Archive for the ‘PTSD’ Category

mdma

By DAVE PHILIPPS

After three tours in Iraq and Afghanistan, C. J. Hardin wound up hiding from the world in a backwoods cabin in North Carolina. Divorced, alcoholic and at times suicidal, he had tried almost all the accepted treatments for post-traumatic stress disorder: psychotherapy, group therapy and nearly a dozen different medications.

“Nothing worked for me, so I put aside the idea that I could get better,” said Mr. Hardin, 37. “I just pretty much became a hermit in my cabin and never went out.”

Then, in 2013, he joined a small drug trial testing whether PTSD could be treated with MDMA, the illegal party drug better known as Ecstasy.

“It changed my life,” he said in a recent interview in the bright, airy living room of the suburban ranch house here, where he now lives while going to college and working as an airplane mechanic. “It allowed me to see my trauma without fear or hesitation and finally process things and move forward.”

Based on promising results like Mr. Hardin’s, the Food and Drug Administration gave permission Tuesday for large-scale, Phase 3 clinical trials of the drug — a final step before the possible approval of Ecstasy as a prescription drug.

If successful, the trials could turn an illicit street substance into a potent treatment for PTSD.

Through a spokeswoman, the F.D.A. declined to comment, citing regulations that prohibit disclosing information about drugs that are being developed.

“I’m cautious but hopeful,” said Dr. Charles R. Marmar, the head of psychiatry at New York University’s Langone School of Medicine, a leading PTSD researcher who was not involved in the study. “If they can keep getting good results, it will be of great use. PTSD can be very hard to treat. Our best therapies right now don’t help 30 to 40 percent of people. So we need more options.”

But he expressed concern about the potential for abuse. “It’s a feel-good drug, and we know people are prone to abuse it,” he said. “Prolonged use can lead to serious damage to the brain.”

The Multidisciplinary Association for Psychedelic Studies, a small nonprofit created in 1985 to advocate the legal medical use of MDMA, LSD, marijuana and other banned drugs, sponsored six Phase 2 studies treating a total of 130 PTSD patients with the stimulant. It will also fund the Phase 3 research, which will include at least 230 patients.

Two trials here in Charleston focused on treating combat veterans, sexual assault victims, and police and firefighters with PTSD who had not responded to traditional prescription drugs or psychotherapy. Patients had, on average, struggled with symptoms for 17 years.

After three doses of MDMA administered under a psychiatrist’s guidance, the patients reported a 56 percent decrease of severity of symptoms on average, one study found. By the end of the study, two-thirds no longer met the criteria for having PTSD. Follow-up examinations found that improvements lasted more than a year after therapy.

“We can sometimes see this kind of remarkable improvement in traditional psychotherapy, but it can take years, if it happens at all,” said Dr. Michael C. Mithoefer, the psychiatrist who conducted the trials here. “We think it works as a catalyst that speeds the natural healing process.”

The researchers are so optimistic that they have applied for so-called breakthrough therapy status with the Food and Drug Administration, which would speed the approval process. If approved, the drug could be available by 2021.

Under the researchers’ proposal for approval, the drug would be used a limited number of times in the presence of trained psychotherapists as part of a broader course of therapy. But even in those controlled circumstances, some scientists worry that approval as a therapy could encourage more illegal recreational use.

“It sends the message that this drug will help you solve your problems, when often it just creates problems,” said Andrew Parrott, a psychologist at Swansea University in Wales who has studied the brains of chronic Ecstasy users. “This is a messy drug we know can do damage.”

Allowing doctors to administer the drug to treat a disorder, he warned, could inadvertently lead to a wave of abuse similar to the current opioid crisis.

During initial studies, patients went through 12 weeks of psychotherapy, including three eight-hour sessions in which they took MDMA. During the sessions, they lay on a futon amid candles and fresh flowers, listening to soothing music.

Dr. Mithoefer and his wife, Ann Mithoefer, and often their portly terrier mix, Flynn, sat with each patient, guiding them through traumatic memories.

“The medicine allows them to look at things from a different place and reclassify them,” said Ms. Mithoefer, a psychiatric nurse. “Honestly, we don’t have to do much. Each person has an innate ability to heal. We just create the right conditions.”

Research has shown that the drug causes the brain to release a flood of hormones and neurotransmitters that evoke feelings of trust, love and well-being, while also muting fear and negative emotional memories that can be overpowering in patients with post-traumatic stress disorder. Patients say the drug gave them heightened clarity and ability to address their problems.

For years after his combat deployments, Mr. Hardin said he was sleepless and on edge. His dreams were marked with explosions and death. The Army gave him sleeping pills and antidepressants. When they didn’t work, he turned to alcohol and began withdrawing from the world.

“I just felt hopeless and in the dark,” he said. “But the MDMA sessions showed me a light I could move toward. Now I’m out of the darkness and the world is all around me.”

Since the trial, he has gone back to school and remarried.

The chemist Alexander Shulgin first realized the euphoria-inducing traits of MDMA in the 1970s, and introduced it to psychologists he knew. Under the nickname Adam, thousands of psychologists began to use it as an aid for therapy sessions. Some researchers at the time thought the drug could be helpful for anxiety disorders, including PTSD, but before formal clinical trails could start, Adam spread to dance clubs and college campuses under the name Ecstasy, and in 1985, the Drug Enforcement Administration made it a Schedule 1 drug, barring all legal use.

Since then, the number of people seeking treatment for PTSD has exploded and psychiatry has struggled to keep pace. Two drugs approved for treating the disorder worked only mildly better than placebos in trials. Current psychotherapy approaches are often slow and many patients drop out when they don’t see results. Studies have shown combat veterans are particularly hard to treat.

In interviews, study participants said MDMA therapy had not only helped them with painful memories, but also had helped them stop abusing alcohol and other drugs and put their lives back together.

On a recent evening, Edward Thompson, a former firefighter, tucked his twin 4-year-old girls into bed, turned on their night light, then joined his wife at a backyard fire.

“If it weren’t for MDMA … ” he said.

“He’d be dead,” his wife, Laura, finished.

They both nodded.

Years of responding to gory accidents left Mr. Thompson, 30, in a near constant state of panic that he had tried to numb with alcohol and prescription opiates and benzodiazepines.

By 2015, efforts at therapy had failed, and so had several family interventions. His wife had left with their children, and he was considering jumping in front of a bus.

A member of a conservative Anglican church, Mr. Thompson had never used illegal drugs. But he was struggling with addiction from his prescription drugs, so he at first rejected a suggestion by his therapist that he enter the study. “In the end, I was out of choices,” he said.

Three sessions with the drug gave him the clarity, he said, to identify his problems and begin to work through them. He does not wish to take the drug again.

“It gave me my life back, but it wasn’t a party drug,” he said. “It was a lot of work.”

http://mobile.nytimes.com/2016/11/29/us/ptsd-mdma-ecstasy.html

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Deep in the Amazon rainforest, a group of veterans chokes down a gritty, gut-wrenching shot of liquid absolution. They try to drink away their severe mental disturbances, but not the way you drink away your ex-girlfriend with a bottle of whiskey. They’re looking for a cure. Their leader: 27-year-old retired infantryman Ryan LeCompte. Their goal: to hallucinate away their terrible memories.

From a few fringe psychiatrists to veterans like LeCompte, there is a budding belief that extreme hallucination can save our brains from themselves. Several organizations, including the Multidisciplinary Association for Psychedelic Studies (MAPS), and adventurous doctors around the world test out psychedelics such as MDMA, psilocybin and ayahuasca for possible medical uses.

Ayahuasca is a devilish brew. It’s made of vines and roots found in the Amazon; drinking it equals a heavy psychedelic experience and profuse vomiting. “As the shapes and colors continued to move about, they sometimes converged to create the face of a woman, who of course I immediately labeled as Aya,” says an ayahuasca user on the underground drug website Erowid. Aya is known as the spirit or soul of the ayahuasca world. LeCompte described having kaleidoscope vision during his ayahuasca trip, and he even began to dance and went to look at leaves and other pieces of the nature around him at points.

Ryan LeCompte is a scruffy former Marine who, today, is studying at the eccentric Naropa University in Boulder. The school was founded by Tibetan Buddhist teacher and Oxford University scholar Chögyam Trungpa and includes schools such as the Jack Kerouac School of Disembodied Poetics. The beat poets used to flock to there. It’s a Buddhist-inspired school infamous for attracting people who are looking for an alternative education in an attractive location.

For his part, LeCompte didn’t ever face a PTSD diagnosis during his time in service. But he’s lucky, because many of his peers did. What he did experience still shook him. In 2008, while stationed in 8th and I Marine Barracks in Washington, D.C., LeCompte walked into the room of a good friend in his barracks one morning to find Sgt. Jorge Leon-Alcivar dead—a suicide. He was not the only Marine LeCompte encountered who would take his own life. At least 22 veterans kill themselves every day. Leon-Alcivar’s death was the final straw, and three years later LeCompte retired from the Marines to start fighting PTSD. He received his End of Active Service honorable discharge after four years in the Marines and didn’t look back.

LeCompte began traveling to the VA hospital in Birmingham, Alabama, where he was living, to learn what was ailing disturbed veterans and soldiers. He hung around in waiting rooms, cautiously approaching the soldiers, wheedling their stories out. But it didn’t take much persuasion; the men were “so beat,” he recalls, that they opened up to him instantly. This took course over several years, during his free time, while he did contract work building helicopters.

Soon, LeCompte had amassed the information from about 100 cases in Birmingham; Veterans spilled almost everything to him: their meds, their dosages, their choice of therapy. It all added up. Over and over again, he discovered his peers were taking the same types of medicines such Zoloft and Paxil, in the same dosages, 50 to 200mg of Zoloft a day or 20 to 60mg of Paxil a day were common, and with the same form of EMDR therapy. EMDR is a somatic therapy that follows eye movements and dream states.

LeCompte didn’t see anything wrong with the therapy. How about the drugs? Yeah, it’s probably the drugs. LeCompte’s complaints ring of an old story these days in American psychiatry: we’re too drugged up, we’re overdosed and overdiagnosed. It’s a complaint plenty of professionals agree with, but only a handful of psychiatrists are taking alternate routes. “There are some veterans who actually do respond to those meds, but it’s rare,” Dr. Sue Sisley, an expert on PTSD in veterans who has studied treating the illness with marijuana, told ATTN:. “The vets who respond to the standard FDA approved meds like Zoloft or Paxil is probably less than 10 percent. The rest come in looking like zombies.”

LeCompte had tried almost all the drugs they were offering, from “highly addictive anxiolytics like Klonopin, and … Prozac as an anti-depressant and Ambien for a sleep aid,” he said. “These different drugs sort of mixed together in a cocktail just as a recipe for disaster,” he said. He never tried to contact U.S. Veteran’s Affairs to inform them of these problems, because he didn’t think they would do anything about it. VA psychiatrists like Dr. Basimah Khulusi of Missouri have been fired for simply refusing to increase medication dosages that they didn’t think their patients needed shows the kind of system LeCompte was dealing with.

LeCompte looked into how these drugs work and found they’re just mind blockers, they’re not helping you deal with your problems. “Medications do not entirely eliminate symptoms but provide a symptom reduction and are sometimes more effective when used in conjunction with an ongoing program of trauma specific psychotherapy,” according to the VA website.

LeCompte looked at research from people like Julie D. Megler, watched videos of the academic conferences focusing on psychedelics called Psychedemia from Penn State and went on websites like Erowid to look at ayahuasca experiences people had posted to the site. What did he learn? “Something like ayahuasca or MDMA is used to bridge severed connections in the brain that trauma plays a big part in creating,” he said.

“Ayahuasca opens the limbic pathways of the brain to affect the emotional core of the trauma in a way similar to affective psychotherapy for trauma, and also impacts higher cortical areas … to allow the patient to assign a new context to their trauma,” wrote brain experts J. L. Nielson and J. D. Megler, in the book The Therapeutic Use of Ayahuasca.

Soon, LeCompte started having conversations with veterans and began informing people of the possible benefits of ayahuasca, wondering if anyone else was daring enough to start considering the idea of drinking a shot of psychedelics for their PTSD. LeCompte had never tried ayahuasca, but he was willing to try anything to help his comrades. Eventually he heard of an ayahuasca retreat, the Phoenix Ayahuasca retreat in Peru, where he could test out his medicine.

It took him six months to do what any sane person would do before planning a group outing to South America to hallucinate in a forest together… he started a nonprofit. Its name? The Veterans for Entheogenic Therapy. Other vets started to find him; some were suicidal, exhausted by the daily challenge of deciding whether or not they wanted to be alive. He didn’t know them, but he felt he intimately understood – or at least sympathized with – their minds. He rounded up a trip: five other vets, and him. MAPS helped pay for two of the trips for veterans who couldn’t afford it, and the rest paid for themselves.

The prep was strangely regimented: LeCompte had to ensure the veterans were off their medication for a month leading up to the trip; anti-depressants plus ayahuasca equal a lethal mix. That task amounted to phone therapy and keeping a close eye on everyone: He called the guys every day, even their friends and family, to make sure the men had quit their pills, he said. But he made it work. The families may have thought the idea was strange, but LeCompte says none of them tried to stop their family members because of their knowledge that the drugs weren’t helping treat the PTSD symptoms, and they just wanted to help their family.

The veterans flew into Iquitos, Peru, from Lima – from Iquitos, they sat in a van all the way to the Amazon, winding past motorbikes and rickshaws “on back roads in the middle of bum fuck,” LeCompte says.

Then their lives collided and things got weird.

They were stationed for 10 days at Phoenix Ayahuasca. The camp was little more than a set of huts in the jungle, made from wood and leaves. They would drink the ayahuasca on ceremony nights and be led through their experience by the shaman, and they would stay in their personal huts on days off to reflect on their experiences alone.

LeCompte said the ayahuasca drink “tastes like shit.” The shaman leading the experience dressed in all white scrub-like clothes, like a nurse lost in the jungle. After you drink the brew, the shaman’s job is simply to observe. He diagnoses: Is anyone losing it? Some people have been known to begin convulsing. Is this the moment they need to hear a song that will send them burrowing into a different dimension? “I don’t know how he does it. It’s beyond my rational mind,” LeCompte said. “It” amounts to singing, blowing smoke on trippers’ faces and using instruments like a rattler to change their state of mind.

For his part, LeCompte only wanted two out of the four drink ceremonies, since they were so powerful. It certainly wasn’t about the PTSD for LeCompte; he was trying to get past his experiences of fallen friends and broken relationships. He says just returning home to family and friends from military service or an ayahuasca trip is a difficult experience of its own. “You’re a changed person and there’s no doubting or denying that.”

“Most people get a cut, and they put a bandaid on it,” he said. “These people have had these wounds for so long that they’ve become infected. The infection can’t be fought off with a bandaid.” LeCompte sees ayahuasca as an antibiotic, not a bandaid.

LeCompte is now planning to do an official study to look at how ayahuasca could treat PTSD, which will serve as his thesis for Naropa University. It is being sponsored by MAPS, and it will focus on 12 veterans with treatment resistant PTSD who will try using ayahuasca to treat it. The plan is to conduct the study over 10 days in early 2016. LeCompte is currently running an Indiegogo campaign to fund research and education around the medicinal use of ayahuasca.

http://www.stumbleupon.com/su/2KDuBh/:1EfXhqlsu:Y+0NYw4t/www.attn.com/stories/2301/semicolon-tattoo-mental-health

Researchers from Louisiana State University have found that blueberries may be effective in the treatment for post-traumatic stress disorder (PTSD). Findings from the study have been presented at the Experimental Biology Meeting in Boston, MA.

Presently, the only therapy approved by the Food and Drug Administration (FDA) for PTSD is selective serotonin reuptake inhibitors (SSRIs) such as sertraline and paroxetine. Study authors have previously shown that SSRIs increase the level of serotonin (5-HT) and norepinephrine, and that the increased norepinephrine be a possible reason for the reduced efficacy of SSRI therapy.

For this study, the team studied the ability of blueberries to modulate neurotransmitter levels in a rat model of PTSD. Some of the rats received a 2% blueberry-enriched supplement diet and others received a control diet. A third control group consisted of rats without PTSD and received a standard diet without blueberries. Scientists used high-performance liquid chromatography to to measure monoamines and related metabolite levels.

Rats with PTSD who did not receive blueberries showed a predictable increase in 5-HT and norepinephrine level compared with the control group. But rats with PTSD that received blueberries showed a beneficial increase in 5-HT levels with no impact on norepinephrine levels, which suggest that blueberries can alter neurotransmitter levels in PTSD. More studies are needed to understand the protective effects of blueberries and its potential target as a treatment for PTSD.

http://www.empr.com/benefits-of-blueberries-for-post-traumatic-stress-disorder-explored-in-study/article/405810/

In the inner city, a health problem is making it harder for young people to learn. inner-city kids suffer from post-traumatic stress disorder (PTSD).

“Youth living in inner cities show a higher prevalence of post-traumatic stress disorder than soldiers,” according to Howard Spivak M.D., director of the U.S. Centers for Disease Control and Prevention’s Division of Violence Prevention.

Spivak presented research at a congressional briefing in April 2012 showing that children are essentially living in combat zones. Unlike soldiers, children in the inner city never leave the combat zone and often experience trauma repeatedly.

One local expert says national data suggests one in three urban youth have mild to severe PTSD. “You could take anyone who is experiencing the symptoms of PTSD, and the things we are currently emphasizing in school will fall off their radar. Because frankly it does not matter in our biology if we don’t survive the walk home,” said Jeff Duncan-Andrade, Ph.D. of San Francisco State University.

In 2013, there were 47 recorded lockdowns in Oakland public schools – again, almost all in East and West Oakland.

Students at Fremont High showed where one classmate was shot.

“If someone got shot that they knew or that they cared about… they’re going to be numb,” one student said. “If someone else in their family got shot and killed they will be sad, they will be isolated because I have been through that.”

Gun violence is only one of the traumas or stressors in concentrated areas of deep poverty.

“Its kids are unsafe, they’re not well fed,” Duncan-Andrade said. “And when you start stacking those kids of stressors on top of each other, that’s when you get these kinds of negative health outcomes that seriously disrupt school performance.”

Duncan-Andrade said doctors at Harvard’s School of Public Health have come up with a new diagnosis of complex PTSD, describing people who are repeatedly re-exposed to trauma, which Duncan-Andrade said, would include many inner-city youth.

In Oakland, about two-thirds of the murders last year were actually clustered in East Oakland, where 59 people were killed.

Teachers and administrators who graduated from Fremont High School in East Oakland and have gone back to work there spoke with KPIX 5.

“These cards that (students) are suddenly wearing around their neck that say ‘Rest in peace.’ You have some kids that are walking around with six of them. Laminated cards that are tributes to their slain friends,” said teacher Jasmene Miranda.

Jaliza Collins, also a teacher at Fremont, said, “It’s depression, it’s stress, it’s withdrawal, it’s denial. It’s so many things that is encompassed and embodied in them. And when somebody pushes that one button where it can be like, ‘please go have a seat,’ and that can be the one thing that just sets them off.”

Even the slang nickname for the condition, “Hood Disease,” itself causes pain, and ignites debate among community leaders, as they say the term pejoratively refers to impoverished areas, and distances the research and medical community from the issue.

“People from afar call it ‘Hood Disease,’ – it’s what academics call it,” said Olis Simmons, CEO of Youth UpRising working in what she describes as the epicenter of the issue: East Oakland.

She said the term minimizes the pain that her community faces, and fails to capture the impact this has on the larger community.

“In the real world where this affects real lives, people are suffering from a chronic level of trauma that doesn’t have a chance to heal because they’re effectively living in a war zone within your town,” said Simmons.

“Terms like ‘hood disease’ mean it’s someone else’s problem, but it’s not. That’s a lie. It’s a collective problem, and the question is what are we prepared to do about it?”

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

http://sanfrancisco.cbslocal.com/2014/05/16/hood-disease-inner-city-oakland-youth-suffering-from-post-traumatic-stress-disorder-ptsd-crime-violence-shooting-homicide-murder/

pot

by Jon Hamilton

Veterans who smoke marijuana to cope with post-traumatic stress disorder may be onto something. There’s growing evidence that pot can affect brain circuits involved in PTSD.

Experiments in animals show that tetrahydrocannabinol, the chemical that gives marijuana its feel-good qualities, acts on a system in the brain that is “critical for fear and anxiety modulation,” says Andrew Holmes, a researcher at the National Institute on Alcohol Abuse and Alcoholism. But he and other brain scientists caution that marijuana has serious drawbacks as a potential treatment for PTSD.

The use of marijuana for PTSD has gained national attention in the past few years as thousands of traumatized veterans who fought in Iraq and Afghanistan have asked the federal government to give them access to the drug. Also, Maine and a handful of other states have passed laws giving people with PTSD access to medical marijuana.

But there’s never been a rigorous scientific study to find out whether marijuana actually helps people with PTSD. So lawmakers and veterans groups have relied on anecdotes from people with the disorder and new research on how both pot and PTSD works in the brain.

An Overactive Fear System

When a typical person encounters something scary, the brain’s fear system goes into overdrive, says Dr. Kerry Ressler of Emory University. The heart pounds, muscles tighten. Then, once the danger is past, everything goes back to normal, he says.

But Ressler says that’s not what happens in the brain of someone with PTSD. “One way of thinking about PTSD is an overactivation of the fear system that can’t be inhibited, can’t be normally modulated,” he says.

For decades, researchers have suspected that marijuana might help people with PTSD by quieting an overactive fear system. But they didn’t understand how this might work until 2002, when scientists in Germany published a mouse study showing that the brain uses chemicals called cannabinoids to modulate the fear system, Ressler says.

There are two common sources of cannabinoids. One is the brain itself, which uses the chemicals to regulate a variety of brain cells. The other common source is Cannabis sativa, the marijuana plant.

So in recent years, researchers have done lots of experiments that involved treating traumatized mice with the active ingredient in pot, tetrahydrocannabinol (THC), Ressler says. And in general, he says, the mice who get THC look “less anxious, more calm, you know, many of the things that you might imagine.”

Problems with Pot

Unfortunately, THC’s effect on fear doesn’t seem to last, Ressler says, because prolonged exposure seems to make brain cells less sensitive to the chemical.

Another downside to using marijuana for PTSD is side effects, says Andrew Holmes at the National Institute on Alcohol Abuse and Alcoholism. “You may indeed get a reduction in anxiety,” Holmes says. “But you’re also going to get all of these unwanted effects,” including short-term memory loss, increased appetite and impaired motor skills.

So for several years now, Holmes and other scientists have been testing drugs that appear to work like marijuana, but with fewer drawbacks. Some of the most promising drugs amplify the effect of the brain’s own cannabinoids, which are called endocannabinoids, he says. “What’s encouraging about the effects of these endocannabinoid-acting drugs is that they may allow for long-term reductions in anxiety, in other words weeks if not months.”

The drugs work well in mice, Holmes says. But tests in people are just beginning and will take years to complete. In the meantime, researchers are learning more about how marijuana and THC affect the fear system in people.

At least one team has had success giving a single dose of THC to people during something called extinction therapy. The therapy is designed to teach the brain to stop reacting to something that previously triggered a fearful response.

The team’s study found that people who got THC during the therapy had “long-lasting reductions in anxiety, very similar to what we were seeing in our animal models,” Holmes says. So THC may be most useful when used for a short time in combination with other therapy, he says.

As studies continue to suggest that marijuana can help people with PTSD, it may be unrealistic to expect people with the disorder to wait for something better than marijuana and THC, Ressler says. “I’m a pragmatist,” he says. “I think if there are medications including drugs like marijuana that can be used in the right way, there’s an opportunity there, potentially.”

http://www.npr.org/blogs/health/2013/12/23/256610483/could-pot-help-veterans-with-ptsd-brain-scientists-say-maybe

green-image

The flip of a single molecular switch helps create the mature neuronal connections that allow the brain to bridge the gap between adolescent impressionability and adult stability. Now Yale School of Medicine researchers have reversed the process, recreating a youthful brain that facilitated both learning and healing in the adult mouse.

Scientists have long known that the young and old brains are very different. Adolescent brains are more malleable or plastic, which allows them to learn languages more quickly than adults and speeds recovery from brain injuries. The comparative rigidity of the adult brain results in part from the function of a single gene that slows the rapid change in synaptic connections between neurons.

By monitoring the synapses in living mice over weeks and months, Yale researchers have identified the key genetic switch for brain maturation a study released March 6 in the journal Neuron. The Nogo Receptor 1 gene is required to suppress high levels of plasticity in the adolescent brain and create the relatively quiescent levels of plasticity in adulthood. In mice without this gene, juvenile levels of brain plasticity persist throughout adulthood. When researchers blocked the function of this gene in old mice, they reset the old brain to adolescent levels of plasticity.

“These are the molecules the brain needs for the transition from adolescence to adulthood,” said Dr. Stephen Strittmatter. Vincent Coates Professor of Neurology, Professor of Neurobiology and senior author of the paper. “It suggests we can turn back the clock in the adult brain and recover from trauma the way kids recover.”

Rehabilitation after brain injuries like strokes requires that patients re-learn tasks such as moving a hand. Researchers found that adult mice lacking Nogo Receptor recovered from injury as quickly as adolescent mice and mastered new, complex motor tasks more quickly than adults with the receptor.

“This raises the potential that manipulating Nogo Receptor in humans might accelerate and magnify rehabilitation after brain injuries like strokes,” said Feras Akbik, Yale doctoral student who is first author of the study.

Researchers also showed that Nogo Receptor slows loss of memories. Mice without Nogo receptor lost stressful memories more quickly, suggesting that manipulating the receptor could help treat post-traumatic stress disorder.

“We know a lot about the early development of the brain,” Strittmatter said, “But we know amazingly little about what happens in the brain during late adolescence.”

Other Yale authors are: Sarah M. Bhagat, Pujan R. Patel and William B.J. Cafferty

The study was funded by the National Institutes of Health. Strittmatter is scientific founder of Axerion Therapeutics, which is investigating applications of Nogo research to repair spinal cord damage.

http://news.yale.edu/2013/03/06/flip-single-molecular-switch-makes-old-brain-young

drinking_drosophila

Rejection stinks. It literally hurts. But worse, it has an immediate and negative impact on our brains, producing withdrawal symptoms as if we’re quitting a serious addiction cold turkey. It’s no wonder, then, that we are tempted to turn to drugs to makeourselves feel better. But we’re not the only species that drowns our sorrows when we’re lonely – as a new study in Science reveals, rejected Drosophila do, too. Scientists have found not only will these sexually frustrated flies choose to consume more alcohol than their happily mated peers, sex and alcohol consumption activate the same neurological pathway in their brains.

Drosophila melanogaster males sure know how to woo a lady. When placed in the same container as a potential mate, a male fly will play her a delicate love song by vibrating one wing, caress her rear end, and gently nuzzle her most private of parts with his proboiscis to convince her that he is one heck of a lover. But even the most romantic fly can’t convince an already mated female Drosophila to give up the goods, so scientists were able to use the girls’ steely resolve to see how rejection affects fly drinking behavior.

“Alcohol is one of the most widely used and abused drugs in the world,” explains lead author Galit Shohat-Ophir. “The fruit fly Drosophila melanogaster is an ideal model organism to study how the social environment modulates behavior.” Previous studies have found that Drosophila melanogaster exhibit complex addiction-like behaviors. So in the controlled setting of Ulrike Heberlein’s lab at the University of California San Francisco, researchers paired male fruit flies with three types of females: 1) unmated females, which were willing and happy to mate; 2) mated females, which actively rejected the men; and 3) decapitated females, which didn’t actively reject the guys but, well, weren’t exactly willing partners either. After the flies were satisfied or frustrated, they were offered regular food and food spiked with ethanol, and the researchers measured which type they preferred to see if there was any connection between sex and drinking.

The flies that were rejected drank significantly more than their satisfied peers, but so did the ones paired with incapacitated girls, suggesting that it wasn’t the social aspect of rejection but sexual deprivation that drives male flies to increase their ethanol consumption (see the video at the end!). This alcoholic behavior was very directly related to the guy fly ever getting laid, for even after days of blue balls, if he was allowed to spend some time with a willing woman, he no longer preferred the spiked food.

What the scientists really wanted to understand, though, was why. What drives a frustrated fly to the flask? So to look at the underlying mechanism of this phenomenon, the scientists examined the flies’ brains. A body of scientific literature has connected one particular neurotransmitter, neuropeptide F (NPF), to ethanol-related behaviors in Drosophila, so it was a logical place to start. A very similar neurotransmitter in our brains, called neuropeptide Y (NPY), is linked to alcoholism.

Increased expression of NPF in mated male brains, as shown through immunochemistry.

The team found that sexual frustration caused an immediate decrease in the expression of NPF, while sex increased expression. Furthermore, when they used genetics to artificially knock down NPF levels in the satisfied flies, they drank as much as their not-so-satisfied friends. Similarly, when the researchers artificially increased NPF levels, flies stayed sober. This is the first time NPF levels have connected sexual activity to drinking. Clearly, NPF levels controlled the flies’ desire to drink, so the team further explored how NPF works in the fly’s brain.

Many animals, including ourselves, possess a neurological reward system which reinforces good behavior. Through this system, we ascribe pleasure or positive feelings to things we do that are necessary for species survival, including sex, eating, and social interaction. Drugs tap into this system, stimulating pleasure which can lead to addiction. Previous studies have shown that flies find intoxication rewarding, so the researchers hypothesized that NPF may play a role in the reward system.

Preference tests showed that artificially increasing NPF levels in the absence of sex or ethanol was rewarding to the flies, confirming the scientists’ hypothesis. This was further supported by the discovery that constantly activating NPF abolished the flies’ tendency to consider ethanol rewarding.

“NPF is a currency of reward” explains Shohat-Ophir. High NPF levels signal good behavior in Drosophila brains, thus reinforcing any activities which led to that state. This is a truly novel discovery, for while NPF and the mammal version, NPY, have been linked to alcohol consumption, no animal model has ever placed NPF/NPY in the reward system.

Understanding the role of NPF in reward-seeking behaviors may lead to better treatments for addicts. “In mammals, including humans, NPY may have a similar role [as NPF],” says Shohat-Ophir. “If so, one could argue that activating the NPY system in the proper brain regions might reverse the detrimental effects of traumatic and stressful experiences, which often lead to drug abuse.” Already, NPY and drugs that affect the function of its receptors are in clinical trials for anxiety, PTSD, mood disorders and obesity. This study suggests that perhaps they should be tested as treatment for alcoholism, too, as well as other reward-based addictions.

Research: Shohat-Ophir, G, KR Kaun & R Azanchi (2012). Sexual Deprivation Increases Ethanol Intake in Drosophila. Science 335: 1351-1355.

Click  http://blogs.scientificamerican.com/science-sushi/2012/03/15/flies-drink-upon-rejection/

to view a sequence of  three videos that show a male fly courting and successfully mating with a female fly, another male fly being rejected by a female, and a male choosing to consume an alcohol-infused solution over a non-alcohol solution. Video © Science/AAAS