Why has no one died from Cannabis? – Pharmacology Perspective
Earlier this year, a study was published in the Journal Forensic Science International which is sparking controversy. Hartung and coworkers described the first cases of suspected fatal cannabis intoxications and conducted full postmortem investigation (e.g., autopsy, toxicological, histological, immunohistochemical examinations). Until now, no cases of fatal overdose from cannabis have been reported in the literature. At first glance, the tragic deaths described in their study paint a negative picture for cannabis. However, there is more to this and let’s dig into that. The following two cases are outlined below.
A 23 year-old male with no known relevant illnesses collapsed while using public transport and died after 40 min of unsuccessful cardiopulmonary resuscitation with a clinical picture of ventricular fibrillation. Small amounts of cannabis were found in his pockets.
A 28-year-old male with a history of substance abuse (e.g., alcohol, amphetamines and cocaine until about 2 years before death) and occasional cannabis use. No known cardiovascular diseases and was found dead at his home by girlfriend. Following items were found next to his body: ash tray, rolling paper, and a sealable plastic bag with trace amounts of cannabis.
So, did these two men overdose on cannabis?
These two men did not overdose on cannabis. The researchers who reviewed their deaths concluded that the 23 year-old had a serious preexisting cardiovascular condition and the 28 year-old had a history substance abuse. Since all other causes of death were ruled out, the researchers assumed that cannabis drastically increased their heart rates and blood pressures.
In the absence of underlying health conditions, it is highly improbable to die from smoking cannabis. However, it should be noted that individuals who are at risk for cardiovascular conditions should avoid using cannabis.
Is there a lethal dose for cannabis?
The LD50 is a classic toxicological data point defined as the dose required to kill 50 % of the subjects in a test population. The LD50 of THC is currently unknown but one report has indicated that it is theoretically between 15 and 70 grams for the average human (150 lb). Let’s put this into perspective. The casual user (once a month or so) generally only needs about 2-3 mg of THC to become intoxicated, while habitual users may need between five and ten times that amount to reach intoxication. Since 2 mg = 0.002 g, a casual user would need to smoke about 5000 times (15g / .002g) their normal amount to approach a potentially lethal dose.
A separate report estimates that the LD50 of cannabis is approximately 1:20,000 or 1:40,000. In other words, in order to induce death, an individual would have to consume 20,000 to 40,000 times as much cannabis as is contained in one cannabis cigarette. The National Institute on Drug Abuse (NIDA) supplies cannabis cigarettes that weigh approximately 0.7 to 1 gram. One would theoretically have to consume approximately 1,500 pounds of cannabis within about fifteen minutes to induce a lethal response.
Cannabis and the brain
The brainstem controls several critical functions of the body including the regulation of the cardiovascular system (modulates heart rate) and respiratory system (modulates breathing). The minimal presence of the cannabinoid receptors in the brainstem nuclei may account for the low toxicity of cannabinoids when administered in overdose. The reason why there hasn’t been a single case report directly linking cannabis use as the primary cause of death could be due to the fact that the concentration of cannabinoids is low in the brain stem. In contrast, opioid use can result in respiratory depression and potentially death.
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