These results underscore the importance of assessing drug-taking behavior in the human laboratory. For example, using a choice procedure during which participants had several opportunities to self-administer oral d-amphetamine (5 mg) or placebo, Johanson and Uhlenhuth reported that d-amphetamine-related subjective effects were comparable in all subjects but did not predict choice to self-administer the drug. Results from studies indicating that drug-related subjective effects and self-administration can be dissociable highlight this point. Although these measures provide potentially useful information about the abuse potential of a given drug, they are indirectly related to actual drug-taking behavior and may not correspond with self-administration data. It is also important to note that previous comparisons of oral methamphetamine and d-amphetamine primarily examined drug-related effects on mood and/or drug discrimination. There have been no direct comparisons of these amphetamines using a route commonly associated with abuse. Thus, it is possible that potential differences between methamphetamine and d-amphetamine may only be detected following a route of administration associated with a faster onset of effects. The onset speed of drug-related effects is a critical determinant of the intensity of mood and behavioral effects of a drug. Recreational methamphetamine use is purportedly used in larger doses via routes of administration that produce a more rapid onset of effects (e.g., intranasal, intravenous, and smoked: ). It is unclear to what degree these findings generalize to illicit methamphetamine use. An important consideration of these studies, however, is that they compared relatively low oral doses (i.e., 2.5–30 mg). Ĭoncordant with the literature obtained with laboratory animals, direct comparisons of the effects of oral methamphetamine and d-amphetamine in humans indicate the drugs produce overlapping effects on measures of cardiovascular activity, mood, and drug discrimination. Finally, data from studies comparing the two amphetamines on measures believed to be predictive of abuse potential (i.e., drug discrimination and self-administration) indicate that equivalent doses of the drugs produced similar responses, further indicating that the drugs are equipotent. Furthermore, although some researchers observed that larger methamphetamine doses (e.g., 2.5–10 mg/kg) increased locomotor activity to a greater extent than d-amphetamine in mice, others reported that, at smaller doses (e.g., 0.5–1 mg/kg), the drugs were equipotent at activating locomotion. In contrast, others found that, although the amphetamines similarly increased dopamine in the rat nucleus accumbens, methamphetamine released dopamine in the prefrontal cortex less effectively than d-amphetamine. For example, Melega and colleagues observed that the drugs had equivalent pharmacokinetic profiles and similarly increased striatal dopamine in rats. It is important to note, however, that data from studies directly comparing the amphetamines in laboratory animals do not support the notion that methamphetamine is more potent. Consequently, methamphetamine may more readily cross the blood brain barrier, making it more potent than d-amphetamine. One possible explanation for the greater incidence of methamphetamine abuse is that illicit methamphetamine is more readily available due to its purported ease of synthesis.Īnother explanation is that the addition of the N-methyl group to the basic amphetamine structure makes methamphetamine more lipophilic compared to d-amphetamine. Treatment Episode Data Set, in 2007 methamphetamine users comprised approximately 96% of all amphetamine treatment admissions. Furthermore, epidemiological evidence indicates that methamphetamine abuse rates are greater than those of d-amphetamine. A comparable literature for d-amphetamine does not exist. For example, there is an extensive human literature suggesting that illicit methamphetamine produces cognitive impairments and psychological disturbances. It is possible that methamphetamine is infrequently used therapeutically because of the perception that it produces greater deleterious effects. Despite their structural similarities, d-amphetamine is commonly regarded as a safe and effective therapeutic, whereas methamphetamine is rarely prescribed. Methamphetamine is the N-methylated analog of d-amphetamine and both are FDA-approved for similar medical conditions. Methamphetamine and d-amphetamine have nearly identical chemical structures.
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