Emerging roles for endocannabinoids in long-term synaptic plasticity

Preparations from the herb Cannabis sativa (such as marijuana, hashish and bhang) have been used across numerous cultures for thousands of years, and it is reasonable to say that this impressive history of use can be attributed in large part to profound effects of cannabis on mental state. There are commonly recognized euphoric or rewarding properties of cannabis (Maldonado & Rodriguez de Fonseca, 2002), but more negative consequences include impairments of attention, working memory (Hampson & Deadwyler, 1999) and executive function (Fried et al., 2002). These multiple behavioral effects are consistent with the findings that cannabinoids (the active constituents of cannabis, especially Δ9-tetrahydrocannabinol or Δ9-THC) have widespread actions upon neural function in the brain. Recent years have seen a rapid series of discoveries about the targets and actions of cannabinoids, including the identification of cannabinoid receptors and their endogenous ligands, the endocannabinoids. This growing body of research has revealed numerous ways in which the endocannabinoid system functions to regulate fast synaptic transmission in multiple brain areas (Alger, 2002; Wilson & Nicoll, 2002). Important roles are emerging for endocannabinoid signaling in molecular pathways that underlie both transient and long-lasting alterations in synaptic strength (Alger, 2002). Thus, the critical involvement of endocannabinoids in some mechanisms of synaptic plasticity may refine current cellular models of learning and memory, and likewise these models may be pivotal in understanding both the rewarding and amnestic actions of cannabinoid drugs.