Skip to content

Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia

Amir I. A. Ahmed, G. A. H. van den Elsen, A. Colbers, C. Kramers, D. Burger, M. A. van der Marck, M. O. Olde Rikkert

Psychopharmacology March 11, 2015 DOI: 10.1007/s00213-015-3889-y (opens in new tab)

Read Full Text
Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind, placebo-controlled, crossover trial Peer reviewed
Sample size 10
Population Patients with dementia, mean age 77.3 ± 5.6
Intervention Tetrahydrocannabinol (THC)
Dose 0.75 mg and 1.5 mg twice daily
Duration 3 days per dose (with 4-day washout between doses)
Topics Cannabis
Key findings Low-dose oral THC (0.75 mg and 1.5 mg) produced only minor pharmacodynamic effects and few related adverse events in dementia patients, with dose-linear pharmacokinetics and wide interindividual variability.

Abstract

Data on safety, pharmacodynamics, and pharmacokinetics of tetrahydrocannabinol (THC) are lacking in dementia patients. In this randomized, double-blind, placebo-controlled, crossover trial, we evaluated the safety, pharmacodynamics, and pharmacokinetics of THC in ten patients with dementia (mean age 77.3 ± 5.6). For 12 weeks, participants randomly received oral THC (weeks 1–6, 0.75 mg; weeks 7–12, 1.5 mg) or placebo twice daily for 3 days, separated by a 4-day washout period. Only 6 of the 98 reported adverse events were related to THC. Visual analog scale (VAS) feeling high, VAS external perception, body sway-eyes-open, and diastolic blood pressure were not significantly different with THC. After the 0.75-mg dose, VAS internal perception (0.025 units; 95 % CI 0.010–0.040) and heart rate (2 beats/min; 95 % CI 0.4–3.8) increased significantly. Body sway-eyes-closed increased only after 1.5 mg (0.59°/s; 95 % CI 0.13–1.06). Systolic blood pressure changed significantly after both doses of THC (0.75 mg, −7 mmHg, 95 % CI −11.4, −3.0; 1.5 mg, 5 mmHg, 95 % CI 1.0–9.2). The median Tmax was 1–2 h, with THC pharmacokinetics increasing linearly with increasing dose, with wide interindividual variability (CV% up to 140 %). The mean Cmax (ng/mL) after the first dose (0–6 h) was 0.41 (0.18–0.90) for the 0.75-mg dose and 1.01 (0.53–1.92) for the 1.5-mg dose. After the second dose (6–24 h), the Cmax was 0.50 (0.27–0.92) and 0.98 (0.46–2.06), respectively. THC was rapidly absorbed and had dose-linear pharmacokinetics with considerable interindividual variation. Pharmacodynamic effects, including adverse events, were minor. Further studies are warranted to evaluate the pharmacodynamics and efficacy of higher THC doses in older persons with dementia.

Comparable studies

Other randomized controlled trials on cannabis, most cited first.

Study Year Design Participants
Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants 2012 Randomized controlled trial n = 48
Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... 2009 Double-blind, randomized, placebo-controlled crossover trial n = 15
Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects 2012 Randomized controlled trial n = 16
Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... 2009 Randomized controlled trial n = 15
Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use 2019 Randomized, double-blind, within-subjects crossover n = 14

Citations in the library

Cited by 3

Cites 3

Related reading

Explore topics

Cannabis