Discriminative Stimulus Effects of Hallucinogenic Drugs: a Possible Relation to Reinforcing and Aversive Effects

The subjective effects of drugs, such as euphoria or dysphoria, can be studied using the drug discrimination procedure. Over the past two decades, abuse of hallucinogenic club drugs like PCP, MDMA, LSD, and ketamine has increased, especially among younger people, but the mechanisms behind their discriminative stimulus effects remain unclear. This review of recent animal research identifies at least two plausible mechanisms: one mediated mainly by 5-HT2 receptors, and another mediated through sigma-1 (σ1)-receptor chaperone regulated by an endogenous hallucinogenic ligand.

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Abstract

The subjective effects of drugs are related to the kinds of feelings they produce, such as euphoria or dysphoria. One of the methods that can be used to study these effects is the drug discrimination procedure. Many researchers are trying to elucidate the mechanisms that underlie the discriminative stimulus effects of abused drugs (e.g., alcohol, psychostimulants, and opioids). Over the past two decades, the patterns of drug abuse have changed, so that club/recreational drugs such as phencyclidine (PCP), 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), and ketamine, which induce perceptual distortions, like hallucinations, are now more commonly abused, especially in younger generations. However, the mechanisms of the discriminative stimulus effects of hallucinogenic drugs are not yet fully clear. This review will briefly focus on the recent findings regarding hallucinogenic/psychotomimetic drug–induced discriminative stimulus effects in animals. In summary, recent research has demonstrated that there are at least two plausible mechanisms that can explain the cue of the discriminative stimulus effects of hallucinogenic drugs; one is mediated mainly by 5-HT2 receptors, and the other is mediated through sigma-1 (σ1)-receptor chaperone regulated by endogenous hallucinogenic ligand. Keywords:: discriminative stimulus effect, hallucinogen, serotonin, sigma-1 (σ1) receptor