Figure · v1

Why does cannabis make THC or CBD?

Pick a plant. We'll trace the answer back — from what it makes, through the enzyme, all the way to the gene.

Based on Grassa 2021, Laverty 2019, Sirikantaramas 2004, Taura 2007, de Meijer 2003. The full interactive figure is available on larger screens.

Figure · v1

Why one cannabis plant makes THC and another makes CBD

A single locus on chromosome 6 — and the enzymes encoded there — decides where flux from the shared precursor CBGA is sent. This diagram traces the full path: from the B-locus haplotypes, through the biosynthetic pathway and its trichome-specific regulation, to the three canonical chemotypes that segregate in Mendelian ratios.

Cannabis sativa · THC vs CBDA genome-to-chemotype map of cannabinoid biosynthesis and its regulation — hover any element for detailsTHC branchCBD branchCBC (minor)Shared precursorsRegulationGenome1Genome — cannabinoid synthase locusChromosome 6 (cs10 reference) · ~250 kb, LTR-retrotransposon–rich · Grassa 2021, Laverty 2019centromereB-locus ▼B-locus · ~250 kb>70% LTR retrotransposons · tandem cannabinoid synthase paralogsB_Tdrug-type haplotypeTHCASfunctionalCBDASψpseudogene (ψ)CBCASfunctionalB_Dhemp-type haplotypeTHCASψpseudogene (ψ)CBDASfunctionalCBCASfunctional≈ 50 kb2Biosynthetic pathwayPolyketide + MEP inputs converge on CBGA; paralog-specific oxidocyclases partition flux · Sirikantaramas 2004, Taura 2007, Luo 2019Hexanoyl-CoA3 × Malonyl-CoAOlivetolic acid (OA)GPP (MEP pathway)OLS · OACCBGAS (PT4)CBGAcentral precursorcannabigerolic acid · branchpointCBDASTHCASCBCASCBDAcannabidiolic acidTHCAΔ9-THC acidCBCAcannabichromenic acidΔ heat · UVΔ heat · UVCBDnon-psychoactiveΔ9-THCpsychoactiveCBCminor3RegulationTrichome-specific expressionGlandular trichomeCannabinoid synthases aresecreted into the storage cavityTranscription factorsCsMIXTA-likeMYBSpecifies glandular trichome cell fate on young floral …bHLH / WD40MBW complexPartners with MYB; activates trichome developmental pro…HY5bZIPIntegrates UV-B / blue-light cues; upregulates cannabin…MYC2bHLH (JA)Jasmonate signalling amplifies flux upon herbivory and …AP2/ERFAP2/ERFCo-regulates MEP pathway enzymes that feed GPP into CBG…Environmental cuesUV-B lightElevates THCAS/CBDAS tr…Jasmonate (JA)Wounding / herbivory am…TemperatureModerate heat raises ca…PhotoperiodShort days trigger flow…4Genotype → ChemotypeThe B-locus segregates as a single Mendelian factor · de Meijer 2003, Grassa 2021Type IDrug-typeB_T / B_TTHC ≫ CBDrelative cannabinoid fraction (THC vs CBD)THC 99%CBD 1%typical dry-weight concentrationsΔ9-THC~20%CBD<0.3%THCAS functional on both B-locus allelesType IIIntermediateB_T / B_DTHC ≈ CBDrelative cannabinoid fraction (THC vs CBD)THC 50%CBD 50%typical dry-weight concentrationsΔ9-THC~8%CBD~8%Heterozygous: THCAS and CBDAS both expressedType IIIHemp / fiber-typeB_D / B_DCBD ≫ THCrelative cannabinoid fraction (THC vs CBD)THC 2%CBD 98%typical dry-weight concentrationsΔ9-THC<0.3%CBD~15%CBDAS functional; THCAS present as pseudogeneReferences[Grassa 2021] Grassa C. J. et al. (2021). A new cannabis genome assembly associates elevated …[Laverty 2019] Laverty K. U. et al. (2019). A physical and genetic map of Cannabis sativa iden…[van Bakel 2011] van Bakel H. et al. (2011). The draft genome and transcriptome of Cannabis sati…[Taura 2007] Taura F. et al. (2007). Cannabidiolic-acid synthase, the chemotype-determining …[Sirikantaramas 2004] Sirikantaramas S. et al. (2004). The gene controlling marijuana psychoactivity:…[de Meijer 2003] de Meijer E. P. M. et al. (2003). The inheritance of chemical phenotype in Cann…Reference genome: Cannabis sativa cs10 · NCBI GCA_900626175.2
Figure 1 · Genome-to-chemotype map of cannabinoid biosynthesis in Cannabis sativa. Functional THCAS and CBDAS segregate on alternative haplotypes (B_T / B_D) at a ~250 kb, retrotransposon-rich locus; the non-functional paralog is typically retained as a pseudogene (ψ). Pathway flux from CBGA is committed by whichever synthase is active in the glandular trichome. Compiled from Grassa 2021, Laverty 2019, Sirikantaramas 2004, Taura 2007, and de Meijer 2003.