By Deandra Grant, J.D., M.S. (Pharmaceutical Science), ACS-CHAL Forensic Lawyer-Scientist
The prosecution’s theory in every drug DWI case rests on a simple equation: the defendant had drugs in their system, therefore the defendant was impaired. The relationship between blood alcohol concentration and impairment is well-established and reasonably consistent across individuals. But for virtually every other substance (cannabis, benzodiazepines, opioids, amphetamines, antidepressants, sleep medications) this reasoning is scientifically wrong.
The reason it is wrong has a name: tolerance. And understanding tolerance at the pharmacological level is one of the most powerful defense tools in drug DWI cases.
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What Is Tolerance?
In pharmacology, tolerance refers to the body’s progressive adaptation to repeated drug exposure, resulting in a diminished response to the same dose over time. A drug that produces significant impairment on first exposure may produce little or no impairment after weeks or months of regular use even though the blood concentration is the same or even higher.
There are three main types of tolerance, each operating through a different biological mechanism:
1. Pharmacodynamic Tolerance
This is the most important type for defense purposes. Pharmacodynamic tolerance occurs when the brain’s receptors adapt to the chronic presence of a drug. With repeated exposure, receptors may downregulate (decrease in number), desensitize (become less responsive), or trigger compensatory changes in neural circuits. The result: the same drug concentration at the receptor site produces a smaller effect.
Cannabis is the clearest example. Chronic cannabis users develop significant tolerance to the psychoactive effects of THC through downregulation of CB1 cannabinoid receptors in the brain. Studies have shown that chronic users can function normally (i.e. performing cognitive and psychomotor tasks within normal limits) at THC blood concentrations that would significantly impair a naive user. This is why per se THC limits are scientifically indefensible: the same blood concentration means entirely different things in different people.
2. Pharmacokinetic (Metabolic) Tolerance
Pharmacokinetic tolerance occurs when the body becomes more efficient at metabolizing and eliminating a drug with repeated exposure. This happens through enzyme induction which is the upregulation of the cytochrome P450 enzyme systems in the liver that metabolize drugs. With chronic exposure, the liver produces more of the relevant enzymes, which metabolize the drug faster, resulting in lower peak concentrations and shorter duration of effect from the same dose.
Alcohol is the classic example: chronic heavy drinkers induce CYP2E1, which increases the rate of ethanol metabolism. This is why chronic drinkers can consume quantities that would incapacitate a non-drinker and appear relatively functional. Their livers are processing the alcohol faster.
3. Acute Tolerance (The Mellanby Effect)
Acute tolerance occurs within a single episode of drug exposure. For alcohol, this is known as the Mellanby Effect: impairment is greater during the rising phase of the blood alcohol curve (absorption) than during the falling phase (elimination) at the same BAC. A person at 0.08 on the way up is more impaired than a person at 0.08 on the way down.
This has direct implications for retrograde extrapolation and for the timing of DWI observations relative to the BAC curve. An officer’s observations at the roadside may reflect peak impairment during absorption, while the BAC tested 60 minutes later reflects the elimination phase — a higher number but lower impairment.
Drug-Specific Tolerance in DWI Cases
Cannabis
Chronic cannabis users develop substantial pharmacodynamic tolerance. Peer-reviewed research has demonstrated that regular users can maintain normal driving performance in simulator studies at THC blood concentrations that impair occasional users. The National Institute of Justice concluded that THC levels in bodily fluids are not reliable indicators of marijuana intoxication. Any prosecution theory that relies on a THC blood concentration to prove impairment must account for the defendant’s usage history and tolerance status.
Benzodiazepines
Patients prescribed benzodiazepines for anxiety, insomnia, or seizure disorders develop significant tolerance to the sedating and psychomotor-impairing effects within weeks of regular use. A chronic benzodiazepine patient with a therapeutic blood concentration may show no impairment, while a naive user at the same concentration may be severely impaired. DRE evaluations frequently flag benzodiazepine-positive individuals as “CNS depressant” impaired without any consideration of whether the person is a chronic therapeutic user.
Opioids
Chronic pain patients on stable opioid regimens (oxycodone, morphine, fentanyl patches, buprenorphine) develop tolerance to the sedating and psychomotor-impairing effects. Studies have shown that patients on stable opioid doses perform comparably to controls on driving simulation tasks. A blood opioid concentration in a chronic pain patient does not carry the same impairment significance as the same concentration in an opioid-naive individual.
Amphetamines and Stimulants
Patients prescribed amphetamine-based medications (Adderall, Vyvanse) for ADHD develop tolerance to the stimulant’s side effects while maintaining therapeutic benefit. These patients may have detectable amphetamine in their blood at all times while being completely functional. Charging a stable ADHD patient with drug DWI based on a positive amphetamine result ignores the pharmacology of therapeutic use.
Case Results
Why Per Se Drug Limits Are Scientifically Indefensible
Some jurisdictions have enacted or proposed per se limits for drugs in blood which is a specific concentration above which a person is presumed impaired, regardless of observed behavior. For alcohol, the 0.08 per se limit has a reasonable scientific basis (though it is still an imperfect proxy for individual impairment). For other drugs, per se limits have no comparable scientific foundation.
The fundamental problem is that unlike alcohol, the relationship between blood drug concentration and behavioral impairment is not consistent, not linear, and not predictable from a single measurement. Tolerance, individual pharmacokinetic variability, polypharmacy, the timing of the measurement relative to the drug’s absorption and elimination curve, and the specific pharmacological profile of the drug all affect the relationship between concentration and effect. A single number cannot capture this complexity.
Defense Strategy: Using Tolerance in Your Case
- Establish your client’s medication and use history. A documented history of chronic, stable use (whether therapeutic or recreational) provides the foundation for a tolerance defense.
- Obtain medical records and prescription history. Pharmacy records, prescriber notes, and dosing histories establish the chronicity and stability of drug use.
- Retain a pharmacologist or toxicologist. An expert who can explain tolerance mechanisms to the jury in plain language is essential. The science is counterintuitive but jurors need to understand why a positive drug test does not automatically mean impairment.
- Challenge the DRE’s failure to account for tolerance. DRE evaluations do not include any assessment of the subject’s drug use history or tolerance status. This is a fundamental gap that should be highlighted on cross-examination.
- Challenge per se arguments. If the prosecution argues that any detectable level equals impairment, demand the scientific literature supporting that position for the specific drug at issue. For most drugs, that literature does not exist.
At Deandra Grant Law, the tolerance defense draws directly on Deandra Grant’s Master’s Degree in Pharmaceutical Science. Pharmacodynamics (the study of how drugs interact with biological systems to produce their effects, including tolerance) is core curriculum in pharmaceutical science education. When we argue that a blood drug concentration does not equal impairment, we are applying graduate-level pharmacology, not legal argument. Call (214) 225-7117 or visit texasdwisite.com.
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