ABSTRACT
Despite the prevalent worldwide abuse of stimulants, such as amphetamines and cocaine, no medications are currently approved for treating this serious public health problem. Both preclinical and clinical studies suggest that the opioid antagonist naltrexone (NTX) is effective in reducing the abuse liability of amphetamine, raising the question of whether similar positive findings would be obtained for cocaine. The purpose of this study was to evaluate the ability of oral NTX to alter the cardiovascular and subjective effects of D-amphetamine (D-AMPH) and cocaine (COC). Non-treatment-seeking COC users (N=12) completed this 3-week inpatient, randomized, crossover study. Participants received 0, 12.5, or 50 mg oral NTX 60 min before active or placebo stimulant administration during 10 separate laboratory sessions. Oral AMPH (0, 10, and 20 mg; or all placebo) was administered in ascending order within a laboratory session using a 60-min interdose interval. Smoked COC (0, 12.5, 25, and 50 mg; or all placebo) was administered in ascending order within a laboratory session using a 14-min interdose interval. Active COC and AMPH produced dose-related increases in cardiovascular function that were of comparable magnitude. In contrast, COC, but not AMPH, produced dose-related increases in several subjective measures of positive drug effect (eg, high, liking, and willingness to pay for the drug). NTX did not alter the cardiovascular effects of AMPH or COC. NTX also did not alter positive subjective ratings after COC administration, but it did significantly reduce ratings of craving for COC and tobacco during COC sessions. These results show that (1) oral AMPH produces minimal abuse-related subjective responses in COC smokers, and (2) NTX reduces craving for COC and tobacco during COC sessions. Future studies should continue to evaluate NTX as a potential anti-craving medication for COC dependence.
Subject(s)
Central Nervous System Stimulants/pharmacology , Cocaine-Related Disorders/physiopathology , Cocaine-Related Disorders/psychology , Cocaine/pharmacology , Dextroamphetamine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Naltrexone/pharmacology , Narcotic Antagonists/pharmacology , Administration, Oral , Adult , Cardiovascular System/drug effects , Central Nervous System Stimulants/administration & dosage , Cocaine/administration & dosage , Cross-Over Studies , Dextroamphetamine/administration & dosage , Dopamine Uptake Inhibitors/administration & dosage , Double-Blind Method , Female , Humans , Male , Middle Aged , Naltrexone/administration & dosage , Narcotic Antagonists/administration & dosage , SmokingABSTRACT
AIM: To estimate the general and racial/ethnic specific cumulative probability of remission from nicotine alcohol cannabis or cocaine dependence, and to identify predictors of remission across substances. DESIGN: Data were collected from structured diagnostic interviews using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version. SETTING: The 2001-2002 National Epidemiological Survey of Alcohol and Related Conditions (NESARC) surveyed a nationally representative sample from US adults (n = 43,093) selected in a three-stage sampling design. PARTICIPANTS: The subsamples of individuals with life-time DSM-IV diagnosis of dependence on nicotine (n = 6937), alcohol (n = 4781), cannabis (n = 530) and cocaine (n = 408). MEASUREMENTS: Cumulative probability estimates of dependence remission for the general population and across racial/ethnic groups. Hazard ratios for remission from dependence. FINDINGS: Life-time cumulative probability estimates of dependence remission were 83.7% for nicotine, 90.6% for alcohol, 97.2% for cannabis and 99.2% for cocaine. Half of the cases of nicotine, alcohol, cannabis and cocaine dependence remitted approximately 26, 14, 6 and 5 years after dependence onset, respectively. Males, Blacks and individuals with diagnosis of personality disorders and history of substance use comorbidity exhibited lower hazards of remission for at least two substances. CONCLUSIONS: A significant proportion of individuals with dependence on nicotine, alcohol, cannabis or cocaine achieve remission at some point in their life-time, although the probability and time to remission varies by substance and racial/ethnic group. Several predictors of remission are shared by at least two substances, suggesting that the processes of remission overlap. The lower rates of remission of individuals with comorbid personality or substance use disorders highlight the need for providing coordinated psychiatric and substance abuse interventions.
