Will Adial’s AD04 revolutionize alcohol and drug addiction treatment?
For the past century, doctors and scientists have searched for the answers to treating addiction successfully. Early on, experts realized that alcoholism, and addiction in general, were conditions connected to complex brain chemistry.
Over the decades, many medications were discovered and developed to treat anxiety and depression by affecting neurotransmitters. Of these brain communication chemicals, serotonin has been a primary focus of much of this research.
Today, we have many available drugs, marketed for anxiety and depression, that work to make serotonin more available in key areas of the brain. These include medications such as Prozac, Paxil, Zoloft, Celexa, and Lexapro.
Unfortunately, while these drugs can be highly effective in treating depression and anxiety, they have not been helpful in addressing addiction to drugs and alcohol. Addiction is believed to be a complex condition, involving a blend of environmental, psychosocial, and genetic issues.
Addiction is described by experts as a chronic neurobiologic disease. The signs and symptoms that best describe addiction are ongoing drug use, in spite of harm to self and others, drug cravings, compulsive drug use, and a difficulty in controlling the use of drugs.
Addiction is considered to be a chronic disease. And, it can involve behaviors other than alcohol and drug use.
There has been some success in using drugs to treat specific types of drug addiction. Buprenorphine is highly effective for treating opioid use disorder (OUD). Naltrexone is also effective in treating opioid addiction as well as alcohol use disorder (AUD). These drugs both work on opioid receptors in the central nervous system.
Is it possible that serotonin is involved in addiction?
While the selective serotonin reuptake inhibitors, such as Prozac and others, work well for some mental health issues, why do they not help with addiction? They work by making serotonin more available at the neuron synapses. Maybe the solution to treating addiction lies in having a different effect on serotonin.
Ondansetron is an anti-emetic, available as the brand-name drug, Zofran. It is a medication that helps with nausea that can be caused by chemotherapy, radiation therapy, and gastroenteritis. It has also been used to treat nausea associated with pregnancy.
Where SSRIs work by blocking the reuptake of serotonin, making more serotonin available, ondansetron blocks the effects of serotonin at a specific receptor, 5-HT3. One of the effects of being a 5-HT3 antagonist is to reduce nausea.
The fascinating thing about ondansetron is that it shows promise in the treatment of some types of addiction, specifically alcohol addiction, stimulant addiction, and opioid addiction. In fact, this year, 2020, there has been significant, advanced research involving the drug and its effectiveness in treating addiction to alcohol and opioids.
Ondansetron for alcoholism: how does it work?
Apparently, some people who are addicted to alcohol and drugs have a genetic variation, known as an LL + TT polymorphism, affecting the expression of the 5-HT3 receptor. They have more post-synaptic receptors for serotonin.
By using ondansetron to block these serotonin receptors, serotonin function is stabilized. As a result, alcohol and drug cravings are reduced. Current research is being performed by Adial Pharmaceuticals on a low-dose variation of Ondansetron, currently known as AD04.
Will AD04 work for all people addicted to alcohol and other drugs?
Unfortunately, the beneficial effects of AD04, or low-dose ondansetron, only benefits patients with the specific gene that is responsible for encoding the serotonin transporter (SERT). The LL-genotype is believed to be involved in early onset alcoholics.
Because of this limitation, Adial is proposing that patients get genetic testing and undergo questioning to determine if they are good candidates for the treatment. By pairing the biomarker genetic test with AD04 treatment, they are calling it genetically targeted therapy for biologically predisposed alcoholics. They believe that this will result in a much higher overall efficacy of the drug in treatment.
Is it possible that ondansetron is more effective than naltrexone or Campral?
Currently, there are two drugs on the market approved for the treatment of AUD. These are naltrexone and acamprosate (Campral). Soon, we may have a third, a low-dose form of ondansetron. Will it work as well as or better than the current medications?
Dr. Bankole Johnson is a board-certified psychiatrist who has served as Alumni Professor and Chairman of the Department of Psychiatry and Neurobehavioral Sciences at the University of Virginia. He is also chief medical officer for Adial.
Dr. Johnson states that he has treated alcohol use disorder for over 30 years. AD04 (ondansetron) is the most meaningful addiction treatment he has yet seen developed. He describes the process of bringing the new form of this drug with genetic testing to market to be an emotional experience and the apex of his career in treating alcohol dependent patients as well as patients dependent on various drugs.
In time, we will have a better understanding of where AD04 will fit into the set of tools we have for addiction treatment.
The use of medications in conjunction with genetic testing is intriguing. By studying genetic profiles of patients, it can be determined which medications will work best for each patient.
Hopefully, this form of genetically targeted therapy can be further applied in medical addiction treatment. For the time being, we can look forward to the release of this new therapy from Adial.
After it is on the market, we will have a better understanding of how well it works by getting feedback from patients. Also, the pharmaceutical company will have an opportunity to collect far more data on its effectiveness.
Finland has long been on the forefront of the development of alcohol addiction treatment.
Dr. John David Sinclair spent many years in Finland, studying the effectiveness of naltrexone in treating alcohol use disorder. He was able to discover the pharmacological extinction effect of giving naltrexone to patients before they consumed alcohol.
This lead to the development of The Sinclair Method, which promotes reduced alcohol consumption by reducing craving for alcohol. Patients are able to quickly reduce their drinks per day to a minimum and alter drinking behavior.
Interestingly, the research by Adial on AD04 to treat alcoholism also began in Finland. Professor Hannu E.R. Alho, Emeritus Professor of Addiction Medicine at the University of Helsinki, Finland, and investigator in ongoing trials for AD04 believes that the world needs a drug like AD04.
In reviewing studies of AD04 with placebo controls, Dr. Alho has seen that the efficacy of this new drug is significant. While research is now being performed at many sites around the world, again, it seems that important alcohol addiction research has been initiated in Finland.
From Finland to the United States, we have been slow to accept effective medical treatment for alcohol use disorder.
The Sinclair Method (TSM) has been understood for many years, and naltrexone has long been available as an affordable generic drug for doctors to prescribe. Unfortunately, even with solid evidence of a high level of success in increasing the abstinence rate, doctors and rehabs have been slow to adopt this form of medication-assisted treatment for alcohol addiction.
One major advantage of TSM is that there is less of an issue with alcohol withdrawal. With reduced alcohol consumption and increased involvement in therapy and support groups, TSM patients tend to do very well in recovering from alcoholism or even gray area drinking.
Integration and integrative therapy are the keys to success in addiction treatment.
The abstinence-based treatment culture that permeates US rehabs and even advanced educational institutions in addiction medicine has held us back in recent decades in the effective treatment of substance abuse. We are still relying on the 12-step spiritual program that is nearly a century old for medical conditions when we already have effective modern medical therapies.
I hope that we can further educate the public, and even addiction treatment professionals, on the importance of medication-assisted treatment for alcohol use disorder, opioid use disorder, and other forms of addiction. Hopefully, when AD04 is finally FDA approved and available for doctors to prescribe to their patients to help them stop drinking, we will be better prepared to integrate it into the practice of addiction treatment.
With AD04 and other cutting-edge technologies on the horizon to further improve outcomes in addiction treatment, we must come to accept that the old world of Alcoholics Anonymous-based 12-step programs and modern medical therapy can work together. We must also include advanced psychological techniques, including cognitive behavioral therapy as well as other forms of group therapy.
There is no reason why these scientific and spiritual approaches cannot work together. It is time that we work together to improve the integration of various effective therapies for the treatment of alcohol dependent and drug dependent patients.