Rethinking Addiction: The Complex Problem of Comorbidities.

In 2010, National Institute of Drug Abuse (NIDA) Director Nora Volkow, M.D. posted an article giving a general overview on the topic of comorbidities titled, Comorbidity: Addiction and Other Mental Illnesses (1). As the article made clear, with the recognition of substance dependence (addiction) as a mental health disorder, the next step was unavoidable: this would thrust addiction into the discussion of mental health comorbidities (two or more mental health disorders/illnesses occurring in the same person). While comorbidities with addiction are a common occurrence, establishing causality is difficult. Three scenarios are generally suggested: 1) Drug abuse can cause addicts to experience one or more symptoms of another mental illness (Substance-induced disorders). 2) Mental illness can lead to drug abuse. 3) Both drug use disorders and other mental illnesses are caused by overlapping factors. These three possible scenarios contribute to the already complex story of addiction and other mental health disorders, as well as their implications for mental health in general.

The relatively small numbers of articles that concentrate on comorbidities with addiction all end with the discussion of treatment options. To date, effective pharmacotherapies exist for treating opioid, alcohol, and nicotine addiction and for alleviating the symptoms of many other mental disorders, yet most have not been well studied in comorbid populations. It is also well accepted that behavioral therapy in combination with medication for patients are most likely to lead to more positive outcomes, including those with a single diagnosis and those with comorbid conditions. While these articles provide a good over view of the issues, they fail to propose possible treatment pathways to move forward in addressing comorbidities with addiction.(2)

Today we are well placed to recognize that mental health, while complex, does have a well-defined neurochemical profile. This profile includes reliance on several conserved and well characterized neurochemicals consisting of glutamate, dopamine, serotonin, gaba, and acetycholine. Different mental health diseases (such as depression, anxiety, and PTSD) are most likely to involve the aberrant functioning of one or more of these neurochemicals or an overlap of dysfunctions in multiple neurological pathways. At the same time, system overlap can also be the reason a single drug or combination of drugs, targeting single or multiple aberrant pathways may have the potential to treat addiction together with comorbidities. While the logic of this situation is clear, it remains the case that comorbidities with addiction can be very complex, hard to study, and even harder to treat.

Animal models are paramount in studying diseases and developing effective treatments. Most current animal models are designed to examine one or more aspects of a single disease. The lack of reliable behavioral animal models for mental health and the subsequent comorbidities, especially those involving addiction, is a major roadblock to studying and treating them. Studying a drug or drugs in two behavioral animal models of distinct yet potentially overlapping mental health diseases may not translate into an effective treatment when given to a patient with mental health comorbidities. To develop an effective approach, the priority will need to be given to animal models designed to model comorbid behaviors. However, the current state of science in the field of mental health is still focused on elucidating the important aspects of each mental health disease alone. Therefore, a critical step forward in knowledge in the field of mental health requires attention to developing comorbid behavioral animal models for the effective treatments for addiction with comorbidities.

There are other challenges. Sharing of knowledge is paramount in efficiently moving ideas forward to the forefront of science and developing treatments. Current treatments in medicine including mental health were developed through bringing together many small or large pieces of knowledge gained over many years of successful as well as failed experiments. Pathways and avenues to publish experiments have for many years relied on print (and recently online) scientific, peer-reviewed journal articles. While most journals typically only publish positive results, new avenues for failed experiments have emerged (PLOS and PNAS). The inherent limitations of this slow and somewhat archaic system for sharing knowledge has become somewhat of a bottle neck in the speed of innovation. A full overhaul and/or replacement of the current system may not be necessary to circumvent the peer-reviewed journal bottle neck if a parallel system for efficiently sharing knowledge can be established. Another possibility is the establishment of a consortium of mental health stakeholders where private, academic, government, and treatment institutions openly share ideas, data, and information. In the future, all mental health patients and stakeholders could benefit from a new knowledge sharing system.

A significant step forward is placing greater reliance on working in partnership with others. Progressive biotech companies (such as EncepHeal Therapeutics) have the unique opportunity to become a hub of innovation and place themselves as a collaborative leader of mental health discovery. Through the creation of partnerships and collaboration, biotech companies could then begin to establish a much needed mental health consortium that can accelerate the development of testing and research that addresses the more complex challenges that comorbidities present.

(1) Volkow, 2010 <https://www.drugabuse.gov/publications/research-reports/comorbidity-addiction-other-mental-illnesses/letter-director>.

(2) < https://www.morningsiderecovery.com/blog/understanding-comorbid-addiction-and-mental-illnesses/; https://www.apa.org/about/gr/issues/substance-abuse/comorbid.pdf>