A Novel Compound for Cocaine Addiction

Experimental drug may block cocaine’s action in the brain
Drs. Wade H. Berrettini and Kyle Kampman

University of Pennsylvania School of Medicine, Philadelphia, PA

Grant Program:

Clinical Neuroscience Research

Funded in:

December 2015, for 2 years

Funding Amount:


Lay Summary

Experimental drug may block cocaine’s action in the brain

Investigators who are part of a University of Pennsylvania expert group studying drug addiction will conduct a Phase II clinical trial in 40 adult cocaine users of an experimental drug that may block cocaine’s action in the brain. If the drug proves promising, the research will lead to a large-scale Phase III clinical trial and, if successful, the likely availability of the first federal Food and Drug Administration (FDA)-approved treatment for cocaine addiction.

Cocaine inhibits “transporter” proteins that ordinarily help brain cells take back up any dopamine, serotonin and norepinephrine that they have released in excess. When there is no “re-uptake” of these excitatory neurotransmitters, brain cells become overly active and systems that ordinarily keep brain cells’ excitation at proper levels are altered. An experimental chemical agent manufactured by Saniona pharmaceutical company, however, may be able to compete successfully with cocaine to bind to these transporter proteins. An initial small (Phase I) study of the experimental agent in 24 moderate to heavy users of cocaine suggested that the agent does not produce an addicting euphoria, but blocks the euphoria of cocaine.

With the Phase I results, the investigators have secured IRB and FDA approvals to conduct a Phase II study of the agent in 40 additional moderate to heavy cocaine users. The research will be the gold-standard—“randomized double-blind, placebo controlled”—study in which neither participants nor clinicians will know which 20 participants receive the experimental agent and which receive the placebo over a nine-week period. The investigators hypothesize that participants receiving the experimental agent will achieve three weeks of cocaine abstinence during the final three weeks of the trial.

Saniona will donate the experimental agent for the study, and the Groff Foundation has provided $70,000 towards this study. While the experimental agent was tested for effectiveness in treating major depressive disorder and in attention deficit disorder, but the compound did not have efficacy in those studies. Testing for cocaine use disorder in this study is an example of academic-pharmaceutical industry collaboration to show proof of concept and the early Phase II testing.

Significance: If the Phase II trial is successful, the manufacturer and University of Pennsylvania will work with the FDA to determine the design of a large-scale (Phase III) trial that is most likely to meet regulatory requirements. If approved, this would be the first approved drug to treat cocaine use.

Investigator Biographies

Drs. Wade H. Berrettini and Kyle Kampman

Dr. Berrettini is the Karl E. Rickels Professor of Psychiatry, at the University of Pennsylvania Perelman School of Medicine. He earned his MD (1977) degree and PhD degree (Pharmacology, 1979) from Thomas Jefferson University (TJU). After completing residency training in Psychiatry, he studied genetics of behavioral disorders at the National Institute of Mental Health for ten years. Since 1997, Dr. Berrettini has served as the Director of the Center for Neurobiology and Behavior, a group of interdisciplinary scientists studying genetic and biologic influences on brain disorders and behavior. The author of more than 350 peer-reviewed scientific publications, his research interests include genetics, pharmacogenetics and medical treatment of addictions, mood disorders, schizophrenia and epilepsy.

The Berrettini lab is currently studying somatic mutation in neurons as a potential causative factor in risk for addictions, psychotic illnesses and epilepsy. Another focus of the lab is the study of a novel triple reuptake inhibitor as a therapeutic agent in cocaine addiction. This compound is not FDA-approved for any indication, but it holds great promise as the first effective medication for cocaine addiction.

Dr. Kyle Kampman graduated from Northwestern University in 1981 and Tulane University School of Medicine in 1985. He interned at the National Naval Medical Center at Bethesda Maryland and served in the United States Navy from 1985 until 1990. He came to the University of Pennsylvania and served as a resident in Psychiatry from 1990 until 1993. He then completed a fellowship in Addiction Psychiatry. In 1994 he joined the faculty in the Department of Psychiatry as an assistant professor. He was promoted to associate professor in 2003 and to professor in 2012. Dr. Kampman has had extensive experience in the treatment of alcohol cocaine and opiate dependence. He has conducted a number of trials testing medications for the treatment of cocaine alcohol and opiate dependence and is a recognized authority on the cocaine withdrawal syndrome. In addition to research, he works at the Addiction Recovery Unit of the Philadelphia VA Medical Center where he continues to treat cocaine, alcohol and opiate dependent patients with both medications and psychotherapy.