Hemp versus marijuana: Chemistry- and pharmacology-associated regulatory framework

Abstract

Cannabis is a chemically diverse plant with bioactive cannabinoids that exert a wide range of therapeutic and psychoactive effects. This review comprehensively explores the botanical, chemical, pharmacological, and regulatory distinctions between hemp and marijuana, focusing particularly on the contrasting actions of Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD). We examine cannabinoid biosynthesis, structure–activity relationships (SARs) in relation to receptor interactions and activation, and metabolic pathways to highlight the scientific basis for their different effects and clinical applications. Additionally, the paper critically evaluates detection techniques and surveys international legal frameworks, highlighting disparities that often reflect cultural rather than scientific understanding. By integrating emerging clinical data and public policy trends, this review underscores the need for evidence-based reform and education, especially regarding non-intoxicating cannabinoids such as CBD. It also offers a scientific foundation to inform both health professionals and regulators in shaping future cannabis policy.

Keywords

Marijuana hemp cannabidiol (CBD)cannabinoids: regional regulation

Introduction

The chemical diversity and pharmacological complexity of cannabinoids position them uniquely within both medical and regulatory frameworks. While Δ⁹-tetrahydrocannabinol’s (THC's) psychoactivity necessitates strict control, CBD's wide therapeutic index has driven its rapid acceptance in pharmaceutical and wellness sectors.¹ However, global regulation remains inconsistent, reflecting deep-rooted cultural, religious, and political influences rather than purely scientific evidence.² Moreover, the growing availability of synthetic and semi-synthetic cannabinoids introduces both opportunities and risks.³ While structure–activity research enables precision drug design, it also raises concerns about abuse potential and regulatory lag.⁴ As more clinical trials validate CBD's efficacy, the demand for legal approaches that distinguish between psychoactive and non-psychoactive cannabinoids is pressing.⁵ Educational initiatives and accurate testing protocols are essential to shifting public perception and informing legislation. The convergence of cannabinoid chemistry, pharmacology, law, and policy underscores the need for an interdisciplinary approach to regulation and reform.

Methodology of the review

This review is conducted through a comprehensive literature search across major scientific databases, including PubMed, Scopus, ScienceDirect, and Google Scholar, covering publications up to January 2025. Keywords such as “cannabinoids,” “THC,” “CBD,” “hemp regulation,” “marijuana pharmacology,” and “cannabis legal framework” were used in various combinations. Peer-reviewed journal articles, governmental and international regulatory documents, and academic books were prioritized to ensure scientific rigor and relevance. Inclusion criteria comprised English-language sources that provided experimental data, pharmacological insights, or legal/regulatory analysis related to cannabinoids. Exclusion criteria included non-scientific web sources and non-peer-reviewed reports. Reference management and screening were performed manually by all contributing authors to ensure accuracy and consistency.

Botanical and genetic distinctions between hemp and marijuana

The Cannabis family of flowering plants is recognized for its diverse applications and chemical properties, encompassing industrial, therapeutic, and recreational purposes.^6,7 The genus Cannabis within this family comprises several species, including Cannabis sativa and Cannabis indica, which exhibit distinct morphological and chemical characteristics.⁸ C. sativa typically exhibits greater height and narrower leaves, while C. indica is generally shorter, more bushy, and characterized by broader leaves.^6,9

Hemp and marijuana both belong to the plant species C. sativa L., a flowering herb in the Cannabaceae family, each characterized by unique morphological traits and cannabinoid compositions. The primary chemical distinction between hemp and marijuana lies in their natural concentrations of THC and CBD. Hemp, characterized by its low THC content, notably richer in CBD and fibrous stalks, primarily derives from C. sativa, making it ideal for industrial applications such as textiles and biofuels. In contrast, marijuana is typically cultivated from C. indica or hybrid strains due to its higher THC levels and psychoactive properties, making it suitable for recreational and medicinal use.¹⁰

A study aimed to evaluate the genetic structure of commonly cultivated Cannabis by analyzing a diverse collection of marijuana and hemp samples.¹¹ Principal components analysis (PCA) revealed a clear genetic structure that distinctly separates marijuana from hemp. Interestingly, the study found that the genetic differences between marijuana and hemp are distributed throughout the genome and are not limited to loci involved in cannabinoid production. The genetic divergence between marijuana and hemp has important legal implications, as many countries classify Cannabis plants as drug or non-drug based on cannabinoid content (primarily THC and CBD). Forensic applications often focus on distinguishing between the two to determine legality, but this study emphasizes that the genetic differences extend beyond cannabinoid production.¹¹

Comparative pharmacology, metabolism, and safety profiles of THC and CBD

THC and CBD interact with the body's endocannabinoid system (ECS) in distinct ways. ECS is an extensive regulatory system that plays a vital role in maintaining homeostasis by modulating key functions such as mood, memory, pain, inflammation, and energy balance.¹² It is composed of two primary G-protein‒coupled receptors: cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2).¹³ CB1 receptors are mainly concentrated in the brain and central nervous system, playing a key role in regulating emotions and cognitive functions. They are also found in peripheral tissues such as the liver, pancreas, muscles, and digestive system.¹⁴ Activation of CB1 receptors in the hippocampus and limbic system is associated with euphoric and psychoactive effects. In contrast, CB2 receptors are primarily located in immune cells, bone marrow, and the spinal cord, and they have little to no psychoactive effects when stimulated.¹⁵

THC binds directly to CB1, which, as previously mentioned, is highly concentrated in the brain and central nervous system.¹⁶ This binding triggers a cascade of psychoactive effects, including euphoria, altered perception, and cognitive impairment.¹⁷ In contrast, CBD does not activate CB1 receptors. Instead, it exhibits a more complex pharmacological profile by modulating other receptors, such as serotonin (5-HT1A) and vanilloid (TRPV1) receptors, which contribute to its anxiolytic, anti-inflammatory, and analgesic properties without producing a high.^16,18 This fundamental difference explains why CBD is increasingly used in medical treatments without the legal and social associated concerns (Figure 1).¹⁹

The pharmacokinetics of THC and CBD vary significantly, driven in part by differences in their solubility, metabolism, and elimination. Both compounds are lipophilic, highly soluble in fats and require specific metabolic pathways for absorption and excretion.^20,21 The metabolism of both THC and CBD predominantly occurs in the liver, primarily through cytochrome P450 (CYP) enzymes, including CYP2C9, CYP2C19, and CYP3A4.²² THC undergoes significant first-pass metabolism in the liver, where it is converted to its active metabolite, 11-hydroxy-THC (11-OH-THC), which is more potent and psychoactive than THC itself.²³ Additionally, THC is further metabolized to 11-carboxy-THC (11-COOH-THC), a non-psychoactive metabolite that undergoes glucuronidation and is excreted in feces and urine.^20,23 CBD is similarly metabolized in the liver, primarily by CYP2C19 and CYP3A4.²⁴ The primary metabolite of CBD is 7-hydroxy-CBD (7-OH-CBD), which undergoes further hepatic metabolism and is excreted primarily through feces.^21,25 Unlike THC, CBD's metabolites do not pose any psychoactive risk, which is a key consideration for its safety profile and legal status.^26,27

The plasma half-life of THC varies significantly depending on the dose, frequency of use, and route of administration. For occasional users, the half-life ranges from 1 to 2 days, but it can extend to over 5 days in chronic users due to its lipophilic nature and accumulation in fatty tissues.^28,29 In contrast, CBD has a shorter half-life, typically ranging from 18 to 32 hours after oral administration.^30,31 At low doses, THC provides analgesic and anti-emetic effects, but as the dose increases, the risk of side effects such as anxiety, paranoia, hallucinations, and impaired motor coordination also rises.³² In contrast, CBD has a much broader therapeutic window, making it safer for medical use.³³ Studies have demonstrated that high doses of CBD (up to 1500 mg/day) are generally well-tolerated, with only mild side effects, such as drowsiness, dry mouth, or gastrointestinal discomfort (Figure 2).³⁴

Beyond their therapeutic windows, the toxicity levels and potential for drug interactions further highlight the importance to distinguish between THC and CBD products. THC has a relatively low toxicity threshold, with high doses resulting in acute cannabinoid intoxication, characterized by severe anxiety, panic attacks,³⁵ psychosis,³⁶ and cardiovascular effects like tachycardia and hypertension.^37,38 Chronic use of THC has also been linked to cognitive decline, dependence, and a heightened risk of psychiatric disorders, including schizophrenia, in individuals predisposed to mental health conditions.³⁹ Conversely, CBD has a significantly higher toxicity threshold and does not produce intoxicating effects at high doses.^34,40 However, CBD can still interact with medications metabolized by CYP enzyme system, potentially altering the effectiveness of drugs such as anticoagulants, anticonvulsants, and antidepressants.⁴¹

These side effect profiles are crucial for determining how each compound should be regulated. THC's potential to cause significant cognitive and psychological impairments makes it unsuitable for over-the-counter use, necessitating strict controls. CBD, on the other hand, with its minimal side effects and lack of psychoactivity, is better suited for general medical use and wellness products. This distinction has been acknowledged in many countries, where hemp-derived CBD products are legal and widely available, while THC-containing products remain highly controlled.

Cannabinoid chemical diversity and relation to psychoactive properties

Cannabinoids are a chemically diverse group of meroterpenoids, classified as C21 or C22 terpenophenolic compounds.⁴² Cannabis produces multiple cannabinoids, categorized into distinct chemical classes, each contributing to its unique therapeutic and psychoactive effects.⁴³ The most abundant cannabinoids in cannabis plants are Δ⁹-tetrahydrocannabinolic acid (THCA) and its decarboxylated form. Δ⁹-THC, the primary psychoactive compound responsible for the high associated with Cannabis.¹ In contrast, hemp plant predominantly contains other cannabinoids as cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), which upon decarboxylation yields cannabidiol (CBD) and cannabigerol, respectively^43,44 (Figure 3).

Figure 1.

Divergent Interactions of THC and CBD with cannabinoid and non-cannabinoid receptors. This figure illustrates the distinct molecular targets and downstream effects of THC and CBD within the human body, focusing on their interactions with cannabinoid receptors and other associated receptor systems. THC directly binds to CB1 receptors in the brain, leading to psychoactive effects such as euphoria and memory impairment. In contrast, CBD does not strongly bind CB1 but indirectly modulates other receptors, resulting in anxiolytic, neuroprotective, and anti-inflammatory effects (figure created with BioRender).

Figure 2.

Comparative overview of THC and CBD. This figure compares THC and CBD across key pharmacological properties. THC directly binds to CB1 and CB2 receptors, producing psychoactive effects and a higher risk of intoxication. In contrast, CBD indirectly modulates ECS through 5-HT₁A and TRPV1 receptors, with no psychoactive effects and a better safety profile. THC's half-life ranges from 1 to 2 days (occasional use) to over 5 days (chronic use), while CBD's is 18–32 hours when taken orally.

Figure 3.

Structural variations of cannabinoids. THC; Δ⁹-tetrahydrocannabinol, THCA; Δ⁹-tetrahydrocannabinolic acid, CBD; cannabidiol, CBN; cannabinol, CBNA; cannabinolic acid, 11-OH-THC; 11-hydroxy-THC, 11-COOH-THC; 11-carboxy-THC, THCV; tetrahydrocannabivarin, AJA; Ajulemic acid, HU-210; synthetic cannabinoid.

Unlike Δ⁹-THC, CBD and cannabigerol lack psychoactivity and exhibit therapeutic potential.⁴⁵ Additionally minor cannabinoids, such as cannabichromenic acid, cannabinolic acid, cannabichromene, tetrahydrocannabivarin and cannabinol, further enrich this chemical diversity.⁴⁶ Notably, cannabinolic acid and cannabinol are oxidative degradation products of Δ⁹-THCA and Δ⁹-THC, respectively. Cannabichromene has weak CB1 activity, showing mild psychoactive effects, whereas cannabinol has lower potency compared to Δ⁹-THC but retains sedative properties (Figure 3). Cannabinoid metabolites 11-OH-THC and 11-COOH-THC influence cannabis pharmacology, with 11-OH-THC being more potent than THC, while 11-COOH-THC is an inactive product.⁴⁷ Synthetic cannabinoids, such as Ajulemic acid (AJA) and HU-210, demonstrate a structural modification that refines the therapeutic and receptor-binding capabilities, highlighting the dynamic nature of cannabinoid chemistry.³

Biosynthesis of the cannabinoids THC and CBD

The biosynthesis of CBD and THC in C. sativa follows a shared metabolic pathway, beginning with olivetolic acid and geranyl pyrophosphate (GPP).⁴⁴ Enzymes such as tetraketide synthase (TKS) and olivetolic acid cyclase (OAC) catalyze the formation of olivetolic acid, which is then prenylated by aromatic prenyltransferase (APT) to produce CBGA, the central precursor for major cannabinoids.⁴⁴ From CBGA, tetrahydrocannabinolic acid synthase (THCAS) converts it into THCA, while cannabidiolic acid synthase (CBDAS) produces CBDA.⁴⁴ Cannabinoids in plants exist as acids and decarboxylate into active forms through heat, light, or aging. This process converts non-psychoactive THCA to THC and CBDA to CBD, altering their pharmacological effects. The specificity of enzymatic activity and environmental conditions ultimately dictate the cannabinoid profile and potency of cannabis products.

Structure–activity relationships (SARs) of cannabinoids in relation to psychoactivity

SAR studies highlight the challenge of balancing cannabinoid therapy with psychoactive and addictive risks. CB1 activation drives psychoactive effects, while CB2 selectivity offers safer therapeutic potential (Figure 4). Structural modifications can refine receptor interactions and functional outcomes.⁴⁸ Since both therapeutic and psychoactive effects involve CB1, cannabinoids carry abuse risks similar to opioids and benzodiazepines.⁴⁹ Research focuses on developing compounds that retain benefits, while minimizing psychoactivity with high specificity to CB1, CB2, or novel receptor targets.⁴

Figure 4.

Psychoactivity-related SAR.

Stereoselectivity plays a critical role in cannabinoid activity, with trans THC enantiomer strongly binding to CB1 for psychoactive effects, while its cis enantiomer shows reduced affinity.⁵⁰ The C-3 alkyl side chain is essential for cannabinoid receptor binding, with its length, branching and substitution influencing affinity, potency, and selectivity. Natural cannabinoids typically feature chains from pentyl (C₅H₁₁) to methyl (CH₃), where longer, branched chains enhance CB receptor binding and agonistic effects.⁴⁷ For example, HU-210 a synthetic analogue with a 1,1-dimethylheptyl group, is 800 times more potent than THC due to its 670-fold higher CB1 binding affinity.³ Conversely, shorter chains like propyl (C3) lower CB1 affinity, reducing psychoactivity⁴⁷ as seen in THCV, a C3 propyl THC analogue that exhibits weaker CB1 binding,⁴⁷ demonstrating how a small structural change alters cannabinoids pharmacological effects.

Hydrogen bonding and functional group modifications further influence receptor selectivity with the C-1 hydroxyl group forms hydrogen bonds crucial for CB1 binding and activation. Removing or modifying it to methoxy (–OCH₃) disrupts H-bonding, adds steric hindrance, weakens CB1 affinity, and shifts selectivity to CB2. This enhances anti-inflammatory effects, making CB2-selective cannabinoids promising therapeutics⁴⁷ (Figure 4). Similarly, modifying the C-11 methyl group to (–CH₂OH) enhances CB1 affinity, as seen in the potent 11-OH-THC metabolite.⁵¹ Further oxidation to carboxyl (–COOH) prevents CB1 activation, while maintaining CB2 affinity, making AJA a non-psychoactive cannabinoid analogue with potential for pain management and inflammatory disorders.⁵²

Ring opening in CBD structurally modifies the molecule, hindering CB1 binding and preventing psychoactivity. This allows CBD to interact with CB2, contributing to its neuroprotective and anti-inflammatory effects.⁵³ These pharmacophore features guide synthetic cannabinoid development, where structural modifications optimize efficacy and minimizing abuse potential.

Cannabinoid detection methods and their limitations

The detection of cannabinoids has evolved significantly, progressing from simple qualitative techniques to highly precise analytical methods. Thin-layer chromatography (TLC) and high-performance thin-layer chromatography (HPTLC) were among the earliest methods, offering a simple and inexpensive approach but with low sensitivity and qualitative results.^54,55 Gas chromatography (GC) is widely used for cannabinoid detection as gas chromatography-flame ionization detection (GC-FID) and gas chromatography–mass spectrometry (GC–MS) for compound identification.⁵⁶ High-performance liquid chromatography (HPLC) became a preferred method, particularly HPLC-UV/Vis, which allows direct analysis of cannabinoids without derivatization.⁵⁷ However, its lower sensitivity compared to mass spectrometry led to the development of liquid chromatography–tandem mass spectrometry (LC–MS/MS) method, which is now considered the gold standard for quantitative cannabinoid analysis due to its high precision, broad dynamic range, and ability to detect minor cannabinoids.⁵⁸ In forensic and clinical settings, immunoassays were introduced as rapid screening tools, offering speed and affordability but suffering from false positives and limited specificity.⁵⁹ More recently, biosensors have emerged as a promising real-time detection technology, though they are still in early development stages.⁶⁰

Sampling techniques have also evolved, with dried blood spots (DBS) providing high recovery rates but limited metabolite detection, while dried oral fluid spots (DOFS) offer practical sample collection but suffer from low cannabinoid recovery.⁶¹ To address these limitations, new extraction methods like WAX-S tips have significantly improved cannabinoid recovery and process efficiency, paving the way for more accurate and reliable cannabinoid detection in forensic, medical, and regulatory applications.⁶¹ Despite significant advancements, each cannabinoid detection method presents inherent trade-offs between sensitivity, specificity, cost, and practicality, emphasizing the ongoing need for innovation in forensic, medical, and regulatory applications to enhance accuracy, reliability, and efficiency.

Legalized cannabinoids therapeutic potential

CBD has gained global attention for its therapeutic potential, with clinical studies demonstrating its efficacy in treating conditions such as epilepsy, anxiety, and chronic pain.^62,63 For instance, the U.S. Food and Drug Administration (FDA) has approved Epidiolex, a CBD-based medication⁶⁴ for the treatment of Dravet syndrome,⁶⁵ Lennox–Gastaut syndrome,^66,67 and tuberous sclerosis complex (TSC),⁶⁸ rare and severe forms of epilepsy that are often resistant to traditional anti-seizure medications.

The global acceptance of cannabinoids is closely tied to their documented therapeutic efficacy, with countries adopting regulatory frameworks based on local healthcare priorities and clinical evidence.^69,70 In the United States, dronabinol which is a synthetic form of THC, was approved by the FDA in 1985 for chemotherapy-induced nausea and vomiting, and later in 1992 for the management of anorexia associated with HIV/AIDS-related cachexia.⁷¹ Likewise, the United Kingdom authorized the use of nabilone, a synthetic cannabinoid analogue, for alleviating chemotherapy-related side effects in cancer patients. Currently, two more cannabis-derived medicinal products, nabiximols (marketed as Sativex) and a purified CBD formulation (Epidyolex), hold UK marketing authorizations, permitting their clinical prescription for specific indications.⁷²

Germany has also progressively integrated cannabinoid-based treatments into its healthcare system. Following the results of a pivotal randomized, placebo-controlled trial, which demonstrated significant improvements in spasticity among multiple sclerosis patients, Sativex was approved in Germany as an oromucosal spray containing a standardized 1:1 ratio of THC to CBD. The study reported that Sativex not only reduced the severity of spasticity but also improved patient-reported outcomes related to pain and sleep disturbances.^70,73 Based on this evidence, the German Joint Federal Committee acknowledged modest therapeutic advantage in 2012, and issued a temporary license, which later evolved into broader access. Furthermore, Under German law, cannabinoid-based treatments are available either through prescribed synthetic or standardized formulations such as dronabinol, nabilone, or nabiximols or via herbal cannabis under special exemption.^70,74

Global legal and regulatory status of THC and CBD

Several countries have legalized hemp, recognizing its medical, industrial, and economic benefits with the United States, Canada, and China emerging as the top global players (Table 1). In the United States, the 2014 Farm Act⁷⁵ first laid the groundwork for hemp legalization by distinguishing industrial hemp as C. sativa containing no more than 0.3% delta-9 THC on a dry weight basis, separating it from marijuana, which typically has higher THC levels.⁷⁶ The 2014 Farm Act permitted states to implement pilot research programs for cultivating industrial hemp, primarily for academic and research purposes, while still restricting its widespread commercial production.⁷⁷ The Act importantly made an exception to the Controlled Substances Act (CSA)⁷⁸ by removing industrial hemp from the list of Schedule I substances, if it is grown under state-approved programs. This exception also applied to CBD derived from industrial hemp, making it legal at the federal level and in states with matching regulations. The 2014 Farm Act served as a foundational policy that allowed for research into hemp's industrial and medical potential and paved the way for the more comprehensive legalization of hemp in the 2018 Farm Bill. The 2018 Farm Bill expanded upon this foundation, fully legalizing hemp cultivation and unlocking significant economic potential.⁷⁹ By 2019, the U.S. hemp industry generated $1.1 billion in revenue, showcasing its rapid growth following the legalization of hemp under the 2018 Farm Bill. Cultivated acreage expanded by 455% from 2018 to 2019,⁸⁰ driven by hemp's diverse applications in textiles, biofuels, pharmaceuticals, and bioplastics.⁸¹ Globally, the hemp market reached $4.7 billion in 2020, with projections estimating a compound annual growth rate (CAGR) of 22.5% from 2023 to 2028, reaching $14.6 billion by 2026.^82,83

Table 1.

Comparative overview of CBD and THC legal regulations by country/region.

Country/region	CBD legal status	THC legal status
USA	FDA-approved (Epidiolex); hemp-derived CBD federally legal	State-level medical/recreational; federally restricted
UK	Approved (Epidyolex, Sativex)	Medicinal use only (e.g., Sativex)
Germany	Available via prescription; special access for herbal forms	Medical use via standardized/synthetic forms
Canada	Fully legal; includes flowers/leaves (Cannabis Act 2018)	Legal (medical and recreational)
China	Restricted to licensed provinces	Prohibited except in industrial hemp
South Korea	Legal for medical use only	Prohibited recreationally; medical use restricted
Japan	Illegal	Fully prohibited
Saudi Arabia	Illegal	Fully prohibited

China, like the U.S. 2018 Farm Bill, classifies industrial hemp as C. sativa containing no more than 0.3% THC. China plays a pivotal role in the global hemp industry, firmly establishing itself as the world's largest producer of industrial hemp.⁸⁴ In 2019, approximately 66,700 hectares of hemp were cultivated in China, with over 50% of the area dedicated to fiber production. By 2017, the country's hemp industry was valued at $1.7 billion USD, with fiber accounting for 75% of the market, followed by food products at 7%, CBD extraction at 5%, and other uses at 13%.⁸⁴ This dominance reflects China's historical focus on industrial hemp for textiles, food, and construction materials.

China's regulatory system aligns with the United Nations Single Convention on Narcotic Drugs of 1961, which exempts hemp grown exclusively for fiber and seed production from strict drug control measures.⁸⁵ This compliance allows China to freely cultivate industrial hemp for non-psychoactive purposes without breaching international agreements. Cultivation for fiber and seed is largely unregulated across most provinces, enabling large-scale production.⁸⁴ However, the cultivation of hemp flowers and leaves, which are used for CBD extraction, is tightly regulated and restricted to Yunnan and Heilongjiang provinces. In these regions, government oversight ensures that THC levels remain within the legal threshold, maintaining strict compliance with both domestic and international laws.⁸⁶ Hemp seeds are widely exported as a source of protein and omega-3 fatty acids, contributing to the country's agricultural exports.⁸⁷ While fiber remains China's primary focus, the country also exports significant quantities of hemp-derived CBD to markets such as Europe and the United States, where the demand for CBD products is surging.⁸⁸

Canada's journey into hemp industry began in 1998, when hemp cultivation was first legalized under strict regulations for food, fiber, and seed production.⁸⁹ However, it was the Cannabis Act of 2018, which allowed for the cultivation and use of all parts of the hemp plant, including flowers and leaves for CBD extraction, that significantly boosted the industry.⁹⁰ Since 2018, the cannabis and hemp sectors have collectively contributed over $43.5 billion CAD to Canada's GDP.⁹¹ This includes direct contributions through agricultural activities and indirect contributions through manufacturing, processing, and retail sectors. The cannabis industry has supported approximately 151,000 jobs nationwide, spanning cultivation, research, product development, and distribution. Additionally, it has generated $15.1 billion CAD in government revenue, driven by taxes and fees associated with production and sales.⁹¹ Canada has become a global leader in hemp exports, particularly in hemp seeds and hemp oil, which are widely used in foods, cosmetics, and dietary supplements.^92,93 The total value of hemp seed exports was estimated at $53.6 million USD in the same year.⁸⁹

Despite cannabis’ success following decriminalization in many countries, prohibition remains firmly enforced in other countries due to cultural, religious, and historical factors. In Japan, the Cannabis Control Law of 1948 criminalized unlicensed cannabis use and sales, influenced by post-World War II societal reforms and international anti-drug movements.⁹⁴ Similarly, South Korea's Cannabis Control Act of 1976 banned cannabis, heavily influenced by international drug treaties and a desire to align with global standards.⁹⁵ However, South Korea amended its Narcotics Control Act in 2018, becoming the first East Asian country to legalize medical cannabis under strict regulations. Patients can access approved cannabis-based medications like Epidiolex and Sativex for conditions such as epilepsy and cancer-related symptoms,⁹⁶ but recreational use remains strictly prohibited, with harsh penalties for violations.⁹⁷

The Middle East maintains some of the world's most stringent laws on cannabis, reflecting the region's cultural, religious, and legal framework.⁹⁸ For instance, Saudi Arabia enforces severe penalties for cannabis possession, including long prison sentences and fines, under its Law of Combating Narcotics and Psychotropic Substances^99,100 (Table 1). The strict prohibition stems from Islamic teachings that view intoxicants as morally and spiritually detrimental, alongside societal concerns about substance abuse and public health.¹⁰¹

Legal and regulatory Status of THC and CBD in the UAE

In the United Arab Emirates (UAE), all forms of cannabis, including hemp-derived CBD, are classified as narcotics under Federal Law No. 14 of 1995.¹⁰² The law was repealed and replaced by Federal Decree-Law No. 30/2021, which renders the use, possession, cultivation, and distribution of cannabis products illegal, with no legal distinction made between psychoactive cannabis containing THC and non-psychoactive hemp-based products such as CBD.¹⁰³ The penalties for cannabis-related offenses are severe, including imprisonment, heavy fines, and deportation for non-citizens,¹⁰³ reflecting the country's strict zero-tolerance drug policy

The UAE's strict regulations on cannabis are deeply rooted in its cultural and religious principles, heavily influenced by Islamic law, which prohibits intoxicating substances. The government has also prioritized public safety and health concerns, citing the potential for substance abuse and its impact on society as reasons for maintaining strict cannabis laws. Even medicinal cannabis products, widely accepted in other countries, remain prohibited in the UAE.¹⁰³ However, exceptions have been made for certain non-intoxicating cannabis-derived products. For example, Dubai Police has legalized hemp seed oil, provided that it contains no traceable amounts of THC.¹⁰⁴ This recognition highlights the importance to distinguish between non-intoxicating products like hemp seed oil and psychoactive cannabis substances, a critical differentiation for any future discussions on cannabis reforms in the UAE.

Despite this exception, the UAE's strict stance continues to pose significant challenges, particularly in a country known for its large expatriate population and as a global tourist destination.¹⁰⁵ Many expatriates and tourists who depend on CBD products prescribed for medical purposes in their home countries find themselves unable to access these treatments in the UAE. This leaves them without essential medications needed to manage chronic conditions or severe illnesses during their visit. In some cases, individuals carrying CBD products into the country have faced severe legal consequences, including imprisonment.^106,107 However, the UAE has demonstrated its ability to adapt to societal needs through recent legal reforms, particularly with Federal Decree-Law No. 30 of 2021 on Combating Narcotics and Psychotropic Substances.¹⁰⁸ Notably, Article 43 offers first-time offenders an opportunity to avoid prison sentences by placing them in specialized treatment and rehabilitation units instead of imposing criminal penalties. This marks a significant shift from punitive measures to a more rehabilitative approach, focusing on addressing substance dependency. Additionally, provisions in Article 96 ensure that products containing small amounts of narcotics or psychotropic substances, when seized for personal use at state-approved entry points, are handled administratively rather than criminally, further reflecting the UAE's evolving stance towards practical and human drug policies.¹⁰⁸

The global trend towards decriminalization and legalization of cannabis has led to growing discussions about the UAE's rigid approach.^109,110 Legalizing cannabis for medicinal purposes in the UAE would require a strong focus on public education to address misconceptions and foster acceptance. Additionally, it is crucial for the UAE to invest in research and establish testing laboratories capable of differentiating between hemp, which contains less than 0.3% THC, and marijuana, which has higher THC levels.¹¹¹ Accurate testing would ensure effective regulation, prevent misuse, and build public trust in cannabis reforms.¹¹²

Conclusion

The distinctions between THC and CBD are not merely chemical curiosities but are central to the regulatory, medical, and societal treatment of cannabis-derived products. THC, with its psychoactive properties and potential for abuse, demands cautious legal oversight. In contrast, CBD offers a broad therapeutic window, minimal side effects, and no intoxicating effects, making it an ideal candidate for wide clinical application and wellness use. Cannabinoids represent a complex class of bioactive compounds with vast therapeutic potential and significant sociopolitical implications. The molecular distinctions between THC and CBD are critical in defining their pharmacological roles and regulatory classifications. Advances in biosynthesis, SAR studies, and analytical detection methods continue to shape the understanding of these compounds. Despite scientific progress, discrepancies in global cannabis policy highlight the disconnect between evidence and enforcement. Bridging this gap will require targeted public education, investment in cannabinoid research, and harmonized legal frameworks. As cannabis reform progresses globally, nuanced, science-based regulation will be essential to maximize benefits, while minimizing risks.

Footnotes

ORCID iDs

Abdalla Ahmad

Sameh SM Soliman

Ethics considerations

The authors declare that the work reported herein did not require ethics approval because it did not involve animal or human participation.

Authors contributions

LR, RH, AN, and OR conceived the review; conducted the literature searches; screened and selected relevant publications; extracted and organized data and regulatory documents; drafted the initial manuscript. NA and SSMS contributed to designing review and defining the review scope and inclusion/ exclusion criteria; helped with database searches and verification of sources; critically revised all review sections. NA reviewed and analyzed legal and regulatory frameworks across jurisdictions; integrated and compared regulatory texts. SSMS provided subject-matter expertise on cannabinoid pharmacology and regulatory science; reviewed and revised the entire manuscript for scientific accuracy and coherence. All authors participated in interpreting the evidence, discussed and agreed with the final structure and content of the paper, reviewed and approved the final version to be submitted, and are jointly accountable for all aspects of the work.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Guarantor

SSMS accepts full responsibility as guarantor for the integrity of the work, from inception to submission.

References

Kanabus

, et al. Cannabinoids—characteristics and potential for use in food production. Molecules 2021; 26: 6723.

Quarshie

. Implication of regulated cannabis legalisation on wellbeing and economic growth. Johannesburg: University of the Witwatersrand, 2022.

Castaneto

, et al. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend 2014; 144: 12–41.

Mechoulam

. Chemistry of cannabis. In: Psychotropic agents: part III: alcohol and psychotomimetics, psychotropic effects of central acting drugs. Berlin, Heidelberg: Springer, 1982, pp.119–134.

Cooper

et al. Challenges for Clinical Cannabis and Cannabinoid Research in the United States. J Natl Cancer Inst Monogr 2021; 2021: 114–122.

Chandra

Lata

ElSohly

. Cannabis sativa L.-botany and biotechnology. 2017.

Appendino

, et al. Antibacterial cannabinoids from Cannabis sativa: a structure−activity study. J Nat Prod 2008; 71: 1427–1430.

Russo

. History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodiversity 2007; 4: 1614–1648.

Hazekamp

. Cannabis review. Leiden University, Netherlands, 2009.

10.

Rupasinghe

, et al. Industrial hemp (Cannabis sativa subsp. sativa) as an emerging source for value-added functional food ingredients and nutraceuticals. Molecules 2020; 25: 4078.

11.

Sawler

, et al. The genetic structure of marijuana and hemp. PLoS One 2015; 10: e0133292.

12.

H-C

Mackie

. An introduction to the endogenous cannabinoid system. Biol Psychiatry 2016; 79: 516–525.

13.

Stella

. THC and CBD: similarities and differences between siblings. Neuron 2023; 111: 302–327.

14.

Pacher

Bátkai

Kunos

. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006; 58: 389–462.

15.

Munro

Thomas

Abu-Shaar

. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365: 61–65.

16.

Pertwee

. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol 2008; 153: 199–215.

17.

Grotenhermen

. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 2003; 42: 327–360.

18.

Mechoulam

Shvo

. Hashish—I: the structure of cannabidiol. Tetrahedron 1963; 19: 2073–2078.

19.

Devinsky

, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 2014; 55: 791–802.

20.

Huestis

. Human cannabinoid pharmacokinetics. Chem Biodiversity 2007; 4: 1770–1804.

21.

Gaston

Friedman

. Pharmacology of cannabinoids in the treatment of epilepsy. Epilepsy Behav 2017; 70: 313–318.

22.

Watanabe

, et al. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci 2007; 80: 1415–1419.

23.

Schwope

, et al. Identification of recent cannabis use: whole-blood and plasma free and glucuronidated cannabinoid pharmacokinetics following controlled smoked Cannabis administration. Clin Chem 2011; 57: 1406–1414.

24.

Ondřej

, et al. Cannabinoids and cytochrome P450 interactions. Curr Drug Metab 2016; 17: 206–226.

25.

Jiang

, et al. Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes. Life Sci 2011; 89: 165–170.

26.

Perez-Reyes

, et al. A comparison of the pharmacological activity in man of intravenously administered 1368-11368-11368-1, cannabinol, and cannabidiol. Experientia 1973; 29: 1368–1369.

27.

Ujváry

Hanuš

. Human metabolites of cannabidiol: a review on their formation, biological activity, and relevance in therapy. Cannabis Cannabinoid Res 2016; 1: 90–101.

28.

Garrett

Hunt

. Physicochemical properties, solubility, and protein binding of Δ⁹-tetrahydrocannabinol. J Pharm Sci 1974; 63: 1056–1064.

29.

Johansson

, et al. Prolonged apparent half-life of Δ1-tetrahydrocannabinol in plasma of chronic marijuana users. J Pharm Pharmacol 1988; 40: 374–375.

30.

Britch

Babalonis

Walsh

. Cannabidiol: pharmacology and therapeutic targets. Psychopharmacology 2021; 238: 9–28.

31.

SirichaiChayasirisobhon. Mechanisms of action and pharmacokinetics of Cannabis. Perm J 2021; 25: 1–3.

32.

D'Souza

, et al. The psychotomimetic effects of intravenous Delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 2004; 29: 1558–1572.

33.

García-Gutiérrez

, et al. Cannabidiol: a potential new alternative for the treatment of anxiety, depression, and psychotic disorders. Biomolecules 2020; 10: 1575.

34.

Mateus Machado

, et al. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf 2011; 6: 237–249.

35.

D’Souza

, et al. Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol Psychiatry 2005; 57: 594–608.

36.

Di Forti

, et al. High-potency cannabis and the risk of psychosis. Br J Psychiatry 2009; 195: 488–491.

37.

Benowitz

Jones

. Prolonged delta-9-tetrahydrocannabinol ingestion; effects of sympathomimetic amines and autonomic blockades. Clin Pharmacol Ther 1977; 21: 336–342.

38.

Pacher

, et al. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol 2018; 15: 151–166.

39.

Morrison

Stone

. Synthetic delta-9-tetrahydrocannabinol elicits schizophrenia-like negative symptoms which are distinct from sedation. Hum Psychopharmacol Clin Exp 2011; 26: 77–80.

40.

Iffland

Grotenhermen

. An update on safety and Side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res 2017; 2: 139–154.

41.

Balachandran

Elsohly

Hill

. Cannabidiol interactions with medications, illicit substances, and alcohol: a comprehensive review. J Gen Intern Med 2021; 36: 2074–2084.

42.

Pugazhendhi

, et al. Cannabinoids as anticancer and neuroprotective drugs: structural insights and pharmacological interactions—a review. Process Biochem 2021; 111: 9–31.

43.

Pellati

, et al. Cannabis sativa L. and nonpsychoactive cannabinoids: their chemistry and role against oxidative stress, inflammation, and cancer. BioMed Res Int 2018; 2018: 1691428.

44.

Tahir

, et al. The biosynthesis of the cannabinoids. J Cannabis Res 2021; 3: 1–12.

45.

Śmiarowska

Białecka

Machoy-Mokrzyńska

. Cannabis and cannabinoids: pharmacology and therapeutic potential. Neurol Neurochir Pol 2022; 56: 4–13.

46.

Walsh

McKinney

Holmes

. Minor cannabinoids: biosynthesis, molecular pharmacology and potential therapeutic uses. Front Pharmacol 2021; 12: 777804.

47.

Hazekamp

, et al.

3.24—Chemistry of cannabis

Comprehensive natural products II. 3. Oxford: Elsevier, 2010, pp.1033–1084.

48.

Wiley

Marusich

Thomas

. Combination chemistry: Structure-activity relationships of novel psychoactive cannabinoids. Curr Top Behav Neurosci 2017: 231–248.

49.

Connor

, et al. Cannabis use and cannabis use disorder. Nat Rev Dis Primers 2021; 7: 16.

50.

Russo

, et al. Enantioseparation of chiral phytocannabinoids in medicinal cannabis. J Chromatogr B 2023; 1221: 123682.

51.

Bow

Rimoldi

. The structure-function relationships of classical cannabinoids: CB1/CB2 modulation. Perspect Medicin Chem 2016; 28: 17–39.

52.

Burstein

, et al. Ajulemic acid: a novel cannabinoid produces analgesia without a “high”. Life Sci 2004; 75: 1513–1522.

53.

Bragança

, et al. Impact of conformational and solubility properties on psycho-activity of cannabidiol (CBD) and tetrahydrocannabinol (THC). Chem Data Collections 2020; 26: 100345.

54.

Sherma

Rabel

. Thin layer chromatography in the analysis of cannabis and its components and synthetic cannabinoids. J Liq Chromatogr Relat Technol 2019; 42: 613–628.

55.

Liu

, et al. High performance thin-layer chromatography (HPTLC) analysis of cannabinoids in cannabis extracts. Forensic Chem 2020; 19: 100249.

56.

Ruppel

Kuffel

Shelton

. Cannabis analysis: potency testing identification and quantification of THC and CBD by GC/FID and GC/MS. MS. PerkinElmer, 2017.

57.

Steiner

Lurie

. Applicability of liquid and supercritical fluid chromatographic separation techniques with diode array ultraviolet detection for forensic analysis. Forensic Chem 2021; 26: 100359.

58.

McRae

Melanson

. Quantitative determination and validation of 17 cannabinoids in cannabis and hemp using liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem 2020; 412: 7381–7393.

59.

Schwope

Milman

Huestis

. Validation of an enzyme immunoassay for detection and semiquantification of cannabinoids in oral fluid. Clin Chem 2010; 56: 1007–1014.

60.

Harpaz

, et al. Portable biosensors for rapid on-site determination of cannabinoids in cannabis, a review. Biotechnol Adv 2022; 61: 108031.

61.

Gorziza

, et al. Study of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) extraction FROM dried oral fluid spots (DOFS) and LC–MS/MS detection. J Cannabis Res 2021; 3: 1–11.

62.

Jana

, et al. Therapeutic potential of cannabinoids in schizophrenia. Recent Patents CNS Drug Discov 2014; 9: 13–25.

63.

SirichaiChayasirisobhon. The role of cannabidiol in neurological disorders. Perm J 2021; 25: 1–1.

64.

Biosciences

. Epidiolex (package insert). Carlsbad, CA: Greenwich Biosciences, 2018.

65.

Devinsky

, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 2017; 376: 2011–2020.

66.

Thiele

, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018; 391: 1085–1096.

67.

Devinsky

, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med 2018; 378: 1888–1897.

68.

Thiele

, et al. Add-on cannabidiol treatment for drug-resistant seizures in tuberous sclerosis complex: a placebo-controlled randomized clinical trial. JAMA Neurol 2021; 78: 285–292.

69.

Bridgeman

Abazia

. Medicinal cannabis: history, pharmacology, and implications for the acute care setting. P T 2017; 42: 180–188.

70.

Grotenhermen

Müller-Vahl

. The therapeutic potential of cannabis and cannabinoids. Dtsch Arztebl Int 2012; 109: 495–501.

71.

O’Donnell

Meissner

Gupta

. Dronabinol. 2020.

72.

Duddy

. Medical use of cannabis, in House of Commons. 2025.

73.

Novotna

, et al. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol 2011; 18: 1122–1131.

74.

Lipnik-Štangelj

Razinger

. A regulatory take on cannabis and cannabinoids for medicinal use in the European Union. Arh Hig Rada Toksikol 2020; 71: 12–18.

75.

States

. Agricultural Act of 2014, Public Law 113-79. 2014.

76.

Johnson

. Defining industrial hemp: a fact sheet (CRS Report No. R44742), C.R. Service, Editor. 2017.

77.

Lee

. The Legalization of Hemp. FDLI Update, 2019: p. 17.

78.

States

. 21 U.S.C. § 801-Congressional findings and declarations: Controlled Substances Act. Cornell Law School Legal Information Institute, n.d.

79.

States

. Agricultural Improvement Act of 2018, H.R. 2, 115th Congress. 2018.

80.

University

. 3 ways the hemp industry is changing agriculture and the economy forever. 2020; Available from: https://unity.edu/sustainability/3-ways-the-hemp-is-changing-agriculture-and-the-economy-forever/.

81.

Fortenbery

Bennett

. Is Industrial Hemp Worth Further Study in the US? A Survey of the Literature. 2001.

82.

Research

. Industrial hemp market report and forecast 2023-2028. n.d. 21/01/2025]; Available from: https://www.expertmarketresearch.com/reports/industrial-hemp-market.

83.

Kaur

Kander

. The sustainability of industrial hemp: a literature review of its economic, environmental, and social sustainability. Sustainability 2023; 15: 6457.

84.

Service

UFA

. 2019 hemp annual report. Beijing, China: People's Republic of China, 2020.

85.

(UNODC), U.N.O.o.D.a.C. Single Convention on Narcotic Drugs, 1961. 1961.

86.

Zhao

Xiong

Chen

. Regional comparison and strategy recommendations of industrial hemp in China based on a SWOT analysis. Sustainability 2021; 13: 6419.

87.

Farinon

, et al. The seed of industrial hemp (Cannabis sativa L.): nutritional quality and potential functionality for human health and nutrition. Nutrients 2020; 12: 1935.

88.

Horner

, et al. Comparative analysis of the industrial hemp industry: guide to the evolution of the US industrial hemp industry in the global economy. 2019.

89.

Service

UFA

. Update on industrial hemp production, trade, and regulation. Ottawa, Canada: USDA, 2023.

90.

Canada, G.o. Cannabis Act (S.C. 2018, c. 16). 2018.

91.

Deloitte. An annual report on the Canadian cannabis industry. 2021.

92.

Canada

. About cannabidiol (CBD). n.d. 23/01/2025]; Available from: https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis/about/cannabidiol.html.

93.

Alliance

CHT

. Submission to the House of Commons Standing Committee on Agriculture and Agri-Food. 2018.

94.

Japan

. Cannabis Control Act. n.d.

95.

(KLRI), K.L.R.I. Narcotics Control Act (amended). 2019.

96.

Kim

. Medicalization of cannabis in South Korea. 2022.

97.

McCurry

. ‘Bong arm of the law': South Korea says it will arrest citizens who smoke weed in Canada, in The Guardian. 2018.

98.

Robins

. Middle East drugs bazaar production, prevention and consumption. Oxford University Press, 2016.

99.

Ministry of Interior, K.o.S.A. Official portal. n.d. 25/01/2025]; Available from: https://www.moi.gov.sa/wps/portal/.

100.

Arabia

GoS

. Law of Combating Narcotics and Psychotropic Substances. n.d.

101.

Safian

. An analysis on Islamic rules on drugs. Int J Educ Res 2013; 1(9): 2.

102.

Emirates, U.A. Federal Law No. 14 of 1995 on Combating Narcotics and Psychotropic Substances. 1995.

103.

Law, U.F.D.-L.N.A.O.o.t.N.D.

104.

News

. Hemp seed oil: Is it legal in Dubai? 2019.

105.

Ministry of Economy

. UAE tops MENA region and climbs seven places globally in WEF's Tourism & Travel Development Index 2024. 2024 26/01/2025]; Available from: https://www.moec.gov.ae/en/-/uae-tops-mena-region-and-climbs-seven-places-globally-in-wef-s-tourism-travel-development-index-2024?p_l_back_url=%2Fen%2Ftest1%3Fdelta%3D60%26tag%3D2014%26start%3D33.

106.

News

. Britons issued travel warning over CBD oil products and potential criminal charges abroad. n.d.; Available from: https://www.gbnews.com/travel/britons-travel-warning-cbd-oil-products-criminal-charges-abroad.

107.

News

. Billy Hood: British football coach has sentence reduced in Dubai CBD case. 2021.

108.

Emirates, U.A. Federal Decree-Law No. 30 of 2021 on Combating Narcotics and Psychotropic Substances. 2021.

109.

Fouché

, et al. Alcohol and substance dependence in the United Arab Emirates: a scoping review protocol. BMJ Open 2023; 13: e071208.

110.

Sarhan

HAS

. Drugs abuse in the United Arab Emirates. Newcastle University, 1995.

111.

Salehi

, et al. Differentiating cannabis products: drugs, food, and supplements. Front Pharmacol 2022; 13: 906038.

112.

Justice

NIo

. New forensic methods to accurately determine THC in seized cannabis. 2020; Available from: https://nij.ojp.gov/topics/articles/new-forensic-methods-accurately-determine-thc-seized-cannabis.