Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential

• Published in: Psychopharmacology 2015-03, Vol.232 (5), p.871-883
• Main Authors: Reissig, Chad J., Harrison, Joseph A., Carter, Lawrence P., Griffiths, Roland R.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Alprazolam; Alprazolam - administration & dosage; Biomedical and Life Sciences; Biomedicine; Care and treatment; Cognition - drug effects; Comparative analysis; Cross-Over Studies; Diagnosis; Dosage and administration; Dose-Response Relationship, Drug; Double-Blind Method; Drug abuse; Drug delivery systems; Female; Humans; Inhaled medication; Male; Mental Recall - drug effects; Middle Aged; Neuropsychological Tests; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Psychomotor Performance - drug effects; Psychopharmacology; Risk factors; Substance-Related Disorders - psychology; Surveys and Questionnaires; Young Adult
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-014-3721-0

Rationale Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. Objectives This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Methods Placebo, inhaled alprazolam (0.5, 1, and 2 mg), and oral alprazolam (1, 2, and 4 mg) were administered under double-blind, double-dummy conditions using a crossover design in 14 healthy participants with histories of drug abuse. Participant and observer ratings and behavioral and cognitive performance measures were assessed repeatedly during 9-h sessions. Results Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer-lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 min after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose–response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., “drug liking”) were similar across the two routes. On other measures (e.g., sedation and performance), the routes were equipotent. Conclusions The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low.