The cannabis plant contains more than 144 different cannabinoids, contributing to the complexity of its regulation and market development.
Paranoia has surrounded cannabis—in the form of marijuana—for years, thanks to its primary psychoactive chemical delta-9 THC, the constituent typically under fire when “THC” has been discussed in the past.
Lately cannabis’ star has been on the rise, thanks in large part to CBD, a nonpsychoactive chemical predominant in the hemp form of cannabis that may offer a variety of potential health benefits.
Hemp was legalized in the U.S. for agricultural purposes in the 2018 Farm Bill, but is not yet legal in food or supplements, though that is the form in which it is most commonly found. Cannabis regulations have also been changing, with 15 U.S. states now allowing adult use and 36 allowing medicinal use, and 47 countries allowing it in some form. As attitudes have changed, so have regulations in sport.
Naturally present cannabinoids in cannabis
To understand the issues, one must know something about cannabis and cannabinoids. Things would be easy if marijuana only contained THC and hemp only contained CBD, but that’s not the case. Cannabis is a complex plant that contains more than 144 different cannabinoids that can change with heat, time or pressure.1 Cannabis varieties have been bred for specific aims, with marijuana focused on the infamous THC and low in CBD, while hemp is high in nonpsychoactive CBD with trace amounts of THC. Both marijuana and hemp varieties may contain other cannabinoids in various combinations, as can CBD products, which is in part what makes the cannabis species and CBD products unique.
THC and CBD are the most common cannabinoids, but others are becoming popular and may be found alone or in combination with CBD. Several like CBN (cannabinol), THCV (tetrahydrocannabivarin) and delta-8 THC have some psychoactive effects, while many other cannabinoids are generally considered nonpsychoactive.
CBN is a degradation product created by oxidation of THC. THCV is a homologue of THC found in certain types of cannabis varieties, usually in small amounts. Delta-8 can be found in small amounts in some cannabis types, but most delta-8 on the market is likely made through isomerization of CBD by heat and pressure or chemical reagents. The “A” forms of cannabinoids are acid forms, present in plants that are converted during decarboxylation through heating and/or drying to the parent form. For example, THCA (tetrahydrocannabinolic acid) converts to THC, and CBDA (cannabidiolic acid) converts to CBD. This is why sometimes test results report “max THC” or “max CBD,” which represents the total amount that could be present after conversion.
With this in mind, common naturally present cannabinoids (phytocannabinoids) include: CBD, CBDA, CBN, CBG (cannabigerol), CBC (cannabichromene), CBDV (cannabidivarin), delta-8 THC, delta-9 THC, THCA and THCV.
Synthetic cannabinoids
The popularity of natural cannabinoids has also driven the rise of synthetic cannabinoids, or cannabimimetics, substances made to mimic the effects of cannabinoids. Many categories and subcategories exist, with more than 300 variants. These come with a variety of naming conventions, including AM-411, AM-906, JWH-018, JWH-073, HU-210, STS-135, O-1184, UR-144, AB-CHMINACA, APICA, APINACA and related substances. Some of these were developed as synthetic alternatives to THC and sold under various names, including K2, Spice, Joker, Black Mamba, Kush and Kronic. FDA issued a warning against synthetic cannabinoids in 2018 due to their potentially harmful effects.
Cannabis regulations in sport and federal workplace drug testing
Cannabis has been prohibited in sport and federal workplaces for years, but one must scrutinize the details of the language and how drug testing is applied and adjudicated to determine whether CBD products may or may not be allowed. The focus in the application of sport drug testing—and also in workplace or military drug testing—has been on metabolites of THC, and more recently on cannabimimetics. Historically, the scope of testing has not included CBD or any other phytocannabinoids naturally present in CBD products in small amounts.
A primary difference separates workplace drug testing and sport drug testing. Workplace testing uses a more general immunoassay screening as a first step, with confirmation testing by mass spectrometry to verify a specific agent is present. While immunoassays are not likely to detect CBD, they may cross-react with different variants of THC, like delta-8 and delta-10, making those detectable.2 Mass spectrometry detection is specific to THC metabolites and is used exclusively in sport testing.
The key elements to consider in what kind of cannabis products may or may not be acceptable are:
Does the prohibited list language ban cannabinoids in general, or does it make an exception for CBD or other natural phytocannabinoids?
Is cannabis treated as a performance-enhancing substance with heavy sanctions, or is it treated as a drug of abuse with lighter sanctions and treatment?
What threshold level of THC metabolites or other cannabimimetics are considered a positive?
How does this work in the application of drug testing at the end of the day?
The answers to these questions have changed a lot recently, as detailed by the following.
Department of Defense (DOD) and federal workplace drug testing
The Substance Abuse and Mental Health Services Administration (SAMSHA) THC thresholds are used for federal workplace drug testing and DOD purposes. They have not changed since 2010, and remain at 50 ng/ml for initial immunoassay-based testing with a 15 ng/ml threshold applied in mass spectrometry analysis. Synthetic cannabinoids have an initial screen threshold of 10 ng/ml with a confirmation threshold at 1 ng/ml. Positive drug tests are serious business and may result in termination. DOD currently prohibits hemp and CBD product use in any form.
World Anti-Doping Agency (WADA)
Formed in 1999, WADA is known as the gold standard in sport drug testing. The WADA Prohibited List governs Olympic sport and is used as a model by many other sports. THC became prohibited in Olympic sport in 1998, after Canadian snowboarder Ross Rebagliati became the first to test positive for THC at the 1998 Nagano Olympic Games. He originally lost his medal, but had it returned as the rules had not yet been changed by the International Ski Federation (FIS), the governing body.
When THC was first prohibited in Olympic sport, it was at a level of 15 ng/ml, or 15 parts per billion. In 2013, that level was increased to 150 ng/ml in an effort to reduce positive drug tests from secondhand smoke (a threshold of 0.5 ng/ml applies to synthetic cannabinoids). This change also helped to reduce the strain on legal resources needed to arbitrate cases. Adverse analytical findings for THC fell from an average of 485 per year from 2006 to 2012 to 129 from 2013 to 2019.
In 2018, WADA excluded CBD from the Prohibited List, but that doesn’t exactly give the green light for CBD products in the Olympics. Unfortunately, the list language technically includes other natural cannabinoids that might be present in CBD products. While the other cannabinoids are not targeted in drug testing, they can still be interpreted as prohibited as the education from WADA, USADA and UKAD demonstrate. This leads to the perception that only CBD isolate that contains no other cannabinoids would be appropriate in Olympic realms, or the pharmaceutical drug form of CBD, Epidiolex. Hopefully the WADA Prohibited List language can be further refined in the future to make room for other natural cannabinoids in CBD products and represent the true scope of the testing.
In practice, THC metabolites and synthetic cannabinoids are the targets in sport or workplace drug testing; no other natural cannabinoids are included as of yet, but that can easily change at any time if motivation arises. The statistics for WADA accredited laboratories from 2006 to 2019 reported 4,314 adverse analytical findings for cannabinoids, 4,302 from THC metabolites and 12 from synthetic cannabinoids JWH018 and JWH073. It seems unlikely that WADA would add other minor natural cannabinoids to the testing scope unless they are perceived to enhance performance, be potentially harmful, or against the spirit of sport—the three listing conditions. WADA along with Professor Marilyn A. Huestis working on behalf of the National Institute of Drug Abuse (NIDA) put together an extensive anti-doping perspective, “Cannabis in Sport,” in 2011.3
In 2021, WADA made the move to treat THC positives as substances of abuse with significantly reduced sanctions. The 2021 WADA Prohibited List language reads:
“S8 – Cannabinoids
PROHIBITED IN-COMPETITION
All prohibited substances in this class are Specified Substances.
Substance of Abuse in this section: tetrahydrocannabinol (THC).
All natural and synthetic cannabinoids are prohibited, e.g.
• In cannabis (hashish, marijuana) and cannabis products
• Natural and synthetic tetrahydrocannabinols (THCs)
• Synthetic cannabinoids that mimic the effects of THC.
Exceptions – Cannabidiol”
The treatment of cannabinoids and CBD in the prohibited lists varies quite a bit throughout sport, particularly in the language used. Some of the regulations seen across sport today include:
NCAA
The NCAA prohibits cannabinoids in general and discourages the use of CBD products as well. However, important changes have been made regarding the level of THC considered a positive with the threshold raised from 5 ng/ml to 15 ng/ml in 2017 and moved up again in 2019 to the current level of 35 ng/ml, all in an effort to avoid positives from “passive inhalation.” The 2020-2021 NCAA Banned Substance list language reads as follows, “Cannabinoids – Marijuana, Synthetic cannabinoids (Spice; K2; JWH-018; JWH-073), Tetrahydrocannabinol (THC).”
MLB
Until 2019, MLB had been managing THC as a performance-enhancing substance with a urine threshold set at 50 ng/ml. In December 2019, MLB recategorized cannabinoids and cannabimimetics as drugs of abuse, while also announcing new testing for opioids. The organization moved the THC threshold up to the 150 ng/ml level used by WADA. Today the MLB Joint Drug Prevention and Treatment Program language reads: “1. Natural Cannabinoids (e.g., THC, Hashish and Marijuana), 2. Synthetic THC and Cannabimimetics (e.g., K2 and Spice).”
NFL
In early 2020, the NFL made changes in how it handles THC and cannabis. The league had been treating THC as a drug of abuse, but it will no longer suspend players for positives. The threshold was increased from 35 ng/ml to 150 ng/ml. Synthetic cannabinoids have a threshold of 2.5 ng/ml. CBD products are not specifically mentioned or excluded. The NFL 2020 Policy and Program on Substances of Abuse reads, “Delta 9-THC-carboxylic acid (marijuana)≥ 150 ng/mL[≥ 35-149 ng/mL in Stage Two for clinical purposes only], Synthetic Cannabinoids≥ 2.5 ng/mL.” Testing is now limited to an annual test during a two-week period at the start of training camp.
NHL
The NHL banned substance list has typically mirrored significant portions of the WADA Prohibited List, but the league has never treated THC as a banned substance. When it comes to THC, the league manages it under the NHL/NHLPA Program for Substance Abuse and Behavioral Health, and only “dangerously high levels” are considered a concern.
NBA
The NBA employs the lowest THC threshold in sport today at 15 ng/ml, at least through 2019. Testing for THC was suspended for the pandemic-shortened 2020-2021 season, perhaps signaling big changes ahead similar to other leagues. THC is treated as a drug of abuse with the current policy titled, “Marijuana and its By-Products, Synthetic Cannabinoids.”
UFC
The UFC has the most advanced language when it comes to CBD products. The mixed martial arts giant adjusted its policy on cannabinoids in January 2021. THC is now treated as a drug of abuse, with the 150 ng/ml WADA threshold applied. The UFC also made a key language change specifically allowing all other “phyto” cannabinoids, making room for CBD products as long as they are certified by an approved third-party certification provider. The UFC Prohibited List language now reads, “Cannabinoids: natural or synthetic delta-9-tetrahydrocannabinol (THC) or Cannabimimetics (e.g., “Spice,” JWH-018, JWH-073, HU-210).”
CBD and positive THC tests
One of the biggest questions surrounding CBD products is whether a user can test positive for THC. The answer is yes—but it is unlikely, unless the product contains significant amounts of THC. A 2001 study on workplace drug tests examined how much THC via hemp oil could be ingested without testing positive.4 The study administered THC in an oil matrix at various doses to subjects over 10 days and analyzed the amount of THC metabolites in their urine. At a maximum dose of 0.6 mg/day of THC, the highest THC concentration reached by mass spectrometry was 5.2 ng/ml, with only one subject reaching the 50 ng/ml immunoassay screening threshold. At 0.45 mg/day of THC ingestion, no subjects went above the 50 ng/ml screening threshold or above 5 ng/ml by mass spectrometry. A person staying below 0.5 mg of THC/d would be unlikely to test positive in any drug testing system evaluated herein.
The future of cannabinoids in sport
CBD is growing in popularity in sport, thanks in large part to the array of potential benefits it can offer to athletes, in particular with pain management and improved recovery.5 Once the regulations finally take shape to allow CBD as a legal dietary supplement ingredient, sport will likely fully embrace the compound. The popularity of CBD in sport might just lead the way. However, other issues loom when it comes to cannabinoids in sport.
Delta-8 THC is on the rise as a psychoactive alternative to THC, which is something sport should watch. It is suggested to have about two-thirds of the psychoactive effect as its cousin THC. Delta-8 can perhaps be legal if truly derived from hemp, but not if it is synthesized. Even when derived from hemp, if it is made with the use of harsh chemical solvents, significant health concerns could be a consideration. Delta-8 has been the subject of much discussion of late. DEA has clarified it is a Class I Controlled Substance, with the list now including, “Tetrahydrocannabinols – THC, Delta-8 THC, Delta-9 THC, dronabinol and others.”
Delta-10 THC, another psychoactive alternative to THC, is the dark horse, but it too is on the rise. Unlike delta-8, which does have the potential to be derived from hemp and CBD, delta-10 is a purely synthetic compound and, as such, it does not qualify as a dietary supplement or a hemp product. Nonetheless, that has not stopped it from being sold. If it continues to grow in popularity, delta-10 will likely be targeted in sport and workplace drug testing as well.
With CBD still shrouded in mystery and operating in an unregulated environment, it is no wonder healthy skepticism remains. Quality control (QC) concerns over products not containing what they claim, containing too much THC, or being contaminated with pesticides or synthetic cannabinoids have been noted. These are all serious concerns that athletes and other consumers need to be aware of and consider if they are going to use CBD products.
However, plenty of optimism surrounds CBD, too. Despite a lack of clear guidelines that define it as a legal supplement ingredient, CBD recently eclipsed turmeric as the No. 1-selling natural product ingredient. Its earthshattering rise in popularity has likely established a permanent place for CBD products in society, and in sport. More changes in the regulations can be expected as this exciting category continues to grow.
Editor’s note: This article is part of Natural Products Insider’s “CBD and Hemp Month” coverage. Click the link for additional content.
Oliver Catlin is the longtime president and co-founder of BSCG (Banned Substances Control Group), an international third-party certification and testing provider. With a background in sports anti-doping, he is widely regarded as a thought-leader in the field of sports nutrition and dietary supplements.
References
1 Freeman TP et al. “Medicinal use of cannabis based products and cannabinoids.” BMJ. 2019;365:1141.
2 ElSohly MA et al. “Cross-reactivity of selected compounds in the Abbott TDx cannabinoid assay.” J Anal Toxicol. 1990;14(5):277-279.
3 Huestis MA et al. “Cannabis in sport: anti-doping perspective.” Sports Med. 2011;41(11):949-966.
4 Leson G et al. “Evaluating the impact of hemp food consumption on workplace drug tests.” J Anal Toxicol. 2001;25(8):691-698.
5 Kasper AM et al. “High Prevalence of Cannabidiol Use Within Male Professional Rugby Union and League Players: A Quest for Pain Relief and Enhanced Recovery.” 2020;30(5):315-322.
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