Abstract
Cannabis is one of the most commonly used recreational drugs worldwide. Rrecent epidemiology studies have linked increased cardiac complications to cannabis use. However, this literature is predominantly based on case incidents and post-mortem investigations. This study elucidates the molecular mechanism of Δ9-tetrahydrocannabinol (THC), and its primary metabolites 11-Hydroxy-Δ9-THC (THC-OH) and 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THC-COOH). Treatment of cardiac myocytes with THC-OH and THC-COOH increased cell migration and proliferation (p < 0.05), with no effect on cell adhesion, with higher doses (250-100 ng/mL) resulting in increased cell death and significant deterioration in cellular architecture. Conversely, no changes in cell morphology or viability were observed in response to THC. Expression of key ECM proteins α-SMA and collagen were up-regulated in response to THC-OH and THC-COOH treatments with concomitant modulation of PI3K and MAPK signalling. Investigations in the planarian animal model Polycelis nigra demonstrated that treatments with cannabinoid metabolites resulted in increased protein deposition at transection sites while higher doses resulted in significant lethality and decline in regeneration. These results highlight that the key metabolites of cannabis elicit toxic effects independent of the parent and psychoactive compound, with implications for cardiotoxicity relating to hypertrophy and fibrogenesis.
Original language | English |
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Article number | 1401 |
Number of pages | 21 |
Journal | International Journal of Molecular Sciences |
Volume | 23 |
Issue number | 3 |
DOIs | |
Publication status | Published - 26 Jan 2022 |
Bibliographical note
Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.This article is an open access article distributed under the terms and
conditions of the Creative Commons Attribution (CC BY) license (https://
creativecommons.org/licenses/by/4.0/)
Keywords
- Cannabis
- Cardiac myocytes
- Cardiac toxicity
- Cytoskeleton
- Planaria
- THC
- cardiac myocytes
- cardiac toxicity
- planaria
- cytoskeleton
- cannabis
ASJC Scopus subject areas
- Molecular Biology
- Spectroscopy
- Catalysis
- Inorganic Chemistry
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry