An antidote for cannabis intoxication

The use of “antidotes” or drugs that reverse the action of another drug are very familiar to the public today as the opioid crisis continues to grow. Naloxone, otherwise known as Narcan, is the most commonly known drug to treat opioid overdoses. Like Narcan for heroin, rimonabant is an antidote for cannabis intoxication. Most people are not familiar with the concept of cannabis intoxication. While there is little to no chance of death, there are symptoms, such as anxiety, that cause numerous number of emergency room visits a year.¹ Scientist have worked a treatment for this intoxication, rimonabant, but unfortunately, the mental health side effects have caused it to be unacceptable for patient use.²

As more and more states and countries are legalizing both medical and recreational cannabis, the instance of intoxication cases have increased as well. For example, when Colorado legalized recreational cannabis, cases of intoxication increased to almost twice the rate of the rest of the United States, about 6 per 100,000 people.³ The average user may think it is impossible to overdose on cannabis like heroin or other opioids. While cannabis intoxication is not known to be deadly, it does exist, and emergency room cases are not uncommon. The most prevalent symptom of the intoxication is severe anxiety. Other symptoms can range from confusion and paranoia to a rapid heartbeat and hallucinations.³ Currently there is no standardized dosing method for the various strains of cannabis. Without dosing, intoxication is possible, especially in edibles, as the effects take longer to manifest and lasts longer.³

Benzodiazepines and sedatives are the usual treatment for cannabis intoxication in the ER. Unfortunately, these medicines can increase the sedative effects of cannabis.¹ An alternative to these treatments exists and actually works very well as an antidote to cannabis intoxication. Rimonabant, the generic name of Acomplia, is a CB1 endocannabinoid receptor antagonist.² It was designed to be an anti-obesity drug. In the body, CB1 and CB2 receptors are G-protein linked receptors of the endocannabinoid system. CB1 is found in the central nervous system while CB2 is found in the immune system. These receptors normally bind to endocannabinoids found naturally in the body. When cannabis is ingested, THC binds to the CB1 receptor to cause psychoactive effects.¹ Rimonabant is a CB1 antagonist. This means that it binds to the CB1 receptor, kicking off the bound THC is the process. Being an antagonist, it deactivates the receptor.¹

Looking purely at the antagonist activity, rimonbant is an excellent antidote to cannabis intoxication. It reverses the symptoms without the lethargy of benzodiazepines or sedatives. Unfortunately, the drug has severe mental health implications. Suicidal tendencies and depression were rampant among patients taking rimonbant.⁴In 2006, Europe approved it for weight reduction.² In 2007, the FDA recommended against approval due to the serious side effects. The equivalent agency in Europe, the European Medicines Agency, withdrew the drug from production in 2009 for the same reasons. Today, rimonabant is no longer produced or used in Europe or the US.⁴

Since the legalization of cannabis has started to become widespread, instances of cannabis intoxication have increased as well. Emergency room doctors commonly use benzodiazepines and sedatives to treat symptoms such as anxiety, paranoia, and hallucinations but these treatments tend to exacerbate the drowsiness associated with cannabis use. Rimonabant, a CB1 antagonist initially created to fight obesity, can replace THC on the CB1 receptor and counteract the THC psychoactive effects. While rimonabant was very effective in weight loss and reversing cannabis intoxication, its side effects had significant impacts on mental health in patients including suicidal tendencies and major depression. Accordingly, the FDA and European equivalent banned its use. Therefore, while an effective antidote to cannabis intoxication does exist, its side effects prevent it from being used by the medical community.