Current and Potential Use of Biologically Active Compounds Derived from Cannabis sativa L. in the Treatment of Selected Diseases

Abstract

Cannabis sativa L. contains numerous compounds with antioxidant and anti-inflammatory properties, including the flavonoids and the cannabinoids, particularly Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabinoids have an effect on the endocannabinoid system (ECS), a cellular communication network, and are, hence, widely studied for medical applications. Epidiolex^®, a 99% pure oral CBD extract, has been approved by the FDA for the treatment of epilepsy. Nabiximols (Sativex) is an oromucosal spray containing equal volume of THC and CBD, and it is commonly used as an add-on treatment for unresponsive spasticity in multiple sclerosis (MS) patients. Several in vitro and in vivo studies have also shown that cannabinoids can be used to treat various types of cancer, such as melanoma and brain glioblastoma; the first positive clinical trials on the anticancer effect of a THC:CBD blend with temozolomide (TMZ) in the treatment of highly invasive brain cancer are very promising. The cannabinoids exert their anticancer properties in in vitro investigations by the induction of cell death, mainly by apoptosis and cytotoxic autophagy, and the inhibition of cell proliferation. In several studies, cannabinoids have been found to induce tumor regression and inhibit angiogenic mechanisms in vitro and in vivo, as well as in two low-numbered epidemiological studies. They also exhibit antiviral effects by inhibiting ACE2 transcription, blocking viral replication and fusion, and acting as anti-inflammatory agents; indeed, prior CBD consumption (a study of 93,565 persons in Chicago) has also been associated with a much lower incidence of SARS-CoV-2 infections. It is postulated that cannabis extracts can be used in the treatment of many other diseases such as systemic lupus erythematosus, type 1 diabetes, or various types of neurological disorders, e.g., Alzheimer's disease. The aim of this review is to outline the current state of knowledge regarding currently used medicinal preparations derived from C. sativa L. in the treatment of selected cancer and viral diseases, and to present the latest research on the potential applications of its secondary metabolites.

Keywords: anti-inflammatory properties; anticancer properties; antioxidant effects; antiviral effects; cannabidiol; cannabinoids; tetrahydrocannabinol.

Figure 1

Structural formulas of cannabinoids occurring in C. sativa L.

Figure 2

The therapeutic potential of C. sativa L. compounds. The up arrows indicate improved memory and increased immunity and appetite, while the down arrow indicates a pain reduction. The crossed red lines underline the potential protective role of C. sativa L. compounds in cancer, viruses, and cardiovascular diseases. Created in BioRender. Bukowska, B. (2024) BioRender.com/k65p423 (accessed on 1 September 2024).

Figure 3

Mechanism of anticancer properties of C. sativa L. compounds by induction of apoptosis (e.g., by increase caspase 3/7 activity, upregulated TP53 and Bax—expression [100]), induction of autophagy (e.g., upregulates LC3BII, downregulates p62,and inhibits p-PI3K, p-AKT, and p-mTOR pathways [101]), induction of tumor regression (e.g., decreases colony-stimulating factor 1 (CSF-1) level [102], induces DNA fragmentation, and arrests cell progression at the G1 cell cycle checkpoint) [103], decrease in tumor proliferation (e.g., by inhibiting ERK1/2 signaling pathway phosphorylation [104]), and suppression of cell invasion (e.g., by increased expression of TIMP-1, which mediates an anti-invasive effect [105]) in cells and animals. Created in BioRender. Bukowska, B. (2024) BioRender.com/p40b597 (accessed on 1 September 2024).

Figure 4

Molecular mechanism of antiviral effects of C. sativa L. compounds. (1) Downregulating serine protease TMPRSS2 and lowering ACE2 transcription levels [130], (2) preventing SARS-CoV-2 spike protein-mediated membrane fusion [131], (3) blocking the virus translation and replication by suppressing enzyme of SARS-CoV-2 i.e., M^pro protease (in silico and in vitro experiments) [132], (4) upregulation of apelin level [133], and (5) blocking viral replication, in part by upregulating the host IRE1α RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways [32]. Created in BioRender. Bukowska, B. (2024) BioRender.com/k57l772 (accessed on 1 September 2024).