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The Miracle Question
Yesterday I did an education group on solution focused therapy. I love the solution focus approach and have been an advocate for it in our agency and we have incorporated it into our treatment planning. Its based on the idea that when working with someone with problems you don’t really have to know the origins of those problems but you just have to identify where you would like your life to go and what are the steps you need to take now that will move you in that direction. Prior to a solution focused approach we took a problem solving approach which is not as motivating which is really the key factor in personal change. Its far more about motivation than it is about knowledge. You begin with “the miracle question”. “If you woke up tomorrow and your life was perfect how would you know it was different?” Its phrased in the form of a miracle because a lot of people mired in nonsense have lost any notion that their lives can be any different. It has to be a miracle for them to wrap their minds around the possibility of change. I also like it because it moves me out of the problem solving business and into the miracle business. Most people’s miracle is to have a safe home with their family with or without a relationship and with or without a dog. On rare occasions people have impossible miracles, bringing back dead relatives, winning the lottery, living in glass domes on mars and the like. The follow up question is “how would that make you feel?” There’s their real miracle. Its future focused rather than driven by hindsight and regret. I wove in some stuff from narrative therapy, looking at your life like a novel only instead of turning back to look for lessons you skip to the end. Ask the character who has it all figured out and is leading a happy life what did they do now that made that happen? It was well received and a really big group. Afterward I did the process group and it had hit home with folks. After dinner Dad and I watched The Time Traveler’s Wife (not to bad but no where near as good as the most excellent novel). It opens with a future version of the main character coming back to advise his younger self. Just beautiful.
marijuana’s effect on the brain – notes
Neurological effects
Experiments on animal and human tissue have demonstrated disruption of short-term memory,[10] which is consistent with the abundance of CB1 receptors on the hippocampus, the region of the brain most closely associated with memory. Cannabinoids inhibit the release of several neurotransmitters in the hippocampus, like acetylcholine, norepinephrine, and glutamate, resulting in a major decrease in neuronal activity in that region. This decrease in activity resembles a “temporary hippocampal lesion.”[10] In the end, this process could lead to the blocking of cellular processes that are associated with memory formation.
Cannabis consumption affects motor skills, reflexes, and attention, which is important when considering its effects on driving; however, this does not necessarily reflect impairment in terms of performance effectiveness, since few studies report increased accident risk.
Fungi
The fungi Aspergillus flavus,[28] Aspergillus fumigatus,[28] Aspergillus niger,[28] Aspergillus parasiticus, Aspergillus tamarii, Aspergillus sulphureus, Aspergillus repens, Mucor hiemalis (not a human pathogen), Penicillin chrysogenum, Penicillin italicum and Rhizopus nigrans have been found in moldy cannabis.[27] Aspergillus mold species can infect the lungs via smoking or handling of infected cannabis and cause opportunistic and sometimes deadly Aspergillosis.[citation needed] Some of the microorganisms found create aflatoxins, which are toxic and carcinogenic. Researchers suggest that mouldy cannabis thus be discarded.
Mould is also found in smoke from mould infected cannabis,[27][28] and the lungs and nasal passages are a major means of contracting fungal infections. “Levitz and Diamond (1991) suggested baking marijuana in home ovens at 150 °C [302 °F], for five minutes before smoking. Oven treatment killed conidia of A. fumigatus, A. flavus and A. niger, and did not degrade the active component of marijuana, tetrahydrocannabinol (THC).”[27]
Bacteria
Cannabis contaminated with Salmonella muenchen was positively correlated with dozens of cases of salmonellosis in 1981.[29] “Thermophilic actinomycetes” were also found in cannabis.[28]Research shows that although marijuana is in many ways detrimental to a person’s health, it is not so much on the physical side, but more psychological that is apparent. You can get in the habit of using it to fall asleep and get the mind to stop racing or review the thoughts about the day, a person in your past or job and financial anxiety. The body’s cerebellum and serotonin then gets used to this being a way to tune things out rather than developing a way to process emotions and stay calm in the midst of negative feelings. Over long term marijuana use (over five years, per adum), there have been numerous harmful effects of marijuana to the body’s ability to create natural and necessary “feel good” chemicals. In a recent study conducted by Imperial College London, subjects who had smoked cannabis during a five trial, presented with 68% less serotonin than subjects who were unexposed to cannabis.
Marijuana’s Effects Linger in the Brain
WebMD Health News
Feb. 7, 2005 – The effects of marijuana in the brain may linger long after the last joint goes out.
A new study shows that blood flow to the brain in people who smoked marijuana remained altered up to a month after they last smoked pot.
Researchers say the findings may help explain the problems with memory and thinking found in previous studies of chronic marijuana users.
Marijuana’s Effects on the Brain
In the study, which appears in the Feb. 8 issue of Neurology, researchers studied the blood flow in brain arteries of 54 marijuana users and 18 nonusers.
The marijuana users volunteered to participate in an inpatient program and abstained from marijuana use for a month.
Blood flow in the brain was analyzed at the beginning of the study and at the end of the month for the marijuana users.
Researchers found blood flow was significantly higher in marijuana users than in nonusers, both at the beginning and at the end of the study.
However, the marijuana users also had higher scores on the pulsatility index (PI), which is a measure of resistance to blood flow.
Researchers say the level of resistance to blood flow among light and moderate marijuana users improved over the course of the abstinence month. But there was no improvement among heavy marijuana users.
This resistance is thought to be caused by the narrowing of blood vessels that happens when the body’s own ability to regulate the circulatory system becomes impaired.
“The marijuana users had PI values that were somewhat higher than those of people with chronic high blood pressure and diabetes,” says researcher Ronald Herning, PhD, of the National Institute on Drug Abuse in Baltimore, Md., in a news release. “However, their values were lower than those of people with dementia. This suggests that marijuana use leads to abnormalities in the small blood vessels in the brain, because similar PI values have been seen in other diseases that affect the small blood vessels.”
Light marijuana users smoked two to 15 joints per week, moderate users smoked 17 to 70 joints per week, and heavy users smoked 78 to 350 joints per week.
ScienceDaily (Oct. 15, 2008) — Brain imaging shows that the brains of teens that use marijuana are working harder than the brains of their peers who abstain from the drug.
At the 2008 annual meeting of the American Academy of Pediatrics in Boston, Mass., Krista Lisdahl Medina, a University of Cincinnati assistant professor of psychology, presented collaborative research with Susan Tapert, associate professor of psychiatry at the University of California, San Diego.
Medina’s Oct. 12 presentation, titled, “Neuroimaging Marijuana Use and its Effects on Cognitive Function,” suggests that chronic, heavy marijuana use during adolescence – a critical period of ongoing brain development – is associated with poorer performance on thinking tasks, including slower psychomotor speed and poorer complex attention, verbal memory and planning ability. Medina says that’s evident even after a month of stopping marijuana use. She says that while recent findings suggest partial recovery of verbal memory functioning within the first three weeks of adolescent abstinence from marijuana, complex attention skills continue to be affected.
“Not only are their thinking abilities worse, their brain activation to cognitive tasks is abnormal. The tasks are fairly easy, such as remembering the location of objects, and they may be able to complete the tasks, but what we see is that adolescent marijuana users are using more of their parietal and frontal cortices to complete the tasks. Their brain is working harder than it should,” Medina says.
She adds that recent findings suggest females may be at increased risk for the neurocognitive consequences of marijuana use during adolescence, as studies found that teenage girls had marginally larger prefrontal cortex (PFC) volumes compared to girls who did not smoke marijuana. The larger PFC volumes were associated with poorer executive functions of the brain in these teens, such as planning, decision-making or staying focused on a task.
Medina says adolescence is a critical time of brain development and that the findings are yet another warning for adolescents who experiment with drug use. She says more study is needed to see if the thinking abilities of adolescent marijuana users improve following longer periods of abstinence from the drug. “Longitudinal studies following youth over time are needed to rule out the influence of pre-existing differences before teens begin using marijuana, and to examine whether abstinence from marijuana results in recovery of cognitive and brain functioning,” says Medina.
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.
old dog, new dog, feel alright
Its been a strange time, very busy lots of changes, lots of talking to very bright people whose first language is not english. it stretches your mind, as does the new job at work, as do the canine changes at home. Wednesday I met Belen downtown and we went for icecream at sparkies. it was good i had a wafflecone. we stayed for 4 hours talking about psychology and metaphysics. its been ages since i’ve had such an intense talk about stuff. i didn’t get home til after ’10 and if you know me lately that’s my bed time. going to bed at the same time is one of the things that keeps me sane, but sometimes there are higher purposes than mere sanity and i headed for bed at 11. i was devastated to see oni had pissed in it. thursdays my long day, jamming from 7:30 to 8:30 and i don’t mean an hour.
i stripped the wet stuff off, the good news badnews was she had hit the comforter, and tossed it in the hall, grabbed a flanel sheet and closed the blinds in the living room and laid down on the couch. sometimes when i can’t sleep rather than do progressive relaxation i take the easier route of zoning in front of the tv to manage rushing thoughts. but after asking dad to turn down the tv and turn off his lamp i explained his dog had pissed my bed. he seemed mad at me about it and turned off his movie right before the end and went to bed.
said he was taking oni to the humane society and i didn’t tell him not to. just tired of it. lowering the quality of my life. it had come that close so many times before i couldn’t get up the motivation to give her a final farewell goodbye but knew it was happening so i said something. “take care now” or something.
they were both gone at lunch. didn’t mean anything. enjoyed the quiet.
after the day job dad was subdued. dog was nonexistent. i was apologetic and sad. for 10 minutes and then i had to go. i was already 10 minutes late. my life is too hard.
group was alright but last week had been super great. therapeutic and meaningful, cool because we had an intelligent observer who gave good feedback, a therapist from Taiwan in a PHD program in an exchange program. this group was not quite perfunctory but more educational and less deep. but had made it through a long day.
friday, work was work. its new reality is do one thing after another from the time until you leave and leave some things undone. jamming all day. home, change clothes, weed the garden for 10 minutes and go downtown for the 100th anniversary of the wabash station. toured the artrageous gallery 1st floor which had been a storage building for supplies. its a cool old building with a neat rehab into studios. train art and toy trains. no tour of old underground train repair space in the catacombs as promised. there was a ’26 model t, they had three petals i learned from dad and an old dude who’d wandered up. brake, clutch and shift. never noticed the windshield was two small windshields on pivots. i added the fact they got better gas mileage than the ford explorer.
we met amy and some friends of hers at sycamores, we sat at the bar. christina was one of them and we talked about her friend the harvard professor whose study that showed happiness and sadness followed disease models of contagion (you’re 11% more likely to be happy if you have a happy friend, twice that for a sad friend). more people showed up and there was a shortage of bar stools and a surplus of weirdness so we split. probably should have just got a table.
dad and i were going to go to the casino but we had words and i said i didn’t want to go and didn’t. mowed the lawn and ordered pizza and felt a little bad. i was deadheading the roses when he arrived and pointed out the beautiful sunset i was oblivious too and what it was doing to the tiger lillies til he mentioned it and asked to take a picture. i said “sure, in the sweet light”. and we talked about that, the hour before sunset and the hour after sunrise when light comes in obliquely and makes for better photos. softer, less glare. he hadn’t heard of it but had sorta discovered it. sweet.
today was up and do dishes. drink coffee with sarah and talk about sociopaths. i think its a curable condition if they’re motivated. we went to the market. they’re awesome this time of year. melons are out and got a nice little watermelon, plus peaches, concord grapes, this and that.
home to meet the new dog. dad had found one in the free classifieds. a cockapoo four months old. named him fido. he’s barking at the cat right now, first peep i’ve heard out of him. he’s a little black and white fuzzy guy with big paws and goofy eyes. shy and charming. i put away my stuff and left (after having swapped vehicles with sarah) to pick up the girls from taiwan.
we went out to devil’s ice box trail at rockbridge state park. more of its open and everyone enjoyed climbing down to anderson cave where it was cool and very cool. watching the little ones play, the real little ones sitting down on rocks because they didn’t want to cross the underground stream.
after stopping by the Pierpont Store we went back and hung out while dad smoked a pork loin and grilled some chicken breast on the grill. we had the watermelon as well as red potatoes and corn on the cob. they took almost as many pictures of the meal as they did the cave.
needless to say i was bushed and coasted through the evening. through it all i’ve been re-reading neal stephenson’s anathem. brilliant book, i’ll post on it.
spirituality
On Tuesday I promised the guys in treatment when I did my education group on Saturday I would talk about spirituality. Prayer had come up and there was some question. I always walk a careful line on issues of religion and spirituality, its something where you really want to honor personal choice. But we do know some stuff about prayer and its power in the treatment of chemical dependency. The only practical stuff about letting go i have ever found in clinical literature is on prayer. Plus the Bible is extremely quotable. Today’s quotation i couldn’t pass up was “everyone is righteous in his own eyes”. Many are Christians and being able to cite stuff adds credibility. I try to mix it up with you can always bow to someone’s Buddha nature, good Mormons save 10%, tithe 10%, invest 10% and store up a years supply of food. But mostly i stay rooted in science. I have never done an entire presentation on spirituality and am a little excited about it. I am going to open up with a Dali Lama quote:
I believe an important distinction can be made between religion and spirituality. Religion I take to be concerned with faith in the claims to salvation of one faith tradition or another. Spirituality I take to be concerned with qualities of the human spirit, love and compassion, patience, tolerance, forgiveness, contentment, a sense of responsibility, a sense of harmony, that bring happiness both to self and others.
Spirituality comes from the Latin spiritus, spirit, or breath. It represents our animating force, our connection to something larger than ourselves. There is an in and out that comes with breathing that implies interaction. It is far less important what we believe as what we experience. Spirituality provides a connection, an engagement with the ineffable. Something larger than ourselves. Kabbalists believe that the imagination is the horse that we ride to see the divine. It is not the divine but its the means by which we travel to it.
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,”
strategic planning et al
I got back this afternoon from a strategic planning session of the Missouri Cadre for Co-Occurring Excellence. It was a really cool experience…. Right now its Elvis night in Texas and the Detroit Tigers are pitching to Elvis Andrus in the bottom of the 9th, tied bases loaded. Strike 1. Fouled one, strike 2. There’s 1 out. Earlier they had a bunch of Elvi’s on mini bikes eating jelly donuts. Fudge, base hit. ‘Elvis did it on Elvis day”. what are you gonna do? great game….
The conference was at Innsbrook this resort in Wentzville that was pretty neat. I stayed in a condo all by my lonesome, fireplace, sliding glass door looking out on a wooded lake, 1 1/2 baths, just really excessive. They were going for seasonal food too so spinach and asparagus in every meal. A lot of their meals though just fell a little flat, chewy risotto and salty overcooked couscous. but fancy, and largely good, i’m not complaining.
The strategic planning itself was pretty interesting and i think i caught the gist of what we did to do it myself in a pinch. We were organized on a focus question which we took out of our mission statement to make the systems of care more responsive to people with complex needs. So we first identified what we would like to do on it and just made lists. We then got in diads or triads and by consensus put up what we could agree on 1/2 sheets of paper in 3-7 word statements and stuck them on a “sticky wall”. We put them together by similarities and then identified commonalities in each group and wrote those in 3-7 words. That was our vision. Than we wrote our blocks in the same fashion, individual lists diads and triads on 3-7 word cards, clusters, underlying themes, these our are our underlying contradictions. We then problem solve those in the same way individual lists, diads and triads (we did a group with four and it wasn’t as cool), put on the board, condense by similarities, name those. Than we clustered those five things into two things. Those are our goals. finally we wrote down four quarters and split up our nine identified activities under our two goals. Very consensus based but focused and productive. Valerie our facilitator rocked.
It took all day though so couldn’t really utilize the resort. did walk by the lake and stroll through the woods in a fruitless search for morels. I did see lots of wildflowers most noticeably wild sweet william. Saw lots of others coming along, looks like they’re doing fire ecology and they’ve got a nice looking woods there at Innsbrook. I also saw a bluebird. Looked just like the license plate, thank you showme state.
When I got home i took straight to gardening. Turned my compost and scooped out a bushel. Planted my new strawberries. earlyglories? i think. extended the bed. Dad got the rhubarb in. in three years i’ll bake you a pie. It smelled really clean with the rain. the lettuces and such are coming in nice. i thinned the first round and we got some along with dandelions, wild onions, and oregano in our local greens salad for dinner.
The strawberries look like they’re really going to produce. lots of green berries. the herb garden really came in nice this year. the taragon is booming, as is the oregano and thyme as well. The chives are blooming very pretty, i’m hoping some of them go to seed and they increase. The sage has, i have a bunch of plants to dig up, if anyone wants one let me know. The bergamont also has spread nicely. Its looking sharp.
Bunnies have been a problem, took out a cabbage? and a kale. They might come back. I’m going to try and build a garden wall and plant some marigolds. There was also a stem cut off a tomato plant, but i couldn’t find a worm. So much to do. Got bulbs to plant and i have 6 horseradish i might plant up in the higher ground.
Gotta love spring and new beginnings.
Multiconstruct 
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