Faculty Bibliography

In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combination with naloxone. Peak concentration (Cmax) and area under the concentration-time curves (AUCs) increased for both buprenorphine and naloxone with escalating doses. Significant differences were found across the range of doses administered for dose-adjusted Cmax for both tablet formulations and for the dose-adjusted AUCs for the buprenorphine-naloxone tablets. For both formulations, the maximal buprenorphine-induced decreases in respiratory rate and pupil diameter did not vary significantly across doses. Several of the subjective effects of buprenorphine did not increase as the dose of buprenorphine administered was increased. These findings are consistent with the ceiling effect associated with the partial agonist actions of buprenorphine. They also indicate a lack of dose proportionality for buprenorphine sublingual tablets, at least during the times at which levels of this agent are highest.

Chronic food restriction increases exploratory behavior, cognitive function, and the rewarding effects of abused drugs. Recently, striatal neuroadaptations that may be involved in these effects were observed. Specifically, D-1 dopamine (DA) receptor agonist challenge produced stronger activation of extracellular signal-regulated kinase (ERK), calcium-calmodulin-dependent kinase II (CaMKII), and the nuclear transcription factor cAMP response element binding protein (CREB) in nucleus accumbens (NAc) of food-restricted (FR) relative to ad libitum fed (AL) rats. Further, when FR rats were injected intracerebroventricularly (i.c.v.) with vehicle (saline) they displayed stronger activation of c-Jun N-terminal protein kinase (JNK), ERK and CaMKII than did AL rats. It is not known to what extent the latter effects represent the basal state of FR rats or an amplified response to the brief handling involved in the i.c.v. injection procedure. Using Western blotting it was found that basal phospho-JNK is higher in caudate-putamen (CPu) and NAc of FR relative to AL rats. Interestingly, brief handling decreased phospho-JNK levels in FR subjects. Basal phospho-ERK1/2 also tended to be elevated in CPu and NAc of FR rats but the elevation was not significant. However, phospho-MEK--the activated kinase upstream of ERK1/2--was significantly elevated in NAc of FR rats. Neither ERK1/2 nor MEK were activated by brief handling. CaMKII was selectively activated by handling in NAc of FR rats, suggesting a state-dependent response to a salient event. Given the established involvement of mitogen-activated protein kinase (MAPK) and CaMKII in synaptic plasticity, learning and memory, the increase in basal phospho-MEK and hyperresponsiveness of CaMKII in NAc may represent adaptive cellular responses to persistent negative energy balance that facilitate associative learning in connection with food-seeking

The authors reviewed the empirical literature concerning the use of twelve-step programs and treatments by patients with co-occurring substance use disorders and other psychiatric disorders. Strong evidence was found that dually diagnosed individuals (DDI), with the possible exception of those with psychotic disorders, attend twelve-step programs at rates comparable to non-DDI. Twelve-step involvement is consistently associated with improved substance use outcomes. Although there have been numerous clinical trials involving twelve step-oriented interventions for DDI, most of the studies suffered from substantial methodological limitations. More work is needed to determine what kinds of twelve-step treatments and programs are effective for various types of patients and elucidate the mechanisms by which these approaches facilitate recovery.

Methadone and buprenorphine are treatments for heroin-dependent patients. Methadone is available through highly-regulated treatment centers while buprenorphine was approved in 2002 for prescription by certified physicians. Just prior to the approval of buprenorphine, we conducted a random postal survey of 770 physicians in New York City to determine willingness to prescribe methadone or buprenorphine for heroin-dependent patients to be picked up at a pharmacy. Among 247 respondents, 36.3% would consider prescribing methadone and 17.9% were unsure, while 25.8% would consider prescribing buprenorphine and 31.8% were unsure. Willingness to prescribe methadone or buprenorphine was associated with more recent year of licensure (p = 0.044; p = 0.033), working in a hospital or clinic as opposed to an office setting (p = 0.009; p = 0.024), and being the director of a clinic or program (p = 0.031; p = 0.008). This preliminary study suggests that a substantial proportion of New York City physicians would prescribe methadone or buprenorphine to heroin-dependent patients.

This article examines individual and social factors associated with initiation of illicit drug injection, with a focus on racial differences. Data were derived from across-sectional survey of young injection and noninjection drug users in Baltimore, Maryland. Participants were aged 15 to 30 and had initiated use of heroin, cocaine, and/or crack within the prior five years. Bivariate and multivariate logistic regression models were used to identify correlates of injection initiation. Of 579 drug users, 73% were injectors, 56% were male, and 41% were African American. In a multivariate model controlling for age, correlates of injection initiation were: being an African American male [Adjusted Odds Ratio (AOR): 0.08; 95% Confidence Interval (CI): 0.04, 0.17] or female (AOR = 0.12; 95%CI: 0.06, 0.27) compared to being a White male; younger age of first use of alcohol, marijuana, or inhalants (AOR=0.73; 95%CI: 0.65, 0.82); shorter time between first use of alcohol, marijuana, or inhalants and first use of heroin, crack, or cocaine (per year decrease, AOR=0.63, 95%CI: 0.40, 0.87); parental drug use (AOR=0.54, 95%CI: 0.32, 0.92); seeing someone inject prior to injection, AOR=1.96, 95%CI: 1.01, 3.50); and crack smoking (AOR=1.77, 95%CI: 1.07, 2.99). Early drug use patterns and drug exposure factors are associated with initiation injection. Interventions are needed that target noninjection drug users to prevent transition to injection drug use.

This article describes the debates leading to Puerto Rico's Mental Health Law of 2000, which defined addiction as a spiritual and social problem rather than a mental disorder, in order to trace three competing approaches to addiction in Puerto Rico: evangelist, biomedical, and harm-reductionist. Highlighting the ways in which the evangelist approach of Puerto Rican street ministries challenges the individualism underlying US faith-based initiatives and the punitive approach of the US War on Drugs, this article concludes that the virtues of the evangelist approach to addiction would be best supported by public funding for biomedical and harm-reduction approaches within a pluralistic system of treatment for addiction