Psychologists explore potential benefits of hallucinogens for mental health disorders

Many people think of psychedelics as relics from the hippie generation or something taken by ravers and music festival-goers, but they may one day be used to treat disorders ranging from social anxiety to depression, according to research presented at the annual convention of the American Psychological Association.

“Combined with psychotherapy, some psychedelic drugs like MDMA, psilocybin and ayahuasca may improve symptoms of anxiety, depression and post-traumatic stress disorder,” said Cristina L. Magalhaes, PhD, of Alliant International University Los Angeles, and co-chair of a symposium on psychedelics and psychotherapy. “More research and discussion are needed to understand the possible benefits of these drugs, and psychologists can help navigate the clinical, ethical and cultural issues related to their use.”

Hallucinogens have been studied in the U.S. for their potential healing benefits since the discovery of LSD in the 1940s. However, research has mostly stalled since psychedelics were outlawed in the late 1960s.

A shift may be coming soon though, as MDMA, commonly known as ecstasy, is beginning its third and final phase of clinical trials in an effort to win Food and Drug Administration approval for treatment of post-traumatic stress disorder, said Adam Snider, MA, of Alliant International University Los Angeles, and co-chair of the symposium.

Findings from one study presented at the symposium suggested that symptoms of social anxiety in autistic adults may be treatable with a combination of psychotherapy and MDMA. Twelve autistic adults with moderate to severe social anxiety were given two treatments of pure MDMA plus ongoing therapy and showed significant and long-lasting reductions in their symptoms, the research found.

“Social anxiety is prevalent in autistic adults and few treatment options have been shown to be effective,” said Alicia Danforth, PhD, of the Los Angeles Biomedical Research Institute at the HarborUCLA Medical Center, who conducted the study. “The positive effects of using MDMA and therapy lasted months, or even years, for most of the research volunteers.”

Research discussed also explored how LSD, psilocybin (known colloquially as “magic mushrooms”) and ayahuasca (a brew used by indigenous people of the Amazon for spiritual ceremonies) may benefit people with anxiety, depression and eating disorders.

Adele Lafrance, PhD, of Laurentian University, highlighted a study of 159 participants who reported on their past use of hallucinogens, level of spirituality and relationship with their emotions.

Using hallucinogens was related to greater levels of spirituality, which led to improved emotional stability and fewer symptoms of anxiety, depression and disordered eating, the study found.

“This study reinforces the need for the psychological field to consider a larger role for spirituality in the context of mainstream treatment because spiritual growth and a connection to something greater than the self can be fostered,” said Lafrance.

Other research presented suggested that ayahuasca may help alleviate depression and addiction, as well as assist people in coping with trauma.

“We found that ayahuasca also fostered an increase in generosity, spiritual connection and altruism,” said Clancy Cavnar, PhD, with Núcleo de Estudos Interdisciplinares sobre Psicoativos.

For people suffering from life-threatening cancer, psilocybin may provide significant and lasting decreases in anxiety and distress.

When combined with psychotherapy, psilocybin helped a study’s 13 participants grapple with loss and existential distress. It also helped the participants reconcile their feelings about death as nearly all participants reported that they developed a new understanding of dying, according to Gabby Agin-Liebes, BA, of Palo Alto University, who conducted the research.

“Participants made spiritual or religious interpretations of their experience and the psilocybin treatment helped facilitate a reconnection to life, greater mindfulness and presence, and gave them more confidence when faced with cancer recurrence,” said Agin-Liebes.

Presenters throughout the symposium discussed the need for more research to fully understand the implications of using psychedelics as an adjunct to psychotherapy as well as the ethical and legal issues that need to be considered.

Since legalization, the illegal marijuana market now hides in plain sight.


Law enforcement officers uproot a large-scale illegal marijuana grow, one of several masquerading as legal operations in Okanogan County.

by Martin Kaste

On a big-sky plateau on the eastern slope of the Cascades, a 10-acre parcel of land has been trashed by illicit pot farmers. Abandoned equipment rusts and jugs of chemicals molder.

Marijuana legalization wasn’t supposed to look like this.

Five years into its experiment with legal, regulated cannabis, Washington state is finding that pot still attracts criminals.

Okanogan County Chief Criminal Deputy Steve Brown helped raid this farm last fall. What was striking, he says, is how brazen it was: located just off the road, within sight of neighbors. Before legalization, an operation like this would at least have been hidden up in the hills.

“Now it’s just out in the open, because everywhere you drive in the county you see the fencing, and everybody just assumes it must be just another legal grow going on.”

This particular grow was just a few hundred feet from licensed, state-regulated pot farms. Brown recalls how the growers tried to “blend in.”

“They acted like it was legal,” he says, and he says they even tried to fool the tax assessor, filing to pay agricultural property taxes at the rate for licensed pot growers.

After an investigation, it turned out the growers were part of a network with connections to California and Thailand, who had purchased six properties in the Okanogan area. They’d been growing pot illegally on five.

Legalization was also supposed to end pot smuggling, but that hasn’t worked out either.

Deputy Brown keeps track of the people from this area who’ve been arrested transporting big loads of marijuana through other states, such as Arkansas and Wyoming. At least one of them had ties to a licensed marijuana store in the Okanogan area, according to investigators.

The reason is simple economics. Overproduction in Washington and other states with legal pot, such as Oregon, has led to a market glut — and rock-bottom wholesale prices in the legal market.

“You’re going to get maybe $1,500 a pound — tops,” says Jeremy Moberg. He runs a licensed outdoor marijuana farm in Okanogan called CannaSol. “And a lot of people in farms around here are going to be lucky to get $250 a pound.”

In states where marijuana is still illegal, the same product would easily fetch three or four times that price, Moberg says. That’s a powerful temptation for licensed farmers who aren’t covering production costs right now.

“[For] those that are just totally underwater, and lost all their money, I think it’s a huge incentive to think that they could divert [legally-grown pot to the black market],” Moberg says. But he says he wouldn’t take that risk.

“I have a strong enough fear for prison and enforcement to not think about that too much,” he says.

A couple of licensed farms nearby have been caught not keeping proper track of their marijuana. Another is accused of using marijuana to pay a contractor. That’s a major violation of the state’s tracking rules for legally-grown pot.

“I could see where it’s definitely tempting for someone to take it out of state,” says Steve Morehead, an enforcement officer for the Washington State Liquor and Cannabis Board. He does surprise inspections of licensed growers to make sure they’re keeping all their marijuana inside the tracking system, meant to prevent diversion.

“Every plant that is 8 inches or taller needs to have a [bar-coded] tag on it,” he says.

But he acknowledges the system isn’t foolproof, especially if someone decides to “set aside” some of the buds from those tagged plants.

“There is a lot of the honor system, of how many ounces or how many pounds did you take off these plants,” he says. “We’re trusting them to input good information.”

This may be the Achilles’ heel of Washington state’s marijuana tracing system. “The amount of product that a plant produces depends on lots of different things, it’s not a constant,” says Mark Kleiman. He’s a professor of public policy at New York University and his consulting company BOTEC studies the pot market for the Washington State Liquor and Cannabis Board.

“So it’s certainly possible that someone could ship some out the back door,” he says.

This matters for many reasons. Off-the-books pot feeds the glut, depressing prices further and tempting producers to sell more into the black market, tax-free.

Still, diversion is hard to prove, unless investigators are tipped off and know to check the thousands of hours of surveillance videos that licensed growers are required to keep.

Illegal grows are easier to catch. The Thai-California network operating in Okanogan was not unique.

Last November, law enforcement on the Washington coast said they’d discovered a large network of illegal marijuana grows run by Chinese nationals. Police in three counties served 50 search warrants, confiscated 32,000 pot plants, 26 vehicles and $400,000 in cash and gold. They also arrested 44 people.

Given the low wholesale prices in Washington, investigators believe the illegal grows are producing for other states where prices are higher, and are here simply to use the local legal pot industry as cover.

Raids like that are ominous for the supporters of Washington’s regulated pot system. Organized crime and cross-border trafficking are just the problems that the Justice Department said states with legalized marijuana should keep a lid on. Such incidents could give the feds a reason to crack down on the state’s licensed growers and retailers, which are still illegal in the eyes of federal law.

That worries licensed producers such as Moberg.

“If it’s organized crime, building operations made to look like [legal grows], in order to export out, I’m much more concerned,” he says. “Obviously this is what the feds are mostly concerned about. So if they are able to do this, and the attention is brought upon us that this is happening, then I don’t think that is great for all of us.”

https://www.npr.org/2018/05/16/610579599/despite-legalization-marijuana-black-market-hides-in-plain-sight

Many thanks to Ray Gaudette, for bringing this to the It’s Interesting community.

A drug originally developed for treating osteoporosis may also help fight baldness


Immunofluorescence of β-catenin protein (red) and cell nuclei (blue) in the human hair follicle bulb, the command center for maintaining hair growth.

A new drug could ease the distress of men and women who suffer from baldness, according to researchers from The University of Manchester’s Centre for Dermatology Research.

The study from the laboratory of Prof Ralf Paus, is published last week in the open access journal PLOS Biology

It shows that a drug originally designed as a treatment for osteoporosis has a dramatic stimulatory effect on human hair follicles donated by patients undergoing hair transplantation surgery.

Currently only two drugs – minoxidil and finasteride – are available for treatment of male-pattern balding (androgenetic alopecia).

However, both agents have moderate side effects and often produce disappointing hair regrowth results. The only other option available to patients is hair transplantation surgery.

The PhD project, led by Dr Nathan Hawkshaw and colleagues, sought to develop new ways to promote human hair growth with the hope of finding novel, well-tolerated agents for treating androgenetic alopecia.

The approach was to first identify the molecular mechanisms of an old immunosuppressive drug, Cyclosporine A (CsA).

Cyclosporine A has been commonly used since the 1980s as a crucial drug that suppresses transplant rejection and autoimmune diseases.

However, it often has severe side-effects, the least serious – but most interesting – of which is that it enhances cosmetically unwanted hair growth.

The team carried out a full gene expression analysis of isolated human scalp hair follicles treated with CsA. This revealed that CsA reduces the expression of SFRP1, a protein that inhibits the development and growth of many tissues, including hair follicles.

This identifies a completely novel mechanism of action of this old and widely used immunosuppressant.

The research also explanains why CsA so often induces undesired hair growth in patients as it removes an inbuilt and potent molecular brake on human hair growth.

The inhibitory mechanism is completely unrelated to CsA’s immunosuppressive activities, making SFRP1 a new and highly promising therapeutic target for anti-hair loss strategies.

After some detective work, Dr Hawkshaw found that a compound originally developed to treat osteoporosis, called WAY-316606, targets the same mechanism as CsA by specifically antagonising SFRP1.

When he then treated hair follicles with WAY-316606, the unrelated agent also effectively enhanced human hair growth like CsA.

The external application of WAY-316606 or similar compounds to balding human scalp, he argued, may promote hair growth to the same magnitude as CsA or even better, but without its side effects.

“The fact this new agent, which had never even been considered in a hair loss context, promotes human hair growth is exciting because of its translational potential: it could one day make a real difference to people who suffer from hair loss
Dr Nathan Hawkshaw

Dr Hawkshaw said: “Thanks to our collaboration with a local hair transplant surgeon, Dr Asim Shahmalak, we were able to conduct our experiments with scalp hair follicles that had generously been donated by over 40 patients and were then tested in organ cultures.

“This makes our research clinically very relevant, as many hair research studies only use cell culture.”

He added: “When the hair growth-promoting effects of CsA were previously studied in mice, a very different molecular mechanism of action was suggested; had we relied on these mouse research concepts, we would have been barking up the wrong tree.

“The fact this new agent, which had never even been considered in a hair loss context, promotes human hair growth is exciting because of its translational potential: it could one day make a real difference to people who suffer from hair loss.

“Clearly though, a clinical trial is required next to tell us whether this drug or similar compounds are both effective and safe in hair loss patients.”

http://www.manchester.ac.uk/discover/news/fringe-benefits-drug-side-effects-could-treat-human-hair-loss/

What Blind People Experience When They Take LSD

By Bahar Gholipour

The consciousness-altering drug LSD is best known for its bizarre visual effects: even a small dose of the drug can turn the flat walls of your living room into something out of Wonderland. Objects bend, colors blend and intricate patterns cast a shimmer on everything you see. But what would LSD feel like if you couldn’t see?

In an unusual case report published in the April issue of the journal Cognition and Consciousness, a blind 70-year-old former rock musician has some answers.

The man, who is referred to as “Mr. Blue Pentagon” after his favorite kind of LSD, gave researchers a detailed account of what he experienced when taking the drug during his music career in the 1970s. Mr. Pentagon was born blind. He did not perceive vision, with or without LSD. Instead, under the influence of psychedelics, he had strong auditory and tactile hallucinations, including an overlap of the two in a form of synesthesia, according to the report.

“I never had any visual images come to me. I can’t see or imagine what light or dark might look like,” Mr. Blue Pentagon told the researchers. But under the influence of LSD (lysergic acid diethylamide, also known as acid), sounds felt unique and listening to music felt like being immersed in a waterfall, he said. “The music of Bach’s third Brandenburg concerto brought on the waterfall effect. I could hear violins playing in my soul and found myself having a one hour long monologue using different tones of voices … LSD gave everything ‘height.’ The sounds coming from songs I would normally listen to became three dimensional, deep and delayed.”

Mr. Blue Pentagon’s account is a rare glimpse into how LSD may feel in the absence of vision. Beyond a few Q&A threads on Reddit, the only other resource is a 1963 study of 24 blind people, which was actually conducted by an ophthalmologist to test whether a functioning retina (the part of the eye that senses light) is enough for visual hallucinations (it’s not), and didn’t include the participants’ psychological experiences beyond vision.

Understanding Mr. Blue Pentagon’s experience with the drugmay give unique insights about how novel synesthetic experiences through multiple senses are concocted by the brain — especially a brain that is wired differently due to lack of vision, according to the researchers from the University of Bath in the U.K. who published the report. Synesthesia is a rare condition in which one sense is perceived in the form of another; for example, a person may “hear” colors or “taste” sounds. This overlap of senses may ocurr because of cross communication between brain networks processing each sense, scientists have proposed.

As numerous anecdotal reports suggest and a few studies have documented, LSD causes auditory-visual synesthesia, an experience in which sounds and sights influence each other. Mr. Blue Pentagon appeared to experience a similar phenomenon, but rather than mixing sound and sight, it involved the senses that were available to him: sound and touch, the researchers suggested.

Still, there’s only so much to be gleaned from a qualitative report based on a single person.

“It is next to impossible to gain ‘general’ insights from individual narratives,” said Ilsa Jerome, a clinical researcher for the Multidisciplinary Association for Psychedelic Studies (MAPS) who was not involved with the report.

Jerome, who is visually impaired herself, said she is unconvinced that having a visual impairment provides any special insight on how LSD alters sensory processes. “But it might provide greater motivation or interest in the sensory impact of psychedelic compounds,” she told Live Science.

The brain in blindness
The details of what exactly LSD does in the brain are still unclear, but research suggests that the drug’s psychedelic effects occur because LSD alters neuronal communication in the brain. Specifically, LSD latches onto receptors for serotonin, one of the neurotranmitters neurons use to communicate. The visual hallucinations are likely a result of LSD stimulating these receptors in the visual cortex, the part of the brain that processes light, color and other visual information. [10 Things You Didn’t Know About the Brain]

The first studyto look at the brain effects of LSD using modern technology was published recently, in 2016, in the journal Proceedings of the National Academy of Sciences. In that study, when people took LSD, the researchers observed that the visual cortex was unusually activeand showed greater synchronous activity with many areas of the brain. This connectivity was correlated with the complex visual hallucinations reported by the participants.

The visual cortex develops into a fully functioning system during early life in response to sensory information from the eyes. But in the absence of early visual experience, which is the case for people born blind, the visual cortex doesn’t develop normally. Instead, it rewires to process sound and touch.

This could explain the nature of Mr. Blue Pentagon’s experience with LSD.

“I expect that the cortical ‘real estate’ that would have housed vision does not do so in Mr. Pentagon’s case,” Jerome said. “So LSD may be doing the same thing with that area of cortex, but since that area is, for him, connected with other senses, those experiences — such as sound, touch or sense of self in space — are altered.”

Visual or other sensory hallucinations are only one part of LSD’s effects. The compound can cause profound changes in emotions and consciousness, all of which are reported by both blind and sighted people. The few studies that exist on the subject suggest LSD may be doing this by lowering the barriers between brain networks, allowing them to communicate in a more flexible way.

Original article on Live Science.

https://www.livescience.com/62343-psychedelics-lsd-effects-blind-people.html

Chemical analysis of sewage suggests that people in Western Kentucky used more drugs on the day of the solar eclipse

By Nala Rogers

Even drugs that clear the body quickly leave traces about when and where they were used. In fact, many traces get flushed down the toilet — and those traces can be surprisingly revealing.

In a study published last month in the journal Science of the Total Environment, researchers analyzed sewage from two towns in western Kentucky. By testing for active ingredients and metabolites of marijuana, cocaine, amphetamine, methamphetamine, ecstasy and several opioids, they were able to estimate the average quantity of each drug consumed per 1,000 people in the population on any given day. This allowed them to infer how drug use changed during special events in the summer of 2017.

In both communities, significantly higher levels of amphetamine, methamphetamine, cocaine, morphine and methadone were found in the wastewater on July 4 than on a typical day. In particular, methamphetamine levels were high on Independence Day, with levels doubling in one town and rising by half in the other.

One of the towns was in the path of the total solar eclipse that crossed the country August 21. In that town, the eclipse brought a significant uptick in amphetamine, methamphetamine, cocaine, morphine and marijuana. The measurements suggested that 1,450 milligrams of amphetamine per 1,000 people was consumed on the day of the eclipse — enough to get about 2.9 percent of the town’s population high. That represented a roughly 60 percent increase over the amphetamine residues found on a typical day.

Of course, it’s likely that some people took more than one dose, said Bikram Subedi, an analytical chemist at Murray State University in Kentucky and one of the study’s authors. Moreover, he added, some of the drugs used on eclipse day likely came from visitors who came to see the eclipse, not the town’s regular population.

“This is an interesting study and provides valuable information on the magnitude of increase in the use of illicit drugs during specific holidays,” wrote Kurunthachalam Kannan, an environmental health researcher at the Wadsworth Center, New York State Department of Health in Albany, New York, in an email. “One interesting find is that meth usage in communities surveyed seems to be higher than in urban communities.” Kannan was not involved in the study.

Researchers have used sewage to track drug use in other parts of the world, but the technique has rarely been used in the United States, despite its potential to complement traditional data sources such as surveys and toxicology reports, said Subedi. Sewage can’t lie like a person on a survey, and it offers a relatively unbiased look at all drug use in a community, not just the extreme cases that end up in a hospital. And unlike traditional methods, sewage analysis can track changes from day to day.

“This will give the semi-real-time drug consumption in communities,” said Subedi. “That information could be really helpful for the authorities.”

https://www.livescience.com/62237-people-got-high-2017-solar-eclipse.html

13 percent of us have traces of cocaine or heroin on our fingers

By Rafi Letzter

There’s a lot of cocaine and heroin in the world, and there’s a pretty good chance you’ve got a tiny bit of it on your body right now — even if you’ve never knowingly touched the stuff.

That’s the conclusion of a new paper published in the journal Clinical Chemistry today (March 22), which found that 13 percent of drug-free study participants had traces of the drugs on their fingertips. The participants, residents of the United Kingdom tested at the University of Surrey, didn’t have enough heroin or cocaine on their fingers for it to be visible, and certainly not enough to get them (or anyone) high. But they did have enough cocaine or heroin on their hands to trip very sensitive instruments called mass spectrometers.

But the point of the study wasn’t just to reveal that there’s a whole lot of trace narcotics floating around out there.

Instead, researchers were trying to establish a baseline for how much trace heroin or cocaine would turn up in a non-drug user’s fingerprint. (When a person does a fingerprint test, some of the substances on their fingertips are transferred to the print.) They compared non-drug users’ fingerprints to the fingerprints of recent heroin or cocaine users, in hopes of establishing a level over which they could confidently say the fingerprint belonged to someone who had recently used drugs.

While they did arrive at such a cutoff, they also found that there’s a lot of environmental contamination on people’s fingers — and that it doesn’t go away when study participants wash their hands.

Chemists already knew that trace amounts of cocaine and heroin are everywhere, said Rolf Halden, director of the Biodesign Center for Environmental Health Engineering at Arizona State University.

“Think of cocaine on paper money,” Halden told Live Science. “We know that a lot of currency is contaminated with cocaine.”

Halden would know: His lab collects sewage water samples from all over the world and tests them for traces of drugs. While most people might not admit to using drugs, he can tell how much certain drugs are actually getting used in a given city based on the traces they leave in the sewage system.

Still, Halden said, the fingerprint finding is new and interesting, and could represent a method of quick drug testing that’s less invasive than drawing blood or collecting hair samples.

That said, Halden cautioned that the results would be much more uncertain than those existing methods. Where people live and which things they regularly touch might lead to a wide range of baseline-level drug traces among different people. A bank teller or tollbooth operator, he speculated, might have much more significant drug traces just from touching cash all day.

“If I’m a lawyer and my client tested for drugs this way, this would be an easy way out [of a conviction],” he said. “I predict it could be potentially helpful [for drug testing], but it would not very rapidly replace other types of testing, like bodily fluids.”

While it might surprise readers to learn they have a reasonably good chance of having drugs they’ve never used on their fingertips, Halden said it’s nothing to worry about.

“The levels are way too low to be consequential,” he said.

The reality is that chemists’ instruments are so sensitive that they can detect even the tiniest traces of substances.

“We also can detect a lot of prescription drugs in drinking water,” Halden said. “There [are] a few molecules in there — enough for us to detect them as analytical chemists, but not enough to have a measurable impact on people.”

In other words, no one’s getting high from finger-molecules of old cocaine on their banknotes. And they don’t represent any kind of individual danger to anyone.

That said, Halden added, there just isn’t enough data yet to know if there might be some kind of population-level effect from this kind of widespread contamination. But if it’s there, he said, it’s vanishingly subtle — to the point of having zero measurable effect on any one individual — and people should not worry about it.

https://www.livescience.com/62099-cocaine-heroine-drug-finger-fingerprints.html?utm_source=notification

New Drug Compounds Help Prevent Hearing Loss

Researchers from St. Jude Children’s Research Hospital have discovered that inhibiting an enzyme called cyclin-dependent kinase 2 (CDK2) protects mice and rats from noise- or drug-induced hearing loss. The study, which will be published March 7 in the Journal of Experimental Medicine, suggests that CDK2 inhibitors prevent the death of inner ear cells, which has the potential to save the hearing of millions of people around the world.

According to the World Health Organization, 360 million people worldwide, including 32 million children, suffer from hearing loss caused by congenital defects or other factors. These factors include infectious disease, use of certain medicines, or exposure to excessive noise. Yet, there are currently no FDA-approved drugs to prevent or treat hearing loss.

A team of researchers led by Dr. Jian Zuo screened over 4,000 drugs for their ability to protect cochlear cells from the chemotherapy agent cisplatin. Cisplatin is used to treat a variety of cancers but causes irreversible hearing loss in up to 70% of patients.

Zuo and colleagues identified multiple compounds that protected cochlear cells from cisplatin, several of which are already approved to treat other conditions. Three of the ten most effective compounds were inhibitors of an enzyme called CDK2. One of these CDK2 inhibitors, kenpaullone, was more effective than four other compounds that are currently in clinical trials for treating hearing loss.

Injecting kenpaullone into the middle ear protected both mice and rats from cisplatin-induced hearing loss. Moreover, kenpaullone also protected the hearing of mice to noise as loud as 100 dB. “Given that 100-dB noise is in the range of noise insults commonly experienced by people in our society, kenpaullone could have significant clinical application in treating noise-induced hearing loss,” says Zuo.

In the case of cisplatin-induced hearing loss, kenpaullone appears to protect hair cells by preventing CDK2 from stimulating the production of toxic reactive oxygen species from the cells’ mitochondria.

“The robust protection conferred by one-time local delivery of kenpaullone suggests that CDK2 inhibitors may transform the clinical prevention and treatment of cisplatin- and noise-induced hearing loss in patients,” Zuo says. “Modifications of the treatment regimens, additional optimization of the delivery methods via the use of hydrogels, and structural modifications of the compounds via medicinal chemistry could ensure even better results with CDK2 inhibitors in treating hearing loss in humans.”

https://www.technologynetworks.com/drug-discovery/news/new-drug-compounds-help-prevent-hearing-loss-298358?utm_campaign=Newsletter_TN_BreakingScienceNews&utm_source=hs_email&utm_medium=email&utm_content=61208436&_hsenc=p2ANqtz-9wXzuHgjTCBE-kfjy2aI1t3MUL9sd_5yCjnzo0oJb_R1HQdkMueXmiVXpB290Xv_tYEY8WdZxoDvtPtxyl3ajVpcPK1Q&_hsmi=61208436

Key Link Between Mitochondria and Cocaine Addiction Discovered

For years, scientists have known that mitochondria—the power source of cells—play a role in brain disorders such as depression, bipolar disorder, anxiety and stress responses. But recently scientists at the University of Maryland School of Medicine (UMSOM) have identified significant mitochondrial changes in brain cells that take place in cocaine addiction, and they have been able to block them.

In mice exposed repeatedly to cocaine, UMSOM researchers were able to identify an increase in a molecule that plays a role in mitochondria division (or fission) in a reward region of the brain. Researchers were able to block this change by using a special chemical, Mdivi-1. The researchers also blocked responses to cocaine by genetically manipulating the fission molecule within the mitochondria of brain cells, according to research published in Neuron.

“We are actually showing a new role for mitochondria in cocaine-induced behavior, and it’s important for us to further investigate that role,” said Mary Kay Lobo, PhD, Associate Professor of Anatomy and Neurobiology.

The researchers initially studied the mitochondria in cocaine-exposed mice and determined that mitochondria fission increased in the major reward region of the brain. To confirm this same change in humans, researchers were able to identify similar changes in the mitochondrial fission molecule in tissue collected from post mortem individuals who were cocaine dependents.

Dr. Lobo said that this latest research could help UMSOM researchers better understand changes in brain cells and mitochondria from other addictive disorders. “We are interested to see if there are mitochondrial changes when animals are taking opiates. That is definitely a future direction for the lab,” she said.

“This research is another great example of our ground-breaking work at the University of Maryland School of Medicine to better understand the biology behind drug addiction,” said E. Albert Reece, MD, PhD, MBA, University Executive Vice President of Medical Affairs and the John Z. and Akiko K. Bowers Distinguished Professor and Dean at the University of Maryland School of Medicine.

http://www.medschool.umaryland.edu/news/2018/University-of-Maryland-School-of-Medicine-Researchers-Discover-Key-Link-Between-Mitochondria-and-Cocaine-Addiction.html

New heroin vaccine offers promise for treatment

Scientists at The Scripps Research Institute (TSRI) have achieved a major milestone toward designing a safe and effective vaccine to both treat heroin addiction and block lethal overdose of the drug. Their research, published today in the journal Molecular Pharmaceutics, shows how a new anti-heroin formulation that is safe in animal models remains stable at room temperature for at least 30 days. As a result, the vaccine is close to being ready for human testing.

“The heroin vaccine is one step closer to clinical evaluation,” says Candy S. Hwang, PhD, first author of the study and a research associate at TSRI.

According to the National Institute on Drug Abuse, 15,446 Americans died from heroin overdose between 2000 and 2016, and the mortality rates are increasing. Heroin abuse has been further fueled by a rise in prescription opioid abuse—studies show that opioid pain reliever users are 40 times more likely to abuse heroin.

The first formulation of the heroin vaccine was developed in 2013 by a team led by Kim D. Janda, PhD, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI. It has been shown to be effective—and safe—in both mouse and non-human primate models.

The vaccine works by training the immune system antibodies to recognize and bind to heroin molecules, blocking the drug from reaching the brain to cause a “high.” Researchers believe that blocking the high of heroin will help eliminate the motivation for many recovering addicts to relapse into drug use.

The heroin molecule does not naturally prompt an antibody response, so researchers attach it to a carrier protein that alerts the immune system to start making antibodies. Scientists also add an ingredient called an adjuvant to the vaccine, which boosts the immune response and makes the vaccine more effective.

Hwang says, “Our goal was to prepare a vaccine that could be advanced to clinical trials. As such, we were looking for the best combination of ‘hapten’ (the heroin molecule), carrier protein and adjuvant to keep the vaccine both stable for transport and storage but still efficacious.”

For the new study, the researchers investigated how 20 different carrier protein/adjuvant combinations worked, including shelf stability based on temperature and storage time and whether the formulation was a liquid or powder.

Their experiments in rodent models showed that the best vaccine formulation contained a carrier protein called tetanus toxoid (TT) and adjuvants called alum and CpG ODN. The discovery that alum worked best as an adjuvant was especially significant since alum is one of the few adjuvants used in vaccines already approved by the U.S. Food and Drug Administration. The researchers also found that there was no difference in how well it worked between the liquid and powder versions of this formulation.

Hwang notes that the best vaccine formulation showed protection against lethal doses of heroin. This is particularly important as many heroin addicts have succumb to overdose and death during their attempts to quit the drug.

With this new study, the researchers have shown that the vaccine is safe and effective in animal models, stable under clinical conditions and reliant on an already-approved adjuvant. The next step is to find a producer to make the vaccine on a large scale.

“We believe that a heroin vaccine would be tremendously beneficial for people who have a heroin substance use disorder but have found difficulty in trying to quit,” says Hwang.

In addition to Hwang and Janda, authors of the study, “Enhancing Efficacy and Stability of an Anti-Heroin Vaccine: Examination of Antinociception, Opioid Binding Profile, and Lethality,” were Paul T. Bremer, Cody J. Wenthur, Beverly Ellis and Bin Zhou of The Scripps Research Institute; and Sam On Ho, SuMing Chiang and Gary Fujii of Molecular Express, Inc.

The study was supported by the National Institutes of Health (grants UH3DA041146, F32AI126628, F32DA043323, R42DA040422 and R44AI094770).

https://www.scripps.edu/news/press/2018/20180213janda.html

Kratom

by MARY JO DILONARDO

Fans of the herb kratom say it offers pain relief, calms anxiety, and can help ease opioid withdrawal symptoms. However, a new report from the Food and Drug Administration says the popular herbal substance acts like a prescription-strength opioid and is associated with several dozen deaths.

What exactly is this polarizing botanical drug?

What is kratom?
Kratom is a tropical tree (Mitragyna speciosa) related to coffee that is native to Southeast Asia. Leaves from the tree have been used for centuries as a traditional remedy for pain.

The leaves can be eaten raw, but are usually crushed and made into a powder. The powder is then consumed in capsules, smoked or brewed in teas.

According to the U.S. Drug Enforcement Administration, consumption of kratom in low doses produces simulating effects. However, in large amounts it acts as a sedative, and can lead to psychotic symptoms, as well as psychological and physiological dependence.

Why there is concern
The DEA includes kratom on its Drugs of Concern list (substances that aren’t regulated by the Controlled Substances Act, but that could pose risks to people who abuse them), and the National Institute of Drug Abuse has identified kratom as an emerging drug of abuse.

Between 2010 and 2015, the Centers for Disease Control and Prevention noted a tenfold increase in calls about kratom to poison control centers across the U.S., from 26 to 263. About 42 percent of those cases involved non-life-threatening symptoms that required some treatment. About 7 percent were classified as major and life-threatening.

In the February 2018 report, FDA Commissioner Scott Gottlieb, M.D. said, “There is no evidence to indicate that kratom is safe or effective for any medical use. And claiming that kratom is benign because it’s ‘just a plant’ is shortsighted and dangerous. After all, heroin is an illegal, dangerous, and highly-addictive substance containing the opioid morphine, derived from the seed pod of the various opium poppy plants.”

Gottleib warned of potential side effects including changes in neurologic and cardiovascular function. He also cited 44 reported deaths “associated with the use of kratom.”

Consumer Reports points out other possible dangers associated with kratom:

Kratom has been found to be laced with opioids, including tramadol and hydrocodone.
There’s little research about drug interactions, and users are mixing kratom with legal and illegal drugs, which can be dangerous.
Some users who have turned to kratom to kick an opioid addiction have become hooked on kratom instead.
It kratom legal?
In 2016, the DEA announced plans to list kratom as a Schedule 1 substance, which would add it to the ranks of LSD, heroin, marijuana and ecstasy. The plan would have essentially banned kratom, but the DEA changed course and instead gave the public a chance to comment.

Now, the substance is mostly legal in the U.S., depending on where you live. According to the American Kratom Association, several cities, counties and seven states (Alabama, Arkansas, Indiana, Rhode Island, Tennessee, Vermont and Wisconsin) and the District of Columbia have banned or seriously restricted the use of kratom.

While supporters are working hard to keep kratom legal, the DEA and detractors argue that the substance is not safe.

“We’ve learned a tragic lesson from the opioid crisis,” Gottleib said. “That we must pay early attention to the potential for new products to cause addiction and we must take strong, decisive measures to intervene.”

https://www.mnn.com/health/fitness-well-being/stories/what-kratom-and-it-dangerous