Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2015 Jul;232(14):2587-95.
doi: 10.1007/s00213-015-3889-y. Epub 2015 Mar 11.

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

Amir I A Ahmed  1 , Geke A H van den Elsen, Angela Colbers, Cornelis Kramers, David M Burger, Marjolein A van der Marck, Marcel G M Olde Rikkert
Affiliations
Clinical Trial

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

Amir I A Ahmed et al. Psychopharmacology (Berl). 2015 Jul.

Abstract

Rationale: Data on safety, pharmacodynamics, and pharmacokinetics of tetrahydrocannabinol (THC) are lacking in dementia patients.

Methods: 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.

Results: 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 T max was 1-2 h, with THC pharmacokinetics increasing linearly with increasing dose, with wide interindividual variability (CV% up to 140%). The mean C max (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 C max was 0.50 (0.27-0.92) and 0.98 (0.46-2.06), respectively.

Conclusions: 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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Overview of the treatment period (THC and placebo were administered at random) (this is an example of random allocation of treatment)
Fig. 2
Fig. 2
The mean concentration time profiles of THC and 11-OH-THC for both the 0.75- and 1.5-mg doses over 24 h
Fig. 3
Fig. 3
Individual pharmacokinetic parameter graphs
See this image and copyright information in PMC

References

    1. Ahmed AI, van den Elsen GA, Colbers A, van der Marck MA, Burger DM, Feuth TB, Olde Rikkert MG, Kramers C. Safety and pharmacokinetics of oral delta-9- tetrahydrocannabinol in healthy older subjects: a randomized controlled trial. Eur Neuropsychopharmacol. 2014;24:1475–1482. doi: 10.1016/j.euroneuro.2014.06.007. - DOI - PubMed
    1. Ahmed AI, van den Elsen GA, van der Marck MA, Olde Rikkert MG. Medicinal use of cannabis and cannabinoids in older adults: where is the evidence? J Am Geriatr Soc. 2014;62:410–411. doi: 10.1111/jgs.12661. - DOI - PubMed
    1. Arons AM, Krabbe PF, van der Wilt GJ, Olde Rikkert MG, Adang EM. Visual analogue scales: scale recalibration by patients with dementia and their proxies. Qual Life Res. 2013;22:979–986. doi: 10.1007/s11136-012-0226-3. - DOI - PMC - PubMed
    1. Aso E, Ferrer I. Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic. Front Pharmacol. 2014;5:37. doi: 10.3389/fphar.2014.00037. - DOI - PMC - PubMed
    1. Aso E, Palomer E, Juvés S, Maldonado R, Muñoz FJ, Ferrer I. CB1 agonist ACEA protects neurons and reduces the cognitive impairment of AβPP/PS1 mice. J Alzheimers Dis. 2012;30:439–459. - PubMed

Publication types

LinkOut - more resources