Cannabis use patterns and perception of acute pain during brief abstinence: sex-dependent associations with circulating cannabinoid levels
Year: 2026
Type: article
Study design: Observational Study
Abstract: RATIONALE: The impact of cannabis use patterns on pain perception during abstinence remains unclear. OBJECTIVES: This study examined whether cannabis use frequency and weekly delta-9-tetrahydrocannabinol (THC) exposure are associated with pain perception and circulating cannabinoid levels during biochemically verified brief abstinence. METHODS: Healthy adults (N = 75; 29 females, 46 males; ages 21–55) reporting past-month cannabis use were categorized into “Occasional” (< 5 days/week) or “Frequent” (≥ 5 days/week) groups. Weekly THC exposure (mg) was estimated from self-reported frequency, quantity, and THC concentration of cannabis used. After ≥ 12 h of biochemically verified abstinence, blood samples were analyzed by LC-MS/MS for THC, 11-OH-THC, 11-COOH-THC, anandamide (AEA), 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA). Participants completed Cold Pressor Test pain threshold and tolerance assessments and subjective pain ratings. Mixed-effects models examined relationships between cannabis use patterns, circulating cannabinoids, and pain outcomes. RESULTS: Frequent users (N = 37; 6.2 ± 1.4 days/week) exhibited higher plasma THC, 11-OH-THC, and 11-COOH-THC than occasional users (N = 38; 2.6 ± 1.6 days/week; all p < 0.05). Weekly THC exposure positively correlated with plasma THC and 11-COOH-THC (p < 0.05). Females showed higher AEA, OEA, and PEA than males (p < 0.05), independent of use patterns. Pain outcomes did not differ by cannabis use frequency or weekly THC exposure and were not associated with cannabinoid levels. CONCLUSIONS: Neither cannabis use frequency nor weekly THC exposure related to acute pain perception during brief abstinence, though weekly THC exposure was positively associated with circulating THC and 11-COOH-THC levels. Short-term abstinence did not produce hyperalgesia in healthy cannabis users. Studies with longer abstinence periods and in clinical populations are needed to elucidate cannabis-related pain mechanisms. [ClinicalTrials.gov ID: NCT04385082; 5/11/2020]
Source: Psychopharmacology
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Awards: Sex-dependent effects of cannabis: Assessing abuse-related and pharmacokinetic differences between men and women, Age-and sex-dependent pharmacodynamics and pharmacokinetics of oral and smoked delta-9-THC, UCLA Training Program in the Translational Neuroscience of Drug Addiction (TNDA), IRACDA at UCLA, Analgesic and subjective effects of terpenes administered alone and in combination with THC: Potential THC- and opioid-sparing effects of myrcene and ß-caryophyllene, UCLA Clinical and Translational Science Institute, Impact of Cannabinoid Across the Lifespan (ICAL)
OpenAlex ID: W7154995738