Cannabis use patterns and perception of acute pain during brief abstinence: sex-dependent associations with circulating cannabinoid levels

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]