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
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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.
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/