Delta-8 THC Products Are Full of Unintended Byproducts: Should We Be Worried?

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Key Takeaways

• The cyclization reactions used to make delta-8 THC from CBD can (and generally do) lead to unintended byproducts like iso-THCs and even molecules never before encountered.
• We do not know if these components are dangerous, but any conclusions about risk drawn from the FDA’s adverse event reporting system (FAERS) or calls to poison control centers are probably misleading.
• Producers could use chromatographic purification (or even truly “synthetic” production methods) to minimize the risk, but this would increase costs for them in a way they are apparently unwilling to do.
• Customers should be wary of delta-8 THC products, but it’s crucial to remember that for many people, there is no other option to get high legally. Solutions that ignore this are not solutions at all.

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Delta-8 THC has been controversial since it first appeared on the market. With a reputation as “weed lite,” it quickly gained popularity and became a target of legal action and specifically targeted bans.

The main line of attack is pretty straightforward: it’s produced using chemical reactions from a starting-point of CBD, so it is a “synthetic cannabinoid” and is therefore dangerous.

Something being synthetic doesn’t automatically make it dangerous, but there is more in most commercial delta-8 THC products than just the cannabinoids you’re looking for.

In fact, most products contain unintended and sometimes even unknown byproducts, and these often go unreported in the Certificates of Analysis (COAs) companies use to keep customers informed. So should we be worried?

Here’s a run-down of what we know about how delta-8 THC is produced, what we know about the byproducts, and how manufacturers could minimize or even remove them.

Producing Delta-8 THC From CBD: How Most Products Are Made

Delta-8 THC does occur naturally in the cannabis plant in very small amounts, but the majority of products on the market are created using “isomerization” or cyclization reactions starting from CBD.

The cyclization reactions used to produce delta-8 (or delta-9) THC from a CBD starting point are catalyzed by acid and high temperature.

The specific outcome depends on which double-bond from the CBD structure is activated: if it’s the delta-8 double bond, it creates the “scaffold” for THCs, but if it’s the delta-1 double bond, it creates iso-THCs.

The THC pathway of this reaction initially leads to delta-9 THC, but delta-8 is favored when the reaction time is longer.

From this it’s important to note a few things:

• Firstly, much of the hemp-derived delta-9 THC on the market is created through essentially the same process.
• Secondly, there are two distinct “pathways” that the reaction can follow, and only one of these leads to the intended product.
• And thirdly, the process depends on strong acids (as well as solvents) that could potentially remain in the mixture if the result isn’t sufficiently purified.

The Byproducts from the Reactions

The cyclization reactions are the main source of byproducts in commercial delta-8 THC products, and from the above, it should be clear that iso-THC is one of the most common of these.

Research shows that the formation of Δ8-iso-THC and Δ4(8)-iso-THC depends on many factors, including the specific acids and solvents used, as well as how long the reaction is given.

For careful and trained chemists, this would basically be a non-issue. Researchers are easily able to identify the optimal conditions, solvents and acids to maximize delta-8 THC formation while minimizing any side products.

However, in practice, this is one of many byproducts commonly found in delta-8 THC products.

One study of delta-8 THC vaporizers found that Δ4(8)-iso-THC was present in every sample product studied. Olivetol was detected in 22 of 27 products, and the researchers also identified 9-ethoxyhexahydrocannabinol in two samples, and one previously un-described molecule, iso-tetrahydrocannabifuran was detected in all but two of the products tested.

These authors also note that levels of delta-8 THC in these products can vary by up to 40% of the advertised amount (a finding that matches our own study into delta-8 products), but for one brand, they point out that adding the delta-8 THC to the Δ4(8)-iso-THC was consistent with the advertised dose.

This suggests that high-performance liquid chromatography with UV detection (HPLC-UV) testing cannot differentiate between these two components. We’ll get back to this issue shortly.

Another study put together a more comprehensive listing of the byproducts of the cyclization reactions used to create delta-8 THC. While we don’t need to go into detail about each one, the most important thing to note is that there are a lot of them.

Back in 2021, Dr. Christopher Hudalla, President and Chief Scientific Officer at ProVerde Labs, commented to Chemical and Engineering News that he has “not seen one that I would consider a legitimate delta-8-THC product. There’s some delta-8 in there, but there’s very frequently up to 30 [chromatographic] peaks that I can’t identify.” We asked him if this was still an issue today:

“Yes, but the situation has gotten even worse. As consumers have warmed up to the acceptance of the conversion of CBD to produce THC, and producers have convinced the masses that since CBD is natural and safe, that these products should be considered a natural-derivative and therefore safe, the producers have continued to push the envelope of what they are willing to dose consumers with.”

How COAs Fail Consumers and the Challenges of Testing for Unknown Components

If you’ve been buying hemp products for some time, you may be wondering why these components aren’t shown on the COAs companies offer with their products. Isn’t that the whole point of COAs?

We asked Dr. Hudalla about this issue. He explained that:

“The analytical methods used by almost every lab were developed and optimized for phyto-cannabinoids, the cannabinoids produced by the cannabis plant. These methods, most often HPLC, are not very good at differentiating these synthetic contaminant byproducts from the synthetic targets (like Delta-8-THC).”

“Under almost all HPLC conditions being used, these ‘iso-THC’ compounds can be found ‘hiding’ behind the signal for the Delta-8-THC. In analytical chemistry, we call this ‘co-eluting signals,’ but it means that the contaminants are not being identified, and to make it worse, their presence as a percentage, is actually included with the percentage of the target (D8-THC), over-estimating the purity of these products.”

In other words: labs generally use methods that have difficulty distinguishing between delta-8 THC and byproducts such as delta-8 iso-THC and delta 4(8) iso-THC.

Dr. Hudalla’s comment matches with the findings of a study referenced above, which found that adding the delta-8 THC to the iso-THCs resulted in the advertised quantity. But in fact, this is not what was advertised, because a substantial proportion of it was actually a contaminant.

Dr. Hudalla emphasized this point, “We have seen these impurities as high as 40%, so the D8-THC that was reported as 92% purity, was really only 52% purity, with 40% impurities, of unknown toxicology.”

Adding that, “Producers know that these contaminants are present, and actively seek out labs that do not, or will not report these compounds. Is it incompetence? Ignorance? Malfeasance? We are the only lab that I am aware of that calls out these contaminants on our Certificates of Analysis (COAs) with a warning statement that says:

‘In addition to compounds reported here, multiple cannabinoid isomers or byproducts, which do not occur naturally, were observed in this sample and cannot be identified. No toxicity data is available for these unknown compounds, and as such would not be recommended for human consumption.’”

While there could be many reasons other labs don’t report the presence of these compounds, and many reasons companies appear to be willing to sweep it under the rug, it’s clear that COAs presented to consumers are not doing the job they’re intended to.

Are the Byproducts Dangerous?

Unfortunately, we don’t know very much at all about the risks from the byproducts. We asked Dr. Hudalla whether consumers should be worried about byproducts from delta-8 THC production such as 4(8)-iso-THC and whether they’re likely to be dangerous:

There is certainly a chance. We have tested 1000’s of these products, and to date, have not found one to be without contaminants. It is not unusual to find 30 or more unidentified chemical compounds, many of which do not exist in nature [like 4(8)-iso-THC], for which no toxicity information exists. We do not know if iso-THC is dangerous or not. It could be the next big cancer drug, or it could be the next big cause of cancer. We just don’t know.

This idea – that it could be the next big cancer drug or a cause of cancer – really emphasizes what the lack of evidence means. A lack of evidence is not evidence that these components are dangerous, nor is it evidence that they are safe. This is crucial to keep in mind during all of the discussions on this topic. 

And there really is a lack of data. Searching PubMed for “iso-THC” results in just 8 hits, with all but one of these discussing how to derive and identify the molecules. More wide-ranging searches turn up articles like this review which mentions iso-THC but again cannot find toxicological information about it. One study investigated its ability to kill cancer cells (molecule 2 = delta-4 iso-THC, molecule 3 = delta 4(8)-iso-THC), but it didn’t cause cancer cell death.

In fact, very little is known about it at all other than that it likely isn’t intoxicating.  

Does the FDA’s Adverse Event Reporting System (FAERS) Show the Risk of Byproducts (or Delta-8)?

One of the most common points raised in this discussion is that the FDA’s Adverse Events Reporting System (FAERS) shows an increase in adverse events relating to delta-8 THC, other non-standard THCs, and “synthetic cannabinoids.” Given the lack of other information, it’s pretty understandable that this might seem like the best source of data we have.

Dr. Hudalla made this exact point to us when we spoke to him:

What we do know is that the reported adverse events is going up dramatically, and includes almost 200 fatalities, based on the FDA’s database. But we know these numbers are under-reported as many of these events do not make it into the database. It is not uncommon for us to get reports from parents, teachers, physicians and law enforcement for cases where Jr. High School students are going to the hospital for respiratory failure, adults who are experiencing breathing difficulties, momentary black outs, and psychosis.

He again emphasized the lack of certainty on this issue, “We do not know which contaminant is responsible for which event, but we do know that the products (that we have tested) are all contaminated, and the Adverse Events can be pretty serious, even life-threatening.

The events are probably relatively small compared to the scale of usage of these products, so the reality is that most of these products on the market will not kill you. But that is a pretty piss-poor basis to build a multi-billion dollar industry. We call the consumption of these products ‘Frankenoid Roulette.’ Do you feel lucky?”

However, this sounds much scarier than the data would suggest. We searched through the FAERS database for all delta-8 THC, delta-10, synthetic cannabinoid, and unspecified/mixed THC cases. From this, we identified a total of 222 deaths.

The problems for this argument start when you look into the cases in more detail than simply the outcome. Of these 222 deaths, only 7 (3.2%) did not involve some other substance, and in fact the majority had fentanyl, cocaine, morphine, methadone, Xanax, or some other clearly serious exposure.

If we ignored mixtures with only “common” medications (e.g. acetaminophen or insulin) and THCs, only 15 (6.8%) could potentially have been related to THC.

Additionally, if you look at the cases that ended up in the hospital, the database shows that in 56% of cases, there were other substances involved. And again, since we don’t know the risks of the byproducts we’re concerned about, even for the remaining cases, we still can’t be sure the THC products had anything to do with the cases.

It is incredibly difficult to draw any conclusions based on reports in this way; we simply do not have enough information.

More broadly, the issues with making conclusions based on this database are explained by the FDA. Not all events are reported, reports don’t prove causality, they are not verified and there may be duplicates in the database.

The problem with making conclusions based on these reports is much like the issues with the way anti-vaccination activists use VAERS (Vaccine Adverse Events Reporting System) – just because something happened after you got a vaccine or vaped some delta-8 doesn’t mean it was caused by it.  

What Do Calls to Poison Control Centers Tell Us About the Risks?

Another point often raised about delta-8 THC, likely inspired by the FDA’s “5 Things To Know About Delta-8 Tetrahydrocannabinol” post, is that there are increasing numbers of calls to poison control centers about them, including one pediatric death.

This is certainly true. When announcing their 2022 report, America’s Poison Centers noted that there were 3,358 exposures to delta-8 THC, increasing 82% compared to 2021.

However, it’s unclear exactly where in the main report this figure comes from (possibly from unpublished information), but in the section for cannabinoids (page 912), there were 15,828 single-substance exposures to products classed as some form of marijuana (e.g. plant material, concentrates, edibles and other preparations). None of these resulted in death.

There were also 3,419 single-substance exposures to CBD reported to poison control centers. Although it’s unclear whether these were multi-substance cases, two CBD-related cases resulted in death.

These comparisons show the limitations of using poison control center data to assess the risks of a substance.

It is not common to claim that CBD is a uniquely dangerous substance or draw attention to the poison control center calls related to it, nor to the two unfortunate deaths in cases involving CBD. However, if we were to use the implied logic behind the delta-8 THC claims, we would be forced to conclude that CBD is more dangerous than delta-8.

Similarly, looking at the much higher number of exposures to “marijuana” in some form, we are forced to wonder why America’s Poison Centers chose to draw attention to delta-8 THC while not even mentioning this in the press release.

As with the FAERS database, calls to poison control centers can give us some limited information when nothing else is available, but it is hard – if not impossible – to draw firm conclusions from.

Simple factors like availability and how many people have a substance in their homes can have an overwhelmingly large impact on the number of calls. You cannot simply look at the number of exposures from a substance and conclude that it is particularly dangerous.

There Are No Easy Answers on Delta-8 THC and the Risks of Byproducts – So Don’t Believe Any You’re Given

We truly do not know if byproducts like iso-THC are dangerous to people. It’s even difficult to determine how many people are exposed to how much of it, and we don’t even have the core toxicological information we’d need to start estimating.

The industry ignores this issue, hiding behind COAs which usually don’t even tell you that these chemicals are present, and never commenting on or acknowledging the uncertainty customers face with every purchase. Likewise, those opposed to the industry lean hard on insinuation and scary-sounding statistics with all context and nuance removed.

In reality, neither of these groups is approaching the issue fairly and honestly. There is an inherent danger in consuming chemicals with an unknown safety profile, but “unknown” means “it could be good, bad or neutral,” not “it must be bad in a way we aren’t sure of yet.”

There are no easy answers. The byproducts from the CBD-to-THC conversion pathway are usually present, but we have no idea if they’re dangerous or not. It’s crucial to remember that knee-jerk fear can be just as misleading as trusting ignorance.

A Word on the Rhetoric of the “Synthetic”

Before we move on to some final practical issues, it’s a good idea to dismantle some of the rhetoric around things that are “synthetic.”

In this discussion, as in most, pointing out that a chemical or product is “synthetic” is effectively used as a way to say it’s alien, unknown or otherwise bad.

The problem is that synthetic things are not always bad and natural things are not always good.

For example, the THC in dronabinol/Marinol is completely synthetic, but it’s still very safe. Arsenic is totally natural but very dangerous. And even worse, the synthetic THC in Marinol is literally identical to the THC produced by the cannabis plant naturally.

Getting into the details about delta-8 THC also shows the more subjective aspects of this distinction very clearly. Delta-8 THC is produced naturally by the cannabis plant, but all commercial products include delta-8 which is produced in a lab. So can we call delta-8 THC synthetic?

RELATED: Is Delta-8 THC Synthetic?

You might have an answer to this, but hopefully, you can at least see why somebody might come to the opposite conclusion. It’s kind of both. And what if someone recreated the natural production process perfectly in a lab – would that make a difference to whether you consider it synthetic?

The message here is simple: something being synthetic is not a statement about its risks (or its benefits), and the line between “natural” and “unnatural” is not always as sharp as people may like to think.

Couldn’t The Industry Make Safer Delta-8 THC Products, With No Byproducts?

Simply put, the answer to this is a resounding “yes.” It is totally possible to produce delta-8 THC from CBD or otherwise without leaving unintended byproducts in essentially every product.

Dr. Hudalla commented to us, “These are synthetic drugs, and just like those manufactured in the pharmaceutical industry, will always have unintended synthetic byproducts produced in the reaction, and like the pharmaceutical industry, these byproducts can be removed. We have shown through our collaborations, that most of these contaminants can be removed (see below). But when I present this approach to producers, they ask me: ‘Why would we do that? That would increase the cost of production and reduce our profits!’ or ‘nobody makes us do that!’”

We asked for more information about this, and he clarified, “Under FDA regulations, the pharmaceutical producer has two ways to deal with these unintended byproducts:

1. Identify these byproducts and study them to understand their toxicity, to ensure that inclusion of these byproducts in a finished consumer product does not represent a risk to consumer safety. This can take years.
2. One of the most common ways to deal with these is to just remove the contaminants from the product. There are multiple ways of doing this, but often times may include some chromatographic purification.”

He explained that his example was of chromatographic purification, “So it is an extra step, that does take extra time, and it would increase the cost of production. I have been working with a couple of researchers that have been focusing on producing a clean product, straight out of the reaction, so that clean-up would not be necessary, but so far, all attempts at this have been unsuccessful.”

Chromatographic purification is basically using the molecular separation that occurs during chromatography to isolate the part you’re looking for and remove other components.

While the details get a little complex, the most important thing to note is that even if it increases costs, it is totally possible to isolate one “peak” in the chromatographic profile and end up with a much purer product. Dr. Hudalla’s approach brought delta-8 THC to 99% purity.

Discussing why this doesn’t happen already, Dr. Hudalla commented that, “No producers want to lose out on profits. One of the larger producers spent an estimated $5.5M in NASCAR sponsorship over the course of two years, but they can’t afford to remove contaminants from their products?”

Clearly, brand awareness is more valuable to these companies than producing pure products that are less likely to pose risks to consumers. While we can’t force companies to care about customers, regulation with a focus on identifying and reducing the quantities of these byproducts could help to rectify the situation.

An Unexpected Solution: Making Delta-8 THC Purely Synthetically

Perhaps unexpectedly, these risks wouldn’t really exist if they didn’t have to start from CBD and could just make a purely synthetic delta-8 THC. In other words, it would be safer if they didn’t use cannabinoids like CBD as a starting material.

You can make THC – delta-8 or delta-9 – through a process called Friedel–Crafts alkylation, with olivetol (one of the byproducts noted above) and verbenol. This was first developed in the 60s, and is used to make the THC for medicines like Marinol.

Even though this is genuinely “synthetic” and that is a common justification for attacks on delta-8, making it this way is very likely to be safer than current approaches.

The big difference is the number of “pathways” the reaction can go down. With the now-common CBD to THC approach, there are many ways it can stray from the plan and produce some of the many byproducts or unintended products discussed above. For the olivetol-verbenol combination, there are considerably fewer ways this can go wrong and produce something unintended.

However, given the huge legal controversy over using CBD to make delta-8 THC – unambiguously as a derivative of hemp cannabinoids, as defined by law – it’s unlikely that this would survive any legal challenge.

In fact, since it’s made from non-cannabis starting materials (page 5), it would likely be considered synthetic cannabis by law enforcement.

Should Consumers Be Worried About Delta-8 THC Products?

So for all the technical and scientific discussions about impurities and byproducts in delta-8 THC products, there is one question that still doesn’t have an answer: is this something consumers should be worried about?

While the lack of evidence makes it very difficult to be sure about this, we would urge caution when purchasing delta-8 THC products for this reason, particularly products that you vape or smoke.

We say “be cautious” rather than “be worried” because it’s unlikely that delta-8 THC, in itself, poses any more of a risk than delta-9 THC. And while many manufacturers don’t take adequate care over the reactions to prevent byproducts from finding their way into your product, not all manufacturers are equal.

There is unfortunately not much you can do about labs misreporting something like iso-THC alongside the delta-8 you’re looking for, but if you choose products that are tested for safety (e.g. heavy metals, pesticides and residual solvents) then you minimize your chance of issues.  

As always, with hemp, it likely isn’t that delta-8 THC products are inherently dangerous, but that if they’re made poorly by less-reputable companies, they may expose you to unknown risks.

Additionally, since approximately half of hemp delta-9 THC products in our study were made using the same cyclization reactions used to make delta-8, the same warnings and conclusions hold true for hemp delta-9 too.  

Conclusion: Not Everyone Has the Option to Avoid Intoxicating Hemp

The huge, gaping issue with this whole discussion is one of privilege. Many US citizens have the privilege of having access to legal, well-regulated cannabis products and can easily avoid questionable hemp products. Many others do not, and this is where delta-8 THC and other intoxicating hemp products are more popular.

So we can get up on our high horses and complain (correctly) that there are unknown byproducts in intoxicating hemp products, but it’s crucial to remember what things look like on the ground.

Your choice isn’t always “should I buy delta-8 or go to the dispensary for some safe weed?” sometimes it’s, “do I roll the dice on the street corner dealer or just get some legal delta-8 from the store?”

No true solution to this problem should drive the second person back to the street corner dealer. If we do that, who are we really helping? The hemp industry needs robust regulation, but overstating the risks of hemp products based on the unknown properties of unknown components is really just pushing people back into the arms of cannabis sellers, whether legal or not.