What Did My Patient Actually Take? An Overview of Marijuana (THC) Results

Clinical Update
February 2022

What Did My Patient Actually Take? An Overview of Marijuana (THC) Results

 Marijuana Overview

The interpretation of marijuana results differs when considering presumptive vs. definitive testing methods, and may also differ among laboratories.  The information provided here is intended to assist providers with deciphering positive delta-9-THC (THC)/marijuana results from Aegis, which have undergone definitive testing by liquid chromatography tandem mass spectrometry (LC-MS/MS) prior to reporting.

Marijuana is the most commonly used illicit drug in the United States.  The 2020 National Survey on Drug Use and Health reported that 59.3 million people aged 12 or older used illicit drugs in the past year, with 49.6 million (~84%) using marijuana.1 A national survey from 2016 found that 1 in 10 individuals aged 12 or older have used marijuana in the past month.2 Cannabis is the drug with the highest prevalence in cases involving driving under the influence of drugs and the source of more positive results in workplace drug tests than any other drug of abuse.3
 
Marijuana False Positives on Immunoassay
Immunoassay, or point of care testing, has the highest risk of false positives among all testing methods.4 The following medications and over-the-counter products have chemical structures similar enough to THC to trigger a presumptive positive result that would not confirm via LC-MS/MS on an Aegis test: Acetylsalicylic acid, baby wash/soaps5, efavirenz4,6, NSAIDs (ibuprofen, naproxen)7-8, proton pump inhibitors (pantoprazole)4,9, tolmetin10, and more.
 
Marijuana False Negatives on Immunoassay
People using marijuana may attempt to tamper urine samples to produce negative results. Addition of Visine® eyedrops to urine samples has been shown to cause false-negative results for THC. Chemical analysis of Visine® eyedrops has shown that the ingredients, benzalkonium chloride and the borate buffer, can directly decrease the concentration of the 9-carboxy-THC metabolite in the urine with no effects on the antibodies in the immunoassay. However, these ingredients do not chemically alter 9-carboxy-THC, which will still be detected by mass spectrometry.8,11
 
Period of Detection Considerations
The detection time for marijuana in urine depends heavily on the body composition of the patient and the frequency of use. Daily use of marijuana is expected to be detectable in urine for a period up to 10 days; light use (such as one joint) may only be detectable for up to 3 days.12  One study demonstrated that 73% of 37 chronic marijuana users had THC concentrations below a cutoff of 15 ng/mL within two weeks of last ingestion.13  Patients with a large amount of adipose tissue and/or those with heavy use over a chronic period may store marijuana and excrete metabolites for a longer period of time. In such rare cases, marijuana has been reported with a period of detection up to 30 days, with the longest period published as 95 days. Such a period of detection is the exception, not the rule.4,12,14  
 
Oral Fluid Considerations
Marijuana positives in oral fluid are generally due to a depot effect after smoking, which limits interpretation to recent use.15 Passive inhalation of marijuana is also unlikely to cause a positive test in oral fluid at typical laboratory thresholds, except in circumstances of heavy smoke exposure, long duration of exposure, lack of ventilation, and if exposure occurs on the same day as sample collection.16-17  Ingestion of dronabinol (Marinol®) is unlikely to cause a positive test for THC in oral fluid at a two ng/mL threshold, which is used at Aegis.18 Oral ingestion of THC produces lower and later peak blood concentrations and effects than smoked THC, and only 6-20% of an orally administered dose reaches systemic circulation.18-19 Using oral fluid as a specimen type may, therefore, be beneficial when assessing patients who claim to ingest Marinol® to explain marijuana positives in urine.
 
Passive Inhalation
A common issue that confuses the interpretation for marijuana testing is “passive inhalation.” The argument presented is that exposure to marijuana smoke by a non-user will result in a positive urine cannabinoid test, and therefore, a person will be wrongfully accused of drug use. Historically, multiple studies were performed in the 1980s that demonstrated that passive exposure to marijuana in extreme conditions did sometimes result in positive delta 9-carboxy-THC in urine.20-24
 
In the study by Cone et al. which reported concentrations obtained by chromatography/mass spectrometry methods, positive results were found under repeated exposure or exposure conditions so extreme that the study subjects were offered goggles to wear in order to prevent eye and mucous membrane irritation due to the test area being visibly saturated with marijuana smoke. Anecdotal evidence of study subjects who had taken off their goggles concluded that prolonged exposure would be unlikely to be tolerable to most subjects.23 Most of the studies were conducted in unventilated areas (closed cars or specifically built rooms of small size). Furthermore, Cone et al. conducted a test of room air THC exposure levels in the same test room as their studies with ventilation, which resulted in THC levels <10% that of the room unventilated.23
 
One criticism of studies conducted in prior decades is that marijuana is available at increased potency today, which could influence drug test results. More recent studies conducted to investigate urinary concentrations of carboxy-THC following passive exposure include Rohrich et al. where subjects were exposed to marijuana smoke for three hours in a Netherlands coffee shop. Urinary concentrations of delta 9-carboxy-THC were no greater than 5 ng/mL (without hydrolysis) or 8 ng/mL (with hydrolysis).25 A second study performed by Cone et al. evaluated passive exposure using high-potency marijuana (11.3%) being smoked by six smokers for one hour in the presence of six non-smokers in unventilated and ventilated conditions.17 The researchers demonstrated that with ventilation consistent with typical air conditioning, some study subjects did excrete detectable delta 9-carboxy-THC.  The maximum concentration observed in a non-smoker with unventilated conditions was 57 ng/mL, whereas with ventilated conditions the maximum was 15 ng/mL, both occurring at 4-6 hours following exposure.17
 
Cone et al. also researched the likelihood of positive oral fluid results under similar conditions as above. Maximum oral fluid concentrations of THC were present in non-smokers up to 308 ng/mL in unventilated conditions and 75 ng/ mL in ventilated conditions.26 Maximum concentrations occurred immediately post exposure and dropped rapidly within 1-3 hours, with subjects in unventilated conditions testing below 2 ng/mL after 12 hours, and subjects in ventilated conditions after 2 hours. During the unventilated studies, smoke accumulation was rapid, and goggles were used to alleviate eye irritation, whereas ventilated sessions produced visible smoke at lower levels. Niedbala et al. measured THC in oral fluid following passive exposure to marijuana for 20 minutes in an unventilated van with four smokers and found THC concentrations did not exceed 1.2 ng/mL following exposure, with all specimens below 2 ng/mL. Urine concentrations of delta 9-carboxy-THC were also assessed and did not exceed 15 ng/mL.16 Moore et al. measured THC in oral fluid following less extreme exposure in a Dutch coffee shop. Oral fluid specimens collected outside the coffee shop during exposure reached a maximum THC concentration of 17 ng/mL at 3 hours; in specimens collected 12-22 hours following exposure THC was either not present or less than 2 ng/mL.27
 
Overall, the likelihood of positive marijuana results from passive inhalation will depend on the amount and duration of exposure, ventilation during exposure, and time since exposure. In circumstances of true passive inhalation, levels of THC (oral fluid) or 9-carboxy-THC (urine) would be expected to be low, and the exposure would have occurred very recent to the time of collection.
 
Cannabidiol (CBD) Products
The Cannabis sativa plant contains over 500 compounds, with at least 100 of which are cannabinoids, the most widely studied being THC and CBD.28 Hemp and marijuana are two varieties of Cannabis sativa and differ in THC content with hemp containing 0.3% THC or less.  THC is responsible for the characteristic “high” of marijuana, while CBD has not been shown to have the same cognitive effects. CBD has been studied as a treatment for multiple disease states and health conditions, including bipolar mania, Huntington’s disease, inflammation, insomnia, multiple sclerosis, nausea, social anxiety disorder, schizophrenia, and seizures. Prescription cannabidiol (Epidolex®) was developed to contain negligible amounts of THC; thus, it is unlikely to cause a marijuana positive.29
 
Although CBD itself will not be detected as THC on a urine drug test, it is possible for CBD products to contain THC given both are extracted from the Cannabis plant. The product descriptions “medical marijuana”, “high CBD,” and “low THC” are often used interchangeably, and no standard definition exists for these individual terms.
The legal limit for the amount of THC allowed in CBD products is variable, ranging from 0.3% to 5% depending on state-specific regulations.30 Importantly, the manufacturing and purification processes for CBD products are not regulated by the Food and Drug Administration (FDA), leaving little opportunity for mandated CBD to THC ratios to be enforced.30-31 THC content varies among unregulated hemp and cannabidiol products; the ability of these products to cause a positive marijuana result will depend on the amount of THC present in the product, the amount and frequency of the ingestion, and individual patient pharmacokinetics.32-34  Given these factors, it is possible for the use of a CBD product to result in a THC-positive urine drug test. It is vital that healthcare providers use caution when recommending or reviewing CBD products for patients due to little regulation and inaccurate labeling of quantities within products.35
To be inclusive of all states’ regulations and possible causes for positive marijuana results, Aegis has combined the marijuana and Marinol® compliance calls on the urine lab report to read as “Marijuana/Marinol®” with the comment mentioning CBD- and hemp-containing products as shown in Figure 1 below.

Figure 1


 
Delta-8-Tetrahydrocannabinol (delta-8 THC)
Similar to THC, delta-8 THC is a psychoactive cannabinoid of the Cannabis sativa plant.  Delta-8 THC is nearly identical to THC in chemical structure, differing only in the placement of a double bond.  Both compounds have similar binding affinities at CB1 and CB2 cannabinoid receptors36 and produce similar effects with the psychotropic potency of delta-8 THC being estimated to be approximately two-thirds that of THC.37 A recent survey of delta-8 THC users suggests delta-8 THC produces the same experiential effects as THC but with less cognitive distortion and distressing mental states such as paranoia and anxiety than THC.38 In addition to having similar pharmacodynamic properties, delta-8 THC and THC share the same metabolic pathways.39 Thus as delta 9-carboxy-THC is the main metabolite for THC in urine, delta 8-carboxy-THC is the main metabolite for delta-8 THC in urine.40
 
Delta-8 THC is not present in the Cannabis sativa plant in significant amounts.  The percentage of delta-8 THC in cannabis plant material was determined to be on average 0.65% with a maximum observed percentage of 3%.41  In a recent study, urine samples containing delta 9-carboxy-THC were evaluated for the presence of  delta 8-carboxy-THC, which was detected in low concentrations (0.22-8.9 ng/mL), presumably from plant origin.  The average percentage of delta 8-carboxy-THC to delta 9-carboxy-THC observed was 0.68% and ranged from 0.05 to 2.83%.40  
 
Although delta-8 THC is present in low abundance in the cannabis plant, it may be readily synthesized from CBD.  Recently delta-8 THC products such as gummies and vapes are available over-the counter with some being marketed as “legal hemp” products.  Due to the naturally low levels of delta-8 THC in hemp it is thought that delta-8 THC is being synthesized from CBD and added to hemp plant material in high concentrations that far exceed what is naturally found in cannabis and then sold as “legal hemp”.36 There is currently confusion regarding the legal status of such products because tetrahydrocannabinols, natural or synthetic, are classified as controlled in schedule I by the Controlled Substances Act (CSA).  However, the CSA excludes from control tetrahydrocannabinols in hemp.  Some states are choosing to define delta-8 THC as a controlled substance and others are prohibiting production and sale of delta-8 THC.
 
Being similar in chemical structure, immunoassay tests are not able to distinguish between the delta-8 and delta-9 THC isomers.  Thus use of delta-8 THC will likely produce a non-negative cannabinoid presumptive test result.  Confirmatory testing using chromatography/mass spectrometry may not be able to distinguish between the isomers unless they are separated in the test method.  Through definitive confirmatory testing at Aegis, we do not expect delta 8-carboxy-THC to produce a positive delta 9-carboxy-THC result.  Although it is important to note that like CBD products, some delta-8 THC products may contain THC and are not regulated by the FDA.42  Thus depending on the amount of THC present in the product, the amount and frequency of the ingestion, and individual patient pharmacokinetics, it may be possible for the use of a delta-8 THC product to result in a THC-positive urine drug test.
 

NOTICE: The information above is intended as a resource for health care providers. Providers should use their independent medical judgment based on the clinical needs of the patient when making determinations of who to test, what medications to test, testing frequency, and the type of testing to conduct.

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References:

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42. https://www.fda.gov/consumers/consumer-updates/5-things-know-about-delta-8-tetrahydrocannabinol-delta-8-thc