Initial development of a brief assessment of cocaine demand.

Cocaine demand is a behavioral economic measure assessing drug reward value and motivation to use drug. The purpose of the current study was to develop a brief assessment of cocaine demand (BACD). Results from the BACD were compared with self-report measures of cocaine use. Participants consisted of treatment-seeking individuals with cocaine use disorder (N = 22). Results revealed that indices of brief demand were significantly associated with various self-report measures of cocaine use. Overall, these results support the utility of a BACD for assessing cocaine demand.

Behavioral economic analysis of the effects of N-substituted benztropine analogs on cocaine self-administration in rats.

RATIONALE AND OBJECTIVES: Benztropine (BZT) analogs and other atypical dopamine uptake inhibitors selectively decrease cocaine self-administration at doses that do not affect responding maintained by other reinforcers. Those effects were further characterized in the current study using a behavioral economic assessment of how response requirement (price) affects reinforcers obtained (consumption) in rats. METHODS: Two groups of rats were trained to press levers with food (45-mg pellet) or cocaine (0.32 mg/kg/injection) reinforcement under fixed-ratio (FR) 5-response schedules. In selected sessions, the FR requirement was increased (5-80) during successive 20-min components to determine demand curves, which plot consumption against price. An exponential function was fitted to the data to derive the consumption at zero price (Q 0) and the rate of decrease in consumption (essential value, EV) with increased price. The BZT analogs, AHN1-055, AHN2-005, JHW007 (3.2-10 or 17.8 mg/kg, each), vehicle, or comparison drugs (methylphenidate, ketamine), were administered i.p. before selected demand-curve determinations. RESULTS: Consumption of cocaine or food decreased with increased FR requirement. Each drug shifted the demand curve rightward at the lowest doses and leftward/downward at higher doses. The effects on EV and Q 0 were greater for cocaine than for food-reinforced responding. Additionally, the effects of the BZT analogs on EV and Q 0 were greater than those obtained with a standard dopamine transport inhibitor, methylphenidate, and the NMDA antagonist, ketamine (1.0-10.0 mg/kg, each). With these latter drugs, the demand-curve parameters were affected similarly with cocaine and food-maintained responding. CONCLUSIONS: The current findings, obtained using a behavioral economic assessment, suggest that BZT analogs selectively decrease the reinforcing effectiveness of cocaine.

Costs and Effectiveness of Treating Homeless Persons with Cocaine Addiction with Alternative Contingency Management Strategies.

BACKGROUND: Between 1990 and 2006 in Birmingham, Alabama USA, 4 separate randomized controlled studies, called "Homeless 1" through "Homeless 4", treated cocaine substance abuse among chronically homeless adults, largely black men, many with non-psychotic mental health problems. The 4 studies had 9 treatment arms that used various counseling methods plus, in some arms, the provision of housing and work therapy usually with a contingent requirement of urine-test verified abstinence from substances. Participants in the abstinent-contingent arms who lapsed on abstinence were removed from housing and sent to an evening public shelter from which they were daily transported to day treatment until they returned to abstinence. AIMS OF THE STUDY: This paper compares the cost effectiveness of the treatment arms. METHODS: Societal cost per participant (in 2014 dollars) for each arm is defined as direct treatment cost plus cost of jail or hospital plus societal expense of public shelter use by lapsed participants. An untreated Base Case is defined as 5 percent abstinence with 95 percent usage of a public shelter. Incremental Cost Effectiveness Ratios (ICERs) for paired arms are defined as the change in cost per participant divided by the change in abstinence. Bootstrapping estimates confidence intervals. RESULTS: Average cost per participant at the end of 6 months of active treatment in 7 arms with comparable data ranged from USD 10,447 to USD 36,194 with corresponding average weeks abstinent ranging from 6.1 to 15.3 out of a possible 26 weeks. In contrast, the Base Case would cost USD 6,123 for 1.3 weeks of abstinence. Compared to the Base Case, the least expensive "DT2" treatment has an ICER of USD 901 (95% CI = USD 571 to USD 1,681) per additional week of abstinence and the most expensive "CMP4" has an ICER of USD 2,147 (95% CI = USD 1,701 to USD 2,848). Additionally, the Homeless 3 study found that the abstinent contingent housing (ACH3) treatment compared to the Non Abstinent Contingent Housing (NAC3), analogous to "Housing First", achieved better abstinence (12.1 v. 10 weeks) at higher average cost (USD 22,512 v. USD 17,541) yielding an ICER for this comparison of (USD 2,367, 95% CI=USD -10,587 to USD 12,467). Similar results are found at 12 months (6 months after active treatment). DISCUSSION: More intensive methods of counseling improved abstinence but 4 of the 7 treatments were inefficient ("dominated"). Bootstrapping shows that results are sensitive to which individuals were randomly assigned to each arm. A limitation of the analysis is that it does not consider the full societal cost of lost wages, crime costs beyond jail expenses and deterioration of neighborhood quality of life. Additionally, populations treated by Housing First programs may differ from the Birmingham Homeless studies in the severity of addiction or co-occuring psychological problems. IMPLICATIONS FOR TREATMENT: The Homeless studies show that abstinent contingent safe housing with counseling can substantially improve abstinence for homeless cocaine abusers. Incremental costs rise sharply with more intensive counseling; modest programs of counseling may be more cost effective in a stepped treatment strategy.

Comparing exponential and exponentiated models of drug demand in cocaine users.

Drug purchase tasks provide rapid and efficient measurement of drug demand. Zero values (i.e., prices with zero consumption) present a quantitative challenge when using exponential demand models that exponentiated models may resolve. We aimed to replicate and advance the utility of using an exponentiated model by demonstrating construct validity (i.e., association with real-world drug use) and generalizability across drug commodities. Participants (N = 40 cocaine-using adults) completed Cocaine, Alcohol, and Cigarette Purchase Tasks evaluating hypothetical consumption across changes in price. Exponentiated and exponential models were fit to these data using different treatments of zero consumption values, including retaining zeros or replacing them with 0.1, 0.01, or 0.001. Excellent model fits were observed with the exponentiated model. Means and precision fluctuated with different replacement values when using the exponential model but were consistent for the exponentiated model. The exponentiated model provided the strongest correlation between derived demand intensity (Q0) and self-reported free consumption in all instances (Cocaine r = .88; Alcohol r = .97; Cigarette r = .91). Cocaine demand elasticity was positively correlated with alcohol and cigarette elasticity. Exponentiated parameters were associated with real-world drug use (e.g., weekly cocaine use) whereas these correlations were less consistent for exponential parameters. Our findings show that selection of zero replacement values affects demand parameters and their association with drug-use outcomes when using the exponential model but not the exponentiated model. This work supports the adoption of the exponentiated demand model by replicating improved fit and consistency and demonstrating construct validity and generalizability. (PsycINFO Database Record

Modeling the structure and operation of drug supply chains: The case of cocaine and heroin in Italy and Slovenia.

Multiple layers of dealers connect international drug traffickers to users. The fundamental activity of these dealers is buying from higher-level dealers and re-selling in smaller quantities at the next lower market level. Each instance of this can be viewed as completing a drug dealing "cycle". This paper introduces an approach for combining isolated accounts of such cycles into a coherent model of the structure, span, and profitability of the various layers of the domestic supply chain for illegal drugs. The approach is illustrated by synthesizing data from interviews with 116 incarcerated dealers to elucidate the structure and operation of distribution networks for cocaine and heroin in Italy and Slovenia. Inmates' descriptions of cycles in the Italian cocaine market suggest fairly orderly networks, with reasonably well-defined market levels. The Italian heroin market appears to have more "level-jumpers" who skip a market level by making a larger number of sales per cycle, with each sale being of a considerably smaller weight. Slovenian data are sparser, but broadly consistent. Incorporating prices allows calculation of how much of the revenue from retail sales is retained by dealers at each market level. In the Italian cocaine market, both retail sellers and the international supply chain outside of Italy each appear to receive about 30-40% of what users spend, with the remaining 30% going to higher-level dealers operating in Italy (roughly 10% to those at the multi-kilo level and 20% to lower level wholesale dealers). Factoring in cycle frequencies permits rough estimation of the number of organizations at each market level per billion euros in retail sales, and of annual net revenues for organizations at each level. These analyses provide an approach to gaining insight into the structure and operation of the supply chain for illegal drugs. They also illustrate the value of two new graphical tools for describing illicit drug supply chains and hint at possible biases in how respondents describe their drug dealing activities.

Safety and tolerability of intranasal cocaine during phendimetrazine maintenance.

RATIONALE: Phendimetrazine appears to have limited abuse potential and reduces cocaine self-administration in preclinical studies. No human studies have evaluated the safety and tolerability of cocaine in combination with phendimetrazine, which is a necessary next step in evaluating the efficacy of phendimetrazine for treating cocaine use disorder. OBJECTIVES: This study determined the safety and tolerability of acute cocaine doses during chronic phendimetrazine treatment. METHODS: Ten subjects completed this within-subject, placebo-controlled, inpatient study. Subjects were maintained on ascending oral phendimetrazine doses (0, 70, 140, and 210 mg/day). After at least seven maintenance days at each dose, subjects received ascending doses of intranasal cocaine (0, 10, 20, 40, and 80 mg), separated by 90 min, within one session. RESULTS: Cocaine produced prototypical cardiovascular and subject-rated effects (e.g., increased blood pressure and ratings of like drug). The cardiovascular effects of cocaine alone were not clinically significant for an acute drug response (e.g., average heart rate did not approach tachycardia, 100 beats/min). Phendimetrazine enhanced peak heart rate following placebo and low cocaine doses, but these effects were also not clinically significant. Phendimetrazine was otherwise devoid of effects alone and did not alter the subject-rated effects of cocaine or hypothetical demand for cocaine on a purchase task. CONCLUSIONS: Cocaine was safe and well tolerated during maintenance on a threefold range of phendimetrazine doses. Given this safety profile, the reduced abuse potential of phendimetrazine and promising preclinical research, future human laboratory studies, and possibly clinical trials should evaluate the efficacy of phendimetrazine for reducing cocaine use.

Cost-effectiveness analysis of a continuing care intervention for cocaine-dependent adults.

INTRODUCTION: The study conducts a cost-effectiveness analysis (CEA) of a continuing care Telephone Monitoring and Counseling (TMC) intervention for adults diagnosed with cocaine dependence. Participants were randomly assigned to a control condition of intensive outpatient treatment only (treatment-as-usual, or TAU; N=108), or to one of two treatment conditions featuring TMC (N=106) and TMC plus incentives (TMC-plus; N=107). Follow-up assessments were conducted over a 2-year period. METHODS: Intervention and client costs were collected with the program and client versions of the Drug Abuse Treatment Cost Analysis Program (DATCAP). Effectiveness was measured as the number of days abstinent during follow-up. Secondary analyses consider alternative measures of effectiveness and the reduced societal costs of physical and mental health problems and criminal justice involvement. RESULTS: From the societal perspective, TMC dominates both TAU and TMC-plus as a cost-effective and cost-saving intervention. Results varied by substance-using status, however, with the subgroup of participants in TMC-plus that were using drugs at intake and early in treatment having the greatest number of days of abstinence and generating similar savings during follow-up than the TMC subgroup using drugs at intake. CONCLUSIONS: Telephone monitoring and counseling appears to be a cost-effective and potentially cost-saving strategy for reducing substance use among chronic substance users. Providing client incentives added to total intervention costs but did not improve overall effectiveness. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov Number: NCT00685659.

Cocaine's fall and marijuana's rise: questions and insights based on new estimates of consumption and expenditures in US drug markets.

AIMS: Drug policy strategies and discussions often use prevalence of drug use as a primary performance indicator. However, three other indicators are at least as relevant: the number of heavy users, total expenditures and total amount consumed. This paper stems from our efforts to develop annual estimates of these three measures for cocaine (including crack), heroin, marijuana and methamphetamine in the United States. METHODS: The estimates exploit complementary strengths of a general population survey (National Survey on Drug Use and Health) and both survey and urinalysis test result data for arrestees (Arrestee Drug Abuse Monitoring Program), supplemented by many other data sources. RESULTS: Throughout the 2000s US drug users spent in the order of $100 billion annually on these drugs, although the spending distribution and use patterns changed dramatically. From 2006 to 2010, the amount of marijuana consumed in the United States probably increased by more than 30%, while the amount of cocaine consumed in the United States fell by approximately 50%. These figures are consistent with supply-side indicators, such as seizures and production estimates. For all the drugs, total consumption and expenditures are driven by the minority of users who consume on 21 or more days each month. CONCLUSIONS: Even for established drugs, consumption can change rapidly. The halving of the cocaine market in five years and the parallel (but independent) large rise in daily/near-daily marijuana use are major events that were not anticipated by the expert community and raise important theoretical, research, and policy issues.

A cost-benefit/cost-effectiveness analysis of an unsanctioned supervised smoking facility in the Downtown Eastside of Vancouver, Canada.

BACKGROUND: Smoking crack involves the risk of transmitting diseases such as HIV and hepatitis C (HCV). The current study determines whether the formerly unsanctioned supervised smoking facility (SSF)-operated by the grassroot organization, Vancouver Area Network of Drug Users (VANDU) for the last few years-costs less than the costs incurred for health-care services as a direct consequence of not having such a program in Vancouver, Canada. METHODS: The data pertaining to the attendance at the SSF was gathered in 2012-2013 by VANDU. By relying on this data, a mathematical model was employed to estimate the number of HCV infections prevented by the former facility in Vancouver's Downtown Eastside (DTES). RESULTS: The DTES SSF's benefit-cost ratio was conservatively estimated at 12.1:1 due to its low operating cost. The study used 70% and 90% initial pipe-sharing rates for sensitivity analysis. At 80% sharing rate, the marginal HCV cases prevented were determined to be 55 cases. Moreover, at 80% sharing rate, the marginal cost-effectiveness ratio ranges from $1,705 to $97,203. The results from both the baseline and sensitivity analysis demonstrated that the establishment of the SSF by VANDU on average had annually saved CAD$1.8 million dollars in taxpayer's money. CONCLUSIONS: Funding SSFs in Vancouver is an efficient and effective use of financial resources in the public health domain; therefore, Vancouver Coastal Health should actively participate in their establishment in order to reduce HCV and other blood-borne infections such as HIV within the non-injecting drug users.

Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat.

Development of new treatments for drug addiction will depend on high-throughput screening in animal models. However, an addiction biomarker fit for rapid testing, and useful in both humans and animals, is not currently available. Economic models are promising candidates. They offer a structured quantitative approach to modeling behavior that is mathematically identical across species, and accruing evidence indicates economic-based descriptors of human behavior may be particularly useful biomarkers of addiction severity. However, economic demand has not yet been established as a biomarker of addiction-like behavior in animals, an essential final step in linking animal and human studies of addiction through economic models. We recently developed a mathematical approach for rapidly modeling economic demand in rats trained to self-administer cocaine. We show here that economic demand, as both a spontaneous trait and induced state, predicts addiction-like behavior, including relapse propensity, drug seeking in abstinence, and compulsive (punished) drug taking. These findings confirm economic demand as a biomarker of addiction-like behavior in rats. They also support the view that excessive motivation plays an important role in addiction while extending the idea that drug dependence represents a shift from initially recreational to compulsive drug use. Finally, we found that economic demand for cocaine predicted the efficacy of a promising pharmacotherapy (oxytocin) in attenuating cocaine-seeking behaviors across individuals, demonstrating that economic measures may be used to rapidly identify the clinical utility of prospective addiction treatments.

Cocaine use disorders and acute myocardial infarction, excess length of hospital stay and overexpenditure.

INTRODUCTION AND OBJECTIVES: To investigate the relationship between the prevalence of cocaine use disorders and acute myocardial infarction in patients aged ≥ 18 years and to estimate the influence of cocaine use disorders on mortality, excess length of stay, and overexpenditure among hospitalized patients with acute myocardial infarction. METHODS: Retrospective study of the minimum basic data set of 87 Spanish hospitals from 2008 to 2010. RESULTS: Among 5 575 325 admissions reviewed, there were 24 126 patients with cocaine use disorders and 79 076 cases of acute myocardial infarction. The incidence of acute myocardial infarction among patients with cocaine use disorders increased with age and reached a peak at 55 years to 64 years (P < .0001). Multivariate analysis showed that cocaine use disorders were more prevalent among patients with acute myocardial infarction independently of age, sex, other addictive disorders, and 30 other comorbidities (odds ratio = 3.0). Among patients with acute myocardial infarction, those with cocaine use disorders did not show an increase of in-hospital death, but did show excess length of hospital stay (1.5 days) and overexpenditure (382 euros). CONCLUSIONS: Cocaine use disorders are associated with acute myocardial infarction and increase the length of hospital stay and overexpenditure among acute myocardial infarction patients. Cessation of cocaine use among these patients should be one of the primary therapeutic goals after hospital discharge.

Cocaine behavioral economics: from the naturalistic environment to the controlled laboratory setting.

BACKGROUND: We previously observed that behavioral economic factors predict naturalistic heroin seeking behavior that correlates with opioid seeking in the experimental laboratory. The present study sought to replicate and extend these prior findings with regular cocaine users. METHODS: Participants (N=83) completed a semi-structured interview to establish income-generating and cocaine-purchasing/use repertoire during the past month. Questions addressed sources/amounts of income and expenditures; price (money and time) per purchase; and frequency/amounts of cocaine purchased and consumed. Naturalistic cocaine purchasing and use patterns were: (1) analyzed as a function of income quartile, (2) perturbed by hypothetical changes in cost factors to assess changes in purchasing/use habits, and (3) correlated with experimental cocaine seeking. RESULTS: Income was positively related to naturalistic cocaine seeking/use pattern (i.e., income elastic), and behaviors were cost-efficient and sensitive to supply chain. Income was unrelated to proportional expenditure on cocaine (≈55%) but inversely related to food expenditure. In all hypothetical scenarios (changes in income or dealer, loss of income assistance from government or family/friends, and increasing arrest risk when purchasing), the high-income group reported they would continue to use more cocaine daily than other groups. Number of laboratory cocaine choices significantly correlated with cocaine purchase time (positively) and purity of cocaine (negatively) in the naturalistic setting. CONCLUSIONS: These results replicate and extend findings with regular heroin users, demonstrate the importance of income, cost-efficiency and supply-mindedness in cocaine seeking/use, and suggest that this interview-based approach has good external validity.

Demand curves for hypothetical cocaine in cocaine-dependent individuals.

RATIONALE: Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. OBJECTIVES: This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. METHODS: Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. RESULTS: Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. CONCLUSIONS: Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use.

Can price get the monkey off our back? A meta-analysis of illicit drug demand.

Because of the increased availability of price data over the past 15 years, several studies have estimated the demand for illicit drugs, providing 462 estimates of the price elasticity. Results from estimating several meta-regressions reveal that these price elasticity estimates are influenced by a number of study characteristics. For instance, the price elasticity differs across drugs, with its absolute value being smallest for marijuana, compared with cocaine and heroin. Furthermore, price elasticity estimates are sensitive to whether demand is modeled in the short-run or the long-run, measures of quantity and price, whether or not alcohol and other illicit drugs are included in the specification of demand, and the location of demand. However, a number of other factors, including the functional form of demand, several specification issues, the type of data and method used to estimate demand, and the quality of the publication outlet, have less influence on the price elasticity.

An adaptive approach for identifying cocaine dependent patients who benefit from extended continuing care.

OBJECTIVE: Study tested whether cocaine dependent patients using cocaine or alcohol at intake or in the first few weeks of intensive outpatient treatment would benefit more from extended continuing care than patients abstinent during this period. The effect of incentives for continuing care attendance was also examined. METHOD: Participants (N = 321) were randomized to treatment as usual (TAU), TAU and telephone monitoring and counseling (TMC), or TAU and TMC plus incentives (TMC+). The primary outcomes were (a) abstinence from all drugs and heavy alcohol use and (b) cocaine urine toxicology. Follow-ups were at 3, 6, 9, 12, 18, and 24 months. RESULTS: Cocaine and alcohol use at intake or early in treatment predicted worse outcomes on both measures (ps ≤ .0002). Significant effects favoring TMC over TAU on the abstinence composite were obtained in participants who used cocaine (odds ratio [OR] = 1.95 [1.02, 3.73]) or alcohol (OR = 2.47 [1.28, 4.78]) at intake or early in treatment. A significant effect favoring TMC+ over TAU on cocaine urine toxicology was obtained in those using cocaine during that period (OR = 0.55 [0.31, 0.95]). Conversely, there were no treatment effects in participants abstinent at baseline and no overall treatment main effects. Incentives almost doubled the number of continuing care sessions received but did not further improve outcomes. CONCLUSION: An adaptive approach for cocaine dependence in which extended continuing care is provided only to patients who are using cocaine or alcohol at intake or early in treatment improves outcomes in this group while reducing burden and costs in lower risk patients.