The endocannabinoid system plays a key role in regulating emotion, anxiety, and mood. In animal models, THC produces a biphasic effect on anxiety: low doses reduce anxiety by blocking glutamate release, while high doses promote anxiety by blocking GABA release. CBD also reduces anxiety in both preclinical and clinical research, but through a different mechanism. One promising application is for PTSD, where preclinical and small clinical trials suggest that activating the endocannabinoid system may help extinguish aversive memories. The system also regulates the HPA axis, which controls stress hormone release.
Most people who use marijuana do not develop schizophrenia, but there is a modest association between cannabis exposure, especially in adolescence, and later schizophrenia. Whether this link is causal is debated. This chapter reviews evidence for and against a causal relationship and suggests that individuals with a family history of schizophrenia, prodromal symptoms, or cannabis-related psychotic episodes should avoid THC-predominant marijuana.
Activating CB1 receptors throughout the body interferes with short-term memory and the consolidation of new memories in the hippocampus, but does not impair recall of older, established memories. The acute effects of cannabis on memory depend partly on the type of cannabis used: THC impairs short-term memory and new memory formation, while CBD protects against those impairments. Human evidence on whether chronic cannabis exposure causes permanent changes in learning, memory, or brain functioning in adolescents and adults is conflicting.