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 & Biobehavioral Reviews June 3, 2026 DOI: 10.1016/j.neubiorev.2026.106795 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 Δ9-tetrahydrocannabinol |
| Key findings | 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.
Comparable studies
Other systematic reviews and meta-analyses on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of cannabis use on outcomes of psychotic disorders: systematic review People with psychotic disorders, as examined in 13 longitudinal studies | 2008 | Systematic review | |
| The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample Patients with established schizophrenia (meta-analysis: 572) and patients with... | 2010 | Meta-analysis and cross-sectional observational study | n = 700 |
| Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review | 2020 | Systematic review | |
| Neuroimaging in cannabis use: a systematic review of the literature Cannabis users and controls in neuroimaging studies | 2009 | Systematic review | |
| Human Laboratory Studies on Cannabinoids and Psychosis. Healthy human subjects and individuals with schizophrenia | 2016 | Systematic review |
Citations in the library
Cites 36
- Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Current Pharmaceutical Design September 12, 2012
- Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Psychopharmacology May 1, 2019
- Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users Psychopharmacology October 30, 2010
- Neurophysiological functioning of occasional and heavy cannabis users during THC intoxication Psychopharmacology October 5, 2011
- Cannabis smoking impairs driving performance on the simulator and real driving: a randomized, double‐blind, placebo‐controlled, crossover trial Fundamental and Clinical Pharmacology May 12, 2018
and 31 more in the library