This study shows a plateau on buprenorphine effects, consistent with its partial agonist classification, and that single doses of buprenorphine up to 70 times the recommended analgesic dose are well tolerated by nondependent humans.
We find that the reinstatement model has adequate criterion validity in the broad sense of the term, as evidenced by the fact that reinstatement in laboratory animals is induced by conditions reported to provoke relapse in humans. The model's criterion validity in the narrower sense, as a medication screen, seems promising for relapse to heroin, nicotine, and alcohol. For relapse to cocaine, criterion validity has not yet been established primarily because clinical studies have examined medication's effects on reductions in cocaine intake rather than relapse during abstinence. The model's construct validity faces more substantial challenges and is yet to be established, but we argue that some of the criticisms of the model in this regard may have been overstated.
SR141716 blocked acute psychological and physiological effects of smoked marijuana without altering THC pharmacokinetics. These findings confirm, for the first time in humans, the central role of CB1 receptors in mediating the effects of marijuana.
Context
In Ecological Momentary Assessment (EMA), participants electronically report their activities and moods in their daily environments in real time, enabling a truly prospective approach to the study of acute precipitants of behavioral events. EMA has greatly enhanced the study of tobacco addiction, but has rarely been attempted in individuals with cocaine or heroin addiction.
Objective
To prospectively monitor the acute daily-life precipitants of craving for, and use of, cocaine and heroin.
Design
Cohort study.
Participants
A volunteer sample of 114 cocaine- and heroin-abusing outpatients who were being treated with methadone provided EMA data on handheld computers for 14,918 person-days (mean 130.9 days per participant, range 6–189). Of those 114, a total of 102 (63 men, 39 women) provided acute pre-craving or pre-use data and were thus included in the present analyses.
Main outcome measures
Changes in reports of mood and exposure to 12 putative drug-use triggers at random intervals during the five hours preceding each self-reported episode of drug craving or use, analyzed via repeated-measures logistic regression (SAS GLIMMIX macro).
Results
During the five hours preceding cocaine use or heroin craving, most of the 12 putative triggers showed linear increases. Cocaine use was most robustly associated with increases in reports of “Saw Drug” (p<.0001), “Tempted to use out of the blue” (p<.0001), “Wanted to see what would happen if I used” (p<.0001), and “Good mood” (p<.0001). Heroin craving was most robustly associated with increases in reports of “Sad” (p=.0002) and “Angry” (p<.011). Cocaine craving and heroin use showed few reliable associations with any of the putative triggers assessed.
Conclusions
These findings confirm that polydrug-abusing individuals can provide behavioral data in their daily environments using handheld computers, and that those data can reveal orderly patterns, including prospectively detectable harbingers of craving and use, which may differ across drugs.
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