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In this clip, Dr. Roland Griffiths discusses the reorganizational effects that psychedelic experiences have on the brain and their potential use in treating mental disorders.
Science on refined sugar: mortality, aging, brain function, memory, neuroinflammation, cancer, sex hormones, addiction & more.
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In this clip, Dr. Roland Griffiths discusses the reorganizational effects that psychedelic experiences have on the brain and their potential use in treating mental disorders.
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Science on refined sugar: mortality, aging, brain function, memory, neuroinflammation, cancer, sex hormones, addiction & more.
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News & Publications
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Smoking cessation cuts lung cancer risk by nearly 40 percent just five years after quitting. www.sciencedaily.com
Cigarette smoking is the number one risk factor for lung cancer, the second most common form of cancer and a leading cause of death worldwide. A 2017 study found that heavy smokers' lung cancer risk drops by nearly 40 percent just five years after quitting smoking,
The study involved more than 8,900 people enrolled in two large cohort studies. Researchers tracked the participants' health for an average of 30 years and determined their cancer risk based on whether they were current, former, or never smokers.
They found that current and former smokers had a higher risk of developing lung cancer than those who never smoked, but that risk increased tenfold if they were heavy smokers (defined as smoking one pack daily for 21 years or longer), with nearly 93 percent of lung cancers occurring in heavy smokers.
Five years after quitting, former heavy smokers saw a 39 percent reduction in their lung cancer risk compared to current smokers, and this risk continued to decrease over time. However, even 25 years after quitting, heavy smokers' risk of lung cancer was still more than three times higher than that of people who had never smoked.
These findings suggest that smoking, especially heavy smoking, markedly increases a person’s risk of developing lung cancer. And although quitting smoking reduces lung cancer risk, former smokers' risks remain higher than never smokers'.
Many harmful behaviors, such as smoking or overeating, are rooted in reward-based processes. Consequently, people often engage in these behaviors in response to triggers, such as emotional or mental stressors, or external prompts, such as advertising and social pressures. Cognitive behavioral approaches like mindfulness can help people who engage in harmful behaviors become more mindful of these triggers. In turn, they can reevaluate their habits and develop strategies that help them avoid engaging in harmful behaviors. Learn more in this clip featuring Dr. Ashley Mason.
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A ketogenic diet decreases alcohol cravings in people with alcohol use disorder, offering an alternative to the brain's energy needs. www.frontiersin.org
Alcohol use disorder accounts for approximately 2.8 million deaths worldwide. It’s a chronic condition marked by a strong desire to drink and persistent alcohol use despite its harmful effects. A recent study found that a ketogenic diet reduces alcohol cravings in people with alcohol use disorder.
The study involved 33 adults with an alcohol use disorder enrolled in a three-week inpatient alcohol detoxification program. Slightly more than half of the patients received a ketogenic diet, while the remainder received a standard American diet. Once a week, using functional magnetic resonance imaging, researchers assessed the participants' brain function and craving responses during exposure to alcohol-related triggers. In addition, the participants reported their perceived alcohol cravings when exposed to the triggers.
The imaging revealed that participants who ate a ketogenic diet showed reduced neural activity related to alcohol cravings than those who ate the standard American diet across the entire three weeks of treatment. Those who ate a ketogenic diet also reported fewer perceived cravings.
Following alcohol consumption, the brain uses acetate, a metabolic byproduct of alcohol, for energy instead of glucose. As a result, glucose levels in the brain drop, and acetate levels increase – even after the effects of alcohol wear off. These alterations in fuel can contribute to withdrawal symptoms, cravings for alcohol, and a higher risk of relapse, especially when acetate levels drop. Ketones are structurally similar to acetate and can serve as an alternative energy source for the brain, providing energy in place of glucose.
This was a small study, but its findings suggest that a ketogenic diet reduces alcohol cravings among people with alcohol use disorders. Other evidence suggests vigorous exercise reduces alcohol cravings, likely due to exercise’s effects on FGF21 – a hormone produced during vigorous activity. Learn more in this short video featuring Dr. Rhonda Patrick.
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Estrogen may protect against cocaine-induced brain dysfunction by improving brain blood flow - progesterone and testosterone may be detrimental.(2001) www.sciencedaily.com
From the article:
Lead researcher Marc Kaufman and his colleagues first established the rate of blood flow to the brain in male and female occasional cocaine users. An intravenous dose of cocaine (0.4 mg/kg) was administered to nine men and 13 women. Men were studied once while women were examined during different phases of their menstrual cycle phases (days 3-8, follicular phase and 18-24, leutial phase) after the beginning of menstruation.
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In the follicular phase, when estrogen levels are high and progesterone levels are low, cocaine did not alter the amount of blood in the brain. By contrast, a 10 percent reduction in blood was found in women during their luteal menstrual cycle phase, when progesterone levels rise; male subjects incurred a 20 percent loss. These findings suggest that cocaine’s effects on blood vessels in the brain differ as a function of sex and menstrual cycle phase, and imply that progesterone in women and testosterone in men may enhance cocaine-induced vasoconstriction, while estrogen in women may blunt cocaine’s vascular effects.
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Such benefits could extend beyond drug using populations. For example, treatments that improve brain blood flow might also benefit the elderly, many of whom experience reductions of blood flow to the brain as a result of aging.
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Estrogen increased the quantity and half-life of dopamine released by rat neurons in response to cocaine, making them addicted more quickly. (2017) www.sciencedaily.com
From the article:
The Mount Sinai research team sought to understand why women, once they try cocaine, are much more likely than men to become addicted. While the overall rate of addiction is higher in males, previous research has shown that when females have the opportunity to try cocaine and other drugs, they are more likely than men to continue use and they transition to full addiction significantly faster than their male counterparts. Addiction investigators have also uncovered that women are more likely to use cocaine at an earlier age, take the drug in larger quantities, and have greater difficulty remaining abstinent compared to men. Additionally, women report that when estrogen levels are rising during their menstrual cycles, they experience a greater “high” from cocaine administration.
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The research team found that estrogen affects the quantity of dopamine released by neurons in response to cocaine, as well as how long the dopamine stays in the synapse between brain cells. Both actions increase the pleasurable effects of cocaine, and each was significantly bolstered as estrogen levels increased in the female mice. Both male and female mice linked pleasure/reward to where it occurred in their cages, spending more time on the side of their cage that was previously paired with cocaine. Female mice did so to a greater extent, indicating enhanced reward to cocaine use.
“The mice quickly learned that a particular environment is linked to drugs, and we demonstrated that when these mice, especially females at the height of their estrous cycle, were put into that environment, it stimulated a dopamine reward signal even without cocaine use,” Dr. Calipari says. “It is the same kind of strong, learned response that we know happens in humans.”
Researchers surmise that the evolutionary mechanism underlying the link between estrogen and the reward pathway is pleasure from seeking a mate and having sex, actions which promote the survival of the species. Another evolutionary hypothesis is that heightened estrogen could promote food seeking, via effects on dopamine signaling, to ensure females are healthy enough to carry offspring.
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The brain's reward center may be much more sensitive to the addictive effects of alcohol during estrogen-rich periods of the menstrual cycle. (2017) www.sciencedaily.com
From the article:
“When estrogen levels are higher, alcohol is much more rewarding,” said Lasek, who is the corresponding author on the paper and a researcher in the UIC Center for Alcohol Research in Epigenetics. “Women may be more vulnerable to the effects of alcohol or more likely to overindulge during certain stages of their cycle when estrogen levels are higher, or may be more likely to seek out alcohol during those stages.”
Studies indicate that gender differences in psychiatric disorders, including addiction, are influenced by estrogen, one of the primary female sex hormones. Women are more likely to exhibit greater escalation of abuse of alcohol and other drugs, and are more prone to relapse in response to stress and anxiety.
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“In mice in diestrus, estrogen levels increase to about 10 times higher than they are in estrus, the phase in which ovulation occurs and estrogen levels drop,” Lasek said.
VTAs [ventral tegmental area - “reward center”] were taken from mice in both estrus and diestrus and kept alive in special chambers. Electrodes recorded the activity of individual dopamine-sensitive neurons in the VTA. Next, the researchers added alcohol to the chamber. Activity increased twice as much in neurons from mice in diestrus compared to the response of neurons from mice in estrus.
Lasek and her colleagues then blocked estrogen receptors on dopamine-sensitive neurons in VTA in mice in estrus and diestrus. With the blocker present, the response to alcohol in neurons from mice in diestrus was significantly lower compared with neurons where estrogen receptors remained functional. The estrogen receptor blocker reduced the alcohol response to levels seen in mice in estrus. The responses to alcohol in neurons from mice in estrus were unaffected by the estrogen receptor blocker.
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Microglial TNF-alpha suppresses cocaine-induced plasticity and behavioral sensitization in a mouse model. (2016) www.sciencedaily.com
From the article:
“What we discovered is that cocaine activates these microglia, which causes the release of an inflammatory signal which then tries to reverse the changes that cocaine is inducing in the neurons,”
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The team found that TNF suppresses specific synaptic changes caused by cocaine-changes that are thought to underlie addiction. But Dr. Stellwagen explains that this beneficial mechanism doesn’t last. “The microglia response fades over time. One of the things that could transition somebody from just casual use into chronic dependency might be the fading of this adaptive signal which then allows the drugs to solidify their change to the neural circuitry.”
So can microglia be enticed to keep going? To find out, the team used a pharmaceutical agent that stimulates microglial production of TNF. Researchers observed that a cocaine-induced behavioral change in mice, the progressive increase in movement induced by cocaine,-was reduced in the animals who received this agent.
This exciting result holds promise for one day developing treatments that could cut down on drug relapse rates, which can run as high as 80 per cent.
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Pregnenolone could be a potential therapy to treat the detrimental effects of prenatal exposure to marijuana. (2019) www.sciencedaily.com
From the article:
A University of Maryland School of Medicine study using a preclinical animal model suggests that prenatal exposure to THC, the psychoactive component of cannabis, makes the brain’s dopamine neurons (an integral component of the reward system) hyperactive and increases sensitivity to the behavioral effects of THC during pre-adolescence. This may contribute to the increased risk of psychiatric disorders like schizophrenia and other forms of psychosis later in adolescence that previous research has linked to prenatal cannabis use, according to the study published today in journal Nature Neuroscience.
The team of researchers, from UMSOM, the University of Cagliari (Italy) and the Hungarian Academy of Sciences (Hungary), found that exposure to THC in the womb increased susceptibility to THC in offspring on several behavioral tasks that mirrors the effects observed in many psychiatric diseases. These behavioral effects were caused, at least in part, by hyperactivity of dopamine neurons in a brain region called the ventral tegmental area (VTA), which regulates motivated behaviors.
More importantly, the researchers were able to correct these behavioral problems and brain abnormalities by treating experimental animals with pregnenolone, an FDA-approved drug currently under investigation in clinical trials for cannabis use disorder, schizophrenia, autism, and bipolar disorder.
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From linked article:
The researchers gave the monkeys a two-bottle choice between water and ethanol, and administered one group an analog of FGF21 to see what effect it had. Sure enough, the test monkeys drank 50 percent less alcohol than the control group. Similar tests in mice also saw a 50-percent reduction in alcohol consumption after being given either human FGF21 or an analog. Interestingly though, the mice and monkeys still chose the ethanol just as often as before, but they drank far less each time.
Fibroblast growth factor 21 happens to be modulated by aerobic exercise:
In a new study published in the scientific Journal of Clinical Investigation – Insight, the researchers show that cardio training on an exercise bike causes three times as large an increase in the production of the hormone FGF21 than strength training with weights. FGF21 has a lot of positive effects on metabolism.
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Vitamin D deficiency increases addictive behaviors. www.eurekalert.org
Opioid use disorder is defined as a problematic pattern of opioid use that leads to serious impairment or distress. It has emerged as a public health crisis in the United States, affecting as many as two million people aged 12 years and older. A multifaceted approach to reducing opioid use disorders involves targeting preventable environmental factors in addition to restricting opioid prescriptions. One group of researchers investigated the effects of vitamin D status on reward-seeking behaviors like opioid use and sunlight exposure in mice.
Opioid drugs are highly addictive due to their effects on the reward-seeking centers in the brain. Previous research suggests sunbed tanning may be addictive in ways similar to effects of opioids. Exposure to ultraviolet (UV) light causes the skin to produce vitamin D. It also induces the production of beta-endorphins, which are natural opioids with addictive properties. Humans' UV light-seeking behavior may have developed as an evolutionary strategy to maintain adequate vitamin D levels. Whether vitamin D status has an effect on UV light-seeking or prescription opioid-seeking behavior is unclear.
To assess the relationship between vitamin D levels and opioid use disorder, the authors analyzed data from the National Health and Nutrition Examination Survey (NHANES), a long-term study collecting lifestyle and health data from participants in the United States. To determine the effects of vitamin D deficiency on opioid reward sensitivity, opioid-seeking behavior, and pain, the researchers performed multiple experiments with normal mice, mice without functioning vitamin D receptors, and mice without functioning opioid receptors.
Compared to NHANES participants with normal serum vitamin D levels (greater than 20 nanograms per milliliter), those with insufficient vitamin D levels (12 to 20 nanograms per milliliter) were 1.27 times more likely to have opioid use disorder. Participants with vitamin D deficiency (less than 12 nanograms per milliliter) were 1.62 times more likely to have opioid use disorder. In mice, vitamin D deficiency increased the rewarding and pain-relieving effects of UV exposure through altered gene expression in key brain regions. Finally, vitamin D deficiency sensitized mice to the pain-relieving and rewarding effects of opioid drugs, while restoring vitamin D levels to normal decreased both UV-seeking and opioid-seeking behavior.
The authors concluded that the addictive effects of sunlight exposure may be an evolutionary strategy to maintain adequate vitamin D levels and that opioid-seeking may be a consequence of vitamin D deficiency. Their results imply that obtaining and maintaining adequate vitamin D levels through UV light exposure or supplementation may help prevent or treat opioid use disorder.
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BDNF genetic variant predicts success in alcohol dependence treatment. www.sciencedaily.com
Alcohol dependence is a complex disorder that increases a person’s risk of death from all causes. Findings from a 2009 study suggest that variations in certain genes can impact the likelihood of relapsing following treatment.
BDNF is involved in neuronal growth and survival, as well as influencing neurotransmitters – chemical signals from the nervous system. Low BDNF levels have been linked to the development of depression, anxiety, and alcohol dependence.
Previous research has demonstrated that alcohol dependence has a genetic component. The current study investigated whether common variations in certain genes would have an effect on post-treatment relapse.
The prospective study involved 154 participants who met the criteria for alcohol dependence and were admitted to a treatment facility. The patients provided blood samples for genetic analysis and completed self-assessment questionnaires about depression, hopelessness, impulsivity, and the severity of their alcohol use. The authors followed up with participants for approximately one year to assess whether they had relapsed. Relapse was defined as any drinking during the observation period, with heavy drinking considered as more than four drinks per day for more than four consecutive days. During the follow-up period, 59 (48 percent) participants relapsed, with 48 returning to heavy drinking. The average time to relapse was 218 days.
The authors tested a genetic variant that resides in the BDNF gene, known as Val66Met. They observed that participants with the Val form of this gene were more likely to relapse compared to those with the Met version. Participants with two copies of the Val allele – one from each parent – had higher rates of relapse and shorter times to relapse when compared to carriers of at least one Met allele.
These findings suggest that BDNF influences a person’s ability to remain abstinent following treatment for alcohol dependence. With further evaluation, these findings may help clinicians to identify people at increased risk for post-treatment relapse and tailor their care plans.
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Brain-derived neurotrophic factor may be able to disrupt cocaine-seeking when applied directly to the nucleus accumbens in the brain [animal research] www.sciencedaily.com
From the article:
Cocaine relapse was significantly reduced in a preclinical model when brain-derived neurotropic factor (BDNF) was applied to the nucleus accumbens deep in the brain immediately before cocaine-seeking behavior, report investigators at the Medical University of South Carolina (MUSC) in an article published online in June 2018 by Addiction Biology.
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While other research groups have studied how BDNF administration affects drug self-administration and relapse, no one has looked at what happens if BDNF is given immediately before relapse.
Since low serum BDNF levels are seen in cocaine-dependent patients compared to non-addicts, the MUSC researchers sought to better understand the connection between BDNF and cocaine relapse. The nucleus accumbens was selected as the focal point for BDNF administration since it is a central component of the brain reward circuit.
“An important aspect of this study is that while others have shown that BDNF is important for establishing the state of addiction, we find that can also be used to reverse addiction,” says Peter Kalivas, Ph.D., professor and chair in the Department of Neuroscience. “This exemplifies that the primary effect of BDNF is to promote changes in the brain, and that this capacity to change the brain contributes to how people get addicted, but also can be harnessed to remove brain pathologies such as drug addiction.”
The findings reported in Addiction Biology are the first to show that applying BDNF to the nucleus accumbens immediately before the reinstatement phase, when the rats are once again seeking cocaine due to cue exposure, greatly reduces relapse.