Synthetic cannabinoids (SCs) are cannabimimetic compounds that represent a large and diverse class of novel psychoactive substances. SCs can exert full- or even super-agonist activity at cannabinoid receptors, while Δ9-tetrahydrocannabinol (THC), the main psychoactive phytocannabinoid in cannabis, has weak, partial agonist activity at cannabinoid receptors. SCs may therefore have higher addictive liability than natural cannabis. SC consumption has been associate with psychotomimetic effects, the induction of psychotic disorders, and other clinically relevant effects of acute toxicity. Synthetic Cannabinoids and Synthetic Cannabinoid These conditions are qualitatively and quantitatively different from those observe after cannabis intake, with SC ingestion also being associate with increasing numbers of confirmed fatalities. Since the publication of initial reports in the 1960s linking cannabis use to schizophrenia and other psychotic disorders, the nature and strength of this relationship have been areas of controversy. In this chapter, we present four possible explanations for the robust association between cannabis use and schizophrenia. First, we present evidence for direct causality; that is, that cannabis use makes its own unique contribution to the risk of developing schizophrenia. We then present limited evidence for reverse causation (i.e., the “self-medication hypothesis”), meaning that schizophrenia causes cannabis use; that is, those already experiencing early symptoms use cannabis in an attempt to cope with negative or depressive symptoms, or in an attempt to reduce the side effects of antipsychotic medication.
Next, we present evidence for a shared etiology between cannabis use and schizophrenia; specifically, that both cannabis use and schizophrenia are brought about by one or more common etiological factors, such as childhood trauma, low socioeconomic position, urbanicity, adverse prenatal environment, and/or tobacco use. We then discuss evidence for gene-by-environment interactions, providing evidence that cannabis use may trigger schizophrenia only in persons already at genetic risk of developing schizophrenia. Finally, we conclude with a section on plausible biological mechanisms of how the use of cannabis could set off biological processes that could lead to schizophrenia.