A Case Report of Treatment-Resistant Agitation in Dementia With Lewy Bodies: Medical Marijuana as an Alternative to Antipsychotics.

Palliative care teams are often consulted to assist in treating persistent dementia-related behavioral issues. Delta-9-tetrahydrocannabinol (THC) offers an alternative to traditional antipsychotic drugs in the long-term management of dementia with behavioral change. We present the case of an 85-year-old man with dementia with Lewy bodies with worsening aggression refractory to antipsychotic management. Multiple regimens of antipsychotics failed both in the outpatient and inpatient settings. After exhausting other options and in the setting of worsening agitation, a tincture of THC was prescribed. After starting THC tincture, the patient's behavior rapidly improved, and he was discharged home to the care of his spouse. The challenges of prescribing and obtaining THC are discussed.

Adaptive Treatment for Youth With Substance Use and Depression: Early Depression Response and Short-term Outcomes.

OBJECTIVE: To investigate prevalence and predictors of early depression response (EDR) in adolescents with substance use and depression receiving cognitive-behavioral therapy (CBT) for substance use and to test the efficacy of supplemental CBT targeting depression (CBT-D) for non-EDR adolescents in an adaptive treatment approach. METHOD: At 2 sites, 95 youths (ages 14-21, mean [SD] = 17.4 [1.8]) with alcohol or cannabis use and depressive symptoms received up to 12 sessions of CBT for substance use over 14 weeks. Assessments were at baseline and weeks 4, 9, and 14. The Children's Depression Rating Scale-Revised was the primary depression measure, with a reduction of 50% or more on this scale at week 4 defining EDR. The primary substance use outcomes of alcohol use, heavy alcohol use, and cannabis use frequency were assessed via interview report on the Alcohol Consumption Questionnaire and the Drug Checklist. Urinalysis provided a secondary measure of cannabis use. Non-EDR adolescents were randomly assigned to supplemental CBT-D or enhanced treatment as usual (ETAU). RESULTS: Thirty-five adolescents (37%; 95% CI, 27%-47%) demonstrated EDR. Fewer days of cannabis use (odds ratio 0.977; 95% CI, 0.961-0.992) and absence of conduct disorder (odds ratio 0.149; 95% CI, 0.031-0.716) predicted EDR. Frequency of drinking (F1,82 = 11.09, η2 = 0.119, p = .001), heavy drinking (F1,82 = 19.91, η2 = 0.195, p < .0001), and cannabis use (F1,220 = 35.01, η2 = 0.137, p < .001) decreased over time for EDR, CBT-D, and ETAU adolescents, with EDR adolescents evidencing earlier lower cannabis use (F2,220 = 4.16, η2 = 0.036, p = .0169). Negative (clean) urine screens increased over time (F1,219 = 5.10, η2 = 0.023, p = .0249). Comparison of CBT-D and ETAU indicated that depression significantly decreased over time in both groups (F1,48 = 64.20, η2 = 0.572, p < .001), with no advantage for CBT-D. CONCLUSION: Approximately one-third of adolescents with substance use and depression attain EDR during substance use treatment. Less frequent cannabis use facilitates depression response. The relatively small sample may have precluded identification of additional EDR predictors. CLINICAL TRIAL REGISTRATION INFORMATION: Treatment for Teens With Alcohol Abuse and Depression; https://clinicaltrials.gov/; NCT02227589.

Role of Human NADPH Quinone Oxidoreductase (NQO1) in Oxygen-Mediated Cellular Injury and Oxidative DNA Damage in Human Pulmonary Cells.

Supplemental oxygen administration is frequently used in premature infants and adults with pulmonary insufficiency. NADPH quinone oxidoreductase (NQO1) protects cells from oxidative injury by decreasing reactive oxygen species (ROS). In this investigation, we tested the hypothesis that overexpression of NQO1 in BEAS-2B cells will mitigate cell injury and oxidative DNA damage caused by hyperoxia and that A-1221C single nucleotide polymorphism (SNP) in the NQO1 promoter would display altered susceptibility to hyperoxia-mediated toxicity. Using stable transfected BEAS-2B cells, we demonstrated that hyperoxia decreased cell viability in control cells (Ctr), but this effect was differentially mitigated in cells overexpressing NQO1 under the regulation of the CMV viral promoter, the wild-type NQO1 promoter (NQO1-NQO1), or the NQO1 promoter carrying the SNP. Interestingly, hyperoxia decreased the formation of bulky oxidative DNA adducts or 8-hydroxy-2'-deoxyguanosine (8-OHdG) in Ctr cells. qPCR studies showed that mRNA levels of CYP1A1 and NQO1 were inversely related to DNA adduct formation, suggesting the protective role of these enzymes against oxidative DNA injury. In SiRNA experiments entailing the NQO1-NQO1 promoter, hyperoxia caused decreased cell viability, and this effect was potentiated in cells treated with CYP1A1 siRNA. We also found that hyperoxia caused a marked induction of DNA repair genes DDB2 and XPC in Ctr cells, supporting the idea that hyperoxia in part caused attenuation of bulky oxidative DNA lesions by enhancing nucleotide excision repair (NER) pathways. In summary, our data support a protective role for human NQO1 against oxygen-mediated toxicity and oxidative DNA lesions in human pulmonary cells, and protection against toxicity was partially lost in SNP cells. Moreover, we also demonstrate a novel protective role for CYP1A1 in the attenuation of oxidative cells and DNA injury. Future studies on the mechanisms of attenuation of oxidative injury by NQO1 should help in developing novel approaches for the prevention/treatment of ARDS in humans.

Retention and Treatment Outcome of Youth with Cannabis Use Disorder Referred By the Legal System.

BACKGROUND: Youth with Substance Use Disorders (SUDs) referred to treatment from the Juvenile Justice System (JJS) account for approximately half of the treatment admissions nationwide. The objective of this paper is to report a comparison of retention and outcomes for JJS referrals to those from the general community. METHODS: A total of 172 adolescents, 13-18 years of age, 83% males, 70% JJS referrals, diagnosed with DSM-IV Cannabis Use Disorder (CUD), enrolled in this outpatient, randomized, continued care study. Following a 7-session weekly motivational enhancement and cognitive behavioral therapy intervention (MET/CBT-7), only poor responders were randomized into a 10-week second phase of either an individualized enhanced CBT or an Adolescent Community Reinforcement Approach (ACRA) intervention. RESULTS: JJS referrals' retention rates were significantly higher than those of non-JJS referrals (X 2 (1) = 11.21, p < .01) at the end of Phase I (i.e. week 7). However, there was no difference in abstinence rates between the groups at the end of phase I or II and any of the quarterly additional follow-up assessments up to one year from treatment onset. CONCLUSIONS: Additional research examining how to capitalize on improved retention rates among youth JJS referrals is necessary in order to advance abstinence.

Goal commitment predicts cannabis use for adolescents in treatment.

Background: Commitment to change is an innovative potential mediator and mechanism of behavior change (MOBC) that has not been examined in adolescents with cannabis use. The Adolescent Substance Abuse Goal Commitment (ASAGC) questionnaire is a reliable and valid 2-scale measure developed to assess the adolescent's commitment to either abstinence or harm reduction model for adolescents, which in addition to decrease in negative consequences includes consumption reduction as a stated treatment goal. The objective of this paper is to examine the ASAGC's ability to predict adolescent substance use treatment outcome. Methods: During Sessions 3 and 9 of a 10-week treatment program, therapists completed the ASAGC for 170 adolescents 13-18 years of age with alcohol use disorders, the majority of whom (82%) were diagnosed with co-occurring cannabis use disorder (CUD). Results: Logistic regression analyses assessing goal commitment regarding cannabis use at Session 3 indicated that commitment to both abstinence and harm reduction predicted cannabis use at Session 3. However, only commitment to abstinence predicted later cannabis use (assessed at Session 9 and during aftercare). When goal commitment at Session 9 was examined, only commitment to abstinence predicted cannabis use, concurrently and longitudinally. These results indicated that adolescents who had higher scores for commitment to abstinence were less likely to be positive for cannabis use. In contrast, harm reduction was not a significant predictor of cannabis use. Conclusions: Findings demonstrate that goal commitment consistently predicts cannabis use treatment outcome. Commitment to abstinence specifically is a salient predictor for concurrent and future cannabis use. Further prospective study is necessary to determine whether harm reduction may be an attainable goal for some youth given normative delayed neurodevelopmental processes of inhibitive behaviors.

Adolescents with cannabis use disorders: Adaptive treatment for poor responders.

OBJECTIVE: Treatment response as measured by both retention and abstinence attainment rates for adolescents with cannabis use disorders (CUD) has been unsatisfactory. This study tested the hypothesis that adaptive treatment (AT) will improve outcomes for poor responders (PR) to evidence-based practice interventions. METHOD: A total of 161 adolescents, 13-18years of age, diagnosed with DSM-IV CUD, enrolled in this outpatient, randomized, AT study. Following a 7-session weekly motivational enhancement and cognitive behavioral therapy intervention (MET/CBT-7) only poor responders (defined as failing to achieve abstinence at week seven for any reason) were randomized into a 10-week AT phase of either an individualized enhanced CBT or an Adolescent Community Reinforcement Approach (ACRA) intervention. Good responders (GR) enrolled only in follow-up assessments starting at the completion of the AT phase (week 17). RESULTS: Eighty adolescents (50%) met the criterion for poor response to treatment. Thirty seven percent of poor responders completed the AT phase and 27% of them achieved abstinence. There was no significant difference in retention and abstinence rates between the AT conditions. Although the majority of GR relapsed by week 17, they significantly differed from PR both for drug use (71% vs. 91%, respectively; p<0.05) and reporting to scheduled assessment on that week (78% vs. 54%, respectively; p<0.01). CONCLUSION: Continuity of care to achieve abstinence among poor responders remains a therapeutic necessity and a research challenge. Examining innovative AT designed interventions including potential integrative approaches should be further studied in order to improve treatment outcomes.