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MDMA’s effect on the brain – wikipedia notes
The effects of MDMA (3,4-methylenedioxy-N-methylamphetamine, commonly known as “ecstasy”) on the human brain and body are complex, interacting with several neurochemical systems. It induces serotonin, dopamine, and norepinephrine release, and can act directly on a number of receptors, including a2-adrenergic (adrenaline) and 5HT2A(serotonin) receptors[1]. MDMA promotes the release of several hormones including prolactin, oxytocin, ACTH, dehydroepiandrosterone (DHEA), and the antidiuretic hormone vasopressin (which may be important in its occasional production of water intoxication or hyponatremia).
It’s not fully understood why MDMA induces these unusual psychoactive effects. Most explanations focus on serotonin release. MDMA causes serotonin vesicles in the neurons to release quantities of serotonin into the synapses. Studies using pretreatment with an SSRI to block the ability of MDMA to release serotonin in volunteers suggest serotonin release is necessary for most effects of MDMA in humans.[2] Released serotonin is believed to stimulate several receptors that contribute to the experiential effects of MDMA. Laboratory rodent experiments have shown MDMA to activate oxytocin-containing neurons in the hypothalamus by stimulating 5-HT1A receptors.[3] This appears to contribute to some of the social effects of MDMA: upon administering a drug that blocked brain receptors for oxytocin, the effects of the drug on social behavior were reduced.[4] A second serotonin receptor, 5-HT2A receptors (which are important for the effects of hallucinogens), makes mild contributions to MDMA effects. When the receptor was blocked, volunteers given MDMA reported decreases in MDMA-induced perceptual changes, emotional excitation, and acute adverse responses [5]. In contrast, blocking these 5-HT2A receptors had little effect on MDMA-induced positive mood, well-being, extroversion, and most short-term sequelae. One possible explanation for some of these 5-HTA-mediated effects is that 5-HT2A stimulation induces dopamine release.
Although serotonin is important to the effects of MDMA, other drugs that release serotonin, such as fenfluramine, do not have effects like MDMA.[6] This indicates that other neurochemical systems must be important for the MDMA experience. In addition to serotonin, dopamine and noradrenaline may play important roles in producing MDMA effects. The dopaminergic D2 receptor antagonist haloperidol selectively reduced the euphoric effects of MDMA in volunteers while increasing feelings of anxiety.[7] Although not yet examined in humans, several studies in rodents, indicate the noradrenergic mechanisms contribute to the stimulating effects of MDMA.[8] Finally, currently unexplored effects of MDMA may turn out to be important, such as trace amine receptors.[9]
The effects of MDMA on regional cerebral blood flow (CBF) have been studied in humans using [H215O]-Positron Emission Tomography (PET)[10] MDMA was found to produce alteration of brain activity in cortical, limbic, and paralimbic structures. The dose of MDMA, 1.7 mg/kg, was psychoactive and participants reported heightened mood, increased extroversion, feelings of altered reality, and mild perceptual alterations. Feelings of “extraversion” correlated with CBF in the temporal cortex, amygdala, and orbitofrontal cortex.
Effects beginning after the main effects of MDMA have ended, which can last several days, include:
- Lowered mood or even depression (comedown) after the effects have worn off
- Increased anxiety, stress, and other negative emotions
- Residual feelings of empathy, emotional sensitivity, and a sense of closeness to others (afterglow)
short-term effects
Acute physiological effects include:[14]
- Increased heart rate and blood pressure
- Increased body temperature
- Increased perspiration and sweating
- Pupil dilation
- Blurred vision
- Nystagmus (rapid involuntary eye movements and jittering)
- Trisma (jaw-clenching) and bruxia (grinding of the teeth)
- Difficulty sleeping
- Loss of appetite
- Nausea and emesis
Hyponatremia
An important cause of death following MDMA use is hyponatremia, low blood sodium levels as a result of drinking too much water.[20] While it is important to avoid becoming dehydrated, especially when out dancing in a hot environment, there have been a number of users suffering from water intoxication and associated hyponatremia (dilution of the blood that can cause swelling of the brain).[21] Although many cases of this clearly involved individuals drinking large amounts of water, there are cases where there is no evidence of excessive water consumption. Their cases may be caused by MDMA inducing release of the antidiuretic hormone vasopressin by the pituitary gland.[22] The action of vasopressin on the renal tubules leads to the retention of water, resulting in users producing less urine. (This is unrelated to having difficulty passing urine, a phenomenon known colloquially as E-wee).[23] Hyponatremia also affects marathon runners and bodybuilders, who have been known to die from similar causes, as a result of drinking too much water and sweating out too much salt. It affects women more than men.
Hyponatremia is preventable by drinking fluid containing sodium, such as that contained in sports drinks (typically ~20mM NaCl).[24]
[edit] Hyperthermia
The primary acute risks of taking MDMA resemble those of other stimulant amphetamines. The second most important cause of death from MDMA use is hyperthermia, core body temperature rising too high until the major organs shut down at about 42°C. This is comparatively more problematic than blood salt imbalance, harder to treat and to avoid. Ecstasy-related hyperthermia may occur as a symptom of serotonin syndrome, which is where too much serotonin is released into the brain. This can occur with MDMA if too much 5HTP or other serotonergic drugs are consumed together. 50–200 mg of 5HTP is believed by some users to make MDMA work better and last longer, but anecdotally more than 300 mg 5HTP may increase risk of serotonin syndrome[citation needed], which can lead into lethal hyperthermia if it becomes too severe. It has been suggested that hyperthyroidism may also increase risk of ecstasy-related hyperthermia.[25]
Note that this is different from normal hyperthermia. Dance parties are an obvious hyperthermia risk environment, the venue often being hot and crowded, and the attending public dancing whilst on stimulant drugs. Ideally the temperature inside the dance rooms should be maintained in the range 24–27°C; ecstasy affects the body’s ability to regulate temperature and it is easy to become either too hot or too cold if the temperature is outside of this range.
Mild hyperthermia and/or dehydration can occur from dancing too long, and users may recover with administration of fluids and rest in a cooler environment. However, if the user expresses concern about how hot they feel, or if their body temperature is still rising even when they have stopped dancing and are in a cooler environment, and their skin is hot and dry to the touch, then they may be developing more dangerous drug-induced hyperthermia, and these cases should be taken to and handled by a medical professional immediately.
Overdose
Due to the difference between the recreational dose and the lethality dose, it is extremely rare for a death to be accredited just to the consumption of MDMA. While a typical recreational dose is roughly 100–150 mg (often being measured by eye and dealt with as fractions of a gram), this dose is often then repeated but remains well below the lethal dose. Consumption of the drug can be self-reinforcing while under the influence, and overdoses can occur. People who are grossly obese, or who have diabetes, high blood pressure or heart conditions have a greater risk of overdose death from any stimulant, and should generally avoid MDMA and similar drugs.In very rare cases, MDMA has been associated with serious neurological problems such as subarachnoid hemorrhage, intracranial bleeding, or cerebral infarction. Similar problems have been noted with amphetamines. The mechanisms are thought to involve the short-term hypertension leading to damage of cerebral blood vessels, especially in patients with pre-existing conditions such as arteriovenous malformations or cerebral angiomas.
Serotonergic changes
Experiments indicate that both moderate and high dose or rapidly repeated MDMA exposure may lead to long-lasting changes in neurons that make serotonin. Serotonergic changes have been demonstrated experimentally in the brains of all mammalian species studied, with most studies involving rats. In these studies, the brains of animals who are given high or repeated doses of MDMA show long-term decreases in all measures of serotonergic functioning, including concentrations of serotonin, tryptophan hydroxylase, and binding of the serotonin transporter protein. Although measures of serotonin are decreased, there are no decreases in the number of cells in the dorsal raphe, which indicates that the serotonin neurons have not died. Limited studies attempting to stain and photograph serotonergic axons shortly after high-dose MDMA exposure have reported that axons appear swollen and misshapen, as if they might be degenerating. However, few studies have attempted to stain and examine axons and with the measures commonly used in MDMA studies it is difficult or impossible to distinguish axon loss from decreases in production of markers of serotonin.[41][42]
Animal studies show that there is recovery of serotonergic markers. However, if axons are actually regrowing, there is no assurance that they will reform their original connections. While rats show extensive recovery that sometimes appears complete [43][44], some primate studies show evidence of lasting alterations in serotonergic measures. Human studies, discussed below, show recovery, but these studies use indirect measures that may lack sensitivity for detecting subtle changes.
It is not known what dose(s) of MDMA would produce similar toxic effects in humans. This is because there are some difficulties in translating animal MDMA toxicity studies to humans. Firstly, it is difficult to equate rat doses to human doses, because rats metabolize MDMA twice as fast as humans and often larger doses or multiple doses are administered to simulate human plasma levels. Second, if the neurotoxicity of MDMA depends on its metabolites (Jones 2004;[45]), it may be difficult or impossible to translate an MDMA dose between species since different species metabolize MDMA to different extents. Therefore, it is difficult to say what dose in humans would produce the effects seen in animals.
Keeping these limitations in mind, comparisons of MDMA exposures can be made between animal neurotoxicity studies and human clinical studies. One (uncertain) estimate suggests that the neurotoxic dose may be only moderately higher than amounts given in clinical studies (1.5 or 1.7 mg/kg, about 100 or 120 mg).[46] That published comparison was made based on data from rats.
Further comparisons can be made using monkey data. In a recent study by Mechan et al. (2006), the lowest repeated dose regimen that produced serotonergic effects, detectable after 2 weeks, in squirrel monkeys was 2.4 mg/kg given orally three times in a row (every 3 hours). The peak plasma MDMA concentrations seen after that dose was 787 ± 129 ng/ml (mean ± SEM, range: 654 to 1046 ng/ml) and the area-under-the-concentration-vs-time-curve (AUC, a measure of overall drug exposure) was 3451 ± 103 hr*ng/ml. In comparison, 1.6 mg/kg oral (112 mg in a 70 kg / person) in humans produces peak MDMA concentrations of 291.8 ± 76.5 ng/ml (range: 190 – 465 ng/ml) and an AUC of 3485.3 ± 760.1 hr*ng/ml (Kolbrich et al. 2008). Thus, a typical human dose produces peak MDMA concentrations that are about 37% of a known neurotoxic dose and has a very similar AUC. Because MDMA has nonlinear kinetics, it is likely that fewer than three of these doses would be needed to produce an exposure in humans greater than the dose schedule that produced decreased brain serotonin and decreased serotonin transporter binding in monkeys.
[edit] Mechanisms of serotonergic changes
The mechanism proposed for this apparent neurotoxicity involves the induction of oxidative stress. This stress results from an increase in free radicals and a decrease in antioxidants in the brain. (Shankaran, 2001) Oxidation is part of the normal metabolic processes of the body. As the cell goes about its life, by-products called oxidative radicals are formed, also called free radicals. These molecules have an unpaired electron that makes them highly reactive. They pull strongly on the electrons of neighboring molecules and destabilize the electrical balance of those molecules, sometimes causing those molecules to fall apart. This can become a chain reaction.
In normal functioning, there are antioxidants in the system that act as free radical scavengers. These are molecules with an extra electron that they are willing to give up to the free radicals, making both the free radical and the antioxidant more stable. MDMA rapidly increases the levels of free radicals in the system, which is thought to overwhelm the reserves of scavengers. The radicals then damage cell walls, reduce the flexibility of blood vessels, destroy enzymes, and cause other molecular damage in the neurological pathways. (Erowid, 2001) It has been shown that MDMA’s neurotoxic effects in rodents are increased by a hyperthermic environment and decreased by a hypothermic one. (Yeh, 1997)
Studies have suggested that the neurotoxic molecules are not hydroxyl free radicals, but superoxide free radicals. When rats are injected with salicylate, a molecule that scavenges hydroxyl free radicals, the neurotoxic effects of MDMA are not attenuated, but actually potentiated. Further evidence of this superoxide theory comes from the observation that CuZn-superoxide dismutase transgenic mice (mice with excess human antioxidant enzyme) demonstrate neuroprotective mechanisms that protect the mice from MDMA-induced depletion of 5-HT (serotonin) and 5-HIAA and lethal effects. (Baggott, 2001 and Yeh, 1997)
MDMA itself does not seem to be neurotoxic as infusing it into an animal’s brain does not produce long-term serotonergic changes. This suggests that another molecule may be triggering the oxidative stress. Different scientists have suggested that either a dopamine or an MDMA metabolite (such as 3,4-dihydroxy-methamphetamine) might be important for initiating the cascade of oxidative stress. However, no consensus has emerged as of yet.
[edit] Possible neuroprotective strategies
There are a number of factors that have been shown to protect animals from long-term MDMA-induced serotonin changes. These include dose, temperature, antioxidants, and SSRIs. Some MDMA users have attempted to use analogous strategies to decrease their risks of long-term serotonin changes, although there is uncertainty as to how well this works in people[citation needed].
The most obvious strategy is reducing dose. Long-term serotonergic changes are dose dependent in animals. Taking higher or repeated doses of MDMA is therefore likely to increase chances of similar changes in people. Although the threshold dose to cause toxicity is unknown in humans, lower doses are almost certainly less risky[citation needed].
Studies in rats also find that environments or activities that increase the animals’ body temperature increase serotonergic changes. However, this finding has not been replicated in primates, possibly because rodents are less able to regulate body temperature than primates. Nonetheless, it is possible that higher body temperature also increases serotonergic changes in people[citation needed].
Antioxidants may decrease possible MDMA-induced serotonergic changes. Studies in rats have shown that injections of ascorbic acid, alpha lipoic acid, or some other radical scavengers are effective in reducing oxidative stress caused by MDMA. (Erowid, 2001) It has been speculated that humans may be able to similarly achieve protection using a combination of antioxidants, such as Vitamin A, C, and E or multivitamins including selenium, riboflavin, zinc, carotenoids, etc. may help reduce oxidative damage. No published studies have confirmed that this works. In addition, many of these vitamins, though, are water soluble, and are quickly excreted from the body. The typical MDMA user is psychoactive for 4–6 hours and may not have an appetite from the time of taking until the following sleep cycle or many hours later. Damage occurs in the absence of these antioxidants.Selective serotonin reuptake inhibitors (SSRIs) have been shown to decrease or block MDMA neurotoxicity in rodents, even if they are given several hours after MDMA. Because of this, some MDMA users administer an SSRI while, or shortly after taking MDMA, in an attempt to prevent possible neurotoxicity. These SSRIs are typically antidepressants such as fluoxetine or sertraline. The theory of some scientists[who?] is that SSRIs prevent dopamine or a neurotoxic MDMA metabolite from entering through the serotonin reuptake transporter, where it is theorized that it may contribute to formation of reactive oxygen species, including hydrogen peroxide. There are several concerns with taking SSRIs with MDMA. On a practical level, administration of SSRIs will block the desired effects of the drug if taken too early. This blocking effect can last several weeks, depending on the half-life of the SSRI. In addition, MDMA and the SSRI will often mutually reduce each other’s metabolism, causing them to last longer in the body. Theoretically, this might increase risk of overdosing on the SSRI, leading to serotonin syndrome. Although this appears to occur rarely (if ever), it is considered a theoretical possibility.
Evidence for serotonergic changes in humans
Studies have used positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging methods to estimate brain serotonin transporter levels in ecstasy users. These studies have found reduced levels of the transporter in recently abstinent MDMA users as well as evidence of partial or full recovery with prolonged abstinence. However, the sensitivity of these methods is unknown and changes may not have been detected. Three studies of 5-HT2A receptors in human MDMA users have been published by one group of researchers (Reneman and colleagues). Together, these studies find possibly reduced receptor binding during active MDMA use and increased receptor binding in longer-abstinent subjects. The authors argue that long-lasting reductions in 5-HT release may have caused compensatory up-regulation of 5-HT2A receptors. Other studies have measured cerebrospinal fluid concentrations of the serotonin metabolite 5HIAA. Three of four published studies have reported concentrations to be lower in ecstasy users than non-users.
One difficulty in interpreting these studies is that it is difficult to know if serotonergic differences predated MDMA use. In addition, none of these studies can address whether any changes are neurotoxicity proper or neuroadaptation. A recent review concluded that “the current state of neuroimaging in human MDMA users does not permit conclusions regarding the long-term effects of MDMA exposure”.[49]In addition, mood is sometimes found to be worse and impulsivity greater in ecstasy users. At least two meta-analyses of these studies have been completed (Morgan 2000; Sumnall & Cole 2005). Morgan’s analysis of 17 studies showed that ecstasy users had a slight tendency to be more impulsive and have lower mood than controls. Sumnall and Cole’s analysis showed a slight increase in the prevalence of depressive symptoms in ecstasy users over controls. (Mood measured in these studies does not indicate clinical levels of depression, which has not been associated with MDMA use.) Of course, studies like these raise a cause-consequence question: did these impulsive and depressed people use ecstasy to self-medicate or did otherwise normal people become depressed and impulsive after using ecstasy?[52][53][54]A recent important study (the NeXT Netherlands XTC toxicity study) prospectively examined 25 people before and after their first episode of ecstasy use (mean 2.0 ± 1.4 ecstasy pills, on average 11.1 ± 12.9 weeks since last ecstasy use). The study measured working memory, selective attention, and associative memory using fMRI. No significant effects were found of the reportedly modest dose(s) of ecstasy on any of these measures, suggesting that the first few exposures to ecstasy typically do not cause significant residual toxicity.[55] Thus, if ecstasy does cause cognitive-behavioral changes, it would likely require repeated use for these changes to occur (or become detectable). Contrary to this another recent report has shown that a single exposure to MDMA can result in cognitive-behavioral changes.
Addiction and tolerance
The potential of MDMA to produce addiction is controversial. Some studies indicate that many users may be addicted, but this depends on the definition of addiction; while many ecstasy users may take the drug regularly and develop significant tolerance to its effects, relatively few users exhibit cravings or physical symptoms of dependence, or find it difficult to stop using the drug when they decide to do so
PCP & the brain – notes & links
What Are the Effects of PCP?
From National Institute on Drug Abuse
Updated September 07, 2009
PCP, developed in the 1950s as an intravenous surgical anesthetic, is classified as a dissociative anesthetic: Its sedative and anesthetic effects are trance-like, and patients experience a feeling of being “out of body” and detached from their environment.
In powdered form, the drug is sprinkled on marijuana, tobacco, or parsley, then smoked, and the onset of effects is rapid. Users sometimes ingest PCP by snorting the powder or by swallowing it in tablet form. Normally a white crystalline powder, PCP is sometimes colored with water-soluble or alcohol-soluble dyes.
When snorted or smoked, PCP rapidly passes to the brain to disrupt the functioning of sites known as NMDA (N-methyl-D-aspartate) receptor complexes, which are receptors for the neurotransmitter glutamate. Glutamate receptors play a major role in the perception of pain, in cognition – including learning and memory – and in emotion. In the brain, PCP also alters the actions of dopamine, a neurotransmitter responsible for the euphoria and “rush” associated with many abused drugs.
At low PCP doses (5 mg or less), physical effects include shallow, rapid breathing, increased blood pressure and heart rate, and elevated temperature. Doses of 10 mg or more cause dangerous changes in blood pressure, heart rate, and respiration, often accompanied by nausea, blurred vision, dizziness, and decreased awareness of pain.
Muscle contractions may cause uncoordinated movements and bizarre postures. When severe, the muscle contractions can result in bone fracture or in kidney damage or failure as a consequence of muscle cells breaking down. Very high doses of PCP can cause convulsions, coma, hyperthermia, and death.
PCP’s effects are unpredictable. Typically, they are felt within minutes of ingestion and last for several hours. Some users report feeling the drug’s effects for days. One drug-taking episode may produce feelings of detachment from reality, including distortions of space, time, and body image; another may produce hallucinations, panic, and fear. Some users report feelings of invulnerability and exaggerated strength. PCP users may become severely disoriented, violent, or suicidal.
Repeated use of PCP can result in addiction, and recent research suggests that repeated or prolonged use of PCP can cause withdrawal syndrome when drug use is stopped. Symptoms such as memory loss and depression may persist for as long as a year after a chronic user stops taking PCP.
PCP was used in veterinary medicine but was never approved for human use because of problems that arose during clinical studies, including delirium and extreme agitation experienced by patients emerging from anesthesia.
Effects of Long Term Use 26
- “Runs” – Chronic users may binge use PCP, taking it repeatedly for 2 or 3 days at a time without eating or sleeping, followed by a period of sleep. These runs may occur as many as four times in a month.
- Impaired memory
- “Flashbacks” similar to those experienced by chronic LSD users
- Persistent speech problems, such as stuttering, inability to articulate, or the inability to speak at all
- Chronic and severe anxiety and depression, possibly leading to suicide attempts
- Social withdrawal and isolation
- Toxic psychosis may appear in chronic users who do not have a prior history of psychiatric disturbances. The symptoms of toxic psychosis are aggressive or hostile behavior, paranoia, delusional thinking and auditory hallucinations.
PCP and Violence
Despite its reputation in the media as a drug that causes bizarrely violent behavior and gives users superhuman strength, research does not support the idea that PCP itself is the cause of such behavior and strength. Instead, those who experience violent outbursts while under the influence of PCP often have a history of psychosis or antisocial behavior that may or may not be related to their drug abuse.27
black outs (notes)
Blackout (alcohol-related amnesia)
A blackout is a phenomenon caused by the intake of alcohol or other substance in which long term memory creation is impaired or there is a complete inability to recall the past. Blackouts are frequently described as having effects similar to that of anterograde amnesia, in which the subject cannot create memories after the event that caused amnesia. ‘Blacking out’ is not to be confused with the mutually exclusive act of ‘passing out‘, which means loss of consciousness. Research on alcohol blackouts was begun by E. M. Jellinek in the 1940s. Using data from a survey of Alcoholics Anonymous (AA) members, he came to believe that blackouts would be a good predictor of alcoholism.[1] However, there are conflicting views as to whether or not this is true.[2]
Alcohol and long-term memory
Various studies have also proven links between general alcohol consumption and its effects on memory creation.[3] Particularly, these studies have shown that associations made between words and objects when intoxicated are less easily recalled than associations made when not intoxicated. Later blackout-specific studies have indicated that alcohol specifically impairs the brain’s ability to take short-term memories and experiences and transfer them to long-term memory.[4]
It is a common misconception that blackouts generally occur only to alcoholics; research suggests that social drinkers, such as college students, are often at risk as well. In a 2002 survey of college students by researchers at Duke University Medical Center, 40% of those surveyed who had consumed alcohol recently reported having experienced a blackout within the preceding year.[5]
Types of blackouts
Blackouts can generally be divided into two categories, “en bloc” blackouts, and “fragmentary” blackouts. En bloc blackouts are classified by the inability to later recall any memories from the intoxicated period, even when prompted. These blackouts are characterized also by the ability to easily recall things that have occurred within the last 2 minutes, yet inability to recall anything prior to this period. As such, a person experiencing an en bloc blackout may not appear to be doing so, as they can carry on conversations or even manage to accomplish difficult feats. It is difficult to determine the end of this type of blackout as sleep typically occurs before they end.[6] Fragmentary blackouts are characterized by the ability to recall certain events from an intoxicated period, yet be unaware that other memories are missing until reminded of the existence of these ‘gaps’ in memory. This phenomenon is also termed a brownout. Research indicates that fragmentary blackouts, or brownouts are far more common than en bloc blackouts.[7]
Causes
Blackouts are commonly associated with the consumption of large amounts of alcohol; however, surveys of drinkers experiencing blackouts have indicated that they are not directly related to the amount of alcohol consumed. Respondents reported they frequently recalled having “drunk as much or more without memory loss”, compared to instances of blacking out.[6] Subsequent research has indicated that blackouts are most likely caused by a rapid increase in a person’s blood-alcohol concentration. One study, in particular, resulted in subjects being stratified easily into two groups, those who consumed alcohol very quickly, and blacked out, and those who did not black out by drinking alcohol slowly, despite being extremely intoxicated by the end of the study.[8]
Benzodiazepines
Benzodiazepines such as clonazepam (Klonopin), diazepam (Valium), and alprazolam (Xanax), which also act as GABA agonists, are known to cause blackouts as a result of high dose use.
Predisposition to blackouts
Research indicates that some users of alcohol, particularly those with a history of blackouts, are predisposed to experience blackouts more frequently than others.[9] One such study indicated a link between prenatal exposure to alcohol and vulnerability towards blackouts, in addition to the oft-cited link between this type of exposure and alcoholism.[10] Alternatively, another study has indicated that there appears to be a genetic predisposition towards blacking out, suggesting that some individuals are made to be susceptible to alcohol related amnesia.[11]
What Happened? Alcohol, Memory Blackouts, and the Brain
Aaron M. White, Ph.D.
Mechanisms underlying alcohol–induced memory impairments include disruption of activity in the hippocampus, a brain region that plays a central role in the formation of new auotbiographical memories.
In addition to impairing balance, motor coordination, decisionmaking, and a litany of other functions, alcohol produces detectable memory impairments beginning after just one or two drinks. As the dose increases, so does the magnitude of the memory impairments.
Early anecdotal evidence suggested that blackouts might actually reflect state–dependent information storage—that is, people might be able to remember events that occurred while they were intoxicated if they returned to that state. Regardless of how compelling such stories can be, clear evidence of state–dependent learning under the influence of alcohol is lacking. In one recent study, Weissenborn and Duka (2000) examined whether subjects who learned word lists while intoxicated could recall more items if they were intoxicated again during the testing session. No such state–dependency was observed. Similarly, Lisman (1974) tried unsuccessfully to help subjects resurrect lost information for events occurring during periods of intoxication by getting them intoxicated once again.
During the 2 weeks preceding the survey, an equal percentage of males and females experienced blackouts, despite the fact that males drank significantly more often and more heavily than females. This outcome suggests that at any given level of alcohol consumption, females—a group infrequently studied in the literature on blackouts—are at greater risk than males for experiencing blackouts. The greater tendency of females to black out likely arises, in part, from well–known gender differences in physiological factors that affect alcohol distribution and metabolism, such as body weight, proportion of body fat, and levels of key enzymes. There also is some evidence that females are more susceptible than males to milder forms of alcohol–induced memory impairments, even when given comparable doses of alcohol (Mumenthaler et al. 1999).
a recent study by Hartzler and Fromme (2003a) suggests that people with a history of blackouts are more vulnerable to the effects of alcohol on memory than those without a history of blackouts.
n an impressive longitudinal study, Baer and colleagues (2003) examined the drinking habits of pregnant women in 1974 and 1975, and then studied alcohol use and related problems in their offspring at seven different time points during the following 21 years. These authors observed that prenatal alcohol exposure was associated with increased rates of experiencing alcohol–related consequences, including blackouts, even after controlling for the offsprings’ general drinking habits.
Substantial evidence now indicates that alcohol selectively alters the activity of specific complexes of proteins embedded in the membranes of cells (i.e., receptors) that bind neurotransmitters such as gamma–aminobutyric acid (GABA), glutamate, serotonin, acetylcholine, and glycine (for a review, see Little 1999)
More than 30 years ago, both Ryback (1970) and Goodwin and colleagues (1969a) speculated that alcohol might impair memory formation by disrupting activity in the hippocampus. This speculation was based on the observation that acute alcohol exposure (in humans) produces a syndrome of memory impairments similar in many ways to the impairments produced by hippocampal damage. Specifically, both acute alcohol exposure and hippocampal damage impair the ability to form new long–term, explicit memories but do not affect short–term memory storage or, in general, the recall of information from long–term storage.
Research conducted in the past few decades using animal models supports the hypothesis that alcohol impairs memory formation, at least in part, by disrupting activity in the hippocampus (for a review, see White et al. 2000b). Such research has included behavioral observation; examination of slices of and brain tissue, neurons in cell culture, and brain activity in anesthetized or freely behaving animals; and a variety of pharmacological techniques.
Power
A friend requested I tackle the topic of power. In the absence of clarification I am going to assume she meant that sense of personal power that allows us to change the world. I am talking about more than confidence though that is a natural by product of personal power. A heightened sense of your own efficacy. An awareness that you can do things beyond the pale of ordinary reality. Most of us live lives of quiet desperation because we are chained by our own limited sense of reality. We may live in the universe but we exist in our conception of the universe.
Changing our conception of reality is the truest path to increasing our sense of personal power. Our changes in belief can translate into changes within ourselves and with changes in the world that increase our personal power.
Neitchze talked of a will to power. Our will, our motivating force is in some ways the part of us that is the most true. What we want and what we are willing to do to have it is who we most are. Mao Tse Tung for example had a conception of a China free from dominance of foreign powers or the traditional elites and he set out to make it so. His army was decimated, twice I believe to a handful of men but he persevered through his indomitable will and the world was changed.
Paolo Coehlo teaches that our world is as large as our vision. Most of look at our feet as we walk making for a very small world of possibility. He advises looking to the horizon, enlarging the world to the maximum of our vision. This is not just metaphor but a practical exercise anyone can do to enlarge their world.
Power in its most basic sense is the ability to make change in the world. Our biggest limitation in making change is our inability to believe that change is possible. Our basic decisions on what things mean, who we are, and what is the nature of reality will largely determine what change we can make and what is outside of our power.
Cocaine and the brain
Cut – N – Paste Notes for my education group, except for the first one the web page is on the top. Emphasis is mine.
Cocaine in the Brain
Melissa Hoegler
“Cocaine delivers an intensity of pleasure – and despair – beyond the bounds of normal human experience.”
When a person takes cocaine, it causes a rush. There is between one or two minutes of intense pleasure. This is followed by five to 8 minutes of euphoria, then as the high comes down, an overwhelming urge for more, which may last for a day. When a user is between cocaine doses or halts usage, the opposite effects occur. The user is depressed and tired.
Cocaine is attractive to users because it triggers dopamine. Dopamine is a neurotransmitter that is present in many regions of the brain. In normal mice, the introduction of cocaine increases dopamine by 150 percent. Dopamine regulates movement, emotion, motivation, and the feeling of pleasure. In a normal brain, dopamine is released by a neuron into a synapse and then it moves to dopamine receptors on other neurons. It is then moved back to the neuron that transmitted the dopamine initially.
When cocaine enters the area of the brain where the dopamine is located, it blocks the reuptake pumps that remove the dopamine from the synapse of the nerve cell. Thus, more dopamine gathers at the synapse and feelings of intense pleasure result. This feeling continues until cocaine is naturally removed from the system. Research findings by the National Institute of Drug Addiction (NIDA) demonstrate that cocaine not only effects the level of dopamine in the brain, but also the level of seratonin. In a study using mice without dopamine transporters, the mice were given cocaine and they still experienced rewarding effects. This was obvious because the animals kept on attempting to get or self-administer more. These researchers speculate that more than one neurotransmitter is responsible for the pleasurable feeling cocaine yields. Although main hypothesis as to why cocaine is so pleasurable, is that it alters levels of dopamine, norepinephrine, and seratonin, some scientists report that cocaine effects approximately 90 different parts of the brain, not just the two main regions of the amygdala and the nucleus accumbens. However, it is interesting that it is these two regions of the brain that remain active after the cocaine has left the system, and the powerful, uncontrollable desire for the drug has set in.
It was recently discovered through newer imaging techniques that cocaine hinders blood flow. This is why is it can cause brain damage or defects. Recent research demonstrates that if a cocaine user even thinks about cocaine, the blood flow is altered . This suggests that the addictive nature of the drug is stronger than we think, because simply thinking about it produces similar results in addicts’ brains’. This is likely to be a result of the way in which cocaine changes the structure of an abuser’s brain. For example n experiments done with lab rats, scientists reported that after repeated exposure to cocaine, the rats’ dendrites changed by becoming bigger and denser. This means that an increase in synaptic connectivity results from cocaine use which triggers people and animals to work harder to attain the drug.
When Is It Best To Take Crack Cocaine?
As a rule of thumb, it is profoundly unwise to take crack-cocaine. The brain has evolved a truly vicious set of negative feedback mechanisms. Their functional effect is to stop us from being truly happy for long. Nature is cruelly parsimonious with pleasure. The initial short-lived euphoria of a reinforcer as uniquely powerful as crack will be followed by a “crash”. This involves anxiety, anhedonia, depression, irritability, extreme fatigue and possibly paranoia. Physical health may deteriorate. An intense craving for more cocaine develops. In heavy users, stereotyped compulsive and repetitive patterns of behaviour may occur. So may tactile hallucinations of insects crawling underneath the skin (“formication”). Severe depressive conditions may follow; agitated delirium; and also a syndrome sometimes known as toxic paranoid psychosis. The neural after-effects of chronic cocaine use include changes in monoamine metabolites and uptake transporters. There is down-regulation of dopamine D2 receptors to compensate for their drug-induced overstimulation. Thus the brain’s capacity to experience pleasure is diminished.
/www.drugabuse.gov/infofacts/cocaine.html
Researchers have found that the human liver combines cocaine and alcohol to produce a third substance, cocaethylene, which intensifies cocaine’s euphoric effects. Cocaethylene is associated with a greater risk of sudden death than cocaine alone.
Behavioral interventions—particularly, cognitive-behavioral therapy—have been shown to be effective for decreasing cocaine use and preventing relapse. Treatment must be tailored to the individual patient’s needs in order to optimize outcomes—this often involves a combination of treatment, social supports, and other services.
Currently, there are no FDA-approved medications for treating cocaine addiction
www.drugabuse.gov/NIDA_notes/NNvol22N2/LongTerm.html
Chronic exposure to cocaine depresses neural activity. Initially, the effect shows up mostly in the brain’s reward areas. With longer exposure, however, neural depression spreads to circuits that form cognitive and emotional memories and associations.
All the monkeys that had self-administered cocaine showed some localized depression of glucose metabolism. In the monkeys that self-administered cocaine daily for just 5 days, neural depression was largely restricted to pleasure and motivation areas, especially the reward circuit and areas that process expectations of rewards.
In the 100-day test, animals that had received the high dose of the drug revealed less neural activity in 40 of the 77 brain regions analyzed as compared with animals that had received only food morsels (see table). The high-dose monkeys incurred a 16 percent drop, on average, in overall cerebral glucose metabolism. The low dose of cocaine depressed metabolism in 14 of the regions, but not overall.
The tests suggest that with longer exposure to cocaine, reductions in neural activity expand within and beyond the pleasure and motivation centers, says Dr. Porrino. “Within the structure called the striatum, the blunting of activity spreads from the nucleus accumbens, a reward area, to the caudate-putamen, which controls behavior based on repetitive action,” she says. Long-term cocaine use also depressed memory and information-processing areas.
The findings accord well with those of human imaging studies, which have found general depression in cerebral blood flow among chronic cocaine abusers compared with nonabusers. By using animals, however, Dr. Porrino eliminated two sources of uncertainty in those clinical studies: differences in metabolic rates that may have predated cocaine abuse and abuse of drugs other than cocaine. “My team can directly attribute to cocaine the depressed brain metabolism observed in the study,” says Dr. Porrino.
“Our 100-day experimental protocol for rhesus monkeys gives a good picture of what might happen in the brains of cocaine abusers,” she says. “Some addiction researchers believe that the shift in activity within the striatum may, in part, underlie the progression from voluntary drug taking to addiction. Moreover, human imaging research has linked drug craving with the amygdala and insula, temporal lobe areas depressed by cocaine in our study.”
COCAINE SELF-ADMINISTERED BY MONKEYS FOR 100 DAYS DEPRESSES NEURAL ACTIVITY IN SPECIFIC BRAIN AREAS. Name of area Selected roles in behavior Depression of metabolic activity* (percentage) Nucleus accumbens (ventral striatum) Processes reward and motivation 16-31 Caudate-putamen (dorsal striatum) Controls behaviors based on repetitive action 10-23 Hypothalamus Controls eating, fighting, mating, and sleep 18-22 Insula Translates body signals into subjective feelings 17-19 Hippocampus Consolidates memories and influences mood 15-23 Amygdala Forms emotional and motivational memories, e.g., linking a cue and a drug to produce craving 13-19 Temporal cortex areas Processes emotional and cognitive information, e.g., recognition and short-term memory 17-22
alcoholism.about.com/cs/coke/a/blyale030835.htm
A diuretic commonly used to treat hypertension and congestive heart failure may improve brain blood flow in cocaine addicts, according to a study in the August 2003 issue of Drug and Alcohol Dependence.
Chronic cocaine use is associated with decreases in blood flow to the brain, but the mechanism for this decrease is not fully understood. Researchers theorize cocaine-induced constriction of the arteries in the brain and/or increased blood clotting may be involved.
The problems associated with decreased brain blood flow in some cocaine abusers are the results of major stokes such as paralysis, loss of ability to speak, severe cognitive impairment and in the worst cases death. The patients in these studies with reduced blood flow to their brain had significant impairment in thinking, concentrating, reading and remembering things. They also had significant depressive symptoms that may be related to these deficiencies in brain functioning due to lack of sufficient blood flow to the neurons.
Thus, increasing blood flow back to normal can reverse these cognitive impairments and make these patients more responsive to our behavioral treatments which require learning of new skills to refuse drugs. These improvements in cognition can also enable these patients to return to productive employment and be active members of society.
To gauge the effects of the diuretic amiloride on cocaine dependent subjects, Thomas Kosten, M.D., professor of psychiatry at Yale School of Medicine, and colleagues administered amiloride, aspirin or placebo to 49 patients for one month while they resided on a research unit. Blood flow in the brain was measured on admission to the unit and at the end of treatment.
At the time they were enrolled in the study, cocaine-dependent subjects showed decreased cerebral blood flow compared to 18 control subjects. After four weeks of treatment the researchers found that the amiloride, but not aspirin or placebo, improved blood flow in the brain. None of the treatments affected blood clotting.
The authors speculate that the improvement by amiloride may be due to the medication’s ability to dilate the arteries in the brain. The authors also pointed out that amiloride may be used in combination with other medications that also increase cerebral blood flow to treat cocaine dependent patients.
Meth and the brain (notes)
rough notes for my education group. People were into the presentation even non-Meth users. I was surprised by how many had tried it. Next week we take on crack.
Wikipedia: Methamphetamine is a potent central nervous system stimulant that affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions. The acute physical effects of the drug closely resemble the physiological and psychological effects of an epinepherine-provoked fight, flight or freeze, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite.
Methamphetamine is a potent neurotoxin, shown to cause dopaminergic degeneration. High doses of methamphetamine produce losses in several markers of brain dopamine and serotonin neurons. Dopamine and serotonin concentrations, dopamine and 5HT uptake sites, and tyrosine and tryptophan hydroxylase activities are reduced after the administration of methamphetamine. It has been proposed that dopamine plays a role in methamphetamine-induced neurotoxicity because experiments that reduce dopamine production or block the release of dopamine decrease the toxic effects of methamphetamine administration. When dopamine breaks down it produces reactive oxygen species such as hydrogen peroxide.
Physical effects can include anorexia, hyperactivity, dilated pupils, flushing, restlessness, dry mouth, headache, tachycardia, bradycardia, tachypnia, hypertension, hypotension, hyperthermia, diaphoreses, diarrhea, constipation, blurred vision, dizziness, twitching, insomnia, numbness, palpitations, arrhythmias, tremors, dry and/or itchy skin,acne,pallor, and with chronic and/or high doses, convulsions, heart attack, stroke, and death can occur.
Psychological effects
Psychological effects can include euphoria, anxiety, increased libido, alertness, concentration, energy, self-esteem, self-confidence, sociability, irritability, aggression, psychosomatic disorders, psychomotor agitation, hubris, excessive feelings of power and invincibility, repetitive and obsessive behaviors, paranoia, and with chronic and/or high doses, amphetamine psychosis can occur.
Withdrawal effects
Withdrawal is characterized by excessive sleeping, increased appetite and depression, often accompanied by anxiety and drug-craving.
Short-term tolerance can be caused by depleted levels of neurotransmitters within the synaptic vesicles available for release into the synaptic cleft following subsequent reuse (tachyphylaxis). Short-term tolerance typically lasts until neurotransmitter levels are fully replenished; because of the toxic effects on dopaminergic neurons, this can be greater than 2–3 days. Prolonged overstimulation of dopamine receptors caused by methamphetamine may eventually cause the receptors to downregulate in order to compensate for increased levels of dopamine within the synaptic cleft. To compensate, larger quantities of the drug are needed in order to achieve the same level of effects.
Methamphetamine is addictive. While not dangerous, withdrawal symptoms are common with heavy use and relapse is common. Methamphetamine use causes hyperstimulation of pleasure pathways which leads to anhedonia. It is possible that daily administration of the amino acids L-Tyrosine and L-5HTP/Tryptophan can aid in the recovery process by making it easier for the body to reverse the depletion of dopamine, norepinephrine, and serotonin. The mental depression associated with methamphetamine withdrawal is longer lasting and more severe than that of cocaine withdrawal.
ScienceDaily (Mar. 28, 2000) —In an article published in the March 28 issue of Neurology, scientists at the Harbor-UCLA Medical Center in Torrance, California, used magnetic resonance spectroscopy to take measurements of three parts of the brains of 26 participants who had used methamphetamine and then compared them with measurements of the same regions in the brains of 24 people who had no history of drug abuse.
“the meth users in this study hadn’t used the drug for some time–anywhere from two weeks to 21 months, this research strongly suggests that methamphetamine abuse causes harmful physical changes in the brain that can last for many months and perhaps longer after drug use has stopped,” In their study, Dr. Linda Chang and Dr. Thomas Ernst measured levels of brain chemicals that indicate whether brain cells are healthy or are diseased or damaged.
“We found abnormal brain chemistry in the methamphetamine users in all three brain regions we studied. In one of the regions, the amount of damage is also related to the history of drug use–those who had used the most methamphetamine had the strongest indications of cell damage,” Dr. Chang said.
The researchers found that levels of one chemical marker, N-acetyl-aspartate, were reduced by at least five percent in the methamphetamine abusers. “Many diseases associated with brain cell loss or damage, such as Alzheimer’s disease, stroke, and epilepsy, are also associated with reduced N-acetyl-aspartate,” said Dr. Ernst. “Reduced concentrations of N-acetyl-aspartate in the drug users’ brains suggest that long-term methamphetamine abuse results in loss or damage to neurons, the cells we use in thinking.” Two other chemical markers, myo-inositol and choline-containing compounds, are associated with glial cells, which act to support neurons. “Methamphetamine abusers showed increases of 11 percent and 13 percent in levels of these markers compared with normal individuals,” Dr. Ernst said. “This suggests an increased number or size of glial cells as a reaction to the injurious effects of methamphetamine.”
Abstinence Can Reverse Some Brain Damage
From JAMA News Release
Updated April 08, 2005
Adaptive changes in chemical activity in certain regions of the brain of former methamphetamine users who have not used the drug for a year or more suggest some recovery of neuronal structure and function, according to an article in the April 2005 issue of Archives of General Psychiatry, one of the JAMA Archives journals.
Methamphetamine use has been shown to cause abnormalities in brain regions associated with selective attention and regions associated with memory, according to background information in the article. Recent animal and human studies suggest that neuronal changes associated with long-term methamphetamine use may not be permanent but may partially recover with prolonged abstinence.
Thomas E. Nordahl, M.D., Ph.D., of the University of California, Davis, and colleagues compared eight methamphetamine users who had not used methamphetamine for one to five years and 16 recently abstinent methamphetamine users who had not used the drug for one to six months with 13 healthy, non-substance-using controls using a method of brain imaging, proton magnetic resonance spectroscopy (MRS), that allows the visualization of biochemical markers that are linked with damage and recovery to the neurons in the brain.
The researchers measured biomarkers in the anterior cingulum cortex, a region of the brain associated with selective attention. Levels of N-acetylaspartate (NAA), which is present only in neurons, were measured as a marker of the amount of damage (neuronal loss). Choline (Cho), which is generated by the creation of new membranes and, the authors write, “may be an ideal marker to track changes consistent with neuronal recovery associated with drug abstinence,” was measured as a biomarker of recovery.
Levels of NAA were abnormally low in all the methamphetamine users, the authors found. Levels were lower relative to the length of methamphetamine use, but did not change relative to the amount of time that the methamphetamine users had been abstinent. The researchers found elevated Cho levels in the methamphetamine users who had not used the drug in one to six months, but normalized levels in the longer abstainers.
Normalization of Function
“In the early periods following methamphetamine exposure, the brain may undergo several processes leading to increased membrane turnover. The relative Cho normalization across periods of abstinence suggests that when drug exposure is terminated, adaptive changes occur, which may contribute to some degree of normalization of neuronal structure and function,”
Alcohol’s Effect on the Brain
I put together some facts on the topic for a radio interview on KFRU. It went pretty well, the hosts (simon and renee) were engaging and funny, and we talked for about 45 minutes and got out a lot of good information. The four pages of notes made me feel a lot more comfortable and i think it came across in the interview. A couple of things really struck me. One was the idea of neurogenesis. I had always read that you had all the brain cells you would ever have and alcohol kills them. In fact it says that on the info web site but i am going to edit that out because its not true. What really happens is the brain makes more brain cells all the time unless you are chronically drinking large amounts of alcohol. The good news is after a week of abstinence brain cell production booms. The fact that hit on the radio was brain shrinkage. Renee Hulshoff seemed aghast to learn your brain shrinks as you age and she referenced it on another story i caught on the drive back to the salt mines. I think I will do my next education group on the same topic, my as well learn the rap. On a practical note i will be promoting thiamine,. exercise and antidepressants for chronic alcoholics.
(lifted from NIAAA’s alcohol alert)
Equal numbers of men and women reported experiencing blackouts, despite the fact that the men drank significantly more often and more heavily than the women. This outcome suggests that regardless of the amount of alcohol consumption, females—a group infrequently studied in the literature on blackouts—are at greater risk than males for experiencing blackouts.
Using imaging with computerized tomography, two studies compared brain shrinkage, a common indicator of brain damage, in alcoholic men and women and reported that male and female alcoholics both showed significantly greater brain shrinkage than control subjects. Studies also showed that both men and women have similar learning and memory problems as a result of heavy drinking.
Wernicke–Korsakoff Syndrome
Up to 80 percent of alcoholics, however, have a deficiency in thiamine, and some of these people will go on to develop serious brain disorders such as Wernicke–Korsakoff syndrome (WKS)). WKS is a disease that consists of two separate syndromes, a short–lived and severe condition called Wernicke’s encephalopathy and a long–lasting and debilitating condition known as Korsakoff’s psychosis.
The symptoms of Wernicke’s encephalopathy include mental confusion, paralysis of the nerves that move the eyes (i.e., oculomotor disturbances), and difficulty with muscle coordination. For example, patients with Wernicke’s encephalopathy may be too confused to find their way out of a room or may not even be able to walk. Many Wernicke’s encephalopathy patients, however, do not exhibit all three of these signs and symptoms, and clinicians working with alcoholics must be aware that this disorder may be present even if the patient shows only one or two of them. In fact, studies performed after death indicate that many cases of thiamine deficiency–related encephalopathy may not be diagnosed in life because not all the “classic” signs and symptoms were present or recognized.
Approximately 80 to 90 percent of alcoholics with Wernicke’s encephalopathy also develop Korsakoff’s psychosis, a chronic and debilitating syndrome characterized by persistent learning and memory problems. Patients with Korsakoff’s psychosis are forgetful and quickly frustrated and have difficulty with walking and coordination). Although these patients have problems remembering old information (i.e., retrograde amnesia), it is their difficulty in “laying down” new information (i.e., anterograde amnesia) that is the most striking. For example, these patients can discuss in detail an event in their lives, but an hour later might not remember ever having the conversation
Prolonged liver dysfunction, such as liver cirrhosis resulting from excessive alcohol consumption, can harm the brain, leading to a serious and potentially fatal brain disorder known as hepatic encephalopathy ammonia and manganese, have a role in the development of hepatic encephalopathy. Alcohol–damaged liver cells allow excess amounts of these harmful byproducts to enter the brain, thus harming brain cells.
Hepatic encephalopathy can cause changes in sleep patterns, mood, and personality; psychiatric conditions such as anxiety and depression; severe cognitive effects such as shortened attention span; and problems with coordination such as a flapping or shaking of the hands (called asterixis). In the most serious cases, patients may slip into a coma (i.e., hepatic coma), which can be fatal.
More facts from: www.bloodalcohol.info
Alcohol can affect several parts of the brain, but in general, alcohol contracts brain tissue and depresses the central nervous system. Excessive drinking over a prolonged period of time can cause serious problems with cognition and memory.
When alcohol reaches the brain, it interferes with communication between nerve cells, by interacting with the receptors on some cells. The alcohol suppresses excitatory nerve pathway activity and increases inhibitory nerve pathway activity. Among other actions, alcohol enhances the effects of the inhibitory neurotransmitter GABA. Enhancing an inhibitor has the effect of making a person sluggish. Also, alcohol weakens the excitatory neurotransmitter glutamine, which enhances the sluggishness even farther.
The cerebral cortex processes information from your senses, processes thoughts, initiates the majority of voluntary muscle movements and has some control over lower-order brain centers. In the cerebral cortex, alcohol can:
- Affect thought processes, leading to potentially poor judgement.
- Depresses inhibition, leading one to become more talkative and more confident.
- Blunts the senses and increases the threshold for pain.
The limbic system, which consists of the hippocampus and septal area of the brain, controls memory and emotions. The affect of alcohol on this sytem is that the person may experience some memory loss and may have exaggerated states of emotion.
The cerebellum coordinates muscle movement. The cerebral cortex initiates the muscular movement by sending a signal through the medulla and spinal cord to the muscles. As the nerve signals pass through the medulla, they are influenced by nerve impulses from the cerebellum, which controls the fine movements, including those necessary for balance. When alcohol affects the cerebellum, muscle movements become uncoordinated.
The hypothalamus controls and influences many automatic functions of the brain (through the medulla), and coordinates hormonal release (through the pituitary gland). Alcohol depresses nerve centers in the hypothalamus that control sexual arousal and performance. With increased alcohol consumption, sexual desire increases – but sexual performance declines.
By inhibiting the pituitary secretion of anti-diuretic hormone (ADH), alcohol also affects urine excretion. ADH acts on the kidney to reabsorb water, so when it is inhibitted, ADH levels drop, the kidneys don’t reabsorb as much water and the kidneys produce more urine.
The medulla (brain stem) influences or controls body functions that occur automatically, such as your heart rate, temperature and breathing. When alcohol affects the medulla, a person will start to feel sleepy. Increased consumption can lead to unconscious. Needless to say, alcohol’s effect on the medulla can be fatal if it is excessive.
More stuff:
Detoxified alcoholics often have visuospatial and visuoperceptual deficits, characterized by difficulties completing tasks such as putting pieces of a puzzle together or map reading. A new study has found that, even with prolonged sobriety, alcoholics show deficits in visuoperception and frontal executive functioning of the brain.
Furthermore, alcoholics utilize a more complex higher-order cognitive system, frontal executive functions, to perform the same tasks as individuals without a history of alcoholism. Results are published in the November 2004 issue of Alcoholism: Clinical & Experimental Research.
The UNC findings, from research at UNC’s Bowles Center for Alcohol Studies, were based on an animal model of chronic alcohol dependence, in which adult rats were given alcohol over four days in amounts that produced alcohol dependency. The study is in the Nov. 3 issue of the Journal of Neuroscience.
In 2002, Dr. Fulton T. Crews, Bowles Center director, and Bowles Center research associate Dr. Kim Nixon were the first to report that alcohol, during intoxication, has a detrimental effect on the formation of new neurons in the adult rat hippocampus. This brain region is important for learning and memory – in animals and humans – and is linked to psychiatric disorders, particularly depression.
“When used in excess, alcohol damages brain structure and function. Alcoholics have impairments in the ability to reason, plan or remember,” said Crews, also professor of pharmacology and psychiatry in UNC’s School of Medicine. “A variety of psychological tests show alcoholics have a difficulty in ability to understand negative consequences.”
In the new study, senior co-author Crews and co-author Nixon found inhibition of neurogenesis, or brain cell development, during alcohol dependency, followed by a pronounced increase in new neuron formation in the hippocampus within four-to-five weeks of abstinence. This included a twofold burst in brain cell proliferation at day seven of abstinence.
“And when they stop drinking, you can show in a period of weeks, months, years, the brain grows back, there’s a return of metabolic activity, and cognitive tests show a return of function,” Crews said.
“Pharmacological agents such as antidepressants and behaviors such as running, increased physical activity and learning experiences apparently help regulate the process of neurogenesis,” he added. “Our research suggests they could be considered in the treatment of chronic alcohol dependency.”
In their report, Nixon and Crews also said that their findings for the first time provide a neuronal regeneration mechanism that may underlie the return of normal cognitive function and brain volume associated with recovery from addiction during abstinence from alcohol.
“This is really the first biological measure of a major change in neuronal structure consistent with changes that are known to occur when individuals are able to stop drinking,” said Crews.
Number of Brain Cells Not Fixed
For decades, neuroscientists believed the number of new cells, or neurons, in the adult brain was fixed early in life. Adaptive processes such as learning, memory and mood were thought tied to changes in synapses, connections between neurons.
More recently, studies have shown that the adult human brain is capable of producing new brain cells throughout life, a neurogenesis resulting in formation of hundreds of thousands of new neurons each month. “Prior to our work, everyone merely assumed that glia, the supporting cells of the brain, regenerated or that existing brain cells altered their connections,” said Nixon. “We have shown a burst in new cell birth that may be part of the brain’s recovery after the cessation of alcohol.”
Chronic alcoholism, a disease affecting more than 8 percent of the adult U.S. population, or more than 17 million Americans, produces cognitive impairments and decreased brain volumes, both of which are partially reversed during abstinence.
“FREEZING MY ASS OFF IN ANZA BORREGO BY TEALIGHT”
After Amee and I split up I went to camp alone in the desert for some weeks. It was January so I went to the Anza Borrego desert in San Diego county. Very stark and beautiful and cold at night. The nights are long in January, so i spent a lot of time shivering in my tent thinking, reading by candlelight, and a little writing. So this would have been written in January 2002, and less a dark night of the soul then a time to really reflect on my purpose in the world. i got some good answers and it was time well spent. Anyone who comments on this post i will give a copy of my book “America: Its Land and Its People”. (Facebook comments don’t count, they have no history.)
I need to get real with people
Its easiest to do with strangers
With no history
Preconceived conceptions
Or formulaic patterns
To escape reality.
The fascination of discovery
Wonder
Total attention
The Universe condensed
To an understandable packet.
The most beautiful times
Are when that packet
Is the interaction.
The unity of two
The most difficult
To harmonize into the One.
As zero is nonbeing
And one is existance
Than two is one and not one.
Duality, the first separation
But between two is the
First Possibility of communication
A process that is One.
But if only one is being one
There is no communication
Only projections
Of the not one received by the one
And the Universe is the Other
And i am no more
Lost and forgotten
By even myself
I wander not in the unity of the One
Where I belong
Where I am nurtured
Where i am inexplicably me.
But in the Zero
Oblivion
Nothingness
The abyss
So excuse me
If I try
To make you get real
With me
I am only trying to exist.
prose poem with lots of unatributed quotes
The Kingdom of heaven is like writing in the margins. For all of the writing in the book there is always room for more words. The kingdom of heaven is within you, heaven and earth will pass away but my words will never pass away, in the beginning was the word and the word was god and was with god and everyone who loves is a child of god because god is love. Solomon says truly there is nothing new under the sun and yet i am a new creation. i sing a new song, i love the truth, i fall short of the glory of god and write obscenities in the book of life, i fall short, but the wind rocks me, i lay each night in the cradle and feel at home, i fall short, i am selfish and self centered but mostly lazy and yet i am rocked by the winds of change. i feel at home on the dusty plains, i feel at home in the snowy mountains, i feel at home in the winter’s rain. god loves a cheerful giver a forthright spirit and an upright heart. Plato says rightly that we are in a cave looking at flickering lights cast upon the darkness of our cave all these things that will Pass away. How many walls that limited Plato’s walks still stand? How many bowls from which he supped his soups or knives that carved his bread? hath not moth & rust destroyed? yet the idea of Knife guides every hand that makes to cut anything anywhere ever. heaven and earth shall pass away but my words will never die. this world is illusion only in the eye of the eternity and for now walls still stand the cave still surrounds us with darkness. but it is only contrast on the page of the limitless light of the now. dare to read your life as a book, your experiences as words on a page in the book of life. store up treasures in heaven, someday all there will be is communication, isn’t that what communion really means? but now there are walls and roads and knives and bowls and soup and bread and the stuff that Stories are made of. tales to be told when the weather just doesn’t matter anymore. heaven and earth shall pass away but my words shall never die. time is a fire that burns away all the things that in the end are dust, but star dust nothing less, “its the cosmos that gave us life its from stardust that we’re made of”. “we are all stars”. “every woman and every man is a star” because of the truth. not the idea of truth but the truth itself, the known and the unknown, the beginning and the end. just as our bodies, molded clay of life stuff, for a time, a temple of finite properties but infinite possibilities. we are born into a world in which we are a part and we live and we die like the birds in the field. but our fallible material shells generate consciousness. a self. an entity capable of knowing and being known. remembering and being remembered. the kingdom of heaven is within you. The kingdom of heaven is at hand, to be grasped. to be known to love and be loved for god is love and what is love but a knowing a being known. [the book of wisdom says the great build up walls of lies, great houses and lands and things that twinkle and gleam, that block out the light of eternity, (an experience of both truth & love) and leave them huddled alone in darkness. a land of dark despair] just as every hand that cuts is guided by the same perfect knife every heart that loves is guided by the same perfect love. God and heaven and all the saints and angels are an “a priori” assumption, a self evident fact by anyone who has ever been lost in the moment of love, the sharing, the knowing of another soul be it our neighbor or the god who made the universe its really all the same eternity, if you do it right. do you want to know if you are going to live forever? are you living forever right now? my home is the planet earth and my family has six billion children and i yearn to know their names and know their stories. i have a name, i have asked to be remembered and promised to remember. i have loved and am loved, i sing songs to the angels, i love everyone i have ever loved and that love lives inside of me. moments of eternity when we shined brighter together, lost in the moment, timeless and so eternal. heavenly treasures, stories to tell when the weather just doesn’t matter anymore because heaven and hell have passed away and there is only the word. the word is truth. the word is love. the word is beauty. the word is.
curriculum vita (a prose poem found in my paint by # calendar Dec. 06)
What is my story, what is the essence of my being? From where does come this hunger to know, to be known? Why mar the blank page? in what hubris it must lay, lie, die.
Oh to be of one and now, but what cost history, even to gain eternity, oh blessed now, the razor’s edge of existence that i can only pretend exists as by the time the light has hit my eyes its history, pure history. And oh, memory, the purest form of imagination. When the brain is eaten through with plaquey-tentacles and the mind from which is sprung is thin and patchy, the mind holds onto childhood. the earliest stories, the purest, the best, the core. oh history i sing your praise and yearn to never forget, even at the cost of the now.
My life a taut quivering string of ambivilance. the cost of a vivid imagination. There’s good reason to believe in everything. any damn thing.
At what cost freedom? At what cost power, even unsought, unutilized, unspent this currency weighs heavy in my pocket. Makes me want to walk all cockeyed, or spend it. or just fucking lay down, rest, forget, dream perhaps, not without struggle but how’s it going to drag you down, when your laying on the bottom?
Multiconstruct 
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