Table 5.

Published controlled non-randomized trials, case series, case report and qualitative studies of mindfulness or mindfulness meditation based interventions (MM) used for the treatment of substance use, misuse or disorders: methods and results. Results from the final follow-up are reported, unless stated otherwise.

Study	Indication	Subjects	Intervention	Outcome measures	Results	Methodological quality/ comments
Controlled non-randomized trials
Study 1. Margolin et al. 2007 (47)	Substance use (as a part of HIV risk behavior assessment) in HIV-positive, opiate dependent, methadone maintenance out-patients.	38 (19 F); mean age 45.3 (33–57 yrs); PSR 4; 55% cocaine use disorder; 45% have continued using drugs; 71% were prescribed an HIV Tx.	Per subject choice: • MM (N=21), SOC + 3-S, 12 wks, therapist-led individual (60 min/wk) & group (60 min/wk) sessions; • CG (N=17): SOC only.	• Collected at 0, 12 wks; • substance use (self- report, UTox); • drug- and sex-related HIV risk behaviors; • impulsivity, spirituality, religiosity; • Tx experiences.	• Retention: MM 67%, CG 65%; PP: • compared to CG, MM showed trend to decreased alcohol and drug use (p=0.08 [ES 0.25]), and improved impulsivity, spirituality and motivation for abstinence (p<0.05); • 3-S attendance correlated to decreased substance use (r= 0.49 [ES 0.2], impulsivity, and increased influence of spirituality on abstinence and HIV prevention motivation (p<0.05).	MQS: 7/17; CBS: N/A per ITT (+2 PP) Subject meditation practice was not reported; adverse effects and side effects were not mentioned.
Study 2a. Bowen et al. 2006 (44)	Substance use among prisoners of the minimum- security jail.	305 (63 F), mean age 37.5 (19–58 yrs); PSR 2; alcohol use 83%, tobacco use 83%, drug use 73% during 90 days prior to incarceration.	Per subject choice: • MM (N=63): SOC + vipassana meditation (VM), 10 consecutive days: silent, gender- specific course, 8–10 hrs/day, led by a trained instructor; • CG (N=242): SOC only.	• Collected at 0, 1 wk post-intervention, 3 & 6 mos post-release; • substance use (self- report), related adverse consequences; • psychological health.	• Retention at 3 & 6 mos: MM 46% & 43%; CG 24% & 21%. PP: • at 3 mos, compared to CG, MM reduced (p<0.05) alcohol [ES 0.6], cocaine [ES 0.35] and marijuana [ES 0.5] use, and alcohol-related consequences [ES 0.35], and improved psychiatric symptoms, drinking-related locus of control and optimism; the changes were related to the VM participation; • at 6 mos, recidivism rates (the only results reported for 6 mos) were low, and comparable between the groups.	MQS: 6/17; CBS: N/A per ITT (+2 PP) Subject post-intervention meditation practice was not recorded; adverse effects and side effects were not mentioned.
Study 2b. Bowen et al. 2007 (45) (secondary analysis of Study 2a).	Relationship between substance use & thought suppression; prisoners.	See Bowen et al. 2006 (44) N=81 (for the main analysis of 0–3 month outcomes)	See Bowen et al. 2006 (44)	See Bowen et al. 2006 (44)	PP: • at 3 mos, compared to CG, MM decreased thought avoidance (p<0.05); this change partially mediated the relationship between the VM participation, and alcohol use and related consequences.	See Bowen et al. 2006 (44)
Study 2c. Simpson et al. 2007 (48) (secondary analysis of Study 2a).	Relationship between substance use & PTSD severity; prisoners	See Bowen et al. 2006 (44) ~ 22% of the subjects scored positively for PTSD; N=88 : 29 MM and 59 CG (for the main analysis of 0–3 month outcomes)	See Bowen et al. 2006 (44)	See Bowen et al. 2006 (44)	PP: • no differences in the PTSD symptom severity between the MM and CG groups; VM participation and baseline substance use, but not PTSD severity, predicted alcohol and drug use at 3 mos; baseline PTSD severity predicted adverse drinking consequences and psychological distress at 3 mos; PTSD subjects tolerated the VM course well;	See Bowen et al. 2006 (44)
Study 3. Altner 2002 (43)	Smoking cessation among tobacco dependent hospital employees	114 (71 F), mean age ~ 38.5 (20–65 yrs); PSR 2	Per subject choice: • MM (N=49): NRT + MBSR, 8 wks: therapist-led (2.5 hr/wk) group sessions; • CG (N=65): NRT only	• Collected at 0, 1.5, 3, 6, 15 mos (quit date likely at ‘0’); • % subjects who stopped, reduced or did not reduce smoking (self-report, exhaled CO); • Tx experiences among meditators (N=23, qualitative) at 3 mos.	• Retention: MM 100%; CG 97%. Descriptive statistics: • MM vs. CG subjects reported quit rate of 32.6% vs. 24.6% [ARR 8%, NNT 12.5], reduced smoking by 42.3% vs. 26.2%, continued smoking by 22.4% vs. 46.2%; • qualitative data: meditators reported positive opinions on the MBSR therapy and its usefulness as a coping strategy.	MQS: 6/17; CBS: N/A* *No statistical assessment of the significance of in-between group differences or pre-post changes was provided; only descriptive statistics were used. Exhaled CO-related results were not reported.
Study 4. Marcus et al. 2001 (46)	Psychological health in alcohol or drug dependent patients of therapeutic community	36 (2 F), mean age ~ 34 years; PSR 4	Per subject choice: • MM (N=18): SOC + MBSR, 8 wks, therapist-led (2.5 hrs/wk) group sessions; • CG (N=18): SOC only	• Collected at 0, 8 wks; • psychopathology (SCL-90R), coping styles	• Retention: MM & CG 100%; ITT=PP: • compared to CG, MM group tended to report a more self- controlling coping style (p=0.05, eta squared effect size: 0.11); no other differences between the groups were found (p>0.05); • effect sizes (eta squared 0.05–0.06) tended to favor the MM group in seeking social support, on hostility and paranoid ideation scores (per authors, eta squared effect size: 0.01– small, 0.06– medium, 0.14– large).	MQS: 8/17; CBS: −1 per ITT (−1 PP) CES: −8 per ITT (−8 PP) Group were derived from separate residential facilities.
Case series
Study 5. Zgierska et al. 2008 (53)	Relapse prevention in alcohol dependent adults, graduates of the Intensive Outpatient Program	19 (10 F), mean age 38.4 (21–50 yrs); PSR 4; alcohol-related Tx in the past: 63%	Mindfulness Based Relapse Prevention, 8 wks, therapist-led (120 min/wk) group sessions; MM component was based on the MBSR & MBCT programs, and Relapse Prevention component was based on Cognitive Therapy.	• Collected at 0, 4, 8, 12, 16 wks; • alcohol use (self- report); • severity of alcohol relapse triggers: stress, anxiety, depression, craving; • salivary cortisol, serum IL-6, liver enzymes at 0, 16 wks; • meditation-related outcomes; Tx services utilization; Tx experiences.	• Retention: 78.9% PP: • During the study, HDD decreased (p=0.056, ES 0.3), total number of drinks (ES 0.3) and PDA (ES 0.03) did not significantly change; • stress, depression, anxiety severity improved (p<0.05, ES 0.7- 1.4); IL-6 level decreased (p=0.05, ES 0.6); craving severity (ES 0.5), cortisol and liver enzymes levels did not significantly change; • degree of mindfulness increased (p<0.05, ES 0.7); all completers meditated at 16 wks, on average 4.6 days/wk during the study; • high Tx satisfaction; no adverse events.	MQS: 7/17; CBS: N/A per ITT (+1 PP) The only study that directly reports (lack of) side effects and adverse events, and describes evaluating distributional characteristics of the data, with the use of parametric or non-parametric tests, when appropriate.
Study 6. Davis et al. 2007 (50)	Smoking cessation, community setting	18 (10 F), mean age 45.2 (22–67 yrs); PSR 2; on average, subjects smoked 19.9 cigarettes/day for 26.4 yrs.	MBSR-based, with minor modifications, 8 wks, therapist-led group sessions (six 150 min/wk sessions + one 7 hr retreat); quit date at wk 7 (after the retreat).	• Collected at 0–8 wks weekly, then 6 wks post-quit (12 wks post- entry); • smoking (self-report, exhaled CO); • stress, psychopathology symptom severity.	• Retention: 72% (however, 100% data collection rate for self-reported smoking). ITT=PP: • 10/18 (56%) quit smoking; PP: • compared to non-quitters, those who quit meditated more (p<0.05), with a possible dose-effect: 100% highly compliant, 40% moderately compliant, and 0% non-compliant meditators quit; • compared to moderately compliant, highly compliant meditators decreased severity of stress one day post-quit (p<0.05); baseline interest in meditation and affective distress were related to abstinence (p<0.05).	MQS: 8/17 CBS: +2 per ITT (+2 PP) Due to 100% data collection rate for the primary outcome, the primary analysis includes all subjects.
Study 7a. Bootzin & Stevens 2005 (49)	Sleep and sleepiness problems as relapse triggers among adolescents with SUDs	55 (21 F), age 13–19 yrs; PSR 3; adolescents with sleep or daytime sleepiness problems, graduates or graduating from out- patient addiction Tx programs.	MBSR-based, therapist-delivered in a small group format over 5 sessions, during 7 wks: 1st session – other interventions, not MBSR; 2nd-6th sessions: 45 min MBSR + 45 min other Tx (stimulus control, bright light therapy, sleep hygiene, CT).	• Collected at 0–9 wks (weekly), 13, 52 wks; • self-reported and objective sleep and sleepiness related measures; • self-reported substance use and psychological distress.	• Retention: 93%; PP: • drug use, low at baseline, increased during the Tx - no details provided; • substance problem index plateaued for Tx completers (42% of the subjects), while it kept rising for those who did not complete Tx (p<0.2, no details provided); • sleep improved (p<0.05) among Tx completers only; sleepiness, worry and mental health distress decreased during the study (p<0.05).	MQS: 4/17; CBS: N/A per ITT (+2 PP) Study focused on methods description; only preliminary results were reported, without details on substance use outcomes. The study intervention included MM (MBSR-based; slightly less than 50%), but MM was not its primary focus.
Study 7b. Haynes et al. 2006 (57) (secondary analysis of Study 3a)	Is sleep improvement related to improved aggressive behavior among adolescents with SUDs	23 (13 F), mean age 16.4 (13–19 years); see Bootzin & Stevens 200549 for other details	See Bootzin & Stevens 2005 (49)	• See Bootzin & Stevens 2005 (49); • two questions on presence or absence of aggressive thoughts or actions.	• Retention: 91%; PP: • Those reporting aggression at baseline, compared to others, had lower self-efficacy in resisting substance use urges (p<0.05); • post- Tx, those reporting aggression, compared to others, reported more frequent substance use, especially alcohol use (p<0.05); • all subjects improved some aspects of their sleep; poor sleep was related to aggression, after controlling for substance use.	See Bootzin & Stevens 2005 (49); Substance use was used as a covariate in the analysis, but was not the focus. No details on substance use are reported.
Study 7c. Stevens et al. 2007 (52) (secondary analysis of Study 3a)	Is sleep improvement related to improved trauma symptoms severity among adolescents with SUDs	20 (10 F), mean age 16.3 (13–19 years); see Bootzin & Stevens 2005 (49) for other details.	See Bootzin & Stevens 2005 (49)	• See Bootzin & Stevens 2005 (49); • Trauma Severity Index.	• Retention: unclear; PP: • Those with elevated trauma score at baseline, compared to others, had higher Substance Problem Index (p<0.05). Substance use did not play a significant role in the analyses. • Those with better sleep characteristics had greater improvements in trauma scores than others.	See Bootzin & Stevens 2005 (49); Substance use was used as a covariate in the analysis, but was not the focus. No details on substance use are reported.
Study 8. Marcus et al. 2003 (51)	Stress severity among substance dependent patients in residential Tx settings	21 (3 F), mean age 33.4 (21–51 yrs); PSR 4; therapeutic community patients with SUDs.	SOC + MBSR, 8 wks, therapist-led (150 min/wk) group sessions.	• Collected at 0, 8 wks; • salivary cortisol upon awakening; • Perceived Stress Scale.	• Retention: 85.7% (data collection rate: 57% cortisol, 76% surveys); PP: • cortisol level decreased (p<0.05, ES 0.65); • perceived stress severity did not change (p>0.05, ES 0.44).	MQS: 4/17; CBS: N/A per ITT (+1 PP) The study did not report substance use data.
Other studies
Study 8 – case report. Twohig et al. 2007 (54)	Marijuana dependence, community settings	3 (1 F), ages 19, 20, 43; PSR 2; marijuana dependent (5 were enrolled, 2 dropped out)	ACT, 8 wks, therapist-led (90 min/wk) individual therapy sessions.	• Collected at 0–8 wks (daily), and 13 wks; • marijuana use (self- report, salivary swab); • withdrawal severity, psychological outcomes;	• Retention: 3/5 (60%); • although the 3 subjects did not use marijuana at 8 wks, they resumed its use by 13 wks (one to the pre-Tx level, and two at less than pre-Tx levels); • withdrawal, anxiety and depression severity seemed to improve compared to baseline.	Methodological quality not scored. Manualized intervention.
Study 9- qualitative study. Carroll et al. 2008 (56)	MBSR-related treatment experiences among substance dependent patients in residential Tx settings	36 (6F), mean age 32.6 (19–54 yrs); PSR 4; residents of therapeutic community with SUDs.	MBSR, adapted to therapeutic community settings, 6 wks, therapist-led (180 min/wk) group sessions.	• 356 stories were reviewed (written as a part of guided expressive writing); • 38 stories of stress that referenced the MBSR therapy were identified and analyzed.	Analysis of 38 stories identified 3 main MBSR qualities: • utility (usefulness for calming self, stress- reduction, coping), • portability (ability to apply learned skills in real- life), and • sustainability (application of skills to a variety of different situations, goals).	This report was based on the ongoing unpublished trial.(72) Manualized intervention - the intervention description (MBSR for therapeutic community, MBSR-TC) was published elsewhere.(87)
Study 10- qualitative study. Beitel et al. 2007 (55) (based on Margolin et al. 2006 (42) and 2007 (47) studies)	3-S treatment experience in methadone maintenance patients, a part of the studies by Margolin et al. 2006 (42) and 2007.(47)	39 (34 F), mean age 43 (28–54 yrs); PSR 4; opiate dependent patients of methadone maintenance program, cocaine use disorder 77%, HIV- positive 38%.	3-S therapy: individual (46%) or individual + group (54%) – see Margolin et al. 2006 (42) and 2007 (47) for details.	• Collected at post-Tx (8–12 wks post-entry); • Tx experiences questionnaire and interview.	• Preferred Tx format: 43% group, 14% individual, and 43% equally liked individual and group sessions; • all subjects meditated, on average 26 min/day; • 3-S was viewed as helpful for recovery, and different from the received SOC; • meditation was the most liked and helpful aspect of the 3-S therapy; 49% reported a positive change resulting from 3-S therapy; subjects were satisfied with 3-S, and 97% would like to continue it; • no significant adverse events were reported.	See Margolin et al. 2006 (42) and 2007 (47) for details. Subjects did not describe any significant negative effects (side effects or adverse events) or problems associated with 3-S therapy.

Values (presented in [square brackets]) calculated for the systematic review: ARR: Absolute Risk Reduction; CBS: Clinical Benefit Score; CES: Cumulative Evidence Score; ES: Effect Size (Cohen's d); MQS: Methodological Quality Score; NNT: Number Needed to Treat; PSS: Population Severity Score.

CG: comparison group; CO: carbon monoxide; MM: mindfulness meditation; HIV: Human Immunodeficiency Virus; ITT: intention to treat analysis; MBCT: Mindfulness-Based Cognitive Therapy; MBSR: Mindfulness-Based Stress Reduction; min: minutes; mos: months; NRT: Nicotine Replacement Therapy; PP: per protocol analysis; PTSD: post-traumatic stress disorder; 3-S: Spiritual Self Schema; SOC: "standard of care" therapy; SUDs: Substance Use Disorders; Tx: treatment; UTox: urine toxicology test; VM: vipassana meditation; wks: weeks; yrs: years.