Marijuana's interaction with brain reward systems: update 1991.

The most pervasive commonality amongst noncannabinoid drugs of abuse is that they enhance electrical brain stimulation reward and act as direct or indirect dopamine agonists in the reward relevant dopaminergic projections of the medial forebrain bundle (MFB). These dopaminergic projections constitute a crucial drug sensitive link in the brain's reward circuitry, and abused drugs derive significant abuse liability from enhancing these circuits. Marijuana and other cannabinoids were long considered "anomalous" drugs of abuse, lacking pharmacological interaction with these brain reward substrates. It is now clear, however, that delta 9-tetrahydrocannabinol (delta 9-THC), marijuana's principal psychoactive constituent, acts on these brain reward substrates in strikingly similar fashion to noncannabinoid drugs of abuse. Specifically, delta 9-THC enhances MFB electrical brain stimulation reward, and enhances both basal and stimulated dopamine release in reward relevant MFB projection loci. Furthermore, delta 9-THC's actions on these mechanisms is naloxone blockable, and delta 9-THC modulates brain mu and delta opioid receptors. This paper reviews these data, suggests that marijuana's interaction with brain reward systems is fundamentally similar to that of other abused drugs, and proposes a specific neural model of that interaction.