Antineoplastic Activity of Cannabinoids2

Abstract

Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-tetrahydrocannabinol (delta9-THC), delta8-tetrahydrocannabinol (delta8-THC), and cannabinol (CBN), but not cannabidiol (CBD). Animals treated for 10 consecutive days with delta9-THC, beginning the day after tumor implantation, demonstrated a dose-dependent action of retarded tumor growth. Mice treated for 20 consecutive days with delta8-THC and CBN had reduced primary tumor size. CBD showed no inhibitory effect on tumor growth at 14, 21, or 28 days. Delta9-THC, delta8-THC, and CBN increased the mean survival time (36% at 100 mg/kg, 25% at 200 mg/kg, and 27% at 50 mg/kg, respectively), whereas CBD did not. Delta9-THC administered orally daily until death in doses of 50, 100, or 200 mg/kg did not increase the life-spans of (C57BL/6 times DBA/2)F1 (BDF1) mice hosting the L1210 murine leukemia. However, delta9-THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for actinomycin D. Experiments with bone marrow and isolated Lewis lung cells incubated in vitro with delta9-THC and delta8-THC showed a dose-dependent (10(-4)-10(-7)) inhibition (80-20%, respectively) of tritiated thymidine and 14C-uridine uptake into these cells. CBD was active only in high concentrations (10(-4)).

Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma

“…Thus far, no studies have been undertaken to assess whether CB1 might serve as a future target for therapeutic intervention in this tumor. Evidence exists since 1975 that cancer cell growth can be inhibited by treatment with cannabinoid receptor agonists, as first described by Munson et al in Lewis lung carcinoma cells (8). Since then, additional cancer cell types such as glioblastoma (9), breast carcinoma (10), or melanoma (11) were reported to be sensitive to the antiproliferative action of cannabinoids.…”

“…In general, the antitumoral actions of diverse cannabinoid receptor agonists are mediated through the cannabinoid receptor types CB1 and CB2, as reviewed by Guzman et al (12). Notably, not only in vitro cell culture systems are subject to this treatment response but also in vivo experiments using either xenografts or syngeneic mouse models have shown the potential of cannabinoids as anticancer agents, without observing major psychoactive or immune-suppressive effects (8,13). Recently, the first clinical study using Δ 9 -tetrahydrocannabinol (THC) in severe cases of glioblastoma has been reported (14).…”

A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

“…Other potential palliative effects of cannabinoids in oncology -supported by phase III clinical trials -include appetite stimulation and pain inhibition (Guzmán, 2003;Hall et al, 2005). In addition, cannabinoids have been proposed as potential antitumoral agents owing to their ability to inhibit the growth and angiogenesis of various types of tumour xenografts in animal models (Munson et al, 1975;Guzmán, 2003). However, the antitumoral effect of cannabinoids has never been tested in humans.…”

Δ9-Tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells

“…In recent years, there is a renewed interest in the role of cannabinoids in cancer therapy. Antitumoral effects of cannabinoid on various types of tumor xenografts including lung adenocarcinoma [6], glioma [7], and thyroid epithelioma [8] in animal models have been identified.…”