The subjective effects of △9-tetrahydrocannabinol: A systematic review and dose-response meta-regression.
Isabella Goodwin, Dominic Oliver, Edward Chesney, Alexandra Gaillard, Simiao Wang, Andrea Wong Koo, Kat Petrilli, Martine Skumlien, Amir Hossein Dakhili, Stina Wigroth, Stiliyana Obreshkova, Suhal Yusufzai, Ryan Vandrey, Michael Krausz, Tom P. Freeman, Philip Mcguire, John Strang, Valentina Lorenzetti, Amir Englund
Neuroscience and Biobehavioral Reviews September 1, 2026 DOI: 10.1016/j.neubiorev.2026.106795 (opens in new tab) via PubMed
Summary
AI-generated from the abstractA meta-analysis of 41 double-blind, placebo-controlled experiments involving 1,020 infrequent cannabis users found that acute THC administration increases feelings of high, anxiety, and tiredness, while decreasing alertness and contentedness, with no effect on calmness. Inhaled THC dose-dependently increased high and contentedness but decreased calmness, with greater consistency in high and contentedness at higher doses. On a 100-point scale, inhaling 5 mg THC increased high by 34.3 points, anxiety by 14.4, tiredness by 26.3, and calmness by 4.5, while decreasing alertness by 40.2 and contentedness by 71.0. Oral THC showed no significant subjective effects, though higher oral doses produced more consistent alertness. These findings can inform public health guidance on expected THC effects.
Study at a glance
| Characteristics | Systematic review and meta-analysis Randomized Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 1,020 |
| Population | Healthy individuals with infrequent cannabis use (<2 weekly; <100 lifetime) |
| Intervention | Δ9-tetrahydrocannabinol (THC) |
| Topics | Cannabis |
| Keywords | Meta-analysis Meta-regression Subjective effects |
| Key finding | Acute THC increases feelings of high, anxiety, and tiredness, and decreases alertness and contentedness, with inhaled but not oral dose affecting some subjective effects. |
Abstract
Global shifts towards the liberalisation of cannabis policies have increased the potency of cannabis products, alongside their accessibility, diversity, and the number of inexperienced cannabis consumers. There is a lack of systematic evidence on the subjective effects of cannabis' main psychoactive compound, Δ9-tetrahydrocannabinol (THC). We systematically reviewed and meta-analysed data from 41 randomised, double-blind, and placebo-controlled experimental studies on the acute subjective effects of THC in 1020 healthy individuals with infrequent cannabis use (<2 weekly; <100 lifetime). Pairwise meta-analyses estimating the mean difference of peak subjective effects between THC and placebo showed greater feelings of high, anxiety, and tiredness (all p < 0.001), lower alertness and contentedness (both p < 0.01), and no difference on calmness (p = 0.414). Meta-regressions of dose were stratified by inhaled and oral administration. Greater inhaled THC dose increased feeling high (b=1.06, p = 0.0024) and contentedness (b=1.06, p = 0.025), and decreased calmness (b=-0.96, p = 0.048); with no change in anxiety (b=-0.03, p = 0.845), tiredness (b=0.39, p = 0.129), or alertness (b=0.11, p = 0.837). Variability meta-analyses showed that greater inhaled dose of THC produced greater consistency between individuals in feeling high (b=-0.05, p = 0.021) and contentedness (b=-0.04, p < 0.0001). On a 100-point scale, inhaling 5 mg THC resulted in: increased high, anxiety, tiredness, and calmness by 34.3 (95%CI: 30.8-37.7), 14.4 (95%CI: 12.8-16.0), 26.3 (95%CI: 23.8-28.8), 4.5 (95%CI: -0.3-9.3), respectively; decreased alertness and contentedness by 40.2 (95%CI: -45.4--34.9) and 71.0 (95%CI: -75.7--66.4), respectively. Oral dose was not associated with any subjective effects (p > 0.05), although variability meta-analyses showed that greater oral dose of THC produced greater consistency between individuals in alertness (b=-0.13, p = 0.049). This evidence can inform public health efforts to guide consumers on the expected subjective effects of THC.