Cannabis is the most widely used illicit drug. It has acute and chronic effects on physical and mental health; adverse effects include rapid heartbeat, disorientation, lack of physical coordination, panic attacks or anxiety, depression or sleepiness, deterioration in cognitive function, and brain abnormalities after long-term use1–3. The pharmacological effects of cannabis are due primarily to tetrahydrocannabinol (THC), which mimics the activity of endocannabinoids such as anandamide. Both THC and endocannabinoids efficiently bind to the G-protein-coupled cannabinoid receptor, CB1, in the brain and transiently inhibit the release of either the inhibitory neurotransmitter γ-aminobutyric acid (GABA) or the excitatory transmitter glutamate4. Although there is another well-characterized cannabinoid G-protein-coupled receptor, CB2, only CB1 receptors are abundantly expressed in the brain, where they are localized specifically on axons and axon terminals. These effects are largely responsible for the psychoactive effects of cannabis, which include potentially therapeutic ones (e.g., analgesia) and reinforcing effects (e.g., relaxation, hallucination, or altered perception)3,5. Our understanding of the biology of cannabis-induced hallucinations (Ca-HL) remains limited.
