Reversing Acute Cannabinoid Overdose

Our Approach

Specific receptors (“cannabinoid or CB-1 receptors”) in the brain are responsible for the psychoactive effects of both THC and SCs. Following the identification of CB-1 receptors almost 30 years ago, multiple compounds were developed to block (antagonize) the effects of both THC and SCs at CB-1 receptors.  We are currently developing drinabant (OPNT004), a high affinity, CB-1 antagonist for the treatment of Acute Cannabinoid Overdose (ACO). The rationale for using drinabant to treat ACO is based on multiple studies demonstrating that CB-1 antagonists like drinabant compete with agonists (THC and SCs) for CB-1 receptors, terminating their pharmacological actions.

The principle of using a competitive receptor antagonist to reverse the pharmacological actions of a drug in an emergency setting has been successful, resulting in multiple FDA approved products, including naloxone to reverse opioid overdose and flumazenil to reverse benzodiazepine overdose. We believe we can extend this principle to achieve a rapid and effective reversal of ACO in an emergency department setting.

Our Programs and Progress

In late 2018, we licensed drinabant, a selective, high affinity, CB-1 antagonist from Sanofi for the treatment of ACO. A proof of principle study has shown that orally administered drinabant blocked both objective (body sway, heart rate changes) and subjective (measures of feeling ‘high’ and alertness) effects of inhaled THC in healthy male volunteers.  In clinical studies, drinabant has been shown to be safe and well-tolerated for up to 24 weeks following oral administration. However, the slow absorption of oral drinabant is not suitable for producing a rapid reversal of ACO. Thus, we are developing an injectable formulation of drinabant for use in an emergency department setting.