Ketamine Research in the United States Ketamine Research in the United States
Dr. John Crystal and Dr. Eli Kolp Psychopharmacology study at Yale

As part of his one-year study of ketamine psychopharmacology in alcoholics at Yale, Dr. Evgeny Krupitsky will work on the overlap of ketamine and ethanol. Both agents block, with varying potency, the actions of glutamate at the N-methyl-D-aspartate. Dr. Krupitsky has had a particular interest in the utility of the calcium channel blocking agent, nimodipine, in treating alcoholism. He will explore this by examining the relationship between nimodipine and ketamine.

The overlap between ketamine and ethanol at the NMDA receptor is important for several reasons: 1) it now appears that some of the behavioral effects of ethanol arise through blockade of NMDA receptorsÑ new knowledge about an old drug. If ethanol doses get high enough, you get ketamine-like effects. 2) this means that some problems associated with ethanol may arise from its actions at this site. Areas to explore include cognitive impairment, withdrawal, and neurotoxicity. As a result, agents enhancing NMDA receptor function become potential targets for the treatment of alcoholism.

Nimodipine is primarily employed as an antihypertensive medication. It blocks a type of channel that allows calcium to enter neurons. The NMDA receptor is a different type of channel, but it also controls the entry of calcium into neurons. We have been studying the capacity of nimodpine, which has very low abuse potential, to enable alcohol dependent individuals to dry out from alcohol dependence. The objective is to see whether we can develop treatments that avoid giving people benzodiazepines or related drugs. The reason for this objective is that benzodiazepines have some alcohol-like subjective effects and we have been concerned that it may promote relapse in some people.

Dr. John Krystal
West Haven VA Medical Center
950 Campbell Avenue
West Haven CT, 06516
Tel: (203) 932-5711 ext 2570 or 2540
Fax: (203) 937-3886

Protocol review in Tampa, FL

I have completed the first round of approval of the Ketamine Research Protocol to take place in Tampa, Florida. The protocol has been changed seven (!) times, including the very important change from non-blind study to double-blind study. Eventually, after several meetings, the Research Committee has recommended to present the protocol to the Institutional Review Board (IRB) of the Tampa Veterans Administration Hospital. I missed the deadline for the April meeting of the IRB, but have three more weeks before the May meeting deadline.

Meanwhile, I secured the letters of support from all involved services (Anesthesiology, Psychiatry, Pharmacy and Psychology). In addition, the protocol was reviewed by the Chief of Medical Administration for compliance with the requirements of the Hospital Privacy Act and was approved as well.

I also presented the Ketamine Protocol to the staff of the Alcohol and Drug Abuse Treatment Program where the study will take place. The vast majority of staff supported the study enthusiatically, except for two people who became alarmed at the idea of treating drug addiction with a "dangerous drug". Both dissenting counselors are recovered addicts themselves, who recovered strictly through Alcoholics Anonymous and Narcotics Anonymous 12-step recovery fellowships and have different views about pharmacological treatment of addiction. I will continue to work with the staff of ADATP to dispel any misconception about ketamine-assisted therapy to treat alcoholism. I will continue keeping you informed of future developments of ketamine research in Florida. Thank you for your interest and support.

Eli Kolp, MD
James A. Haley Veterans' Hospital
USF College of Medicine
Department of Psychiatry
13601 Bruce B. Downs Blvd.
Suite 241
Tampa, Florida 33613
email: kolp.eli@tampa.va.gov