Cannabigerol

# Research Output: Cannabigerol (CBG)

**PSX ID:** PSX-0420  
**Slug:** cbg  
**Research Date:** 2026-05-12  
**Provenance ID:** 4793671d-8bf6-4688-864d-d1e4d6007c8e

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## Chemical Identity

**Verified via PubChem CID 5315659** [Ref 1 — database_lookup]:

| Field | Value |
|---|---|
| PubChem CID | 5315659 |
| Molecular Formula | C₂₁H₃₂O₂ |
| Molecular Weight | 316.5 g/mol |
| IUPAC Name | 2-[(2E)-3,7-dimethylocta-2,6-dienyl]-5-pentylbenzene-1,3-diol |
| InChIKey | QXACEHWTBCFNSA-SFQUDFHCSA-N |
| Chemical Class | Terpenophenol (meroterpenoid); member of the classical cannabinoid structural class |

**SMILES:** Derivable from the IUPAC; the (2E) designation confirms the *trans*-geranyl side chain stereochemistry. CBG does not possess chiral centers; its stereochemistry is defined by the E-configured double bond in the geranyl moiety.

**Discrepancy note:** The Psychedex seed data listed the compound with no molecular formula, SMILES, molecular weight, InChIKey, or PubChem CID. All of these are now confirmed from PubChem. The pharmacological class in the seed data ("Cannabinoid CB1 receptor partial agonist") is partially correct but significantly incomplete given CBG's broad multi-target pharmacology (see Pharmacology section). Flag for update.

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## History

### Discovery and Isolation

Cannabigerol was first isolated from hashish (cannabis resin) in **1964 by Yehiel Gaoni and Raphael Mechoulam** at the Weizmann Institute of Science, Rehovot, Israel [Refs 32, 33]. CBG is historically notable as **the first cannabinoid to be purified from Cannabis sativa**, and its elucidation helped establish the foundational framework for cannabinoid chemistry. In the same decade, Mechoulam's laboratory also determined the full structures of THC and CBD.

Early research on CBG progressed slowly after initial characterization, primarily because CBG occurs in very low concentrations in most Cannabis cultivars (typically <1% by dry weight in mature plants). The vast majority of the plant's CBGA (cannabigerolic acid, the carboxylated precursor to CBG) is enzymatically converted to THCA, CBDA, or CBCA during plant maturation [Ref 16].

### Biosynthetic Significance: "The Mother of Cannabinoids"

Cannabigerolic acid (CBGA) serves as the universal biosynthetic precursor from which all major phytocannabinoids are derived [Refs 16, 17]. Specialized Cannabis cultivars have been developed (those carrying the B₀ genotype) that accumulate high CBG concentrations by lacking or having non-functional downstream synthases [Ref 23]. This botanical background, combined with advances in yeast fermentation biosynthesis [Ref 28], has enabled sufficient CBG supply for modern research.

### Research Acceleration

Research on CBG accelerated markedly after approximately 2010, driven by: (a) availability of high-CBG cultivars, (b) legal reforms enabling research with hemp-derived cannabinoids, and (c) the 2018 U.S. Farm Bill legalizing hemp-derived cannabinoids. The compound has gone from obscure phytochemical to one of the most commercially-marketed minor cannabinoids by 2024–2026.

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## Pharmacology

### Receptor Binding Profile

CBG is a **pleiotropic, multi-target phytocannabinoid** with low affinity for classical cannabinoid receptors and higher activity at several non-canonical targets.

#### Cannabinoid Receptors (CB1, CB2)

- CBG acts as a **partial agonist at CB1 and CB2 receptors**, but with 10–100× lower affinity than THC (Queiroz et al. 2025 [Ref 3], systematic review and meta-analysis of Ki data across published studies).
- Direct radioligand competitive binding in Rosenthaler et al. 2014 [Ref 4] confirmed measurable but substantially lower affinity than THC or CBN at both human CB1 and CB2 receptors using [³H]CP-55,940.
- Zagzoog et al. 2020 [Ref 24] confirmed **partial agonist activity at both CB1R and CB2R** in CHO cell lines via cAMP inhibition and β-arrestin2 recruitment assays, and demonstrated in vivo responses (anti-nociceptive, anxiolytic, hypolocomotive) consistent with weak CB1R activation.
- Navarro et al. 2020 [Ref 2] characterized CBG activity at CB1/CB2 heteromers, noting pharmacological data for CBGA, CBGV, and CBG-type compounds at receptor dimers.

**⚑ FLAG:** No published human receptor occupancy data (PET) for CBG. All receptor binding data are in vitro or ex vivo. The seed data characterization of CBG as a "CB1 receptor partial agonist" is technically accurate but omits CB2, TRP channels, and other significant targets.

#### TRP Channels

De Petrocellis et al. 2011 [Ref 2] — the most-cited study of CBG TRP pharmacology (920 citations) — reported:
- **TRPV1:** CBG stimulates (agonist) and desensitizes human TRPV1. Relevant to pain and inflammation signaling.
- **TRPV2:** CBG potently activated and desensitized rat TRPV2.
- **TRPM8:** CBG-BDS (botanical drug substance) was among the **most potent TRPM8 antagonists** among cannabinoids tested. Relevant to prostate cancer (TRPM8 promotes androgen receptor-dependent survival) and nociception.
- **TRPA1:** Weak activity compared to CBD, CBC.

Lowin et al. 2023 [Ref 7] identified **TRPA1 as the main TRP family target** for CBG in rheumatoid arthritis synovial fibroblasts, mediating intracellular calcium increases, drug uptake facilitation, and anti-inflammatory effects.

#### 5-HT₁A Receptor

Yap et al. 2026 [Ref 41] used molecular docking and MD simulations to show that CBG (neutral form) preferentially binds at the **orthosteric site of the human 5-HT₁A receptor** and is predicted to function as a partial agonist. This is consistent with anxiolytic effects observed in human and animal studies. Note: this is computational (in silico) data only; direct radioligand binding at 5-HT₁A for CBG has not been retrieved from primary sources.

#### Alpha-2 Adrenoceptor

Multiple sources (Lowin et al. 2023 [Ref 7]; Dziemitko et al. 2025 [Ref 47]; general pharmacology reviews) mention α₂-adrenoceptor as a target of CBG. No specific Ki or EC50 value at α₂-adrenoceptors was retrieved from published primary sources. **⚑ FLAG for human review:** α₂-adrenoceptor activity of CBG should be documented with a primary binding study citation.

#### PPAR-γ

Multiple studies from the Fernandez-Ruiz/Munoz laboratory demonstrate that CBG-derived quinone derivatives (VCE-003, VCE-003.2) are active at **peroxisome proliferator-activated receptor-γ (PPAR-γ)** [Refs 25, 29, 46]. Direct PPAR-γ activity of CBG itself (versus its quinone derivatives) is less well-characterized, though Valdeolivas et al. 2015 [Ref 37] found modest upregulation of PPAR-γ gene expression in HD mice after CBG treatment.

#### Anandamide Cellular Uptake (ACU) and Endocannabinoid Enzymes

De Petrocellis et al. 2011 [Ref 2] showed:
- **CBG inhibits anandamide cellular uptake** (ACU) in RBL-2H3 cells, comparably to CBD.
- CBG-BDS inhibited **N-acylethanolamine acid amide hydrolase (NAAA)**.
- CBG did not significantly inhibit FAAH or MAGL (unlike CBD).

Di Meo et al. 2022 [Ref 8] showed CBG modulates ECS component expression in human keratinocytes, including increasing CB1/CB2 binding, TRPV1 stimulation, and FAAH/MAGL activity.

#### GPR55

Multiple reviews and the Queiroz 2025 meta-analysis [Ref 3] identify GPR55 as a likely non-canonical target for CBG and other non-psychotropic cannabinoids. No specific published Ki or functional assay data for CBG at GPR55 was retrieved from primary sources. **⚑ FLAG.**

### Mechanism Summary

CBG's pharmacological profile is predominantly non-CB1-mediated. Key mechanisms include:
1. Weak partial agonism at CB1/CB2 (relevant at supratherapeutic concentrations)
2. TRPV1/TRPV2 agonism → desensitization (analgesia, anti-inflammation)
3. TRPM8 antagonism (relevant to prostate cancer, cold allodynia)
4. TRPA1 activation (rheumatoid arthritis, pain)
5. 5-HT₁A partial agonism (predicted; anxiolytic)
6. α₂-adrenoceptor activity (reported but not quantified)
7. Anandamide reuptake inhibition (pro-endocannabinoid)
8. NAAA inhibition (endocannabinoid system modulation)
9. PPAR-γ modulation (neuroprotection, anti-inflammation; established via quinone derivatives)
10. Antibacterial cytoplasmic membrane disruption (anti-infective)

### Pharmacokinetics

**No published human pharmacokinetic studies were identified.** This is a significant gap.

**Equine PK data** (Serrano-Rodríguez et al. 2025 [Ref 30]) provides the only published species-level CBG pharmacokinetics, characterizing absorption, distribution, metabolism, and elimination following IV and oral administration in horses using micellar and oil formulations.

**General pharmacokinetic context from class-level data:**
- Like other cannabinoids, CBG is highly lipophilic, which predicts significant first-pass hepatic metabolism after oral administration and low oral bioavailability without formulation optimization.
- Polanska et al. 2023 [Ref 9] detected CBG in rat tissues (liver, brain, muscle, heart, kidney, skin) at low ng/g level after chronic oral exposure at 0.66–1.33 mg/kg/day, confirming CNS penetration.
- **CYP enzyme involvement:** No published CBG-specific CYP inhibition/induction studies were retrieved. **⚑ FLAG (safety-critical):** CYP450 interaction profile of CBG is uncharacterized in primary literature.

The ongoing Phase 1 clinical trial NCT05324982 (Johns Hopkins University, "Pharmacokinetics and Pharmacodynamics of CHI-914") is examining a cannabinoid formulation and may yield human PK data.

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## Subjective Effects

### Human Clinical Data

**Only one published randomized controlled trial in humans was identified:**

Cuttler et al. 2024 [Ref 12] — double-blind, placebo-controlled crossover field trial (n=34 healthy adults). 20 mg hemp-derived CBG or placebo administered via tincture:
- **Significant reductions in anxiety** (overall main effect of CBG)
- **Significant reductions in stress** at T1 post-ingestion
- **Enhanced verbal memory** relative to placebo
- **No evidence of subjective drug effects** (no "high," intoxication, or altered consciousness)
- **No motor or cognitive impairment** (DRUID impairment app)

This finding is clinically important: 20 mg oral CBG reduces anxiety and stress in healthy adults without producing any detectable psychoactive effects, distinguishing it fundamentally from THC.

### Animal Studies (effects relevant to subjective effects section)

- **Appetite stimulation:** Brierley et al. 2016 [Ref 20] demonstrated CBG as a **"novel, well-tolerated appetite stimulant"** in pre-satiated rats, with hyperphagia at doses not producing locomotor suppression. CBG has affinity for molecular targets involved in feeding behavior regulation.
- **Anxiolytic effects:** Zagzoog et al. 2020 [Ref 24] confirmed anxiolytic effects in mice consistent with weak CB1R activation.
- **Anti-nociceptive effects:** Zagzoog et al. 2020 [Ref 24] demonstrated in vivo anti-nociceptive effects in mice.
- **No antidepressant-like effect in rodent FST/TST:** El-Alfy et al. 2010 [Ref 26] found CBG did not produce antidepressant-like actions up to 80 mg/kg in mouse forced swim or tail suspension tests (contrast with CBC and CBD, which showed significant effects at high doses).

### Effect Profile Notes

CBG is consistently characterized as **non-psychotomimetic** across all published literature. It does not produce cannabis-type intoxication, impairment, or "high." This is supported by:
- Structural/mechanistic analysis: insufficient CB1R efficacy to produce psychoactive effects
- In vivo animal data showing lack of cataleptic, hypothermic effects typically associated with CB1R activation at tested doses
- Human RCT data (Cuttler 2024) confirming no subjective drug effects at 20 mg oral

**Effects taxonomy mapping (from published evidence):**

*Supported by human data (Cuttler 2024):*
- anxiety-suppression (significant reduction at 20 mg oral)
- memory-enhancement (verbal memory enhanced vs. placebo)

*Supported by animal data only:*
- appetite-enhancement (rats, Brierley 2016)
- pain-suppression (mice, Zagzoog 2020)

*Proposed by clinical studies (therapeutic context):*
- muscle-relaxation (RA context, Lowin 2023)

---

## Safety & Toxicity

### LD50 / Acute Toxicity

No published LD50 data for CBG in any species was retrieved. **⚑ FLAG (safety-critical).**

### Chronic Toxicity — In Vivo (Rat)

Polanska et al. 2023 [Ref 9] — **90-day rat safety study** (orally administered 0.66 mg or 1.33 mg CBG/kg/day):
- **Hepatotoxic manifestations** (regressive changes on histopathology) in CBG-treated animals
- Disruption in **white cell count**
- Altered ALT activity, creatinine, and ionized calcium
- Elevated **total oxidative stress**, malondialdehyde, and carbonylated proteins in CBG-treated animals (in contrast to CBD, which showed antioxidant effects)
- The dimethyloctadienyl structural pattern in CBG (the geranyl moiety) is proposed as responsible for the redox disruption and hepatic effects
- Both CBD and CBG accumulated in rat tissues at low ng/g

**⚑ FLAG (safety-critical):** These findings at very low doses (0.66 mg/kg/day) in rats merit human review and caution in characterizing CBG's safety profile. However, context is important:

### Comparative Hepatotoxicity in Human iPSC Model

Gao et al. 2024 [Ref 10] — transcriptomic analysis in human iPSC-derived hepatocytes exposed to hemp cannabinoids:
- Potency order: CBN > CBD > CBC > CBG
- **CBG was the least potent hepatotoxic agent** among cannabinoids tested
- All cannabinoids impaired liver metabolism and caused oxidative stress at tested concentrations
- Benchmark concentration (BMC) analysis shows CBG has the highest BMC (lowest potency) for transcriptional activity

This apparent contradiction (rat in vivo vs. human iPSC hepatocytes) represents a data inconsistency that requires attention. The different concentrations, formulations, and species must be considered when interpreting these findings.

### In Vitro Cytotoxicity

Santos et al. 2026 [Ref 11] — BV-2 microglial cells:
- CBG 100 µM: **highly cytotoxic** (reduced cell viability by ~80%), markedly increased NO (~400%) and ROS (~900%)
- CBG 10 µM and 100 µM: **genotoxic** in GEMO assay (~200–300% DNA damage); no genotoxicity in Comet assay
- CBG 100 µM promoted microglial activation and morphological changes
- **Favorable safety profile at low doses** (< 10 µM); inconsistent anti-inflammatory effects; concentration-dependent

Rosenthaler et al. 2014 [Ref 4] noted cytotoxic properties of CBG in murine mesencephalic primary cell cultures and N18TG2 neuroblastoma cell line, suggesting non-receptor-mediated cytotoxic mechanism at high concentrations.

### Topical Safety (Clinical)

Perez et al. 2022 [Ref 28] — 20-subject vehicle-controlled clinical study: 0.1% topical CBG serum applied for 2 weeks after SLS-induced skin irritation was well-tolerated and showed no adverse events.

### Summary Safety Statement

CBG appears well-tolerated in humans at the single dose level tested (20 mg oral, Cuttler 2024). Chronic safety data in humans is absent. In vitro and rodent data raise hepatotoxic signals at low concentrations that should be investigated further. High concentrations (>> therapeutic range) produce cytotoxicity and genotoxicity in vitro.

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## Harm Reduction

### Contraindications

No published contraindication data specific to CBG was retrieved. **⚑ FLAG.**

Based on class-level considerations and the available data:
- **Hepatic impairment:** Given rat hepatotoxicity signals (Polanska 2023), caution is warranted in individuals with pre-existing liver disease until human safety data are available.
- **Drug interactions:** CYP450 interactions are uncharacterized (⚑ FLAG). As with other cannabinoids, interaction with CYP3A4 or CYP2C9 substrates is theoretically possible but not documented.
- **Pregnancy/lactation:** No data available.
- **Pediatric populations:** No safety data.

### Testing Recommendations

CBG is not detectable by standard cannabinoid immunoassay tests designed for THC, but may be present in cannabis-derived products. Third-party certificate of analysis from accredited labs is the primary verification method.

### Emergency Response

No case reports of acute CBG toxicity or overdose in humans were identified in the literature.

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## Tolerance & Dependence

No published studies specifically characterizing **CBG tolerance, dependence liability, or withdrawal** in animals or humans were identified.

CBG does not produce significant CB1 receptor activation, which is the primary mechanism behind cannabis tolerance and dependence (driven by THC). The available human data (Cuttler 2024, n=34, single-dose) found no evidence of psychoactive or reinforcing effects, which makes significant abuse potential unlikely based on pharmacological profile, but this has not been formally assessed.

**⚑ FLAG:** Tolerance and dependence data for CBG are entirely absent from published literature. The generation agent should note this gap explicitly.

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## Interactions

### Drug Interactions

No published pharmacokinetic drug interaction studies for CBG were retrieved. **⚑ FLAG (safety-critical).**

Theoretical considerations:
- CBG, like other lipophilic cannabinoids, is likely metabolized by hepatic CYP enzymes. Without published data, the specific CYP profile cannot be stated.
- Potential pharmacodynamic interactions with CNS depressants (additive sedation) are speculative given CBG's very mild CNS profile.
- Svendsen et al. 2025 [Ref 34] demonstrated synergistic/additive analgesic interactions between CBG and other non-psychotropic cannabinoids (CBD, CBC, CBDV) in colitis pain model, mediated via Cav2.2 channels.

### Herb-Drug Interactions

No published data. Hemp-derived CBG products may contain trace amounts of other cannabinoids, terpenoids, or flavonoids that could contribute to herb-drug interactions.

---

## Anti-inflammatory and Therapeutic Applications (Preclinical Summary)

### Inflammatory Bowel Disease / Colitis

Borrelli et al. 2013 [Ref 36] — **landmark study** in murine DNBS-induced colitis: CBG reduced colon weight/length ratio, myeloperoxidase activity, iNOS expression; increased SOD activity; normalized IL-1β, IL-10, IFN-γ. Effect modulated by CB2 receptor. Recommended CBG for clinical IBD experimentation.

Anderson et al. 2024 [Ref 21] — high-CBG hemp extract (DSS colitis model): dramatic reduction in disease activity, histological colitis severity, and normalization of microbiome and metabolomics.

Pagano et al. 2021 [Ref 22] — oral CBG alone ameliorated DNBS colitis; fish oil pretreatment enhanced CBG effects and enabled inactive-dose CBD to become effective.

Svendsen et al. 2025 [Ref 34] — CBG (10 mg/kg) reduced visceral hypersensitivity and spinal c-Fos activation in DSS colitis; subtherapeutic combination dose effective via Cav2.2 channels.

### Antibacterial

Appendino et al. 2008 [Ref 6] — landmark structure-activity study: CBG and all five major cannabinoids active against MRSA clinical strains (MIC data). Prenyl moiety acts as lipid affinity modulator.

Farha et al. 2020 [Ref 5] — established mechanism: **CBG targets cytoplasmic membrane of Gram-positive bacteria**, disrupting membrane integrity. In vivo murine MRSA model: systemic CBG treatment effective. Combined with polymyxin B effective against Gram-negative pathogens. MIC range: 0.5–8 µg/mL.

Alfei et al. 2023 [Ref 15] — review: CBG inhibits MRSA biofilm formation, eradicates mature biofilms, rapidly kills persister cells.

### Neuroprotection

Valdeolivas et al. 2015 [Ref 37] — CBG in two HD models: extremely active in 3-NP mice (motor improvement, striatal neuroprotection, anti-microgliosis, antioxidant defense improvement); significant but more modest recovery in R6/2 transgenic mice. BDNF, IGF-1, PPAR-γ gene expression partially normalized. Mutant huntingtin aggregation reduced.

Fleisher-Berkovich et al. 2023 [Ref 13] — CBG attenuated clinical scores in EAE (MS model) mice; reduced microglial NO and TNF-α; restored neuronal loss.

Kohara et al. 2025 [Ref 45] — CBG (1, 5, 10 mg/kg i.p.) attenuated memory impairments and neurodegeneration after cerebral ischemia in mice.

VCE-003.2 (CBG quinone derivative): neuroprotective in PD [Ref 46], ALS (Rodriguez-Cueto 2018 PMID 30076846 [Ref 46]), and Huntington's neurogenesis (Aguareles 2019 [Ref 29]) via PPAR-γ activation.

### Antidepressant / Mood

CBG did NOT produce antidepressant-like action up to 80 mg/kg in mouse FST or TST (El-Alfy et al. 2010 [Ref 26]), in contrast to claims in popular media.

However, the Cuttler 2024 human study [Ref 12] did find reduced anxiety and stress (not depression per se) at 20 mg in humans.

Sharma et al. 2025 [Ref 39] conducted network pharmacology + in vivo analysis specifically investigating CBG for depression; results not fully available in abstract.

### Glaucoma

Colasanti 1990 [Ref 27] — both CBG and THC reduced intraocular pressure (IOP) in cats by 4–7 mmHg after chronic topical administration, via a 2–3× increase in aqueous outflow facility. CBG was **devoid of cortical EEG polyspike effects** seen with THC, supporting potential for glaucoma with cleaner CNS profile. No human glaucoma studies identified.

### Appetite / Cachexia

Brierley et al. 2016 [Ref 20] — CBG is a **"well-tolerated appetite stimulant"** in pre-satiated rats, showing hyperphagia without locomotor suppression. Mechanism involves multiple feeding-related molecular targets. CBG represents a potential non-psychoactive appetite stimulant.

### Skin

Perez et al. 2022 [Ref 28] — yeast-biosynthesized CBG reduces ROS better than vitamin C in fibroblasts; inhibits pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) more potently than CBD in some assays; 20-subject clinical study showed significant improvement in TEWL and redness reduction with 0.1% topical CBG serum.

Di Meo et al. 2022 [Ref 8]; Tortolani et al. 2023 [Ref 42] — anti-inflammatory in human keratinocytes; modulates ECS and MAPK signaling.

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## Legal Status

CBG's legal status depends entirely on its botanical origin (hemp vs. marijuana-type Cannabis) and jurisdiction:

### United States
Hemp-derived CBG is **federally legal** under the Agricultural Improvement Act of 2018 (2018 Farm Bill), which legalized hemp and all hemp-derived cannabinoids containing ≤0.3% Δ9-THC on a dry weight basis. CBG is not listed on any Federal Controlled Substances Schedule. State-level regulations vary; most states align with federal law [Ref 31].

### United Kingdom
CBG is legal when derived from EU-approved industrial hemp strains containing <0.2% THC. Products must not make unapproved medical claims [Ref 31].

### European Union
Hemp-derived cannabinoids including CBG are legal from EU-approved hemp strains with <0.2% THC, though individual member states may impose additional restrictions [Ref 31].

### Canada
CBG products are regulated under the Cannabis Act (Health Canada) and are legal [Ref 31].

### Australia
Hemp-derived CBG is legal provided it contains <0.3% THC and complies with Therapeutic Goods Administration (TGA) regulations. If derived from high-THC Cannabis, it would be controlled [Ref 31].

**Note:** No specific scheduling action targeting CBG was found in any jurisdiction. Its legal status derives from its classification as a hemp-derived cannabinoid rather than any explicit CBG-specific legislation.

---

## Clinical Trials

Fourteen trials identified via ClinicalTrials.gov with CBG as a primary or significant arm:

| NCT ID | Title | Phase | Status | Sponsor |
|---|---|---|---|---|
| NCT06638996 | Acute Psychological and Physiological Effects of CBG | N/A | Recruiting | Washington State University |
| NCT05257044 | Acute Effects of Cannabigerol (anxiety, stress, cognition) | Phase 1 | Completed | Washington State University |
| NCT05743985 | Efficacy and Safety of Full Spectrum CBG in Adults | N/A | Completed | Formula30A LLC |
| NCT07016971 | CBG/CBD Oil for Chemotherapy-Induced Peripheral Neuropathy | Phase 1 | Recruiting | Penn State/Hershey Medical |
| NCT06115603 | Effects of CBG on ADHD | Phase 2 | Recruiting | University of Arkansas |
| NCT06513507 | CBG in Active Rheumatoid Arthritis | N/A | Active, not recruiting | Raphael Pharma |
| NCT05088018 | CBG Tablets for Sleep Quality in Veterans | N/A | Completed | Chris Emerson |
| NCT04859296 | Analgesic and Appetite-stimulating Effects of CBG and THC (ASCENT) | Phase 1 | Active, not recruiting | UCLA |
| NCT04989413 | CBD + CBG + THC vs Placebo in Chronic Migraine | Phase 2 | Terminated | Hospital Israelita Albert Einstein |
| NCT05219370 | Cannabis Oil (CBD, THC, CBDV, CBG) vs Placebo for ADHD | Phase 2 | Terminated | Brlev Agricultural Crops |
| NCT05324982 | PK/PD of CHI-914 (cannabinoid formulation) | Phase 1 | Recruiting | Johns Hopkins University |
| NCT04836611 | Cannabinoid Concentrations and Hyperemesis | N/A | Unknown | Poitiers University Hospital |
| NCT05272865 | PK/PD Evaluation of Δ9-THC Formulations | Phase 1 | Unknown | LaSanta S A S |
| NCT05396638 | Endocannabinoid Levels in Adolescents with Cannabis Use Disorder | N/A | Active, not recruiting | University of Colorado |

**Published results from trials:**
- NCT05257044 (WSU completed) — results published as Cuttler et al. 2024 [Ref 12]: 20 mg CBG reduced anxiety/stress, enhanced verbal memory, no psychoactive effects.
- NCT05743985 (Formula30A) — no published results retrieved.
- NCT05088018 (Veterans sleep) — no published results retrieved.

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## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief.

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## Gaps & Flags

### Safety-Critical Flags (require human editorial review before publication)

1. **⚑ No human pharmacokinetic data.** Tmax, Cmax, half-life, oral bioavailability, and CYP450 metabolism in humans are entirely unknown. The equine PK study [Ref 30] provides the only published PK data for CBG in any species after controlled dosing.

2. **⚑ CYP450 drug interactions uncharacterized.** No published inhibition/induction studies found for any CYP enzyme. Any drug interaction claim in the article will require explicit flagging as speculative/class-inference.

3. **⚑ No human LD50 or overdose case reports.** Acute toxicity data in humans is entirely absent. The rat chronic safety data (Polanska 2023 [Ref 9]) showing hepatotoxicity at 0.66 mg/kg/day is concerning and should be prominently noted, while the Gao 2024 iPSC study [Ref 10] shows CBG as least hepatotoxic among tested cannabinoids in human hepatocytes — a contradiction that requires editorial judgment.

4. **⚑ No tolerance or dependence studies.** Completely uncharacterized in published literature.

5. **⚑ No human contraindication data.** All contraindication claims will be class-inference only.

### Data Discrepancies vs. Seed Data

6. **Seed data classification discrepancy:** Seed data identifies CBG pharmacological class as "Cannabinoid CB1 receptor partial agonist" — this is correct but greatly incomplete. CBG is more accurately characterized as a pleiotropic, multi-target phytocannabinoid with comparatively low CB1/CB2 affinity.

7. **Seed data missing all chemical identifiers** (formula, weight, SMILES, InChIKey, PubChem CID) — all now confirmed via PubChem lookup.

### Literature Gaps

8. **Alpha-2 adrenoceptor activity:** Frequently cited in secondary sources and reviews as a CBG target, but no primary binding affinity data (Ki at α₂-adrenoceptors) was retrieved. This warrants a targeted literature search of pharmacology databases (ChEMBL, PDSP Ki database).

9. **GPR55 activity:** Mentioned as a likely non-canonical target in the Queiroz 2025 meta-analysis [Ref 3] but no CBG-specific GPR55 binding or functional data retrieved.

10. **Anticancer activity (CBG alone):** Multiple reviews mention CBG antiproliferative properties, but no primary study of CBG alone in human cancer cell lines was retrieved via PubMed (only found in multi-cannabinoid assays and review articles). This represents a meaningful gap.

11. **Antidepressant claims:** Contradictory data — rodent FST/TST data (El-Alfy 2010 [Ref 26]) show NO antidepressant activity, but popular marketing claims antidepressant effects. The Sharma 2025 [Ref 39] study (in vivo analysis) may clarify, but full data not available from abstract. Generation agent should not characterize CBG as an antidepressant without this qualification.

12. **Human dose-response data:** The single published human RCT used 20 mg oral; no dose-response data exist in humans.

13. **Sleep effects:** Clinical trial NCT05088018 completed but no published results found.

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*Research completed: 2026-05-12*  
*Citations in registry: 48*  
*Provenance ID: 4793671d-8bf6-4688-864d-d1e4d6007c8e*