Archive for the ‘glutamate’ Category

Humans have been ingesting mind-altering substances for a very long time. Hallucinogen-huffing bowls 2,500 years old (http://www.livescience.com/5240-ancient-family-heirlooms-snort-hallucinogens.html) have been found on islands in the Lesser Antilles, and traditional cultures from the Americas to Africa use hallucinogenic substances for spiritual purposes. Here are some notable substances that send the mind tripping.

LSD is commonly known as “acid,” but its scientific name is a mouthful: lysergic acid diethylamaide. The drug was first synthesized in 1938 from a chemical called ergotamine. Ergotamine, in turn, is produced by a grain fungus that grow on rye.

LSD was originally produced by a pharmaceutical company under the name Delysid, but it got a bad reputation in the 1950s when the CIA decided to research its effects on mind control. The test subjects of the CIA project MKULTRA proved very difficult to control indeed, and many, like counter-culture writer Ken Kesey, started taking the drug for fun (and for their own form of 1960s enlightenment).

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Ayahuasca is a hallucinatory mixture of Amazonian infusions centered around the Banisteriopsis caapi vine. The brew has long been used by native South American tribes for spiritual rituals and healing, and like other hallucinogens, ayahuasca often triggers very intense emotional experiences (vomiting is also common). In 2006, National Geographic writer Kira Salak described her experience with ayahuasca in Peru for the magazine.

” I will never forget what it was like. The overwhelming misery. The certainty of never-ending suffering. No one to help you, no way to escape. Everywhere I looked: darkness so thick that the idea of light seemed inconceivable,” Salak wrote. “Suddenly, I swirled down a tunnel of fire, wailing figures calling out to me in agony, begging me to save them. Others tried to terrorize me. ‘You will never leave here,’ they said. ‘Never. Never.'”

Nonetheless, Salak wrote, when she broke free of her hallucinations, her crippling depression was alleviated. It’s anecdotal experiences like this that have led researchers to investigate the uses of hallucinogens as therapy for mental disorders such as anxiety, depression and post-traumatic stress disorder.

Peyote is a cactus that gets its hallucinatory power from mescaline. Like most hallucinogens, mescaline binds to serotonin receptors in the brain, producing heightened sensations and kaleidoscopic visions.

Native groups in Mexico have used peyote in ceremonies for thousands of years, and other mescaline-producing cacti have long been used by South American tribes for their rituals. Peyote has been the subject of many a court battle because of its role in religious practice; currently, Arizona, Colorado, New Mexico, Nevada and Oregon allow some peyote possession, but only if linked to religious ceremonies, according to Arizona’s Peyote Way Church of God.

The “magic” ingredient in hallucinogenic mushrooms is psilocybin, a compound that breaks down into psilocin in the body. Psilocin bonds to serotonin receptors all over the brain, and can cause hallucinations as well as synesthesia, or the mixture of two senses. Under the influence, for example, a person might feel that they can smell colors.

In keeping with the human tradition of eating anything that might alter your mind, people have been ingesting psilocybin-continuing mushrooms for thousands of years. Synthetic psilocybin is now under study as a potential treatment for anxiety, depression and addiction.

Best known by its street name, “angel dust,” PCP stands for phencyclidine. The drug blocks receptors in the brain for the neurotransmitter glutamate. It’s more dangerous than other hallucinogens, with schizophrenia-like symptoms and nasty side effects.

Those side effects are why PCP has no medical uses. The drug was tested as an anesthetic in the 1950s and used briefly to knock out animals during veterinary surgeries. But by the 1960s, PCP had hit the streets and was being used as a recreation drug, famous for the feelings of euphoria and invincibility it bestowed on the user. Unfortunately, a side effect of all that euphoria is sometimes truly destructive behavior, including users trying to jump out of windows or otherwise self-mutilating. Not to mention that high enough doses can cause convulsions.

Derived from the African iboga plant, ibogaine is another hallucinogen with a long history of tribal use. More recently, the drug has shown promise in treating addiction, although mostly in Mexico and Europe where ibogaine treatment is not prohibited as it is in the U.S.

Using ibogaine as therapy is tricky, however. The drug can cause heart rhythm problems, and vomiting is a common side effect. The Massachusetts-based Multidisciplinary Association for Psychedelic Research (MAPS) reports that an estimated 1 in 300 ibogaine users die due to the drug. The group is studying the long-term effects of ibogaine on patients in drug treatment programs in New Zealand and Mexico.

Salvia divinorum, also known as seer’s or diviner’s sage, grows in the cloud forest of Oaxaca, Mexico. The native Mazatec people have long used tea made out of the leaves in spiritual ceremonies, but the plant can also be smoked or chewed for its hallucinogenic effects.

Salvia is not currently a controlled substance, according to the National Institute on Drug Abuse, but it is under consideration to be made illegal and placed in the same drug class as marijuana.

Ecstasy, “E” or “X” are the street names for MDMA, or (get ready for a long one) 3,4-methylenedioxymethamphetamine. The drug acts on serotonin in the brain, causing feelings of euphoria, energy and distortions of perception. It can also nudge body temperatures up, raising the risk of heat stroke. Animal studies suggest that MDMA causes long-term and potentially dangerous changes in the brain, according to the National Institute on Drug Abuse.

MDMA was first synthesized by a chemist looking for substances to stop bleeding in 1912. No one paid the compound much mind for the next half-decade, but by the 1970s, MDMA had hit the streets. It was popular at raves and nightclubs and among those who liked their music psychedelic. Today, ecstasy is still a common street drug, but researchers are investigating whether MDMA could be used to treat post-traumatic stress disorder and cancer-related anxiety.

http://www.livescience.com/16286-hallucinogens-lsd-mushrooms-ecstasy-history.html

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Thousands of jumbo squid have recently beached themselves on central California shores, committing mass “suicide.” But despite decades of study into the phenomenon in which the squid essentially fling themselves onto shore, the cause of these mass beachings have been a mystery.

But a few intriguing clues suggest poisonous algae that form so-called red tides may be intoxicating the Humboldt squid and causing the disoriented animals to swim ashore in Monterey Bay, said William Gilly, a marine biologist at Stanford University’s Hopkins Marine Station in Pacific Grove, Calif.

Each of the strandings has corresponded to a red tide, in which algae bloom and release an extremely potent brain toxin, Gilly said. This fall, the red tides have occurred every three weeks, around the same time as the squid beachings, he said. (The squid have been stranding in large numbers for years, with no known cause.)

For decades, beach lovers have reported bizarre mass strandings where throngs of Humboldt squid (Dosidicus gigas), also called jumbo squid, fling themselves ashore, said Hannah Rosen, a marine biology doctoral candidate at the Hopkins Marine Station.

“For some reason they just start swimming for the beach,” Rosen told LiveScience. “They’ll asphyxiate because they’re out of the water too long. People have tried to throw them back in the water, and a lot of times the squid will just head right back for the beach.”

Before this, scientists in 2002 and 2006 noticed mass squid strandings from the Gulf of Mexico all the way to Alaska, Gilly said.

But the cause of the mass squid deaths was an enigma. The strandings seem to happen whenever schools of squid invade new territory, leading some to suggest the creatures simply get lost and don’t realize they are out of the water until it is too late. The squid washing ashore are juvenile size, about 1 foot (0.3 meters) long, and hadn’t been traveled to Monterey Bay before this fall. This season’s stranding, which started Oct. 9, happened around the time Humboldt squid entered the bay.

Other scientists have proposed that red tides that release a lethal toxin called domoic acid may be intoxicating the squid and disorienting them. But when researchers tested the stranded squid for domoic acid, they found only trace amounts of the chemical, Gilly said.

The poisonous chemical mimics a brain chemical called glutamate in mammals, though domoic acid is 10,000 times more potent than glutamate. The similar structure means domoic acid can bind to glutamate receptors on neurons. In turn, the receptor opens channels that let calcium into the cell. At high levels the poison causes brain cells to go haywire and fire like crazy, so much that they fill up with calcium, burst and die, Gilly said. [10 Weird Facts About the Brain]

Humans who eat shellfish contaminated with this red-tide toxin get amnesic shellfish poisoning, because the toxin destroys their brain’s memory center called the hippocampus. Sea lions that eat similarly poisoned anchovies or krill go into seizures or become disoriented and behave bizarrely.

However, no one has tested the effects of lower levels of the chemical on squid.

Potential cause?

But new evidence points to the red tide as at least one cause of the mass strandings. While most sea life follows daily tidal or lunar cycles, the mass deaths seem to be happening every three weeks. That led one of Gilly’s graduate students, R. Russell Williams, to see if something in the environment was leading them astray.

“He was fixated in finding some kind of environmental signal,” Gilly said.

Russell found that red tides occurred every three weeks, around the same time as the squid strandings, suggesting a link, Gilly said.

While past researchers have only found trace levels of the toxic red-tide chemical in stranded squid, low doses of domoic could essentially be making the squid drunk. Combined with navigating unfamiliar waters, that could cause the mass die-offs.

“They could be tipped over the edge by something like domoic acid that might cloud their judgment,” Gilly said.

This isn’t the first time Gilly and his colleagues have been led on a CSI-like hunt for Humboldt squid. In 2011, they figured out why the elusive jumbo squid left their usual feeding grounds off the Baja California coast in the winter of 2009 to 2010. Apparently, the squid had moved north, following their prey, small, bioluminescent fish called lantern fish, which had also moved north due to El Niño weather patterns.

http://www.livescience.com/25550-mass-squid-suicide.html

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A drug used for decades to treat high blood pressure and other conditions has shown promise in a small clinical trial for autism. The drug, bumetanide, reduced the overall severity of behavioral symptoms after 3 months of daily treatment. The researchers say that many parents of children who received the drug reported that their children were more “present” and engaged in social interactions after taking it. The new findings are among several recent signs that treatments to address the social deficits at the core of autism may be on the horizon.

Several lines of evidence suggest that autism interferes with the neurotransmitter GABA, which typically puts a damper on neural activity. Bumetanide may enhance the inhibitory effects of GABA, and the drug has been used safely as a diuretic to treat a wide range of heart, lung, and kidney conditions. In the new study, researchers led by Yehezkel Ben-Ari at the Mediterranean Institute of Neurobiology in Marseille, France, recruited 60 autistic children between the ages of 3 and 11 and randomly assigned them to receive either a daily pill of bumetanide or a placebo. (Neither the children’s parents nor the researchers who assessed the children knew who received the actual drug.)

As a group, those who got bumetanide improved by 5.6 points on a 60-point scale that’s often used to assess behaviors related to autism, the researchers report today in Translational Psychiatry. That was enough to nudge the group average just under the cutoff for severe autism and into the mild to medium category. The study did not look directly at whether the drug improved all symptoms equally or some more than others. “We have some indications that the symptoms particularly ameliorated with bumetanide are the genuine core symptoms of autism, namely communication and social interactions,” Ben-Ari says. More work will be needed to verify that impression. Ben-Ari says his team is now preparing for a larger, multicenter trial in Europe.

The current study already looks interesting to some. “It’s enough to make me think about trying it in a few of my autism patients who haven’t responded to other interventions,” says Randi Hagerman, a pediatrician who studies neurodevelopmental disorders at the University of California, Davis. Social interactions tend to be reinforcing, Hagerman adds, so getting an autistic child to start interacting more can have a positive effect on subsequent brain development.

Other drugs have recently shown promise for autism. In September, Hagerman and colleagues reported that arbaclofen, a drug that stimulates a type of GABA receptor, reduced social avoidance in people with fragile X syndrome, a genetic disorder that shares many features with autism. Many researchers are also hopeful about clinical trials under way with drugs that block certain receptors for glutamate, the main neurotransmitter in the brain that excites neural activity. Results from those trials should come out next year.

All of this work, including the new study, suggests that drugs that reduce neural excitation by blocking glutamate or enhance inhibition by boosting GABA may be helpful for treating autism, says Elizabeth Berry-Kravis, a pediatric neurologist at Rush University in Chicago, Illinois, and a collaborator on the recent arbaclofen study. “There seems to be this imbalance between excitation and inhibition in people with autism.”

That’s a potentially game-changing insight. Now doctors can only prescribe drugs that treat individual symptoms of autism rather than the underlying cause of the disorder, Berry-Kravis says. Doctors often prescribe antipsychotic drugs to reduce irritability, for example, but those drugs don’t address the social and communication problems at the heart of the disorder. “It’s exciting that now we’re thinking about the underlying mechanisms and treating those.”

http://news.sciencemag.org/sciencenow/2012/12/diuretic-drug-offers-latest-hope.html