Disorders - Opioid Use
Connery, H. S.
Medication-assisted treatment of opioid use disorder with physiological dependence at least doubles
rates of opioid-abstinence outcomes in randomized, controlled trials comparing psychosocial treatment of opioid use disorder with medication versus
with placebo or no medication. This article reviews the current evidence for medicationassisted treatment of opioid use disorder and also presents
clinical practice imperatives for preventing opioid overdose and the transmission of infectious disease. The evidence strongly supports the use of
agonist therapies to reduce opioid use and to retain patients in treatment, with methadone maintenance remaining the gold standard of care. Combined
buprenorphine/naloxone, however, also demonstrates significant efficacy and favorable safety and tolerability in multiple populations, including
youth and prescription opioid-dependent individuals, as does buprenorphine monotherapy in pregnant women. The evidence for antagonist therapies is
weak. Oral naltrexone demonstrates poor adherence and increased mortality rates, although the early evidence looks more favorable for extended-
release naltrexone, which has the advantages that it is not subject to misuse or diversion and that it does not present a risk of overdose on its
own. Two perspectives-individualized treatment and population management-are presented for selecting among the three available Food and Drug
Administration-approvedmaintenance therapies for opioid use disorder. The currently unmet challenges in treating opioid use disorder are discussed,
as are the directions for future research
Harvard
Review of Psychiatry, 23(2) : 63-75
- Year: 2015
- Problem: Opioid Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Medications used to treat substance abuse
Gonzalez, G., DiGirolamo, G., Romero-Gonzalez,
M., Smelson, D., Ziedonis, D., Kolodziej, M.
Background: Opioid use disorders are considered a serious
public health problem among young adults. Current treatment is limited to long-term opioid substitution therapy, with high relapse rates after
discontinuation. This study evaluated the co-administration of memantine to brief buprenorphine pharmacotherapy as a treatment alternative.; Methods:
13-week double-blind placebo-controlled trial evaluating 80 young adult opioid dependent participants treated with buprenorphine/naloxone 16-4mg/day
and randomized to memantine (15mg or 30mg) or placebo. Primary outcomes were a change in the weekly mean proportion of opioid use, and cumulative
abstinence rates after rapid buprenorphine discontinuation on week 9.; Results: Treatment retention was not significantly different between groups.
The memantine 30mg group was significantly less likely to relapse and to use opioids after buprenorphine discontinuation. Among participants
abstinent on week 8, those in the memantine 30mg group (81.9%) were significantly less likely to relapse after buprenorphine was discontinued
compared to the placebo group (30%) (p<0.025). Also, the memantine 30mg group had significantly reduced opioid use (mean=0, SEM±0.00) compared to the
placebo group (mean=0.33, SEM±0.35; p<0.004) during the last 2 weeks of study participation.; Conclusions: Memantine 30mg significantly improved
short-term treatment with buprenorphine/naloxone for opioid dependent young adults by reducing relapse and opioid use after buprenorphine
discontinuation. Combined short-term treatment with buprenorphine/naloxone may be an effective alternative treatment to long-term methadone or
buprenorphine maintenance in young adults.; Published by Elsevier Ireland Ltd.
Drug And Alcohol Dependence, 156 : 243-
253
- Year: 2015
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder), Relapse prevention
-
Treatment and intervention: Biological Interventions
(any), Medications used to treat substance abuse, Other biological interventions, Psychological Interventions
(any), Cognitive & behavioural therapies (CBT)
Karimyar J. M., Mosallanejad, L.
Introduction: Drug dependence is a major
problem in our country and in international level. Reality therapy is an internal control system that determines why and how to choose the options
that are set for our lives. This study aimed to investigate the effect of reality therapy on metacognition, stress and decline in hope in drug
addicts.; Materials& Methods: This study is quasi-experimental study. Samples were chosen convenient among 60 drug addicts in Jahrom in 2012. Samples
were randomly divided into two groups (each group = 30) of intervention and control groups. Control group received usual care and experimental group
received reality therapy.; Results: Results revealed that there was significant difference between the mean scores of metacognition and hope before
and after the intervention of experimental group (p < 0.05). Also, there was statistically significant difference between the two groups from these
two variables (p < 0.05).but, Stress level wasn't statistically different in two groups.; Discussion: Reality therapy is a method that emphasizes
the accountability and the current behavior of individuals. Setting negative emotions, reality therapy promotes metacognition and, through increasing
accountability to self-behavior improves hope.;
Global Journal of Health Science, 6(6) : 281-
287
- Year: 2014
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions
(any), Other Psychological Interventions
Crowley,
D. M., Jones, D. E., Coffman, D. L., Greenberg, M. T.
Purpose: Prescription drug abuse has reached epidemic proportions. Nonmedical prescription opioid use carries increasingly high costs.
Despite the need to cultivate efforts that are both effective and fiscally responsible, the cost-effectiveness of universal evidence-based-
preventive-interventions (EBPIs) is rarely evaluated. This study explores the performance of these programs to reduce nonmedical prescription opioid
use.; Methods: Sixth graders from twenty-eight rural public school districts in Iowa and Pennsylvania were blocked by size and geographic location
and then randomly assigned to experimental or control conditions (2002-2010). Within the intervention communities, prevention teams selected a
universal family and school program from a menu of EBPIs. All families were offered a family-based program in the 6th grade and received one of three
school-based programs in 7th-grade. The effectiveness and cost-effectiveness of each school program by itself and with an additional family-based
program were assessed using propensity and marginal structural models.; Results: This work demonstrates that universal school-based EBPIs can
efficiently reduce nonmedical prescription opioid use. Further, findings illustrate that family-based programs may be used to enhance the cost-
effectiveness of school-based programs.; Conclusions: Universal EBPIs can effectively and efficiently reduce nonmedical prescription opioid use.
These programs should be further considered when developing comprehensive responses to this growing national crisis.; Copyright © 2014 Elsevier Inc.
All rights reserved.
Preventive
Medicine, 62 : 71-77
- Year: 2014
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Universal prevention
-
Treatment and intervention: Psychological Interventions
(any), Skills training, Other Psychological Interventions
Minozzi, S., Amato, L., Bellisario, C., Davoli, M.
BACKGROUND: The scientific literature examining effective treatments for opioid dependent adults clearly indicates that
pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless, no studies have been published
that systematically assess the effectiveness of the pharmacological detoxification among adolescents.\rOBJECTIVES: To assess the effectiveness of any
detoxification treatment alone or in combination with psychosocial intervention compared with no intervention, other pharmacological intervention or
psychosocial interventions on completion of treatment, reducing the use of substances and improving health and social status.\rSEARCH METHODS: We
searched the Cochrane Central Register of Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January
2014), CINHAL (January 1982 to January 2014), Web of Science (1991-January 2014) and reference lists of articles.\rSELECTION CRITERIA: Randomised
controlled clinical trials comparing any pharmacological interventions alone or associated with psychosocial intervention aimed at detoxification
with no intervention, placebo, other pharmacological intervention or psychosocial intervention in adolescents (13 to 18 years).\rDATA COLLECTION AND
ANALYSIS: We used standard methodological procedures recommended by The Cochrane Collaboration\rMAIN RESULTS: Two trials involving 190 participants
were included. One trial compared buprenorphine with clonidine for detoxification. No difference was found for drop out: risk ratio (RR) 0.45 (95%
confidence interval (CI): 0.20 to 1.04) and acceptability of treatment: withdrawal score mean difference (MD): 3.97 (95% CI -1.38 to 9.32). More
participants in the buprenorphine group initiated naltrexone treatment: RR 11.00 (95% CI 1.58 to 76.55), quality of evidence moderate.The other trial
compared maintenance treatment versus detoxification treatment: buprenorphine-naloxone maintenance versus buprenorphine detoxification. For drop out
the results were in favour of maintenance treatment: RR 2.67 (95% CI 1.85, 3.86), as well as for results at follow-up RR 1.36 [95% CI 1.05to 1.76);
no differences for use of opiate, quality of evidence low.\rAUTHORS' CONCLUSIONS: It is difficult to draw conclusions on the basis of two trials
with few participants. Furthermore, the two studies included did not consider the efficacy of methadone that is still the most frequent drug utilised
for the treatment of opioid withdrawal. One possible reason for the lack of evidence could be the difficulty in conducting trials with young people
due to practical and ethical reasons.
Cochrane Database of Systematic Reviews, 4 : CD006749
- Year: 2014
- Problem: Opioid Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Medications used to treat substance abuse
Minozzi, S., Amato, L., Bellisario, C., Davoli, M.
BACKGROUND: The scientific literature examining effective
treatments for opioid-dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component. Nevertheless, no reviews have
been published that systematically assess the effectiveness of pharmacological maintenance treatment in adolescents.\rOBJECTIVES: To assess the
effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological
intervention or psychosocial interventions for retaining adolescents in treatment, reducing the use of substances and improving health and social
status.\rSEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group's Trials Register (January 2014), the Cochrane Central Register of
Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January 2014), CINAHL (January 1982 to January
2014), Web of Science (1991 to January 2014) and reference lists of articles.\rSELECTION CRITERIA: Randomised and controlled clinical trials of any
maintenance pharmacological interventions either alone or associated with psychosocial intervention compared with no intervention, placebo, other
pharmacological intervention, pharmacological detoxification or psychosocial intervention in adolescents (13 to 18 years).\rDATA COLLECTION AND
ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration.\rMAIN RESULTS: We included two trials involving 189
participants. One study, with 35 participants, compared methadone with levo-alpha-acetylmethadol (LAAM) for maintenance treatment lasting 16 weeks,
after which patients were detoxified. The other study, with 154 participants, compared maintenance treatment with buprenorphine-naloxone and
detoxification with buprenorphine. We did not perform meta-analysis because the two studies assessed different comparisons.In the study comparing
methadone and LAAM, the authors declared that there was no difference in the use of a substance of abuse or social functioning (data not shown). The
quality of the evidence was very low. No side effects, such as nausea, vomiting, constipation, weakness or fatigue, were reported by study
participants.In the comparison between buprenorphine maintenance and buprenorphine detoxification, maintenance treatment appeared to be more
efficacious in retaining patients in treatment (drop-out risk ratio (RR) 0.37; 95% confidence interval (CI) 0.26 to 0.54), but not in reducing the
number of patients with a positive urine test at the end of the study (RR 0.97; 95% CI 0.78 to 1.22). Self reported opioid use at one-year follow-up
was significantly lower in the maintenance group, even though both groups reported a high level of opioid use (RR 0.73; 95% CI 0.57 to 0.95). More
patients in the maintenance group were enrolled in other addiction treatment programmes at 12-month follow-up (RR 1.33; 95% CI 0.94 to 1.88). The
quality of the evidence was low. No serious side effects attributable to buprenorphine-naloxone were reported by study participants and no patients
were removed from the study due to side effects. The most common side effect was headache, which was reported by 16% to 21% of patients in both
groups\rAUTHORS' CONCLUSIONS: It is difficult to draft conclusions on the basis of only two trials. One of the possible reasons for the lack of
evidence could be the difficulty of conducting trials with young people for practical and ethical reasons.There is an urgent need for further
randomised controlled trials comparing maintenance treatment with detoxification treatment or psychosocial treatment alone before carrying out
studies that compare different pharmacological maintenance treatments. These studies should have long follow-up and measure relapse rates after the
end of treatment and social functioning (integration at school or at work, family relationships).
Cochrane Database of
Systematic Reviews, 6 : CD007210
- Year: 2014
- Problem: Opioid Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Medications used to treat substance abuse
Veilleux,
Jennifer C., Colvin, Peter J., Anderson, Jennifer, York, Catherine, Heinz, Adrienne J.
Opioid dependence is a problem of national concern, especially with
dramatically increased rates of abuse and dependence of prescription opioids. The current article provides an up-to-date review of the literature on
opioid dependence treatment, with a focus on conclusions drawn by experts in the field (e.g., Cochrane reviews and meta-analyses) and
methodologically rigorous studies (e.g., randomized controlled trials). We describe the major classes of drug treatments available, including opioid
agonist (e.g., methadone, buprenorphine, LAAM), antagonist (e.g., naltrexone) and non-opioid pharmacotherapies (e.g., alpha2 adrenergic agonists).
These treatments are discussed in the context of detoxification and long term treatment options such as abstinence-based and maintenance strategies.
We review the state of the literature as to prevention of opioid overdose and discuss the widespread problem of comorbidity among opioid-dependent
populations. We also focus prominently on evidence for inclusion of psychosocial approaches in treatment regimens, either as stand-alone or in
conjunction with psychopharmacological options.\rCopyright 2009 Elsevier Ltd. All rights reserved.
Clinical Psychology Review, 30(2) : 155-
166
- Year: 2010
- Problem: Opioid Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder), Relapse prevention
-
Treatment and intervention: Biological Interventions
(any), Medications used to treat substance abuse
Woody, G.E., Poole, S.A., Subramaniam, G., Dugosh, K., Bogenschutz, M., Abbott, P., Patkar, A., et-al
Context The usual treatment for opioid-addicted youth is detoxification and counseling.\rExtended medication-assisted therapy may be more
helpful.\rObjective To evaluate the efficacy of continuing buprenorphine-naloxone for 12\rweeks vs detoxification for opioid-addicted youth.\rDesign,
Setting, and Patients Clinical trial at 6 community programs from July\r2003 to December 2006 including 152 patients aged 15 to 21 years who were
randomized\rto 12 weeks of buprenorphine-naloxone or a 14-day taper (detox).\rInterventions Patients in the 12-week buprenorphine-naloxone group were
prescribed\rup to 24 mg per day for 9 weeks and then tapered to week 12; patients in the\rdetox group were prescribed up to 14 mg per day and then
tapered to day 14. All\rwere offered weekly individual and group counseling.\rMain Outcome Measure Opioid-positive urine test result at weeks 4, 8,
and 12.\rResults The number of patients younger than 18 years was too small to analyze separately,\rbut overall, patients in the detox group had
higher proportions of opioidpositive\rurine test results at weeks 4 and 8 but not at week 12 ( 2\r2=4.93, P=.09). At\rweek 4, 59 detox patients had
positive results (61%;95%confidence interval [CI]=47%-\r75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI=14%-38%).\rAt week 8, 53
detox patients had positive results (54%; 95% CI=38%-70%) vs 52\r12-week buprenorphine-naloxone patients (23%; 95% CI=11%-35%). At week 12,\r53 detox
patients had positive results (51%; 95% CI=35%-67%) vs 49 12-week buprenorphine-\rnaloxone patients (43%; 95% CI=29%-57%). By week 12, 16 of
78\rdetox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphinenaloxone\rpatients (70%; 2\r1=32.90, P .001). During weeks 1
through 12, patients\rin the 12-week buprenorphine-naloxone group reported less opioid use ( 2\r1=18.45,\rP .001), less injecting ( 2\r1=6.00,
P=.01), and less nonstudy addiction treatment\r( 2\r1=25.82, P .001). High levels of opioid use occurred in both groups at follow-up.\rFour of 83
patients who tested negative for hepatitis C at baseline were positive for\rhepatitis C at week 12.\rConclusions Continuing treatment with
buprenorphine-naloxone improved outcome\rcompared with short-term detoxification. Further research is necessary to assess\rthe efficacy and safety of
longer-term treatment with buprenorphine for young\rindividuals with opioid dependence.
JAMA, 300(17) : 2003-2011
- Year: 2008
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Medications used to treat substance abuse, Medication dose
reduction/discontinuation
Neri, S., Bruno, C. M., Pulvirenti, D., Malaguarnera, M., Italiano, C., Mauceri, B., Abate, G., et-al
RATIONALE: Buprenorphine may be a useful alternative option
to methadone in addicts. Opioids can produce severe changes in the immune system. OBJECTIVES: The objectives of this study are to compare the effect
of sublingual buprenorphine and methadone on the immune system and to compare the two substances on the drying-out program compliance. METHODS: We
studied 62 randomized outpatients for a period of 12 months. Subjects (55 males and 7 females; mean age 25+/-4 years; average history of heroin abuse
being 2 years) on maintenance treatment were assigned in two groups (A and B). Methadone chloride (medium dose 100 mg/day) was administered to group
A, whereas group B received sublingual buprenorphine (32.40+/-2.8 mg/day). Urine toxicological screening, plasma levels of TNF-alpha interleukin-1,
interleukin-beta, lymphocyte CD14 and a self-rating depression questionnaire were measured. RESULTS: Urine screening was negative for opiates in
17.6% of group A and in 10.7% of group B (p<0.001; r = 0.62). Depression score was 62+/-2 in group A and 55+/-3 in group B (p < 0.01). Cytokine and
CD14 revealed higher concentrations both in groups A and B without significant differences (p > 0.05) between the two groups. CONCLUSIONS: The
effects of buprenorphine and methadone tested on the immune system were overlapping in our patients. The elevated cytokine levels observed may
suggest that the two drugs stimulate immunologic hyperactivation of an immune system that was formerly inhibited by heroin. Furthermore, our data
suggest that buprenorphine can be a valid alternative to methadone in maintenance treatment of chronic heroin abuse and referred a marked decline in
depression.
Psychopharmacology, 179(3) : 700-
4
- Year: 2005
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Medications used to treat substance abuse
Marsch, Lisa A., Bickel, Warren K., Badger, Gary J., Stothart, Marne E., Quesnel, Kimberly J., Stanger, Catherine, Brooklyn, John
CONTEXT: The prevalence of heroin and other opioid use has markedly increased among
adolescents in the last decade; however, virtually no research has been conducted to identify effective treatments for this population. OBJECTIVE: To
evaluate the relative efficacy of 2 pharmacotherapies, the partial opioid agonist buprenorphine hydrochloride and the centrally active alpha(2)-
adrenergic blocker clonidine hydrochloride, in the detoxification of opioid-dependent adolescents. DESIGN, SETTING, AND PATIENTS: A double-blind,
double-dummy, parallel-groups randomized controlled trial conducted in a university-based research clinic from October 2001 to December 2003.
Patients were a volunteer sample of 36 adolescents who met DSM-IV criteria for opioid dependence (ages 13-18 years eligible). INTERVENTIONS:
Participants were randomly assigned to a 28-day, outpatient, medication-assisted withdrawal treatment with either buprenorphine or clonidine. Both
medications were provided along with thrice weekly behavioral counseling and incentives contingent on opiate abstinence. Postdetoxification, all
participants were offered the opportunity for continued treatment with the opiate antagonist, naltrexone hydrochloride. MAIN OUTCOME MEASURES:
Treatment retention, opiate abstinence, and human immunodeficiency virus risk behavior, along with measures of withdrawal and medication effects.
RESULTS: A significantly greater percentage of adolescents who received buprenorphine were retained in treatment (72%) relative to those who received
clonidine (39%) (P<.05). For those in the buprenorphine group, a significantly higher percentage of scheduled urine test results were opiate negative
(64% vs 32%; P = .01). Participants in both groups reported relief of withdrawal symptoms and drug-related human immunodeficiency virus risk
behavior. Those in the buprenorphine condition generally reported more positive effects of the medication. No evidence of opioid intoxication or
psychomotor impairment was observed. Sixty-one percent of participants in the buprenorphine condition and 5% of those in the clonidine group
initiated treatment with naltrexone. CONCLUSION: Combining buprenorphine with behavioral interventions is significantly more efficacious in the
treatment of opioid-dependent adolescents relative to combining clonidine and behavioral interventions.
Archives of General Psychiatry, 62(10) : 1157-
64
- Year: 2005
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Medications used to treat substance abuse
Jimenez-Lerma, Juan, Landabaso, Miguel, Iraurgi, Ioseba, Calle, Ricardo, Sanz, Juan, Gutierrez-Fraile, Miguel
Evaluated the use of L-type calcium channel blockers (CaCB) in outpatient opiate detoxification
in a controlled trial with sequential allocation of patients to groups. Three groups of individuals subject to opiate detoxification were involved:
(1) the experimental group (n=30) received a course of nimodipine and dextropropoxiphen; (2) one control group (n=20) was detoxified with a course of
dextropropoxiphen and benzodiazepine; and (3) a second control group (n=30) was treated with a standard course of alpha -2-adrenergic agents and
naltrexone. In all cases, the detoxification course was scheduled to last 7 days. All the groups showed a significant opiate withdrawal syndrome
(OWS) during detoxification, but from the first day the group treated with CaCB manifested fewer symptoms than the control groups. From the start,
the intensity of the OWS was reduced by half in the CaCB group compared with that manifested by the two other groups. The clinical impression of the
evolution of the detoxification was that it was comfortable and free of complications (significant side-effects were not observed). The results of
the study suggest that the use of calcium channel blockers (CaCB) may be an effective method in opiate detoxification. Full randomized trials are
warranted. (PsycINFO Database Record (c) 2007 APA, all rights reserved).
Addiction, 97(7) : 819-824
- Year: 2002
- Problem: Opioid Use
- Type: Controlled clinical trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Medications used to treat substance abuse, Other biological interventions
Krupitsky, E. M., Burakov, A. M., Didenko, T.
Y., Romanova, T. N., Grinenko, N. I., Slavina,
T. Y., Grinenko, A. Y., et-al
Objective: Soon after termination of withdrawal, many detoxified heroin addiction patients
experience affective instability (i.e., depression, dysphoria, anxiety), insomnia, and craving for opiates. Previously, the authors have described
these symptoms as the syndrome of anhedonia (SA). The search for novel pharmacologic agents able to optimize treatment of this syndrome is an
important component in the prevention of future relapses and stabilization of remissions. This study examines the new pharmacologic treatment of SA.
The choice of antidepressants as possible medication for SA is based on the fact that depressive symptoms are the most prominent features of SA. The
authors compare the effect of the selective serotonin reuptake inhibitor citalopram on SA with the tricyclic antidepressant amitriptyline and
placebo. Methods: Immediately after detoxification, 73 heroin addiction patients were randomly assigned to one of three groups: 26 patients received
20 mg/d citalopram during 3 weeks; 24 patients received 75 mg/d amitriptyline; and 23 patients received placebo. Results: The results of the
randomized, single-blind, placebo-controlled study showed that both medications, citalopram and amitriptyline, are more effective than placebo in
treatment of SA. However, patients in the amitriptyline group reported a statistically greater number of side effects in comparison with patients in
the two other groups. Conclusion: Citalopram significantly reduces the severity of SA in patients with heroin addiction. Copyright copyright 2002
Lippincott Williams & Wilkins, Inc.
Addictive Disorders & their Treatment, 1(1) : 29-
33
- Year: 2002
- Problem: Opioid Use
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Selective serotonin reuptake inhibitors (SSRIs), Tricyclic antidepressants, Medications used to treat substance abuse