What is Delta-8-Tetrahydrocannabinol (Delta-8 THC)?

What is Delta-8 THC?

To date, scientists have identified more than 100 phytocannabinoids in cannabis plants, spanning 11 chemical classes and several cannabinoids, such as delta-9-tetrahydrocannabiniol (Delta-9 THC), may have related isomers (i.e., 2+ compounds with the same chemical formula but a different arrangement of atoms in the molecule). [i] Delta-8-tetrahydrocannabiniol (Delta-8 THC), an isomer of Delta-9 THC, was isolated from cannabidiol (CBD) in the 1940s, although it was initially referred to as Delta-6 THC or Delta-1(6) THC. [ii]^,[iii]  By the 1960s, it was recognized that Delta-8 THC is present in only negligible amounts in natural hemp and cannabis but could be synthesized from CBD.[ii]^,[iii]

Delta-8 THC differs from Delta-9 THC due to a double bond that is present on the eighth, rather than the ninth, carbon atom.[iv] Pharmacologic studies suggest Delta-8 THC may have less affinity to CB1 receptors (found primarily in the central nervous system) than Delta-9 THC, but a similar affinity to CB2 receptors (found primarily in the immune system and in hematopoietic cells).  Preclinical studies suggest the scope of these differences in affinity with CB receptors may vary between species. [ii] A limited number of human studies (k=7) suggest that Delta-8 THC may have similar psychoactive effects as Delta-9 THC, but is significantly weaker (e.g., Delta-9 THC may be between 2- to 3-times more potent than Delta-8 THC).[ii] Differences in Delta-8 THC side-chain analogues may be associated with predictable changes in CB receptor ligand affinity and efficiency, and thus its pharmacological effects.[v]  In their 2022 review, Tagen and Klumpers state that to date no publications have detailed the pharmacokinetic profile of Delta-8 THC in humans.[ii] There is limited information suggesting that its action, distribution in the body, metabolism and excretion may be similar to Delta-9 THC, which is well-studied and generally understood.[ii]

Part of the problem posed by Delta-8 THC is the fact that in gas chromatography it produces a peak similar to Delta-9 THC, thereby complicating medical and/or legal testing for cannabis exposure.[iii] To meet the challenge posed by the growth in the marketing and use of Delta-8 THC products, new laboratory tests are required.[iii],[vi] As noted by one author, in most medical settings, distinguishing the two types of THC analogues can be difficult.  Fortunately, this has relatively little impact on medical management as symptoms and treatment are similar.[vii]

Delta-8 THC in the American Market

The popularity of Delta-8 THC in the U.S. is rooted in the issues raised by the legal status of cannabis.  Although cannabis remains a Schedule 1 substance (i.e., a drug or substance with no currently accepted medical use and a high potential for abuse), in 2018 the Farm Act excluded hemp and other cannabis derivates as long as the total content of THC was less than 0.3% by weight. This exemption was seized by some as a “grey area”, in that hemp or low-THC cannabis could be used to derive or synthesize commercially-viable amounts of Delta-8 THC.[vii] Subsequently, several Delta-8 THC products were marketed as a “more mellow” alternative to Delta-9 THC, often in easily-accessible retail outlets such as convenience stores, pharmacies and grocery stores.

Some interest groups, such as the U.S. Cannabis Council, reject the argument that the Farm Act constituted a legal loophole for Delta-8 THC. [viii] However, in 2020, in the face of increasing commercialization of Delta-8 THC products, the Department of Drug Enforcement Administration (DEA) issued new regulations classifying Delta-8 THC (either synthetic or derived) as falling under the Schedule 1 regulations.  This action made research difficult but had little effect on sales.[vii]  Complicating the situation is the variability in cannabis regulations between different U.S. states.  A consumer-oriented website states that as of 2022, only 12 states have established limits or bans on Delta-8 THC sales; the remaining states either have no regulations or consider it similar to recreational cannabis. [ix] An online survey of 252 American users of Delta-8 THC found that many considered it legal and less potent than Delta-9 THC, making it a “safer” substitute. [x] As indicated by Google search trends, interest in Delta-8 THC tends to be higher in states in which recreational cannabis is illegal.[xi]

Analysis by the U.S. Cannabis Council of 16 commercial products found significant variability in their potency; on average, products contained ten times more THC than allowed under applicable regulations.  In addition, the U.S. Cannabis Center reported inaccurate labelling, heavy metal and pesticide contamination, and unsubstantiated health claims. [xii] A privately-funded 2021 study of 51 of the most popular hemp-deprived Delta-8 THC products in the U.S. found that 76% exceeded the Delta-9 THC limit and had an average of 15% less Delta-8 THC than advertised.  Moreover, only 16% of the companies had substantive measures to verify the age of customers. [xiii]  In May, 2022, the FDA issued warning letters to five manufacturers of Delta-8 THC products, citing issues such as misbranding, inadequate instructions for use, illegal marketing of products for medical conditions (although the FDA has never evaluated such health claims), and adding Delta-8 THC to foods (e.g., gummies, chocolates and other consumables).[xiv]

In a little more than two years (December 1, 2020 – February 28, 2022), the Food and Drug Administration (FDA) received 104 adverse event reports concerning Delta-8 THC, of which 55% required emergency and/or medical interventions. [xv] Over the same time period, national poison control centres received 2,362 reports. A significant proportion (41%) involved minors <18 years; overall, 70% required an evaluation at a healthcare facility, 8% admission to a critical care unit, and there was one pediatric death.[xv] A case report of a previously healthy 2-year-old who experienced sedation and acute encephalopathy after ingestion of Delta-8 THC gummies, reported the need for intubation and admittance to a pediatric intensive care unit (PICU). [xvi] As reported by Bozman et al, common side effects of Delta-8 THC include confusion, anxiety, drowsiness, bradycardia, numbness and depression, with less common but more concerning adverse effects being depression, suicidality, and acute encephalopathy. [iv]

Delta-8 THC in the Canadian Context

In Canada, cannabis regulations do not distinguish between Delta-8 THC and Delta-9 THC.  Thus, under the 2019 amendments to the Canadian Cannabis Act, it is legal to purchase and consumer Delta-8 THC products as long as they meet current cannabis standards (e.g., sold only by licensed retailers, do not exceed total THC limits, and are clearly labelled with cannabinoid contents). [xvii] Although cannabis products can be ordered online in most provinces, they can only be obtained from licensed producers, require a proof of age and adult signature at the time of delivery, and cannot cross the Canadian/American border. Even Delta-8 THC products that contain less than the legal limits of THC cannot be shipped into Canada from another country.  For example, an American company wishing to sell their products to Canadians (e.g., CBD products) must apply to have specifics products registered and approved by Health Canada and obtain import licenses.  This can be an expensive, time-consuming process. [xviii]

Popularity and Use

Analysis of online searches have demonstrated significant growth in consumer interest in Delta-8 THC products. Leas reports that between 2011 and 2019, the number of searches tended to be stable, but subsequently increased rapidly: 257% in the period 2019-2020 and 705% for 2020-2021. [xix]  Much of the growth was due to searches by Americans, particularly those living in states in which cannabis was not legal. Using a different indicator (Relative Search Index [RSI]), Livingstone et al. reported that during 2020 and 2021 searches for information on Delta-8 THC increased more than other cannabis-related terms (in one year, from 5% of marijuana-related searches to 35%).[xi] For both studies, it is important to note that online information searches may not reflect behaviour or use.

Online surveys have been conducted of Delta-8 THC users.  A 2021 survey of 521 Americans living in New York State conducted in collaboration with a Delta-8 THC manufacturer found that about half used these products to treat sleep issues or health or medical conditions such as anxiety/panic attacks, chronic pain, depression or bipolar disorder, and stress. Only a minority (22%) told their primary care providers about their use of Delta-8 THC, perhaps because 48% lacked confidence their providers would be knowledgeable about it or able to integrate it into their care. Overall, the users surveyed appeared to share the perception that Delta-8 THC was not only effective but was less addictive than pharmaceuticals and associated with fewer side effects. [xx]

A subsequent, smaller study (52 users, of whom 59% were American) by the same team found high proportions reported benefits (71% a great deal of relaxation, 68% euphoria and 55% pain relief).  However, adverse effects were also common (81% a moderate or lot of cognitive distortions such as difficulty concentrating, 80% impact on short-term memory, and 74% altered sense of time.  Over half (57%) reported that they were using Delta-8 THC as a substitute for Delta-9 THC and 59% as a substitute for a pharmaceutical medication.[xxi]

Another 2022 online survey of Americans who used Delta-8 THC in the past year (n=252, of whom 36% reported weekly use) identified three related themes: 1) the perception that Delta-8 THC was “legal”; 2) its use as a substitute for Delta-9 THC; and 3) the belief that it was a less potent and intense (and thus safer) agent than Delta-9 THC.[x] Users reported that Delta-8 THC was less beneficial in treating their health issues (chronic pain, anxiety and stress) than Delta-9 THC but also fewer or more mild adverse effects (sickness, anxiety, paranoia, irritability, restlessness, memory problems or trouble with routine tasks).  Users who were familiar with CBD believed Delta-8 THC was more beneficial than CBD but also had more adverse effects (memory problems, trouble with routine tasks, and paranoia).[x]

The largest online survey to date that has looked at Delta-8 THC may be Livne’s 2022 survey of 4,348 American adult cannabis users. Of the entire sample, 58% reported hearing about Delta-8 THC and 16.7% (n=725) had used it in the past 30 days.  Over half (52%) of the Delta-8 THC users obtained it from a store that was not a cannabis dispensary, such as a convenience store, pharmacy, or grocery store.  Almost a third (30.1%) said they used it to treat depression, nervousness or anger and a quarter (26.1%) because of its legal status.  Those living in states in which cannabis use was illegal were more likely to use Delta-8 THC than those in states with medical and/or recreational use.[xxii]

Conclusions

The isomer Delta-8 THC has a number of similarities to Delta-9 THC, but there are also important differences between the two compounds (e.g., in nature Delta-8 THC is present in cannabis and hemp in only negligible amounts and it appears to have less affinity to CB1 receptors).  These differences have been exploited by some commercial enterprises to create a thriving market for Delta-8 THC products.  Much of this market is based upon the public perception that Delta-8 THC is a “more mellow” and thereby safer form of THC (e.g., that Delta-8 THC is somehow the “younger sibling” of Delta-9 THC).  Reports of adverse effects and poisoning call into question the perceived “safeness” of Delta-8 THC.  It is important that more research is conducted on the action, risks and benefits of Delta-8 THC products for an evidence base to inform public policy.

[i] Thomas BF, El Sohly A. Biosynthesis and pharmacology of phytocannabinoids and related chemical constituents. The Analytical Chemistry of Cannabis, Quality assessment, assurance, and regulation of medicinal marijuana and cannabinoid preparations.  2016; Elsevier. (excerpt)

[ii] Tagen M, Klumpers LE. Review of delta-8-tetrahydrocannabinol (Delta⁸-THC): Comparative pharmacology with Delta⁹-THC. Br J Pharmacol 2022;179(15):3915-3933 (article)

[iii] Chan-Hosokawa A, Nguyen L, Lattanzio N, Adams WR. Emergence of Delta-8 Tetrahydrocannabinol in DUID investigation casework: method development, validation and application. J Analytical Toxicology 2022;46(1):1-9 (article)

[iv] Bozman ME, Manoharan SVRR, Vasvada T. Marijuana variant of concern: Delta 8-tetrahydrocannabinol (Delta-8-THC, Delta⁸-THC). Psychiatry Res Case Rep 2022;1(2):1000028 (article)

[v] Griffin G, Williams S, Aung MM, Razdan RK, Martin BR, Abood ME. Separation of cannabinoid receptor affinity and efficacy in delta-8-tetrahydrocannabinool side-chain analogues. Br J Pharmacology 2001;132:525-535 (article)

[vi] Helander A, Johansson M, Andersson A, Villen T. Analytical and medico-legal problems linked to the presence of delta-8-tetrahydrocannabinol (delta-8-THC): Results from urine drug testing in Sweden. Drug Testing and Analysis 2021;14(2):371-376 (article)

[vii] Babalonis S, Raup-Konsavage WM, Akpononu PD, Balla A, Vrana KE. Delta⁸-THC: legal status, widespread availability, and safety concerns. Cannabis Cannabinoid Res 2021;6(5): 0007 (abstract)

[viii] United States Cannabis Council. The unregulated distribution and sales of consumer products marketed as delta-8 THC. Position Paper, June 2, 2021. US Cannabis Council (uscc.org) Last access 31/8/2022

[ix] Smith A. Is delta 8 THC legal in your state? Our guide. Discover (discovermagazine.com) Aug 18, 2022. Last accessed 31/8/2022

[x] Bergeria CL, Strickland JC, Spindle TR, Kalaba M, Satyavolu PU, Feldner M, Vandrey R, Bonn-Miller M, Peters EN, Weerts E. A crowdsourcing survey study on the subjective effects of delta-8-tetrahydrocannabinol relative to delta-9-tetrahydrocannabinol and cannabidiol. Exp Clin Psychopharmacol 2022. Advance online publication  https://doi.org/10.1037/pha0000565

[xi] Livingston MD, Walker A, Cannell MB, Rossheim ME. Popularity of delta-8 THC on the internet across US states, 2021. Am J Pub Health 2021;112(2):296-299 (article)

[xii] United States Cannabis Council. Delta-8 THC Independent Test Results. Position Paper, June 2, 2021, U.S. Cannabis Council (uscc.org). Last accessed 31/8/2022

[xiii] CBD Oracle Lab study shows some delta-8 THC products reach 7700% of the legal delta-9 THC limit. Source: CBD Oracle, October 26, 2021. Published by PRNewswire; CISION website (prnewsire.com). Last accessed 31/8/2022

[xiv] Hipp D. Delta-8 vs. delta-9: what’s the difference? Forbes Health (forbes.com/health). Published Jun 16, 2022.  Last accessed 31/8/2022.

[xv] Food and Drug Administration (FDA). 5 things to know about delta-8 tetrahydrocannabinol – delta-8 THC. Consumer Update, current as of 5/4/2022. US Government (fda/gov/consumers). Last accessed 31/8/2022.

[xvi] Akpononu P, Baum RA, Reckers A, Davidson B, Ellison R, Riley M, Trecki J, Gerona R. Sedation and acute encephalopathy in a pediatric patient following ingestion of delta-8-tetrahydrocannabinol gummies. Am J Case Reports 2021;22:e933488-1-e933488-4. (article)

[xvii] Comparing the legality of delta-8 and delta-9 THC in Canada and the US. Montreal Times (mtltimes.ca).  Last accessed 31/8/2022

[xviii] Marshall E. Canadian hemp laws: is it legal to buy US CBD from Canada online? Plain Jane Blog (blogl.painjane.com). No date.  Last accessed 7/9/2022.

[xix] Leas EC, Nobles AL Shi Y, Hendrickson E. Public interest in Delta⁸-tetrahydrocannabinol (delta-8-THC) increased in US states that restricted Delta⁹-tetrahydrocannabinol (delta-9-THC) use. Int J Drug Policy 2022;101:103557 (article)

[xx] Kruger DJ, Kruger JS. Consumer experiences with delta-8-THC: medical use, pharmaceutical substitution, and comparisons with delta-9-THC. Cannabis Cannabinoid Res 2021; Online ahead of print. (article)

[xxi] Kruger JS, Kruger DJ. Delta-8-THC: Delta-9-THC’s younger sibling? J Cannabis Res 2022; 4: 4. (article)

[xxii] Livne O, Budney A, Borodovsky J, Walsh C, Shmulewitz D, Fink DS, Struble CA, Habib M, Aharonovich E, Hasin DS. Delta-8 THC use in US adults: sociodemographic characteristics and correlates. Addict Behav 2022;133:107374. (abstract)