Clinical Research on Addiction Psychiatry: Opportunities and Challenges

Dear Colleagues,

Substance use disorder (SUD) is the nation’s most pressing unmet public health challenge. Use, dependence, and overdose were epidemics long before COVID-19, and the situation has continued to deteriorate. At least 275 million people used drugs worldwide in the last year and over 36 million people meet the criteria for drug use disorders, according to the 2021 World Drug Report by the United Nations Office on Drugs and Crime (UNODC). Currently, 20% of U.S. deaths are attributed to tobacco, alcohol, and other drugs; risky substance use and addiction are the largest preventable causes of death. Globally, over 11 million people are estimated to inject drugs, half of whom are living with Hepatitis C.

Opioids continue to account for the largest burden of disease attributed to drug use. Opioid use disorder (OUD) is a complex physical and emotional disease with important mood and anhedonic deficits, as well as concurrent medical and infectious disease requiring evaluation and treatment. OUD is part of the SUD spectrum. However, it is unique among other SUDs in that we have a solid understanding of the neurobiology of opioid dependence and withdrawal and have access to Food and Drug Administration (FDA)-approved treatments for OUDs. The treatment for this condition is similar to existing treatments for OUD in the 1970s, with agonists like methadone and antagonists like naltrexone, along with the addition of buprenorphine a few decades ago.

Drug use changes the brain, behavior, and motivational hierarchy; the patient with OUD acquires a chronic, progressive disease that shortens life, reduces career opportunities and earning potential, increases the risks of other diseases, and often ends in death. None of the treatments that exist today are anywhere near as compelling as the drugs. Today, with almost all heroin users taking fentanyl as their primary drug of abuse, fentanyl has become highly effective at producing OUD, overdose, depression and anhedonia.

Deaths due to drug overdose had previously fallen to 2500 per year in the 1908s. The Just Say No era, from 1981 to 1989, overdoses in the USA ranged from 2500 to 5000 per year. It is hard to imagine that drug overdose deaths have increased from the time of the prescription opioid epidemic through the heroin epidemic and now the fentanyl epidemic to >120,000 per year. Despite much awareness, and dramatic increases in access, funding,  and attention to the public health threat, overdoses and for many, outcomes have been worsening with increased fentanyl, cocaine, and methamphetamine exposures. The primary approach to OUD treatment has been stagnant, focusing on existing medications that work at the opioid receptor, namely buprenorphine and naltrexone. Incredibly, some of the most common SUDs have no treatment whatsoever. The FDA has not approved treatments for cannabis, cocaine use disorder or amphetamine use disorder. 

While considerable progress has been made in developing algorithms for use in treatment in medicine, oncology or cardiology based on testing and genetics, little progress has been made in addiction medicine and addiction psychiatry in terms of personalizing treatment. Still, genes matter, especially dopamine and related genes. So too does gene expression. Developing the idea of preaddiction in a similar fashion to the important and actionable concept of prediabetes may be an interim answer. While expanding access to treatment and adopting harm reduction approaches are important in saving lives, to really reverse the concerning trends in OUD, we also need novel treatments that patients will take, and which are therefore more durable and effective. Promising potential treatments include neuromodulating modalities such as TMS and DBS, which target different areas of the neural circuitry involved in addiction. Some of these modalities are already FDA-approved for use to treat other neuropsychiatric conditions and there is evidence of effectiveness in reducing substance use, with several clinical trials in progress. In addition to neuromodulation, psychedelics have been gaining much interest due to their potential for use in treating various SUD, with mounting evidence for the use of psychedelics to treat psychiatric conditions.

Ketamine has been reported to be useful and is being actively studied in alcohol use disorders. If FDA approves psilocybin and MDMA after successful phase 3 trials, there will be reduced barriers to investigating applications of psychedelics despite their current classification as Schedule I substances. Vaccine or neuroimmune modulating approaches to treating addiction are like psychedelics, only with less evidence for their efficacy. Using agents that target pathways leading to changes in the synaptic plasticity seen in addiction can prevent addiction and/or reverse damages caused by addiction. Our primary focus is to provide research that clinical providers can use and put into context in their practices, allowing researchers to share their work and provide insights to help patients and clinicians.

We intend to solicit papers from groups developing and studying new treatments for SUDs and clinical experts treating SUDs and complex co-morbid substance use disorders today. 

Dr. Mark Gold
Guest Editor

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• cannabis use disorders
• opioid use disorders
• cocaine use disorders
• substance use disorders
• alcohol use disorders
• treatment
• naloxone
• buprenorphine
• suboxone
• naltrexone
• vivitrol
• naloxone
• dopamine
• preaddiction
• addiction
• ASAM
• aaaP
• NIDA
• NIAAA
• NIMH