfp.6804269
This book is about fentanyl: The Memory Thief: The Secrets Behind How We Remember—A Medical Mystery. Lauren Aguirre, 2021, Pegasus Books, ISBN: 9781643136523
Sometimes, it’s not the discovery that’s hard – it’s convincing others that you’re right. The Memory Thief chronicles an investigation into a rare and devastating amnesia first identified in a cluster of fentanyl overdose survivors. When a handful of doctors embark on a quest to find out exactly what happened to these marginalized victims, they encounter indifference and skepticism from the medical establishment.
But after many blind alleys and occasional strokes of good luck, they go on to prove that opioids can damage the hippocampus, a tiny brain region responsible for forming new memories. This discovery may have implications for millions of people around the world.
Through the prism of this fascinating story, Aguirre recounts the obstacles researchers so often confront when new ideas bump up against conventional wisdom. She explains the elegant tricks scientists use to tease out the fundamental mechanisms of memory. And finally, she reveals why researchers now believe that a treatment for Alzheimer’s is within reach.
FINALIST FOR THE 2022 PEN/E.O. WILSON LITERARY SCIENCE WRITING AWARD
"Aguirre writes clearly, concisely, and often cinematically. The book succeeds in providing an accessible yet substantive look at memory science and offering glimpses of the often-challenging process of biomedical investigation.”— Science
Certainly LSD, which was for a time considered in the Western world,
above all in the United States, to be the number-one inebriant, has
relinquished this leading role to other inebriants such as hashish and the habituating, even physically destructive drugs like heroin and amphetamine. The last-mentioned drugs represent an alarming sociological and public health problem today.
Albert Hofmann. LSD: My Problem Child (1979, 1980), ISBN: 9780070293250. 5. From Remedy to Inebriant / Sandoz Stops LSD Distribution
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