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 h b l d h f but there are active metabolites and other constituents of marijuana.

• 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
• ut of the brain.

THC l l di ib i h l f hi h

• THC slowly redistributes to peripheral fat, which

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. Th j ff f k d ij i h fi

• The major effects of smoked marijuana occur in the first

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

l d h d b l b d d f released so that it and metabolites can be detected for 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

f k h d i i performance on tasks such as driving.

• 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

• f 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

h f l driving, there is some degree of tolerance and compensatory behavior with marijuana.

• Alcohol and marijuana have synergistic effects on

performance.