Rehashing the Minor League Drug Program

The United States’ population is rapidly shifting its attitudes towards cannabis. In an October 2018 Pew survey, 62 percent of Americans supported the legalization of marijuana, more than twice the share of respondents who did so in 2000. As of this writing, 33 states have legalized medical marijuana, and ten states and the District of Columbia have legalized the recreational use of marijuana.

Looking at marijuana itself doesn’t provide the full story, however, as the drug is more than just its most infamous chemical constituent, tetrahydrocannabinol. In 2018, the U.S. Food and Drug Administration approved the use of Epidiolex, comprising cannabinoid cannabidiol (CBD) without THC; CBD is also a major component of cannabis plants, and has demonstrated efficacy for the treatment of epilepsy and generalized seizure. There is a burgeoning market for CBD infused products — it’s in everything from beverages to mascara — and it’s advertised for the treatment of everything from anxiety to acne.

Given the purported benefits, increased legalization, and seemingly few downsides, it’s no surprise that more people are exploring marijuana and CBD for the treatment of a variety of conditions. But our focus today will be a little narrower. We are concerned with both the benefits and risks of CBD as an intervention for baseball players. Unlike most of the discussions we’ve had of drugs and supplements as they pertain to baseball players, however, we need to recognize that in this case, the risks are a little different for major league players and minor league players.

While players on the 40-man roster are subject to MLB’s Joint Drug Prevention and Treatment Program, minor league players must adhere to the Minor League Drug Prevention and Treatment Program. The most glaring disparity between these two lists is the prohibition of marijuana, which is listed as a “drug of abuse” in the MiLB program, and conspicuously absent from the major league program. It has been noted that this discrepancy may simply serve as a proxy for assessing character or work ethic, which can lable players who use marijuana with stubborn stereotypes, though there is some anecdotal evidence that suggests that front offices vary in their willingness to work with players when it comes to marijuana use.

The reason for the disparity between the major league and minor league drug programs comes down to the Collective Bargaining Agreement and the MLBPA: “The player’s union has consistently opposed strict punishment for marijuana offenses going back to MLB’s first Joint Drug Agreement in 2002. Minor league players are not protected by the union, so MLB can impose whatever punishment they want.”

As far as that punishment goes, a second offense for testing positive for a “drug of abuse” is a 50-game suspension. Bear in mind that in the Minor League Drug Program, “drugs of abuse” lumps together substances like marijuana (THC, hashish), cocaine, LSD and opioids. When suspensions are announced, the violation is always flagged as the use of a “drug of abuse”; there isn’t usually clarification regarding which substance triggered the positive test, unless the player or team volunteers this information. Essentially, a player will receive a 50-game suspension, whether the drug was heroin or marijuana.

Creating a genus of “drugs of abuse” that includes such a wide variety of disparate substances is a bit incongruous with the state of these substances as they are viewed scientifically and legally, at both the federal and state levels. The Drug Enforcement Administration Controlled Substances classification schedule divides the generic “drugs of abuse” based on legality, addiction potential, and therapeutic benefit, providing a bit more of a delineation between substances such as marijuana and opioids.

Of course, the DEA operates on the federal level, where marijuana is still illegal and is classified as a Schedule I drug. But as we mentioned, more states than not have now legalized medical marijuana, and recreational marijuana is now legal in 10 states and Washington, D.C. And we can’t forget that major league baseball also operates in Canada, where marijuana was legalized in July 2018. Including major league and minor league teams, there are 35 MLB-affiliated baseball teams located in jurisdictions where pot is legal. Teams travel for away games, which might be played at one of these sites. This all means there are a number of baseball-adjacent locations where players may come into contact with cannabinoid products, intentionally or accidentally, or through secondary exposure.

Let’s examine the verbiage of the Minor League Drug Program; included in “drugs of abuse” are “Natural Cannabinoids (e.g., THC, Hashish and Marijuana)” and “Synthetic THC and Cannabimimetics (e.g., JWH-018, JWH-073, and ‘Spice’)”. It’s relatively easy to recognize that THC, JWH-018 and JWH-073 are names for specific chemical compounds. But marijuana and hashish refer to products derived from Cannabis sativa plants. What exactly is a “Natural Cannabinoid”? It’s a bit vague. “Natural Cannabinoids” would reasonably encompass any compound derived from cannabis. Cannabinoid is a term that encompasses compounds derived from cannabis.

Cannabis, marijuana, hashish and other hemp-based products contain numerous compounds. Cannabis comprises over 100 cannabinoid compounds — and those are just the compounds that have been identified. The non-THC cannabinoid that one is most likely to run across nowadays is cannabidiol (CBD), a non-psychoactive component of marijuana. It’s a bit silly to say “Natural” cannabinoid, though; THC is THC, regardless of whether you extract it from a cannabis plant, or synthesize it through chemical reactions in a laboratory. We’ll presume that the use of the term “natural” refers to a chemical compound that can be found in the plant, regardless of its actual source, while a synthetic cannabinoid is a chemical compound that is not found in nature.

Regardless of the source of the “Natural Cannabinoid”, it’s still not entirely clear what compounds the Drug Program encompasses. It’s highly unlikely that the drug testing extends beyond THC. When we’re just testing for one compound, it’s a lot easier to figure out what metabolites we’re looking for in our detection tests. But when we’re looking at plant products, particularly cannabis plants that contain several different compounds, we have to cast a wider net to detect multiple metabolites of multiple compounds. If there are 100 cannabinoids in marijuana, does testing look for all 100 compounds and their metabolites? Even if we limit ourselves to a handful of cannabinoids, this could be overwhelming. The metabolites of THC are different from the metabolites of CBD. So if you take a product that only contains CBD, it should not result in a positive test for THC. But we’ll revisit this later.

For now, let’s take this list literally, and assume the testers are looking only for the chemical compound THC and its metabolites, since THC is the psychoactive component of cannabis plants. Similarly, the cannabimimetics are specific compounds; a test would look for those specific compounds and their metabolites. It’s worth noting that these are called “cannabimimetics” because they mimic the activity of marijuana, although their chemical structures are different from THC.

Even assuming that these compounds have a therapeutic effect, we need to consider their other effects, and study the pharmacology of cannabinoids. We don’t know much about how long marijuana stays in the body, or how long the effects will last — or even what the effects are. Is this a performance enhancer? Or does it actually hinder performance? Perhaps it eases anxiety. Maybe it leads to weight gain through secondary effects.

This is an issue for the public at large, as marijuana legalization becomes more widespread. What are the safety thresholds? We do have some limited studies regarding the pharmacology of THC. Interestingly, the effects of secondhand marijuana smoke — from a roommate or a car mate — suggest that secondhand exposure to marijuana could result in a positive drug test. What amount of marijuana would meet the limitations of Driving Under the Influence or Driving While Intoxicated?

The fact is, we just don’t know. Researchers haven’t been able to conduct experiments with the scientific rigor one would expect of an investigational study of a therapeutic intervention, primarily due to the extreme limitations placed upon cannabis research by the federal government. The strains of cannabis that are approved for research within the U.S. are not representative of the cannabis currently available on the market.

Minor league players may enjoy some therapeutic benefits from CBD use, and they may be tempted to give it a try, thinking that it won’t violate the MiLB Drug Program. However, CBD is unregulated, and may contain THC. CBD oils may not be free of THC and other marijuana metabolites that would trigger a positive test. Because these CBD-containing products are not regulated by the Food and Drug Administration, there is very little oversight as to their sourcing and purity, never mind their efficacy.

When we take all of this into account, while there might be therapeutic benefits to cannabinoids for minor leaguers who might want to try CBD, rules are rules, and as of now, a positive test for THC is a punishable offense for minor league player Thus, it’s clear that they should be wary of cannabis products, even those that purport to contain only CBD and not THC, unless they can be absolutely certain that their CBD oil contains no THC whatsoever.

Major league baseball players are not in danger of a suspension for marijuana use, so they should be safe to indulge. Marijuana and CBD likely have some sort of therapeutic benefits for certain people. In theory, major league baseball players can use marijuana and cannabinoid products to their heart’s content, enjoying whatever benefits cannabinoids provide, so long as it doesn’t interfere with their play on the field or training regimen, right?

As always, we need to weigh both risks and rewards. The risk for a minor leaguer is a 50-game suspension — but what is the risk for a major leaguer?

One issue often overlooked when it comes to over-the-counter products is the issue of drug-drug interactions. While medical practitioners, pharmacists and research scientists recognize that even substances that aren’t prescription drugs can cause a “drug-drug interaction,” the public may assume that an over-the-counter product is safe, and free of such interactions. If substances like Tylenol and dietary supplements are sold over the counter, they can’t really be that dangerous, can they?

While cannabinoids aren’t prohibited, we need to be aware that the small molecule compounds derived from cannabis can have side effects. Some of the side effects may arise from the activity of the compound, but some could be the result of how these compounds cause other compounds to behave.

You may be familiar with the conventional wisdom that reminds you not to drink grapefruit juice if you’re taking certain medications — the interaction of the juice and certain drugs has been extensively studied. Grapefruit juice contains furanocoumarin compounds, which can inhibit an enzyme known as Cytochrome P450 3A4 (CYP3A4). Cytochrome P450 enzymes are part of your body’s mechanism for eliminating substances from your body. When the furanocoumarin compounds found in grapefruit juice inhibit this enzyme, they can interfere with the metabolism of other drugs — in fact, this is a modality that can play a role in the metabolism of other prohibited substances.

These furanocoumarin compounds aren’t found just in grapefruit juice; they are also in other citrus fruit, such as blood oranges and pomelos. If furanocoumarins are inhibiting CYP3A4, other compounds can’t be processed by CYP3A4 for elimination, and they may remain in the system for a longer period. If you continue to take your medication as prescribed, while also drinking grapefruit juice semi-regularly, there may be an unsafe level of drug accumulating in your body.

And on the flip side, certain compounds induce Cytochrome P450 activity. Instead of inhibiting the enzyme, an inducer will cause the activity of the CYP450 to increase. In this case, the drug won’t remain in your body for as long, and may not have enough time to really have a therapeutic effect.

Why is this important for our discussion today? Although there is limited research around the pharmacokinetics of CBD, there is evidence suggesting that cannabinoids can inhibit certain of these cytochrome P450 enzymes or induce other cytochrome P450 enzymes; one paper goes so far as to suggest that these effects can be observed in subjects smoking more than two marijuana joints per week. Ultimately, the exact risk of drug interactions is something that should be discussed with a doctor or a pharmacist, who will be able to provide guidance based on knowing someone’s full complement of medications.

This is an ever-changing landscape, with more and more states easing restrictions on marijuana use, and CBD becoming an increasingly popular additive to food and drink products. It’s possible that regular, sustained CBD use could trigger a positive drug test. Thus minor league players should stay away. It’s also possible that CBD could interfere with other substances that a major league player may be taking. Ultimately, all players should use the same caution with CBD that they do with any supplement. If you can’t be certain of its provenance, and the beneficial effects are questionable, it’s best to steer clear.

All that said, the Minor League Drug Program is explicit: marijuana and “natural cannabinoids” are considered drugs of abuse. Whether or not one agrees with this, they are prohibited substances. Minor leaguers must serve their suspension if they test positive for cannabis metabolites. But it seems clear that it is time to revisit the policy.

In 2018, there were 22 minor leaguers suspended for “drug of abuse” violations; unless a player comes forward to acknowledge the drug in question, we don’t know if these violations are due to the use of marijuana, cocaine, opioids or LSD. It is a bit unfair to penalize minor leaguers for the use of a substance that is acceptable among major leaguers, and is increasingly demonstrated to have legitimate therapeutic benefits. It’s also unclear if a player could also receive a Therapeutic Use Exemption (TUE) for medical marijuana use.

Unfortunately, because the MLBPA continues to disregard considerations for its future members, there is no one really speaking on behalf of the minor league players. Even the U.S. surgeon general has voiced support for revisiting our approach to marijuana; it is time for minor league baseball to revisit its  approach as well.

References and Resources

• • Bobby Mueller, “Major League Baseball and Marijuana,” Call to the Pen, December 11, 2016
  • Jeff Passan, “Loophole offers potential path for some minor league players to smoke way onto major league rosters,” Yahoo! Sports, July 1, 2014
  • Aaron Carroll, “The Reasonable Way to View Marijuana’s Risks,” The New York Times, January 14, 2019
  • Christelle M. Andre, Jean-Francois Hausman, and Gea Guerriero, “Cannabis sativa: The Plant of the Thousand and One Molecules,” Frontiers in Plant Science, 2016, vol. 7, article 19
  • István Ujváry and Lumír Hanuš, “Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy,” Cannabis Cannabinoid Res., March 2016, vol. 1, no. 1, pages 90–101
  • John R. Horn and Philip D. Hansten, “Drug Interactions with Marijuana,” Pharmacy Times, December 9, 2014
  • Ondrej Zendulka et al., “Cannabinoids and Cytochrome P450 Interactions,” Current Drug Metabolism, March 2016, vol. 17, no. 3, pages 206-226
  • Nicole Fisher, “Surgeon General Believes It’s High Time To Think About Science-Driven Policy For Cannabis Research,” Forbes, January 7, 2019
  • Elizabeth Brico, “We Looked Into Whether CBD Would Show Up in a Drug Test,” Vice, December 14, 2018