Understanding THC & Detection Time

Marijuana (THC) is a mixture of dried leaves and flowering tops of the hemp plant Cannabis sativa. The agents that produce the hallucinogenic and other biological effects of marijuana are called cannabinoids. Marijuana is usually smoked, but may also be ingested, either incorporated into food or as a tea. It is rapidly absorbed from the lungs into the blood with rapid onset of effects; the onset is slower but prolonged when ingested.

The cannabinoid 9-tetrahydrocannabinol (Δ9-THC) is generally accepted as the principal psychoactive ingredient in marijuana and its sister drug hashish although other cannabinoids may contribute to the psychological and physiological actions of these drugs. Δ9-THC is distributed in and absorbed by various fatty tissues and then is very slowly released to the plasma; it is then metabolized in the liver to over 24 metabolites and eventually excreted in the urine and feces. The metabolite 11-nor-Δ9-THC-9-carboxylic acid (THCCOOH) is the primary urinary marker of THC use. While immunoassays will react to THCCOOH and other THC metabolites to varying degrees, the confirmation assays are designed to detect only this metabolite.

THC use continues to be a major problem for law enforcement personnel as well as drug counseling and treatment professionals. Various surveys or studies show that THC is still the most frequently used illicit drug. Only tobacco and Ethanol have higher usage rates reported in most surveys. Reliable testing services are an important tool in detecting and monitoring drug use and/or compliance with treatment protocols or drug free orders.

Much of our understanding of detection times is based on research that was done on older, less specific methods and on non-clinical studies. New reagent systems have improved the specificity of commonly employed immunoassays to the THCCOOH metabolite, thus reducing the rate of false positives. This increased specificity has also apparently narrowed the window of detection, particularly for the casual user.

The results of a new controlled clinical study (1) published in the October 1995 issue of the Journal of Analytical Toxicology, shows that the window of detection for casual users is much narrower than previously assumed. It also emphasizes the inter and intra-individual variability that is part of the problem in monitoring drug use.

The study involved measuring all urine samples from a group of subjects for a period of one week after smoking a placebo, low dose THC cigarette and a high dose THC cigarette on three separate occasions. Dosing was random and spaced a week apart so as not to bias results by the effects of one dose on the following dose. The individuals in the study were all chronic users that demonstrated a series of consecutive negative urines prior to starting the dosing studies.

The data showed that using the 100 ng/ml positive cutoff resulted in a detection time of as little as 6 hours to about 24 hours after smoking the low dose cigarette and 5.6 hours to about 51 hours after smoking the high dose cigarette. There was no difference in the time of last consecutive positive and the last detected positive after smoking the low dose cigarette.

However, after the high dose cigarette, there were individuals whose last positive result occurred significantly later than their last consecutive positive result. The last consecutive positive result occurred at as little as 4 hours after dosing to as much 40 hours later.

The individual whose last consecutive positive occurred at 4 hours was the same individual who had the last reported positive result of about 51 hours, thus emphasizing the extreme variability of excretion rates in randomly collected drug specimens (Table 1.).

When the positive cutoff is lowered to 50 ng/ml the window increases somewhat but the variation in detection times is greater. Detection time at 50 ng/ml ranged from of as little as 6.4 hours to about 48.5 hours after smoking the low dose cigarette and 18 hours to about 78 hours after smoking the high dose cigarette. The last consecutive positive after smoking the low dose cigarette occurred at as little as 6.4 hours up to about 45 hours. The last consecutive positive result after the high dose cigarette occurred at as little as 4 hours after dosing to as much 48 hours later. As with the data collected at 100 ng/ml, there were individuals whose last positive result occurred significantly later than their last consecutive positive result. In this group, the individual whose last consecutive positive occurred at 4 hours had a last reported positive result of about 57 hours (Table 2.).

Even when using a cutoff level of 20 ng/ml (Table 3.) or GC/MS (Table 4.), the detection window only exceeded four days in two of the six individuals who smoked the low dose cigarette. After a high dose cigarette, the last detectable positive was at 149.5 hours ( 6 days) for one individual, but most fell between 2.5 days and 3.5 days.

Table 1. DETECTION TIME RANGES at 100 ng/ml CUTOFF
Type of cigarette:	Last consecutive pos.	Last positive
Low dose cigarette	6 to 24 hours	6 to 24 hours
High dose cigarette	4 to 80 hours	5.6 to 51 hours

Table 2. DETECTION TIME RANGES at 50 ng/ml CUTOFF
Type of cigarette:	Last consecutive pos.	Last positive
Low dose cigarette	6.4 to 45 hours	6.4 to 48.5 hours
High dose cigarette	4 to 48 hours	18 to 78 hours

Table 3. DETECTION TIME RANGES at 20 ng/ml CUTOFF
Type of cigarette:	Last consecutive pos.	Last positive
Low dose cigarette	9.3 to 68.5 hours	23.3 to 127.2 hours
High dose cigarette	4 to 78.4 hours	58.5 to 149.5 hours

Table 4. DETECTION TIME RANGES at GC/MS 15 ng/ml CUTOFF
Type of cigarette:	Last consecutive pos.	Last positive
Low dose cigarette	8.0 to 68.5 hours	8.0 to 68.5 hours
High dose cigarette	4 to 78.4 hours	57.0 to 122.3 hours

The same authors published a paper in Clinical Chemistry in 1994 (2.) showing the value of lowering the screening cutoff level from 100 ng/ml to the current federal guideline of 50 ng/ml. For the purposes of this study, they used the following definitions:

• "True positive" = immunoassay positive (≥ 50 ng/ml) and GC/MS positive (≥ 15 ng/ml);
• "True negative" = immunoassay negative (< 50 ng/ml) and GC/MS negative (< 15 ng/ml);
• "False positive" = immunoassay positive (≥ 50 ng/ml) and GC/MS negative (< 15 ng/ml);
• "False negative" = immunoassay negative (< 50 ng/ml) and GC/MS positive (≥ 15 ng/ml).

The study examined approximately 1000 specimens at the 100 ng/ml and 50 ng/ml cutoffs for several of the currently available THC immunoassays. As might be expected, lowering the cutoff to 50 ng/ml significantly increased the rate of recovery of true positives, decreased the rate of false negatives and had only a small increase in false negatives (Table 5.).

The data presented for the assay we use at SRL showed a more than doubling of the true positive rate from 4.7% to 11.2%, with the false negative rate dropping from over 10% to under 4%. The false positive rate increased slightly from 0.4% to 1.2%. Our experience with this assay agrees with this study, i.e. when using the 50 ng/ml positive cutoff the recovery rate of true positives is significantly increased without a significant increase in the risk of false positives.

Table 5. EFFECT OF LOWERING POSITIVE CUTOFF
Cutoff level	True Positives	False negatives	False positives
100 ng/ml	4.7%	10.4%	0.4%
50 ng/ml	11.2%	3.9%	1.2%

These two studies show the difficulty of detecting and monitoring drug use. Successful detection of infrequent low-level marijuana use is enhanced by using assays employing the lowest practical detection limits and totally random and unpredictable sample collections. Scientific advances have improved our ability to reliably identify and quantify cannabinoids in urine, but the interpretation of these results remains a difficult task.

The following is some information that you may find helpful in interpreting positive marijuana (THC) results.

The only truly reliable way to pinpoint time of use is through serial plasma studies (3.), but quantitative urine THC values can give you some indication of the level and timing of drug use when serial samples are collected. The quantitative value is influenced by many factors, such as frequency and duration of use, quality of the marijuana, personal metabolism, etc. and can vary significantly throughout the day. As a general rule of thumb, the higher the value, the more likely the use of marijuana has been heavy and/or recent.

• Levels below 100 ng/ml are relatively low and would correlate with light use or heavier use more than 48 hours prior to the urine collection.
• Levels between 100 and 250 ng/ml are moderate and are best interpreted in relationship to previous results or reliable data on usage history.
• Levels between 250 and 750 ng/ ml are high and are more likely to represent current use (within the prior 72 hours), but are still best interpreted in relationship to the factors mentioned above.
• Levels exceeding 750 ng/ml are very high and have a good correlation with usage within the past 48 to 72 hours.

The half-life of THC can vary markedly, but for most people it is one to three days (3.). That means that the THC level can be expected to decrease by about 1/2 every 24 to 72 hours during a period of abstinence. Typically, levels drop to below 100 ng/ml fairly quickly, with low levels (below 50 ng/ml) persisting for longer periods of time. Levels between 20 and 50 ng/ml have been reported in individuals with histories of chronic heavy use for as much as 2 or 3 months after use is discontinued.

Current research has shown that passive exposure may result in low level positives (up to about 30 ng/ml) if the exposure conditions are severe enough. That means heavy smoke in a confined, non-ventilated space for an extended period of time. The data also suggests that THC is not likely to be detectable for more than about 24 hours after such exposure. It is unlikely that most people would tolerate the extreme conditions necessary to produce a positive result from passive exposure. The federal guidelines for work place testing have reduced the cutoff level for positive results from 100 ng/ml to 50 ng/ml, because it can be safely assumed that levels exceeding 50 ng/ml represent use of THC rather than exposure to side stream smoke.

References:

1. Heustis, M. A., et. al., Journal of Analytical Toxicology, Vol. 19, October 1995, pp.443-449
2. Heustis, M. A., et. Al., Clinical Chemistry, 40/5 1994, pp. 729-733
3. Heustis, M. A., AACC TDM/Tox., Vol. 14, No. 6, June, 1993, pp 131-138
4. Abuscreen®ONLINE , Automated Assays for Drug Abuse, THC, Roche Diagnostic Systems, Inc., Branchburg, NJ, September, 1992

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