Archive for May, 2013

Cocaine vaccine passes key testing hurdle

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.

Breaking the Addiction

“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.

Immune System Fights Cocaine

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.

Booster Shots to Dampen the Cocaine High

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.

Reducing Cocaine Occupancy

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.

Frequency of Vaccine?

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.”

May 11th, 2013  in Illegal Drugs No Comments »

Cigarettes are gateway to marijuana

Teen smokers who rationalize their use of cigarettes by saying, “At least, I’m not doing drugs,” may not always be able to use that line.

New research to be presented Sunday, May 5, at the Pediatric Academic Societies (PAS) annual meeting in Washington, DC, supports the theory that cigarettes are a gateway drug to marijuana.

Smoking More Tobacco

“Contrary to what we would expect, we also found that students who smoked both tobacco and marijuana were more likely to smoke more tobacco than those who smoked only tobacco,” said study author Megan Moreno, MD, MSEd, MPH, FAAP, an investigator at Seattle Children’s Research Institute and associate professor of pediatrics at the University of Washington.

Dr. Moreno and her colleagues randomly selected incoming college students from two universities — one in the Northwest and one in the Midwest — to participate in the longitudinal study. Students were interviewed prior to entering college and again at the end of their freshman year regarding their attitudes, intentions and experiences with substances.

One-Third Smoke Tobacco

Specifically, students were asked if they had used tobacco or marijuana ever in their lives and in the past 28 days. Researchers also assessed the quantity and frequency of marijuana and tobacco use in the past 28 days.

Results showed that prior to entering college, 33 percent of the 315 participants reported lifetime tobacco use, and 43 percent of lifetime users were current users. In addition, tobacco users were more likely to have used marijuana than those who did not use tobacco.

By the end of their freshman year, 66 percent of participants who reported tobacco use prior to entering college remained current users with an average of 34 tobacco episodes per month. Of these, 53 percent reported concurrent marijuana use. Overall, users of both substances averaged significantly more tobacco episodes per month than current users of tobacco only (42 vs. 24).

Increased Use of Tobacco

“These findings are significant because in the past year we have seen legislation passed that legalizes marijuana in two states,” Dr. Moreno said. “While the impact of these laws on marijuana use is a critical issue, our findings suggest that we should also consider whether increased marijuana use will impact tobacco use among older adolescents.”

Future work should involve designing educational campaigns highlighting the increased risks of using these substances together, Dr. Moreno concluded.

May 9th, 2013  in Tobacco No Comments »

Breath study brings roadside drug testing closer

A group of researchers from Sweden have provided further evidence that illegal drugs can be detected in the breath, opening up the possibility of a roadside breathalyzer test to detect substances such as cocaine, amphetamines and cannabis.

Using a simple, commercially available breath sampler, the researchers have successfully identified a range of 12 substances in the breath of 40 patients recruited from a drug emergency clinic in Stockholm.

Their findings have been published in IOP Publishing’s Journal of Breath Research.

Advantages of Breath Tests

Blood, urine and saliva are the most popular methods for detecting illegal drugs and are already used by law enforcement in a number of countries; however, exhaled breath is seen as a promising alternative as it’s easier to collect, non-invasive, less prone to adulteration and advantageous when location becomes an obstacle, such as at the roadside.

Exhaled breath contains very small particles that carry non-volatile substances from the airway lining fluid. Any compound that has been inhaled, or is present in the blood, may contaminate this fluid and pass into the breath when the airways open. The compounds will then be exhaled and can subsequently be detected.

In this study, researchers from the Karolinska Institute in Stockholm collected breath, blood plasma and urine samples from 47 patients (38 males, 9 females) who had taken drugs in the previous 24 hours and were recovering at a drug addiction emergency clinic.

Analyzing the Samples

Interviews were also undertaken with each patient to assess their history of drug use.

The breath samples were taken using a commercially available sampling device – SensAbues – and then analysed using liquid chromatography and mass spectrometry.

The portable sampling device consists of a mouth piece and a micro-particle filter. When a patient breathes into the mouth piece, saliva and larger particles are separated from the micro-particles that need to be measured.

The micro-particles are able to pass through and deposit onto a filter, which can then be sealed and stored ready for analysis. Breath samples were analysed for twelve substances.

Alprazolam and benzoylecgonine were detected in exhaled breath for the first time, whereas for methadone, amphetamine, methamphetamine, cocaine, morphine, 6-acetylmorphine, tetrahydrocannabinol, buprenorphine, diazepam and oxazepam, the results confirmed previous observations.

Detected 24 Hours Later

“Considering the samples were taken 24 hours after the intake of drugs, we were surprised to find that there was still high detectability for most drugs,” said lead author of the study Professor Olof Beck.

“In cases of suspected driving under the influence of drugs, blood samples could be taken in parallel with breath when back at a police station. Future studies should therefore test the correlation between blood concentration of drugs of abuse and the concentrations in exhaled breath.”

May 1st, 2013  in Substance Abuse No Comments »