Faculty Bibliography

Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms. TRIAL REGISTRATION: NCT02061293.

Aims: ED-based SBIRT for alcohol and drug use has the potential to impact public health greatly. Time and resource constraints limit implementation. Targeted intervention may be more efficient and practical. We hypothesized that we could use chief complaints to identify patients at highest risk of positive drug or alcohol use assessments. Methods: Using baseline data from NIDA CTN0047: SMARTED, free text chief complaints of 14,972 subjects from six sites were coded using a tested algorithm (Thompson, 2006). Multiple team members manually reviewed and further collapsed the chief complaint categorization to ensure agreement. We excluded subjects having missing data or complaints related to substance use and chief complaints stated by <15 subjects. Positive screens were defined as AUDIT-C > 4 for men and >3 for women (alcohol) and DAST > 2 (drugs). We ranked-ordered the chief complaints by their sensitivity and positive predictive value to (1) minimize the number of chief complaints and (2) assess the fewest number of ED patients. Our goal was to identify 75% of ED patients having positive assessments using these strategies. Results: The screening assessments were positive in 5805/14,561 (39.9%) for alcohol and 2454/14,494 (16.9%) for drugs. We collapsed the free-text chief complaints into 50 usable categories. To identify 75% of all ED patients having positive assessments using the first strategy would require including 19 chief complaints for alcohol screening and 20 chief complaints for drug screening. Adapting the second strategy, we would need to screen at least 71% and 68% of all ED patients for alcohol and drugs respectively to identify 75% of those having positive assessments. Conclusions: Based on this large, multicenter study, chief complaints provide little assistance in targeting SBIRT for alcohol or drug use in the ED

Aims: To determine if specific single-nucleotide polymorphisms (SNPs) in stress-related genes are associated with heroin addiction. Methods: Case-control hypothesis-driven association study of 112 SNPs from 26 stress-related genes. The sample consists of 852 case subjects and 238 controls. The case subjects are former heroin addicts with a history of at least 1 year of daily multiple uses of heroin, treated at a MMTP. European ancestry was verified by ancestry informative markers (AIMs). Association analysis was performed by logistic regression. Results: Nineteen SNPs in 9 genes (AVP, CRHR1, CRHR2, FKBP5, NR3C2, AVPR1A, GAL, GLRA1 and NPY1R) showed nominally significant association (p < 0.05) with heroin addiction. Two tightly linked FKBP5 SNPs, rs1360780 and rs3800373, from intron 2 and the 3' UTR, respectively, remained significant after correction for multiple testing (experiment-wise p = 3.0E-04;OR= 2.35; 95% CI, 1.5-3.7 and p = 1.6E-05; OR= 2.85; 95% CI, 1.8-4.6, respectively). Conclusions: The study provides evidence for the association of FKBP5 SNPs with heroin addiction. These SNPs were previously associated with diverse affective disorders and showed functional differences in gene expression and stress response. The FKBP5 gene encodes a co-chaperone that regulates glucocorticoid sensitivity. The modulation of the stress response by FKBP5 may contribute to the development of opiate dependence and in turn FKBP5 may also mediate the abuse potential of opioids. The study also corroborates our and others previous reports of association of GAL SNP rs694066 and AVPR1A SNPs rs11174811, rs1587097 and rs10784339 with specific general drug addictions and suggests several new associations

Aims: Implementation of substance use screening in general medical settings is hindered by the lack of a brief yet precise and comprehensive screening tool that is compatible with clinical workflows. To address this need, we developed the Substance Use Brief Screen (SUBS); a 4-item screener for tobacco, alcohol, and drug use (illicit and prescription) that is self-administered and may be easily integrated with electronic health records. Methods: Adult patients were recruited consecutively in the waiting area of an urban safety net primary care clinic. The SUBS was self-administered in English on touchscreen tablet computers. Reference standard measures of unhealthy substance use and substance use disorders were then administered, including self reported measures and saliva drug tests. The SUBS was compared against the reference standards to determine its sensitivity, specificity, and area under the curve (AUC) for each substance class. Results: Among the 390 participants, rates of past year use reported on the SUBS were 37% tobacco, 43% alcohol (4+ drinks/day), 20% illicit drugs, and 12% prescription drugs. Sensitivity and specificity of the SUBS for detecting past year unhealthy use were: tobacco 99% and 91% (AUC = .95); alcohol 94% and 68% (AUC = .81); drugs (illicit or prescription) 84% and 89% (AUC = .86). Sensitivity was lower for prescription drugs (57%) than for illicit drugs (78%). For detecting a substance use disorder, sensitivity and specificity were: tobacco 100% and 73% (AUC = .87); alcohol 93% and 64% (AUC = .79); drugs 85% and 82% (AUC = .84). Conclusions: The SUBS accurately identified unhealthy tobacco, alcohol, and drug use in this primary care sample, and had high sensitivity but lower specificity for identifying substance use disorders. Individuals screening positive on the SUBS should receive further assessment. Our findings support use of the SUBS for substance use screening in primary care, but additional tools may be needed for prescription drugs

Ketamine is known within the medical field for its anesthetic properties, yet its unique psychedelic and antidepressant properties are being increasingly recognized. We document the case of a patient with bipolar I disorder and an extensive history of substance dependence who used large doses of ketamine (1-3 g) on a daily basis over a period of 5 years, and described acute antidepressant effects as well as diminished cravings for alcohol. While his use was untenable and ultimately led to an inpatient admission, it is notable that he did not experience a withdrawal syndrome nor did he have any observable cognitive deficits upon cessation of use. Such a unique drug profile suggests that further exploration of its risks and therapeutic potential in treating mood and addiction disorders is warranted. (Am J Addict 2015;24:7-9).

Individuals with alcohol use disorders (AUDs) have deficits in cognitive control, but how they change with treatment is unclear. Seven patients with AUD and anxiety from an open-label trial of disulfiram plus lorazepam performed a multisensory Stroop task during fMRI (both pre and post initiation of treatment), and were compared to nine healthy controls (HCs) (n = 16; Albuquerque, NM; years 2009-2012). Evoked BOLD signal and resting state functional connectivity were compared (HC vs. AUD; Scan 1 vs. Scan 2). AUD demonstrated hyperactivity and altered connectivity in the cognitive control network compared to HC, but treatment did not normalize function.

BACKGROUND: Drug addiction is influenced by genetic factors. AIM: To determine if genetic variants in the serotonergic and adrenergic pathways are associated with heroin and/or cocaine addiction. SUBJECTS & METHODS: The study examined 140 polymorphisms in 19 genes in 1855 subjects with predominantly European or African ancestries. RESULTS: A total of 38 polymorphisms (13 genes) showed nominal associations, including novel associations in S100A10 (p11) and SLC18A2 (VMAT2). The association of HTR3B SNP rs11606194 with heroin addiction in the European ancestry subgroup remained significant after correction for multiple testing (p corrected = 0.04). CONCLUSION: The study strengthens our previous findings of association of polymorphisms in HTR3A, HTR3B and ADRA1A. The study suggests partial overlap in genetic susceptibility between populations of different ancestry and between heroin and cocaine addiction.