Rats trained to press a lever for water on a fixed-ratio schedule (FR-10) developed tolerance to the disruptive effects of LSD and mescaline when the drugs were given daily before testing. Rats that received the same daily doses after each session did not become tolerant when later tested before a session. This suggests that tolerance to the performance-disrupting effects of these hallucinogens depends on the opportunity to practice the behavior while under the drug's influence, indicating a behavioral compensatory mechanism rather than a purely pharmacological one.
The authors argue that the term "dissociative" is outdated and imprecise for describing the subjective effects of ketamine and related drugs. Originally coined in 1966 to describe feelings of being in outer space or lacking limbs, the term does not capture the full range of psychedelic experiences measured by modern rating scales like the Bowdle Visual Analogue Scale and Hallucinogen Rating Scale. The authors suggest that drugs such as phencyclidine, dextromethorphan, salvinorin A, and nitrous oxide—often grouped as "dissociative anesthetics"—produce subjective effects that are not identical to each other and can resemble those of classic psychedelics like dimethyltryptamine or psilocybin. They recommend describing these drugs primarily by their mechanism of action, such as "the NMDA antagonist ketamine," rather than by the term dissociative.