man with alcohol bottle

Alcohol Use Disorder

Like other addictions, Alcohol Use Disorder (AUD) is a chronic, relapsing brain disease. AUD is generally characterized by compulsive drinking, an inability to control intake despite negative social or economic consequences, and a negative emotional and physical state when not consuming alcohol. People diagnosed with AUD can still be functional, with their level of functionality dependent upon the severity of their disorder. Hence, we believe that a reduction in drinking can have a meaningful impact, especially since most drinkers do not want to stop drinking entirely (abstinence).

Although not necessarily classified as AUD unless other criteria are met, binge drinking is the most common, costly and deadly pattern of excessive alcohol use in the United States according to the CDC. For men and women, this translates to about 5 or more drinks and 4 or more drinks in a single session, respectively.  Over 90% of American adults who drink excessively report binge drinking in the past 30 days.

About 17 million people in the United States suffer from some form of AUD. The economic costs of AUD are staggering: roughly $250 billion annually are spent on alcohol-related healthcare, lost productivity, and criminal justice costs (binge drinking accounts for 77% or $191 billion). AUD is the third leading preventable cause of death in the United States. More Americans die from alcohol-related causes each year (estimated at 88,000) than all other drug poisoning fatalities combined. Healthwise, excessive alcohol consumption can lead to alcoholic liver disease (liver damage).  Liver damage usually manifests in the following order: accumulation of fat, inflammation, and cirrhosis, which is irreversible, may require a transplant and can be fatal.

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Americans suffer from some form of AUD

What constitutes an Alcohol Use Disorder?

According to the National Institute on Alcohol Abuse and Alcoholism, “Alcohol Use Disorder” or AUD is a medical diagnosis given when problem drinking becomes severe. AUD is a chronic relapsing brain disease characterized by compulsive use of alcohol, the inability to control intake, and the negative emotional state of not drinking.

Signs and Symptoms of Alcohol Use Disorder

To be diagnosed with AUD, individuals must meet certain criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM). Under the current version of the DSM, anyone meeting any two of the following 11 criteria during the same 12-month period receives a diagnosis of AUD, with severity based on the number of criteria met.

  • Drinking more than or for a longer period of time than intended
  • Undergoing repeated, unsuccessful attempts to either reduce or halt drinking
  • Spending more time or much of free time drinking
  • Having intense cravings during times when not drinking
  • Experiencing difficulty fulfilling obligations at work, school, or home because of drinking
  • Continuing to drink despite having recurrent social problems related to drinking
  • Ceasing activities that used to be important because of drinking
  • Putting yourself at physical risk (e.g., driving, unsafe sex practices) after drinking
  • Continuing to drink despite health problems or unpleasant feelings like anxiety or depression
  • Consuming more than in the past, with the first few drinks having little or no effect
  • Exhibiting withdrawal symptoms (insomnia, aggravation, nervousness, sadness, upset stomach and nausea) when the alcohol wears off

Based on criteria established by the American Psychiatric Association, depending on the number of symptoms an individual exhibits, an AUD can be classified as mild (2-3 symptoms), moderate (4-5 symptoms), or severe (6 or more symptoms).

How Does Alcohol Affect the Brain?

Alcohol affects many of the brain’s neurotransmitter (signaling) systems.  However, the brain’s opioid signaling system is especially important for the rewarding effects of alcohol

Studies in both animals and humans have shown that alcohol releases the brain’s own (endogenous) opioid-like compounds which is critical for its reinforcing (that is, pleasurable) effects.  

What medicines are approved to treat AUD?

Three medications are currently approved by the FDA for AUD. Disulfiram, the first medication approved to treat AUD, interferes with the metabolism of alcohol and results in a buildup of acetaldehyde, a toxic metabolite of alcohol. If a patient is taking disulfiram and consumes alcohol, he can become extremely ill (a deterrent to drinking). Disulfiram is only prescribed for patients who are currently abstinent.  Acamprosate, widely prescribed in Europe before FDA approval in 2005, is used for relapse prevention and is thought to reduce both the physical and emotional distress experienced when patients stop drinking.  While its mechanism of action is not well described, surprisingly, more recent data suggests that it is the calcium in acamprosate, rather than its supposed “active” component (N-acetylhomotaurine) that is responsible for its therapeutic effects in reducing relapse. The opioid antagonist naltrexone, first approved in 1994 and backed by well-established science, has the ability to reduce craving. 

Naltrexone graphic

Our Approach to Treating Alcohol Use Disorder

We are developing OPNT002, a nasal naltrexone, that produces rapid and robust increases in the plasma level of this opioid antagonist. In addition to blocking the opioid receptor, it is hypothesized that these rapid and robust increases in naltrexone concentrations more effectively block the delta subtype of opioid receptor than currently approved naltrexone products.

This nasal spray, used on an ‘as needed/on-demand’ basis when the patient begins to crave alcohol or encounters a “high risk” environment for drinking, offers an innovative approach to the treatment of AUD. This paradigm shift offers some significant advantages over current treatment options by addressing the challenges faced by AUD patients.

  • Most drinkers drink at night
  • Most drinkers don’t want to stop drinking entirely
  • Most drinkers are afraid of undergoing withdrawal or detoxification
  • Most drinkers want to have control

OPNT002 offers the ideal solution for the typical heavy drinker with its ‘as-needed/on-demand’ treatment approach.

graphic of how Naltrexone help Alcohol Use Disorder (AUD)