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Adolescents are more sensitive than adults to acute behavioral and cognitive effects of THC

Abstract

Increased cannabis availability has contributed to increased use with concomitant incidence of adverse effects. One risk factor for adverse drug reactions may be age. There is preclinical evidence that acute effects of delta-9-tetrahydrocannabinol (THC), the primary active constituent of cannabis, are greater during adolescence, but this has not been fully studied in humans. The present study sought to determine whether adolescent men and women are more sensitive than adults to acute THC. Adolescents aged 18–20 (N = 12) and adults aged 30–40 (N = 12), with less than 20 total lifetime uses of THC-containing products, received capsules of THC (7.5, 15 mg) and placebo across three study sessions in randomized order under double blind conditions. During each session, subjective, cardiovascular, behavioral, and EEG measures were obtained. Behavioral measures included Simple Reaction Time, Stop Task, Time Production and N-back and EEG measures included P300 amplitudes during an auditory oddball task and eyes-closed resting state. THC affected subjective state and heart rate similarly in both age groups. However, adolescents were more sensitive to performance impairing effects, exhibiting dose-dependent impairments on reaction time, response accuracy, and time perception. On EEG measures, THC dose-dependently decreased P300 amplitude in adolescents but not adults. Adolescents were more sensitive to behavioral and cognitive effects of THC, but not to cardiovascular effects or subjective measures. Thus, at doses that produce comparable ratings of intoxication, adolescents may exhibit greater cognitive impairment and alterations in brain function.

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Fig. 1: Mean (± SEM) behavioral measures after placebo (0 mg), 7.5 and 15 mg THC across adolescent and adult participants.
Fig. 2: P300 event-related potentials (ERPs) under the Pz electrode in responses to rare (oddball) auditory stimuli in the auditory oddball task. Stimuli presentation occurred at time zero.
Fig. 3: Time frequency analysis of event-related spectral perturbation (ERSPs) under the Pz electrode in responses to rare (oddball) auditory stimuli in the auditory oddball task.
Fig. 4: Effects of THC (7.5 and 15 mg) and placebo on oscillatory power during eyes-closed resting-state over the default mode network.

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Funding

This research was supported by the National Institutes of Health [DA02812]. CHM was supported by the National Institutes of Health [T32DA043469]. The authors declare no biomedical financial interests or potential conflicts of interest related to this project. HdW is or has been scientific advisor to PharmAla Biotech, Awakn Life Sciences, Gilgamesh Pharmaceuticals and Schedule I Therapeutics for projects unrelated to this study, and has received research support from the Beckley Foundation for an unrelated project.

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CHM for conception and design of the work; the acquisition, analysis, of data; and drafting of the manuscript. ZH for acquisition and analysis of data. RL for the interpretation of data; critical revision of manuscript for intellectual content. HdW for conception and design of the work; interpretation of data; critical revision of manuscript for intellectual content. All authors approved final manuscript for submission.

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Correspondence to Harriet de Wit.

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Murray, C.H., Huang, Z., Lee, R. et al. Adolescents are more sensitive than adults to acute behavioral and cognitive effects of THC. Neuropsychopharmacol. 47, 1331–1338 (2022). https://doi.org/10.1038/s41386-022-01281-w

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