Changes in cerebral glucose metabolism during early abstinence from chronic methamphetamine abuse.

Changes in brain function during the initial weeks of abstinence from chronic methamphetamine abuse may substantially affect clinical outcome, but are not well understood. We used positron emission tomography with [F-18]fluorodeoxyglucose (FDG) to quantify regional cerebral glucose metabolism, an index of brain function, during performance of a vigilance task. A total of 10 methamphetamine-dependent subjects were tested after 5-9 days of abstinence, and after 4 additional weeks of supervised abstinence. A total of 12 healthy control subjects were tested at corresponding times. Global glucose metabolism increased between tests (P=0.01), more in methamphetamine-dependent (10.9%, P=0.02) than control subjects (1.9%, NS). Glucose metabolism did not change in subcortical regions of methamphetamine-dependent subjects, but increased in neocortex, with maximal increase (>20%) in parietal regions. Changes in reaction time and self-reports of negative affect varied more in methamphetamine-dependent than in control subjects, and correlated both with the increase in parietal glucose metabolism, and decrease in relative activity (after scaling to the global mean) in some regions. A robust relationship between change in self-reports of depressive symptoms and relative activity in the ventral striatum may have great relevance to treatment success because of the role of this region in drug abuse-related behaviors. Shifts in cortical-subcortical metabolic balance either reflect new processes that occur during early abstinence, or the unmasking of effects of chronic methamphetamine abuse that are obscured by suppression of cortical glucose metabolism that continues for at least 5-9 days after cessation of methamphetamine self-administration.

Gamma-hydroxybutyric acid: patterns of use, effects and withdrawal.

Gamma-hydroxybutyric acid (GHB) is gaining popularity as a drug of abuse. Reports of toxicity and lethality associated with GHB use have increased. This survey study was designed to identify patterns of GHB use, its effects, and withdrawal syndrome. A survey inquiring about the effects of GHB was administered to 42 users. The results showed that GHB was used to increased feelings of euphoria, relaxation, and sexuality. Adverse effects occurred more frequently in daily users and polydrug users than in occasional GHB users. Loss of consciousness was reported by 66%, overdose by 28%, and amnesia by 13% of participants during GHB use and by 45% after GHB use. Three daily users developed a withdrawal syndrome that presented with anxiety, agitation, tremor, and delirium. Participants described GHB intoxication as having similarities to sedative-hypnotic or alcohol intoxication. Regular use has been shown to produce tolerance and dependence. Participants dependent on GHB reported using multiple daily doses around the clock. High frequency users appeared at the greatest risk for developing withdrawal delirium and psychosis after abrupt discontinuation of GHB use.

Gamma hydroxybutyrate (GHB) and gamma butyrolactone (GBL) withdrawal: five case studies.

There is little medical information available about gamma-hydroxybutyrate (GHB) or gamma-butyrolactone (GBL) dependence or withdrawal. In this study the authors treated and reviewed multiple cases of GHB and GBL withdrawal in high-dose users. Five patients during nine hospitalizations were treated for GHB or GBL withdrawal. The authors describe a spectrum of GHB or GBL withdrawal from mild to severe and discuss medications used for treatment. They conclude that patients with GHB or GBL withdrawal may present with agitated psychosis, delirium, and autonomic instability. In this sample, relapse to GHB or GBL use occurred soon after treatment of withdrawal.

Screening for addiction in patients with chronic pain and "problematic" substance use: evaluation of a pilot assessment tool.

Assessing for the presence of addiction in the chronic pain patient receiving chronic opioid analgesia is a challenging clinical task. This paper presents a recently developed screening tool for addictive disease in chronic pain patients, and pilot efficacy data describing its ability to do so. In a small sample of patients (n = 52) referred from a multidisciplinary pain center for "problematic" medication use, responses to the screening questionnaire were compared between patients who met combined diagnostic criteria for a substance use disorder and those who did not, as assessed by a trained addiction medicine specialist. Responses of addicted patients significantly differed from those of nonaddicted patients on multiple screening items, with the two groups easily differentiated by total questionnaire score. Further, three key screening indicators were identified as excellent predictors for the presence of addictive disease in this sample of chronic pain patients.

Substance abuse treatment for "hazardous users": an early intervention.

A six-session cognitive behavioral protocol has been developed for substance abusers who meet the description "hazardous users." This category includes individuals evidencing mild to moderate use of alcohol or other drugs, whose lifestyles are minimally disrupted, or who are displaying signs of problem use or abuse, but are unwilling to enter intensive treatment. The treatment model is nonconfrontational and is designed to motivate the individual to recognize the problems associated with his or her substance use and initiate treatment-seeking behavior. The intervention may be particularly useful in situations where employees have tested positive for substances but deny having a problem, where friends or family members report help is needed but the individual denies any problem, or where an alcohol or other drug problem is clearly evidenced but the individual doesn't acknowledge a problem. A positive outcome is indicated by the client taking action which is consistent with an increased awareness of the problem as conceptualized by Prochaska and DiClemente (1982). This model is an alternative to the traditional confrontational models of "breaking through denial." The philosophies employed by William Miller and associates and by the Matrix treatment models form the basis of the intervention.

Outpatient non-opioid detoxification for opioid withdrawal. Who is likely to benefit?

The authors examined characteristics of successful completers of an outpatient clonidine/oxazepam detoxification procedure for opioid dependence. Of 215 initial applicants, 167 received medication, and 65 successfully completed by taking a dose of naltrexone. Those who completed were more likely to have last used an opioid other than heroin, to be heroin smokers, rather than intravenous users, to have used benzodiazepines in the 30 days before treatment, and to have abstained from opioids for a longer time before presenting for treatment. New users (for less than 2 years) did no better than those using longer than 2 years. These findings may help in the continued refinement of patient placement criteria.

Overdose, suicide attempts and death among a cohort of naltrexone-treated opioid addicts.

In a study evaluating naltrexone with either an intensive psychosocial protocol or standard community treatment for opioid dependence, 13 of 81 subjects overdosed within a 12-month period of study participation. There were four fatalities, one of which was a suicide. Among the nine nonfatal overdoses, there were four suicide attempts. Characteristics of subjects and naltrexone-taking are described.

Diagnosing addictive disease in chronic pain patients.

As opiate therapy is increasingly accepted for the management of chronic pain, the consultation-liaison psychiatrist is often challenged to diagnose and provide treatment recommendations for addictive disease in chronic pain patients. Reviewed are the defining characteristics of addiction within the context of chronic pain, and the interesting commonalities between addictive disease and chronic pain. Guidelines for assessment of addiction in patients with chronic pain are presented, as are suggestions for the management of these concurrent disorders. Underlying this review is a belief that opiates should not be withheld from persons with chronic pain, even in the presence of addictive disease.

Molecular probe analysis of Shigella dysenteriae type 1 isolates from 1940 to 1987.

Fourteen strains of Shigella dysenteriae type 1 (Shiga bacillus) isolated from people in diverse locations from 1940 to 1987 were studied. Southern hybridization with three cloned Escherichia coli genes, Shiga-like toxin I (SLTI), frd, and ompF, was used to determine restriction fragment length polymorphism (RFLP) of the genomic DNA of these strains. Digestion with each of four restriction endonucleases generated fragments of identical size to which the frd and ompF hybridized for each of the 14 strains, indicating the conservation of these genes and their flanking sequences. In contrast, after digestion with HindIII, EcoRV, and ClaI and probing with SLTI, there were RFLP among the strains. The results showed three clones of the Shiga bacillus, and suggested that dissemination of a single clone may continue for decades within a wide geographical area.

Phylogenetic diversity and position of the genus Campylobacter.

RNA sequence analysis has been used to examine the phylogenetic position and structure of the genus Campylobacter. A complete 5S rRNA sequence was determined for two strains of Campylobacter jejuni and extensive partial sequences of the 16S rRNA were obtained for several strains of C. jejuni and Wolinella succinogenes. In addition limited partial sequence data were obtained from the 16S rRNAs of isolates of C. coli, C. laridis, C. fetus, C. fecalis, and C. pyloridis. It was found that W. succinogenes is specifically related to, but not included, in the genus Campylobacter as presently constituted. Within the genus significant diversity was noted. C. jejuni, C. coli and C. laridis are very closely related but the other species are distinctly different from one another. C. pyloridis is without question the most divergent of the Campylobacter isolates examined here and is sufficiently distinct to warrant inclusion in a separate genus. In terms of overall position in bacterial phylogeny, the Campylobacter/Wolinella cluster represents a deep branching most probably located within an expanded version of the Division containing the purple photosynthetic bacteria and their relatives. The Campylobacter/Wolinella cluster is not specifically includable in either the alpha, beta or gamma subdivisions of the purple bacteria.

Widespread inhibition of neuroblastoma cells in the 13- to 17-day-old mouse embryo.

Previous experiments have demonstrated specific inhibition of tumor formation after neuroblastoma cells were injected into fragments of 8.5- to 9.5-day embryonic tissue (A.H. Podesta et al. Proc. Natl. Acad. Sci. USA, 81:7608-7611, 1984). The effect was localized to the somite and appeared specific for neuroblastoma as opposed to a variety of other tumor types. This regulation of neuroblastoma cells was believed to reflect an underlying event in the development of migrating embryonic neuroblasts. The current experiments were done to determine the effect on regulation with further embryonic development. The results indicated that later embryos (13 to 17 days of gestation) have a widespread inhibitory effect in all tissues tested, including the adrenal gland, testis, kidney, liver, limb bud, and heart. In contrast a leukemia cell line was not affected by any of these tissues. In organ culture demonstrable colony formation by neuroblastoma was likewise inhibited, and conditioned media from one of these embryonic sources (limb bud) slowed but did not abrogate growth of neuroblastoma cells.