INTERPRETATION ISSUES WITH BLOOD RESULTS FOR MARIJUANA OPIATES

INTERPRETATION ISSUES WITH BLOOD RESULTS FOR MARIJUANA, OPIATES, DESIGNER DRUGS, AND OTHERAPEUTIC AND ILLICIT DRUGS Bill Anderson, Ph. D, F-ABFT

Issues to be Discussed What can toxicologists tell you about your results? Ø Cannabis Issues Ø Opiates Issues Ø Benzodiazepines Issues Ø Designer Drugs Issues Ø

Toxicologists Testimony_1 Ø Typical Questions § § § What drugs are present? How do the detected drugs affect an individual? • Therapeutic effects, if any, maybe multiple • If impairing, signs/symptoms of impairment What was the concentration of the drugs? • Is the concentration high or low • Is it a therapeutic concentration ØI was once asked what is a normal concentration of heroin – Answer was zero • Is concentration impairing

Toxicologists Testimony_2 Ø If multiple drugs are present would they be additive, synergistic, or would they cancel each other out? • • Ø If methamphetamine and heroin taken together would they mitigate the response of each other? Actually may modify DRE observations. How about tolerance? § § Do impairing affects disappear with long term use? Was a new drug recently added or was a dose recently increased?

What a toxicologist can really say about drugs All of the above Ø Part of the above Ø None of the above Ø Depends not only on toxicologist but what information is available Ø Sometimes the best toxicologist in the world cannot offer opinions without support information Ø § § Driving pattern SFST’s and/or DRE

Cannabis Ø Probably the most challenging drug we have to deal with today- why? § § § Pharmacokinetics and pharmacodynamics of THC Differences in action of THC on individuals Dose from same cigarette may vary tremendously • • § Higher percentage of THC in newer marijuana Each user can titrate their dose Presence of other drugs – especially small amounts of alcohol

MAJOR ISSUE WITH CANNABIS Trying to make it fit the alcohol model of intoxication

Marijuana (Cannabis) Ø Active ingredient § Ø Delta-9 -Tetrahydrocannabinol (THC) Major Metabolites § 11 -nor-9 -carboxy-delta-9 -tetrahydrocannabinol • • • § Major Metabolite Only analyte detected in urine Inactive 11 -hydroxy-delta-9 -tetrahydrocannabinol Active Ø Concentration low; not measured in some labs, may become an issue with oral THC Ø

THC Very different from alcohol Ø Defies category of impairment Ø § § § Ø CNS stimulation CNS depressant Hallucinogen Routes of administration § Smoking • • § Main route for abused marijuana Medical Marijuana may be smoked in some states Oral • Hash brownies, Marinol®, Sativex (oral spray)

THC- Mechanism of Action Ø Two distinct receptors identified § § CB 1 (central), CB 2 (peripheral) Both act like anandamide, an endogenous cannabinoid that is involved with: • • • Ø Control of locomotion, Emotional behavior, Cognitive function, Cardiovascular response Pain, Feeding behavior, Addiction Also acts at dopamine receptors § Pleasure, reward systems

Behavioral Effects of THC Euphoria Ø Relaxation Ø Altered time perception Ø Lack of concentration Ø Impaired learning Ø Impaired memory, especially short term memory Ø Mood changes Ø § Panic reactions, hallucinations

Physiological Effects of THC Ø Ø Ø Ø Increase in heart rate Conjunctival suffusion (red eyes) Dry mouth and throat Increased appetite Hypotension and dizziness Lack of convergence Most behaviors return to baseline within 3 -8 hours Some impairment reported as far out as 24 hours after drug intake

THC (ng/m. L) - Plasma Smoking a Single Cigarette 3. 55 % THC 300 250 200 150 100 50 0 0 1 2 3 4 Time (hrs) 5 6 7

THC (ng/m. L) in Plasma Smoking a Single Cigarette 3. 55 % THC 6 5 4 3 2 1 0 0 2 4 6 8 Time (hrs) 10 12 14

THC Pharmacokinetics THC very lipophilic (fat soluble) molecule Ø Two phases of elimination Ø § § Ø Redistribution (t 1/2 short – few hours) Terminal elimination (t 1/2 long – up to 48 hours) THC goes into fat cells § § Leaches out slowly (rate limiting step for elimination) Metabolized immediately upon leaving fat depots • Explains why THCCOOH can be detected so long in the urine.

THC (ng/m. L) - Plasma Smoking a Single Cigarette 3. 55 % THC 300 250 200 THCCOOH 150 11 -OH-THC 100 50 0 0 2 4 Time (hrs) 6 8

THC (ng/m. L) - Plasma Smoking a Single Cigarette 3. 55 % THC 80 70 60 50 40 30 20 10 0 THCCOOH 11 -OH-THC 0 1 2 Time (hrs) 3 4

THC (ng/m. L) in Plasma Smoking a Single Cigarette 3. 55% THC Casual and Chronic Smoker 14 12 10 8 Casual 6 Chronic 4 2 0 0 5 10 Time (hrs) 15

Study of Karschner et al Addiction. 2009 December; 104(12): 2041– 2048 Twenty-five long term frequent cannabis users studied for 7 days of monitored abstinence Ø 9 had no measured THC Ø On day #7, 3 had values ≥ 1. 0 ng/m. L Ø § § § 3. 0 ng/m. L – 4 blunts/day 1. 0 ng/m. L – 8 blunts/day 2. 2 ng/m. L – 4 blunts/day All with positive results were female Results not correlated with body mass index

THC and Driving Ø Effects have been studied primarily by three methods: § Epidemiological studies • • • § § Odds ratio for potential to be killed in MVA Odds ratio for culpability of causing a non-fatal crash Observations of impairment in multiple studies of arrested drivers Various laboratory test that are markers for impairment Driving studies • • On-road Simulators

General Facts about THC Ø Ø In Northern Nevada, more than half of THC concentrations in DUID cases are between 2 -5 ng/m. L. For casual smoker, THC is <2 ng/m. L within 3 -4 hours. Major effects of THC last for 4 -6 hours, depending upon whom you believe. Impairment for pilots on highly complex task reported after 24 hours.

General Facts about THC -2 Ø There is no proven relationship between THC concentration and impairment. § Ø Ø THC drops so rapidly, it is impossible to know what specimen concentration was at the time of driving. Recent study from Australia, Papafotiou et al. • THC = 6. 2 -13. 8 ng/m. L@ 30 min after smoking with significantly less impairment than at 55 min when THC = 3. 2 -5. 1 ng/m. L. • How can we explain that? • Does THC in CNS peak later than it does in the blood? No correlation of urine with much of anything except use

General Facts about THC 3 Tolerance to some THC effects can occur with heavy smoking Ø Tolerance does NOT develop with all measures of impairment Ø § Ø Big argument in literature about just how much tolerance does develop Cognitive deficits have been observed in chronic smokers for as long as 21 days. § Big debate about degree of impairment exists in chronic smokers

General Facts about THC -4 Oral THC disposition very different than smoked THC Ø THC peaks at 120 min and concentration is low 3 -7 ng/m. L up to 19 ng/m. L Ø Active hydroxy metabolite ≥ than THC, tmax after THC Ø

THC Plus Alcohol Ø Two drugs that impair ability to drive by acting on multiple receptors § § Ø Ø Would expect at least additive affects Many researches report a synergistic effect Multiple studies have demonstrated this phenomenon Significant impairment seen with low doses of alcohol (0. 04 g/100 m. L)

Testimony Last Week THC 8. 7 ng/m. L Ø THCCOOH 19 ng/m. L Ø Issues Ø § § § § Does THC impair driving? Does THC increase crash risk? Does THC sometimes improve driving? Was this a recent smoking? Was subject a chronic smoker? Do SFST’s and/or DRE work for THC? Was he impaired?

Opiates and Opioids Ø Major issues § Dose can vary tremendously from person to person • • § Tolerance develops for almost all opiates • § Therapeutic concentration of methadone can be from 50 ng/m. L up to 800 ng/m. L or higher High dose pain patients can have concentrations of any opiate that would kill naïve users Tolerance can be lost or greatly diminished with only one day of abstinence Do pharmacokinetic calculations allow toxicologist to estimate expected

Opiates – The Good News Ø Non impaired individuals are not or do not: § § § Slow and lethargic Sleepy and “on the nod” Fail SFST’s They will have pin-point pupils Ø Good officer observations and articulation is paramount to making a case. Ø

Benzodiazepines/Carisoprodol and Z Drugs (zolpidem, zopiclone, zaleplon) Therapeutic concentrations known for most conditions, but can vary widely Ø Often prescribed with other CNS depressants and/or opiates Ø Tolerance does develop Ø If severely impaired have look and feel of alcohol intoxication Ø For Z-Drugs, I am often asked if the concentration is therapeutic. It often is, but what are these drugs used for? Ø

Ø Ø People have a right to drive with prescribed drugs. They do not have a right to drive while impaired by prescribed drugs.

Designer Drugs Lab may not have standards Ø No pharmacological or pharmacokinetic studies performed. Ø Concentration in blood may not be available Ø § If it is, we might not know what it means As soon as designer drugs are made illegal, users switch to something new Ø Current favorites are ethylone and butylone, U-47700, designer fentanyls at Ø

What Does it Take to Identify Drugged Driver Observant and articulate arresting officer Ø DRE exam is a great help Ø Competent laboratory analysis Ø DA awareness of issues with drugged driving Ø Competent toxicology testimony Ø