During investigations into using transcranial brain stimulation (TMS) to treat cocaine abuse, two projects take diverging paths. One researcher moves to the next stage, while another is forced to cut his trial short.
Giving mice a modified version of a naturally occurring gene blocks cocaine’s stimulant effects without affecting the animals’ physiological or metabolic health. The new evidence advances the proposed therapy a step closer to readiness for testing in people.
Two researchers share their reasons for researching transcranial magnetic stimulation (TMS) for treating cocaine addiction, and describe challenges to moving forward this potentially promising therapy.
In mice, a cocaine-induced imbalance in the activity of two key populations of neurons in the reward system persists for a longer period after repeated exposure to the drug. For long-term users, this change could both weaken the cocaine “high” and strengthen the compulsion to seek the drug.
A NIDA-supported study has found that a cocaine-addicted person’s chance of managing 1 whole year of abstinence correlates with activity levels in these impaired motivational and decision-making brain areas.
A can-do attitude, ability to cope with potential triggers for drug use, readiness to change, and participation in self-help programs are major assets for people trying to recover from cocaine addiction.
A stressed rat will seek a dose of cocaine that is too weak to motivate an unstressed rat. Researchers traced the physiological pathway that links stress and the stress hormone corticosterone to increased dopamine activity and heightened responsiveness to cocaine.
Dr. Paul E. M. Phillips spoke on “Phasic Dopamine Transmission During Substance Abuse,” describing investigations that he has led into the role of brief, seconds-long bursts of dopamine signaling in addictive processes. Dr. Rita Z. Goldstein spoke on “Targeting the Brain, Cognition, and Motivation for Intervention in Addiction.”
The Scientific Director of NIDA’s Intramural Research Program talks about switching off animals’ compulsive cocaine seeking by optogenetically activating the prefrontal cortex, and the implications of this work for people. In an accompanying podcast, Dr. Bonci walks viewers through experiments that showed that prefrontal cortex activity levels may constitute a simple switch controlling whether or not animals compulsively seek cocaine.
Two recent studies suggest that genotyping may enable clinicians to base therapies on individual patients’ potential responsiveness to opioid drugs’ therapeutic effects and vulnerability to their harmful effects.
A brain response occurs in the nucleus accumbens when rats encounter a cue that they associate with previous cocaine self-administration, but not a cue associated with a pleasurable non-drug experience. Moreover, the response correlates in time and intensity with the animals’ cue-induced relapse to cocaine-seeking.
Exposing rats to THC increases the likelihood that the animals will later self-administer nicotine. THC-exposed rats are also willing to work harder to obtain nicotine. When extrapolated to people, the findings suggest that THC’s pharmacological impact on the brain may make a person who uses marijuana more vulnerable to developing nicotine addiction, an underappreciated health consequence of marijuana use.
Almost one-third (32 percent) of the roughly 42,000 Monitoring the Future survey respondents reported having used marijuana during their lifetime. However, abuse of many other drugs—methamphetamine, heroin, cocaine, and some prescription medications—declined.
Teen mothers on three American Indian reservations improved on several measures of parenting after participating in Family Spirit, a home-visiting intervention developed with NIDA support. At 12 months postpartum, the women’s children exhibited reduced rates of emotional difficulties predicting later drug abuse and other behavioral problems. Infants at highest risk—those whose mothers had histories of drug abuse—benefited the most.
Researchers have shut down laboratory rats’ compulsive cocaine seeking by stimulating an area of the animals’ prefrontal cortex. The finding raises the possibility that stimulating neurons in this brain area may weaken or break cocaine’s grip on the behavior of people who are addicted to the drug.
Dr. Marilyn Huestis of NIDA’s Intramural Research Program talks about conducting research on drug effects with human subjects, developing tests to help law enforcement identify drugged drivers, and an assay to help identify children whose prenatal exposure to anti-HIV drugs may put them at risk for adverse developmental outcomes.
New research demonstrated that, in rhesus monkeys, ongoing cocaine exposure weakens two brain functions that people require for successful behavioral change: cognitive flexibility and memory. But the study determined that these changes may not be permanent.
When the goal is to avoid using alcohol and illicit substances after being released from jail, it’s who one’s friends are that counts most. Self-control is important because it helps a person have the right kind of friends.
Fewer teens are using cigarettes, alcohol, and most illicit drugs, according to NIDA’s latest Monitoring the Future study. Troubling trends persist in marijuana use, however, and nonmedical prescription drug use remains a concern.
Nicotine sensitizes the mouse brain to the addictive effects of cocaine, according to recent NIDA-supported research. The results accord with the hypothesis that a person’s initial use of an addictive substance physiologically sensitizes his or her brain to the rewarding and addictive effects of other substances. If the findings carry over to people, then preventing youths from smoking might reduce their vulnerability to cocaine abuse and addiction, and cocaine-dependent individuals might ease their path to recovery by quitting smoking.
The immune system has an extraordinary ability to recognize compounds foreign to the body and eliminate them. NIDA-sponsored scientists are working to harness this ability to create vaccines that will protect individuals against the psychogenic and addictive effects of abused drugs. This animation shows one of the most promising strategies, which has already yielded partial success in producing effective vaccines against nicotine, cocaine, and other drugs.
NIDA-supported research suggests that glucocorticoid receptor levels during early brain development affect the hard wiring of neural circuits that shape an individual’s basic emotional makeup. In mice, overexpression of the glucocorticoid gene in the first weeks after birth increased anxiety and response to cocaine in adulthood. These findings may help researchers understand the genetic background and the developmental trajectory of addiction.
New vaccines that aim to promote recovery from cocaine and heroin abuse showed promise in animal testing. Both vaccines induced rats’ immune system to produce high titers of antibodies that inhibit the target drug from reaching the brain. The rats’ behaviors when given access to the target drug indicated that the vaccines reduced the reinforcing effects that, in recovering people, can cause lapses to turn into relapses.
Prenatal drug exposure can have behavioral effects that last well into adulthood, according to two studies of adult monkeys prenatally exposed to cocaine. In the first study, drug-exposed monkeys exhibited less flexibility than controls in adjusting to changing circumstances; in the second study, drug-exposed males exhibited a greater preference than controls for having rewards right away, a sign of impulsivity.
Dr. J. David Jentsch is the recipient of the 2011 Jacob P. Waletzky Memorial Award for Innovative Research in Drug Addiction and Alcoholism. Dr. Jentsch and colleagues at the University of California, Los Angeles, are studying genetic and neurochemical factors that influence individual differences in inhibitory control.
Illicit drug use in the United States in 2010 was at its highest level since 2002, according to the most recent report from the National Survey on Drug Use and Health. A rise in marijuana use drove the increase. A favorable trend of falling cocaine use continued.
New studies show that microRNAs, snippets of RNA implicated in a wide variety of biological processes, are involved in promoting and inhibiting cocaine addiction. The findings could pave a new path for the development of anti-addiction therapies.
Reports on the results of a clinical trial that tested the effectiveness of a cocaine vaccine designed as a therapy for cocaine abuse and plans underway for a new study of 300 patients to confirm these results.
Describes a series of experiments that have added to evidence that a brain enzyme controls key memory processes that link drug experiences, the surroundings in which they take place, and the urge to repeat them.