Abuse liability reinforcement effects

Abuse potential abuse liability, reinforcing property, drug-seeking, craving, psychological effect. Intoxication acute pharmacological effects. 

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

Tolerance to nicotine s effects develops rapidly and most likely involves multiple processes, although the pattern and extent of tolerance development is not identical for all of nicotine s effects. It has been proposed that rapid tolerance or desensitization occurs to the behavioral or reinforcing effects of nicotine. These effects are of such a short duration that a smoker continually cycles between a sensitized and desensitized state. This notion is consistent with the fact that drugs with high abuse liability have a rapid onset and short duration of action. 

Negus SS Woods JH (1995). Reinforcing effects, discriminative stimulus effects, and physical dependence liability of buprenorphine. In Cowan A Lewis JW (eds.) Buprenorphine Combatting Drug Abuse with a Unique Opioid. New York Wiley-Liss, pp. 71-101... 

The euphoria, indifference to stimuli, and sedation usually caused by the opioid analgesics, especially when injected intravenously, tend to promote their compulsive use. In addition, the addict experiences abdominal effects that have been likened to an intense sexual orgasm. These factors constitute the primary reasons for opioid abuse liability and are strongly reinforced by the development of physical dependence. This disorder has been linked to dysregulation of brain regions mediating reward and stress (see Chapter 32). 

From the published clinical studies, it would appear that the partial agonists bretazenil and abercamil are less likely to cause physiological dependence, have lower reinforcing effects and a lower incidence of subjective effects associated with abuse liability than the conventional 1,4-benzodiazepine sedative-hypnotics. It is presently unclear whether the full agonists for the GABA-A receptor, zolpidem and zopiclone, offer a real advance in the treatment of insomnia although their adverse effect profiles and abuse liability may be lower than that of the conventional benzodiazepines. 

Abuse liability is the potential for a drug to produce positive effects that will reinforce a pattern of misuse, abuse, or diversion. To date, there is no evidence that the naltrexone component of combined morphine/ naltrexone will prevent or deter abuse. Novel abuse liability trials have been developed to assess the effects of combined morphine/naltrexone when tampered with. The pharmacodynamic effect of naltrexone in the setting of crushed morphine/naltrexone capsules was examined in two clinical trials an oral and an intravenous abuse liability trial [8]. These were conducted in nondependent recreational opioid abusers, as dependent, daily or habitual users would probably experience a withdrawal syndrome when exposed to the naltrexone component with crushed morphine/ naltrexone capsules. 

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