Why Blood Levels of THC Do Not Reflect the Level of Impairment - PowerPoint PPT Presentation

Why Blood Levels of THC Do Not Reflect the Level of Impairment Reflect the Level of Impairment Jack P. Uetrecht, MD, PHD , Professor, University of Toronto, Toxicology

Alcohol is Simple p • Alcohol exposure is always oral. • Alcohol is not significantly absorbed from the stomach: Alcohol is not significantly absorbed from the stomach: therefore, the time to onset of effects is dependent on gastric emptying – usually less than an hour, but food, especially fat delays gastric emptying especially fat, delays gastric emptying. • Distribution of alcohol in the body is fast and uniform. • Differences in alcohol metabolism are relatively small. Differences in alcohol metabolism are relatively small. • There are no active metabolites of alcohol. • There is little tolerance to the effects of alcohol. • Therefore, blood alcohol is a good indication of impairment.

Marijuana is Complicated Marijuana is Complicated The major active component of marijuana is tetrahydrocannabinol (THC), b but there are active metabolites and other constituents of marijuana. h b l d h f • THC is very lipophilic (fat loving), and it has a very low water solubility. • With chronic use there is down regulation of the cannabinoid receptors and leading to some degree of tolerance. • Marijuana can be smoked, vaped, or ingested. • The effects of smoked marijuana are somewhat different than ingested marijuana.

Smoked Marijuana Smoked Marijuana • Only about 10% of the THC in a cigarette gets into the lungs and is absorbed. • THC is rapidly distributed to the brain, which has a high fat content ( peak effects in 3 ‐ 10 minutes), because there is a high blood flow to the brain. • There are two efflux “pumps” which pump THC out of the brain. • THC slowly redistributes to peripheral fat, which THC l l di ib i h l f hi h has low blood flow but no efflux pumps.

Disconnect Between Brian and Blood Levels • THC has very low water solubility and blood is mostly water. • The major effects of smoked marijuana occur in the first Th j ff f k d ij i h fi two ‐ three hours. • As the THC is redistributed to fat and is metabolized the As the THC is redistributed to fat and is metabolized the blood level drops faster than the brain levels. • With chronic use, THC builds up in fat and is slowly released so that it and metabolites can be detected for l d h d b l b d d f more than a month even though the brain levels may be low because of the efflux transporters. p

Effects of Eatables Effects of Eatables • In contrast to smoked marijuana, effects of eatables may take 2 ‐ 3 hours to peak, a time when the effects of smoked marijuana would have markedly decreased. • This often leads to an overdose This often leads to an overdose. • To reach the blood stream, oral THC must pass through the liver and a significant amount (~ 90%) is metabolized. 11 ‐ OH ‐ THC is an active metabolite. • Exposure to oral and smoked THC can be differentiated by the ratio of 11 ‐ OH ‐ THC to THC the ratio of 11 OH THC to THC. • Because absorption from the gut is much slower, more distributes directly to fat, and the peak THC level is lower. • However, blood levels stay elevated much longer.

Risk of Motor Vehicle Accidents Risk of Motor Vehicle Accidents

Effects of THC on Performance Effects of THC on Performance • There is no question that acute THC exposure impairs performance on tasks such as driving. f k h d i i • The combination of THC and alcohol is synergistic. • As mentioned, the effects of smoked marijuana are maximal , j during the first 2 ‐ 3 hours, but there is not a good correlation between blood levels and performance. • Effects appear to be greater on autonomic functions • Effects appear to be greater on autonomic functions. • In simulated tests, impaired subjects drive more cautiously. • The effects of chronic exposure such as medical marijuana (pure THC, Marinol) are significantly different to some degree because of tolerance; there are no good studies on the effects of medical marijuana on driving.

Summary • Marijuana is much more complex than alcohol, and unlike alcohol, there is not a good correlation between blood THC levels and the degree of impairment. levels and the degree of impairment. • The effect of smoked marijuana and eatables is different. • Although THC does impair performance in tasks such as driving, there is some degree of tolerance and h f l compensatory behavior with marijuana. • Alcohol and marijuana have synergistic effects on performance.