The medical definition of antidote is a drug that counteracts a poison. Narcan (naloxone) is an antidote for opioid overdose with 100% efficacy as an opioid receptor antagonist[1]. When administered during an opioid overdose it competes for the opioid receptors and essentially knocks the opioid drugs (morphine, heroin, fentanyl, etc.) off the opioid receptors and counters its effects.
This is very important with respect to an opioid overdose because an overdose of opioids is fatal due to the depression of the many brainstem opioid receptors in an area called the Pre-Botzinger complex[2]. This is the breathing center in the medulla and overdose of opioids causes a person to stop breathing and they die of hypoxia if not treated.
Cannabis on the other hand has many CB1 receptors in the central nervous system but there is a paucity of these receptors in this area[3] [4] that affects breathing. Therefore, fatal overdoses similar to opioid overdoses are practically non-existent. I say practically, because older research, which has almost always been funded to show that cannabis does harm, did demonstrate a lethal median dose (LD-50) in rats[5]. This is the dose sufficient to kill 50 percent of a population of animals usually within a certain time. And for cannabis oral preparations it was massive doses that would not be realistic in humans, ranging from 800-1270mg/kg. In a 72kg man that would be between 57,600-91,400mg dose of THC.
But with that said, there are incidences of acute cannabis intoxication. The symptoms of cannabis intoxication from an overdose[6] include nausea, vomiting, tachycardia, hypertension, confusion, obtundation, ataxia, anxiety, paranoia, loss of reality and rarely seizures have been reported. Reports of deaths have been linked to the symptoms of paranoia and panic attacks with an occasional report of someone jumping out of window, as well as falls and motor vehicle[7] accidents.
Overdose and intoxication usually occur with oral dosing because of several reasons[8] [9]. Usually it is an unintentional overdose often in kids[10] [11]because edibles look like delicious cookies and candy. But even adults can unintentionally take too much in edible form because of the delayed onset of action, some may ingest more than they should initially thinking the dose is not working. Additionally, because of first pass metabolism of these oral preparations, the resulting metabolite, 11-hydroxy-THC actually more readily crosses the blood-brain-barrier for enhanced potency and lasting pharmacodynamic psychoactive effect.
Which brings us back to the question is there an antidote for cannabis intoxication? Yes, there is a CB1 receptor antagonist, it is called Rimonabant. A literature review[12] looked at using it with other pharmacologic agents such as propranolol to help with tachycardia and panic attacks.
But there are serious issues using Rimonabant[13], which were evident in European clinical trials of this drug related to obesity treatment. It was investigated as an anorectic anti-obesity drug suppressing hunger by working on the anti-hedonistic effect in our reward centers of the brain related to food and emotional eating. And it did work for that, but because our endocannabinoid system is so redundant and neuromodulates virtually every area in our brain, it had a lot of negative psychiatric side effects related to anxiety and depression.
It was eventually banned in the European market (it never made it to the US) because of increased suicide risk after several study participants killed themselves. So, it begs the question, why risk taking a medication like Rimonabant when most overdoses of cannabis unlike opioids, do not result in respiratory depression and death.
Despite the large increases in Colorado emergency rooms visits and calls to poison control centers for unintentional overdoses in children after the legalization of recreational cannabis, a study found 75-85% of children[14] had no or just minor health effects. This was described as excessive sleepiness and ataxia, which typically resolved in 6-24 hours. They did describe about 20-15% of children requiring admission and a few to the intensive care unit, with toddlers being most at risk for that.
And a friend and colleague, Dr. Bonni Goldstein, who is the country’s top pediatric cannabis physician, cautions[15] that many times emergency physicians use the word “coma” for a very obtunded sleepy child presenting with cannabis overdose and jump to intubate them thinking they need to protect their airways. Often this is a precaution she states, and it may be unnecessary, because these children are not truly comatose, and they only need supportive therapy until they wake up.
Which brings us back to the question at hand. In my opinion there is really no need for a cannabis antidote. These patients/people need a safe calm environment and time to metabolize it, whether it be in the hospital for observation of a toddler or at home with caring watchful family member. But like many things in medicine prevention is the key and keeping cannabis secured and away from kids is far more important and useful than an antidote.
[1] Jacobsen D., Relative Efficacy of Antidotes. J Toxicol Clin Toxicol. 1995; 33(6): 705-708.
[2] Smith J., Ellenberger H., Ballanyi K., Ricther D., and Feldman J,. Pre-Botzinger Comples” A Brainstem Region that may Generate respiratory Rhythm in Mammals. Science. 1991; 254(5032): 726-729.
[3] Barcott B., Can you Overdose or Die from Consuming Cannabis. Leafly.com. Published August 7, 2014. https://www.leafly.com/news/science-tech/can-you-overdose-on-cannabis. Accessed November 9, 2019.
[4] Herenham M., Lynn A., LittleM., Cannabinoid Receptor Localization in the Brain. Proc Natl Acad Sci. 1990; 87(5): 1932-1936.
[5] Rosenkrantz H., Heyman I., Braude M., Inhalation Parenteral and Oral LD-50 Values of 9-delta tetrahydrocannabinol in Fischer Rats. Toxicol Appl Pharmcol. 1974; 28(1): 18-27.
[6] Wang, S., Cannabis: Acute Intoxication. Uptodate.com. Updated October 22, 2019. https://www.uptodate.com/contents/cannabis-marijuana-acute-intoxication. Accessed November 9, 2019.
[7] National Academy of Sciences, Engineering and Medicine. Health Effects of Cannabis and Cannabinoids. Published January 12, 2017. https://www.ncbi.nlm.nih.gov/books/NBK423845/pdf/Bookshelf_NBK423845.pdf. Accessed November 9, 2019.
[8] Vandry R., Herrmann E., Mitchel J., Bigelow G., Flegel R., LoDico C., Cone E., Pharmocokinetic Profile of Oral Cannabis in Humans: Blood and Oral Fluid Disposition in Relation to Pharmacodynamic Outcomes. J Anal Toxicol. 2017; 41(2): 83-99.
[9] Barrus D., Capogrossi K., Wiley J., et al. Tasty THC: Promises and Challenges of Cannabis Edibles. Methods Rep RTI Press. Published November 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260817/. Accessed November 9, 2019.
[10] Wang S, LeLait M., Deakyne S., Unintentional Pediatric Exposure to Marijuana in Colorado, 2009-2015. JAMA Pediatr Online. Published September 6, 2016. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2534480. Accessed November 9, 2109.
[11] Heizer J., Borgelt L., Wang S., et al. Marijuana Misadventures in Children: Exploration of a Dose-Response Relationshipand Summary of Clinical Effects and Outcomes. Pediatr Emerg Care. 2018; 34(7): 457-462.
[12] Crippa j., Hallack J., et al. Pharmacologic Intervention in the Treatment of Acute Effects of Cannabis; A Systemic Review of the Literature. Harm Reduct J Online. Published January 25, 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294246/. Accessed November 9, 2019.
[13] Sam A., Salem V., Ghatei M., From RIO to Ban. J Obes Online. Published July 6, 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136184/. Accessed November 9, 2019.
[14] Wang S, LeLait M., Deakyne S., Unintentional Pediatric Exposure to Marijuana in Colorado, 2009-2015. JAMA Pediatr Online. Published September 6, 2016. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2534480. Accessed November 9, 2109.
[15] Krishnan M., We Fact-Checked and ER doctor Who Said Weed Edibles Can Kill Kids. Vice.com. Published August 21, 2018. https://www.vice.com/en_us/article/vbjnam/we-fact-checked-an-er-doctor-who-said-weed-edibles-can-kill-kids. Accessed November 9, 2109
Dr. Leigh Vinocur is a board certified emergency physician, who also has a cannabis consulting practice for patients and industry. She is a member of the Society of Cannabis Clinicians. And in the inaugural class for the first Masters of Science in the country in Cannabis Science and Therapeutics at the University of Maryland School of Pharmacy.
This blog is not written or edited by Hearst. The authors are solely responsible for the content.