Subjective and behavioral effects of diazepam depend on its rate of onset

Abstract

This study addressed the assumption that rate of onset affects the euphorigenic effects of drugs. Drugs with rapid onset are commonly thought to be more euphorigenic than drugs with slower onset, but this idea has rarely been studied directly. Nine healthy male social drinkers, with no history of drug- or alcohol-related problems, participated in three sessions. On each session they received oral doses of placebo (PLAC), diazepam in a rapid onset condition (FAST), or diazepam in a slow onset condition (SLOW). In the FAST condition, they received a single 20 mg dose, whereas in the SLOW condition they received six 4 mg doses administered at 30-min intervals. Plasma levels of diazepam and desmethyldiazepam, subjective effects (including measures of euphoria), psychomotor performance and vital signs were monitored throughout each session. Although the FAST and SLOW conditions led to similar peak plasma levels of drug, the peak was attained earlier in the FAST condition (61 min versus 220 min). Subjects' scores on a measure of euphoria (MBG scale of the ARCI) were significantly higher in the FAST condition compared to the SLOW and PLAC conditions. Subjects exhibited significantly more behavioral signs of intoxication and greater psychomotor impairment in the FAST condition. Sedative effects of the drug were similar in magnitude, but the effects lasted slightly longer in the FAST condition. On several measures diazepam produced similar effects in the two conditions (e.g., ratings of strength of drug effect). These data provide limited support for the notion that a faster rate of onset of drug effects is associated with greater euphoria.

The Rate of Cocaine Administration Alters Gene Regulation and Behavioral Plasticity: Implications for Addiction

“…First, rapidly administered drugs produce more immediate and more intense subjective pleasurable effects (de Wit et al, 1993;Hatsukami and Fischman, 1996). Indeed, subjective reports of drug liking are greatest when psychoactive drugs such as diazepam (de Wit et al, 1993), methylphenidate (Kollins et al, 1998), and cocaine (Fischman and Schuster, 1984;Abreu et al, 2001) are administered rapidly. Second, the rapid administration of cocaine is reported to enhance its reinforcing efficacy.…”

Differential Effects of Passive Immunization with Nicotine-Specific Antibodies on the Acute and Chronic Distribution of Nicotine to Brain in Rats

“…Slower drug delivery to brain, in general, is associated with less intense and reinforcing effects (de Wit et al, 1993;Volkow et al, 2000). The reported efficacy of vaccination against nicotine in attenuating nicotine self-administration in rats, a setting that involves chronic repeated nicotine dosing similar to that used in the current study, supports the potential importance of this early effect (LeSage et al, 2006).…”

Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats

“…Likewise, oral administration of immediate-release methylphenidate produced subjective and cardiovascular effects, while the sustained-release methylphenidate formulation only produced changes in cardiovascular function (Kollins et al 1998). In another drug class, rapid-onset diazepam produced more euphoria, observable signs of intoxication, psychomotor impairment, and longer-lasting sedation as compared with slow-onset diazepam (de Wit et al 1993). In general, these studies demonstrate that rate of administration can alter the physiological, behavioral, and subjective effects of various classes of drugs.…”