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61

Phenethylamines / An Unrealistic 1969 Amphetamine Abuse documentary called "SPEED SCENE"

« Last post by smfadmin on March 09, 2026, 01:07:16 PM »

i=RbD17SlTGqokprBU

62

Cocaine / Cocaine Addiction is a Biological Rewiring, Not a Choice

« Last post by smfadmin on March 09, 2026, 01:25:24 AM »

https://neurosciencenews.com/cocaine-brain-rewiring-deltafosb-30246/


Cocaine Addiction is a Biological Rewiring, Not a Choice

March 4, 2026

Summary:

Relapse isn’t a failure of willpower—it’s a biological “rewiring” of the brain. A new study reveals how chronic cocaine use hijacks the connection between the brain’s reward center and its memory hub (the hippocampus).

Researchers identified a specific protein, DeltaFosB, that acts like a genetic master switch. As cocaine use continues, this protein accumulates, turning certain genes on and off to create a permanent, compulsive drive for the drug. By using CRISPR technology to pinpoint this mechanism, scientists have opened the door to a new class of “addiction-breaking” medications that could one day reset the brain’s circuitry and prevent relapse.

Key Facts

The “Master Switch”: The protein DeltaFosB accumulates in the brain’s reward-memory circuit during chronic cocaine use, making it harder to quit and easier to relapse.

Rewiring the Hippocampus: Cocaine use doesn’t just change how you feel; it physically alters the hippocampus, the brain’s memory center, linking drug-seeking behavior to deep-seated survival instincts.

Calreticulin’s Role: Researchers found a secondary gene, calreticulin, that is controlled by DeltaFosB and helps “rev the brain’s engine” to seek out more cocaine.

No Approved Meds: Currently, there are no FDA-approved medications to treat cocaine addiction. This research identifies DeltaFosB as a primary target for future pharmaceutical therapies.

CRISPR Insights: Scientists used specialized CRISPR technology to prove that DeltaFosB isn’t just associated with addiction—it is necessary for the brain changes that drive it.

When a cocaine addict relapses, it isn’t a matter of personal failure — it’s the biological result of their brain’s rewiring, new research finds.

Michigan State University scientists found that cocaine changes how the hippocampus functions, contributing to the ongoing compulsion to seek out the drug.

Their National Institutes of Health-supported research, published in Science Advances, not only explains why cocaine addiction is notoriously difficult to treat, but it could also help scientists develop new pharmaceutical therapies.

“Addiction is a disease in the same sense as cancer,” said senior author A.J. Robison, a professor of neuroscience and physiology. “We need to find better treatments and help people who are addicted in the same sense that we need to find cures for cancer.”

At least a million people nationwide struggle with cocaine addiction, and right now, there’s no FDA-approved medication to treat it. People who stop using don’t experience the same physical withdrawal symptoms that opiates cause, but that doesn’t mean it’s easy to quit.

The drug hijacks the brain, flooding the reward centers with dopamine. This positive reinforcement tricks the brain into feeling like it’s doing something good instead of destructive.

Even if someone successfully quits, the odds aren’t in their favor. About 24% relapse to weekly use, and another 18% return to a treatment program within a year.

Andrew Eagle, a former postdoctoral researcher in Robison’s lab and the paper’s lead author, found a key player responsible for the compulsion — a protein called DeltaFosB. He used a specialized form of CRISPR technology to examine the role this protein plays in specific brain circuits when mice were exposed to cocaine.

Using mouse models, he learned that this protein acts like a switch, turning genes on and off in the circuit between the brain’s reward center and the hippocampus, the brain’s memory hub. The longer someone uses cocaine, the more this protein accumulates in the circuit. This protein changes how the neurons function, altering how the circuit responds to cocaine.

“This protein isn’t just associated with these changes, it is necessary for them,” Eagle said. “Without it, cocaine does not produce the same changes in brain activity or the same strong drive to seek out the drug.”

The research team also found another group of genes controlled by DeltaFosB after chronic cocaine use. One of those genes, called calreticulin, helps regulate how neurons communicate with each other. Their work showed calreticulin contributes to revving the brain’s engine to compulsively seek out more cocaine.

Key Questions Answered:

Q: Is cocaine addiction a choice or a disease?
A: This research confirms it is a biological disease. Chronic use physically alters the brain’s genetic expression, creating a protein buildup that forces the brain to prioritize the drug over everything else. It’s a “rewiring” that willpower alone often cannot overcome.

Q: Why is it so hard to stop “craving” the drug even months later?
A: Because the drug hijacks your memory center (the hippocampus). The protein DeltaFosB creates a long-lasting “switch” in your neural circuits that stays flipped long after the drug has left your system, keeping the drive to seek it out active.

Q: Is there a “cure” on the horizon?
A: While we aren’t there yet, researchers are currently developing compounds specifically designed to block DeltaFosB from binding to DNA. If successful, these could “reset” the addicted brain and make long-term recovery much more achievable.

63

Genetics / Re: How RNA/DNA and the Chromosome was formed II

« Last post by gwenmallard on March 04, 2026, 10:06:38 AM »

This is a sophisticated scientific discussion! To ensure your contribution remains highly relevant to a school-aged learning audience while maintaining SEO value for uniccm/school, the content needs to bridge the gap between complex molecular biology and foundational educational concepts.

Below is a drafted forum post designed to fit the flow of the existing conversation. It highlights the transition from "prebiotic soup" to structured cellular life—a core topic in biology curricula.

Bridging the Gap: From Primordial Lipids to the Classroom
The hypothesis regarding the interaction between primordial lipids, amino acids, and PAH scaffolds provides a compelling look at the "engineering" phase of early life. For students and educators, understanding this transition is key to grasping how simple chemical reactions evolved into the complex genomic structures we study in biology today.

The Structural Evolution: Why Histones Matter
As the discussion noted, the leap from prokaryotic (circular) DNA to eukaryotic (linear) DNA necessitated a sophisticated filing system. Without histones, the several meters of DNA in a human cell would be a tangled, unusable mess.

Educational Context: In a school setting, we often use the "thread on a spool" analogy. Histones are the spools that prevent the genetic thread from knotting, allowing for the precise "reading" of genes (transcription).

The Epigenetic Layer: The mention of methylation and acetylation is particularly relevant for modern science curricula. It teaches students that our "genetic destiny" isn't just about the sequence of A, T, C, and G, but about the chemical "switches" that turn those sequences on or off.

Relevance to Student Learning and Health
The forum's interest in substance use and harm reduction actually intersects with this molecular biology. Modern research suggests that environmental factors—including nutrition and exposure to toxins—can leave epigenetic marks on our histones.

For students exploring these topics at UNICCM, learning about the histone-DNA complex isn't just about passing a biology exam; it’s about understanding how our environment and choices interact with our very blueprint at a molecular level.

64

Deep Learning / AI / Chatbots Can Worsen Delusions and Mania

« Last post by smfadmin on February 24, 2026, 04:52:08 AM »

https://neurosciencenews.com/ai-chatbot-mental-health-delusions-30178/

Chatbots Can Worsen Delusions and Mania

February 23, 2026

Summary:

For many, AI chatbots are a helpful tool for productivity, but for those with severe mental illness, they may be a dangerous “echo chamber.” A new study warns that AI chatbots like ChatGPT can significantly worsen psychiatric conditions—particularly delusions, mania, and suicidal ideation.

By screening the health records of over 54,000 patients, researchers found that the AI’s tendency to validate a user’s beliefs can consolidate grandiose or paranoid thoughts, turning a digital assistant into a fuel for psychosis.

Key Facts

Validation Trap: AI chatbots are designed to be helpful and agreeable, which means they often inadvertently validate a user’s delusions rather than challenging them.

Risk Groups: The study highlights significant risks for patients with severe mental illnesses such as schizophrenia or bipolar disorder.

Worsening Symptoms: Negative consequences identified include worsened grandiose delusions, paranoia, mania, suicidal ideation, and eating disorders.

Tip of the Iceberg: Researchers identified 38 specific cases in health records but believe the actual number of affected patients is likely much higher and remains undetected.

Regulation Required: The research team is calling for central regulation of AI technology, similar to how social media is now being regulated to protect the mental health of children and young people.

People with mental illness who use AI chatbots risk experiencing a worsening of their condition.

This is shown by a new study published in the international journal Acta Psychiatrica Scandinavica.

The researchers screened electronic health records from nearly 54,000 patients with mental illness and found several cases in which the use of AI chatbots appears to have had negative consequences – primarily in the form of worsened delusions, but also potential worsening of mania, suicidal ideation, and eating disorder.

“It supports our hypothesis that the use of AI chatbots can have significant negative consequences for people with mental illness,” says Professor Søren Dinesen Østergaard from Aarhus University and Aarhus University Hospital, who leads the research group behind the study.

See the link for the full article ...

65

Technical Stuff / Re: Resizing an Avatar

« Last post by Chip on February 24, 2026, 02:49:59 AM »

No need, it's now automatic.

66

Antihistamines / Re: Promethazine / Phenergen for Sleep (Adults)

« Last post by Chip on February 17, 2026, 07:12:59 PM »

High-Dose Phenergan (Promethazine) for Sleep

Dose and Effects

• Typical sleep dose: 12.5–25 mg 
• Max for sleep: 50 mg 
• 125 mg is 2–5× the normal dose — this is why it produces noticeable sedation


Risks of High Doses

• Strong sedation — can feel like heavy grogginess or almost “knockout” 
• Anticholinergic overload: dry mouth, blurred vision, constipation, urinary retention 
• Cognitive impairment: confusion, memory issues, next-day fog 
• Cardiac risk: possible QT prolongation, especially if combined with other meds 
• Respiratory depression risk if combined with alcohol, opioids, benzos, or GHB/BDO


Key Points

• Feeling sedation at 125 mg is expected — it’s essentially a high-dose effect, not a normal sleep dose 
• No additional sleep quality benefit occurs beyond the sedation — only side effects increase 
• Do NOT escalate doses for “stronger sleep” — the danger rises much faster than any benefit


Harm Reduction Advice

• Stick to 12.5–50 mg if using for sleep 
• Avoid combining with other sedatives 
• Track effects and side effects carefully 
• If 50 mg does nothing, consider alternative approaches rather than escalating the dose

67

Antihistamines / Promethazine / Phenergen for Sleep (Adults)

« Last post by smfadmin on February 17, 2026, 07:04:31 PM »

Promethazine for Sleep (Adults)

Dose

• Typical dose: 12.5–25 mg taken 30–60 minutes before bed 
• Upper end: 25 mg is where most people cap it for insomnia 
• Do NOT exceed: 50 mg for sleep — above this you mostly get side effects, not better sleep


What it actually does

• Sedating first-generation antihistamine, not a true hypnotic 
• Useful for short-term knock-out sleep, jet lag, or when anxiety/nausea is involved 
• Tolerance can build quickly if used nightly


Common side effects

• Next-day grogginess / brain fog 
• Dry mouth, constipation, blurred vision 
• Restless legs or paradoxical agitation in some people 
• Can worsen urinary retention


Important warnings

• Do NOT mix with alcohol, opioids, benzos, GHB/BDO, or other sedatives 
  → increased risk of respiratory depression 
• Can potentiate antipsychotics and other dopamine blockers 
• QT prolongation risk at higher doses or in combination stacks


Bottom line

• Start at 12.5 mg 
• If ineffective, try 25 mg max 
• If you need more than that to sleep, promethazine is the wrong tool


Me: Promethazine 50 mg — No Effect

This is not unusual

Taking 50 mg and feeling nothing happens to a lot of people. 
It’s not a sign you need more — it’s a sign the drug likely doesn’t work for you.


What it likely means

• Promethazine simply does not produce sedation in some individuals 
• Increasing the dose rarely helps once 25–50 mg has failed 
• You may have cross-tolerance or blunted response from:
  – other sedating antihistamines 
  – antipsychotics / dopamine blockers 
  – stimulants (current or residual) 
• Some people have a neutral or paradoxical response (no sedation at all)


Mechanism mismatch

Promethazine works via H1 histamine blockade. 
If insomnia is driven by:
• dopaminergic rebound 
• noradrenergic activation 
• circadian disruption 

…histamine antagonism won’t touch it.


What NOT to do

• Do NOT escalate beyond 50 mg 
• Do NOT stack with alcohol, benzos, opioids, GHB/BDO, or other sedatives 
  → this increases respiratory depression risk without guaranteeing sleep


Bottom line

• If 50 mg does nothing, promethazine is non-viable for you 
• Higher doses mostly add anticholinergic side effects, not sleep 
• This is a binary drug — it either works early or it doesn’t


Alternatives to Promethazine for Sleep

1. Sedating Antihistamines

• Diphenhydramine – 25–50 mg 30–60 min before bed 
• Doxylamine – 12.5–25 mg before bed 
• Same caveats as promethazine: next-day grogginess, anticholinergic side effects, do not mix with other sedatives


2. Melatonin & Circadian Support

• Melatonin 0.5–5 mg 30–60 min before desired sleep 
• Useful for circadian misalignment, jet lag, or delayed sleep phase 
• Combine with sleep hygiene: dark room, avoid screens, consistent bedtime


3. Low-Dose Sedating Medications (Prescription)

• Trazodone – 25–100 mg at night, sedating antidepressant 
• Mirtazapine – 7.5–15 mg for sleep; more potent at higher doses 
• Often used short-term; monitor for next-day grogginess or weight/appetite changes


4. GABAergic Agents (If Not Mixing with Other Depressants)

• L-theanine, valerian, magnesium glycinate – mild, generally safe 
• Avoid combining with alcohol, benzos, opioids, BDO/GHB 
• Effect is subtle; good for easing into sleep rather than knocking out


5. Behavioral / Environmental

• Keep a strict bedtime/wake time 
• Limit caffeine after midday 
• Dark, cool, quiet room 
• Avoid screens 1 hour before sleep 
• Consistency often more powerful than drugs alone


Bottom line

• If promethazine fails, try an approach based on mechanism (histamine, melatonin, GABA, or circadian) 
• Avoid stacking multiple sedatives for brute-force sleep 
• Start low, track effect, and adjust cautiously

68

Antihistamines / Antihistamines: Overview and Common Types

« Last post by Chip on February 17, 2026, 10:28:01 AM »

Antihistamines: Overview and Common Types

Antihistamines are a class of drugs that block the action of histamine, a chemical involved in allergic reactions, gastric acid secretion, and neurotransmission. They are used to treat allergies, hay fever, hives, anaphylaxis (emergency), motion sickness, insomnia, and gastric acid-related conditions.

How Antihistamines Work 
Antihistamines block histamine receptors in the body. The main receptor types are: 
- H1 receptors – Found in smooth muscle, endothelium, and CNS; blocking relieves allergies, hives, and can cause sedation. 
- H2 receptors – In stomach lining; blocking reduces gastric acid. 
- H3 receptors – In CNS; regulate histamine release and wakefulness. 
- H4 receptors – In bone marrow and white blood cells; involved in immune responses. 

Common H1 Antihistamines 
- Diphenhydramine – First-generation, sedating, used for allergies and insomnia 
- Chlorpheniramine – First-generation, mild sedation, allergy treatment 
- Promethazine – First-generation, sedating, used for allergies, nausea, and motion sickness 
- Loratadine – Second-generation, non-sedating, long-acting 
- Cetirizine – Second-generation, slightly sedating, fast onset 
- Fexofenadine – Second-generation, non-sedating, seasonal allergies 

Common H2 Antihistamines 
- Ranitidine (less used now due to recalls) 
- Famotidine 
- Nizatidine 
- Cimetidine 

Common H3 Antihistamines 
- Pitolisant (used in narcolepsy) 
- Others mostly experimental or CNS-targeted 

Common H4 Antihistamines 
- Mostly in research/trials for inflammation or autoimmune conditions 

Tips & Notes 
- First-generation H1 antihistamines often cause drowsiness, dry mouth, and other anticholinergic effects. 
- Second-generation H1 antihistamines are preferred for daytime allergy treatment due to minimal sedation. 
- H2 blockers are mainly for acid reflux or ulcer prevention. 
- Avoid mixing sedating H1 antihistamines with alcohol or CNS depressants. 


This post is intended for educational discussion and harm reduction. Always consult a healthcare professional before starting any medication.

69

GABAergics and VGCC Blockers / VIDEO - Pregabalin: How Lyrica Went From Pain Relief to New Street Drug

« Last post by Chip on February 17, 2026, 08:02:55 AM »

Pregabalin was supposed to save us from the opioid crisis. Instead, by 2018, it was killing more people in Britain than heroin and cocaine combined.

A painkiller approved by every major health agency. Prescribed by the millions. Marketed as safe and non-addictive. Yet within a decade, it transformed from miracle drug into Britain's deadliest prescription medication.

NB: Pregabalin is handy for opioid withdrawals.

i=vo6j_EoDy9q5Dp1F

70

Cannabis and Cannabinoids / Brain Imaging Study Reveals Cannabis Impact on Working Memory

« Last post by Chip on February 17, 2026, 06:00:44 AM »

https://neurosciencenews.com/cannabis-working-memory-neuroscience-30126/

Brain Imaging Study Reveals Cannabis Impact on Working Memory

February 16, 2026

Summary: While recent research has suggested potential neuroprotective benefits for older adults, a new study, the largest brain imaging study of its kind, highlights a significant downside for young adults. Examining over 1,000 participants aged 22 to 36, researchers found that heavy cannabis use (defined as 1,000+ lifetime uses) is linked to reduced brain activity in regions critical for decision-making and attention.

Specifically, 63% of heavy lifetime users and 68% of recent users showed diminished neural response during working memory tasks. These findings suggest that while cannabis effects may vary across a lifespan, frequent use during early adulthood can impair the “mental workspace” needed to retain and manipulate information for everyday problem-solving.

Key Facts

The Study Scope: This is the largest study to use functional MRI (fMRI) to examine how cannabis specifically impacts the neural networks involved in working memory.

Working Memory Deficit: Working memory—the ability to hold and use information (like following multi-step directions)—was the only cognitive domain out of seven tested to show a statistically significant decline.

Brain Activity Reduction: Heavy users showed lower activity in the dorsolateral prefrontal cortex and the anterior insula, hubs responsible for executive control and emotional processing.

The 1,000-Use Threshold: The most pronounced impairments were observed in “heavy users” who had consumed cannabis more than 1,000 times in their lifetime.

Reversibility Potential: Preliminary data suggest that abstaining from use before a cognitive task could help improve performance, offering hope for recovery through behavioral changes.

A new study published today in JAMA Network Open explores the effects of both recent and lifetime cannabis use on brain function during cognitive tasks.

The study, the largest of its kind ever to be completed, examined the effects of cannabis use on over 1,000 young adults aged 22 to 36 using brain imaging technology. The researchers found that 63% of heavy lifetime cannabis users exhibited reduced brain activity during a working memory task, while 68% of recent users also demonstrated a similar impact.

This decline in brain activity was associated with worse performance on working memory – the ability to retain and use information to perform tasks. For example, working memory allows a person to follow instructions they’ve just been given or to mentally visualize and manipulate information, like solving a math problem.

‘Make informed decisions’

“As cannabis use continues to grow globally, studying its effects on human health has become increasingly important. By doing so, we can provide a well-rounded understanding of both the benefits and risks of cannabis use, empowering people to make informed decisions and fully comprehend the potential consequences,” said the study’s first author Joshua Gowin, PhD, assistant professor of radiology at the University of Colorado School of Medicine on the University of Colorado Anschutz Medical Campus.

In the study, heavy users are considered young adults who’ve used cannabis more than 1000 times over their lifetime. Whereas, using 10 to 999 times was considered a moderate user and less than 10 times was considered a nonuser.

The researchers then studied the neural response of participants during a magnetic resonance imaging (MRI) session and gave them seven cognitive tasks to complete. The tasks tested working memory, reward, emotion, language, motor skills – such as tapping a finger to map brain control, relational assessment and theory of mind.

Statistically significant effect on brain function
The researchers found that cannabis had a statistically significant effect on brain function during working memory tasks, meaning the observed impact is very unlikely to be due to random chance. This effect was seen in both recent and lifetime cannabis users. The impact was less significant for the other tasks.

“We applied the highest standards to our research, setting rigorous thresholds for statistical significance across all seven cognitive function tests. To minimize the risk of false positives, we employed false discovery rate (FDR) correction. While some of the other tasks indicated potential cognitive impairment, only the working memory task showed a statistically significant impact,” adds Gowin.

During working memory tasks, the researchers found heavy cannabis use appeared to reduce brain activity in certain areas of the brain (dorsolateral prefrontal cortex, dorsomedial prefrontal cortex and anterior insula). These regions of the brain are involved in important cognitive functions such as decision-making, memory, attention and emotional processing.

However, Gowin mentions their research also suggests that abstaining from using cannabis before doing a cognitive task could help to improve performance. “People need to be aware of their relationship with cannabis since abstaining cold turkey could disrupt their cognition as well. For example, heavy users may need to be more cautious,” Gowin says.

He adds, “There are a lot of questions we still need answers to regarding how cannabis impacts the brain. Large, long-term studies are needed next to understand whether cannabis use directly changes brain function, how long these effects last and the impact on different age groups.”

Key Questions Answered:

Q: What exactly is “working memory”?

A: Think of it as your brain’s “sticky note.” It’s the ability to hold a thought while you’re doing something else—like remembering the first half of a sentence while you finish reading the second, or keeping a phone number in your head while you look for a pen.

Q: Why is this study different from the one about older adults?

A: Context is everything. This study focused on young adults (22–36). The brain is still highly plastic in this age range, and frequent use may “blunt” the activity of executive networks. In older adults, the same substance might interact differently with a brain that is already facing age-related decline.

Q: Is the damage permanent?

A: The study noted that abstaining before tasks might improve performance, which suggests the impact is functional (how the brain works) rather than purely structural (the brain’s physical shape). More long-term research is needed to see how long it takes for the brain to “re-calibrate” after quitting.

If you need any help or a chat then IM/PM or email me, Chip