We retrospectively reviewed health records of patients referred to the outpatient substance use program affiliated with the medical school. Information collected from the records included the patients’ background characteristics, reasons for ED visit, current substance use, mental health symptoms, buprenorphine use during their ED visit, and engagement in outpatient substance use treatment after ED discharge. Variables collected regarding outpatient substance use treatment included referral to the program during the index ED visit ; number of days between ED referral to the program and the first appointment ; attendance at the first scheduled appointment ; engagement with the program 30 days after the first scheduled appointment ; number of medical visits during the 30-day period ; and number of support visits during the 30-day period . Two of the authors conducted the health record reviews. One completed the initial review using a data-collection form that matched an Excel spreadsheet where the data were entered. The second reviewed the data after these were entered into the spreadsheet and did a comparison with the health record for these variables. Any discrepancy was corrected , or discussed to reach consensus . Baseline characteristics are summarized in Table 1. Patients were 86% male and 86% Caucasian with a mean age of 41.36 years . Besides opioids, patients reported current cocaine ,indoor cannabis growing, and alcohol use , along with symptoms of mood and anxiety disorders. Two patients had attempted suicide immediately before presenting to the ED; reported SI as a main reason for their visit. Buprenorphine use during the ED visit and engagement with outpatient substance use treatment after discharge are summarized in Table 2.
The doses of buprenorphine given in the ED ranged from 2-16 milligrams . None of the patients required an inpatient hospitalization for SI. All patients received a referral to an outpatient substance use treatment program, attended their first scheduled outpatient substance use treatment visit, and remained engaged with the outpatient substance use treatment program 30 days after their first visit. During the 30 days after their first visit, patients attended between 1-8 medical visits and 7-28 support visits at the outpatient substance use treatment program. This case series provides evidence for the feasibility and potential benefit of initiating buprenorphine in the ED to OUD patients who present with SI. For all the patients in our observational data, ED-initiated buprenorphine was associated with SI resolution, discharge from the ED, and engagement in outpatient substance use treatment. Given that SI rates remain high among OUD patients in outpatient methadone treatment, medication-based treatment by itself is unlikely to explain why the patients in our series experienced SI resolution.Although other factors besides buprenorphine initiation might have contributed to SI resolution, our results provide evidence that ED-initiated buprenorphine may be helpful in the treatment of OUD patients who present to the ED with SI. There could be several explanations for our findings. One explanation might involve buprenorphine’s pharmacology as a partial mu-opioid receptor agonist and kappa-opioid receptor antagonist. KOR activation is known to worsen depressive states, and buprenorphine’s antidepressant effect is thought to result from its KOR antagonism, a property methadone lacks.Studies have shown that there might be a role for buprenorphine to decrease SI for individuals with and without OUD, and it has been hypothesized that buprenorphine’s anti-suicidal property might result from its KOR antagonism.Although pharmacologically compelling, this mechanism of action remains speculative, and no evidence links the KOR to SI. Studies are needed to determine whether KOR activation causes or worsens SI.Another explanation might be that the ED referral to outpatient substance use treatment addressed the non-clinical issue of access to care for OUD treatment that had led these patients to experience SI.It is notable that all 14 patients attended their first outpatient appointment and remained in treatment for 30 days. Other studies of ED-initiated buprenorphine and referral to treatment have found lower percentages of OUD patients attending their first outpatient appointment.
Many patients did not have to wait long to start outpatient treatment: for the seven patients in our case series whose data are available, the range between the ED referral to outpatient treatment and attendance at the first appointment was 1-5 days. Moreover, by treating both the opioid withdrawal symptoms and SI, ED-initiated buprenorphine might have illustrated the benefits of continuing buprenorphine after ED discharge to these patients. It might be that the combination of a quick referral to outpatient substance use treatment and the experience of ED-initiated buprenorphine was enough to promote treatment engagement. Several limitations should be noted. This was a small case series of 14 patients who were not compared with a matched control group that did not receive buprenorphine. We did not examine changes in treatment engagement, opioid use, and SI after 30 days, so we cannot determine how these outcomes might have changed over a longer period of time. We were not able to access data on two variables that might have had an impact on engagement: how patients paid for treatment , or their degree of opioid withdrawal . It would be useful to know whether any patient experienced self-harm or attempted suicide after the 30 days following their first outpatient substance use visit. Future research should follow patients to examine whether self-harm or suicide attempts occur in the early days of outpatient substance use treatment to evaluate more fully the potential benefit of ED-initiated buprenorphine.In 2003, 31% of 12th graders reported getting drunk in the past month, 21% of 12th graders revealed using marijuana in the past month, and 6% of 12th graders disclosed daily marijuana use . Further, 40% of high school students who used marijuana in the past year met criteria for marijuana abuse or dependence . Moreover, 58% of adolescent drinkers also report marijuana use , and alcohol and marijuana use disorders are highly comorbid . Despite the prevalence of heavy alcohol and marijuana use in teenagers, it is unclear how such protracted use may affect brain functioning during youth, particularly as adolescent neuromaturation continues. Neuropsychological studies of teens with alcohol use disorders have reported decrements in language skills, problem solving, verbal and non-verbal retention, working memory, and visuospatial performance . In addition, we previously examined functional magnetic resonance imaging brain response during a spatial working memory task among teens with AUD and demographically similar non-abusing controls . Groups performed comparably on the task, but AUD teens demonstrated less brain response than controls in the midline precuneus/posterior cingulate, and more activation in bilateral posterior parietal cortex, suggesting subtle alcohol-related neural reorganization and compensation.
These neuropsychological and imaging findings suggest that heavy alcohol use during youth adversely affects frontal and parietal circuitry, but the additional impact of marijuana use is less well understood. Few studies have examined neurocognition in youths who use cannabis heavily. Neuropsychological assessments of substance use disordered teens have described marijuana use related deficits in learning and memory and attention . A longitudinal study of marijuana dependent adolescents demonstrated further short term memory decrements that persisted after 6 weeks of monitored abstinence . In addition, compared to individuals with adult-onset cannabis growing supplies use disorder and nonabusing controls, adolescent-onset cannabis use disordered adults showed attenuated electrophysiological response during selective attention , as well as smaller frontal and parietal volumes and increased cerebral blood flow . These studies indicate that heavy marijuana use during youth may adversely affect cognition and brain functioning, particularly short-term memory and attention, and raise questions about the integrity of frontal and parietal brain regions in adolescents with marijuana use disorders. In order to understand the neural correlates of concomitant heavy marijuana and alcohol use during youth, we assessed blood oxygen level dependent fMRI response among short term abstinent teens with comorbid marijuana and alcohol use disorders compared to AUD-only and non-abusing control teens reported in a previous study . We measured BOLD response during an SWM task that typically activates bilateral prefrontal and posterior parietal networks among adults and youths . Based on our earlier findings among AUD and control adolescents, we predicted that MAUD teens would show greater fMRI response than controls in regions sub-serving SWM, including prefrontal and bilateral posterior parietal cortices. We hypothesized further that MAUD teens would show more prefrontal and parietal activation than AUD youths, since we predicted that concurrent heavy marijuana and alcohol use would influence functioning more than protracted alcohol use alone. Flyers were distributed at local high schools to recruit adolescents, as described previously . We obtained written informed consent and assent from interested teens and their guardians, approved by the University of California San Diego Human Research Protections Program. Adolescents were administered a 90-min telephone screening interview to ascertain family history of substance use and psychiatric diagnoses using the Family History Assessment Module screener , lifetime substance use and abuse/dependence criteria using the Customary Drinking and Drug Use Record , and history of psychiatric disorders using the Diagnostic Interview Schedule for Children . Collateral interviews were administered to a guardian, usually a parent. Exclusion criteria included history of head injury with loss of consciousness >2 min, neurological or medical problems, learning disabilities, DSM-IV psychiatric disorder other than conduct disorder, current psychotropic medication use, significant maternal drinking or drug use during pregnancy, family history of bipolar I or psychotic disorder, and left handedness. Teens meeting criteria for conduct disorder were not excluded due to high comorbidity with substance use disorders . Eligible participants were ages 15−17, and groups were demographically similar . Controls had little experience with alcohol or other drugs. AUD adolescents met DSM-IV criteria for current alcohol abuse or dependence, but had limited experience with marijuana . Only two AUD teens disclosed marijuana use in the month before scanning . MAUD adolescents met DSM-IV criteria for both current marijuana and alcohol abuse or dependence, had ≥100 lifetime experiences with marijuana and had used ≥10 days/month in the three months before scanning. One MAUD participant reported stopping marijuana use 4 months prior to scanning; however, the urine toxicology screen indicated recent use. Twelve other MAUD teens reported marijuana use in the week before the scan, with last use 3.3 ± 1.7 days prior to scanning. Participants in each group had little experience with drugs other than alcohol and marijuana , had not used other drugs for 30 days prior to imaging, and had not used marijuana or alcohol for at least 48 h before scanning. Importantly, AUD and MAUD youths demonstrated similar alcohol use disorder characteristics . Both AUD and MAUD teens were primarily weekend heavy drinkers, as evidenced by an overall average 15.13 days since last drink and typical blood alcohol concentration reaching 0.107. Two AUD teens and one MAUD teen reported abstinence from alcohol in the month before scanning. AUD and MAUD teens displayed similar cigarette smoking patterns, but more MAUD teens had experiences with other drugs than AUD and control teens, although such use was limited . Although MAUD and AUD teens had higher rates of conduct disorder than control teens, severity was mild to moderate reflected by the normal range Child Behavior Checklist externalizing scores .Substance involvement and abuse/ dependence diagnoses were assessed using the CDDR . The CDDR collects lifetime and past 3-month information on alcohol, nicotine, and other drug use, and assesses DSM-IV abuse and dependence criteria, withdrawal symptomatology, and other negative consequences associated with substance use. The CDDR also obtains information necessary to estimate typical blood alcohol concentrations reached using the Widmark method, i.e. amount consumed, duration of drinking, height, weight, and gender . Strong internal consistency, test–retest, and inter-rater reliability have been demonstrated with adolescent CDDR assessments . The Timeline Follow back obtained detailed substance use patterns for the 30 days prior to scanning. On the day of the scanning session, all participants submitted samples for Breathalyzer and urine drug toxicology analyses. On the scan day, a neuropsychological battery assessed multiple cognitive domains, including attention, working memory, learning and memory, executive, visuospatial, and language functioning. The Beck Depression Inventory and state scale of the Spielberger State Trait Anxiety Inventory assessed mood at the time of scanning. The Stanford Sleepiness Scale measured alertness immediately before and after scanning with self-report ratings . Parents completed the CBCL .