Marijuana is one of the most commonly used recreational drugs in the United States. As marijuana is illegal in the majority of countries, the use of readily available and unregulated synthetic cannabinoids (SCBs) has increased. Little is known about the potential adverse effects of SCBs especially in regards to their nephrotoxicity. Case reports of acute kidney injury (AKI) from acute tubular injury secondary to their use have been reported. However, the exact pathology, mechanism, and extent of renal injury remain unknown. We report the first case of biopsy proven thrombotic microangiopathy (TMA) associated with SCBs resulting in AKI. The patient suffered significant morbidity with loss of renal function eventually requiring renal replacement therapy.