Most modern consumers understand that tetrahydrocannabinol, better known as THC, is a molecule produced by cannabis (marijuana) that results in psychoactivity in humans (and some mammals). This chemical compound also delivers a slew of medicinal benefits, including significant research-supported anticancer and anti-inflammatory qualities (impacting literally hundreds of disease states).
What most consumers do not know, however, is that “THC” actually involves a family of several analog molecules produced by the cannabis herb—some of which deliver psychoactivity to humans and some of which do not. Often dubbed isomers, analogs are basically chemical siblings that feature very similar molecular structures.
Examples of isomers of THC include delta-9 (the infamous psychoactive version typically cited), THCA (the non-psychoactive acidic precursor that morphs into THC under the right conditions), THCV (the psychoactive varin version), THCVA (the non-psychoactive acidic precursor to THCV), THCP (the newly discovered phoral version; psychoactivity yet to be determined), 11-hydroxy delta-9 (a potent psychoactive version produced when delta-9 THC is metabolized by the liver), delta-10 (a less psychoactive version of delta-9), and delta-8 (a diluted version of delta-9 with the primary benefit of lacking many potential negative side effects of delta-9).
While similar in many respects, THC isomers vary in significant ways. In fact, in some cases, different isomers deliver polar opposite efficacy from one another. For example, delta-8 and delta-9 THC are known to increase appetite. In potent doses and accompanied by the right mix of terpenes, they can do so in a major way (a state referred to colloquially as “the munchies”). THCV, on the contrary, reduces appetite.
One of the chief difficulties in gaining a solid understanding of delta-8 THC, including its medicinal efficacy and how it might be integrated into medical or adult-use cannabis products, is the controversial nature and quickly evolving legal status of this molecule. At the time of this writing, delta-8 is legal in all but 11 U.S. states and—like delta-9 THC—illegal at the federal level.
Both loose-leaf flower and concentrate products containing delta-9 are derived (via a variety of extraction technologies, including CO2, BHO, and live resin) directly from the cannabis plant1, which may yield up to 25 or even 30 percent delta-9 THC in weight by volume of captured resin. In contrast, most cultivars (strains) of cannabis yield less than one percent delta-8 THC. Commercial quantities of delta-8 are typically derived by synthesis in an industrial laboratory via the conversion of hemp-derived CBD.
The molecular structures of both delta-8 and delta-9 are quite similar. Both feature a chain of carbon atoms and something called a molecular double bond. In delta-8 THC, this double bond is located at the eighth carbon atom. In delta-9, it’s at the ninth carbon atom. (Readers now understand how THC isomer molecules are named.)
The different double bond locations of the molecules result in slightly disparate behavior at the microscopic cellular receptors with which they bind within the endocannabinoid system. This modified cellular receptor signaling results in variance between these molecules with respect to potency, onset, and a variety of other efficacy characteristics.
Delta-8 and delta-9 are similar in many other respects, including their ability to act as an analgesic (treat pain), their delivery of euphoria, mutual antiemetic (anti-nausea and anti-vomiting) qualities, amplification of appetite, and their common use in the treatment of conditions such as anxiety, depression, and insomnia. Potential side effects of both analogs may include dry eye, red eye, panic attacks at potent doses (less common with delta-8), negative impacts to short-term memory, and paranoia (especially at strong doses and among novice consumers).
Some anecdotal reports in the form of the testimonies of delta-8 users have indicated that its less-intense psychotropic efficacy is energizing and good for creative types and busy professionals. To avoid increased anxiety and panic attacks in their patients, some wellness professionals are beginning to recommend smaller doses of delta-9 that are combined with delta-8 THC instead of the traditional mix of delta-9 and CBD.
This article focuses on the peer-reviewed scientific research that has been published about delta-8 THC since the early 1970s and compares the various characteristics of this popular molecule—including psychotropic potency and a variety of medicinal qualities.
First, the similarities between delta-8 and delta-9 THC outnumber the differences. In terms of psychoactivity, delta-8 THC delivers roughly one half to two-thirds that of its isomer sibling delta-9. Also, anecdotal testimonies state that the psychoactivity of delta-8 is less likely to result in negative side effects such as an increase in anxiety or disorientation.
Delta-9 Tolerance Break Enabler
Many wellness practitioners and caregivers have found a special role for delta-8 THC as a tool to help heavy consumers of delta-9 take tolerance breaks without the obvious negative effects of abstaining from cannabinoid medicine. Anecdotal testimonies and reports indicate that delta-8 may allow those who are daily consumers of delta-9 to replace it for a period of time in an effort to decrease their tolerance.
Dena Putnam, President and co-founder of Leafwize Naturals in Orange County, California, sells and recommends delta-8 THC products to her customers for a variety of reasons, including as a replacement agent during delta-9 tolerance breaks. She states that she believes this is not only a healthy approach, but also one that can save patients considerable money in the long term by allowing them to consume less to meet their health or lifestyle goals.
“Delta-8 may offer a way to take a delta-9 break while providing a level of medicinal relief that is similar to delta-9,” said Putnam during a February 2021 interview. While such information should be treated as purely anecdotal because it is not based on scientific research, there is validity to such feedback from vendors and consumers within the actual marketplace.
Putnam and her staff found that many of their customers were able to achieve two pivotal goals: 1) The same basic medicinal efficacy from delta-8 that they derived from delta-9 and 2) A discernible decrease in tolerance after resuming consumption of delta-9 THC.
Putnam reported that her company found that “after a period of switching from delta-9 THC to delta-8, delta-8 helped in a manner similar to delta-9. When the user resumed consumption of delta-9, the effects were greater—as if they had taken a conventional tolerance break.” Her observations echo the results of decades of scientific research, as cited below.
Delta-8 & Terpenes
When combined with terpenes, cannabinoids such as delta-8 THC sometimes exhibit enhanced efficacy and other mechanisms that have been found to be of value to human health. The most significant and innovative research in this area that has been conducted over the past quarter century is reviewed below.
In 1998, Israeli researchers Shimon Ben-Shabat and Raphael Mechoulam published their now-famous research study “An Entourage Effect: Inactive Endogenous Fatty Acid Glycerol Esters Enhance 2-arachidonoyl-glycerol Cannabinoid Activity” in the European Journal of Pharmacology.
It was this study that coined the term entourage effect. Via this theory, the scientists hypothesized that cannabinoids such as delta-8 THC commingle with terpenes within the human ECS to enhance the effects of one another. In a nutshell, the theory of entourage effect stipulates that cannabinoids, terpenes, and sometimes other molecules (such as aromatic esters) gain a synergistic value when they commingle that exceeds the mere addition of their individual efficacies. The researchers concluded that the entourage effect “may represent a novel route for molecular regulation of endogenous cannabinoid activity.”
In 2011, American researcher Ethan Russo followed up on the work of Ben-Shabat and Mechoulam by publishing a study entitled “Taming THC: Potential Cannabis Synergy and Phytocannabinoid-terpenoid Entourage Effects” in the British Journal of Pharmacology.
Russo noted that his study’s purpose was to “explore another echelon of phytotherapeutic agents, the cannabis terpenoids2: Limonene, myrcene, a-pinene, linalool, b-caryophyllene, caryophyllene oxide, nerolidol, and phytol.”
The study concluded that cultivars (strains) of cannabis and hemp rich in terpenes offer enhanced efficacy “that may strengthen and broaden clinical applications.” It claimed that its observations “support the concept that selective breeding of cannabis chemotypes rich in phytocannabinoid and terpene content offers complementary pharmacological activities.” Russo noted that the body of available research demonstrates that marijuana products rich in terpenes exhibit an improved “therapeutic index.”
Russo followed this important research with a 2018 study entitled “The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No ‘Strain,’ No Gain” that was published in the journal Frontiers in Plant Science. In the study, Russo employed the term “cannabis synergy” to describe how cannabinoids, terpenes, and related compounds may work together to enhance their overall efficacy.
The study reported that “the concept of botanical synergy has been amply demonstrated contemporaneously, invoking the pharmacological contributions of ‘minor cannabinoids’ and cannabis terpenoids to the plant’s overall pharmacological effect.”
Russo concluded that the current body of research strongly supports the entourage theory and overall concept of the synergistic interplay of cannabinoids and terpenes to create enhanced outcomes. “The case for cannabis synergy via the ‘entourage effect’ is currently sufficiently strong as to suggest that one molecule is unlikely to match the therapeutic and even industrial potential of cannabis itself,” wrote the researcher in reference to the plethora of products available, particularly for CBD and THC, that feature only a single isolated molecule.
Delta-8 Research Studies
Although the emergence of delta-8 THC in the legal cannabis marketplace has occurred only recently, it has captured the attention of scientists and researchers for half a century. In fact, more than 200 peer-reviewed research studies have been conducted on this increasingly popular molecule—which may serve as a supplement or replacement for delta-9 in some cases.
A 1973 study entitled “Delta-8- and Delta-9-tetrahydrocannabinol; Comparison in Man by Oral and Intravenous Administration” that was published in the journal Clinical Pharmacology & Therapeutics explored the similarities and differences between the two phytomolecules.
This research observed that delta-8 conveys roughly two-thirds of the potency of delta-9 THC, supporting anecdotal reports from healthcare professionals that it delivers approximately 50-75 percent of the psychoactivity of delta-9.
A 1975 study entitled “Antineoplastic Activity of Cannabinoids” that was published in the Journal of the National Cancer Institute investigated the efficacy of phytocannabinoids such as delta-8 THC, it’s isomer sibling delta-9, cannabinol (CBN), and cannabidiol (CBD) for a particular type of lung cancer.
The study, which employed animal subjects, found that most of the cannabinoids tested were effective in slowing the growth of cancerous tumors. “Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-THC, delta8-THC, and CBN, but not CBD,” reported the study.
A 1987 study entitled “Effects of Cannabinoids on Levels of Acetylcholine and Choline and on Turnover Rate of Acetylcholine in Various Regions of the Mouse Brain” that was published in the journal Alcohol and Drug Research explored the role of a range of psychoactive cannabinoids, including delta-8, delta-9, 11-hydroxy delta-9, and the non-psychoactive cannabinoids CBD and CBN.
The impact and potential involvement of these chemicals in various brain mechanisms of mice was measured. The study found that these molecules were effective in helping the brain achieve improved health and wellness and preventing biochemical mechanisms known to lead to degenerative conditions such as Alzehimer’s and Parkinson’s.
A 1995 human trial study entitled “An Efficient New Cannabinoid Antiemetic in Pediatric Oncology” that was published in the journal Life Sciences—and was conducted by Mechoulam—explored the ability of delta-8 THC to treat children undergoing chemotherapy for cancer. The goal was to learn if the phytomolecule was capable of reducing the nausea and vomiting experienced by the children following chemotherapy sessions.
The study involved eight children aged 3-13 who were suffering “various hematologic cancers” and had been treated with multiple antineoplastic drugs (for up to eight months). The test subjects consumed the delta-8 THC in the form of an edible oil.
The children received a total of 480 delta-8 THC treatments. Each delta-8 treatment began two hours prior to their antineoplastic treatments and were continued every six hours for 24 hours. The study found that “vomiting was completely prevented” and that observed side effects “were negligible.”
The groundbreaking study supported the fact that delta-8 exhibits “lower psychotropic potency than the main cannabis constituent, delta-9” and reported that only two of the eight test subjects experienced side effects, shedding light on the compound’s positive safety profile.
A 2004 study entitled “Very Low Doses of Delta 8-THC Increase Food Consumption and Alter Neurotransmitter Levels Following Weight Loss” that was published in the journal Pharmacology, Biochemistry, and Behavior investigated “the effect of delta(8) tetrahydrocannabinol (THC) on food consumption, cognitive function, and neurotransmitters in mice.”
The researchers found that delta-8 THC increased appetite in the rodents that consumed it compared to control subjects that did not receive the cannabinoid. “THC-treated mice showed a 16 percent increase in food intake compared with controls; in the long-term schedule, a 22 percent increase in intake was recorded,” reported the scientists.
The study revealed considerably more efficacy than merely appetite and food intake among the test subjects, however. “In addition, [delta-8] THC caused an increase in activity,” reported the study. Of arguably greatest consequence, however, was the study’s observation that “cognitive function showed a tendency to improve.”
Interesting, the research revealed the relative potency of both delta-8 and delta-9 in terms of appetite stimulation. “Delta(8)-THC increased food intake significantly more than did delta(9)-THC,” but reported that resulting performance and activity levels were similar.
A 2018 study entitled “The Cannabinoids Δ8THC, CBD, and HU-308 Act via Distinct Receptors to Reduce Corneal Pain and Inflammation” that was published in the journal Cannabis and Cannabinoid Research explored the ability of cannabinoids to deliver pain relief and anti-inflammatory properties for corneal injuries and dysfunction.
The study observed that “activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory” and reported that its purpose was to “investigate the antinociceptive3 and anti-inflammatory effects of cannabinoids with reported actions at CB1 and CB2 receptors.”
It found that delta-8 THC delivers “antinociceptive and anti-inflammatory effects” and that it achieves this efficacy by binding with CB1 cellular receptors in the endocannabinoid system. The study found that “topical cannabinoids reduce corneal hyperalgesia and inflammation” and that “cannabinoids [such as delta-8 THC] could be a novel clinical therapy for corneal pain and inflammation resulting from ocular surface injury.”
A 2020 human trial study entitled “Oral Cannabidiol Does Not Convert to Δ 8-THC or Δ 9-THC in Humans: A Pharmacokinetic Study in Healthy Subjects” that was published in the journal Cannabis and Cannabinoid Research investigated the urban legend that CBD may convert to delta-8 or delta-9 THC when consumed orally.
If true, this mechanism would be of obvious concern to those who desire no or can tolerate no psychoactive effects and could easily result in anxiety and panic attacks in select patient communities (including children, seniors, and those suffering particular psychological conditions).
The study involved 120 healthy subjects (60 males and 60 females) and could detect zero conversion of CBD to either delta-8 or delta-9 THC and, therefore, no risk of psychoactivity among CBD consumers. Reported the study’s authors, “The results showed that THC was not detected in plasma after the administration of CBD and [that] study participants did not present psychotomimetic effects.”
The study’s authors concluded that their findings “are consistent with previous evidence suggesting that the oral administration of CBD in a corn oil formulation is a safe route for the administration of the active substance without bioconversion to THC in humans.”
Delta-8 THC, one of more than half a dozen THC isomer molecules produced by the cannabis plant, delivers a range of wellness benefits for both patients and lifestyle consumers. Due to its lower psychoactivity and significantly reduced tendency to produce negative reactions such as anxiety, disorientation, or panic, the compound is becoming an increasingly popular treatment option. This is especially true for those who are most sensitive to anxiety or have a history of discomfort or adverse reactions when consuming delta-9 THC.
The legal status of this particular analog of tetrahydrocannabinol remains dependent upon one’s home state. However, the data collected by fifty years of research studies have illustrated the potential role of delta-8 for a variety of patient populations and adult use segments. Reduced inflammation, improved cognitive function, and fewer negative side effects than its sibling delta-9 serve as powerful motivation for caregivers and companies in legal jurisdictions to seriously consider delta-8 THC as a therapeutic agent and for lifestyle enhancement.
1 Hemp, by legal definition in the United States and Canada, contains less than 0.3 percent delta-9 THC.
2 Terpenoids are the supergroup of terpenes and terpene-like molecules.
3 “The action or process of blocking the detection of a painful or injurious stimulus by sensory neurons” according to Merriam-Webster.
About the Author
Curt Robbins is a technical writer, instructional designer, and lecturer who has been developing science-based educational and training content for Fortune 200 enterprise companies for more than 30 years. He is Director of Course Development at Higher Learning LV™ in Las Vegas, Nevada.
Robbins began writing about the biochemistry and science of the various wellness molecules produced by plants such as hemp in 2003. He has since developed more than 600 educational articles about hemp and its health components—including terpenes, cannabinoids, flavonoids, and the human endocannabinoid system.