Influence of Cannabinoids on Somatic Cells <i>in vivo</i>

Abstract

Chromosomal and nuclear aberrations in bone marrow cells were studied in hybrid mice of genotype (C57BL x C3H)F₁ following treatment with specific cannabinoids. In the subacute series, mice were treated for 5 consecutive days with Δ⁹-tetrahydrocannabinol (THC), cannabinol or cannabidiol at a dose of 10 mg/kg, the percentage of micronuclei in cannabinoid-treated mice was 3- to 5-fold greater than in the dimethyl sulfoxide controls. In the acute series, polychromatic erythrocytes were scored after a single exposure. In one acute series there was an approximately twofold increase in the incidence of micronuclei in the cannabinoid-treated mice; in the other acute series of cannabinoid-treated animals the micronuclei values were as high as 6 times the control values. Interaction between dose and frequency of exposure was assessed for THC; the number of micronuclei was affected by THC dosage, but not by frequency of exposure. Further confirmation of nuclear aberrations was obtained from assessment of bone marrow mitosis. In this limited study of mitotic cells the incidence of metaphase aberrations in cannabinoid-treated animals was 5–7 times greater than in controls.

Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis

“…It has been known since 1990 that tetrahydrocannabinol, cannabidiol and cannabinol are associated with micronucleus formation at physiologically relevant doses in rodents ( Zimmerman and Raj, 1980 ; Zimmerman and Zimmerman, 1990 ). Both classical and more recent studies show additional evidence of nuclear blebs and cytoplasmic bridges being formed between dividing daughter cells ( Stefanis and Issidorides, 1976 ; Morishima, 1984 ; Russo et al, 2018 ).…”

Low doses of widely consumed cannabinoids (cannabidiol and cannabidivarin) cause DNA damage and chromosomal aberrations in human-derived cells

“…As described in the introduction, results of older studies are available (when no CBD-containing preparations were sold on the market). They show that CBD causes induction of MN and CA in bone marrow of mice (Zimmerman and Raj 1980 ), while no positive results were obtained in unscheduled DNA synthesis (UDS) experiments with fibroblasts in vitro (Zimmerman et al 1978 ). MN induction was found in three independent experimental series after i.p.…”

“…These latter effects may be due to damage to the genetic material, but only few studies which date back to the 1980s were realized. Zimmerman and Raj ( 1980 ) tested CBD in mice and found evidence for induction of micronuclei (MNi) in bone marrow cells of mice, which are formed as a consequence of structural and numerical chromosomal aberrations in bone marrow cells. Furthermore, the same authors reported increased rates of chromosomal aberrations (CA) in the same target tissue by CBD (Zimmerman and Raj 1980 ).…”

In vitro induction of segregational errors of chromosomes by natural cannabinoids in normal human lymphocytes

“…Although Stenchever et a1 [9] and Gilmour and his associates [ l o ] reported an increased incidence of chromosomal breaks in the lymphocytes of marihuana smokers, others have failed to confirm their findings [ 11,12,131 . Similar negative results were also obtained after in vitro exposurle of cells to cannabis resin, crude marihuana extract, delta-&tetrahydro-cannabinol, or THC [14, 15, 161. More recently, Zimmerman and his co-workers [17], found a positive response in the classic micronucleus test system, when THC was administered in vivo. This observation may arise from either intrachromosomal abnormalities or from anomalies of the mitotic apparatus.…”