The pharmacological interaction between cannabidiol (CBD) and (−)δ
9-trans-tetrahydrocannabinol (δ
9-THC) has been studied in rabbits, mice and rats by administering mixtures containing varying amounts of both substances. CBD blocked the following effects of δ
9-THC: catatonia in mice, corneal areflexia in rabbits, the increased defecation and decreased ambulation after chronic treatment and exposures of rats in an open field arena, and the aggressiveness of rats previously stressed by REM sleep deprivation. On the other hand, CBD potentiated the δ
9-THC-induced analgesia in mice and the δ
9-THC-impairing effect on climbing rope performance of rats. These interactions are tentatively explained by postulating that CBD directly antagonizes the excitatory effects and/or indirectly potentiates the depressant effects of δ
9-THC.

Pharmacological interaction between cannabidiol and delta 9-tetrahydrocannabinol.

The cannabinoid 1 (CB(1)) and cannabinoid 2 (CB(2)) receptor agonist Delta(9)-tetrahydrocannabinol (THC) has been shown to be a broad-range inhibitor of cancer in culture and in vivo, and is currently being used in a clinical trial for the treatment of glioblastoma. It has been suggested that other plant-derived cannabinoids, which do not interact efficiently with CB(1) and CB(2) receptors, can modulate the actions of Delta(9)-THC. There are conflicting reports, however, as to what extent other cannabinoids can modulate Delta(9)-THC activity, and most importantly, it is not clear whether other cannabinoid compounds can either potentiate or inhibit the actions of Delta(9)-THC. We therefore tested cannabidiol, the second most abundant plant-derived cannabinoid, in combination with Delta(9)-THC. In the U251 and SF126 glioblastoma cell lines, Delta(9)-THC and cannabidiol acted synergistically to inhibit cell proliferation. The treatment of glioblastoma cells with both compounds led to significant modulations of the cell cycle and induction of reactive oxygen species and apoptosis as well as specific modulations of extracellular signal-regulated kinase and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique. Our results suggest that the addition of cannabidiol to Delta(9)-THC may improve the overall effectiveness of Delta(9)-THC in the treatment of glioblastoma in cancer patients.

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Cannabidiol Enhances the Inhibitory Effects of Δ9-Tetrahydrocannabinol on Human Glioblastoma Cell Proliferation and Survival

Le cannabidiol administre a dose de 100 mg par os et de 30 mg par injection i.v. fut inactif dans les sujets d'etude. Le cannabinol, a dose orale de 400 mg, le fut aussi. Ces constituants du cannabis ne contribuent donc pas a l'effet pharmacologique.

Cannabidiol and cannabinol in man.

The pharmacological activities of δ9-THC [(−)-δ9-trans-tetrahydrocannabinol], CBN (Cannabinol) and mixtures of δ9-THC + CBN were studied in rabbits, rats and mice.

Pharmacologic interaction between cannabinol and delta9-tetrahydrocannabinol.

Cannabinol (CBN) and Cannabidiol (CBD) were tested in several test procedures known to be altered by δ
9-tetrahydrocannabinol (THC) or crude cannabis preparations. They were inactive in doses up to 80 mg/kg in tests on animal motility, food and water intake, body temperature and catalepsy. In contrast, CBD enhanced the hexobarbitone “sleeping time” more pronounced than δ
9-THC whereas CBN increased the “sleeping time” only slightly. When administered in combination CBD prolonged all actions of THC, whereas CBN selectively blocked the effect of THC on hexobarbitone “sleeping time”. The enhancement by CBD is best explained by an inhibition of THC-metabolism.

Berger Hj

Papers

Blockade of (-)-trans- 9 -tetrahydrocannabinol depressant effect by cannabinol in mice.