Deep Seek

Deep seek

Naturally, phenomenology and neuroscience find a convergence of common interests. However, primarily because of ontological disagreements between phenomenology and philosophy of mind, the dialogue between these two disciplines is still a very controversial subject.[9]

Husserl himself was very critical towards any attempt to “naturalizing” philosophy, and his phenomenology was founded upon a criticism of empiricism, “psychologism“, and “anthropologism” as contradictory standpoints in philosophy and logic.[10][11] The influential critique of the ontological assumptions of computationalist and representationalist cognitive science, as well as artificial intelligence, made by philosopher Hubert Dreyfus has marked new directions for integration of neurosciences with an embodied ontology.

The work of Dreyfus has influenced cognitive scientists and neuroscientists to study phenomenology and embodied cognitive science and/or enactivism. One such case is neuroscientist Walter Freeman, whose neurodynamical analysis has a marked Merleau-Pontyian approach.[12]

Wiki Dreyfus <  Knowing-how and knowing-that. Research in psychology and economics has been able to show that Dreyfus’ (and Heidegger’s) speculation about the nature of human problem solving was essentially correct. Daniel Kahnemann and Amos Tversky collected a vast amount of hard evidence that human beings use two very different methods to solve problems, which they named “system 1” and “system 2”. System one, also known as the  adaptive unconscious, is fast, intuitive and unconscious. System 2 is slow, logical and deliberate.

PD und so weider

Parkinson’s disease

Parkinson’s disease

Parkinson’s Disease: Gene Therapies

Calcium channel blocker

When more than 20 mg of simvastatin, a lipid-lowering agent, are given with amlodipine, the risk of myopathy increases.[40] The FDA issued a warning to limit simvastatin to a maximum dose of 20 mg if taken with amlodipine based on evidence from the SEARCH trial.[41] Giving amlodipine with Viagra increases the risk of hypotension.[7][10 < wiki amlodipine

The prion hypothesis suggests that alpha-synuclein aggregates are pathogenic and can spread to neighboring, healthy neurons and seed new aggregates. Some propose that the heterogeneity of PD may stem from different “strains” of alpha-synuclein aggregates and varying anatomical sites of origin

The incidence rate of falls in Parkinson’s patients is approximately 45 to 68%, thrice that of healthy individuals, and half of such falls result in serious secondary injuries. Falls increase morbidity and mortality.[227]Around 90% of those with PD develop hypokinetic dysarthria, which worsens with disease progression and can hinder communication.[228]Additionally, over 80%

of PD patients develop dysphagia: consequent inhalation of gastric and oropharyngeal secretions can lead to aspiration pneumonia.[229] Aspiration pneumonia is responsible for 70% of deaths in those with PD.[230]

< wiki

Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system[1] and is characterized by poor articulation of phonemes.[2] It is a condition in which problems effectively occur with the muscles that help produce speech, often making it very difficult to pronounce words

For instance, English philosopher Thomas Hobbes was diagnosed with “shaking palsy”—assumed to have been Parkinson’s—but continued writing works such as Leviathan.[289][290][291] Adolf Hitler is widely believed to have had Parkinson’s, and the condition may have influenced his decision making.[292][293][294] Mao Zedongwas also reported to have died from the disorder.[295]

https://en.wikipedia.org/wiki/Gene_therapy_in_Parkinson%27s_disease

https://en.wikipedia.org/wiki/Cell-based_therapies_for_Parkinson%27s_disease

https://en.wikipedia.org/wiki/Management_of_Parkinson%27s_disease#

https://en.m.wikipedia.org/wiki/Hypernasal_speech

The new treatments for PD are in clinical trials and most of them are centered on gene therapy. With this, researchers expect to compensate the loss of dopamine or to protect the dopamine neurons from degeneration.[2] The pharmacological and surgical therapies for PD focus on compensating the ganglia dysfunction caused by the degeneration of the dopaminergic neuron from substantia nigra

As the gut microbiome in PD is often disrupted and produces toxic compounds, fecal microbiota transplants might restore a healthy microbiome and alleviate various motor and non-motor symptoms.[300] Neurotrophic factorspeptides that enhance the growth, maturation, and survival of neurons—show modest results but require invasive surgical administration. Viral vectors may represent a more feasible delivery platform.[304] Calcium channel blockers may be restore the calcium imbalance present in Parkinson’s, and are being investigated as a neuroprotective treatment.[305] Other therapies, like deferiprone, may reduce the abnormal accumulation of iron in PD.[305]

 

Notes on Pollan, The Botany of desire

Notebook Export
The Botany of Desire: A Plant’s-Eye View of the World
Pollan, Michael
Citation (Chicago Style): Pollan, Michael. The Botany of Desire: A Plant’s-Eye View of the World. Random House Publishing Group, 2001. Kindle edition.

Introduction
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All those plants care about is what every being cares about on the most basic genetic level: making more copies of itself.
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Design in nature is but a concatenation of accidents, culled by natural selection until the result is so beautiful or effective as to seem a miracle of purpose.
Chapter 1
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Apples were something people drank. The reason people in Brilliant wanted John Chapman to stay and plant a nursery was the same reason he would soon be welcome in every cabin in Ohio: Johnny Appleseed was bringing the gift of alcohol to the frontier.
Chapter 3
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These ingredients would be combined in a hempseed-oil-based “flying ointment” that the witches would then administer vaginally using a special dildo. This was the “broomstick” by which these women were said to travel.
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(ethnobotanists call them “entheogens,” meaning “the god within”)
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The literary critic David Lenson, for one, believes it was crucial. He argues that Samuel Taylor Coleridge’s notion of the imagination as a mental faculty that “dissolves, diffuses, dissipates, in order to re-create,” an idea whose reverberations in Western culture haven’t yet been stilled, simply cannot be understood without reference to the change in consciousness wrought by opium.
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‘dissolution, diffusion and dissipation’
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One of the things certain drugs do to our perceptions is to distance or estrange the objects around us, aestheticizing the most commonplace things until they appear as ideal versions of themselves. Under the spell of cannabis “every object stands more clearly for all of its class,” as David Lenson writes in On Drugs. “A cup ‘looks like’ the Platonic Idea of a cup, a landscape looks like a landscape painting, a hamburger stands for all the trillions of hamburgers ever served, and so forth.” A psychoactive plant can open a door onto a world of archetypal forms,
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Allen Ginsberg suggested that the negative feelings marijuana sometimes provokes, such as anxiety, fear, and paranoia, are “traceable to the effects on consciousness not of the narcotic but of the law.”
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Taking account of this phenomenon, Andrew Weil describes marijuana as an “active placebo.”
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In 1988 Allyn Howlett, a researcher at the St. Louis University Medical School, discovered a specific receptor for THC in the brain—a type of nerve cell that THC binds to like a molecular key in a lock, causing it to activate.
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The cannabinoid receptors Howlett found showed up in vast numbers all over the brain (as well as in the immune and reproductive systems), though they were clustered in regions responsible for the mental processes that marijuana is known to alter: the cerebral cortex (the locus of higher-order thought), the hippocampus (memory), the basal ganglia (movement), and the amygdala (emotions). Curiously, the one neurological address where cannabinoid receptors didn’t show up was in the brain stem, which regulates involuntary functions such as circulation and respiration.
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Raphael Mechoulam (working with a collaborator, William Devane) found it: the brain’s own endogenous cannabinoid. He named it “anandamide,” from the Sanskrit word for “inner bliss.”
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some of the various direct and indirect effects of cannabinoids: pain relief, loss of short-term memory, sedation, and mild cognitive impairment.
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The purpose of THC could be to protect cannabis plants from ultraviolet radiation; it seems that the higher the altitude at which cannabis grows, the more THC it produces. THC also exhibits antibiotic properties, suggesting a role in protecting cannabis from disease. Last, it’s possible that THC gives the cannabis plant a sophisticated defense against pests. Cannabinoid receptors have been found in animals as primitive as the hydra, and researchers expect to find them in insects. Conceivably, cannabis produces THC to discombobulate the insects (and higher herbivores) that prey on the plant; it might make a bug (or a buck or a rabbit) forget what it’s doing or where in the world it last saw that tasty plant.
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Ma, the ancient Chinese character for “hemp,” depicts a male and a female plant under a roof—cannabis inside the house of human culture.
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Cognitive dysfunction?
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The scientists I spoke to were unanimous in citing short-term memory loss as one of the key neurological effects of the cannabinoids.
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All talk about the difficulty of reconstructing what happened mere seconds ago and what a Herculean challenge it becomes to follow the thread of a conversation (or a passage of prose) when one’s short-term memory isn’t operating normally.
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Yes, forgetting can be a curse, especially as we age. But forgetting is also one of the more important things healthy brains do, almost as important as remembering. Think how quickly the sheer volume and multiplicity of sensory information we receive every waking minute would overwhelm our consciousness if we couldn’t quickly forget a great deal more of it than we remember.
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“If we could hear the squirrel’s heartbeat, the sound of the grass growing, we should die of that roar,” George Eliot once wrote.
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The first part of Nietzsche’s essay is a moving and occasionally hilarious paean to the virtues of forgetting, which he maintains is a prerequisite to human happiness, mental health, and action.
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Like the American transcendentalists, Nietzsche believes that our personal and collective inheritance stands in the way of our enjoyment of life and accomplishment of anything original.
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My lawyer father, once complimented on his ability to see ahead three or four moves in a negotiation, explained that the reason he liked to jump to conclusions was so he could get there early and rest. I’m the same way in my negotiations with reality.
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Colors,” in classical rhetoric, are tropes.)
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Sagan, who was convinced that marijuana’s morning-after problem is not a question of self-deception so much as a failure to communicate—to put “these insights in a form acceptable to the quite different self that we are when we’re down the next day.”
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Memory is the enemy of wonder, which abides nowhere else but in the present. This is why, unless you are a child, wonder depends on forgetting—on a process, that is, of subtraction. Ordinarily we think of drug experiences as additive—it’s often said that drugs “distort” normal perceptions and augment the data of the senses (adding hallucinations, say), but it may be that the very opposite is true—that they work by subtracting some of the filters that consciousness normally interposes between us and the world.
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From a brain’s point of view, the distinction between a natural and an artificial high may be meaningless.

Hippocampus

Remapping revisited: how the hippocampus represents different spaces

André A. Fenton

Nature Reviews Neuroscience  volume 25, pages 428–448 (2024

  https://www.nature.com/articles/s41583-024-00817-x

Yassa, M.A., Stark, C.E.L. (2011) Pattern separation and the hippocampus. Trends in Neuroscience 34(10):515-525

Leal, S.L., Yassa, M.A. (2015) Neurocognitive aging and the hippocampus across species. Trends in Neurosciences 38(12): 800–812.

UC Irvine – Faculty Profile System

Remission from addiction: erasing the wrong circuits or making new ones? – Nature Reviews Neuroscience

 Time, Space and Memory  in the Hippocampal Formation, Derdikman et al.

This will come to you out of the blue. 

I am a 79 yo who retired in 2009 as Dean of Arts at uOttawa. I am also a PwP. Hence my interest in your lecture, which I shall attend with my wife, Nasrin Rahimieh, Associate Dean of Humanities for Academic Personal.

As a (concerned) amateur, I have been reading much popular neuroscience of late, including Erich Kandel, In Search of Memory; Linder,  The Accidental  Mind; MacDermott, 101 Theory Drive; and Brahic, The Power of Prions.

Also, I’ve written a blog piece on what happens when you have classic Parkinson’s, which I link here for what it’s worth: https://alteritas.net/GXL/?p=5189.

Could you suggest an article or two I should read before attending the Feb 4 lecture? I would be much obliged. 

George Lang 

THC and ECS

THC  

https://pmc.ncbi.nlm.nih.gov/articles/PMC6223748/ >>

THC elicits striatal DA release by activating CB1R, which are co-localized with DA receptors in the striatum and substantia nigra, regions implicated in salience processing (Wijayendran et al. 2016). This suggests that the endocannabinoid system (eCS) is involved in regulating DA release during salience attribution (Bloomfield et al. 2016), and that acute THC dysregulates the dopaminergic and endocannabinoid systems which then leads to impairments in salience processing (Wijayendran et al. 2016). These preclinical findings may provide a biological basis for human studies which show impaired salience processing after THC administration. In one study

As described in the Koob and Volkow model (2016), most drugs of abuse result in the hyperactivation of the mesocorticolimbic dopaminergic reward pathway in the binge-intoxication stage of addiction. This hyperactivation seems to be present in cannabis addiction but to a lower extent. Acute THC administration elicits striatal DA release in animals (Bloomfield et al. 2016) and THC challenges were shown to increase striatal DA transmission in humans (Stokes et al. 2010; Bossong et al. 2015); although other studies have found no THC-induced increases in striatal DA (Barkus et al. 2011; Urban et al. 2012). Additionally, there are no baseline differences in dopamine D2/D3 receptor availability between cannabis users and healthy controls (Volkow et al. 2014c; van de Giessen et al. 2017), a finding that does not parallel addiction to other drugs of abuse (including cocaine, alcohol, methamphetamine, nicotine, or heroin) which is associated with substantial reductions in D2R availability in the ventral striatum (Wang et al. 1997; Volkow et al. 2001, 2014c, 2017c; Martinez et al. 2012; Albrecht et al. 2013; Tomasi et al. 2015a; Wiers et al. 2016a; Ashok et al. 2017)

  

In addition, chronic cannabis use has been linked to impaired memory and IQ,suggesting changes in executive functioning after chronic cannabis use. However, IQ deficits appear to be present before initiation of cannabis use which may suggest that lower IQ could be a risk factor for cannabis addiction (Jackson et al. 2016).

 

 cannabis use disorder (CUD)

Dopamine = DA

https://www.apa.org/monitor/2023/06/marijuana-effects-brain

<< 

Researchers at the University of Colorado also found evidence that cannabis may be beneficial for older adults who start using later in life. MRI data showed that users had stronger connectivity than nonusers between parts of the brain that are important for cognitive functions, such as working memory and coordination (Watson, K. K., et al., Frontiers in Aging Neuroscience, Vol. 14, 2022). “Cannabis use could be offsetting normal age-related cognitive decline,” said Rachel Thayer, PhD, an assistant professor of neuropsychology at the University of Colorado, Colorado Springs.

 https://www.cambridge.org/core/journals/journal-of-the-international-neuropsychological-society/article/abs/female-sex-as-a-protective-factor-in-the-effects-of-chronic-cannabis-use-on-verbal-learning-and-memory/437D670F390B4A96B05888FBDFB85C46

 Conclusions:

Results suggest that chronic cannabis use differentially impacts males and females, with females exhibiting better verbal learning and memory despite males demonstrating better attention and cognitive flexibility. Further research is needed to understand the potential protective mechanism of female sex on learning and memory effects of cannabis use.

  

https://www.apa.org/monitor/2015/11/marijuana-brain >>   Also immature in teens is the endocannabinoid system. As its name implies, this system  comprises the physiological mechanisms that respond to THC. That system is important for cognition, neurodevelopment, stress response and emotional control, and it helps to modulate other major neurotransmitter systems, says Krista Lisdahl, PhD, director of the Brain Imaging and Neuropsychology Laboratory at the University of Wisconsin, Milwaukee

Wiki endocannabinoids https://en.wikipedia.org/wiki/Endocannabinoid_system >>

Endocannabinoids are similar to the cannabinoids present in the cannabis sativa (C. sativa) plant. However, the human body naturally produces endocannabinoids. The term “endo” refers to “within,” as in within the body.

example, in rodents, the highest concentration of cannabinoid binding sites are in the basal ganglia and cerebellum, regions of the brain involved in the initiation and coordination of movement.[29] In humans, cannabinoid receptors exist in much lower concentration in these regions, which helps explain why cannabinoids possess a greater efficacy in altering rodent motor movements than they do in humans.

Mice treated with tetrahydrocannabinol (THC) show suppression of long-term potentiation in the hippocampus, a process that is essential for the formation and storage of long-term memory.[52] These results may concur with anecdotal evidence suggesting that smoking cannabis impairs short-term memory.[53] Consistent with this finding, mice without the CB1 receptor show enhanced memory and long-term potentiation indicating that the endocannabinoid system may play a pivotal role in the extinction of old memories?

In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity.[1] Since memories are postulated to be represented by vastly interconnected neural circuits in the brain, synaptic plasticity is one of the important neurochemical foundations of learning and memory (see Hebbian theory).

Evidence for the role of the endocannabinoid system in food-seeking behavior comes from a variety of cannabinoid studies. Emerging data suggests that THC acts via CB1 receptors in the hypothalamic nuclei to directly increase appetite.[59

In considering the efficacy of cannabis-based products, there remains controversy surrounding a concept termed “the entourage effect”. This concept describes a widely reported but poorly-understood synergistic effect of certain cannabinoids when phytocannabinoids are coadministered with other naturally-occurring chemical compounds in the cannabis plant (e.g., flavonoids, terpenoids, alkaloids). This entourage effect is often cited to explain the superior efficacy observed in some studies of whole-plant-derived cannabis therapeutics as compared to isolated or synthesized individual cannabis constituents.[14]

 https://en.m.wikipedia.org/wiki/Portal:Cannabis

 https://www.healthline.com/health/endocannabinoid-system#functions <<

Today, experts believe that maintaining homeostasis if the primary role of the ECS.

https://www.mdpi.com/1422-0067/19/3/833

https://www.health.harvard.edu/blog/the-endocannabinoid-system-essential-and-mysterious-202108112569

<To stimulate these receptors, our bodies produce molecules called endocannabinoids, which have a structural similarity to molecules in the cannabis plant. The first endocannabinoid that was discovered was named anandamide after the Sanskrit word ananda for bliss. All of us have tiny cannabis-like molecules floating around in our brains. The cannabis plant, which humans have been using for about 5,000 years, essentially works its effect by hijacking this ancient cellular machinery

https://pmc.ncbi.nlm.nih.gov/articles/PMC6513728/  

< According to the popular writer Michael Pollan in his bestselling book The Botany of Desire, cannabis is one of the plants that humans have cultivated, or co-evolved with, for thousands of years. This is in part, Pollan writes, because the act of forgetting plays a valuable role in the ability of our brains to function without being overloaded with data from our senses that we are continually bombarded with. Pollan hypothesizes that if we didn’t forget, we wouldn’t function, and cannabis helps us do this. The role that the ECS plays in forgetting also opens up opportunities for the treatment of PTSD, a condition in which there are unpleasant, intrusive memories that people can’t help but remember, and that cause a whole syndrome of troublesome and dangerous symptoms related to the pathological remembering.

The ECS regulates and controls many of our most critical bodily functions such as learning and memory, emotional processing, sleep, temperature control, pain control, inflammatory and immune responses, and eating.

https://pmc.ncbi.nlm.nih.gov/articles/PMC6513728/