Abstract
Cannabis use is rising fastest among older adults in the U.S., and pain is among the most common reasons they use it. No trial, however, has measured the trade-off between the analgesic and abuse-related effects of {Delta}9-tetrahydrocannabinol ({Delta}9-THC) in this population. In a randomized, double-blind, placebo-controlled trial, 20 adults aged 65 and older were assigned to oral {Delta}9-THC (placebo, 5, 10 mg) or vaporized {Delta}9-THC (placebo, 2, 4 mg) across three eight-hour sessions in counterbalanced order. We assessed laboratory-evoked pain sensitivity using quantitative sensory testing, abuse liability using subjective drug effects and reinforcement value, and also sampled plasma {Delta}9-THC and 11-OH-THC. Analgesia and abuse liability outcomes were measured repeatedly within each session. On a pain sensitivity index, oral 5 mg relieved pain relative to placebo (p=.040), although the oral arm's overall dose effect was not significant (p=.108); oral 10 mg and both vaporized doses did not differ from placebo. Subjective effects increased with dose and were greatest after vaporization, whereas reinforcement value increased only after vaporized 4 mg. After oral 5 mg, analgesia exceeded placebo at every assessment (60-360 min), while its pleasurable effects peaked at 150 min. Vaporized {Delta}9-THC produced pleasurable effects within 30 min but did not significantly change thermal pain sensitivity. While abuse liability tracked {Delta}9-THC exposure, analgesia showed no significant association, and all adverse events occurred at vaporized 4 mg. These findings suggest dose and route selection may help maximize {Delta}9-THC analgesia while minimizing abuse liability, a strategy that warrants evaluation in clinical populations.
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