CBG Shows Antipsychotic-Like Effects in Mouse Study

Cannabigerol, better known as CBG, is often overshadowed by tetrahydrocannabinol (THC) and cannabidiol (CBD). New research suggests this minor cannabinoid may deserve considerably more attention, particularly from scientists searching for better ways to address the diverse symptoms of schizophrenia.

A study published in Progress in Neuropsychopharmacology & Biological Psychiatry¹ found that CBG prevented several behavioural changes caused by psychotomimetic drugs in mice. These changes are used in preclinical research to model specific dimensions of schizophrenia, including abnormal activity, impaired sensory filtering, reduced social interaction, and memory deficits.

The results do not demonstrate that CBG treats schizophrenia in people. They do, however, indicate that CBG may act across more than one brain-signalling system and could offer researchers a new starting point for drug development.

Why Schizophrenia Requires More Than One Therapeutic Target

Schizophrenia is a complex psychiatric disorder that can affect perception, thought, motivation, memory, and social functioning. Its symptoms are commonly separated into three broad groups.

• Positive symptoms include hallucinations, delusions, and disorganized thinking.
• Negative symptoms include reduced motivation, social withdrawal, and diminished emotional expression.
• Cognitive symptoms affect attention, memory, processing speed, and problem-solving.

Most conventional antipsychotics primarily reduce dopamine D2 receptor signalling. This approach can control positive symptoms for many patients, but it is generally less effective against negative and cognitive symptoms. Some patients also respond poorly to treatment or discontinue medication because of movement-related, metabolic, or other adverse effects.

These limitations make compounds with broader pharmacology scientifically interesting. According to the World Health Organization’s overview of schizophrenia, the condition can substantially disrupt education, employment, relationships, and quality of life. A compound capable of influencing several symptom domains without reproducing the adverse-effect profile of existing drugs would therefore address an important therapeutic gap.

How Researchers Tested CBG

The study involved 224 adult male Swiss mice. Researchers administered CBG before exposing the animals to either amphetamine or MK-801, two drugs used to produce measurable behaviours associated with different neurochemical theories of schizophrenia.

Amphetamine increases dopamine activity. In rodents, it can cause excessive movement and interfere with prepulse inhibition, a measure of the brain’s ability to filter incoming sensory information. Prepulse inhibition occurs when a weak sound reduces the startle response to a louder sound immediately afterward. Impaired filtering has also been observed in people with schizophrenia, although a mouse test cannot reproduce the full human experience of psychosis.

MK-801 blocks N-methyl-D-aspartate, or NMDA, glutamate receptors. It can produce deficits involving sensory filtering, social behaviour, and recognition memory. This gives researchers a way to investigate behaviours associated with negative and cognitive symptoms, not only dopamine-linked hyperactivity.

The team tested CBG at doses of 1, 3, 10, and 30 milligrams per kilogram. It then used open-field, prepulse-inhibition, social-interaction, and novel-object-recognition tests to assess the animals.

CBG Produced Effects Across Several Behavioural Domains

The breadth of the findings is more notable than any single result. At 1 mg/kg, CBG prevented amphetamine-induced hyperactivity and disruption of prepulse inhibition. The same dose prevented the decline in social interaction caused by MK-801. A 3 mg/kg dose protected recognition memory, while both 1 and 30 mg/kg partially attenuated MK-801-related disruption of sensory filtering.

CBG alone did not alter locomotor activity or prepulse inhibition in the associated control experiments. This is important because a substance could appear to reduce drug-induced hyperactivity simply by sedating the animal. The results instead suggest that CBG modified particular behavioural disturbances without producing a general reduction in movement.

The paper is especially relevant when considered alongside recent research into THC’s psychosis-like effects in mice. THC, CBG, and CBD all interact with the endocannabinoid system, but they do not generate interchangeable effects. Describing them only as cannabinoids conceals major differences in receptor activity and downstream signalling.

CBG Is Not Simply Another Version of CBD

Neither CBG nor CBD typically produces the intoxicating effects associated with THC. Their pharmacological similarities nevertheless have limits.

CBD can act as a negative allosteric modulator of the CB1 receptor, changing how the receptor responds without activating its primary binding site in the same manner as THC. CBG has been characterized as a weak partial agonist or neutral antagonist at cannabinoid receptors under different experimental conditions. It also interacts with targets outside the conventional endocannabinoid system.

The researchers noted that effective CBG doses of 1 to 3 mg/kg were substantially lower than the 30 to 60 mg/kg CBD doses reported in comparable animal models. This does not prove that CBG is more potent or clinically preferable. Differences between experiments, formulations, metabolism, and biological targets prevent a direct therapeutic comparison. Mouse doses also cannot be converted into consumer dosing recommendations without pharmacokinetic and safety data.

What the comparison does establish is that CBG should not be treated as a less abundant substitute for CBD. It may have its own dose-response pattern and combination of molecular effects.

A Multi-Target Mechanism Could Explain the Findings

The study did not directly determine how CBG produced its behavioural effects. The authors instead proposed several mechanisms that future experiments can test.

One possibility involves fatty acid amide hydrolase, or FAAH. This enzyme breaks down anandamide, an endocannabinoid involved in regulating CB1 and CB2 receptor activity. Inhibiting FAAH could raise anandamide levels and indirectly alter dopamine and glutamate signalling.

CBG may also interact with TRPV1 channels and influence communication between CB1 and dopamine D2 receptors. CB1 and D2 receptors can occur in overlapping locations within the striatum, a brain region involved in movement, motivation, and reward. Modulating this relationship could help explain why CBG reduced behaviours produced by excessive dopamine activity.

Another candidate is the alpha-2 adrenergic receptor. CBG is an agonist at this receptor, which participates in the regulation of noradrenaline release and prefrontal-cortex function. Alpha-2 receptor activity could contribute to the improvements in social behaviour and recognition memory. It could also introduce safety considerations because alpha-2 agonism can lower blood pressure and heart rate.

This network-level interpretation is the study’s most useful contribution. Schizophrenia does not arise from one receptor operating in isolation. CBG’s value may lie in its capacity to modestly influence several connected systems rather than completely blocking one of them.

The Findings Do Not Make Commercial CBG a Treatment

There is an important distinction between purified CBG administered under controlled laboratory conditions and retail CBG oils, flower, gummies, or extracts. Product labels do not establish pharmaceutical purity, exposure inside the brain, or equivalence to an intraperitoneal dose used in mice.

CBG is also not an approved schizophrenia therapy. The FDA’s guidance on cannabis-derived products makes clear that widespread commercial availability is not the same as demonstrated medical efficacy. People experiencing psychosis should not replace prescribed medication with CBG or attempt to reproduce a preclinical experiment.

This caution is particularly important because cannabinoid effects differ considerably. High-THC products may increase paranoia or psychosis risk in susceptible individuals, while non-intoxicating cannabinoids may have different actions. Research into how cannabis changes the brain’s electrical rhythms further illustrates that cannabis exposure can alter neural activity across multiple regions and frequency bands. A potentially therapeutic effect from isolated CBG does not make cannabis broadly protective against psychiatric illness.

What Researchers Need to Establish Next

The study used only male mice, acute drug exposure, and CBG pretreatment. This design establishes an initial efficacy signal, but it leaves several major questions unanswered.

Researchers need to determine whether CBG remains effective when administered after behavioural impairments have developed. Chronic studies must assess whether benefits persist, tolerance emerges, or repeated exposure creates new adverse effects. Female animals are essential because sex-related differences could affect cannabinoid metabolism and behavioural responses.

Mechanistic experiments should then identify which receptors are necessary for each effect. A compound that improves memory through one pathway and reduces hyperactivity through another may require different dosing strategies for different clinical goals.

Only after pharmacokinetic, toxicology, interaction, and formulation studies would early human trials become reasonable. Those trials would initially evaluate safety and exposure, not prove effectiveness against schizophrenia.

CBG Research Is Entering a More Serious Phase

This study does not reveal a new cannabis treatment for schizophrenia. It provides something more preliminary but still valuable: evidence that purified CBG can prevent several psychotomimetic drug-induced behaviours involving dopamine and glutamate systems in mice.

The low effective doses and activity across positive-like, negative-like, and cognitive behavioural domains make CBG a compelling research candidate. They also reinforce a broader lesson for cannabis science. Minor cannabinoids should be investigated as pharmacologically distinct molecules, not treated as weaker variations of THC or CBD.

The next stage must move from behavioural observation to mechanism, safety, and reproducibility. If those steps support the initial findings, CBG could become more than a minor constituent of the cannabis plant. It could become a useful molecular tool for understanding how interconnected cannabinoid, dopamine, glutamate, and adrenergic systems shape psychiatric symptoms.

References:

¹ Pedrazzi, J. F. C., Sales, A. J., Hallak, J. E. C., Zuardi, A. W., Guimarães, F. S., Del Bel, E. A., & Crippa, J. A. (2026). Cannabigerol, a minor phytocannabinoid, prevents behavioral changes induced by psychotomimetic drugs. Progress in Neuropsychopharmacology & Biological Psychiatry, 149, 111903. https://doi.org/10.1016/j.pnpbp.2026.111903