Article

Clinical implications for four drugs of the DSM-IV distinction between substance dependence with and without a physiological component.

Department of Psychiatry, University of California, San Diego, VA Medical Center, 92161-2002, USA.
American Journal of Psychiatry (Impact Factor: 13.56). 02/1999; 156(1):41-9. DOI: 10.1176/ajp.156.1.41
Source: PubMed

ABSTRACT The DSM-IV work group asked researchers and clinicians to subtype substance dependent individuals according to the presence or absence of physiological symptoms. A recent report from the Collaborative Study on the Genetics of Alcoholism demonstrated that among alcohol-dependent men and women, a history of tolerance or withdrawal was associated with a more severe clinical course, especially for individuals with histories of alcohol withdrawal. This article evaluates similar distinctions among subjects in the collaborative study who were dependent on marijuana, cocaine, amphetamines, or opiates.
Structured interviews gathered information from 1,457 individuals with a lifetime diagnosis of marijuana dependence, 1,262 with histories of cocaine dependence, 647 with amphetamine dependence, and 368 subjects with opiate dependence. For each drug, the clinical course was compared for subjects whose dependence included a history of withdrawal (group 1), those dependent on each drug who denied withdrawal but reported tolerance (group 2), and those who denied both tolerance and withdrawal (group 3).
The proportion of dependent individuals who denied tolerance or withdrawal (group 3) ranged from 30% for marijuana to 4% for opiates. For each substance, individuals in groups 1 and 2 evidenced more severe substance-related problems and at least a trend for greater intensities of exposure to the drug; those reporting withdrawal (group 1) showed the greatest intensity of problems.
The designation of dependence in the context of tolerance or withdrawal identifies individuals with more severe clinical histories. These results support the importance of the designation of a physiological component to dependence, especially for people who have experienced a withdrawal syndrome.

0 Bookmarks
 · 
104 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Increased depressive and anxiety-like behaviors are exhibited by rats and humans during withdrawal from psychostimulants. Anxiety-like behaviors observed during amphetamine withdrawal are mediated by increased expression and activity of corticotropin releasing factor type 2 (CRF2) receptors in the dorsal raphe nucleus (dRN). Anxiety-like behavior of rats during withdrawal can be reversed by CRF2 receptor antagonism in the dRN, but the efficacy of global central CRF2 receptor antagonism is unknown. Rats were treated with amphetamine (2.5 mg/kg, ip.) or saline daily for 2 weeks, and were tested for anxiety-like behaviors during withdrawal. Rats undergoing withdrawal showed increased anxiety-like behavior, which was reduced by ventricular infusion of the CRF2 antagonist antisauvagine-30 (ASV 2 μg/2 μl). Surprisingly, ventricular ASV increased anxiety-like behavior in rats pre-treated with saline, but had an anxiolytic effect in un-treated rats. Western blots were performed to determine whether differences in CRF receptor densities could explain ASV-induced behavioral results. Saline pre-treated rats showed reduced CRF1 receptor expression in the lateral septum compared to amphetamine pre-treated and un-treated rats. Overall, these results suggest that central CRF2 antagonism reduces anxiety states during amphetamine withdrawal, and that behavioral effects may be dependent upon the balance of CRF1 and CRF2 receptor activity in anxiety-related regions.
    Neuroscience Research 09/2014; · 2.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Withdrawal from amphetamine is associated with increased anxiety and sensitivity to stressors which are thought to contribute to relapse. Rats undergoing amphetamine withdrawal fail to exhibit stress-induced increases in serotonin (5-HT) release in the ventral hippocampus and show heightened anxiety-like behaviors. Therefore, we tested the hypothesis that reduced 5-HT levels in the ventral hippocampus is a causal mechanism in increasing anxiety-like behaviors during amphetamine withdrawal. First, we tested whether reducing 5-HT levels in the ventral hippocampus directly increases anxiety behavior. Male rats were bilaterally infused with 5,7-DHT into the ventral hippocampus, which produced a 83% decrease ventral hippocampus 5-HT content, and were tested on the elevated plus maze (EPM) for anxiety-like behavior. Reducing ventral hippocampus 5-HT levels decreased the time spent in the open arms of the maze, suggesting diminished ventral hippocampus 5-HT levels increases anxiety-like behavior. Next, we tested whether increasing 5-HT levels in the ventral hippocampus reverses anxiety behavior exhibited by rats undergoing amphetamine withdrawal. Rats were treated daily with either amphetamine (2.5 mg/kg, ip.) or saline for 2 weeks, and at 2 weeks withdrawal, were infused with the selective serotonin reuptake inhibitor paroxetine (0.5 μM) bilaterally into the ventral hippocampus and tested for anxiety-like behavior on the EPM. Rats pre-treated with amphetamine exhibited increased anxiety-like behavior on the EPM. This effect was reversed by ventral hippocampus infusion of paroxetine. Our results suggest that 5-HT levels in the ventral hippocampus is critical for regulating anxiety behavior. Increasing 5-HT levels during withdrawal may be an effective strategy for reducing anxiety-induced drug relapse.
    Neuroscience 09/2014; · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since DSM-IV was published in 1994, its approach to substance use disorders has come under scrutiny. Strengths were identified (notably, reliability and validity of dependence), but concerns have also arisen. The DSM-5 Substance-Related Disorders Work Group considered these issues and recommended revisions for DSM-5. General concerns included whether to retain the division into two main disorders (dependence and abuse), whether substance use disorder criteria should be added or removed, and whether an appropriate substance use disorder severity indicator could be identified. Specific issues included possible addition of withdrawal syndromes for several substances, alignment of nicotine criteria with those for other substances, addition of biomarkers, and inclusion of nonsubstance, behavioral addictions.This article presents the major issues and evidence considered by the work group, which included literature reviews and extensive new data analyses. The work group recommendations for DSM-5 revisions included combining abuse and dependence criteria into a single substance use disorder based on consistent findings from over 200,000 study participants, dropping legal problems and adding craving as criteria, adding cannabis and caffeine withdrawal syndromes, aligning tobacco use disorder criteria with other substance use disorders, and moving gambling disorders to the chapter formerly reserved for substance-related disorders. The proposed changes overcome many problems, while further studies will be needed to address issues for which less data were available.
    American Journal of Psychiatry 08/2013; 170(8):834-51. · 14.72 Impact Factor

Full-text (2 Sources)

Download
17 Downloads
Available from
May 20, 2014