Marijuana has been used recreationally and medicinally for centuries. The principle psychoactive component, Δ9-tetrahydrocannabinol (Δ9-THC), activates CB1 cannabinoid receptors (CB1Rs). CB1R agonists and antagonists could potentially treat a wide variety of diseases; unfortunately, therapeutic doses produce unacceptable psychiatric effects. “K2” or “Spice” (K2/Spice), an emerging drug of abuse, exhibits psychotropic actions via CB1R activation. Because of structural dissimilarity to Δ9-THC, these drugs are widely unregulated and touted as “legal” marijuana. This review summarizes current and future therapeutic uses of CB1R ligands and provides a historical perspective of the K2/Spice “phenomenon” so the reader can decide if marijuana-based drugs will truly provide innovative therapeutics or instead perpetuate drug abuse
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