Ignorance Confounds Driving Under the Influence of THC

The unfortunate consequence of the Schedule 1 classification of cannabis is that research was strongly curtailed for the last 50 years. Thus, even the basics of quantitative cause-and-effect relationships were ignored. Even today, research on the pharmacokinetics of D-9-tetrahydrocannabinol (THC) and its 11-hydroxy metabolite is unusual. This confounds efforts for science-based regulation.

For example, we do not have a clear picture of dose and response of THC in humans. Compare this to the generally accepted view that 0.8% blood alcohol is the dividing line between feeling good and drunk driving. This is called a bright line breakpoint supporting “per se” regulations.

Professor Thomas D. Marcotte of UCSD gave a lecture entitled, “Cannabis and Public Safety: The Challenge of Cannabis-Impaired Driving,” at the meeting of the UCSD Center for Medicinal Cannabis Research (CMCR) held June 8, 2018, at the Hilton Hotel Bay Front in San Diego. He led off with some current statistics: 30 states have legalized medicinal cannabis. Of these, 16 focus specifically on cannabidiol (CBD), which is recognized as a nonpsychoactive (impairing) cannabinoid.

There are over 500 cannabinoids in the cannabis plant, but currently only THC and 11-hydroxy THC are recognized as psychoactive. Other derivatives are probable, but Professor Marcotte focused on THC, which is by far the most popular and controversial.

The pharmacological effects of THC are relatively well-understood:

Reduced cognition:

  • Learning
  • Attention span
  • Processing speed
  • Psychomotor effects

This shows up in impaired driving performance:

  • Delayed reactions such as braking
  • Poor lane tracking
  • Reduced spatial/temporal performance
  • Some studies estimated a doubling of crash risk.

I’m not an expert in metabolism and pharmacodynamics, but these results indicate that the metabolism of inhaled THC is not simple. After the first puff, the blood THC level rises rapidly and starts generating the feeling of being high. A histogram of the high feelings versus blood THC shows a cyclic pattern where the high is recorded a few minutes after smoking and lasts for a number of hours. Blood THC levels, however, hit maximum at about 10 minutes and then drop rapidly within an hour. In frequent users, THC can be detected in blood (e.g., at about 1 ng/mL for 79% of users seven days after inhalation).

11-Hydroxy THC is another psychoactive cannabinoid produced during the first pass of THC through the liver. The addition of one more OH empowers 11-hydroxy to pass more easily through the blood–brain barrier than THC. Conversion is complete after about 1.5 hours post-inhalation.

The persistence of detectable THC in blood days after smoking complicates the establishment of per se laws. Eighteen states have zero tolerance per se driving laws for THC and metabolites. Three states have zero tolerance on THC only. Some states have tried per se regulation for blood THC:

Pennsylvania: 1 ng/mL

  • Nevada and Ohio: 2 ng/mL
  • Illinois, Montana, and Washington: 5 ng/mL
  • Colorado sets 5 ng/mL as “reasonable inference.”

Since per se testing seems inconclusive, many rely on drug recognition experts (DREs) who receive special training to triage suspected cases of impairment including alcohol, cannabis, PCP, and opiates. Their training also includes instruction on recognizing disease-related causes of impaired behavior.

Professor Marcotte showed a bar chart comparing 602 cases where the DRE diagnosed driving impairment with the THC blood content. The median was 5.05 ng/mL with an average of 7.04. This shows that half of the 602 cases were not correctly classified based on the blood levels of THC in ng/mL. This may be one consequence of delayed blood collection (typically 1–2 hours after the traffic stop).

On the other hand, low estimates on the crash risk for cannabis users may be impacted by the large number of THC-positive but unimpaired drivers. This may statistically hide the effect of impaired drivers. Potential confounding factors include effect of other substances and compensating behavior (e.g., cannabis users driving more cautiously).

Other body fluids were also investigated. Saliva was not much better as a sample matrix in that it may also be detectable after impairment has subsided. I’ve reported previously that ear wax has also been proposed.

Another problem is that the pharmacokinetic profile differs with inhalation and consumption of processed solids. From a regulatory viewpoint, this may require product-specific potency regulation. Product-specific regulation for pesticide residue, terpenes, and mycotoxins makes sense since these can copurify, especially with nonpolar extraction.

These observations raise serious questions such as: Is the long residence time of THC in a body arising from the difficulty of the analytical method? Are we trying to measure the right analyte? Is there some drug conjugate that harbors THC in the body, so it is slowly released? To me, the pharmacodynamics merits critical examination. This may require new tools and protocols.

Today, identifying individuals whose driving is impaired due to cannabis remains a challenge. Per se laws are most effective when a robust correlation between body fluid concentration and impairment can be demonstrated. This is not yet true for THC and driving performance, and probably many other human endeavors.

Professor Marcotte concluded with the recognition that cannabinoid pharmacology needs much more research to support science-based regulation. These may be specific to the product and administration route. Also, he cites the need for studying the effects in various population segments including the aged, medically ill, and cognitively impaired. However, the first step needs to develop the science surrounding the pharmacology. Without this, harmonized methods and standards between the stakeholders are probably impossible.

Robert L. Stevenson, Ph.D., is Editor Emeritus, American Laboratory/Labcompare; e-mail: [email protected]

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