Posts tagged drug addiction
Articles and news from the latest research reports.
Deep brain stimulation: a fix when the drugs don’t work
Neurological disorders can have a devastating impact on the lives of sufferers and their families.
Symptoms of these disorders differ extensively – from motor dysfunction in Parkinson’s disease, memory loss in Alzheimer’s disease to inescapable cravings in drug addiction.
Drug treatments are often ineffective in these disorders. But what if there was a way to simply switch off a devastating tremor, or boost a fading memory?
Recent advances using Deep Brain Stimulation (DBS) in selective brain regions have provided therapeutic benefits and have allowed those affected by these neurological disorders freedom from their symptoms, in absence of an existing cure.
A pacemaker for the brain
Artificial cardiac pacemakers are typically associated with controlling and resynchronising heartbeats by electrical stimulation of the heart muscle.
In a similar manner, DBS sends electrical impulses to specific parts of the brain that control discrete functions. This stimulation evokes control over the neural activity within these regions.
Prior to switching on the electrical stimulation, electrodes are surgically implanted within precise brain regions to control a specific function.
The neurosurgery is conducted under local anaesthetic to maintain consciousness in the patient. This ensures that the electrode does not damage critical brain regions.
The brain itself has no pain receptors so does not require anaesthetic.
Following recovery from surgery the electrodes are activated and the current calibrated by a neurologist to determine the optimal stimulation parameters.
The patient can then control whether the electrodes are on or off by a remote battery-powered device.
Turning off tremors
Perhaps the most documented success of DBS is in the control of tremors and motor coordination in Parkinson’s disease.
This is caused by the degeneration of neurons in an area of the brain called the substantia nigra. These neurons secrete the neurotransmitter dopamine.
Deterioration of these neurons reduces the amount of dopamine available to be released in a brain area involved in movement, the basal ganglia.
Drug therapy for Parkinson’s disease involves the use of levodopa (L-DOPA), a form of dopamine that can cross the blood brain barrier and then be synthesised into dopamine.
The administration of L-DOPA temporarily reduces the motor symptoms by increasing dopamine concentrations in the brain. However, side effects of this treatment include nausea and disordered movement.
DBS has been shown to provide relief from the motoric symptoms of Parkinson’s disease and essential tremors.
For the treatment of Parkinson’s disease electrodes are implanted into regions of the basal ganglia – the subthalamic nucleus or globus pallidus, to restore control of movement.
These are regions innervated by the deteriorating substantia nigra, therefore the DBS boosts stimulation to these areas.
Patients can then switch on the electrodes, stimulating these brain regions to enhance control of movement and diminish tremors.
Restoring fading memories
Recently, DBS has been used to diminish memory deficits associated with Alzheimer’s disease, a progressive and terminal form of dementia.
The pathologies associated with Alzheimer’s disease involve the formation of amyloid plaques and neurofibrillary tangles within the brain leading to dysfunction and death of neurons.
Brain regions primarily affected include the temporal lobes, containing important memory structures including the hippocampus.
Recent clinical trials with DBS involve the implantation of electrodes within the fornix – a structure connecting the left and right hippocampi together.
By stimulating neural activity within the hippocampi via the fornix, memory deficits associated with Alzheimer’s disease can be improved, enhancing the daily functioning of patients and slowing the progression of cognitive decline.
Deactivating addiction
Another use of DBS is in the treatment of substance abuse and drug addiction. Substance-related addictions constitute the most frequently occurring psychiatric disease category and patients are prone to relapse following rehabilitative treatment.
Persistent drug use leads to long term changes in the brain’s reward system.
Understanding of the reward systems affected in addiction has created a range of treatment options that directly target dysregulated brain circuits in order to normalise functionality.
One of the key reward regions in the brain is the nucleus accumbens and this has been used as a DBS target to control addiction.
Translational animal research has indicated that stimulation of the nucleus accumbens decreases drug seeking in models of addiction. Clinical studies have shown improved abstinence in both heroin addicts and alcoholics.
Studies have extended the use of DBS to potentially restore control of maladaptive eating behaviours such as compulsive binge eating.
In a recent study, binge eating of a high fat food in mice was decreased by DBS of the nucleus accumbens. This is the first study demonstrating that DBS can control maladaptive eating behaviours and may be a potential therapeutic tool in obesity.
Despite its therapeutic use for more than a decade, the neural mechanism of DBS is still not yet fully understood.
The remedial effect is proposed to involve modulation of the dopamine system – and this seems particularly relevant in the context of Parkinson’s disease and addiction.
DBS potentially has effects on the functional activity of other interconnected brain systems. While it can provide therapeutic relief from symptoms of neurological diseases, it does not treat the underlying pathology.
But it provides both effective and rapid intervention from the effects of debilitating illnesses, restoring activity in deteriorating brain regions and aids understanding of the brain circuits involved in these disorders.
Can Virtual Reality Treat Addiction?
Researchers are plugging in smokers, alcoholics, and even crack addicts to expose them to a relapse environment—and teach them how to deal with it. Will it work?
When the addicts enter the room, they haven’t met the people inside. They’ve never been there before, but the setting is familiar, and so is the pipe on the table, or the bottles of booze on the ground. Soon enough, someone’s offering them a hit, or a drug deal’s going down right in front of them.
They’ve been trying to get better—that’s why they’re doing this—but now they have cravings.
It’s about then that a voice instructs them to put down the joystick and look around the room without speaking, “allowing that drug craving to come and go like a wave.” The voice asks them periodically to rate their cravings as, after a couple minutes, they start to relax. The craving starts to dissipate and they hear a series of tones: beep-boop-boop.
It’s all being orchestrated by a wizard behind the virtual curtain: Zach Rosenthal, an assistant professor at Duke. For years now, with funding from the National Institute on Drug Abuse and the Department of Defense, Rosenthal has been running virtual reality trials like this with drug addicts in North Carolina (and veterans, hence the DOD funding) who are trying to recover. About 90 people, passing in and out of the NIDA study, have been coming to Rosenthal for treatment through virtual reality. They’re hooked up to a virtual reality simulator and dumped somewhere (a neighborhood, a crack house) where the researchers can slowly add cues to the environment, or change the environment itself, altering the situation to based on each patient’s history and adding paraphernalia (drugs, a crack pipe) as necessary.
The idea is that people will develop coping strategies, then take those strategies back to the real world. With coping mechanisms in their tool kits, users will get better, faster. But just because someone says no in a fake world, does that mean he’ll say no in real life?
Increased brain activity predicts future onset of substance use
Do people get caught in the cycle of overeating and drug addiction because their brain reward centers are over-active causing them to experience greater cravings for food or drugs? In a unique prospective study Oregon Research Institute (ORI) senior scientist Eric Stice, Ph.D., and colleagues tested this theory, called the reward surfeit model. The results indicated that elevated responsivity of reward regions in the brain increased the risk for future substance use, which has never been tested before prospectively with humans. Paradoxically, results also provide evidence that even a limited history of substance use was related to less responsivity in the reward circuitry, as has been suggested by experiments with animals. The research appears in the May 1, 2013 issue of Biological Psychiatry.
In a novel study using functional Magnetic Resonance Imaging (fMRI) Stice’s team tested whether individual differences in reward region responsivity predicted overweight/obesity onset among initially healthy weight adolescents and substance use onset among initially abstinent adolescents. The neural response to food and monetary reward was measured in 162 adolescents. Body fat and substance use were assessed at the time of the fMRI and again one year later.
"The findings are important because this is the first test of whether atypical responsivity of reward circuitry increases risk for substance use," says Dr. Stice. "Although numerous researchers have suggested that reduced responsivity is a vulnerability factor for substance use, this theory was based entirely on cross-sectional studies comparing substance abusing individuals to healthy controls; no studies have tested this thesis with prospective data."
Investigators examined the extent to which reward circuitry (e.g., the striatum) was activated in response to receipt and anticipated receipt of money. Monetary reward is a general reinforcer and has been used frequently to assess reward sensitivity. The team also used another paradigm to assess brain activation in response to the individual’s consumption and anticipated consumption of chocolate milkshake. Results showed that greater activation in the striatum during monetary reward receipt at baseline predicted future substance use onset over a 1-year follow-up.
Noteworthy was that adolescents who had already begun using substances showed less striatal response to monetary reward. This finding provides the first evidence that even a relatively short period of moderate substance use might reduce reward region responsivity to a general reinforcer.
"The implications are that the more individuals use psychoactive substances, the less responsive they will be to rewarding experiences, meaning that they may derive less reinforcement from other pursuits, such as interpersonal relationships, hobbies, and school work. This may contribute to the escalating spiral of drug use that characterizes substance use disorders," commented Stice.
Although the investigators had expected parallel neural predictors of future onset of overweight during exposure to receipt and anticipated receipt of a palatable food, no significant effects emerged. It is possible that these effects are weaker and that a longer follow-up period will be necessary to better differentiate who will gain weight and who will remain at a healthy weight.
(Image courtesy: West Virginia University)
Researchers identify pathway that may protect against cocaine addiction
A study by researchers at the National Institutes of Health gives insight into changes in the reward circuitry of the brain that may provide resistance against cocaine addiction. Scientists found that strengthening signaling along a neural pathway that runs through the nucleus accumbens — a region of the brain involved in motivation, pleasure, and addiction — can reduce cocaine-seeking behavior in mice.
Research suggests that about 1 in 5 people who use cocaine will become addicted, but it remains unclear why certain people are more vulnerable to drug addiction than others.
“A key step in understanding addiction and advancing treatment is to identify the differences in brain connectivity between subjects that compulsively take cocaine and those who do not,” said Ken Warren, Ph.D., acting director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Researchers at NIAAA, part of NIH, conducted the study.
“Until now, most efforts have focused on finding traits associated with vulnerability to develop compulsive cocaine use. However, identifying mechanisms that promote resilience may prove to have more therapeutic value,” said the paper’s senior author, Veronica Alvarez, Ph.D., acting chief of the Section on Neuronal Structure in the NIAAA Laboratory for Integrative Neuroscience. The study is available on the Nature Neuroscience website ahead of print.
In the study, mice were conditioned to receive an intravenous dose of cocaine each time they poked their nose into a hole in their enclosure. Cocaine was then made unavailable for periods of time during the day. Some of the mice would stop seeking the drug once it was removed while others would obsessively continue to poke the hole in an effort to obtain the drug.
Mice that quickly stopped seeking the drug were found to have stronger connections along the indirect pathway — a neural tract that forms indirect projections into the midbrain and contains cells called medium spiny neurons expressing dopamine D2 receptors (D2-MSNs). A parallel pathway — known as the direct pathway — forms direct projections into the midbrain neurons and contains medium spiny neurons expressing D1 receptors (D1-MSNs). These two pathways are thought to work together in complementary but sometimes opposing ways to affect behavior.
"We were very surprised by the results of the study because we were originally looking for vulnerability factors for developing compulsive drug use,” said Dr. Alvarez. “Instead, we found changes that only happened in subjects that show a resilience to becoming compulsive drug users. Resilient mice had a strong inhibitory circuit that allowed them to exert better control over their drug intake."
To test this observation, researchers used lasers to activate individual neurons, and found that stimulating D2-MSNs in the nucleus accumbens decreased cocaine seeking in the mice. Blocking D2-MSN signaling with a chemical process increased motivation to obtain cocaine.
“This research advances our understanding of how the recruitment, activation and the interaction among brain circuits can either restrain or increase motivation to take drugs,” said David Shurtleff, Ph.D. acting deputy director of the National Institute on Drug Abuse.
Previous studies have shown that people with lower levels of dopamine D2 receptors in the striatum, a brain region associated with reward and working memory, are more likely to develop compulsive behaviors toward stimulant drugs.
Dopamine is a key neurotransmitter involved in reward-based learning and addiction. Cocaine disrupts communication between neurons at the synapse, the small junction between nerve cells, by blocking the reabsorption of dopamine into the transmitting neuron. As a result, dopamine continues to stimulate the receiving neuron, causing feelings of alertness and euphoria.
Research identifies a way to block memories associated with PTSD or drug addiction
New research from Western University could lead to better treatments for Post-Traumatic Stress Disorder (PTSD) and drug addiction by effectively blocking memories. The research performed by Nicole Lauzon, a PhD candidate in the laboratory of Steven Laviolette at Western’s Schulich School of Medicine & Dentistry has revealed a common mechanism in a region of the brain called the pre-limbic cortex, can control the recall of memories linked to both aversive, traumatic experiences associated with PTSD and rewarding memories linked to drug addiction. More importantly, the researchers have discovered a way to actively suppress the spontaneous recall of both types of memories, without permanently altering memories. The findings are published online in the journal Neuropharmacology.
“These findings are very important in disorders like PTSD or drug addiction. One of the common problems associated with these disorders is the obtrusive recall of memories that are associated with the fearful, emotional experiences in PTSD patients. And people suffering with addiction are often exposed to environmental cues that remind them of the rewarding effects of the drug. This can lead to drug relapse, one of the major problems with persistent addictions to drugs such as opiates,” explains Laviolette, an associate professor in the Departments of Anatomy and Cell Biology, and Psychiatry. “So what we’ve found is a common mechanism in the brain that can control recall of both aversive memories and memories associated with rewarding experience in the case of drug addiction.”
In their experiments using a rat model, the neuroscientists discovered that stimulating a sub-type of dopamine receptor called the “D1” receptor in a specific area of the brain, could completely prevent the recall of both aversive and reward-related memories. “The precise mechanisms in the brain that control how these memories are recalled are poorly understood, and there are presently no effective treatments for patients suffering from obtrusive memories associated with either PTSD or addiction,” says Lauzon. “If we are able to block the recall of those memories, then potentially we have a target for drugs to treat these disorders.”
Methamphetamine vaccine shows promise
Methamphetamine is one of the most addictive and thus commonly-used street drugs – according to the United Nations Office on Drugs and Crime, there are currently nearly 25 million meth addicts worldwide. Help may be on the way, however. Scientists from The Scripps Research Institute have had success in using a methamphetamine vaccine to block the effects on meth on lab rats.
The vaccine works by allowing the body’s immune system to attack methamphetamine molecules in the bloodstream, keeping them from entering the nervous system. This keeps the meth from affecting the user’s brain, and thus removes the incentive for using the drug.
Ordinarily, meth molecules are too small to evoke an antibody response from the body. The vaccine, known as M6, gets around this by linking a meth-related chemical to a larger carrier molecule that does cause an antibody response. Once the antibodies are in the bloodstream, they attack both the carrier molecules and the actual meth molecules.
In tests on rats, M6 blocked two of the typical effects of the drug – loss of the ability to regulate body temperature, and in increase in physical activity. In another ongoing Scripps study, meth-targeting antibodies were grown in cultured cells in a lab, then injected into rats in a concentrated dose. This approach also blocked the effects of the drug.
More animal trials are planned for now, with the possibility of human trials occurring in the future.