Combatting Misconceptions About Alcohol Use Disorder: In Conversation With Brigitte Robertson, MD

CLINICAL CONVERSATIONS

Adial Pharmaceuticals recently announced that the US Food and Drug Administration (FDA) has granted their request for an end of phase 2 meeting to discuss a proposed clinical development plan for AD04, a genetically targeted selective serotonin-3 (5-HT₃) receptor antagonist and therapeutic agent for the treatment of alcohol use disorder (AUD) in patients who engage in heavy drinking (defined as < 8 drinks/drinking day).¹ Psychiatric Times sat down with Brigitte Robertson, MD, the acting chief medical officer at Adial Pharmaceuticals, to discuss the latest in treatment options and care for patients with AUD.

Robertson is an accomplished physician-scientist with nearly 20 years of experience in academic, clinical, and pharmaceutical neuroscience, specializing in psychiatric and neurological disorders. She is very passionate about the need to develop new treatments for AUD and views it as a serious unmet need in modern medicine.

Psychiatric Times: What do you think are the most pressing issues in the treatment and management of substance use disorders (SUDs), specifically AUD?

Brigitte Robertson, MD: One of the most pressing challenges is that despite decades of research, no new therapies have been approved in over 20 years. The majority of programs also continue to provide a “one-size-fits-all,” approach, requiring initial abstinence with a therapeutic focus on maintenance of abstinence. In reality, alcohol use and its consequences fall on a continuum; while some may require complete abstinence to prevent further decline in their health, many are seeking alternative approaches to limit their alcohol use and improve their overall well-being.

In addition, there remains a persistent stigma that AUD is a moral failing, which prevents many individuals from considering treatment. Addressing these gaps requires a paradigm shift and disrupting the field, with investment in new systems of treatment and medications that support patients who are seeking to cut back on their drinking and prevent or reduce the inevitable harm associated with heavy drinking.

PT: According to the 2023 National Survey on Drug Use and Health, 28.9 million individuals aged 12 and older (10.2% in this age group) had AUD in the past year.² How is your work at Adial Pharmaceuticals helping to address this population’s needs?

Robertson: The fact that nearly 29 million individuals are estimated to be living with AUD highlights the urgent need for more flexible, evidence-based treatment options. Many individuals do not seek help because they believe treatment means total abstinence or think that they must hit “rock bottom” first. That is a harmful misconception.

Our work focuses on a nonabstinence-based approach that meets patients where they are. For some, reducing alcohol use may be a more realistic and acceptable goal than immediate sobriety. We are investigating the use of AD04, a genetically targeted therapeutic agent, to help reduce cravings and heavy drinking to support behavior change.

The promise of personalized care through genetic biomarker targeting, where abstinence is not required, is Adial’s focus. Our vision is that this approach will help to remove barriers and make treatment accessible to a genetically predisposed population. Our approach is focused on respecting patient autonomy, reducing harm, and helping patients build healthier, more fulfilling lives on their own terms.

PT: On February 11, 2025, the United States Patent and Trademark Office issued a patent for Adial Pharmaceuticals’ identification of patients with specific genetic markers linked to substance use disorders and treatment with AD04.³ Can you share some information with our readers about these genetic markers? Does this represent a new era for AUD/SUD treatment?

Robertson: The newly issued patent focuses on the addition of a genetic marker: the TT genotype of a single nucleotide polymorphism (SNP) in the serotonin transporter gene (SLC6A4) called rs1042173. AD04, Adial’s investigational drug, acts as a serotonin 5-HT₃ receptor antagonist and this SNP, in addition to others that target receptors directly associated with AD04’s mechanism of action, are intertwined with addiction behaviors. These genes play a central role in modulating serotonin activity a neurotransmitter that influences mood, impulse control, and reward processing.

What this means in practice is that some individuals may be biologically more responsive to certain treatment approaches and Adial’s studies suggest that individuals with a specific genotype respond better to AD04. It is a form of precision medicine, tailored not just to a diagnosis, but to the underlying genetic makeup of the person living with that diagnosis.

This represents a significant shift in the way we approach treatment for AUD/SUD. Traditionally, we have treated alcohol and opioid use disorders with a set of tools that, while often effective, do not always account for the deep biological variability among patients. Some individuals do not respond to the standard medications we have. Some relapse, not because they are not trying, but because their biology sets up roadblocks that current treatments just cannot bypass.

What Adial is doing with AD04 reflects a growing shift toward individualized addiction treatment, where therapy is informed not just by symptoms, but by genetics. The goal is to move away from trial-and-error-based treatment strategies, improve adherence, and restore dignity to those who may have experienced treatment-resistance or felt misunderstood in the past.

PT: What other SUD treatments in the pipeline are you excited about?

Robertson: Currently, our sole focus is on the development of AD04 for the treatment of AUD.We are passionate about the potential of AD04 in helping to improve the lives of those who struggle with their relationship with alcohol and are laser-focused on delivering an effective treatment option to improve the lives of these patients.

PT: What types of conversations should psychiatrists and mental health clinicians be having with their patients concerning substance use? How can they best screen for SUD?

Robertson: Any and all clinicians can initiate a conversation about substance use and it is helpful to approach the topic with sincerity and empathy. Asking an open-ended question, such as “Can you tell me about your use of alcohol or other substances?” encourages honesty and reduces shame.

Screening should be a matter of routine and nonjudgmental assessment. Tools like the AUDIT-C or DAST-10 are helpful starting points. Clinical expertise is key, as the results are best explored in the context of the patient’s life circumstances and mental health.

When substance use comes up, reflecting back what you are hearing can often invite collaboration as well. For example: “It sounds like your drinking is starting to impact your sleep and relationships. Have you thought about making a change?” This opens the door for motivation without pressure.

Ultimately, assessing substance use needs to be integrated broadly across health care venues and providers. Acknowledging the interrelationship between behavioral and physical health is essential, as it is important to integrate substance use into our understanding of the whole person.

PT: Thank you!

Dr Robertson is the acting chief medical officer at Adial Pharmaceuticals.

References

1. Kuntz L. FDA has granted request for end of phase 2 meeting to discuss alcohol use disorder treatment, AD04. Psychiatric Times. May 8, 2025. https://www.psychiatrictimes.com/view/fda-has-granted-request-for-end-of-phase-2-meeting-to-discuss-alcohol-use-disorder-treatment-ad04

2. Alcohol's effects on health. National Institute of Health; National Institute on Alcohol Abuse and Alcoholism. Accessed May 9, 2025. https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-use-disorder-aud-united-states-age-groups-and-demographic-characteristics

3. Kuntz L. Patent issued for methods of identifying patients with substance use-associated genetic markers, treatment with AD04. Psychiatric Times. February 12, 2025. https://www.psychiatrictimes.com/view/patent-issued-for-methods-of-identifying-patients-with-substance-use-associated-genetic-markers-treatment-with-ad04