Marijuana is known to affect learning and memory in humans, and cannabinoids block long-term potentiation in the hippocampus, a model for the synaptic changes that are believed to underlie memory at the cellular level. We have now examined the physiological properties of the Schaffer collateral-CA1 synapses in mutant mice in which the CB1 receptor gene has been invalidated and found that these animals exhibit a half-larger long-term potentiation than wild-type controls. Other properties of these synapses, such as paired-pulse facilitation, remained unchanged. This indicates that disrupting CB1 receptor-mediated neurotransmission at the genome level produces mutant mice with an enhanced capacity to strengthen synaptic connections in a brain region crucial for memory formation.