Health Topics — Stress & Anxiety
CBG and Stress Regulation: What the Research Led To
The first controlled human trial of CBG — what it studied, what it found, and what it means for understanding this cannabinoid's relationship to stress.
The research into stress regulation doesn't begin with cannabinoids. It begins much earlier — with the biology of the stress response itself, with what the body does when it perceives threat, and with why some people seem to carry that response long after the threat has passed.
CBG entered that picture through a specific question: whether the endocannabinoid system plays a meaningful role in how the stress response is initiated, sustained, and resolved. The answer, it turned out, was more interesting than expected. And in 2024, for the first time, a controlled human trial produced data that made the question worth asking publicly.
The Stress Response and Why It Stays
The human stress response is not a malfunction. It is a precisely coordinated biological system — the hypothalamic-pituitary-adrenal axis, or HPA axis — designed to mobilize the body's resources in response to perceived threat. Cortisol is released. Heart rate increases. Attention narrows. The body prepares for action.
Under normal conditions, the response is self-limiting. The threat passes, cortisol levels fall, and the system returns to baseline. The problem that occupies researchers — and that occupies anyone who has experienced it — is the system that doesn't fully return. Chronic stress, sustained anxiety, the low-level physiological activation that persists without a clear external cause: these represent a failure of the resolution mechanism, not the activation mechanism.
The endocannabinoid system is one of the biological systems involved in that resolution. Endocannabinoid signaling — primarily through anandamide and 2-AG acting on CB1 receptors — modulates HPA axis activity, dampens excessive stress responses, and participates in the process by which the nervous system distinguishes ongoing threat from resolved threat. When endocannabinoid tone is reduced, stress responses tend to persist longer. When it is supported, resolution appears to be more efficient.
This is the biological context that makes cannabinoid research in the stress domain meaningful. It is also the context that made CBG specifically interesting to researchers who had been following endocannabinoid pharmacology closely.
Why CBG and Not Just CBD
CBD had already attracted significant research attention in stress and anxiety by the time CBG began to receive systematic investigation. The question worth asking was whether CBG offered something pharmacologically distinct — or whether it was simply a less-studied version of the same story.
The answer appears to be: meaningfully distinct. CBG's pharmacological profile differs from CBD's in ways that are relevant to stress biology. CBG acts as an alpha-2 adrenoceptor agonist — a receptor system involved in the regulation of norepinephrine, the neurotransmitter most directly associated with the acute stress arousal response. CBG also inhibits GABA reuptake, which increases GABAergic signaling, the primary inhibitory system in the central nervous system and one of the main mechanisms by which the nervous system moderates excitatory stress responses.
Neither of these mechanisms constitutes clinical evidence for CBG in stress management. Mechanisms are not outcomes. A compound that interacts with alpha-2 receptors in vitro is not proven to reduce stress in living systems. But these pharmacological properties provided the biological rationale that made a controlled human trial worth designing — and worth funding.
On mechanism and outcome
This article describes several pharmacological mechanisms through which CBG interacts with stress-related biological systems. These mechanisms are real and documented. They do not, on their own, establish that CBG reduces stress in clinical populations.
The distinction matters because mechanism-to-outcome is one of the most commonly collapsed distances in cannabinoid writing. A receptor interaction is a finding. A measurable human effect is a different finding. Both are required before a claim has standing.
The Cuttler Trial: What a First Human Study Actually Shows
In 2024, a research team led by Carrie Cuttler at Washington State University published what appears to be the first randomized controlled trial examining the acute effects of CBG in healthy human adults. The trial was published in Scientific Reports.
The design was rigorous for an early-stage investigation. Thirty-four healthy adults participated in a double-blind, placebo-controlled crossover trial — meaning each participant received both CBG and placebo in separate sessions, and neither participants nor researchers knew which was being administered at any given time. Participants received a single 20mg oral dose. Stress and anxiety were measured using validated self-report scales at multiple time points: 20, 45, and 60 minutes post-dose.
The findings were statistically significant. Compared to placebo, participants who received CBG reported measurably lower anxiety at all three time points. They reported measurably lower stress. The effect sizes were sufficient to exceed the threshold for statistical significance in a trial of this size.
The trial also produced an unexpected finding: statistically significant improvement in verbal word recall compared to placebo. The lead author explicitly noted that this was not a primary outcome of the trial, and flagged it for replication before strong conclusions could be drawn. The verbal memory finding is genuine — it appeared in the data — and it is preliminary. Both of those things are true simultaneously.
What this trial establishes and what it does not
The Cuttler (2024) trial is a well-designed acute study in 34 healthy adults. It establishes that a single 20mg dose of CBG produced statistically significant reductions in self-reported anxiety and stress compared to placebo in this population at this timeframe.
It does not establish: that CBG reduces anxiety in clinical anxiety disorder populations; that effects persist beyond the acute measurement window; that repeated dosing produces consistent effects; that these findings generalize to all populations or all doses.
One controlled trial in healthy adults is a meaningful starting point. It is the beginning of a research trajectory, not the end of one.
What the Preclinical Research Adds
Tier 2 — Preclinical Evidence
The human trial does not stand alone. A body of preclinical research — animal models and mechanistic studies — had been building a picture of CBG's interactions with stress-related biological systems before the Cuttler trial was designed. That research provides mechanistic context for the human findings, even though it does not validate them directly.
Animal studies have examined CBG's effects on anxiety-related behavior through several models, including the elevated plus maze — a standard preclinical tool for measuring anxiety responses in rodents. Results have generally shown anxiolytic-like effects at relevant doses. These findings are consistent with the human trial data but are not equivalent to it. Animal models of anxiety capture aspects of the stress response but do not replicate the full complexity of human psychological stress.
The HPA axis research is specifically relevant here. Preclinical work has suggested that CBG may modulate cortisol-related signaling pathways, though direct cortisol measurement was not part of the Cuttler human trial. The relationship between CBG, HPA axis activity, and cortisol regulation in humans remains an open research question — one that the preclinical data makes worth investigating, but one that human trials have not yet directly addressed.
This is the honest state of the science: a human trial that establishes an acute signal, and a preclinical literature that provides mechanistic plausibility without closing the loop on the clinical question.
Why This Research Area Matters to This Company
J.P. Hemp Company exists because someone followed this research. Not the Cuttler trial specifically — that published after the company's direction was already set — but the broader literature on stress regulation, endocannabinoid tone, and the specific pharmacological properties that distinguished CBG from the cannabinoids that had received more attention.
Years of reading led to CBG. Reading led to cultivation decisions, preparation decisions, and the conviction that a company built around this research had a responsibility to represent it accurately rather than enthusiastically. The archive you are reading is the product of that conviction — built to give people who are following the same research trail the same honest picture of what it shows.
That is why this article is the anchor of this pillar rather than a supporting piece. Not because CBG has more human evidence than other cannabinoids in the stress domain — it does not, not yet. Because the stress regulation question is the question that preceded and shaped everything that followed.
The Cuttler (2024) trial is the first published randomized controlled trial of CBG's acute effects on stress and anxiety in healthy humans. It found statistically significant reductions in self-reported anxiety and stress compared to placebo at 20, 45, and 60 minutes. It is one trial. It is in healthy adults. Its findings are worth knowing and worth holding proportionately.
The preclinical research on CBG and HPA axis modulation provides mechanistic context. The direct cortisol question in humans remains uninvestigated. The research trajectory is underway.
What exists is a beginning. A well-designed beginning, with a mechanistic rationale that makes the next studies worth designing. That is where the science is. This archive will update when it moves.
References
- Cuttler, C., Stuber, L., St. Pierre, M., & Theiss, S. (2024). Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover study. Scientific Reports, 14. https://doi.org/10.1038/s41598-024-57363-2
- Borrelli, F., Fasolino, I., Romano, B., Capasso, R., Maiello, F., Coppola, D., Orlando, P., Battista, G., Claro, E., Diamond, M., & Izzo, A.A. (2013). Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease. Biochemical Pharmacology, 85(9), 1306–1316.
- Cascio, M.G., Gauson, L.A., Stevenson, L.A., Ross, R.A., & Pertwee, R.G. (2010). Evidence that the plant cannabinoid cannabigerol is a highly potent alpha-2 adrenoceptor agonist and moderately potent 5-HT1A receptor antagonist. British Journal of Pharmacology, 159(1), 129–141.
- Hill, M.N., McLaughlin, R.J., Bingham, B., Shrestha, L., Lee, T.T.Y., Gray, J.M., Hillard, C.J., Gorzalka, B.B., & Bhagya, V.K. (2010). Endogenous cannabinoid signaling is required for voluntary exercise-induced enhancement of progenitor cell proliferation in the hippocampus. Hippocampus, 20(4), 513–523.
- Morena, M., Patel, S., Bains, J.S., & Hill, M.N. (2016). Neurobiological interactions between stress and the endocannabinoid system. Neuropsychopharmacology, 41(1), 80–102.
- Valdeolivas, S., Navarrete, C., Cantarero, I., Bellido, M.L., Muñoz, E., & Sagredo, O. (2015). Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice. Neurotherapeutics, 12(1), 185–199.
These statements have not been evaluated by the Food and Drug Administration. J.P. Hemp Company products are not intended to diagnose, treat, cure, or prevent any disease.