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.
KanabusJ, et al.Cannabinoids—characteristics and potential for use in food production. Molecules2021; 26: 6723.
2.
QuarshieE. Implication of regulated cannabis legalisation on wellbeing and economic growth. Johannesburg: University of the Witwatersrand, 2022.
3.
CastanetoMS, et al.Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend2014; 144: 12–41.
4.
MechoulamR. Chemistry of cannabis. In: Psychotropic agents: part III: alcohol and psychotomimetics, psychotropic effects of central acting drugs. Berlin, Heidelberg: Springer, 1982, pp.119–134.
5.
CooperZDet al. Challenges for Clinical Cannabis and Cannabinoid Research in the United States. J Natl Cancer Inst Monogr2021; 2021: 114–122.
6.
ChandraSLataHElSohlyMA. Cannabis sativa L.-botany and biotechnology. 2017.
7.
AppendinoG, et al.Antibacterial cannabinoids from Cannabis sativa: a structure−activity study. J Nat Prod2008; 71: 1427–1430.
8.
RussoEB. History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodiversity2007; 4: 1614–1648.
RupasingheHV, et al.Industrial hemp (Cannabis sativa subsp. sativa) as an emerging source for value-added functional food ingredients and nutraceuticals. Molecules2020; 25: 4078.
11.
SawlerJ, et al.The genetic structure of marijuana and hemp. PLoS One2015; 10: e0133292.
12.
LuH-CMackieK. An introduction to the endogenous cannabinoid system. Biol Psychiatry2016; 79: 516–525.
13.
StellaN. THC and CBD: similarities and differences between siblings. Neuron2023; 111: 302–327.
14.
PacherPBátkaiSKunosG. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev2006; 58: 389–462.
15.
MunroSThomasKLAbu-ShaarM. Molecular characterization of a peripheral receptor for cannabinoids. Nature1993; 365: 61–65.
16.
PertweeRG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol2008; 153: 199–215.
17.
GrotenhermenF. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet2003; 42: 327–360.
18.
MechoulamRShvoY. Hashish—I: the structure of cannabidiol. Tetrahedron1963; 19: 2073–2078.
19.
DevinskyO, et al.Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia2014; 55: 791–802.
20.
HuestisMA. Human cannabinoid pharmacokinetics. Chem Biodiversity2007; 4: 1770–1804.
21.
GastonTEFriedmanD. Pharmacology of cannabinoids in the treatment of epilepsy. Epilepsy Behav2017; 70: 313–318.
22.
WatanabeK, et al.Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci2007; 80: 1415–1419.
23.
SchwopeDM, et al.Identification of recent cannabis use: whole-blood and plasma free and glucuronidated cannabinoid pharmacokinetics following controlled smoked Cannabis administration. Clin Chem2011; 57: 1406–1414.
24.
OndřejZ, et al.Cannabinoids and cytochrome P450 interactions. Curr Drug Metab2016; 17: 206–226.
25.
JiangR, et al.Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes. Life Sci2011; 89: 165–170.
26.
Perez-ReyesM, et al.A comparison of the pharmacological activity in man of intravenously administered 1368-11368-11368-1, cannabinol, and cannabidiol. Experientia1973; 29: 1368–1369.
27.
UjváryIHanušL. Human metabolites of cannabidiol: a review on their formation, biological activity, and relevance in therapy. Cannabis Cannabinoid Res2016; 1: 90–101.
28.
GarrettERHuntCA. Physicochemical properties, solubility, and protein binding of Δ9-tetrahydrocannabinol. J Pharm Sci1974; 63: 1056–1064.
29.
JohanssonE, et al.Prolonged apparent half-life of Δ1-tetrahydrocannabinol in plasma of chronic marijuana users. J Pharm Pharmacol1988; 40: 374–375.
30.
BritchSCBabalonisSWalshSL. Cannabidiol: pharmacology and therapeutic targets. Psychopharmacology2021; 238: 9–28.
31.
SirichaiChayasirisobhon. Mechanisms of action and pharmacokinetics of Cannabis. Perm J2021; 25: 1–3.
32.
D'SouzaDC, et al.The psychotomimetic effects of intravenous Delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology2004; 29: 1558–1572.
33.
García-GutiérrezMS, et al.Cannabidiol: a potential new alternative for the treatment of anxiety, depression, and psychotic disorders. Biomolecules2020; 10: 1575.
34.
Mateus MachadoB, et al.Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf2011; 6: 237–249.
35.
D’SouzaDC, et al.Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol Psychiatry2005; 57: 594–608.
36.
Di FortiM, et al.High-potency cannabis and the risk of psychosis. Br J Psychiatry2009; 195: 488–491.
37.
BenowitzNLJonesRT. Prolonged delta-9-tetrahydrocannabinol ingestion; effects of sympathomimetic amines and autonomic blockades. Clin Pharmacol Ther1977; 21: 336–342.
38.
PacherP, et al.Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol2018; 15: 151–166.
39.
MorrisonPDStoneJM. Synthetic delta-9-tetrahydrocannabinol elicits schizophrenia-like negative symptoms which are distinct from sedation. Hum Psychopharmacol Clin Exp2011; 26: 77–80.
40.
IfflandKGrotenhermenF. An update on safety and Side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res2017; 2: 139–154.
41.
BalachandranPElsohlyMHillKP. Cannabidiol interactions with medications, illicit substances, and alcohol: a comprehensive review. J Gen Intern Med2021; 36: 2074–2084.
42.
PugazhendhiA, et al.Cannabinoids as anticancer and neuroprotective drugs: structural insights and pharmacological interactions—a review. Process Biochem2021; 111: 9–31.
43.
PellatiF, et al.Cannabis sativa L. and nonpsychoactive cannabinoids: their chemistry and role against oxidative stress, inflammation, and cancer. BioMed Res Int2018; 2018: 1691428.
44.
TahirMN, et al.The biosynthesis of the cannabinoids. J Cannabis Res2021; 3: 1–12.
45.
ŚmiarowskaMBiałeckaMMachoy-MokrzyńskaA. Cannabis and cannabinoids: pharmacology and therapeutic potential. Neurol Neurochir Pol2022; 56: 4–13.
46.
WalshKBMcKinneyAEHolmesAE. Minor cannabinoids: biosynthesis, molecular pharmacology and potential therapeutic uses. Front Pharmacol2021; 12: 777804.
47.
HazekampA, et al.3.24—Chemistry of cannabisComprehensive natural products II. 3. Oxford: Elsevier, 2010, pp.1033–1084.
48.
WileyJLMarusichJAThomasBF. Combination chemistry: Structure-activity relationships of novel psychoactive cannabinoids. Curr Top Behav Neurosci2017: 231–248.
49.
ConnorJP, et al.Cannabis use and cannabis use disorder. Nat Rev Dis Primers2021; 7: 16.
50.
RussoF, et al.Enantioseparation of chiral phytocannabinoids in medicinal cannabis. J Chromatogr B2023; 1221: 123682.
51.
BowEWRimoldi JM. The structure-function relationships of classical cannabinoids: CB1/CB2 modulation. Perspect Medicin Chem2016; 28: 17–39.
52.
BursteinSH, et al.Ajulemic acid: a novel cannabinoid produces analgesia without a “high”. Life Sci2004; 75: 1513–1522.
53.
BragançaVA, et al.Impact of conformational and solubility properties on psycho-activity of cannabidiol (CBD) and tetrahydrocannabinol (THC). Chem Data Collections2020; 26: 100345.
54.
ShermaJRabelF. Thin layer chromatography in the analysis of cannabis and its components and synthetic cannabinoids. J Liq Chromatogr Relat Technol2019; 42: 613–628.
55.
LiuY, et al.High performance thin-layer chromatography (HPTLC) analysis of cannabinoids in cannabis extracts. Forensic Chem2020; 19: 100249.
56.
RuppelTDKuffelNSheltonC. Cannabis analysis: potency testing identification and quantification of THC and CBD by GC/FID and GC/MS. MS. PerkinElmer, 2017.
57.
SteinerALurieI. Applicability of liquid and supercritical fluid chromatographic separation techniques with diode array ultraviolet detection for forensic analysis. Forensic Chem2021; 26: 100359.
58.
McRaeGMelansonJE. Quantitative determination and validation of 17 cannabinoids in cannabis and hemp using liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem2020; 412: 7381–7393.
59.
SchwopeDMMilmanGHuestisMA. Validation of an enzyme immunoassay for detection and semiquantification of cannabinoids in oral fluid. Clin Chem2010; 56: 1007–1014.
60.
HarpazD, et al.Portable biosensors for rapid on-site determination of cannabinoids in cannabis, a review. Biotechnol Adv2022; 61: 108031.
61.
GorzizaR, et al.Study of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) extraction FROM dried oral fluid spots (DOFS) and LC–MS/MS detection. J Cannabis Res2021; 3: 1–11.
62.
JanaK, et al.Therapeutic potential of cannabinoids in schizophrenia. Recent Patents CNS Drug Discov2014; 9: 13–25.
63.
SirichaiChayasirisobhon. The role of cannabidiol in neurological disorders. Perm J2021; 25: 1–1.
DevinskyO, et al.Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med2017; 376: 2011–2020.
66.
ThieleEA, et al.Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet2018; 391: 1085–1096.
67.
DevinskyO, et al.Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med2018; 378: 1888–1897.
68.
ThieleEA, et al.Add-on cannabidiol treatment for drug-resistant seizures in tuberous sclerosis complex: a placebo-controlled randomized clinical trial. JAMA Neurol2021; 78: 285–292.
69.
BridgemanMBAbaziaDT. Medicinal cannabis: history, pharmacology, and implications for the acute care setting. P T2017; 42: 180–188.
70.
GrotenhermenFMüller-VahlK. The therapeutic potential of cannabis and cannabinoids. Dtsch Arztebl Int2012; 109: 495–501.
71.
O’DonnellBMeissnerHGuptaV. Dronabinol. 2020.
72.
DuddyC. Medical use of cannabis, in House of Commons. 2025.
73.
NovotnaA, 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 Neurol2011; 18: 1122–1131.
74.
Lipnik-ŠtangeljMRazingerB. A regulatory take on cannabis and cannabinoids for medicinal use in the European Union. Arh Hig Rada Toksikol2020; 71: 12–18.
75.
StatesU. Agricultural Act of 2014, Public Law 113-79. 2014.
KaurGKanderR. The sustainability of industrial hemp: a literature review of its economic, environmental, and social sustainability. Sustainability2023; 15: 6457.
(UNODC), U.N.O.o.D.a.C.Single Convention on Narcotic Drugs, 1961. 1961.
86.
ZhaoHXiongHChenJ. Regional comparison and strategy recommendations of industrial hemp in China based on a SWOT analysis. Sustainability2021; 13: 6419.
87.
FarinonB, et al.The seed of industrial hemp (Cannabis sativa L.): nutritional quality and potential functionality for human health and nutrition. Nutrients2020; 12: 1935.
88.
HornerJ, 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.
ServiceUFA. 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.
