Cocaine vaccine shows promise

A vaccine to treat cocaine dependence yielded good results in a phase-2 clinical trial and will be tested next year in a larger study, researchers reported today.

The cocaine vaccine is not intended to prevent addiction but instead is designed for use with other treatments, such as behavioral therapy, to assist people in recovery. The vaccine is among a number of research projects relying on similar technology to treat nicotine, heroin and methamphetamine addiction.

Cocaine is comprised of tiny molecules that sneak across the body’s blood-brain barrier before the immune system recognizes the substance as foreign. By attaching cocaine-like molecules to a larger protein, the vaccine circumvents that problem and allows the immune system to recognize the protein and its cargo. If a sufficient level of antibodies is created through repeated vaccine injections, those antibodies will disable the addictive drug before it enters the brain, causes euphoria and triggers the cascade of brain chemicals that lead to drug cravings.

In the current study, researchers enrolled 115 cocaine-dependent people in a 24-week trial. Half of the individuals received five injections of the experimental TA-CD vaccine (which stands for therapy for addiction-cocaine addiction) over 12 weeks while the other half received placebo injections. The participants’ urine was tested three times per week over the course of the study. The vaccine produced a large enough antibody response to reduce cocaine use in 38% of the 55 addicted individuals who received all five injections. There were no serious side effects.

The study is published in the Archives of General Psychiatry.

“The antibodies slow cocaine’s entry into the brain. And because it is slowed down so much, the drug isn’t reinforcing any more,” said Dr. Thomas Kosten, a psychiatrist at Baylor College of Medicine and lead author of the study. "The most promising thing we found is that once we got those cocaine antibody levels up, they were more effective than we thought they were going to be. The part that we did expect, but that was still disappointing, is about 20% of people don't make much of an antibody response."

About 300 cocaine-dependent individuals will be enrolled in a study beginning in January to further test the vaccine, Kosten said. The vaccine approach is intended for use in people who desire to quit using, said Berma M. Kinsey, a research chemist at Baylor who has worked on the vaccine. It is not meant for preventing addictions from forming in the first place or for people who don't want to quit.

"It's for people who are motivated to get off drugs," she said. "It's not a cure-all."

-- Shari Roan

Photo credit: Guillermo Arias  /  AP

Drug testing could stop 'academic doping'

Students taking important exams could one day find themselves in the same position as professional athletes -- submitting to a drug test before the big event. The practice of students taking cognitive-enhancing drugs, such as methylphenidate, has become so common that those who don't "dope" are at an unfair advantage, argues a psychologist writing in the new issue of Journal of Medical Ethics.

Chemically enhanced academic performance is cheating, says Vince Cakic, of the department of psychology at the University of Sydney, Australia. Already, he notes, medications meant to treat attention deficit hyperactivity disorder are used by college students to improve their test scores. And many other cognitive-enhancing medications, which he calls nootropics, are being developed for diseases such as Alzheimer's. While the ADHD drugs improve performance only modestly, future drugs for dementia may make a big difference in an individual's capacity to study and test scores. "The possibility of purchasing 'smartness in a bottle' is likely to have broad appeal to students with normal or above average cognitive functioning to begin with," he wrote

Rules prohibiting the use of performance-enhancing drugs in sports fail unless athletes are subjected to routine urine tests, Cakic says. The same strategy would likely be necessary to prevent cheating in academics. According to his paper, the use of methylphenidate and amphetamines is as high as 25% on some U.S. college campuses. The most academically competitive schools are thought to have the highest usage rates of these drugs. The more students who take the drugs, the more non-cheating student are put at a disadvantage and thus may feel compelled to cheat, too.

"It is apparent that the failures and inconsistencies inherent in anti-doping policy in sport will be mirrored in academia unless a reasonable and realistic approach to the issue of nootropics is adopted," Cakic wrote.

Cheating is not the only worry for college administrators. The rampant use of nootropics may lead to serious health problems in some students who take them without a doctor's approval.

". . . there is a greater need to examine the safety and efficacy of putative nootropics in the healthy rather than only in clinical populations," he wrote. "However, the widespread non-medical use of methylphenidate suggests that students will use nootropics regardless of their safety and legality."

-- Shari Roan

Photo credit: Keith Beaty / Toronto Star / ZUMA Press

Cocaine laced with veterinary drug causing serious illness

A federal agency warned this week that cocaine laced with levamisole, a veterinary anti-parasitic drug, has caused 20 cases of a serious medical disorder.

Officials at the Substance Abuse and Mental Health Services Administration say they expect to see more cases of people sickened by the adulterated cocaine as doctors learn of the association. The drug mixture has caused agranulocytosis, a life-threatening disorder that causes a drop in the number of white blood cells. Two deaths have occurred among the 20 confirmed or suspected cases related to adulterated cocaine.

Levamisole is used in cattle, sheep and swine to prevent parasites. It is not approved for human use.

It is unclear how and why levamisole is turning up in cocaine. Drug Enforcement Administration testing shows the amount of levamisole-laced cocaine in circulation in the United States has been increasing since 2002. In samples of illicit cocaine analyzed in July, more than 70% contained levamisole. A recent study performed in Seattle found that 80% of people who tested positive for cocaine also tested positive for levamisole.

Agranulocytosis comes on very fast with severe symptoms. People who use cocaine should watch out for high fever, chills, weakness, swollen glands, painful sores in the mouth and anus and any infection that won't go away or gets worse very fast.

-- Shari Roan

Photo: Levamisole is used to treat livestock for parasites but has been showing up in cocaine. Credit: Danny Johnston / Associated Press

Family dinners work some kind of magic

Teenagers who have frequent family dinners are much less likely to drink and use drugs, according to a report released today. It doesn't seem to matter what food is served, the authors point out. The value appears to be in the social interaction between family members and the attention that parents give their children during a meal.

The report, titled "The Importance of Family Dinners V," summarizes research that began more than a decade ago that has found that children who have meals with their parents are less likely to smoke, drink or use drugs. In this year's survey, researchers looked at the link between the frequency of family dinners and teens' substance abuse, teens' relationships with their parents and what effect distractions such as phones and other electronic devices have at the dinner table.

Researchers from the National Center on Addiction and Substance Abuse found that teens who have family dinners fewer than three times a week -- compared with those who have family dinners five or more times a week -- were much more likely to use drugs and alcohol and have less academic success. Teens who say they have family dinners but that there are distractions at the table also have higher rates of substance abuse that teens who have frequent family dinners without interruptions.

The survey found that 59% of teens and 62% of parents reported having dinner with their families at least five times a week. Of those who didn't dine together frequently, 69% said they're too busy with work and other activities to share meals. However, two-thirds of the respondents said they would be willing to give up a weeknight activity to have dinner with their family. The average family dinners lasts about 35 minutes, according to the survey.

"The message for parents could not be any clearer: Turn off your cellphone -- and tell the kids to do the same. Make a regular date with your kids. Let them know how important they are to you. Listen to what they have to say," said Joseph A. Califano Jr., founder and chairman of the center.

The survey of 1,000 teenagers and 452 of their parents was conducted this year. The center an annual "Family Day -- A Day to Eat Dinner with Your Children," which will be held this year on Monday, Sept. 28.

-- Shari Roan

Color-coded pills often don't work for the colorblind

About 8% of men and 0.4% of women are colorblind, many of them having problems distinguishing red and green. That can be a problem for users of asthma inhalers and warfarin, among other drugs, that use different colored pills and containers to distinguish different formulations. A recent survey of 100 colorblind people found that 2% of them had mixed up their medications because of color recognition problems, researchers from the University of Melbourne reported online today in the journal Lancet.

One potential solution, the researchers said, is to use more yellow, blue and gray, which the colorblind can distinguish.

-- Thomas H. Maugh II

Photos, from top: Warfarin tablets and containers in their normal colors (A) and as seen by the colorblind (B); asthma inhalers in their normal colors (C) and as seen by individuals with a loss of red vision (D). Credit: The Lancet

Let them take heroin, study says

To improve the chances that hard-core heroin addicts will stick with their treatment for opioid dependence and forgo the use of illicit drugs, they should take … heroin.

That’s the controversial conclusion of a study being published in Thursday’s edition of the New England Journal of Medicine.

The study focused on addicts who took heroin for at least five years and had already failed two attempts at treatment. One of those attempts had to involve methadone, which helps manage heroin cravings and blocks the drug’s euphoric effects.

The goal wasn’t necessarily to get study participants to stop using heroin altogether, but to turn their addiction into a manageable fact of life instead of a source of high-risk, illegal and/or anti-social behavior.

Canadian researchers randomly assigned 115 addicts in Vancouver and Montreal to receive diacetylmorphine – the active ingredient in heroin – and 111 others to a control group that got standard methadone treatment. Those who took diacetylmorphine injected themselves up to three times a day in treatment clinics with medical supervision. Then they had to remain in the clinic for 30 minutes so they could be monitored for overdoses, seizures and other serious problems.

Overall, the addicts who took diacetylmorphine did better than the ones who took methadone.

After one year, 88% of those in the diacetylmorphine group were still in treatment, compared with 54% in the methadone group. They were also more likely to curb their illegal behavior – including use of illicit drugs – by a margin of 67% to 48%.

Patients treated with diacetylmorphine also saw bigger reductions in their illicit heroin use. They had taken the drug for an average of 26.6 days in the month before the study started, and that number fell to 5.3 days by the end of the study. In the methadone group, illicit heroin use fell from an average of 27.4 days per month to 12.0 days per month during the course of the study.

The researchers also reported that addicts who were treated with diacetylmorphine “had greater improvements with respect to medical and psychiatric status, economic status, employment situation, and family and social relations,” according to the study.

One patient from the methadone group died of an opioid overdose during the 12-month trial. But overall, serious adverse events were more than 2½ times more common among the diacetylemorphine group. Sixteen of those participants experienced a life-threatening seizure or overdose; all received prompt treatment at their clinic and recovered. 

The researchers emphasized that most heroin addicts should continue to be treated with methadone. But when methadone doesn’t cut it, they concluded, “prescribed, supervised use of diacetylmorphine appears to be a safe and effective adjuctive treatment for this severely affected population of patients who would otherwise remain outside the health care system.”

That advice may sound radical, but it has already been followed in several European countries. Switzerland, the Netherlands and Great Britain currently treat some heroin addicts with diacetylmorphine, according to an editorial accompanying the study.

In the United States, only methadone has the imprimatur of a “medical” drug, writes Virginia Berridge of the London School of Hygiene and Tropical Medicine at the University of London. That bias may help explain why the Canadian researchers were unable to collaborate with their colleagues south of the border. Perhaps, Berridge speculates, the Canadian results will have more influence on American policymakers since the study was practically “homegrown.”

-- Karen Kaplan

Photo: Methadone helps many heroin users stay off the drug, but it’s not powerful enough for all addicts. Credit:  Los Angeles Times

Doctors familiar with death by propofol

The inquiry into singer Michael Jackson's death centers on his use of the anesthetic propofol to help him sleep. Three months before Jackson's death, a group of anesthesiologists in Florida warned their colleagues about the inappropriate and dangerous use of the drug.

In their report -- titled "Death From Propofol: Accident, Suicide or Murder?" -- the University of Florida doctors detailed the 2005 death of a 24-year-old woman from propofol toxicity. The woman had no history of drug abuse. But an acquaintance, a registered nurse, did have access to the drug. The suspect fled the country, but investigators found him in Senegal and he was returned to the country, tried and convicted of first-degree murder.

The report was published in the April edition of Anesthesia & Analgesia, a journal for anesthesiologists.

"Propofol is not intrinsically more dangerous than other intravenous sedatives," Dr. Steven L. Shafer, the editor of the journal, said in a news release. "We have known since the days of Paracelsus that it is the dose that renders a drug toxic. Propofol is dispensed in doses intended to produce general anesthesia. Administration of an anesthetic dose of any hypnotic by an untrained individual, or in a setting in which general anesthesia cannot be properly managed, is a recipe for disaster."

The authors of the report cautioned that, since the early 1990s, occasional reports of abuse, accidental overdose and suicide linked to propofol have surfaced. In 2007, a forensic sciences journal reported the death of a female anesthesiologist in Greece who abused the drug. They noted that the toxic effects of the drug differ in non-intubated patients compared to intubated patients who are on an operating table. A report in 2006 described the death in Germany of a drug abuser who bought the intravenous medical supplies to self-administer propofol on Ebay.

-- Shari Roan

Photo: A granite headstone at a Jackson memorial site at Woodlawn Cemetery in Detroit. Credit: Carlos Osorio  /  Associated Press.

One drug for the novice, and one drug for the hard-core

Inhalants and propofol. The two would seem to have little in common, but both were profiled recently in the L.A. Times. One portrait offers a glimpse into middle-school life; the other portrait provides a glimpse into a medical world reliant on pharmaceuticals. Together, they begin to paint a picture of drug use in America.

In the first story, staff writer Carla Rivera documents rising concern about inhalant use among local middle school students: Los Angeles youths' nitrous oxide use has adults taking action

Some parents are particularly worried about whippets -- small containers of nitrous oxide -- but obviously inhalant use doesn't stop there. From that story: "Recently, three students at Madison Middle School in North Hollywood who allegedly had been abusing inhalants were hospitalized. At Roosevelt High, a student who had allegedly been huffing inhalants lost consciousness and had to be resuscitated."

For a closer look at inhalants, here are some numbers from the National Survey on Drug Use and Health. It states: "Inhalants were the most frequently reported class of illicit drugs used in the past year among adolescents aged 12 or 13 (3.4 and 4.8 percent, respectively)."

That may not be surprising. Inhalants are common -- easily obtainable by 12- and 13-year-olds whose access to other drugs is often limited.

But, of note, the choice of inhalant seems to be affected by gender.

"Combined data from 2002 to 2005 indicate that recent female inhalant initiates aged 12 to 17 were more likely than their male counterparts to have used glue, shoe polish, or toluene; spray paints; aerosol sprays other than spray paints; correction fluid, degreaser, or cleaning fluid; and amyl nitrite, 'poppers,' locker room odorizers, or 'rush.' Recent male inhalant initiates were more likely than their female counterparts to have used nitrous oxide or whippets." Here's that breakdown.

The  cheap and easy high of inhalants can be had not just by the traditional model-airplane glue but also via cooking sprays, nail polish remover, markers and more. The National Inhalant Prevention Coalition lists an array of potential problems.

In the second story, staffers Jeff Gottlieb and Rong-Gong Lin II profile the anesthetic recently linked to Michael Jackson: Diprivan, the drug found in Michael Jackson's home, may be more tightly restricted.

From that story: "Also known by the generic name propofol, the drug is among the most widely used general anesthetics in the U.S. Its purpose is to quickly knock out patients or make them semi-conscious during uncomfortable procedures, such as colonoscopies. The drug can be so dangerous that the U.S. Food and Drug Administration says only those trained in general anesthesia should administer it."

The story also notes: "Diprivan is not a drug people can buy on the street. Someone would have to take it from a hospital, surgery center or other medical facility or somehow obtain it from a distributor or manufacturer." And, it points out, most abuse occurs among doctors and other medical workers.

An account of the problem from Anesthesiology News begins:

"One addict fell asleep at his desk so often that his lolling forehead became a perpetual bruise. Another was so desperate for a fix that he started trolling through sharps bins for discarded needles with traces of drug to inject. The addicts were two doctors, an anesthesiologist and a family physician. Their drug of choice: propofol. If that’s surprising, consider this: One in five academic anesthesiology training programs reported at least one case of abuse by physicians or other healthcare workers over the past decade, new research shows. The incidence of propofol abuse has risen fivefold over the last 10 years."

Two drugs. Two types of users. Two worlds. ... One culture.

-- Tami Dennis

Photo: A whippets, at top, is a small canister of nitrous oxide; propofol, below, is an anesthetic.

Credit: Mark Boster / Los Angeles Times (top); Getty Images (below)

Meth use among L.A. workforce twice the national average

Drug use by employees continues to be a major problem for employers. But new statistics show the picture is changing in Los Angeles.

Data from Quest Diagnostics show that cocaine use has decreased in recent years while amphetamine use is up. In particular, the rate of positive workplace drug tests for methamphetamine in Los Angeles is more than twice the national average: 23 positive tests per 10,000 people versus 11 per 10,000 nationwide.

Positive tests for cocaine were found in 27 per 10,000 workers in Los Angeles compared with 39 per 10,000 workers nationwide. Overall, screening shows a decline in positive drug tests in Los Angeles from 320 per 10,000 workers in 2006 to 269 per 10,000 last year. Nationwide, 380 per 10,000 workers tested positive for drug in 2006 compared with 360 per 10,000 last year.

The data are from the annual Quest Diagnostics Drug Testing Index, based on 5.7 million urine drug tests performed by the company.

-- Shari Roan

Photo: A pipe used to smoke crystal meth. Credit: Ann Heisenfelt / AP
 

Rodent of the Week: How the brain gets hooked on drugs

A study in which researchers got mice hooked on drugs without using drugs may yield clues to a key part of the brain involved in drug addiction.

The study, published online today in the journal Science, shows that a naturally occurring protein called brain-derived neurotrophic factor, or BDNF, acts on a part of the brain called the ventral tegmental area and switches the cells in this area from a dopamine-independent system to a dopamine-dependent system, thus causing addiction.

Researchers have known that drug addiction is a disease that disrupts the brain's dopamine response, which is involved in feelings of pleasure and reward. Chronic exposure to drugs increases levels of BDNF in the ventral tegmental area, which is where dopamine circuitry is located. The researchers gave rats who were not dependent on drugs a single injection of BDNF into the ventral tegmental area of the brain. The injection made the rats behave as if they were dependent, causing them to prefer certain smells, lighting and textures and to seek this stimulation for a "fix." The BDNF injection caused specific chemicals that normally inhibit neurons in this part of the brain to instead excite them.

"When someone chronically uses drugs, this system changes. This is the mechanism that makes you feel like you need that drug," said the lead author of the study, Hector Vargas-Perez, of the University of Toronto.

"If we can understand how the brain's circuitry changes in association with drug abuse, it could potentially suggest ways to medically counteract the effects of dependency," Scott Steffensen, a Brigham Young University neuroscientist and co-author of the study, said in a news release.

— Shari Roan

Photo: Courtesy of Advanced Cell Technology Inc.