In 1929, Dr. Lyndon F. Small established the Drug Addiction Laboratory, the ancestor of today's LMC. Seeking to create painkillers which would not cause addiction, Small studied and modified the morphine molecule and related opium products. This work was based on the assumption that the drug's effects were directly related to its molecular structure. Small's assumption proved correct. Metopon, a potent opiate painkiller, was among his most notable contributions. With metopon, partial separation of the painkilling effects from the undesired addictive property was at last achieved. This finding was the underpinning of much research that continues today into a total separation of painkilling and addictive effects.

Dr. Nathan Eddy evaluated Small's compounds for their painkilling effectiveness and potential to be addictive, and Dr. Clifton Himmelsbach conducted the first clinical tests with these drugs in human subjects. Early studies on metopon showed it produced a less severe addiction than morphine and other opiates. This finding encouraged scientists to hope that the addictive side effect could be further separated from the painkilling action.

Dr. Everette May and Dr. Eddy worked to develop opiates that relieved pain without the potential for abuse and to discover synthetic substitutes for opiates--called opioids. Based on May's work on benzomorphans, the drug pentazocine was introduced in the 1960s. Pentazocine was the first drug used in clinical practice as a painkiller which combined the pain-relieving effects of morphine with the effects of opiate antidote. Such drugs are called mixed agonists-antagonists because they produce some opiate effects while blocking the opiate effects of other drugs. But pentazocine was not as effective as morphine for severe pain, and produced hallucinations at higher doses.

The drug buprenorphine was developed using the agonist-antagonist construct. It is a promising drug for the detoxification of heroin addicts because it produces less intensive withdrawal symptoms, is relatively non-toxic, and can be used by outpatients. It is also being studied as a therapy for individuals dependent on cocaine.

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