The dose-dependent psychomotor effects of intravenous delta-9-tetrahydrocannabinol (Δ⁹-THC) in humans

Abstract

Background: Binding studies have demonstrated that levels of the cannabinoid receptor type-1 are highest in the basal ganglia and cerebellum, two areas critical for motor control. However, no studies have systematically examined the dose-related effects of intravenous delta-9-tetrahydrocannabinol, the primary cannabinoid receptor type-1 partial agonist in cannabis, on broad domains of psychomotor function in humans. Aims: Therefore, three domains of psychomotor function were assessed in former cannabis users (cannabis abstinent for a minimum of three months; n=23) in a three test-day, within-subject, double-blind, randomized, cross-over, and counterbalanced study during which they received intravenous delta-9-tetrahydrocannabinol (placebo, 0.015 mg/kg, and 0.03 mg/kg). Methods: Gross motor function was assessed via the Cambridge Neuropsychological Test Automated Battery Motor Screening Task, fine motor control via the Lafayette Instrument Grooved Pegboard task, and motor timing via a Paced Finger-Tapping Task. In addition, the Cambridge Neuropsychological Test Automated Battery Rapid Visual Processing Task was utilized to determine whether delta-9-tetrahydrocannabinol-induced motor deficits were confounded by disruptions in sustained attention. Results/outcomes: Delta-9-tetrahydrocannabinol resulted in robust dose-dependent deficits in fine motor control (Grooved Pegboard Task) and motor timing (Paced Finger-Tapping Task), while gross motor performance (Motor Screening Task) and sustained attention (Rapid Visual Processing Task) were unimpaired. Interestingly, despite the observed dose-dependent increases in motor impairment and blood levels of delta-9-tetrahydrocannabinol, subjects reported similar levels of intoxication in the two drug conditions. Conclusions/interpretation: These data suggest that while several domains of motor function are disrupted by delta-9-tetrahydrocannabinol, subjective feelings of intoxication are dissociable from cannabinoid-induced psychomotor effects. Results are discussed in terms of the potential neural mechanisms of delta-9-tetrahydrocannabinol in motor structures.

The Effect of Long-Term Aronia melanocarpa Extract Supplementation on Cognitive Performance, Mood, and Vascular Function: A Randomized Controlled Trial in Healthy, Middle-Aged Individuals

“…Previous studies have reported improvements in both hands after strength training in healthy elderly people [38] and music training in children [39], focusing more particularly on hand dexterity. Nevertheless, different outcomes for both hands have also been observed in studies determining motor function following sleep deprivation among medical personnel [40] and after an intravenous delta-9-tetrahydrocannabinol challenge [41]. Inconsistent with our results, these two latter studies reported statistically significant alterations for the non-dominant hand, but not for the dominant hand.…”

Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans

“…The timing of the blood samples was selected to maximize the likelihood of detecting changes in drug-induced gene expression. A battery of subjective and cognitive assessments was administered to capture the effects and safety of THC 23,25,26 (See Methods).…”

Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans

“…A battery of subjective and cognitive assessments were administered to capture the effects and safety of THC. 18, 20, 21 We profiled the four PBMC samples (two pre-THC and two post-THC) on the 10X Genomics platform. 22 Quality control processing yielded a total of 15,973 cells and 21,430 genes for analyses ( Figure 1a ).…”