7evenvox22
Iron
- Joined
- May 29, 2025
- Posts
- 94
- Reputation
- 101
Why Cerebrolysin for Neurogenesis?
- Neurogenesis matters for memory, learning, mood, and recovery after brain injury.
- Cerebrolysin is one of the few compounds with clinical human evidence for enhancing brain repair.
- It works not just as a “supplement” but as a therapeutic tool to boost BDNF, mimic neurotrophic factors, and stimulate hippocampal progenitor cells.
Mechanism Made Simple
Think of Cerebrolysin as a “neurotrophic cocktail”:- Supplies small peptides that act like BDNF/NGF - signals stem cells to divide.
- Activates CREB and PI3K/Akt - drives survival and growth of newborn neurons.
- Protects mitochondria - ensures energy stability for cell growth.
- Enhances synaptogenesis - new neurons integrate into working networks.
Clinical Applications
- Stroke rehabilitation: Enhances plasticity, improves motor/cognitive recovery.
- Traumatic brain injury (TBI): Speeds functional improvement alongside rehab.
- Alzheimer’s & dementia: May slow decline by promoting new synaptic connections.
Practical Applications
- Generalized Anxiety Disorder: many cases of it curing people’s GAD completely.
- Depression: Supports hippocampal neurogenesis, which is often suppressed in depression.
- Post drug use: Supports faster neurotransmitter regulation after using recreational drugs.
Protocol Principles
- Administration route: Intramuscular (IM) or intravenous (IV).
- Cycle approach: Typically given in course-like cycles (e.g., 10–20 days of daily injections), repeated as needed.
- Combination strategies: Works synergistically with rehabilitation, cognitive training, exercise, and potentially with other neuroplasticity enhancers (e.g., Semax, nootropic stacks).
How to Maximize Benefits
- Pair with activity: Cerebrolysin-induced neurogenesis is most useful when new neurons are trained into networks via learning, rehab, or therapy.
- Stack with lifestyle: Exercise, sleep, and enriched environments dramatically increase survival of newborn neurons.
- Synergistic compounds:
- Semax/Selank - increase BDNF and support stress resilience.
- Lion’s Mane (NGF inducer) - natural adjunct.
- NAD+ boosters (NMN/NR/Niacin) - enhance mitochondrial energy for neuron growth.
Safety & Considerations
- Generally well tolerated; mild agitation, dizziness, or sweating possible.
- Used clinically in Europe and Asia for decades with a strong safety record.
- Should not be seen as a “magic bullet” - works best as part of a comprehensive neurorehabilitation program.
Key Takeaways
- Cerebrolysin is a clinically validated neurogenic therapy, unlike many experimental compounds.
- Best suited for neurological recovery and age-related cognitive decline.
- Works by mimicking growth factors, boosting BDNF, and protecting mitochondria.
- Gains are maximized when paired with rehab, cognitive training, and neuroplasticity-promoting lifestyle factors.
1. Introduction
Fear Learning and Extinction
- Fear conditioning: Brain learns to associate a neutral cue with threat (e.g., a loud sound → danger).
- Extinction: Repeated exposure to the cue without the threat teaches safety.
- Clinical problem: In PTSD, OCD, and phobias, extinction fails → traumatic or compulsive loops dominate.
Limitations of Current Therapies
- Exposure therapy/CBT: Effective, but many patients relapse.
- Benzodiazepines: Suppress anxiety acutely, but block extinction learning.
- SSRIs: Support extinction gradually, but take weeks to months.
- Need: Fast-acting, durable interventions that reset fear circuits.
Psychedelics as Psychoplastogens
- Psilocybin and LSD are serotonergic psychedelics with strong evidence for rapidly increasing plasticity.
- They modulate fear circuits through 5-HT2A receptor activation, BDNF release, and amygdala dampening.
- This makes them uniquely suited for fear extinction when paired with therapy.
2. Mechanism of Action
5-HT2A Receptor Agonism
- Psychedelics bind to 5-HT2A receptors on cortical pyramidal neurons.
- ↑ Glutamate release in the prefrontal cortex (PFC).
- Activates AMPA/NMDA receptors → BDNF release → mTOR pathway.
Neuroplasticity Effects
- BDNF upregulation → promotes synaptogenesis, dendritic growth.
- mTOR activation → rapid structural changes, similar to ketamine but via serotonergic pathways.
- Hippocampal neurogenesis: Animal studies show psilocybin boosts progenitor proliferation in dentate gyrus.
Amygdala Dampening
- fMRI studies: Psilocybin and LSD reduce amygdala reactivity to negative emotional cues.
- Increased PFC–hippocampal control over the amygdala.
- Result: Traumatic cues feel less overwhelming, making exposure possible.
Network-Level Changes
- Psychedelics increase global connectivity and entropy.
- Breaks rigid pathological loops (trauma replay, compulsions) and opens new pathways for learning safety signals.
3. Fear Extinction in Practice
How They Enhance Extinction
- Reactivation: Traumatic memory is re-experienced in a safe therapeutic context.
- Amygdala dampening: Emotional charge is reduced → memory can be revisited without overwhelming fear.
- Plasticity window: BDNF + mTOR create conditions for new synaptic encoding.
- Extinction memory formation: New “safety” associations are written into circuits.
- Consolidation: Plastic changes persist for days–weeks, making extinction durable.
Why They’re Unique
- Benzodiazepines: reduce fear but block learning.
- SSRIs: improve extinction but take weeks.
- Ketamine: rapid plasticity but less targeted to emotional circuits.
- Psychedelics: combine acute amygdala dampening + lasting plasticity → ideal for fear extinction.
4. Clinical Applications
PTSD
- Trauma memories are “frozen” in hyperactive amygdala–hippocampus circuits.
- Psychedelics allow safe reprocessing and fear extinction with therapy support.
OCD
- Compulsions arise from rigid threat-response loops.
- By boosting plasticity and weakening amygdala-driven responses, psychedelics help disrupt maladaptive cycles.
Phobias
- Extinction learning can be accelerated when psychedelics are paired with exposure to phobic cues.
5. Practical Principles of Use (Educational)
Timing
- Macrodosing: Single high-dose session paired with guided therapy → profound memory reprocessing.
- Microdosing: May subtly enhance learning and reduce avoidance, but not sufficient for deep extinction.
Therapy Integration
- Psychedelics should be paired with exposure therapy, EMDR, or trauma reprocessing.
- The plasticity window (24–72 hrs after) is critical for reinforcement of safety memories.
- Activities like journaling, therapy sessions, and behavioral exposures during this period help extinction consolidate.
Example Session Flow
- Preparation: Safe set & setting, therapist support.
- Administration: Psilocybin or LSD given.
- Memory reactivation: Patient revisits trauma or feared cue with guidance.
- Extinction learning: New safe associations encoded.
- Integration: Follow-up therapy, behavioral practice, journaling in the days after.
6. Evidence Base
- Psilocybin: Pilot trials show reductions in anxiety and avoidance, improvements in trauma processing.
- LSD: Preclinical work shows robust dendritic spine growth and extinction facilitation.
- Animal studies: Both compounds accelerate extinction learning and prevent spontaneous fear recovery.
- Human imaging: Reduced amygdala activity, increased connectivity in circuits governing emotional regulation.
Summary
Psychedelics like psilocybin and LSD are powerful tools for fear extinction. They dampen the amygdala, open a plasticity window via BDNF and mTOR, and increase circuit flexibility so that old fear memories can be overwritten with new safety associations. Their greatest power lies in being paired with therapy during and after the session, making extinction faster, stronger, and more durable than standard approaches.1. Introduction
Why Creativity and Innovation Matter
- Creativity: The ability to generate novel and useful ideas.
- Innovation: The application of creative ideas to solve real-world problems.
- Productivity: The execution and integration of these ideas into sustained outcomes.
The Psychedelic Edge
- Psychedelics like psilocybin and LSD have long been associated with breakthroughs in art, music, and technology.
- Modern neuroscience shows they increase network flexibility, reduce rigid self-censorship, and boost plasticity.
- This makes them uniquely suited for enhancing creative ideation, divergent thinking, and innovative productivity.
2. Mechanism of Action
5-HT2A Receptor Activation
- Both psilocybin and LSD strongly activate 5-HT2A receptors on pyramidal neurons in the cortex.
- This increases glutamate release and drives BDNF → mTOR signaling, leading to rapid plasticity.
Brain Network Effects
- Default Mode Network (DMN) suppression: Reduces self-criticism and habitual thought loops.
- Global connectivity increase: Brain regions that normally don’t interact begin communicating → novel associations.
- Entropy increase: More variability in brain activity, allowing flexible cognition.
Synaptic & Circuit-Level Changes
- Acute: Rapid dendritic spine growth within hours of dosing.
- Subacute (days–weeks): Increased connectivity persists, supporting integration of new ideas.
- Chronic: Lasting changes in openness and cognitive flexibility reported after controlled sessions.
3. Creativity Enhancement
Divergent Thinking
- Expanded network connectivity → generation of more novel ideas.
- Studies: Psilocybin boosts “unconventional thinking” scores in creative problem-solving tasks.
Convergent Thinking
- High-dose sessions may temporarily impair focus, but post-session integration enhances ability to refine and filter ideas.
- Microdosing may help balance divergent + convergent thinking for applied creativity.
Historical Examples
- LSD used by engineers, mathematicians, and artists in the 1950s–60s to solve problems.
- Modern microdosing movement in Silicon Valley emphasizes creativity, flow, and productivity.
4. Innovation and Application
- Idea generation (macro sessions): Macrodoses promote radically novel insights — good for breakthroughs.
- Idea execution (integration phase): Plasticity window supports embedding insights into usable solutions.
- Ongoing productivity (microdoses): Sub-perceptual doses provide subtle boosts in focus, creativity, and mood.
Example Workflow
- Macrodose session → breakthrough concepts, novel associations.
- Post-session integration → journaling, creative sprints, brainstorming.
- Microdosing cycle → maintain flow and translate insights into daily productivity.
5. Productivity Enhancement
Acute Effects
- Macrodoses: Not directly productive during the session (too disruptive), but may inspire breakthroughs.
- Microdoses: Support focus, reduce procrastination, improve motivation.
Long-Term Effects
- Increased openness to experience, a personality trait linked to sustained creativity.
- Enhanced emotional regulation reduces performance anxiety → smoother workflow.
- Greater cognitive flexibility supports adaptation in problem-solving.
6. Practical Principles (Educational)
Macrodosing for Creativity
- Use case: Radical breakthroughs, novel perspectives.
- Format: Guided high-dose psilocybin or LSD session.
- Follow-up: Capture insights through journaling, drawing, or audio recording during/after session.
- Integration: Revisit insights with sober reflection, therapy, or creative practice in the following days.
Microdosing for Productivity
- Use case: Day-to-day creativity, focus, and mood enhancement.
- Format: ~1/10th of a normal dose, taken 1–2 times per week.
- Goal: Subtle mood and focus shift, not hallucinations.
- Risks: Long-term effects less studied; placebo effect possible in some.
7. Evidence Base
- Psilocybin: Increases openness, divergent thinking, and emotional flexibility; boosts creativity in lab studies.
- LSD: Enhances global brain connectivity, correlating with insight and creative thought.
- Microdosing studies: Mixed results — some show improvements in creativity and productivity, others suggest placebo may contribute.
- Anecdotal and historical evidence: Strong cultural and individual reports of breakthroughs in science, art, and tech.
Summary
Psychedelics like psilocybin and LSD enhance creativity by breaking down rigid networks, boosting BDNF-driven plasticity, and increasing global brain connectivity. They support innovation by generating radical new ideas during macrodoses and embedding them into actionable outcomes during integration. Microdoses offer subtler, ongoing boosts to mood, focus, and productivity. Their true power lies not in the trip itself, but in how the plasticity window is used afterward.1. Introduction
Fear Learning and Extinction
- Fear conditioning: The brain links a neutral cue (sound, place) with a threat.
- Extinction: Repeated exposure to the cue without the threat teaches the brain that it is now safe.
- In PTSD, phobias, and OCD, extinction learning is impaired → traumatic associations remain dominant.
The Problem in PTSD & Anxiety Disorders
- Hyperactive amygdala → strong fear recall.
- Weak prefrontal regulation → difficulty suppressing fear responses.
- Poor hippocampal encoding of safety contexts → environment keeps triggering trauma responses.
- Standard therapies (exposure therapy, CBT) rely on extinction learning, but many patients relapse.
Why Epigenetics?
- Extinction is not just “unlearning,” it requires new gene expression to build and stabilize the safety memory.
- If the epigenetic machinery isn’t primed, extinction memories are weak and can fade.
- This is where HDAC inhibitors come in: they boost transcription of plasticity-related genes, strengthening extinction.
2. HDAC Inhibitors: An Overview
What They Are
- HDAC = Histone Deacetylase.
- Function: Remove acetyl groups from histone proteins → DNA winds tightly → gene expression is repressed.
- HDAC inhibitors (HDACi) block this, keeping chromatin “open” → easier transcription of key genes.
Why They Matter in Fear Extinction
- Fear extinction depends on upregulating proteins like BDNF, c-Fos, CREB-driven genes.
- If HDACs are too active, transcription is suppressed → extinction is weak.
- HDAC inhibition amplifies plasticity signals during extinction learning.
Classes of HDAC Inhibitors
- Vorinostat (SAHA): Potent, oncology drug.
- Sodium Valproate (Valproic Acid): Widely used mood stabilizer, weak HDACi but practical.
- Other experimental HDACi: e.g., entinostat, trichostatin A (preclinical).
3. Mechanism in Fear Extinction
- Chromatin Remodeling
- HDAC inhibition → histones remain acetylated → chromatin stays open → transcription factors bind DNA more easily.
- Gene Expression Boost
- ↑ BDNF → promotes synaptic plasticity and hippocampal neurogenesis.
- ↑ Immediate early genes (IEGs like c-Fos, Arc) → strengthen new memory traces.
- ↑ CREB activity → stabilizes extinction-related learning.
- Circuit-Level Effects
- Prefrontal cortex gains stronger control over amygdala.
- Hippocampus encodes “safety contexts” more reliably.
- Amygdala fear circuits are weakened by stronger competing extinction memories.
4. Key Compounds
Sodium Valproate
- Clinical use: Epilepsy, bipolar disorder, mood stabilization.
- HDAC activity: Weak but significant, especially in the hippocampus.
- Other actions: Increases GABAergic inhibition (reduces anxiety acutely).
- Extinction use case: Taken before therapy → enhances extinction memory encoding.
- Pros: Widely available, safe in most adults, long track record.
- Cons: Teratogenic, requires monitoring for liver function and weight/metabolic side effects.
Vorinostat (SAHA)
- Clinical use: FDA-approved for cutaneous T-cell lymphoma.
- HDAC activity: Strong, pan-HDAC inhibitor.
- Evidence: Robust preclinical studies showing enhanced fear extinction when paired with cue exposure.
- Limitations: Cancer drug profile, potential side effects (fatigue, thrombocytopenia). Not practical for wide psychiatric use yet.
Others (Experimental)
- Entinostat, Trichostatin A, MS-275: Used in research; consistently improve extinction learning in animal models.
- Future direction: More selective HDAC2 inhibitors (since HDAC2 is most linked to memory suppression).
5. Practical Application in Therapy
General Principles
- HDACi are adjuncts, not stand-alone cures.
- Work best when paired with extinction training (exposure therapy, EMDR, VR-based therapy).
- Timing and context are critical: must coincide with reactivation of fear memories.
Example Protocol (Educational)
Session design:- Pre-session (drug administration):
- Valproate taken 1–2 hrs before therapy to align with peak plasma levels.
- Vorinostat (if ever used clinically) would also be scheduled shortly before therapy.
- Memory reactivation:
- Patient is exposed to trauma-related cues (e.g., sounds, images, VR, narrative retelling).
- This destabilizes the fear memory.
- Extinction training:
- Therapist guides exposure until fear response decreases.
- With HDAC inhibition, the “safety” memory consolidates more strongly.
- Integration & consolidation:
- Post-session journaling, therapy discussion, or mindfulness helps reinforce the new memory.
- Repetition:
- Multiple sessions needed. Each builds stronger extinction memory traces.
6. Clinical Implications
- PTSD: Strong potential to make exposure therapy more durable, prevent relapse.
- Phobias: Faster reduction in fear, less relapse after treatment ends.
- OCD: Could weaken maladaptive fear–compulsion loops.
- Depression/Anxiety: Indirect benefit by improving emotional flexibility and resilience.
Summary
HDAC inhibitors like sodium valproate and vorinostat enhance fear extinction by keeping chromatin “open” and boosting transcription of neuroplasticity genes like BDNF and CREB. They don’t erase traumatic memories but make new safety associations stronger and longer-lasting. To work, they must be paired with exposure therapy — the drug primes the brain, but the therapy provides the new learning. Valproate is the most practical current option; vorinostat remains experimental.1. Introduction
Critical Periods and Learning
- During childhood, the brain exists in a state of heightened plasticity known as critical periods.
- Skills like language, music, and social learning are absorbed quickly and deeply.
- This is because gene expression supporting synaptic remodeling and neuroplasticity is wide open.
The Adult Limitation
- In adulthood, plasticity declines: learning is slower, less flexible, and more reliant on repetition.
- One reason: epigenetic “braking systems” (like HDACs) tighten gene expression, limiting rapid rewiring.
The HDAC Inhibitor Hypothesis
- HDAC inhibitors (HDACi) can “reopen” some of this childlike learning capacity by unlocking gene expression.
- Preclinical studies suggest they can reinstate critical period-like plasticity in adult brains.
- This offers potential applications in rehabilitation, language acquisition, fear extinction, and skill learning.
2. What are HDAC Inhibitors?
Histone Deacetylases (HDACs)
- HDACs remove acetyl groups from histones → DNA wraps tighter → gene expression shuts down.
- In adult brains, this reduces transcription of BDNF, Arc, c-Fos, and other plasticity genes.
HDAC Inhibition
- Blocking HDACs keeps chromatin open.
- More transcription → more plasticity-related proteins → neurons regain ability to rewire quickly.
Representative Compounds
- Vorinostat (SAHA): Potent pan-HDAC inhibitor; oncology drug.
- Sodium Valproate: Widely used as a mood stabilizer/anticonvulsant; weaker HDACi but clinically practical.
- Entinostat, Trichostatin A (TSA): Research compounds with strong memory effects in animal models.
3. Mechanisms Behind Childlike Learning Reinstatement
- Critical Period Plasticity Reactivation
- HDACi reduce inhibitory tone and promote excitatory–inhibitory balance seen in early development.
- This makes circuits more malleable to environmental inputs.
- Gene Expression Boost
- ↑ BDNF: Key for synapse formation and dendritic growth.
- ↑ Immediate Early Genes (IEGs like Arc, c-Fos): Necessary for rapid memory consolidation.
- Circuit-Level Effects
- Hippocampus: Faster encoding of new memories.
- Cortex: More flexible reorganization (e.g., in sensory or motor learning).
- Prefrontal cortex: Increased ability to update rules and adapt behaviors.
4. Evidence for Enhanced Learning
- Fear extinction studies: Adult animals given HDACi show extinction as robust as young animals.
- Language/skill learning (preclinical): Reopening of auditory plasticity windows suggests potential for second-language learning or musical skill acquisition.
- Stroke recovery models: HDACi improve functional recovery by reactivating plasticity.
- Memory enhancement: Rodents given HDACi show faster acquisition of maze tasks and more durable long-term memory.
5. Practical Application Principles (Educational)
Timing with Learning Tasks
- HDAC inhibitors are most effective when paired with active learning.
- Example: Take valproate before a language lesson → hippocampal plasticity enhanced → words stick faster.
Session Structure
- Pre-session: Administer HDACi (e.g., sodium valproate 1–2 hrs before task).
- Learning phase: Engage in skill training, language acquisition, or therapy session.
- Consolidation: Plasticity window allows stronger encoding of what was practiced.
- Repetition: Multiple cycles reinforce skill with accelerated consolidation.
Integration with Other Plasticity Enhancers
- Combine with environmental enrichment (novelty, challenge, stimulation).
- Potential synergy with psychedelics (acute entropy + epigenetic reopening) for even deeper re-learning.
6. Childlike Learning Applications
- Second-language learning: Adults may acquire vocabulary and grammar faster.
- Music and art skills: Plasticity reactivation could accelerate motor and auditory learning.
- Rehabilitation: Stroke patients relearn movement patterns more efficiently.
- Emotional relearning: Fear extinction and trauma reprocessing occur as if the brain were young and flexible.
8. Safety and Considerations
- Valproate: Safe in adults, but teratogenic → avoid in pregnancy. Monitor liver function and metabolic side effects.
- Vorinostat/oncology-grade HDACi: Too heavy for routine use; used only in research.
- Specificity challenge: Pan-HDAC inhibition can affect many pathways — future goal is selective HDAC2 inhibitors (linked most directly to memory).
- Ethical considerations: Using drugs to “reopen childhood-like plasticity” raises questions about over-enhancement or misuse.
Summary
HDAC inhibitors like valproate and vorinostat can reopen childlike learning windows by unlocking chromatin and boosting plasticity genes. This makes the adult brain more like a child’s — absorbing languages, skills, and emotional relearning faster and more deeply. They work best when paired with active training or therapy during the plasticity window. While promising, current compounds have safety and specificity limits; future HDAC2-targeted drugs may one day make “lifelong critical periods” a reality.- Introduction
Why People Use Alcohol
- Alcohol lowers social anxiety, reduces self-consciousness, and increases confidence by:
- Enhancing GABAergic inhibition (relaxation, anxiolysis).
- Reducing prefrontal control (disinhibition).
- Boosting dopamine in reward circuits.
- Problem: Alcohol carries significant long-term health risks (liver disease, cardiovascular burden, neurotoxicity), as well as short term detriments to our goals (inhibition of mTOR and protein synthesis, caloric burden)
The Search for Better Alternatives
- Compounds that modulate GABA or glutamate signaling reproduce some of alcohol’s desirable effects (anxiolysis, disinhibition, sociability).
- Four notable candidates: Pregabalin, Baclofen, Lamotrigine, Memantine.
- Each targets overlapping but distinct mechanisms in the GABA-glutamate balance.
- Mechanisms of Action
Pregabalin
- Mechanism: Binds α2δ subunit of voltage-gated calcium channels → ↓ glutamate, norepinephrine, substance P release.
- Effects: Strong anxiolysis, relaxation, social ease.
- Similarity to alcohol: GABAergic-like disinhibition without ethanol metabolism.
Baclofen
- Mechanism: GABA-B receptor agonist → ↓ excitatory neurotransmission, ↑ relaxation.
- Effects: Reduces social anxiety, promotes calm confidence.
- Similarity to alcohol: Mimics ethanol’s GABA-B activation (ethanol indirectly activates both GABA-A and GABA-B).
Lamotrigine
- Mechanism: Voltage-gated sodium channel blocker → stabilizes neuronal membranes, ↓ glutamate release.
- Effects: Subtle anxiolysis, mood stabilization, emotional blunting.
- Similarity to alcohol: Doesn’t induce disinhibition directly, but lowers over-excitability that fuels anxiety.
Memantine
- Mechanism: NMDA receptor antagonist (low to moderate affinity).
- Effects: Dampens excitotoxic glutamate activity, improves cognitive flexibility.
- Similarity to alcohol: Provides some disinhibition and calm via reduced glutamate drive, but with clearer cognition.
- Practical Applications (Educational)
Pregabalin
- Best for: Social anxiety, parties, performance situations.
- Profile: Provides alcohol-like calm and sociability; stronger “confidence boost.”
- Cautions: Dependence and tolerance possible with daily use; synergistic sedation with alcohol or benzos.
Baclofen
- Best for: Individuals who want a relaxed, calm social presence without intoxication.
- Profile: More muscle relaxation than euphoria; less reinforcing than alcohol.
- Cautions: Sedation at higher doses; risk of dependence at sustained use.
Lamotrigine
- Best for: Reducing over-arousal and social inhibition in anxious or irritable individuals.
- Profile: Subtle, stabilizing - doesn’t mimic alcohol “buzz,” but may make social interactions easier through calmness.
- Cautions: Rare risk of Stevens-Johnson syndrome; requires slow titration.
Memantine
- Best for: Enhancing openness, curiosity, and reducing social threat perception with preserved cognition.
- Profile: Calms glutamatergic overdrive without dulling mental sharpness.
- Cautions: Can feel dissociative at higher doses; mild headache/dizziness possible.
- Evidence Base
- Pregabalin: Proven effective in generalized anxiety disorder (GAD); studies show strong anxiolysis and improved social functioning.
- Baclofen: Used in alcohol dependence; reduces craving and anxiety; some evidence of pro-social calm.
- Lamotrigine: Evidence for mood stabilization, anger reduction, and anxiety control; indirect effect on inhibition.
- Memantine: Trials in anxiety, OCD, and alcohol dependence show reduction in compulsive over-control and improved social ease.
- Risks and Considerations
- Pregabalin: Risk of tolerance, withdrawal, abuse in some.
- Baclofen: Can cause muscle weakness, dependence at high doses.
- Lamotrigine: Rare but serious rash risk; otherwise very safe.
- Memantine: Few systemic risks, but higher doses may cause derealization.
- General: Combining these with alcohol or other depressants can dangerously amplify sedation.
- Comparison to Alcohol
- Pregabalin is the closest alcohol substitute in terms of social anxiolysis + disinhibition, but safer metabolically.
- Baclofen provides calm relaxation but less “fun” buzz.
- Lamotrigine offers subtle mood-stabilization, not a direct replacement.
- Memantine provides a unique, “clear-headed disinhibition,” possibly the healthiest long-term option.
- The Stack I Usually Take
- 100mg Lamotrigine
- 250-300mg Pregabalin
- 50-75mg Baclofen
- 10mg Memantine
I find this stack to replicate a similar level of inhibitory signaling as a decent alcohol drinking session, but with far less neurological, physiological or financial burden. And achieving this effect through 4 separate pathways allows for much better sustainability and less tolerance build-up. I am not recommending you to take this stack - consult your doctor.
