Influence of acute pretreatment with Δ9-tetrahydrocannabinol on the LD50 of various substances that alter neurohumoral transmission

Δ 9 -THC significantly influenced the acute lethal effects (24 hr after a single dose) in mice of several drugs which alter cholinergic, adrenergic and serotoninergic neurotransmission. The LD50 values of carbachol chloride, arecoline HCl, physostigmine salicylate and neostigmine methylsalicylate were all significantly potentiated after pretreatment with 20.0 mg/kg of Δ 9 -THC. Paradoxically, lethality produced by methacholine and exogenously administered acetylcholine were attenuated. Evidence for an α-adrenergic receptor blocking effect of Δ 9 -THC was noted by the significantly larger LD50 values for 1-norepinephrine bitartrate and phenylephrine HCl when each was given in combination with Δ 9 -THC. Moreover, bretylium tosylate and dl -α-methyl- p -tyrosine toxicities were also attenuated by pretreatment with Δ 9 -THC. Finally, the combination of Δ 9 -THC and cyproheptadine HCl was more toxic than the latter compound alone, suggesting an additive antiserotonin effect.