How does the brain respond to the acute and chronic effects of Schedule I drugs like tetrahydrocannabinol (Δ9-THC), lysergic acid diethylamide (LSD), and psilocybin? Unfortunately, there are federal restrictions limiting research on Schedule I drugs in the US. This is particularly true if the subjects are drug naïve, healthy volunteers. However, these obstacles can be overcome by studying awake animals using multimodal MRI to follow changes in brain function in response to drug administration during the scanning session. To that end, data will be presented on the methods and applications in awake animal imaging on the neurobiology of hallucinogens and cannabis.