11-OH-THC: The High that Comes from Within Us

It’s unsettling how much unwarranted scrutiny delta-9 tetrahydrocannabinol (THC) has generated through the years. The lucid mind should perpetually question why. These days cannabidiol (CBD) rivals THC in attention, including a recent announcement by the US Food & Drug Administration which coincidentally occurred one day prior to the confirmed expiration of US Patent 6630507B1, which regarded cannabinoids as antioxidants and neuroprotectants.

But there are, of course, other cannabinoids that deserve our attention, not in any wild, irrational ways, but as scientists and those who appreciate and want to understand Cannabis sativa, the phyto-molecules therein, and their natural metabolites. One of these metabolites is called 11-OH-Δ9-THC (spoken as eleven-hydroxy-delta-9-tetrahydrocannabinol). If you’ve eaten an edible infused with THC, you’ve already intimately become acquainted with this molecule.

Our bodies break down THC into 11-OH-THC via a process called first pass metabolism that occurs in our livers. This metabolic reaction is a part of the conversation regarding the low bioavailability of THC (said to be 4-20%). Even with the degradation of much of the orally consumed THC, we can still feel the effects of the edible long after. Thus, 11-OH-THC is intoxicating. [1]

In fact, 11-OH-THC was first considered to be the active ingredient within cannabis. [2] A subsequent study, however, questioned this, after the intravenous (IV) injection of 11-OH-THC failed to induce effects. [3] Nevertheless, 11-OH-THC does intoxicate. In a 1973 study, subjects given 11-OH-THC reported a maximum high just 2-3 minutes after IV injection. The high was more intense than that experienced by smoking cannabis. Some found it initially unpleasant as their hearts beat faster, but these people later recanted, saying it was more pleasant than previous experiences from smoking. [4] So, the effects of 11-OH-THC to the nascent user can be a little frightening early on but can segue into something demonstrably serene.

Manno et al found that just five minutes after smoking cannabis, THC measurably degraded to 11-OH-THC. [5] But, 11-OH-THC lingers in the body much longer, which is why the overall high sustains despite potentially having a diminished “peak” high. Researchers have posited that the enzymes responsible for breaking down THC and 11-OH-THC differ. [5] In another study, when a molecule called proadifen was used to inhibit enzymes housed in the liver, the metabolic pathway from THC to 11-OH-THC was barely affected, whereas the degradation of 11-OH-THC to downstream metabolites was more noticeably inhibited. [6]

The scientific literature abounds with forensic methods of detecting 11-OH-THC in urine [7] or hair [8]. This is the realm that we find ourselves in, since until recent times, the Reefer Madness indoctrination all but squashed increasingly relevant scientific inquiry into the molecular treasure chests known as trichomes. Research, therefore, was often centered around enforcing dying laws juxtaposed to helping humankind.

But I did find one study that made me smile, like the one about the mice and the edibles did. In this study, pigeons were intravenously injected with THC or 11-OH-THC. [9] The rate of the pigeons’ key pecking was evaluated. A 30 µg per kg of body weight dose of either cannabinoid decreased the pecking rate, but the rate returned to normal after 30 to 45 minutes. Doses of 100 or 300 µg/kg caused the pigeons to stop pecking. Recovery times ranged from 60-90 minutes and 195-240 minutes for the two doses, respectively.

It just goes to show you, though, that you can teach birds to peck keys, but once they’ve got THC or 11-OH-THC coursing through their blood, they’re no longer so controllable. What’s happening within their bird brains, however, is anyone’s guess.


  1. Huestis, M. “Human Cannabinoid Pharmacokinetics.” Chem Biodivers, vol. 4, no. 8, 2007, p. 1770–1804. [journal impact factor = 1.444; cited by 303 (ResearchGate)]
  2. Lemberger, L. et al. “11-Hydroxy-9-Tetrahydrocannabinol: Pharmacology, Disposition, and Metabolism of a Major Metabolite of Marihuana in Man.” Science, vol. 177, no. 4043, 1972, p. 62-64. [journal impact factor = 41.063; cited by 97 (ResearchGate)]
  3. Agurell, S. et al. “Pharmacokinetics and Metabolism of 1-Tetrahydrocannabinol and Other Cannabinoids with Emphasis on Man.” Pharmacological Reviews, vol. 28, no. 1, 1986, p. 21-43. [journal impact factor = 17.099; cited by 138 (Semantic Scholar)]
  4. Lemberger, L. et al. “Comparative Pharmacology of A-Tetrahydrocannabinol and its Metabolite, 11-OH-A9-Tetrahydrocannabinol.” The Journal of Clinical Investigation, vol. 52, 1973, p. 2411-2417. [journal impact factor = 12.282; cited by 55 (ResearchGate)]
  5.  Manno, J. et al. “Temporal Indication of Marijuana Use Can Be Estimated from Plasma and Urine Concentrations of Δ9-Tetrahydrocannabinol, 11-Hydroxy-Δ9-Tetrahydrocannabinol, and 11-Nor- Δ9-Tetrahydrocannabinol-9-Carboxylic Acid.” Journal of Analytical Toxicology, vol. 25, 2001, p. 538-549. [journal impact factor = 2.858; cited by 58 (ResearchGate)]
  6. Gill, E. and Jones, G. “Brain Levels of Delta-1-Tetrahydrocannabinol and its Metabolites in Mice–Correlation with Behavior, and the Effect of the Metabolic Inhibitors SKF 525A and Piperonyl Butoxide.” Biochem Pharmacol, vol. 21, 1972, p. 2237-2248. [journal impact factor = 5.009; cited by 13 (Google Scholar)]
  7. Lowe, R. et al. “Extended Urinary Δ9-Tetrahydrocannabinol Excretion in Chronic Cannabis Users Precludes Use as a Biomarker of New Drug Exposure.” Drug Alcohol Depend, vol. 105, no. 1-2, 2009, p. 24–32. [journal impact factor = 3.466; cited by 70 (ResearchGate)]
  8. Wilkins, D. et al. “Quantitative Analysis of THC, 11-OH-THC, and THCCOOH in Human Hair by Negative Ion Chemical Ionization Mass Spectrometry.” Journal of Analytical Toxicology, vol. 19, no. 6, 1995, p. 483–491. [journal impact factor = 2.858; cited by 72 (ResearchGate)]
  9.  Kosersky, D. et al. “Δ9-Tetrahydrocannabinol and 11-OH-Δ9-Tetrahydrocannabinol: Behavioral Effects and Tolerance Development.” The Journal of Pharmacology and Experimental Therapeutics, vol. 189, no. 1, 1974, p. 61-65. [journal impact factor = 3.867; cited by 29 (GoogleScholar)]

Image Credit: Boston Magazine

About the author

Jason S. Lupoi, Ph.D.

Jason S. Lupoi, Ph.D.

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