Probing Active Cocaine Vaccination Performance Through Catalytic and Noncatalytic Hapten Design.

Probing Active Cocaine Vaccination Performance through Catalytic and Noncatalytic Hapten Design.

J Med Chem. 2013 Apr 29;
Cai X, Whitfield T, Hixon MS, Grant Y, Koob GF, Janda KD

Presently, there are no FDA-approved medications to treat cocaine addiction. Active vaccination has emerged as one approach to intervene through the rapid sequestering of the circulating drug, thus terminating both psychoactive effects and drug toxicity. Herein, we report our efforts examining two complementary, but mechanistically distinct active vaccines, i.e., noncatalytic and catalytic, for cocaine treatment. A cocaine-like hapten GNE and a cocaine transition-state analogue GNT were used to generate the active vaccines, respectively. GNE-KLH (keyhole limpet hemocyannin) was found to elicit persistent high-titer, cocaine-specific antibodies and blunt cocaine-induced locomotor behaviors. Catalytic antibodies induced by GNT-KLH were also shown to produce potent titers and suppress locomotor response in mice; however, upon repeated cocaine challenges, the vaccine’s protecting effects waned. In depth kinetic analysis suggested that loss of catalytic activity was due to antibody modification by cocaine. The work provides new insights for the development of active vaccines for the treatment of cocaine abuse. HubMed – addiction


Alcohol Use Disorders and Mortality: A Systematic Review and Meta-Analysis.

Addiction. 2013 Apr 30;
Roerecke M, Rehm J

AIMS: To conduct a systematic review and meta-analysis on all-cause mortality in people with alcohol use disorders. METHODS: Using the MOOSE guidelines, studies were identified through MEDLINE, EMBASE, and Web of Science up to August, 2012. Prospective and historical cohort studies including a comparison of alcohol use disorder with a control group investigating all-cause mortality risk were included. RESULTS: This meta-analysis included 81 observational studies with 221 683 observed deaths among 853 722 people with alcohol use disorder. In men, the relative risk (RR) among clinical samples was 3.38 (95% confidence interval [CI]: 2.98-3.84); in women it was 4.57 (95% CI: 3.86-5.42). Alcohol use disorders identified in general population surveys showed a 2-fold higher risk compared with no alcohol use disorder in men; no data were available for women. RRs were markedly higher for those ?40 years old (8-fold in men, 13-fold in women) while still being at least 2-fold among those 60 years or older. CONCLUSIONS: Mortality in people with alcohol use disorders is markedly higher than previously thought. Women have generally higher mortality risks than men. Among all people with alcohol use disorders, people in younger age groups and people in treatment show substantially higher mortality risk than others in that group. HubMed – addiction


Validation of self-reported cannabis dose and potency: an ecological study.

Addiction. 2013 Apr 30;
van der Pol P, Liebregts N, de Graaf R, Korf DJ, van den Brink W, van Laar M

AIMS: To assess reliability and validity of self-reported cannabis dose and potency measures. DESIGN: Cross-sectional study comparing self-reports with objective measures of amount of cannabis and THC concentration. SETTING: Ecological study with assessments at participants’ home or in a coffee shop. PARTICIPANTS: Young adult frequent cannabis users (n=106) from the CanDep study. MEASUREMENTS: The objectively measured amount of cannabis per joint (dose in grams) was compared with self-reported estimates using a prompt card and average number of joints made from one gram of cannabis. In addition, objectively assessed THC concentration in participant’s cannabis was compared with self-reported level of intoxication, subjective estimate of cannabis potency, and price per gram of cannabis. FINDINGS: Objective estimates of doses per joint (0.07-0.88 grams/joint) and cannabis potency (1.1-24.7%) varied widely. Self-reported measures of dose were imprecise, but at group level average dose per joint was accurately estimated with the number of joints made from one gram (limit of agreement (loa) = -0.02 gram, 95% confidence interval (CI) = -0.29; 0.26), whereas the prompt card resulted in serious underestimation (loa = 0.14 gram, 95% CI = -0.10; 0.37). THC concentration in cannabis was associated with subjective potency (‘average’ 3.77% (P=0.002) and ‘(very) strong’ 5.13% more THC (P<0.001) than '(very) mild' cannabis) and with cannabis price (about 1% increase in THC concentration per euro spent on one gram of cannabis, P<0.001), but not with level of intoxication. CONCLUSIONS: Self-report measures relating to cannabis use appear at best to be weakly associated with objective measures. Of the self-report measures, number of joints per gram, cannabis price and subjective potency have at least some validity. HubMed – addiction