Balancing Analgesic Effects and Abuse Liability in Older Adults: A Randomized, Placebo-Controlled Trial of Oral and Vaporized Δ9-Tetrahydrocannabinol
- 1Yale University School of Medicine
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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BibTeX
@misc{costa2026balancing,
title = {{Balancing Analgesic Effects and Abuse Liability in Older Adults: A Randomized, Placebo-Controlled Trial of Oral and Vaporized Δ9-Tetrahydrocannabinol}},
author = {G. P. A. Costa and R. Gueorguieva and M. M. Riggs and T. Dunlap and M. Sofuoglu and J. P. De Aquino},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.02.26367127},
url = {https://www.medrxiv.org/content/10.64898/2026.11.02.26367127v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Balancing Analgesic Effects and Abuse Liability in Older Adults: A Randomized, Placebo-Controlled Trial of Oral and Vaporized Δ9-Tetrahydrocannabinol
AU - G. P. A. Costa
AU - R. Gueorguieva
AU - M. M. Riggs
AU - T. Dunlap
AU - M. Sofuoglu
AU - J. P. De Aquino
PY - 2026
DA - 2026/11/02
PB - medRxiv
DO - 10.64898/2026.11.02.26367127
UR - https://www.medrxiv.org/content/10.64898/2026.11.02.26367127v1
AB - 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.
ER -