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How Psychedelic or Hallucinogenic Drugs Work It works as a serotonin reuptake inhibitor , but the majority of the psychoactivity comes from its kappa-opioid receptor activation. This is the same mechanism used by salvia to produce intense, chaotic, and dissociative hallucinations that can be terrifying to even the most experienced psychonaut. One significant, but rare, consequence of chronic use of psychedelic drugs is the development of a disorder known as hallucinogen-induced persistent perception disorder. This disorder occurs when individuals who no longer use these drugs experience flashbacks weeks, months, or even years after their last use. Likewise, in humans, daily administration of the hallucinogenic amphetamine 2,5-dimethoxy-4-methylamphetamine also led to significant tolerance to the drug effect by day 3 (Angrist et al., 1974). In humans, cross-tolerance occurs between mescaline and LSD and between psilocybin and LSD (Isbell et al., 1961). Tolerance and cross-tolerance t...