🧵 Endogenous DMT: What Do We Really Know?
Two recent papers shed new light on endogenous DMT, its biosynthesis, regulation, and function:
📄 Exploring DMT: Endogenous Role and Therapeutic Potential – by @psychedmt
📄 N,N-Dimethyltryptamine (DMT) in Rodent Brain: Concentrations, Distribution, and Recent Pharmacological Data – by Steven Barker
This thread summarizes key findings.
These studies challenge the idea that DMT exists in only trace amounts and has no biological role.
Let’s dive in. ⬇️🧵
Two recent papers shed new light on endogenous DMT, its biosynthesis, regulation, and function:
📄 Exploring DMT: Endogenous Role and Therapeutic Potential – by @psychedmt
📄 N,N-Dimethyltryptamine (DMT) in Rodent Brain: Concentrations, Distribution, and Recent Pharmacological Data – by Steven Barker
This thread summarizes key findings.
These studies challenge the idea that DMT exists in only trace amounts and has no biological role.
Let’s dive in. ⬇️🧵
1/25 DMT: More Than a Psychedelic?
DMT is an endogenous compound present in plants, animals, and humans. Recent findings show brain levels comparable to classic neurotransmitters, challenging the idea that DMT is only a trace molecule.
DMT is an endogenous compound present in plants, animals, and humans. Recent findings show brain levels comparable to classic neurotransmitters, challenging the idea that DMT is only a trace molecule.
2/25 The Enigma of Low DMT Concentrations
DMT is found in blood, CSF, and various tissues, but its levels in the brain are typically low. However, new research suggests these levels might be biologically significant, fluctuating under stress, hypoxia, or altered states.
DMT is found in blood, CSF, and various tissues, but its levels in the brain are typically low. However, new research suggests these levels might be biologically significant, fluctuating under stress, hypoxia, or altered states.
3/25 DMT production is stress-dependent🐀
Rats in social groups have undetectable brain DMT levels. But isolated show a massive increase in DMT:
📈 502 nM after 21 days
📈 65 nM after 60 days
DMT is physiologically regulated and can reach relevant levels to activate receptors
Rats in social groups have undetectable brain DMT levels. But isolated show a massive increase in DMT:
📈 502 nM after 21 days
📈 65 nM after 60 days
DMT is physiologically regulated and can reach relevant levels to activate receptors
4/25 DMT is present in the developing brain.
In rats, it’s found until at least day 40 of life, peaking at 37 nM and stabilizing at 17 nM.
Its effects on synaptogenesis, neuronal survival, and brain plasticity hint at a fundamental role in early-life neurodevelopment.
In rats, it’s found until at least day 40 of life, peaking at 37 nM and stabilizing at 17 nM.
Its effects on synaptogenesis, neuronal survival, and brain plasticity hint at a fundamental role in early-life neurodevelopment.
5/25 DMT synthesis involves the enzyme INMT, which methylates tryptamine. Alternative pathways may also contribute to its production. Studies indicate that INMT expression is inducible, pointing to dynamic regulation in response to physiological demands.
6/25 DMT Biosynthesis Beyond INMT
While INMT is key in humans, rodents might use alternative pathways. β-carbolines, which also act as MAO inhibitors, may facilitate DMT synthesis and protect it from degradation.
While INMT is key in humans, rodents might use alternative pathways. β-carbolines, which also act as MAO inhibitors, may facilitate DMT synthesis and protect it from degradation.
7/25 DMT Regulation: Enzymes & Energy Barriers
DMT production is self-regulating, limited by enzymatic efficiency and energy barriers. This may prevent excessive accumulation while allowing for adaptive production under stress or altered metabolic states.
DMT production is self-regulating, limited by enzymatic efficiency and energy barriers. This may prevent excessive accumulation while allowing for adaptive production under stress or altered metabolic states.
8/25 DMT & Hypoxia: A Protective Mechanism?
Under low oxygen conditions (hypoxia), DMT levels rise, possibly protecting the brain by reducing oxidative stress. This could explain DMT surges in near-death experiences and altered states.
Under low oxygen conditions (hypoxia), DMT levels rise, possibly protecting the brain by reducing oxidative stress. This could explain DMT surges in near-death experiences and altered states.
9/25 Is DMT a Neurotransmitter?
To qualify as one, DMT must be synthesized, stored, released, and act on receptors. Evidence suggests it co-localizes with key enzymes in the brain, is transported into neurons, and modulates neurotransmitters like serotonin & dopamine.
To qualify as one, DMT must be synthesized, stored, released, and act on receptors. Evidence suggests it co-localizes with key enzymes in the brain, is transported into neurons, and modulates neurotransmitters like serotonin & dopamine.
10/25 How Does DMT Act in the Brain?
DMT binds to serotonin (5-HT) receptors, sigma-1 receptors (σ1R), and possibly trace amine receptors (TAARs). It affects cortical glutamate levels and may have neuroplastic & antidepressant effects.
DMT binds to serotonin (5-HT) receptors, sigma-1 receptors (σ1R), and possibly trace amine receptors (TAARs). It affects cortical glutamate levels and may have neuroplastic & antidepressant effects.
11/25 DMT & Neuroplasticity: Beyond the High
DMT activates 5-HT2A receptors, boosting neuroplasticity, synapse growth, and cognitive flexibility. Even at microdoses, it enhances neurogenesis, suggesting a long-term role in brain adaptation.
DMT activates 5-HT2A receptors, boosting neuroplasticity, synapse growth, and cognitive flexibility. Even at microdoses, it enhances neurogenesis, suggesting a long-term role in brain adaptation.
12/25 DMT & Intracellular 5-HT2A Receptors
Unlike 5-HT, DMT is highly lipophilic, allowing it to cross cell membranes and activate intracellular 5-HT2A receptors which promotes neuroplasticity. Rather than acting like classical serotonin receptors, they could be part of a distinct endogenous neuromodulatory system.
🧬 DMT may also influence microtubule stability by interacting with MAP1A (Microtubule-Associated Protein 1A), which regulates cytoskeletal organization. This suggests a potential role in maintaining neuronal integrity and synaptic remodeling.
If DMT is the primary ligand for these receptors, this challenges conventional neuroscience. It suggests DMT has functional roles beyond psychedelia - perhaps in brain adaptation, plasticity, and cognition.
Unlike 5-HT, DMT is highly lipophilic, allowing it to cross cell membranes and activate intracellular 5-HT2A receptors which promotes neuroplasticity. Rather than acting like classical serotonin receptors, they could be part of a distinct endogenous neuromodulatory system.
🧬 DMT may also influence microtubule stability by interacting with MAP1A (Microtubule-Associated Protein 1A), which regulates cytoskeletal organization. This suggests a potential role in maintaining neuronal integrity and synaptic remodeling.
If DMT is the primary ligand for these receptors, this challenges conventional neuroscience. It suggests DMT has functional roles beyond psychedelia - perhaps in brain adaptation, plasticity, and cognition.
13/25 DMT’s Effects on Neurotransmitters & Brain Function
DMT influences serotonin (5-HT), dopamine (DA), norepinephrine (NE), and glutamate activity. Research shows DMT increases 5-HT and DA levels in key brain regions, suggesting a role in mood regulation and cognitive processing.
🔬 Interestingly, despite activating 5-HT2A receptors (which usually increase glutamate), some studies report no significant glutamate elevation. This contradicts other psychedelics, raising questions about DMT’s unique mechanism.
DMT influences serotonin (5-HT), dopamine (DA), norepinephrine (NE), and glutamate activity. Research shows DMT increases 5-HT and DA levels in key brain regions, suggesting a role in mood regulation and cognitive processing.
🔬 Interestingly, despite activating 5-HT2A receptors (which usually increase glutamate), some studies report no significant glutamate elevation. This contradicts other psychedelics, raising questions about DMT’s unique mechanism.
14/25 DMT & the Autonomic Nervous System
DMT affects the balance between the sympathetic and parasympathetic systems. Initially, it increases sympathetic arousal, followed by a phase where both systems are co-activated, possibly enhancing emotional processing and self-reflection.
DMT affects the balance between the sympathetic and parasympathetic systems. Initially, it increases sympathetic arousal, followed by a phase where both systems are co-activated, possibly enhancing emotional processing and self-reflection.
15/25 DMT’s Role in the Neuroendocrine System
Clinical studies on Ayahuasca (containing DMT) reveal effects on hormones like cortisol, prolactin, and growth hormone. In healthy subjects, it spikes cortisol levels, while in depressed individuals, it normalizes low cortisol, suggesting therapeutic potential.
Clinical studies on Ayahuasca (containing DMT) reveal effects on hormones like cortisol, prolactin, and growth hormone. In healthy subjects, it spikes cortisol levels, while in depressed individuals, it normalizes low cortisol, suggesting therapeutic potential.
16/25 DMT as a Neuroprotective Agent
DMT stimulates sigma-1 receptors (σ1R), which regulate cellular stress responses. This activation protects against oxidative stress, reduces inflammation, and promotes mitochondrial homeostasis - key factors in neurodegenerative disease resilience.
DMT stimulates sigma-1 receptors (σ1R), which regulate cellular stress responses. This activation protects against oxidative stress, reduces inflammation, and promotes mitochondrial homeostasis - key factors in neurodegenerative disease resilience.
17/25 DMT & Immune Modulation
DMT’s effects extend beyond the brain - it modulates the immune system by reducing pro-inflammatory cytokines and enhancing anti-inflammatory responses. This suggests potential therapeutic applications in conditions like autoimmune diseases.
DMT’s effects extend beyond the brain - it modulates the immune system by reducing pro-inflammatory cytokines and enhancing anti-inflammatory responses. This suggests potential therapeutic applications in conditions like autoimmune diseases.
18/25 DMT in Stroke, Brain Injury & Chronic Pain
Studies suggest DMT may help in stroke recovery by reducing brain damage and enhancing neurogenesis. It also shows promise in chronic pain management through sigma-1 receptor activation, which regulates pain pathways.
Studies suggest DMT may help in stroke recovery by reducing brain damage and enhancing neurogenesis. It also shows promise in chronic pain management through sigma-1 receptor activation, which regulates pain pathways.
19/25 DMT & Consciousness: Evolutionary Significance?
DMT biosynthesis is evolutionarily conserved across diverse species, from plants to mammals. This suggests it plays an essential role in cellular adaptation rather than being just a byproduct.
🔬 Its presence in embryonic development, immune function, and hypoxia protection hints at fundamental biological roles. Some researchers propose it may contribute to cognitive evolution and the emergence of complex consciousness.
🧠 DMT’s protective and neuroplastic effects may have been crucial for survival, aiding in stress adaptation, memory consolidation, and environmental responsiveness. Could DMT have shaped the evolution of human cognition?
DMT biosynthesis is evolutionarily conserved across diverse species, from plants to mammals. This suggests it plays an essential role in cellular adaptation rather than being just a byproduct.
🔬 Its presence in embryonic development, immune function, and hypoxia protection hints at fundamental biological roles. Some researchers propose it may contribute to cognitive evolution and the emergence of complex consciousness.
🧠 DMT’s protective and neuroplastic effects may have been crucial for survival, aiding in stress adaptation, memory consolidation, and environmental responsiveness. Could DMT have shaped the evolution of human cognition?
20/25 DMT & Altered States of Consciousness
DMT has been linked to near-death experiences (NDEs), dreams, and mystical states. It is hypothesized that hypoxia-triggered DMT surges could contribute to the intense visual and emotional experiences reported in NDEs.
DMT has been linked to near-death experiences (NDEs), dreams, and mystical states. It is hypothesized that hypoxia-triggered DMT surges could contribute to the intense visual and emotional experiences reported in NDEs.
21/25 🛌 Sleep & DMT:
There’s evidence that DMT levels fluctuate during sleep cycles, particularly in REM sleep. Some theories suggest that DMT, melatonin, and β-carbolines work together in regulating sleep architecture.
There’s evidence that DMT levels fluctuate during sleep cycles, particularly in REM sleep. Some theories suggest that DMT, melatonin, and β-carbolines work together in regulating sleep architecture.
22/25 DMT’s Role in Self-Regulation & Homeostasis
Unlike classic neurotransmitters, DMT may be involved in adaptive biological regulation, responding to:
⚡ Stress & trauma
🫁 Oxygen deprivation (hypoxia)
🛡️ Immune response & inflammation
📉 Under normal conditions, its synthesis is tightly regulated by enzymatic constraints, preventing excessive psychoactive effects while maintaining physiological balance.
Unlike classic neurotransmitters, DMT may be involved in adaptive biological regulation, responding to:
⚡ Stress & trauma
🫁 Oxygen deprivation (hypoxia)
🛡️ Immune response & inflammation
📉 Under normal conditions, its synthesis is tightly regulated by enzymatic constraints, preventing excessive psychoactive effects while maintaining physiological balance.
23/25 DMT: Endogenous Signal or Byproduct?
Is DMT a functional neurotransmitter or just a metabolic byproduct? The evidence suggests it’s actively synthesized and regulated, can be stored in vesicles, and acts on specific synaptic receptors - a profile fitting neurotransmitter criteria, but more research is needed!!!
Is DMT a functional neurotransmitter or just a metabolic byproduct? The evidence suggests it’s actively synthesized and regulated, can be stored in vesicles, and acts on specific synaptic receptors - a profile fitting neurotransmitter criteria, but more research is needed!!!
24/25 DMT’s Potential Therapeutic Applications
DMT’s neuroplastic and anti-inflammatory properties make it a candidate for treating:
✅ Depression & PTSD
✅ Neurodegenerative diseases
✅ Brain injury & stroke
✅ Chronic pain & migraines
25/25 Final Thoughts & Future Directions
DMT is more than just a psychedelic - it is an evolutionarily conserved, multifunctional molecule involved in:
🧬 Brain adaptation & neuroplasticity
⚖️ Homeostatic regulation
💭 Consciousness & altered states
🔬 More research is needed to unlock its therapeutic potential and endogenous functions - are we just scratching the surface of its role in human biology?
DMT’s neuroplastic and anti-inflammatory properties make it a candidate for treating:
✅ Depression & PTSD
✅ Neurodegenerative diseases
✅ Brain injury & stroke
✅ Chronic pain & migraines
25/25 Final Thoughts & Future Directions
DMT is more than just a psychedelic - it is an evolutionarily conserved, multifunctional molecule involved in:
🧬 Brain adaptation & neuroplasticity
⚖️ Homeostatic regulation
💭 Consciousness & altered states
🔬 More research is needed to unlock its therapeutic potential and endogenous functions - are we just scratching the surface of its role in human biology?
@RCarhartHarris @neurodelia @alieninsect @breath_Guy @drmichaellevin @algekalipso @drdluke @dmt_quest @AdamButlerBooks @trikomes @tipado
• • •
Missing some Tweet in this thread? You can try to
force a refresh
