August 21, 2023 – A variety of gene therapy that reboots the brain’s reward system could curb alcohol consumption in individuals with severe alcohol use disorder.
Researchers at Oregon Health & Science University implanted the therapy directly into the brains of rhesus monkeys that were conditioned to drink eight to 10 alcoholic drinks a day. A harmless virus carrying a selected gene was implanted into the region of the brain that regulates dopamine, which mediates feelings of reward and pleasure.
“We wanted to see if we could normalize dopamine in these motivational areas – that is, whether the motivation to drink too much or drink a lot could actually be reduced,” said study creator Kathleen Grant, PhD, professor and director of the Department of Neuroscience on the university's Oregon National Primate Research Center.
The need for brand spanking new treatments for alcohol use disorder could also be more urgent than ever. According to a study published within the journal Alcohol-related deaths within the United States increased dramatically between 2007 and 2020, particularly amongst women. JAMA network opened. The next 12 months, the numbers rose again, to 108,791 alcohol-related deaths in 2021 alone. According to the National Institutes of HealthThis is barely greater than the variety of Drug overdoses recorded in 2021.
For the 29.5 million Americans If you may have alcohol use disorder, also called alcohol abuse or dependence, the road to recovery will be difficult. One reason is that the reward systems in your brain are working against you.
The first sip of alcohol causes your body to release the feel-good brain chemical dopamine. However, if you happen to drink an excessive amount of for too long, your brain reduces dopamine production and you wish much more alcohol to feel good again.
The gene the researchers implanted into the monkeys' brains is known as “glial-derived neurotrophic factor.” It's a “growth factor,” meaning it stimulates cell proliferation. It could help improve the function of brain cells that synthesize dopamine, effectively resetting the complete system and reducing cravings for alcohol.
The study was surprisingly successful. Compared to primates that received a placebo intravenously, the primates that got the expansion factor gene reduced their alcohol consumption by about 90%. They practically stopped drinking, while the primates that got the placebo resumed their habit.
An analogous procedure is already getting used on patients with Parkinson's disease. But more animal studies and human clinical trials are needed before this therapy will be used on individuals with alcohol abuse. This invasive treatment requires brain surgery, which carries risks, so it’s going to likely be reserved for under those with the worst and most dangerous drinking habits.
“I think it would be suitable for people for whom other treatments simply have not worked and who fear for their lives,” Grant said.
Treatments for alcohol abuse disorders
Today, treatment for alcohol use disorder ranges from a temporary conversation with a physician in mild cases to psychiatric treatment or medication in moderate or severe cases.
There are 4 FDA-approved treatments for alcohol abuse and a number of other other medications that doctors can prescribe outside of their approved indications.
“They are not widely used,” says Dr. Henry Kranzler, professor of psychiatry and director of the Center for Studies of Addiction on the Perelman School of Medicine on the University of Pennsylvania. “They are shockingly underused.”
One reason: According to a study, only 4.6% of individuals with alcohol problems seek treatment annually. NIH data.
“The problems include the ubiquity of alcohol and its acceptance in American culture – and the fact that it makes it difficult for people to admit that they have a drinking problem,” says Kranzler.
Another problem, nonetheless, is that many healthcare professionals fail to acknowledge and treat alcohol abuse in patients searching for treatment. Those searching for treatment for alcohol abuse can find a professional provider at American Academy of Addiction Psychiatry or American Society for Addiction Medicine directories.
The way forward for treatment
Ongoing research may lead to more treatment options and make them more available and attractive.
Unlike many other drugs that act on only a single receptor within the body — like opioids, which act on opioid receptors, or nicotine, which acts on choline receptors — alcohol affects many alternative receptors, says Dr. Robert Swift, a professor of psychiatry and human behavior at Brown University Alpert Medical School. In high doses, alcohol also penetrates cells.
“Alcohol has so many different effects that it's very difficult to treat,” he said. “But on the other hand, it gives us an advantage because there are probably different points that we can attack.”
There are other exciting developments underway, but further research, including human clinical trials, is required to implement them.
Some of essentially the most promising:
- Hallucinogens. In the Nineteen Fifties, before they became illegal, these intoxicants helped people drink less. Even Bill Wilson, co-founder of Alcoholics Anonymous, used hallucinogenic treatments during his recovery; they helped him imagine how he might overcome a challenge. Today, there may be a renewed interest in hallucinogens to treat alcoholism. In a study published in JAMA PsychiatryPeople with alcohol use disorder who got the hallucinogen psilocybin along with therapy spent fewer days of heavy drinking over the next 32 weeks than individuals who got one other drug. But don't try to do that yourself. “It's not just taking a hallucinogen and experiencing a trip,” Swift said. “It's a therapy-led session, so it's a combination of taking the hallucinogenic substance with a skilled therapist, sometimes even two skilled therapists, helping to guide the experience.”
- Epigenetic editing. Drinking alcohol can affect the activity of a gene in your amygdala, a region of the brain involved in processing emotions. Researchers at the University of Illinois at Chicago found that by editing this gene in rats using an infusion of genetic material, they reduced the rodents' drinking behavior and anxiety.
- oxytocin. The so-called love hormone that your brain produces whenever you hug your partner could help reset the dopamine system to make alcohol less attractive. “There are oxytocin receptors on dopamine neurons, and oxytocin makes your dopamine system more effective,” Swift said. In a current study from the Medical University of South Carolina showed that mice injected with oxytocin didn’t drink during a stressful situation, which could otherwise have led to a relapse.
- Ghrelin. This stomach hormone, which helps you stay full, could help limit drinking. In a study published in Neuropharmacologyshowed that mice given drugs to extend ghrelin levels reduced their alcohol consumption.