Synthetic cannabinoids: an overview


Introduction: Synthetic cannabinoids (SCs) are a heterogeneous group of substances created in the 1960s as potential therapeutic substances in the context of the endocannabinoid system research. Over the last decade, SCs have become increasingly popular as a substance of abuse and sold under the brand names of “Spice” or “K2”. Growing evidence suggests that, compared to natural cannabis, SCs are associated with more rapid development of dependence, as well as increased psychiatric symptoms/illnesses and serious physical adverse effects.

Objectives: this work provides an overview of the mechanism of action of SCs, as well as the potential physical and psychiatric consequences of its chronic use.

Methods: Review of the literature from Pubmed database.

Results: Unlike delta-9-tetrahydrocannabinol (the primary psychoactive component in the cannabis plant), the majority of SCs are high-potency, high-efficacy, full agonists at the brain’s cannabinoid 1 (CB1) receptors. Because actions at CB1 receptors can regulate the function of dopamine, serotonin and glutamate systems, higher efficacy CB1 receptor agonists might alter to a greater extent the functions of these three neurotransmitter systems, which are knowingly implicated in the development of psychosis and schizophrenia. Moreover, evidence shows that chronic SCs users may have structural central nervous system abnormalities such as overall reduced gray matter volume. Studies have found important impact of SCs in the development of psychiatric symptoms/disorders such as psychosis, acute anxiety and panic, changes in mood, memory and attention. Daily use of high-potency cannabis such as SCs has been linked to the earlier onset of psychosis in cannabis users. In terms of physical consequences, SCs most frequently result in tachycardia, agitation and nausea. Nonetheless, severe adverse events may occur such as strokes, seizures or myocardial infarction, which can lead to death.

Conclusions: growing evidence shows the risks and potential harms of SCs use, with solid evidence linking these substances to psychotic illnesses such as schizophrenia. It is important for clinicians to be aware of these risks, for an improved management of adverse events and a better understanding of cannabinoid pharmacology in humans.


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