Endocannabinoid signaling is implicated in an array of psychopathologies ranging from anxiety to
psychosis and addiction. In recent years, radiotracers targeting the
endocannabinoid system have been used in positron emission tomography (PET) studies to determine whether individuals with
psychiatric disorders display altered
endocannabinoid signaling. We comprehensively reviewed PET studies examining differences in
endocannabinoid signaling between individuals with
psychiatric illness and healthy controls. Published studies evaluated individuals with five
psychiatric disorders: cannabis use disorder,
alcohol use disorder,
schizophrenia,
post-traumatic stress disorder, and
eating disorders. Most studies employed radiotracers targeting
cannabinoid receptor 1 (CB1). Cannabis users consistently demonstrated decreased CB1 binding compared to controls, with normalization following short periods of abstinence. Findings in those with
alcohol use disorder and
schizophrenia were less consistent, with some studies demonstrating increased CB1 binding and others demonstrating decreased CB1 binding. Evidence of aberrant CB1 binding was also found in individuals with
anorexia nervosa and
post-traumatic stress disorder, but limited data have been published to date. Thus, existing evidence suggests that alterations in
endocannabinoid signaling are present in a range of
psychiatric disorders. Although recent efforts have largely focused on evaluating CB1 binding, the synthesis of new radiotracers targeting
enzymes involved in
endocannabinoid degradation, such as
fatty acid amide hydrolase, will allow for other facets of
endocannabinoid signaling to be evaluated in future studies.