We hypothesized that greater reductions in 12-step affiliation and meeting attendance would predict greater increases in drinking and drug use, and that these effects would mediate the superior long-term treatment effects observed for the ICBT condition. The sample for this study includes 201 veterans who participated in a trial of outpatient group psychotherapy for comorbid substance dependence and MDD . We included all participants from the trial who completed at least one follow-up assessment from end-of treatment to the one-year follow-up . Demographics of the sample are presented in Table 1. Study inclusion criteria were lifetime dependence on alcohol, cannabis, or stimulants with recent use, and major depressive disorder with at least one episode occurring independently of substance use. Exclusion criteria included opiate dependence with intravenous administration, bipolar or psychotic disorder, residing excessively far from the research facility, or memory impairments prohibiting accurate recall in study assessments.The procedures for this study were approved by the University of California, San Diego and VA San Diego Healthcare System Institutional Review Boards. Participant referrals were obtained from the VASDHS dual diagnosis clinic by research study staff, who conducted brief screenings prior to meeting with eligible veterans to explain study procedures and obtain informed consent. Participating veterans consented to 6 months of group psychotherapy, recording of sessions, psychotropic medication management appointments, random urine screens, and research assessments conducted at intake and at 3- month intervals for an 18-month period. Veterans agreed to receive no other formal treatment for substance use or depression for the duration of group psychotherapy. Participation in other formal intervention was allowed during follow-up.Group psychotherapy was initiated on a rolling basis,vertical aeroponics farming with starts occurring every 2 weeks. After completing the intake assessment participants were sequentially allocated to the treatment condition with the next start date.
For Twelve-Step Facilitation we modified the TSF protocol from Project MATCH to allow group delivery and discussion of multiple substances. For development of Integrated Cognitive-Behavioral Therapy , material was adapted from two empirically-supported treatments: group cognitive behavioral therapy for depression and cognitive-behavioral relapse prevention from Project MATCH . The two treatments were identically structured with a series of three modules, with each module designed to cover a specific 12-step or cognitive-behavioral topic. Group sessions occurred twice/week for the first 3 months of group treatment, when each topic was covered in a one-month block. Topics were reviewed in the next 3 months during weekly group sessions. The mean session attendance was similar across groups. Interventions were codelivered by senior clinicians and doctoral students trained via manual review, direct observation, and weekly supervision. Therapists were rotated across treatment conditions on a regular basis , and adherence to protocol was assessed via videotape review. Our longitudinal analyses utilized latent growth modeling in the structural equation modeling framework. In LGM a series of repeated measures are used to indicate each individual’s underlying latent “growth curve” on one or more variables. This process creates separate growth curves for each individual, described by “growth factors” such as latent intercept and latent slope . Estimates of the sample mean and variance are obtained for each growth factor, and covariates can be used to predict individual differences in the initial level or rate of change over time. One distinct advantage of LGM is the ability to examine relations between the rates of change in multiple longitudinal processes, as warranted by the aims of this study. Because we were primarily concerned with the 12-month follow-up period, the end-of-treatment time point served as the initial level for each LGM. Thus, in each LGM the latent intercept represents the level at end-of-treatment, while latent slopes represent rates of increase or decrease during the 12 months of follow-up . For each study variable we first fit unconditional growth models to determine the optimal shape of the growth trajectory, before incorporating treatment group as a predictor in conditional models. This allowed us to test whether treatment condition predicted variability in the intercepts and slopes. In the final LGMs for PDD and PDDRG we specified growth curve mediation models , to determine if the slope of 12- step affiliation or meeting attendance mediated the relationship between treatment group and the slope of PDD or PDDRG. To test the significance of mediated effects we used asymmetric 95% confidence intervals obtained with the bias-corrected bootstrap procedure , which has shown greater power to detect mediated effects than other formal mediation tests .
All LGMs utilized the maximum likelihood procedure, which incorporates all available data from each participant under the assumption of missing at random. We then used the LGMs for 12-step and affiliation to predict individual differences in the end-of-treatment level and rate of change in alcohol and drug use from Month 6 to Month 18. In separate models the slopes for 12-step affiliation and meeting attendance were utilized as mediating variables between treatment group and the slopes for PDD and PDDRG , to test whether the greater increases in PDD over time for TSF patients were explained by greater decreases in 12-step variables. Results from these analyses are presented in Table 3. The PDD intercept was significantly and negatively correlated with the intercepts for 12-step affiliation and meeting attendance, indicating that individuals with greater levels of affiliation and meeting attendance at end of-treatment were also drinking less frequently at end-of-treatment. The PDD intercept was significantly and positively correlated with the slopes for 12-step affiliation and attendance, indicating that individuals with lower PDD at end-of-treatment had greater decreases in their 12-step affiliation and attendance during follow-up. Finally, the slopes for 12-step affiliation and meeting attendance were strongly, negatively predictive of PDD slope. This indicated that individuals with greater decreases in 12-step affiliation and meeting attendance from Month 6 to Month 18 had greater increases in PDD over time. As shown by asymmetric 95% confidence intervals obtained via the bias-corrected bootstrap procedure, the indirect effects of treatment group on PDD through slopes of 12-step affiliation and meeting attendance were statistically significant. These results indicate that the greater relative increases in PDD for the TSF patients were mediated by their greater relative decreases in 12-step affiliation and meeting attendance. There were no significant relations between intercepts and slopes of the 12-step variables and PDDRG , indicating that the end-of-treatment level and change during follow-up for drug use frequency was unrelated to end-of-treatment level or change during follow-up for 12-step affiliation or meeting attendance. This study examined post-treatment change in 12-step affiliation and meeting attendance and related effects on substance use outcomes in a sample of veterans with comorbid substance dependence and major depression who received six months of group treatment with TSF or ICBT.
Because fewer studies of mediating variables have focused on substance dependent patients with psychiatric comorbidity, there is relatively less knowledge about processes that sustain long-term change in their substance use outcomes. This study adds to the existing literature by examining post-treatment trajectories of change in 12-step affiliation and attendance in comorbid patients, determining whether treatment condition predicts individual differences in these trajectories,vertical farm cannabis and reporting the mediational effects of reduced 12-step involvement on long-term substance use outcomes. Veterans in the TSF condition had greater levels of 12-step affiliation and meeting attendance at end-of-treatment than those in ICBT. This is consistent with prior studies of this sample and shows that a professionally-delivered TSF intervention can enable greater levels of 12-step involvement than other psychotherapies during active treatment. However, veterans in TSF also evinced a significant nonlinear decline in both 12-stepaffiliation and meeting attendance during the one year follow-up, while those in ICBT had no significant change. Previous studies of non-comorbid patients found no post-treatment decline in affiliation or meeting attendance following 12-step interventions . Our contrasting findings suggest comorbid MDD may interfere with continued attendance at 12- step meetings and affiliation with prescribed 12-step behaviors, even when patients are relatively successful at achieving these goals during active TSF. Potential explanatory mechanisms behind this finding are beyond our current scope, but could be related to persistent depressive symptoms and related low motivation, the sudden absence of accountability provided by a formal treatment group, or difficulty in establishing firm social bonds in 12-step meetings for patients with comorbid MDD. Some patients were evidently successful at sustaining 12-step affiliation as revealed by significant individual variance estimates, but modifications to TSF or continued contact may be necessary to achieve the desired long-term results in the majority of patients with comorbid MDD. Independent of treatment condition, individuals with greater decreases in 12-step affiliation and meeting attendance also had greater increases in drinking frequency during the one-year follow-up. As evidenced by strong standardized coefficients in our latent growth curve models, post-treatment change in 12-step involvement likely plays a large role in determining whether patients with comorbid substance dependence and MDD experience post-treatment increases in drinking. Similar to a prior report of follow-up substance use outcomes in this sample , the current study found patients in TSF had greater post treatment increases in drinking frequency than those in the ICBT condition. We also determined this group difference was mediated through reductions in 12-step affiliation and meeting attendance, which provides a possible explanation for the worse outcomes over time for TSF and supports the long-term efficacy of ICBT. During follow-up the ICBT group as a whole did not increase or decrease in 12-step affiliation or meeting attendance, but their mean levels of attendance and affiliation remained consistently greater than zero. Although it was not a prescribed element of treatment, there is apparently a subset of patients in ICBT who continue 12-step involvement. Superior long-term patterns in other mediating variables may have also occurred for the ICBT condition, and future studies will explore other potential factors related to their superior post-treatment drinking outcomes. Limitations of this study include the restricted demographic characteristics of the veteran sample which curtails the immediate generalizability of these findings. Because we tested relations between concurrent changes in 12-step involvement and substance use, we cannot make conclusions about causal relationships, but other elements of our design and findings enhance the plausibility of causal conclusions . Our measures did not differentiate between different types of 12-step meetings , which could have helped explain the lack of findings for drug use outcomes, and future work might benefit from more detailed measures of 12-step involvement. Also, because our 12-step measures were relatively brief, there may have been important aspects of these behaviors we did not consider.
Finally, while the results have important implications for the broader population of individuals with substance dependence and MDD, replication in other samples and settings is needed.Both opioid dependent and opioid-independent forms of SIA have been identified. These mechanisms are differentially activated according to stressor parameters and duration . SIA elicited by intermittent foot shock is blocked by opioid antagonists , whereas SIA elicited by continuous foot shock is blocked by cannabinoid antagonists . We recently demonstrated that this nonopioid form of SIA is mediated by mobilization of two endocannabinoids, 2-arachidonoylglycerol and anandamide, in the dorsal midbrain . Opioid and nonopioid SIA share similar neuroanatomical substrates. For example, opioid and cannabinoid receptors populate brain regions regulating nociceptive responding, such as the periaqueductal gray and the raphe nuclei of the medulla. Like opioids, cannabinoids modulate distinct circuits within the midbrain PAG and the brainstem rostral ventromedial medulla . The competitive CB1 antagonist/ inverse agonist SR141716A microinjected into either the dorsolateral PAG or RVM also attenuates SIA. By contrast, inhibition of endocannabinoid hydrolysis at these sites enhances SIA . These data support the existence of supraspinal sites of endocannabinoid analgesic action. Cannabinoids produce antinociception through spinal as well as supraspinal mechanisms . The antinociceptive and electrophysiological effects of cannabinoids are attenuated following spinal transection. Nonetheless, a long-lasting residual antinociception remains in spinally transected mice , suggesting the existence of spinal sites of endocannabinoid analgesic action. These data are consistent with the presence of CB1 receptors in the spinal dorsal horn . Intrathecally-administered cannabinoids also produce antinociception and suppress noxious stimulus-evoked neuronal activity in spinal nociceptive neurons , suggesting a functional role for spinal cannabinoid receptors in modulating nociceptive processing. Intrathecal administration of either rimonabant or CB1 antisense oligonucleotides also elicits hyperalgesia , suggesting that endocannabinoids may act tonically to suppress nociceptive responding. However, a physiological role for endocannabinoids at the spinal level has not been identified. Both 2-AG and anandamide fully qualify as endocannabinoids .