Hemp and Health: Why Alternative Cannabinoids Matter for Patients

Quick Answer: Hemp-derived alternative cannabinoids—including CBG, CBN, and THCA—are non-intoxicating or minimally intoxicating compounds that interact with the body's endocannabinoid system to support health without producing the psychoactive effects associated with THC. Recent clinical research from 2024 demonstrates measurable benefits for anxiety, sleep, inflammation, and neuroprotection. As federal legislation threatens to redefine and potentially ban hemp, understanding the science behind these cannabinoids becomes critical for patients, businesses, and advocates working to protect legal access to these compounds.

Key Takeaways

• CBG reduced anxiety by 26.5% in a 2024 Washington State University clinical trial without causing intoxication or cognitive impairment

• CBN increased total sleep time in preclinical studies with effects comparable to prescription sleep medication zolpidem

• THCA demonstrates neuroprotective properties through PPARγ activation without producing psychoactive effects in its raw, unheated form

• The endocannabinoid system regulates pain, inflammation, mood, sleep, and immune function through CB1 and CB2 receptors found throughout the body

• Hemp's legal status under the 2018 Farm Bill is now threatened by proposed federal legislation that could eliminate access to these researched compounds

 

---

 

The American hemp industry—valued at $28.4 billion and supporting 328,000 jobs—faces an existential threat as federal lawmakers consider language that would functionally ban hemp by redefining its legal parameters. For patients who rely on hemp-derived cannabinoids as part of their health routines, this legislative risk underscores the importance of understanding what these compounds actually do, how they work, and why science-backed access matters.

Unlike marijuana, which remains federally illegal and contains intoxicating levels of delta-9 THC, hemp is defined by the 2018 Farm Bill as cannabis containing less than 0.3% delta-9 THC by dry weight. This legal distinction has enabled research into and access to alternative cannabinoids—compounds like cannabigerol (CBG), cannabinol (CBN), and tetrahydrocannabinolic acid (THCA)—that offer therapeutic potential without the high associated with marijuana consumption.

This article examines the current state of research on alternative cannabinoids, how they interact with the body's endocannabinoid system, and why protecting legal hemp access is inseparable from protecting patient choice.

What Makes Hemp-Derived Cannabinoids Different from Marijuana

The cannabis plant produces more than 100 distinct cannabinoids, but not all cannabis is created equal under federal law. The 2018 Farm Bill legalized hemp by establishing a clear THC threshold: cannabis containing 0.3% or less delta-9 THC is hemp, while anything above that threshold is marijuana and remains Schedule I controlled.

This legal framework created space for businesses to produce and consumers to access cannabinoids that occur naturally in hemp—compounds that offer health benefits without the intoxication that has historically driven cannabis prohibition.

Hemp-Derived vs. Marijuana-Derived Cannabinoids

The distinction matters because it determines which products patients can legally access without navigating state-by-state marijuana programs, which often require medical cards, limit product types, and exclude consumers based on employment or other factors.

The Endocannabinoid System: Why Cannabinoids Affect Health

To understand why hemp-derived cannabinoids produce health effects, it's necessary to understand the endocannabinoid system (ECS)—a biological signaling network that regulates homeostasis across multiple physiological processes.

The ECS consists of three primary components: endocannabinoids (naturally produced signaling molecules like anandamide and 2-AG), cannabinoid receptors (CB1 and CB2), and enzymes that synthesize and degrade endocannabinoids. This system is present in all vertebrates and plays documented roles in regulating pain, inflammation, mood, appetite, sleep, memory, and immune function.

CB1 receptors are among the most abundant G-protein-coupled receptors in the human brain, where they modulate neurotransmitter release and influence processes like pain perception, mood regulation, and motor control. CB1 receptors are also found in peripheral tissues including the liver, adipose tissue, and skeletal muscle.

CB2 receptors are expressed primarily in immune system tissues—including T cells, B cells, macrophages, and microglia—where they regulate inflammatory responses and immune cell signaling. CB2 receptors are also present in the brain, particularly in microglial cells, though their role in the central nervous system is still being characterized.

When cannabinoids from hemp enter the body, they interact with these receptors (and sometimes other targets like TRPV1 channels or PPARγ receptors) to produce therapeutic effects. Different cannabinoids have different receptor affinities, which explains why CBG affects anxiety differently than CBN affects sleep.

Table 2: Endocannabinoid System Receptors & Cannabinoid Interactions

 

The ECS operates through "retrograde signaling," meaning endocannabinoids are released from post-synaptic neurons and travel backward across synapses to activate receptors on pre-synaptic neurons, modulating neurotransmitter release. This unique mechanism allows the ECS to fine-tune other neurotransmitter systems on demand, rather than functioning as a primary signaling pathway.

Join AHAA as a Member to support the research and policy work that protects access to these scientifically-studied compounds.

CBG: Anxiety Reduction Without Intoxication

Cannabigerol (CBG) is often called the "mother of all cannabinoids" because it serves as the biosynthetic precursor to CBD, THC, and other cannabinoids. In the cannabis plant, cannabigerolic acid (CBGA) is converted by enzymes into THCA, CBDA, or CBCA. As a result, mature cannabis plants typically contain only trace amounts of CBG—usually less than 1% by dry weight.

Recent breeding efforts have produced high-CBG hemp cultivars that allow for cost-effective extraction and isolation of this cannabinoid. These developments have made CBG products commercially viable and opened the door to clinical research that was previously impractical.

In July 2024, researchers at Washington State University published the first human clinical trial examining CBG's effects on anxiety, stress, and mood. The study, published in Scientific Reports, was a double-blind, placebo-controlled, crossover trial involving 34 healthy adults. Participants received either 20mg of hemp-derived CBG or a placebo, then completed anxiety and stress assessments at multiple time points.

The results demonstrated that 20mg of CBG significantly reduced feelings of anxiety at 20, 45, and 60 minutes after ingestion compared to placebo. Participants reported a 26.5% reduction in anxiety on a visual analog scale. Stress ratings also decreased at the first time point compared to placebo.

Notably, CBG produced these anxiolytic effects without causing intoxication, cognitive impairment, or motor dysfunction. Participants reported low intoxication ratings and minimal side effects such as dry mouth or appetite changes. The study also found an unexpected cognitive benefit: CBG significantly enhanced verbal memory, with participants recalling more words after taking CBG than after taking placebo.

These findings contrast sharply with THC, which is known to impair short-term memory and produce cognitive side effects that limit its clinical utility for many patients. CBG's ability to reduce anxiety while preserving or even enhancing cognitive function positions it as a promising option for individuals who need symptom relief without functional impairment.

The mechanisms underlying CBG's anxiolytic effects appear to involve multiple targets beyond traditional cannabinoid receptors. While CBG shows weak affinity for CB1 and CB2 receptors, it demonstrates strong binding at α2-adrenergic receptors and functions as an antagonist at serotonin 5-HT1A receptors. This pharmacological profile distinguishes CBG from CBD and THC, suggesting unique therapeutic applications.

Preclinical research also indicates that CBG may offer benefits for inflammatory bowel disease, glaucoma (through intraocular pressure reduction), and bladder dysfunction. However, human clinical data for these applications remains limited, and the 2024 anxiety trial represents the most robust human evidence to date.

CBN: Sleep Architecture and Recovery

Cannabinol (CBN) is produced when THC degrades over time through exposure to heat, light, or oxygen. Aged cannabis material naturally contains higher CBN concentrations, which has led to anecdotal claims that "old weed makes you sleepy." Until recently, these claims lacked rigorous scientific support.

In November 2024, researchers at the University of Sydney's Lambert Initiative for Cannabinoid Therapeutics published the first objective study demonstrating that CBN increases sleep in rats. The study, published in Neuropsychopharmacology, used polysomnography to measure sleep architecture—including non-rapid eye movement (NREM) and rapid eye movement (REM) sleep phases.

CBN increased total sleep time in a dose-dependent manner. The cannabinoid increased both NREM sleep (the deep, restorative sleep phase that promotes physical recovery and memory consolidation) and REM sleep (associated with dreaming and emotional processing). The magnitude of effect was comparable to zolpidem (Ambien), a widely prescribed sleep medication.

Importantly, CBN did not appear to produce intoxication in rats. Unlike THC, which strongly activates CB1 receptors to produce psychoactive effects, CBN binds only weakly to CB1. The researchers identified that CBN's sleep-promoting effects may be partially mediated by its metabolite, 11-hydroxy-CBN, which has greater activity at CB1 receptors than the parent compound.

Human trials of CBN for sleep have also shown promise. A 2024 study published in Experimental and Clinical Psychopharmacology examined the effects of CBN alone and in combination with CBD on sleep quality in 293 participants who self-rated their sleep as poor or very poor. Participants received either placebo, 20mg CBN, or CBN combined with varying doses of CBD for seven consecutive nights.

Compared to placebo, 20mg CBN significantly reduced the number of nighttime awakenings and overall sleep disturbance. There was no impact on sleep onset latency (time to fall asleep) or wake after sleep onset (WASO), suggesting CBN's primary benefit is sleep maintenance rather than initiation. Daytime fatigue was not increased, indicating that CBN does not produce next-day sedation—a common problem with conventional sleep medications.

Interestingly, adding CBD to CBN did not enhance the sleep benefits, and in some dose combinations appeared to reduce CBN's effectiveness. This suggests that CBN may be most beneficial as a standalone compound for sleep support.

An independent study presented at the 2024 SLEEP conference found that 50mg of CBN produced sleep quality improvements statistically equivalent to 4mg of melatonin, with comparable tolerability. All side effects reported were mild or moderate, with no significant differences between CBN and placebo groups.

These findings position CBN as a potentially safer alternative to benzodiazepines, Z-drugs (like zolpidem), and even over-the-counter sleep aids, which can carry risks of dependency, tolerance, and adverse cognitive effects.

Major vs. Minor Cannabinoids Profile

THCA: Neuroprotection Without the High

Tetrahydrocannabinolic acid (THCA) is the raw, acidic precursor to THC found in fresh cannabis and hemp flower. In living plants, cannabinoids exist primarily in their acid forms—THCA, CBDA, CBGA—because the plant biosynthesizes them with a carboxyl group attached.

When cannabis or hemp is heated through smoking, vaping, or cooking (a process called decarboxylation), the carboxyl group is removed and THCA converts to THC. This transformation is what produces psychoactive effects. Raw THCA, however, does not bind effectively to CB1 receptors and therefore does not produce intoxication.

Despite being non-intoxicating in its raw form, THCA has demonstrated significant biological activity in preclinical research. A 2017 study published in the British Journal of Pharmacology identified THCA as a potent agonist of peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor involved in metabolism, inflammation, and neuroprotection.

The study tested THCA in cellular models of Huntington's disease and in mice exposed to 3-nitropropionic acid, a mitochondrial toxin that produces neurodegeneration. THCA protected neurons from death, reduced inflammation, and preserved motor function. These neuroprotective effects were mediated through PPARγ activation rather than through cannabinoid receptors.

Additional research has shown that THCA may offer benefits for inflammatory bowel disease. A study examining cannabis extracts found that the anti-inflammatory activity in colon epithelial cells was primarily attributable to THCA, not CBD or THC. THCA inhibited the expression of COX-2 and MMP9, genes involved in inflammation, and showed cytotoxic activity against cancer cells in a CB2-dependent manner.

THCA has also been studied for its effects on nausea and vomiting. Preclinical data suggests antiemetic properties that could benefit chemotherapy patients, though human clinical trials have not yet been conducted.

One challenge with THCA research and product development is stability. THCA degrades to THC at room temperature over time, and any significant heat exposure accelerates this conversion. This is why THCA flower products—when smoked or vaporized—function identically to marijuana, as the heat converts THCA to intoxicating THC.

For patients interested in THCA's non-intoxicating benefits, consumption methods include raw cannabis/hemp juice, tinctures stored in cool conditions, or capsules containing stabilized THCA extracts. However, the compound's instability has limited large-scale clinical research.

Despite these challenges, THCA's preclinical profile—particularly for neurodegenerative conditions and inflammatory diseases—warrants further investigation. The compound demonstrates that cannabinoid acids may offer therapeutic pathways distinct from their neutral, decarboxylated forms.

Take Action on Hemp Policy to protect access to cannabinoids like THCA that are still being researched for their therapeutic potential.

Minor Cannabinoids and the Entourage Effect

While CBG, CBN, and THCA represent the most-studied minor cannabinoids, the cannabis plant produces dozens of others—including cannabichromene (CBC), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV), and cannabicitran (CBT)—each with distinct pharmacological profiles.

Research into these compounds is in its infancy, but preliminary findings suggest diverse therapeutic applications. CBDV, for example, has shown promise in preclinical epilepsy models and is currently in clinical development. THCV appears to function as a CB1 antagonist at low doses and may offer benefits for metabolic disorders and appetite suppression.

The "entourage effect" hypothesis proposes that cannabinoids work synergistically with each other and with terpenes (aromatic compounds also found in cannabis) to produce enhanced therapeutic effects. While this concept is widely cited in the cannabis industry, scientific evidence supporting it remains mixed.

Some studies have found that whole-plant extracts containing multiple cannabinoids produce stronger effects than isolated cannabinoids. For example, a 2011 study found that cannabis extracts containing both THC and CBD were more effective for cancer pain than pure THC. However, other research—including the CBN sleep study mentioned earlier—found no benefit from combining cannabinoids.

The reality is likely more nuanced: certain combinations may produce synergistic effects for specific applications, while other combinations may be antagonistic or additive rather than synergistic. More research is needed to identify which cannabinoid combinations are clinically superior to single-molecule approaches.

What is clear is that the prohibition of hemp would eliminate access not only to well-studied cannabinoids like CBD but also to emerging compounds that may offer unique benefits. A regulatory approach that bans hemp categorically would foreclose research opportunities and patient access before the science has matured.

Safety Considerations and Responsible Use

Hemp-derived cannabinoids are generally well-tolerated, with adverse effects typically mild and self-limiting. Common side effects reported in clinical trials include dry mouth, changes in appetite, mild gastrointestinal discomfort, and drowsiness.

However, several important considerations warrant attention:

Drug Interactions: Cannabinoids are metabolized primarily by cytochrome P450 enzymes in the liver, particularly CYP3A4 and CYP2C19. CBD, in particular, inhibits these enzymes, which can increase blood levels of medications metabolized through the same pathways. Patients taking blood thinners, immunosuppressants, or other medications with narrow therapeutic windows should consult healthcare providers before using cannabinoid products.

Liver Function: High doses of CBD (such as those in the prescription drug Epidiolex) have been associated with elevated liver enzymes in some patients. While this is less common with typical supplemental doses, individuals with existing liver conditions should exercise caution.

Pregnancy and Breastfeeding: Limited research exists on cannabinoid safety during pregnancy and lactation. Given the endocannabinoid system's role in fetal development, avoidance is generally recommended until more data becomes available.

Quality and Purity: The unregulated nature of hemp-derived supplements means product quality varies significantly. Third-party lab testing for cannabinoid content, heavy metals, pesticides, and microbial contamination is essential. Patients should seek products with accessible certificates of analysis (COAs) and avoid products making unverified medical claims.

Legal Considerations: While hemp-derived cannabinoids are federally legal under the 2018 Farm Bill, some states have imposed restrictions. Additionally, THC metabolites from CBN or trace THC in full-spectrum CBD products can trigger positive drug tests. Individuals subject to workplace drug testing should be aware of this risk.

The safety profile of hemp-derived cannabinoids, particularly when compared to conventional pharmaceuticals, is a key argument for preserving legal access. Restricting hemp would not eliminate demand for pain, anxiety, or sleep support—it would simply push consumers toward more dangerous alternatives or illicit markets.

Why Hemp's Legal Status Matters for Patient Access

The science supporting alternative cannabinoids is still emerging, but the trajectory is clear: these compounds offer legitimate therapeutic potential with favorable safety profiles. CBG's anxiety reduction, CBN's sleep benefits, and THCA's neuroprotective properties are not speculative—they are documented in peer-reviewed research using rigorous clinical trial methodologies.

Yet all of this research, and the patient access it supports, is built on the foundation of the 2018 Farm Bill's legal framework. Proposed federal legislation seeking to redefine hemp could eliminate the 0.3% THC threshold or impose restrictions that would functionally ban most hemp-derived products.

For the 328,000 workers employed by the hemp industry, this represents an economic catastrophe. For the millions of Americans who use hemp-derived cannabinoids as part of their health routines, it represents the loss of legal access to compounds that conventional medicine has failed to adequately address.

The American Healthy Alternatives Association (AHAA) is leading the fight to protect hemp's legal status through coordinated advocacy, lobbying efforts, and grassroots mobilization. Bipartisan support is building—led by Rep. James Comer and joined by over 20 members of Congress—but the outcome remains uncertain.

Educated stakeholders are the most effective advocates. Understanding the science behind alternative cannabinoids, the endocannabinoid system, and the distinction between hemp and marijuana equips patients, business owners, and concerned citizens to communicate effectively with policymakers.

Support National Hemp Advocacy With a Donation to fund the legal strategy and lobbying efforts that protect this industry and patient choice.

What’s Next: Research, Regulation, and Access

The ideal regulatory framework for hemp-derived cannabinoids would balance safety oversight with continued innovation and access. This means:

Establishing Clear Standards: Rather than banning hemp outright, federal agencies like the FDA should establish clear standards for manufacturing, labeling, and marketing. This would protect consumers from unsafe or mislabeled products without eliminating the category entirely.

Supporting Research: Federal research restrictions on cannabis have stifled scientific progress for decades. Expanding access to hemp-derived cannabinoids for research purposes would accelerate clinical trials and provide the evidence base needed for informed policy decisions.

Preserving the 0.3% THC Threshold: The existing definition of hemp based on delta-9 THC content is scientifically rational and has enabled a thriving industry. Changing this threshold arbitrarily—or imposing restrictions based on total THC or intoxicating potential—would create legal chaos and eliminate products that pose no public health risk.

Educating Healthcare Providers: Medical schools and continuing education programs should incorporate endocannabinoid system science and cannabinoid therapeutics into curricula. This would enable healthcare providers to counsel patients effectively and recognize drug interactions.

Protecting Consumer Choice: In a healthcare system where conventional treatments often fail to adequately address chronic pain, anxiety, insomnia, and inflammatory conditions—and where prescription medications carry significant risks—hemp-derived cannabinoids offer a harm-reduction approach that respects patient autonomy.

The research base for alternative cannabinoids is expanding rapidly. The 2024 studies on CBG and CBN represent meaningful progress, but they also highlight how much remains unknown. Long-term safety data, optimal dosing protocols, combination therapies, and personalized medicine approaches all require additional investigation.

Eliminating legal hemp access now would be analogous to banning antibiotics in the 1930s because not all infections had been studied. The precautionary principle should protect against known harms, not speculative risks unsupported by evidence.

Final Thoughts: Science, Access, and Advocacy

Alternative cannabinoids derived from hemp represent a frontier in patient-centered health care. CBG's ability to reduce anxiety without cognitive impairment, CBN's sleep-promoting effects without next-day sedation, and THCA's neuroprotective properties without intoxication all demonstrate that therapeutic benefit and psychoactive risk can be decoupled.

These compounds work by modulating the endocannabinoid system—a fundamental regulatory network present in all vertebrates that influences pain, inflammation, mood, sleep, and immune function. The receptors, enzymes, and signaling molecules that comprise this system offer dozens of potential therapeutic targets, most of which remain unexplored.

The $28.4 billion hemp industry exists because the 2018 Farm Bill recognized a scientific reality: not all cannabis produces intoxication, and non-intoxicating cannabis should be regulated as an agricultural commodity rather than a controlled substance.

Proposed federal legislation threatening to redefine or ban hemp ignores this scientific reality and disregards the needs of millions of Americans who benefit from these products. It also ignores the 328,000 workers and thousands of small businesses whose livelihoods depend on this industry.

Protecting hemp's legal status is not about protecting a loophole or enabling intoxication. It is about protecting access to scientifically-studied compounds that offer legitimate health benefits with minimal risk. It is about allowing research to continue. And it is about respecting patient autonomy and consumer choice in a free market.

The American Healthy Alternatives Association is coordinating advocacy efforts across multiple states, engaging lobbyists, funding legal strategies, and mobilizing grassroots support. Thousands have already taken action. The question is whether enough voices will be raised to stop destructive legislation before it eliminates an industry and strips patients of safe alternatives.

Stay Informed — Visit Our Policy News Hub to track legislative developments and access resources for contacting your representatives.

 

---

 

Sources Used for This Article

Cuttler, C., Stueber, A., Cooper, Z.D., et al. (2024). Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover, field trial. Scientific Reports, 14, 16163. https://www.nature.com/articles/s41598-024-66879-0

Arnold, J.C., Occelli Hanbury-Brown, C.V., Anderson, L.L., et al. (2024). A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats. Neuropsychopharmacology, 50(3), 586-595. https://www.nature.com/articles/s41386-024-02018-7

Bonn-Miller, M.O., Feldner, M.T., Bynion, T.M., et al. (2024). A double-blind, randomized, placebo-controlled study of the safety and effects of CBN with and without CBD on sleep quality. Experimental and Clinical Psychopharmacology, 32(3), 277-284. https://pubmed.ncbi.nlm.nih.gov/37796540/

Nadal, X., Del Río, C., Casano, S., et al. (2017). Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity. British Journal of Pharmacology, 174(23), 4263-4276. https://pmc.ncbi.nlm.nih.gov/articles/PMC5731255/

Harvard Health Publishing. (2021). The endocannabinoid system: Essential and mysterious. https://www.health.harvard.edu/blog/the-endocannabinoid-system-essential-and-mysterious-202108112569

Lu, H.C., Mackie, K. (2021). Review of the Endocannabinoid System. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 6(6), 607-615. https://pmc.ncbi.nlm.nih.gov/articles/PMC7855189/

Palomares, B., Ruiz-Pino, F., Garrido-Rodriguez, M., et al. (2020). Tetrahydrocannabinolic acid A reduces adiposity and prevents metabolic disease caused by diet-induced obesity. Biochemical Pharmacology, 171, 113693. https://pubmed.ncbi.nlm.nih.gov/31706843/

Li, S., Li, W., Malhi, N.K., et al. (2024). Cannabigerol (CBG): A Comprehensive Review of Its Molecular Mechanisms and Therapeutic Potential. Molecules, 29(22), 5471. https://pmc.ncbi.nlm.nih.gov/articles/PMC11597810/