Understanding how slight structural changes affect cannabinoid pharmacology is one of the central questions in cannabinoid science. THC-C4 — also known as Δ9-tetrahydrocannabutol (Δ9-THCB) or butyl-THC — provides a fascinating case study. It differs from standard Δ9-THC by just one carbon in its side chain (four carbons instead of five), and yet its CB1 receptor binding affinity is remarkably comparable to Δ9-THC itself. This wasn’t expected given conventional structure-activity relationship models — and it makes THC-C4 one of the more pharmacologically interesting minor cannabinoids isolated in recent years (Linciano et al., 2020).
What Is THC-C4?
Delta-9-tetrahydrocannabinol-C4 (THC-C4) is a naturally occurring minor phytocannabinoid in Cannabis sativa L. It is a structural homolog of Δ9-THC in which the five-carbon (pentyl) alkyl side chain at the 3-position of the resorcinol ring is replaced by a four-carbon (butyl) chain. Its formal name is Δ9-tetrahydrocannabutol (Δ9-THCB), with the CAS number 60008-00-6 (Wikipedia contributors, 2025; MedChemExpress, n.d.).
THC-C4 is the THC-family counterpart to cannabidibutol (CBDB/CBD-C4) — the two compounds represent the butyl-chain versions of the two major phytocannabinoids, Δ9-THC and CBD, respectively. Both were isolated together from the Italian medicinal cannabis variety FM2 in the same 2020 study (Linciano et al., 2020).
CAS Number: 60008-00-6
Side chain: Butyl (C4) — one carbon shorter than Δ9-THC’s pentyl (C5)
CB1 receptor Ki: 15 nM (comparable to Δ9-THC at ~40 nM)
CB2 receptor Ki: 51 nM
First formally isolated: 2020 — Linciano et al., Italian medicinal cannabis FM2
Psychoactive: Presumed yes — partial CB1 agonist confirmed in tetrad test
Legal status: Not internationally scheduled, but may fall under analogue laws
Discovery: The FM2 Study
THC-C4 was formally isolated and fully characterized for the first time in a 2020 study published in the Journal of Natural Products by Linciano et al. from the University of Modena and Reggio Emilia. The research team isolated both Δ9-THCB and its CBD counterpart (CBDB) from the inflorescence of the FM2 Italian medical cannabis variety, performed comprehensive spectroscopic characterization (NMR, UV, IR, ECD, HRMS), and confirmed the structures and absolute configurations by comparison with stereoselectively synthesized reference standards (Linciano et al., 2020).
The compound had been catalogued in earlier cannabinoid surveys but had not been formally isolated in pure form with confirmed structural characterization before this 2020 work. Its natural occurrence is rare — Linciano et al. note that THC-C4 has rarely been isolated from cannabis samples and appears considerably less common than Δ9-THC or THCV (Linciano et al., 2020; Wikipedia contributors, 2025).
Pharmacology: The Surprising CB1 Affinity
The pharmacologically significant finding from the Linciano et al. (2020) study is THC-C4’s receptor binding profile. The butyl compound showed CB1 receptor affinity with a Ki of 15 nM and CB2 affinity with a Ki of 51 nM — figures the authors described as “comparable to that of (−)-trans-Δ9-THC” (Linciano et al., 2020).
This is worth contextualizing. The established structure-activity relationship for THC homologs suggests that a minimum of three carbons is required for receptor binding, and that activity increases with chain length up to approximately eight carbons, then decreases. By this model, the four-carbon THC-C4 would be expected to have lower CB1 affinity than the five-carbon Δ9-THC. Its comparable — and in some measurements, higher — binding affinity challenges this simple linear model and suggests that the relationship between chain length and receptor affinity is more nuanced than previously assumed (Linciano et al., 2020; ScienceDirect, 2024).
| Compound | Side Chain | CB1 Ki (nM) | CB2 Ki (nM) |
|---|---|---|---|
| THCV (propyl, C3) | C3 | ~75.4 nM | Low affinity |
| THC-C4 / Δ9-THCB (butyl) | C4 | 15 nM | 51 nM |
| Δ9-THC (pentyl) | C5 | ~39.5–40.7 nM | ~36 nM |
| THCP (heptyl, C7) | C7 | ~1.2 nM | ~2.4 nM |
THC-C4’s Ki of 15 nM actually places it as a stronger binder than standard Δ9-THC’s ~40 nM in these measurements — a surprising finding that underscores why characterizing individual homologs rather than assuming linear progression is essential (Linciano et al., 2020).
Preclinical Biological Activity
Partial CB1 Agonism (Tetrad Test)
The tetrad test — a standard battery of four behavioral assays used in mice to assess cannabimimetic (THC-like) activity, including hypothermia, catalepsy, analgesia, and motor impairment — was performed on Δ9-THCB. Results confirmed partial agonistic activity at the CB1 receptor, consistent with the binding data. This indicates that THC-C4 is pharmacologically active in vivo and produces THC-like effects in animals, though as a partial rather than full agonist (Linciano et al., 2020).
Analgesic and Anti-Inflammatory Activity (Formalin Test)
The formalin test — a two-phase model of pain involving acute nociceptive (phase 1) and inflammatory (phase 2) components — was also conducted with Δ9-THCB. The test was performed to evaluate the compound’s potential analgesic and anti-inflammatory properties. The 2020 study reported findings from this test, positioning THC-C4 as a candidate for analgesic activity — though detailed quantitative outcomes and dose-response data from this specific test require reference to the full published paper (Linciano et al., 2020; MedChemExpress, n.d.).
THC-C4 in the Emerging THC Homolog Series
THC-C4’s isolation in 2020 was part of a broader wave of THC homolog discoveries in the preceding years. The ScienceDirect (2024) summary of this series notes that three new Δ9-THC homologs with linear alkyl side chains were discovered in rapid succession: Δ9-THCB (butyl, C4) in 2020, Δ9-THCH (hexyl, C6), and Δ9-THCP (heptyl, C7) — each with distinct CB1 receptor affinity profiles. Of these, only THCB and THCP have had their CB1 affinity formally evaluated.
These discoveries collectively challenge the long-held assumption that Δ9-THC was essentially the only naturally occurring phytocannabinoid exerting the “cannabis-like” effect, and that variation in such effects between cannabis samples was attributable only to cannabinoid ratios (THC:CBD) and terpenes (ScienceDirect, 2024).
Biosynthetic Origin
Like CBD-C4 (CBDB), THC-C4 appears to lack a dedicated plant enzyme for its biosynthesis. No plant enzymes specifically responsible for producing the butyl cannabinoid series have been identified. The prevailing hypothesis is that both CBDB and Δ9-THCB arise from microbial ω-oxidation and decarboxylation of their five-carbon pentyl counterparts — a biotransformation pathway involving microorganisms associated with the cannabis plant (Linciano et al., 2020; Linciano et al., 2020, as cited in Citti et al., 2019).
Frequently Asked Questions
Is THC-C4 the same as THCB?
Yes — these are multiple names for the same compound. THC-C4, Δ9-THCB, Δ9-tetrahydrocannabutol, butyl-THC, and (C4)-Δ9-THC all refer to the same molecule (CAS 60008-00-6) — the butyl-chain homolog of Δ9-THC (Linciano et al., 2020; Wikipedia contributors, 2025).
Is THC-C4 psychoactive?
Almost certainly yes. It binds CB1 receptors with high affinity (Ki = 15 nM) and showed partial CB1 agonist activity in the tetrad test in mice — a behavioral profile consistent with psychoactivity. No direct human psychoactivity studies have been conducted (Linciano et al., 2020).
Is THC-C4 legal?
THC-C4 is not internationally scheduled under the Convention on Psychotropic Substances. However, as a structural homolog of Δ9-THC, it may be subject to controlled substance analogue laws in certain jurisdictions — including in the United States under the Federal Analogue Act, which covers substances substantially similar in structure or effects to Schedule I or II substances (Wikipedia contributors, 2025).
Why is THC-C4’s CB1 affinity comparable to Δ9-THC despite a shorter chain?
This is an open question. Conventional structure-activity relationship (SAR) models predict increasing CB1 affinity with increasing alkyl chain length (up to ~C8), which would suggest THC-C4 should be weaker than Δ9-THC. The observed comparable affinity (Ki 15 nM vs ~40 nM) suggests the relationship is more complex — potentially involving specific interactions between the butyl chain and CB1 receptor binding pocket residues that are favorable in ways not captured by the linear SAR model (Linciano et al., 2020).
The Bottom Line
THC-C4 (Δ9-tetrahydrocannabutol) is a minor but pharmacologically notable phytocannabinoid. Its formal isolation in 2020 added it to a rapidly expanding family of characterized THC homologs — and its unexpectedly high CB1 binding affinity was one of the more scientifically surprising findings in recent minor cannabinoid research. Its in vivo partial CB1 agonism and preliminary analgesic signals make it a compound of genuine therapeutic interest, even if the current evidence base consists of a single published isolation and characterization study.
Like many minor cannabinoids, the most important chapter of THC-C4’s story has yet to be written — but the opening paragraph is more interesting than most.
Nothing in this article constitutes medical advice. Always consult a qualified healthcare provider before making any decisions about supplementation or treatment.
References
- Linciano, P., Citti, C., Luongo, L., Belardo, C., Maione, S., Vandelli, M. A., Forni, F., Gigli, G., Laganà, A., Montone, C. M., & Cannazza, G. (2020). Isolation of a high-affinity cannabinoid for the human CB1 receptor from a medicinal Cannabis sativa variety: Δ9-tetrahydrocannabutol, the butyl homologue of Δ9-tetrahydrocannabinol. Journal of Natural Products, 83(1), 88–98. https://doi.org/10.1021/acs.jnatprod.9b00876
- MedChemExpress. (n.d.). Δ9-THCB (Δ9-Tetrahydrocannabutol) | CB1R agonist. https://www.medchemexpress.com/9-thcb.html
- New Phase Blends. (2023). Delta-9-tetrahydrocannabinol-C4 (THC-C4). https://www.newphaseblends.com/delta-9-tetrahydrocannabinol-c4-thc-c4/
- ScienceDirect. (2024). Δ9-Tetrahydrocannabiphorol: Identification and quantification in recreational products. https://www.sciencedirect.com/science/article/abs/pii/S246817092400047X
- Wikipedia contributors. (2025). Tetrahydrocannabutol. Wikipedia, The Free Encyclopedia. https://en.wikipedia.org/wiki/Tetrahydrocannabutol
