Ketamine Does Not Mimic or Block the Subjective Effects of THC or Morphine in Rats

In drug discrimination tests, no form of ketamine (R-, S-, or racemic) substituted for the subjective effects of either morphine or THC. Ketamine also did not block the discriminative effects of either drug. However, all ketamine forms suppressed response rates when combined with THC, suggesting a sedative interaction.

Rats were trained in a two-lever drug discrimination paradigm to distinguish morphine (6.4 mg/kg) or THC (3 mg/kg) from vehicle. Ketamine isoforms were then tested at 5, 10, and 30 mg/kg as substitutes for or blockers of the training drugs. Standard positive controls (fentanyl for morphine, rimonabant for THC) confirmed the assay was working.

Ketamine is increasingly used alongside opioids and cannabinoids in both clinical pain management and recreational settings. This study suggests ketamine does not produce cannabis-like or opioid-like subjective effects, but the sedative interaction with cannabinoids warrants attention.

As ketamine therapy expands for depression and chronic pain, and cannabis use increases broadly, understanding how these drugs interact becomes increasingly important for clinical safety and for understanding polydrug use patterns.

Drug discrimination in rats measures subjective-like effects but cannot perfectly predict human experience. The doses used may not cover all clinically relevant scenarios. The sedation interaction was measured indirectly through response rate suppression.