In life, the sins of the father often pass to the son. Now, new evidence shows an intergenerational effect on the motivation of rats whose genetic forbears had been exposed to marijuana. In experiments, investigators gave half the study population  injections of marijuana’s active ingredient, delta-9-tetrahydrocannabinol. The other half received a saline solution. A generation or two later, the descendents of the first group showed a lowered desire to seek the reward of “highly tasty food,” in laboratory experiments conducted by Yasmin Hurd, of Mount Sinai School of Medicine.

After one generation, male offspring from rats exposed to the drug showed lowered motivation and weight gain, though the metabolic effect disappeared by the third generation, Hurd reported last week at the annual meeting of the Society for Neuroscience.

Analyses by investigators showed numerous epigenetic changes brought by exposure to the drug. Previously, Hurd and her colleagues showed that THC exposure during adolescence increased a later desire for heroin during adulthood. Now, they’re trying to explain the neurological repercussions of exposure to cannabis. "We're nowhere close to figuring out how it is that these mechanisms are passed on across generations," Hurd said at the conference.

In analyzing the expression of mitochondrial RNA among male offspring, investigators say they see a downregulation in glutamatergic receptors, including NMDA and AMPA receptors. The change occurred in adulthood and manifested only as reductions in receptor proteins. Aside from motivational change, the “epigenetic” exposure to THC heightened susceptibility to long-term depression in the dorsal — but not ventral — striatum following electrical stimulation. Moreover, those males showed an “unusual avoidance behavior” when investigators shown a bright light into the laboratory cage. Evidence of methylation, an epigenetic occurence first discovered in plants, shows the intergenerational effects of cannabis.

With funding from the U.S. National Institutes of Health, Hurd and her colleagues continue to study the long-term effects of the drug, as popular support builds for liberalizing America’s marijuana regulatory laws.