New synthetic cannabinoid agonists have been synthesized during the last decades and promoted for their psychoactive effects, mimicking those of delta-9-tetrahydrocannabinol. These newest cannabimimetic drugs show binding affinities for the cannabinoid CB1 and/or the CB2 receptors. They are manufactured by spraying the synthetic cannabinoid onto relatively inert vegetable material or by solubilizing them in ’e-liquids’ for electronic cigarettes. They are lipid soluble and non-polar and volatilize easily when smoked. However, these drugs have been associated with psychiatric and medical complications. The most typical adverse effects of synthetic cannabinoid agonists included agitation, confusion, anxiety, psychosis, nausea, and vomiting, but drowsiness, tachycardia, and hypertension are also reported frequently. Atypical effects can also manifest, including shock, seizures, fever, rhabdomyolysis, myocardial infarction, stroke, acute kidney injury, and multiple organ failure. The cardiovascular and neuropsychiatric effects, which in some cases can be severe and long-lasting, are among the most common reasons for emergency medical treatment. Due to limited knowledge about their pharmacology and toxicity, managing acute intoxications is challenging and treatment strategies are mostly limited to symptomatic and supportive care.