Objective.— To provide clinicians, patients, and the general public with a responsible assessment of the effective approaches to treat opiate dependence. Participants.— A nonfederal, nonadvocate, 12-member panel representing the fields of psychology, psychiatry, behavioral medicine, family medicine, drug abuse, epidemiology, and the public. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 600. Presentations and discussions were divided into 3 phases over 21⁄2 days: (1) presentations by investigators working in the areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that are part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of a third day. The conference was organized and supported by the Office of Medical Applications of Research, National Institutes of Health. Evidence.— The literature was searched through MEDLINE and other National Library of Medicine and online databases from January 1994 through September 1997 and an extensive bibliography of 941 references was provided to the panel and the conference audience. Experts prepared abstracts for their presentations as speakers at the conference with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. Consensus Process.— The panel, answering predefined questions, developed its conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel’s final revisions. Conclusions.— Opiate dependence is a brain-related medical disorder that can be effectively treated with significant benefits for the patient and society, and society must make a commitment to offer effective treatment for opiate dependence to all who need it. All persons dependent on opiates should have access to methadone hydrochloride maintenance therapy under legal supervision, and the US Office of National Drug Control Policy and the US Department of Justice should take the necessary steps to implement this recommendation. There is a need for improved training for physicians and other health care professionals. Training to determine diagnosis and treatment of opiate dependence should also be improved in medical schools. The unnecessary regulations of methadone maintenance therapy and other long-acting opiate agonist treatment programs should be reduced, and coverage for these programs should be a required benefit in public and private insurance programs. JAMA. 1998;280:1936-1943 IN THE UNITED STATES, before 1914, it was relatively common for private physicians to treat patients dependent on opiates in their practices by prescribing narcotic medications. Although the passage of the Harrison Act did not prohibit the prescribing of a narcotic by a physician to treat an addicted patient, this practice was viewed as problematic by US Treasury officials charged with enforcing the law. Physicians who continued to prescribe were indicted and prosecuted. Because of withdrawal of treatment by physicians, various local governments and communities established formal morphine clinics for treating opiate addiction. These clinics were eventually closed when in 1920 the American Medical Association stated that there was unanimity that prescribing opiates to addicts for self-administration (ambulatory treatment) was not an acceptable medical practice. For the next 50 years, opiate addiction was basically managed in this country by the criminal justice system and the 2 federal

Effective medical treatment of opiate addiction

Considerable neurological evidence indicates that the prefrontal cortex mediates complex "executive" functions including behavioral autonomy and self-control Given that impairments of self-control are characteristic of alcoholism and other drug addictions, frontal lobe dysfunction may play a significant role in such compulsive behaviors Consistent with this idea, recent research using brain imaging, neuropsychological testing, and other techniques has revealed that the frontal lobes are particularly vulnerable to the acute and chronic effects of addictive drugs, especially alcohol and cocaine Evidence implicating a hyperdopaminergic mechanism of acute and chronic drug-induced frontal lobe dysfunction and interactions with premorbid factors and stress are discussed

/pdf/loss-of-control-in-alcoholism-and-drug-addiction-a-g6sx36x83j.pdf

"Loss of control" in alcoholism and drug addiction: a neuroscientific interpretation.

Approximately 3.7 million individuals have used heroin and other opiate substances in their lifetime. Despite increasing knowledge of the effects of heroin, it remains the most abused opiate and use among adults has recently increased. The empirical literature examining the neurocognitive effects of acute and chronic opioid use remains limited; however, findings to date suggest that the use of opiates has both acute and long-term effects on cognitive performance. Neuropsychological data indicate deficits in attention, concentration, recall, visuospatial skills and psychomotor speed with both acute and chronic opioid use. The long-term effects of opiate use appear to have the greatest impact on executive functions, including the ability to shift cognitive set and inhibit inappropriate response tendencies. Factors that contribute to addiction and recovery are also discussed, as it is difficult to disentangle the effects of opiate use on cognitive performance from other factors that may affect neurobehavioral measures.

Neuropsychological Consequences of Opiate Use

Rationale
There have been only a few structural brain-imaging studies, with varied findings, of opiate-dependent subjects. Voxel-based morphometry (VBM) is suitable for studying whole brain-wise structural brain changes in opiate-dependent subjects.

Prefrontal and temporal gray matter density decreases in opiate dependence.

Proton magnetic resonance spectroscopy ((1)H MRS) is a noninvasive imaging technique that permits measurement of particular compounds or metabolites within the tissue of interest. In the brain, (1)H MRS provides a snapshot of the neurochemical environment within a defined volume of interest. A search of the literature demonstrates the widespread utility of this technique for characterizing tumors, tracking the progress of neurodegenerative disease, and for understanding the neurobiological basis of psychiatric disorders. As of relatively recently, (1)H MRS has found its way into substance abuse research, and it is beginning to become recognized as a valuable complement in the brain imaging toolbox that also contains positron emission tomography, single-photon-emission computed tomography, and functional magnetic resonance imaging. Drug abuse studies using (1)H MRS have identified several biochemical changes in the brain. The most consistent alterations across drug class were reductions in N-acetylaspartate and elevations in myo-inositol, whereas changes in choline, creatine, and amino acid transmitters also were abundant. Together, the studies discussed herein provide evidence that drugs of abuse may have a profound effect on neuronal health, energy metabolism and maintenance, inflammatory processes, cell membrane turnover, and neurotransmission, and these biochemical changes may underlie the neuropathology within brain tissue that subsequently gives rise to the cognitive and behavioral impairments associated with drug addiction.

/pdf/neurochemistry-of-drug-action-insights-from-proton-magnetic-2xa391bpye.pdf

Neurochemistry of drug action: insights from proton magnetic resonance spectroscopic imaging and their relevance to addiction.

Naloxone (0.8 mg, s.c.) effects on opiate withdrawal signs and symptoms and regional brain function were assessed in 10 methadone-maintained patients and 10 healthy subjects in a double-blind, placebo-controlled study. Regional brain function was assessed using single photon emission computerized tomography (SPECT) by evaluating the uptake of [99mTc]d,l-hexamethylpropyleneamine oxime (HMPAO) in the brain, a process related to regional cerebral perfusion. Comparisons of patients and healthy subjects after saline infusion suggested that chronic opiate dependence was associated with lower corrected activity ratios (regional count density/whole brain count density) in frontal and parietal cortices and greater activity ratios in the thalamus. Opiate-dependent patients, but not healthy subjects, developed opiate withdrawal signs and symptoms after naloxone administration. Following naloxone administration, patients undergoing opiate withdrawal exhibited lower whole brain count density than healthy subjects. They also had lower activity ratios in frontal and parietal cortices and increased thalamic activity ratios relative to healthy subjects receiving naloxone. Naloxone administration in healthy subjects, but not opiate withdrawal in patients, was associated with decreased right parietal cortex and increased right temporal cortex and left basal ganglia activity ratios. Relative to naloxone effects in healthy subjects, opiate withdrawal was associated with decreased whole brain count density and a reduced right temporal cortex activity ratio. This preliminary study reports an initial evaluation of HMPAO-SPECT imaging for assessing regional alterations in brain function during opiate dependence and withdrawal. While group differences were reported, the small magnitude of regional alterations in patients undergoing opiate withdrawal raised concern that HMPAO-SPECT methods employed were inadequate for assessing human regional brain function during phases of opiate addiction. Other emerging functional brain imaging technologies should be evaluated relative to improved HMPAO-SPECT methods for this purpose.

S W Woods

Papers

Opiate Dependence and Withdrawal: Preliminary Assessment Using Single Photon Emission Computerized Tomography (SPECT)