Weight Loss Drug Lorcaserin Cuts Opiate Use in Rats
Lorcaserin is a drug approved for weight loss in very obese patients. It stimulates serotonin 5 HT-2c receptors thought to control appetite by inducing the secretion of the polypeptide pro-opiomelanocortin. In a 2017 article in the journal ACS Chemical Neuroscience, researcher Kathryn Cunningham and colleagues reported that the drug had reduced opiate use and craving in rats. Previous research by Cunningham showed that lorcaserin reduced cocaine seeking in rats.
Most treatments for opiate addiction work by occupying opiate receptors so that opiates are prevented from stimulating them, thus reducing the pleasurable effects of the opiates. It is not yet well understood how drugs like lorcaserin that target serotonin 5 HT-2c receptors affect the brain’s reward system.
In the study, rats were trained to self-administer oxycodone. They were also trained to associate certain lights and sounds with oxycodone availability. Lorcaserin reduced the rats’ drug-seeking behavior and also weakened the link between the light and sound cues and the drug-seeking behavior.
Future research may explore whether drugs like lorcaserin can reduce opiate use in people.
Currently, there are a few options to treat opiate addiction. N-acetylcysteine (NAC) is an over-the- counter (nonprescription) drug that has been shown to decrease opiate use in both animals and humans. NAC also decreases use or craving for many other drugs of abuse including cocaine, alcohol, nicotine, and marijuana. NAC reduces the excitatory glutamate signal in the reward area of the brain (the nucleus accumbens) by increasing the number of transporters carrying glutamate out of the synapse and into glial cells. It has an excellent side effects profile and can readily be used in opiate-addicted patients.
Opiate replacement therapy with methadone or the partial opiate agonist buprenorphine is one treatment option for opiate addiction. Buprenorphine is also combined with the opiate antagonist naloxone in a drug called Suboxone, which can reduce opiate use. Naloxone is a pure opiate antagonist that can rapidly reverse the respiratory-suppressing effects of an overdose of opiates.
RTMS May Treat Cocaine Addictions
In a pilot study, repeated transcranial magnetic stimulation (rTMS) reduced cocaine cravings and usage among people with cocaine addiction.
RTMS is a non-invasive treatment in which a magnetic coil placed near the skull transmits electrical signals to the brain. It is an effective treatment for depression, and there is growing evidence that it may also be able to treat addictions.
Participants in the pilot study by researcher Antonello Bonci and colleagues received rTMS directed at their dorsolateral prefrontal cortex or pharmacological treatments (including medications to manage depression, anxiety, and sleep problems) over a 29-day study period. Among the rTMS recipients, 69% remained cocaine-free during the study period, compared to only 19% of those treated with medications. Those who received rTMS also reported fewer cravings.
There were few side effects among those who received rTMS, and there was a 100% compliance rate among the 32 participants, meaning they all showed up for each of their sessions.
Bonci and colleagues are working on a larger study that will compare rTMS treatment to a sham procedure rather than to a medication regime.
New Study Suggests RTMS Can Reduce Cocaine Use and Cocaine Cravings
Repeated transcranial magnetic stimulation, or rTMS, is a non-invasive treatment in which a magnetic coil placed near the skull transmits electrical signals to the brain. It is an effective treatment for depression, and now it appears it may also be useful in the treatment of addictions.
A pilot study by Alberto Terraneo and colleagues published in European Neuropsychopharmacology in 2016 compared rTMS treatment delivered to the dorsolateral prefrontal cortex to pharmacological treatment in 32 patients who wanted to stop using cocaine. Those in the rTMS group received one session of the treatment per day for five days, followed by one session per week for three weeks. Those who received rTMS had a higher number of cocaine-free urine tests than those who had been treated with pharmacological treatments. Among those who received rTMS, 69% had a positive outcome, compared to 19% of the control group. RTMS also reduced cravings for cocaine. Both treatments improved depression.
Antonello Bonci, another author of the study who is also scientific director at the US National Institute on Drug Abuse, suggested that rTMS may work by “scrambling” the pattern of neural activity that leads to cocaine craving.
Now that there is some evidence suggesting that rTMS may be useful in the treatment of addictions, the researchers are planning a placebo-controlled study of rTMS treatment for cocaine use, in which they will give some patients a sham treatment instead of real rTMS.
Other studies are examining whether rTMS can be used to treat smoking and alcohol use disorders in addition to depression.
Statins Reduce Drug-Craving in Mice
Statins are drugs that are typically used to lower cholesterol. Recent research on the drugs has focused on their effects on the brain.
In 2015 Claudia Chauvet and colleagues reported in the journal Neuropsychopharmacology that the brain-penetrating statins simvastatin and Atorvastatin reduced cocaine seeking behaviors in mice that were taught to self-administer cocaine and then were denied access to it for 21 days compared to pravastatin, a statin that does not penetrate the brain as thoroughly. The researchers found that the brain-penetrating statins also reduced nicotine seeking, but not food reward seeking. The statins also worked in mice that had stopped seeking cocaine but relapsed due to stress, allowing them to abstain from cocaine seeking again.
Statins are considered a very safe treatment in humans. The ability of statins to prevent relapse to addictions in mice may mean that one day they could be used to treat addictions in people as well. A review article by Cassie Redlich and colleagues in the journal BMC Psychiatry in 2014 indicated that statins may reduce recurrence of depression in people. The researchers found that simvastatin had a protective effect while Atorvastatin was associated with increased risk of depression, so the choice of statins may be important for both depression and addiction.
Blockade of Kappa Opiate Receptors Blocks Proneness to Relapse in Addiction
George Koob, the new director of the National Institute for Alcohol Abuse and Alcoholism (NIAAA), showed that animals with extended access to self-administered abuse substances like cocaine or morphine will escalate the amount of drug they self-administer. When the drug is no longer available starting after a delay of one to two weeks, the number of times they press a lever in the presence of a cue previously associated with drug availability progressively increases over a period of one to two months (even through no drug is available). This is called incubation and reflects a measure of “craving” or relapse potential.
This incubation effect, or increasing degree of craving for a drug, is also seen clinically in people who are heavy drug users and then achieve abstinence or are incarcerated and have a period of forced abstinence. As the duration of abstinence increases, they experience an increased proneness to relapse.
Dynorphin is a psychomimetic opiate peptide that is produced in the brain and causes anxiety and dysphoria when it is given to humans. While opiates like morphine and heroin that produce euphoria and antipain effects act at a mu opiate receptor, dynorphin acts at a kappa opiate receptor. Chronic cocaine use gradually increases levels of dynorphin in the brains of addicts and also increases kappa receptors, thus converting what is often initially a euphoric drug experience into an anxiety-producing and dysphoric one.
If kappa receptors are blocked, the incubation effects during abstinence described above do not occur, and presumably addicts would be less relapse-prone. No kappa antagonist is currently available for human use, but if one combines buprenorphine (a mixed opiate agonist/antagonist) with naloxone or naltrexone (which selectively block the mu opiate receptors), one would in effect have a kappa receptor antagonist. Koob showed that this drug combination could prevent the incubation effects in abstinent animals. Further study might lead to advances in the treatment of addition in humans.
