Archive for the ‘National Institute on Drug Abuse’ Category

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

cocaine

Researchers at Weill Cornell Medical College have successfully tested their novel anti-cocaine vaccine in primates, bringing them closer to launching human clinical trials. Their study, published online by the journal Neuropsychopharmacology, used a radiological technique to demonstrate that the anti-cocaine vaccine prevented the drug from reaching the brain and producing a dopamine-induced high.

“The vaccine eats up the cocaine in the blood like a little Pac-man before it can reach the brain,” says the study’s lead investigator, Dr. Ronald G. Crystal, chairman of the Department of Genetic Medicine at Weill Cornell Medical College. “We believe this strategy is a win-win for those individuals, among the estimated 1.4 million cocaine users in the United States, who are committed to breaking their addiction to the drug,” he says. “Even if a person who receives the anti-cocaine vaccine falls off the wagon, cocaine will have no effect.”

Dr. Crystal says he expects to begin human testing of the anti-cocaine vaccine within a year.

Cocaine, a tiny molecule drug, works to produce feelings of pleasure because it blocks the recycling of dopamine — the so-called “pleasure” neurotransmitter — in two areas of the brain, the putamen in the forebrain and the caudate nucleus in the brain’s center. When dopamine accumulates at the nerve endings, “you get this massive flooding of dopamine and that is the feel good part of the cocaine high,” says Dr. Crystal.

The novel vaccine Dr. Crystal and his colleagues developed combines bits of the common cold virus with a particle that mimics the structure of cocaine. When the vaccine is injected into an animal, its body “sees” the cold virus and mounts an immune response against both the virus and the cocaine impersonator that is hooked to it. “The immune system learns to see cocaine as an intruder,” says Dr. Crystal. “Once immune cells are educated to regard cocaine as the enemy, it produces antibodies, from that moment on, against cocaine the moment the drug enters the body.”

In their first study in animals, the researchers injected billions of their viral concoction into laboratory mice, and found a strong immune response was generated against the vaccine. Also, when the scientists extracted the antibodies produced by the mice and put them in test tubes, it gobbled up cocaine. They also saw that mice that received both the vaccine and cocaine were much less hyperactive than untreated mice given cocaine.

In this study, the researchers sought to precisely define how effective the anti-cocaine vaccine is in non-human primates, who are closer in biology to humans than mice. They developed a tool to measure how much cocaine attached to the dopamine transporter, which picks up dopamine in the synapse between neurons and brings it out to be recycled. If cocaine is in the brain, it binds on to the transporter, effectively blocking the transporter from ferrying dopamine out of the synapse, keeping the neurotransmitter active to produce a drug high.

In the study, the researchers attached a short-lived isotope tracer to the dopamine transporter. The activity of the tracer could be seen using positron emission tomography (PET). The tool measured how much of the tracer attached to the dopamine receptor in the presence or absence of cocaine.

The PET studies showed no difference in the binding of the tracer to the dopamine transporter in vaccinated compared to unvaccinated animals if these two groups were not given cocaine. But when cocaine was given to the primates, there was a significant drop in activity of the tracer in non-vaccinated animals. That meant that without the vaccine, cocaine displaced the tracer in binding to the dopamine receptor.

Previous research had shown in humans that at least 47 percent of the dopamine transporter had to be occupied by cocaine in order to produce a drug high. The researchers found, in vaccinated primates, that cocaine occupancy of the dopamine receptor was reduced to levels of less than 20 percent.

“This is a direct demonstration in a large animal, using nuclear medicine technology, that we can reduce the amount of cocaine that reaches the brain sufficiently so that it is below the threshold by which you get the high,” says Dr. Crystal.

When the vaccine is studied in humans, the non-toxic dopamine transporter tracer can be used to help study its effectiveness as well, he adds.

The researchers do not know how often the vaccine needs to be administered in humans to maintain its anti-cocaine effect. One vaccine lasted 13 weeks in mice and seven weeks in non-human primates.

“An anti-cocaine vaccination will require booster shots in humans, but we don’t know yet how often these booster shots will be needed,” says Dr. Crystal. “I believe that for those people who desperately want to break their addiction, a series of vaccinations will help.”

Co-authors of the study include Dr. Anat Maoz, Dr. Martin J. Hicks, Dr. Shankar Vallabhajosula, Michael Synan, Dr. Paresh J. Kothari, Dr. Jonathan P. Dyke, Dr. Douglas J. Ballon, Dr. Stephen M. Kaminsky, Dr. Bishnu P. De and Dr. Jonathan B. Rosenberg from Weill Cornell Medical College; Dr. Diana Martinez from Columbia University; and Dr. George F. Koob and Dr. Kim D. Janda from The Scripps Research Institute.

The study was funded by grants from the National Institute on Drug Abuse (NIDA).

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