GenetixBayEST. 2009
Breeding · Breeder · 3 min read

Chemotype inheritance: how THC and CBD synthase alleles pass on

Whether a plant is THC dominant, CBD dominant or mixed is controlled mainly by a single inheritance block carrying THCA synthase and CBDA synthase genes, which behaves close to codominant: THC x CBD gives mixed (type II) F1s and a 1:2:1 split in the F2. CBG-dominant and cannabinoid-free types come from non-functional synthase alleles. Total cannabinoid amount is a separate, quantitative trait.

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Being reviewed. Our editors are double-checking a few figures in this article against primary sources. Marked passages may change.

Short answer. CBGA is the shared precursor; a THCA synthase turns it into THCA and a CBDA synthase into CBDA. Which functional synthase a plant carries is inherited as one block, close to codominant. THC-dominant x CBD-dominant gives mixed F1s (roughly 1:1 to 1:2 THC:CBD); intercross those and you get about 1 THC : 2 mixed : 1 CBD. Mixed plants never breed true. How much total cannabinoid a plant makes is a separate, many-gene trait.

What's happening

  • The pathway. CBGA sits at a fork. THCAS, CBDAS and CBCAS compete for it. If neither THCAS nor CBDAS works, CBGA builds up (chemotype IV) [2]. If CBGA itself is barely made (or trichome development fails), the plant is near cannabinoid-free (chemotype V) [8].
  • The 2003 model. de Meijer et al. crossed inbred pure-THC and pure-CBD plants and explained the results with one locus, B, with codominant alleles B_T and B_D [1]. The F1 was uniformly mixed; F2s segregated 1:2:1.
  • The genomic picture. THCAS and CBDAS are separate but closely linked genes, sitting in large (>250 kb), retrotransposon-rich, low-recombination regions that differ structurally between drug and hemp types [3][4]. In practice they still inherit together, so the one-locus model predicts well, but "B_T" and "B_D" are really haplotypes (gene blocks), not single genes. Non-functional copies and gene duplications exist [3].
  • CBD in drug-type lines often traces to hemp introgressed into marijuana backgrounds [5] (Supported).

Chemotypes

Chemotype Typical ratio Inferred synthase genotype Breeds true?
I, THC dominant THC:CBD > ~10:1 (often far higher) B_T / B_T Yes, for chemotype
II, mixed ~0.5:1 to 3:1 B_T / B_D No: segregates 1:2:1
III, CBD dominant CBD:THC > ~10:1 (hemp lines often 20-30:1) B_D / B_D Yes, for chemotype
IV, CBG dominant High CBG, low THC and CBD Null (non-functional) synthase alleles, homozygous [2] Yes, once homozygous
V, near zero Trace cannabinoids Pathway blocked upstream [8] Yes

Ratio boundaries are approximate and vary between studies [1][6]. Note: "CBD dominant" plants still make some THC; even good hemp lines show THC:CBD ratios around 1:20 to 1:30 because CBDAS itself makes a little THCAbeing reviewed.

Punnett square: THC x CBD

F1 (B_T/B_D) x F1 (B_T/B_D):

B_T B_D
B_T I (THC) II (mixed)
B_D II (mixed) III (CBD)

Backcross F1 (B_T/B_D) to the CBD parent (B_D/B_D): 1 mixed : 1 CBD. Two backcrosses with selection for type III recover a CBD-dominant line with the THC parent's other traits partly kept.

Step by step: breeding a stable CBD-dominant line

  1. Cross your THC-dominant selection (female) with a stable CBD-dominant male.
  2. Grow F1s; all should be type II. Any type I or III F1 means a parent wasn't homozygous.
  3. Choose the best F1 (or backcross to the CBD parent).
  4. In the F2 or BX1, screen seedlings with a chemotype DNA marker if available [7], or test a leaf or flower sample by chromatography.
  5. Keep only type III plants; select among them for the traits you want.
  6. Confirm the ratio with flower tests (same stage, same lab) on several plants of the final line.

Numbers that matter

Population Expected chemotype split
I x III (both homozygous) 100% II
II x II 25% I : 50% II : 25% III
II x III 50% II : 50% III
II x I 50% I : 50% II
Plants needed for 95% chance of ≥1 type III in an F2 11 (p = 0.25)
...of ≥5 type III in an F2 34 (binomial, p = 0.25)

Common mistakes

  • Expecting a 1:1 cultivar to breed true. It is heterozygous by definition.
  • Selecting "high THC" from small, single-run lab results. Total THC is quantitative and environment- and lab-sensitive.
  • Assuming a seedling leaf test predicts the final ratio exactly. It predicts chemotype class well; ratios shift through flowering (Supported).
  • Forgetting legal limits: in hemp jurisdictions, total THC limits apply to the crop, and type II segregants can exceed them.

Evidence

  • Single inheritance unit, codominant model: Established [1], refined by genomics [3][4].
  • CBG-dominant inheritance via null alleles: Established [2].
  • Chemotype markers for seedling screening: Supported [7]; marker performance may vary by germplasm.
  • Hemp introgression as a CBD source in drug-type lines: Supported [5].

Questions this article answers

If I cross a THC plant with a CBD plant what do I get?

Whether a plant is THC dominant, CBD dominant or mixed is controlled mainly by a single inheritance block carrying THCA synthase and CBDA synthase genes, which behaves close to codominant: THC x CBD gives mixed (type II) F1s and a 1:2:1 split in the F2. CBG-dominant and cannabinoid-free types come from non-functional synthase alleles. Total cannabinoid amount is a separate, quantitative trait.

How is the THC to CBD ratio inherited?

Whether a plant is THC dominant, CBD dominant or mixed is controlled mainly by a single inheritance block carrying THCA synthase and CBDA synthase genes, which behaves close to codominant: THC x CBD gives mixed (type II) F1s and a 1:2:1 split in the F2. CBG-dominant and cannabinoid-free types come from non-functional synthase alleles. Total cannabinoid amount is a separate, quantitative trait.

What are chemotypes I, II, III, IV and V?

Whether a plant is THC dominant, CBD dominant or mixed is controlled mainly by a single inheritance block carrying THCA synthase and CBDA synthase genes, which behaves close to codominant: THC x CBD gives mixed (type II) F1s and a 1:2:1 split in the F2. CBG-dominant and cannabinoid-free types come from non-functional synthase alleles. Total cannabinoid amount is a separate, quantitative trait.

Can a 1:1 THC:CBD plant breed true?

Whether a plant is THC dominant, CBD dominant or mixed is controlled mainly by a single inheritance block carrying THCA synthase and CBDA synthase genes, which behaves close to codominant: THC x CBD gives mixed (type II) F1s and a 1:2:1 split in the F2. CBG-dominant and cannabinoid-free types come from non-functional synthase alleles. Total cannabinoid amount is a separate, quantitative trait.

How are CBG-dominant plants made?

Whether a plant is THC dominant, CBD dominant or mixed is controlled mainly by a single inheritance block carrying THCA synthase and CBDA synthase genes, which behaves close to codominant: THC x CBD gives mixed (type II) F1s and a 1:2:1 split in the F2. CBG-dominant and cannabinoid-free types come from non-functional synthase alleles. Total cannabinoid amount is a separate, quantitative trait.

Can I predict THC percentage from genetics?

Whether a plant is THC dominant, CBD dominant or mixed is controlled mainly by a single inheritance block carrying THCA synthase and CBDA synthase genes, which behaves close to codominant: THC x CBD gives mixed (type II) F1s and a 1:2:1 split in the F2. CBG-dominant and cannabinoid-free types come from non-functional synthase alleles. Total cannabinoid amount is a separate, quantitative trait.

Sources

  1. de Meijer EPM, Bagatta M, Carboni A, et al. 2003. The inheritance of chemical phenotype in Cannabis sativa L. Genetics 163(1):335-346. doi.org/10.1093/genetics/163.1.335
  2. de Meijer EPM, Hammond KM. 2005. The inheritance of chemical phenotype in Cannabis sativa L. (II): Cannabigerol predominant plants. Euphytica 145:189-198. doi.org/10.1007/s10681-005-1164-8
  3. Weiblen GD, Wenger JP, Craft KJ, et al. 2015. Gene duplication and divergence affecting drug content in Cannabis sativa. New Phytologist 208(4):1241-1250. doi.org/10.1111/nph.13562
  4. Laverty KU, Stout JM, Sullivan MJ, et al. 2019. A physical and genetic map of Cannabis sativa identifies extensive rearrangements at the THC/CBD acid synthase loci. Genome Research 29(1):146-156. doi.org/10.1101/gr.242594.118
  5. Grassa CJ, Weiblen GD, Wenger JP, et al. 2021. A new Cannabis genome assembly associates elevated cannabidiol (CBD) with hemp introgressed into marijuana. New Phytologist 230(4):1665-1679. doi.org/10.1111/nph.17243
  6. Hillig KW, Mahlberg PG. 2004. A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae). American Journal of Botany 91(6):966-975. doi.org/10.3732/ajb.91.6.966
  7. de Meijer EPM, Hammond KM, Sutton A. 2009. The inheritance of chemical phenotype in Cannabis sativa L. (IV): cannabinoid-free plants. Euphytica 168:95-112. doi.org/10.1007/s10681-009-9894-7
  8. Toth JA, Stack GM, Cala AR, et al. 2020. Development and validation of genetic markers for sex and cannabinoid chemotype in Cannabis sativa L. GCB Bioenergy 12(3):213-222. doi.org/10.1111/gcbb.12667

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