Serotonin syndrome is a potentially life-threatening condition caused by over-activation of the serotonin (5-HT) system in the CNS. This can occur with the therapeutic use of serotonergic agents or inadvertent complex drug interactions between serotonergic agents. Clinical presentation varies widely in severity and is diagnosed by the decision rules of Hunter Serotonin Toxicity Criteria, utilizing the three main clinical categories: altered mental status, autonomic hyperactivity, and neuromuscular abnormalities.

A 63 year-old male with medical history most notable for restless leg syndrome (on ropinirole), chronic lymphocytic leukemia, depression on duloxetine, and chronic alcohol abuse presented with altered mental status, shaking, diaphoresis, and an inability to walk. He had initiated intake of THC-infused cheese as a neuropathic pain control measure. On examination, he was afebrile, hypertensive and mildly tachycardic, somnolent, diaphoretic, and diffusely hyperreflexic. Urine toxicology screen was positive for tetrahydrocannabinol (THC). He was treated with intravenous fluids and lorazepam with improvement of symptoms. With continued supportive therapy and discontinuation of duloxetine, the patient completely recovered within 48 hours and was discharged home without residual symptoms.

The cannabinoid (CB) receptors and endogenous agonists are widely distributed throughout the CNS and are involved in the regulation of mood. This endocannabinoid system is known to regulate serotonergic system through several mechanisms: modulation of 5-HT release, receptor expression, and regulation of excitability of 5-HT neurons.

With the legalization of marijuana and increasing access to cannabinoid-containing products, it is imperative to raise awareness of the serotonergic effects of these products and to educate patients to avoid use of these products if they are currently taking a serotonergic agent. Complete workup of a patient with serotonin syndrome should include a urine drug screen and comprehensive social history.