2022 Study: Review of Delta-8 & Comparison to Delta-9

Welcome to Higher Learning LV's Study Summary series. This series reviews and summarizes peer-reviewed research studies and was developed specifically for cannabis industry professionals. These study summaries provide easily digested quick reads for a variety of important issues regarding the commerce and chemistry of legal cannabis.

Photo courtesy Leafwize Naturals

A 2022 peer-reviewed research study entitled "Review of Delta-8-tetrahydrocannabinol (Δ8-THC): Comparative Pharmacology with Δ9-THC" that was published in the British Journal of Pharmacology investigated the controversial and popular phytocannabinoid produced by hemp and cannabis called delta-8 THC.

"In this review, we summarize the pharmacological studies of Δ8-THC, including receptor binding, cell signaling, in vivo (in living creatures) cannabimimetic activity, clinical activity, and pharmacokinetics."

"In this review, we summarize the pharmacological studies of Δ8-THC, including receptor binding, cell signaling, in vivo (in living creatures) cannabimimetic activity, clinical activity, and pharmacokinetics," reported the scientists. They gave special focus to "studies that directly compared Δ8-THC to its more commonly studied isomer, Δ9-THC."

The study noted the current debate and controversy over the legal status of delta-8 THC in the United States. "The Agriculture Improvement Act of 2018 (informally called the 'Farm Bill') removed hemp and hemp products containing less than 0.3 percent Δ9-THC from the legal definition of marijuana in the Federal Controlled Substances Act." Technically speaking, delta-8 is legal and increasingly common because the 2018 Farm Bill defined hemp as including "all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers."

The scientists reported that delta-8 was first derived from the "cyclization of cannabidiol (CBD)" and that it was found to be "highly psychoactive in human studies," the first of which was conducted by American chemist Roger Adams in 1942.

While delta-8 THC occurs naturally, it is produced in relatively small quantities by hemp and cannabis (typically below one percent in dry weight by volume). Today, nearly all delta-8 production at industrial volumes involves conversion of more abundant hemp-derived CBD.

"By 1966, it was realized that Δ8-THC was present in only negligible amounts in cannabis and cannabis-derived products such as hash," wrote the scientists.

Many medical professionals and consumers are most concerned with the effects and potency of delta-8 THC, especially in comparison to delta-9 THC. Delta-8 efficacy was first explored by Adams in 1942, who administered CBD-derived delta-8 to a group of 77 volunteer subjects. Participants began with 30 mg of delta-8 THC and escalated their dose in 30 mg increments that occurred every two days.

"Delta-8 efficacy was first explored by American chemist Roger Adams in 1942, who administered CBD-derived delta-8 to a group of 77 volunteer subjects."

"The reported effects were remarkably similar to Δ9-THC," reported the Adams study. It observed several effects from the delta-8, including "(a) apprehension and anxiety, (b) euphoria, (c) loquaciousness, (d) lowering of inhibitions, (e) hunger and thirst, (f) feeling of being ‘high,’ (g) uncontrollable bursts of laughter or giggles and (h) drowsiness, languor, lassitude, and a pleasant feeling of fatigue."

The study reported that both delta-8 and delta-9 THC display similar binding affinity with the CB1 receptor of the human endocannabinoid system and that the studies this review analyzed "demonstrated that both cannabinoids have very similar qualitative effects."

"Both [cannabinoids] resulted in an increase in heart rate and significant increases in a visual analogue scale of feeling high, which are CB1-mediated effects," reported the study's authors, who concluded that delta-8 THC "may have a...subjective effect very similar to Δ9-THC."

The study reported that both delta-8 and delta-9 THC display similar binding affinity with the CB1 receptor of the human endocannabinoid system and that the studies this review analyzed "demonstrated that both cannabinoids have very similar qualitative effects."

Two of the studies reviewed were clinical investigations involving human participants who consumed delta-8 via inhalation (smoking). "Both the 10 and 20 mg doses of Δ9-THC resulted in stronger ratings of high on a graded interview compared with the equivalent Δ8-THC dose." In other words, delta-9 THC was revealed to be, via subjective reporting, more potent than its chemical cousin delta-8.

Reported one study reviewed: "The 10 mg dose of Δ8-THC resulted in similar ratings of [perceived] high as the 5 mg dose of Δ9-THC, indicating that smoked Δ9-THC is approximately two-fold more potent."

Another study reviewed (from 1973) revealed that "an oral dose of 20 mg Δ9-THC resulted in stronger subjective effects than an equivalent dose of Δ8-THC." This study reported that a 40 mg dose of delta-8 "resulted in a stronger subjective effect than the 20 mg dose of either molecule." The authors of the 2022 review study concluded that "these results...indicate that Δ9-THC is less than twice as potent as Δ8-THC."

However, a 1984 study reviewed found that oral doses of delta-8 THC of both 50 and 75 mg "had weaker effects than a 20 mg dose of Δ9-THC on a 0–7 peak high rating." Reported the review study authors: "This [particular study] indicates that Δ9-THC is at least 3.75-fold more potent than Δ8-THC. They also noted that both the 1973 and 1984 studies featured "a low number of subjects, which could produce spurious results considering the large variability in THC effects across subjects."

A 1995 clinical study involving eight children undergoing chemotherapy for cancer dosed participants at 18 mg (the equivalent of 31 mg in a typical adult) reported that the delta-8 was able to "almost completely prevent vomiting." Side effects were observed in two of the subjects and included "mild irritability and euphoria."

The review study revealed that both delta-8 and delta-9 THC molecules bind with both CB1 and CB2 receptors of the human endocannabinoid system.

The review study's authors concluded that "the pharmacology of Δ8-THC is generally very similar to Δ9-THC" in non-animal studies (in vitro), animal studies (typically involving rodents and called in vivo), and in humans, but stressed that key differences exist.

"The most obvious difference is that Δ8-THC has weaker potency than Δ9-THC, even though it appears to have similar intrinsic efficacy...."

"The most obvious difference is that Δ8-THC has weaker potency than Δ9-THC, even though it appears to have similar intrinsic efficacy...." The study theorized that this potency discrepancy may result from a number of mechanisms, including "a different potency at the CB1 receptor [and] a different balance of CB1 versus CB2 receptor activation."
 

Despite all that has been revealed about the delta-8 THC molecule since experimentation began with Adams in 1942, the review study's authors noted that "further clinical pharmacology studies should be performed to understand the pharmacokinetics and pharmacodynamics of Δ8-THC and how it is distinct from Δ9."

View the original study.