Guanfacine attenuates adverse effects of dronabinol (THC) on working memory in adolescent-onset heavy cannabis users: A pilot study
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The cannabinoid-1 receptor (CB1R) agonist Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, adversely effects working memory performance in humans. The α2A-adrenoceptor (AR) agonist guanfacine improves working memory performance in humans. The authors aimed to determine the effects of short-term (6 days) treatment with guanfacine on adverse cognitive effects produced by THC. Employing a double-blind, placebo-controlled crossover design, the cognitive, subjective, and cardiovascular effects produced by oral THC (20 mg) administration were determined twice in the same cannabis users: once after treatment with placebo and once after treatment with guanfacine (3 mg/day). Compared with performance at baseline, THC negatively affected accuracy on spatial working memory trials while participants were maintained on placebo (p=0.012) but not guanfacine (p=0.497); compared with placebo, accuracy was significantly (p=0.003, Cohen's d=-0.640) improved while individuals were treated with guanfacine. Similarly, compared with baseline, THC increased omission errors on an attentional task while participants were maintained on placebo (p=0.017) but not on guanfacine (p=0.709); compared with placebo, there were significantly (p=0.034, Cohen's d=0.838) fewer omissions while individuals were maintained on guanfacine. Although THC increased visual analog scores of subjective effects and heart rate, these increases were similar during treatment with placebo and guanfacine. THC did not significantly affect performance of a recognition memory task or blood pressure while individuals were maintained on either treatment. Although preliminary, these results suggest that guanfacine warrants further testing as a potential treatment for cannabis-induced cognitive deficits.
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Guanfacine treatment reduces cognitive impairment induced by THC.
“Guanfacine treatment was shown to reduce the cognitive impairment induced by THC (Mathai et al., 2018)”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Mathai et al., 2018
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Rice, T., Grasso, J., Dembar, A., Caplan, O., Cohen, A., & Coffey, B. J. (2018) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2018.29154.bjc · Cited by 4 · see citing works
Kittirattanapaiboon, C., SHOPTAW, S. J., Mayes, T. L., Jha, M. K., Ghitza, U. E., & Trivedi, M. H. (2026) · Journal of Substance Use and Addiction Treatment · doi:10.1016/j.josat.2026.209994 · Cited by 1 · see citing works
Molinero, K., & Hinckley, J. D. (2023) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2023.03.007 · Cited by 1 · see citing works
Ferreira, J. V., Correa, L. C., da Costa, D. C., & Hage-Melim, L. I. D. S. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.82184
Attentional and memory processes underlying addiction
Yates, J. R. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-90578-7.00007-4
Neurological Effects of Cannabis
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- Authors
- Mathai, D. S., Holst, M., Rodgman, C., Haile, C. N., Keller, J., Hussain, M. Z., Kosten, T. R., Newton, T. F., & Verrico, C. D.
- Affiliations
- Baylor College of Medicine (US)
- ORCID
- Venue
- The Journal of Neuropsychiatry and Clinical Neurosciences
- Published
- 2018-01
- Volume
- 30
- Issue
- 1
- Pages
- 66-76
- ISSN
- 0895-0172 (ISSN-L)
- 1545-7222
- OpenAlex
- W2685068722
- Cited by
- 12
- References
- 85
- Citations by year
- 2026: 1 · 2023: 3 · 2022: 2 · 2020: 2 · 2019: 3 · 2018: 1
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropsychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Keywords
- guanfacine, dronabinol, tetrahydrocannabinol, cannabis use, working memory, cognitive impairment, cannabinoid 1 receptor, alpha2A-adrenergic receptor, attention, subjective effects, heart rate, blood pressure, recognition memory
- MeSH terms
- Adolescent, Adult, Analysis of Variance, Blood Pressure, Double-Blind Method, Female, Heart Rate, Humans, Male, Marijuana Smoking, Memory Disorders, Memory, Short-Term, Middle Aged, Neuropsychological Tests, Pilot Projects, Dronabinol, Guanfacine, Cross-Over Studies, Young Adult, Adrenergic alpha-2 Receptor Agonists, Cannabinoid Receptor Agonists
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