TY - JOUR
T1 - Guanfacine attenuates adverse effects of dronabinol (THC) on working memory in adolescent-onset heavy Cannabis users
T2 - A pilot study
AU - Mathai, David S.
AU - Holst, Manuela
AU - Rodgman, Christopher
AU - Haile, Colin N.
AU - Keller, Jake
AU - Hussain, Mariyah Z.
AU - Kosten, Thomas R.
AU - Newton, Thomas F.
AU - Verrico, Christopher D.
N1 - Publisher Copyright:
© 2018, American Psychiatric Association. All rights reserved.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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 taskwhile participants were maintained on placebo (p=0.017) but not on guanfacine (p=0.709); comparedwithplacebo, therewere 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.
AB - 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 taskwhile participants were maintained on placebo (p=0.017) but not on guanfacine (p=0.709); comparedwithplacebo, therewere 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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U2 - 10.1176/appi.neuropsych.16120328
DO - 10.1176/appi.neuropsych.16120328
M3 - Article
C2 - 28641496
AN - SCOPUS:85042355836
SN - 0895-0172
VL - 30
SP - 66
EP - 76
JO - Journal of Neuropsychiatry and Clinical Neurosciences
JF - Journal of Neuropsychiatry and Clinical Neurosciences
IS - 1
ER -