Cocaine-specific antibodies blunt the subjective effects of smoked cocaine in humans

Abstract

Background: Rates of relapse among cocaine-dependent patients are high, and new treatment approaches are needed. Clinical data demonstrate that a cocaine vaccine (TA-CD) produces selective anticocaine antibodies, yet the impact of these antibodies on cocaine's direct effects is unknown. The objective of this human laboratory study was to measure the relationship between antibody titers and the effects of smoked cocaine on ratings of intoxication, craving, and cardiovascular effects.

Methods: Ten cocaine-dependent men not seeking drug treatment spent 2 nights per week for 13 weeks inpatient where the effects of cocaine (0 mg, 25 mg, 50 mg) were determined before vaccination and at weekly intervals thereafter. Two doses of TA-CD (82 microg, n = 4; 360 microg, n = 6) were administered at weeks 1, 3, 5, and 9.

Results: Peak plasma antibody levels, which were highly variable, significantly predicted cocaine's effects. Those individuals in the upper half of antibody production had an immediate (within 4 minutes of cocaine smoking) and robust (55%-81%) reduction in ratings of good drug effect and cocaine quality, while those in the lower half showed only a nonsignificant attenuation (6%-26%). Self-reported cocaine use while participants were outpatient tended to decrease as a function of antibody titer (p < .12). By contrast, higher antibody levels predicted significantly greater cocaine-induced tachycardia.

Conclusions: The TA-CD vaccine substantially decreased smoked cocaine's intoxicating effects in those generating sufficient antibody. These data support further testing of cocaine immunotherapy as a treatment for cocaine dependence.

Trial registration: ClinicalTrials.gov NCT00965263.

Conflict of interest statement

Financial Disclosures

Dr. Haney received consultant fees from Celtic Pharmaceuticals in 2007 (<$4000 total), and is a co-investigator on a NIDA-funded multi-site clinical trial to test TA-CD in cocaine-dependent patients. Dr. Haney has also received funding from Bristol-Meyers Squibb to conduct a study assessing the influence of aripiprazole on cocaine self-administration in humans. Dr. Foltin currently receives research support for an investigator-initiated protocol from Aztra Zeneca. Drs. Gunderson, Jiang, and Collins reported no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1

Individual plasma antibody levels as a function of time. Open symbols indicate individuals assigned to the Low Antibody group and filled symbols indicate those assigned to the High Antibody group. Arrows indicate when vaccinations were given (weeks 1, 3, 5, 9). All participants contributed data points for the first 13 weeks, while only a subset returned to the laboratory at followup and thereby contributed to week 26 (n=9), week 39 (n=6), and week 52 (n=8).

Figure 2

Peak VAS ratings of the Good Drug Effect cluster over 13 weeks as a function of cocaine dose (open symbols: 50 mg; filled symbols: 25 mg). Participants (n=10) were evenly divided into High Antibody (AB) and Low Antibody (AB) groups based on their peak antibody levels at Week 13. Vertical bars indicate standard error (SEM). Arrows on x-axis indicate timing of TA-CD vaccination.

Figure 3

Peak VAS ratings of the Good Drug Effect and Cocaine Quality clusters in Week 3 (open bar) and Week 13 (filled bar) as a function of cocaine dose in High and Low AB groups. Vertical bars indicate standard error (SEM). Asterisks indicate a significant difference between Week 3 and Week 13 (* p

Figure 4

VAS ratings of time course within a cocaine session for the Cocaine Quality cluster in Week 3 (open symbols) and Week 13 (filled circles) as a function of cocaine dose. Vertical bars indicate standard error (SEM).

Figure 5

Peak heart rate and plasma cocaine levels in Week 3 (open bar) and Week 13 (filled bar) as a function of cocaine dose in High and Low AB groups. Vertical bars indicate standard error (SEM). Asterisks indicate a significant difference between Week 3 and Week 13 (* p