Beyond THC, how many other cannabinoids have been identified in cannabis plants?

In addition to THC, scientists have identified at least 113 other distinct cannabinoids within cannabis plants, each potentially having unique properties and effects.

What is the chemical formula for THC, and what does it signify?

The chemical formula for THC is C21H30O2. This formula describes the atomic composition of the molecule, but it's important to note that it can represent multiple different chemical structures, known as isomers, which may have different properties.

Which specific isomer is typically referred to when discussing THC, and what is its chemical name?

The term THC usually refers to the specific isomer known as (−)-trans-Δ⁹-tetrahydrocannabinol. This precise chemical name indicates its specific three-dimensional structure and the location of a key double bond.

What is the pharmaceutical name for THC, and what are its approved medical uses?

In a pharmaceutical context, THC is known as dronabinol. It is approved in the United States for medical use in relieving nausea and vomiting associated with chemotherapy, and to combat anorexia related to conditions like HIV/AIDS.

How does THC interact with the body's cannabinoid receptors?

THC primarily interacts with the body's cannabinoid receptors, specifically CB1 and CB2, acting as a partial agonist. This means it binds to these receptors and activates them, but not to the maximum extent possible, influencing various physiological processes.

What are the common routes of administration for THC, and how do they affect its action?

THC can be administered through various routes, including orally, by inhalation (smoking or vaping), and transdermally (through the skin). The route of administration significantly impacts its bioavailability (the amount that reaches the bloodstream) and the speed at which its effects begin.

What are some of the commonly reported side effects associated with THC use?

Common side effects of THC use can include physical symptoms like red eyes and dry mouth, as well as cognitive and psychological effects such as drowsiness, short-term memory impairment, difficulty concentrating, anxiety, and paranoia. Chronic use may also lead to cannabinoid hyperemesis syndrome.

What is cannabinoid hyperemesis syndrome (CHS)?

Cannabinoid hyperemesis syndrome (CHS) is a condition associated with chronic, long-term use of THC. It is characterized by recurring episodes of severe nausea, vomiting, and abdominal pain that can persist for months or even years after discontinuing use.

What is the known lethal dose of THC in humans, and what does research suggest?

The exact median lethal dose (LD50) of THC in humans is not definitively established due to conflicting evidence and the rarity of fatal overdoses. While some animal studies have indicated lethality at certain doses, a 2020 fact sheet from the U.S. Drug Enforcement Administration stated that no deaths from marijuana overdose have been reported.

What are the known interactions between THC and other drugs?

Formal studies on drug interactions with THC are limited. However, it has been observed that THC can increase the elimination half-life of certain drugs, such as the barbiturate pentobarbital, by approximately four hours when administered concurrently.

How does THC's interaction with CB1 receptors influence cellular signaling?

When THC activates CB1 receptors, it leads to a cascade of cellular events, including a decrease in cyclic adenosine monophosphate (cAMP) levels. This occurs through the inhibition of an enzyme called adenylate cyclase, affecting intracellular communication.

What is the significance of THC being a lipophilic molecule?

THC's lipophilic nature means it dissolves readily in fats and lipids. This property allows it to easily cross cell membranes and distribute into fatty tissues, such as adipose tissue, where it can accumulate and be slowly released over time.

How does THC's pharmacodynamic tolerance potentially benefit its therapeutic use?

While THC can lead to pharmacodynamic tolerance (where the body adapts to the drug, potentially reducing its effects), this tolerance may also mitigate some of the drug's undesirable side effects. This could potentially widen the drug's therapeutic window, making it safer for medical use.

What is the bioavailability of THC when administered orally versus inhaled?

When taken orally, THC's bioavailability is relatively low, typically between 6% and 20%, due to first-pass metabolism in the liver. In contrast, inhalation results in a higher bioavailability, generally around 25%, though this can vary significantly based on usage patterns and product type.

How does a high-fat meal affect the absorption of orally administered THC?

Consuming a high-fat meal before taking oral THC can significantly increase its absorption. It delays the time to peak concentration by about four hours and increases the overall exposure (area-under-the-curve) by nearly threefold, partly by allowing THC to bypass some of the liver's first-pass metabolism.

What are the primary enzymes responsible for metabolizing THC in the liver?

THC metabolism primarily occurs in the liver, mainly mediated by cytochrome P450 enzymes, specifically CYP2C9, CYP2C19, and CYP3A4. CYP2C9 and CYP3A4 are considered the most significant in this process.

What is the main active metabolite of THC, and how does it compare to THC?

The principal active metabolite of THC is 11-hydroxy-THC, which is formed in the liver. This metabolite is also psychoactive and contributes to the overall effects of THC consumption.

How does the elimination half-life of THC vary, and what factors influence it?

The elimination half-life of THC is highly variable, with estimates ranging from around 20-30 hours in many studies, but potentially much longer (up to 59 hours) in some cases. Heavy users tend to have longer half-lives, possibly due to THC accumulating in fatty tissues and being released slowly.

What is the relationship between THC and THCA in the cannabis plant?

THCA (tetrahydrocannabinolic acid) is the primary precursor to THC found in the cannabis plant. Through a process called decarboxylation, typically induced by heat, THCA loses a carbon dioxide molecule to become the psychoactive THC.

Who first isolated THC from cannabis, and when?

THC was first isolated from cannabis in 1964 by Raphael Mechoulam and Yehiel Gaoni.

What role might THC play in the plant's evolutionary adaptation?

As a phytochemical, THC is hypothesized to be involved in the cannabis plant's evolutionary adaptation, potentially serving as a defense mechanism against insect predation, protecting against ultraviolet light damage, and aiding in adaptation to environmental stress.

What is the significance of THC's classification under international and US law?

THC's classification varies significantly. Internationally, it's subject to UN conventions, and within the US, it's federally classified as a Schedule I controlled substance, despite its pharmaceutical form (dronabinol) being approved for medical use. Many US states have legalized its medical use.

What evidence supports the medical use of THC for multiple sclerosis symptoms?

Research, including systematic reviews, suggests that THC and oral cannabis extracts are effective for improving subjective experiences of spasticity and centrally mediated pain in multiple sclerosis patients. They are also considered probably effective for improving objective measures of spasticity and pain.

What did the American Academy of Neurology conclude about THC's effectiveness for neurological disorders?

In 2014, the American Academy of Neurology found evidence supporting THC's effectiveness for certain multiple sclerosis symptoms like spasticity and pain. However, they determined there was insufficient evidence to conclude its effectiveness for several other neurological disorders.

How can THC and its metabolites be detected for drug testing purposes?

THC and its primary metabolites, 11-OH-THC and THC-COOH, can be detected and quantified in biological samples like blood, urine, hair, and sweat. This is typically done using a combination of immunoassay screening and more specific chromatographic techniques for confirmation.

What is the legal status of THC in the United States at the federal versus state level?

Federally, cannabis and pure Δ⁹-THC are classified as Schedule I controlled substances under the Controlled Substances Act, indicating a high potential for abuse and no accepted medical use. However, as of 2023, 38 US states, four territories, and Washington D.C. permit the medical use of cannabis, which contains THC.

How does THC's partial agonism at cannabinoid receptors influence its effects compared to full agonists?

As a partial agonist, THC's efficacy is limited compared to full agonists. It appears to cause greater downregulation of cannabinoid receptors than endogenous cannabinoids and may even act as an antagonist to more efficacious endogenous agonists in certain contexts.

What is the chemical relationship between THC and THCA?

THCA (tetrahydrocannabinolic acid) is the biosynthetic precursor to THC. When THCA is heated or ages, it undergoes decarboxylation, losing a carboxyl group to become THC.

What are some examples of THC analogs mentioned in the 'List of related compounds' section?

The list includes several THC analogs, which are compounds with similar structures. Examples provided are Dimethylheptylpyran, Levonantradol, Nabilone, Nabitan, and Tinabinol.

What is the IUPAC name for the primary THC isomer?

The IUPAC name for the primary isomer, (−)-trans-Δ⁹-tetrahydrocannabinol, is (6aR,10aR)-6,6,9-Trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol.

What are the reported boiling points for THC?

THC has a boiling point of 155–157 °C (311–315 °F) at a very low pressure of 0.05 mmHg. It is also cited as boiling between 157–160 °C at the same pressure.

What is the solubility of THC in water?

THC has very low solubility in water, reported as 0.0028 mg/mL at 23 °C, reflecting its hydrophobic nature.

What is the primary mechanism by which THC exerts its psychoactive effects?

The psychoactive effects of THC are primarily mediated by its activation of the CB1 cannabinoid receptor, which is predominantly found in the central nervous system. This activation influences neurotransmitter release and other neural processes.

What potential toxicity risks are associated with prolonged, high-dose THC exposure?

Preliminary research suggests that prolonged exposure to high doses of THC might interfere with chromosomal stability. This could potentially have hereditary effects, influencing cell instability and possibly increasing cancer risk, although carcinogenicity in heavy users is complicated by confounding factors like concurrent tobacco use.

How does THC's partial agonism at CB1 receptors differ from that of endocannabinoids like anandamide?

THC acts as a partial agonist at CB1 receptors, meaning it produces a submaximal response. This differs from endocannabinoids like anandamide, which are full agonists, and may lead to greater downregulation of CB1 receptors with THC use, potentially even causing THC to act antagonistically towards endocannabinoids in some situations.

What is the significance of THC being a 'lipophilic molecule'?

THC being lipophilic means it has a high affinity for fatty substances. This characteristic allows it to readily cross biological membranes, including the blood-brain barrier, and to accumulate in adipose (fat) tissue, influencing its distribution and duration of action in the body.

What is the primary metabolic pathway for THC in the liver?

In the liver, THC primarily undergoes metabolism through hydroxylation, a process where a hydroxyl (-OH) group is added to the molecule. This is mainly carried out by cytochrome P450 enzymes, particularly CYP2C9.

What is the difference between THC's elimination half-life in casual users versus heavy users?

The elimination half-life of THC is generally longer in heavy users compared to casual users. This is thought to be due to the accumulation of THC in deep body compartments, such as fat tissue, from which it is released more slowly.

What is the relationship between THC and the discovery of endocannabinoids?

The study of how THC interacts with cannabinoid receptors in the brain led researchers to discover the body's own natural cannabinoid-like molecules, known as endocannabinoids, such as anandamide and 2-arachidonoyl glyceride (2-AG).

What are some of the 'minor' phytocannabinoids listed in the sidebar?

The sidebar lists several minor phytocannabinoids, including various homologues of THC such as THCB (Cannabutol), THCH (Cannabihexol), THCP (Cannabiphorol), and THCV (Cannabivarin), as well as isomers like Delta-8-THC and Delta-10-THC.

What is the role of THCA in the cannabis plant's biochemistry?

THCA (tetrahydrocannabinolic acid) is the primary form in which THC exists in the cannabis plant before it undergoes decarboxylation. It is synthesized from earlier precursors like cannabigerolic acid.

How does the U.S. federal government classify cannabis under the Controlled Substances Act?

Under the U.S. Controlled Substances Act, cannabis is classified as a Schedule I controlled substance. This classification is based on the federal government's assessment that it has no accepted medical use and a high potential for abuse.

What evidence exists for THC's effectiveness in treating symptoms of multiple sclerosis?

Evidence suggests that THC and oral cannabis extracts are effective for improving subjective experiences of spasticity and centrally mediated pain in multiple sclerosis patients. They are also considered probably effective for improving objective measures of spasticity.

What is the significance of THC's classification as a 'partial agonist'?

Being a partial agonist means THC binds to cannabinoid receptors (CB1 and CB2) but produces a weaker response than a full agonist. This characteristic can influence its overall potency and may contribute to a wider therapeutic window by potentially mitigating some adverse effects.

What is the primary difference between THC and CBD in terms of their effects?

While both are cannabinoids found in cannabis, THC is primarily known for its psychoactive effects, whereas CBD (cannabidiol) is non-psychoactive and is often associated with potential therapeutic benefits like anticonvulsant and anti-inflammatory properties.

How does the metabolism of THC differ between oral administration and inhalation?

Oral administration leads to extensive first-pass metabolism of THC in the liver, converting it into metabolites like 11-hydroxy-THC. Inhalation largely bypasses this first-pass metabolism, leading to higher concentrations of unmetabolized THC in the bloodstream and a faster onset of effects.

What are the potential implications of THC's interaction with autotaxin?

Recent findings suggest THC may act as a partial autotaxin inhibitor. Since autotaxin is involved in generating lysophosphatidic acid (LPA), a mediator in various diseases, this interaction might explain some of THC's effects on inflammation and neurological conditions, though clinical trials are needed to confirm this.

What is the role of CYP2C9 in THC metabolism, and how can genetic variations affect exposure?

CYP2C9 is one of the primary enzymes in the liver responsible for metabolizing THC, particularly through hydroxylation. Individuals with genetic variants that reduce CYP2C9 function may experience significantly higher exposure to THC when taken orally.

What is the difference between THC's 'first-pass metabolism' and its 'elimination half-life'?

First-pass metabolism refers to the initial breakdown of a drug by the liver before it reaches systemic circulation, significantly reducing oral bioavailability. The elimination half-life, on the other hand, is the time it takes for the concentration of the drug in the body to reduce by half after it has been absorbed and distributed.

What are the potential risks associated with long-term, high-dose exposure to THC?

Prolonged exposure to high doses of THC may pose risks such as interference with chromosomal stability, which could have hereditary implications. Additionally, the long-term effects on cognitive function and mental health, particularly in vulnerable individuals, are still areas of active research.

Tetrahydrocannabinol Wiki: Tetrahydrocannabinol: A Deep Dive into its Chemistry, Pharmacology, and Clinical Applications

Tetrahydrocannabinol
INN: Dronabinol
Clinical data


Trade names	Marinol, Syndros
Other names	(6aR,10aR)-delta-9-Tetrahydrocannabinol; (−)-trans-Δ⁹-tetrahydrocannabinol
License data	US FDA: Dronabinol
Dependence liability	Physical: Low Psychological: Low–moderate
Addiction liability	Relatively low: 9%^{[citation needed]}
Routes of administration	By mouth, transdermal, sublingual, inhalation
Drug class	Cannabinoid
ATC code	A04AD10 (WHO)
Legal status
Legal status	AU: Unscheduled: ACT, Schedule 8 (Controlled Drug) BR: Dronabinol: A3; THC <30mg/ml: A3; others: F2 (prohibited).^[1] CA: Unscheduled DE: Dronabinol: Anlage III, Δ⁹-THC: II, other isomers and their stereochemical variants: I. (Does not apply to THC as part of cannabis, which is regulated separately, see Cannabis (drug)) UK: Class B US: Schedule II as Syndros, Schedule III as Marinol,^[2] Schedule I as Δ⁹-THC in pure form UN: Psychotropic Schedule I /II In general Rx-only
Pharmacokinetic data
Bioavailability	Oral: 6–20%^[3] Inhalation: 10–35%
Protein binding	97–99%^[3][4][5]
Metabolism	Mostly hepatic by CYP2C^[3]
Elimination half-life	1.6–59 h,^[3] 25–36 h (orally administered dronabinol)
Excretion	65–80% (feces) 20–35% (urine) as acid metabolites^[3]
Identifiers
IUPAC name (6aR,10aR)-6,6,9-Trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol
CAS Number	1972-08-3^Y
PubChem CID	16078
IUPHAR/BPS	2424
DrugBank	DB00470^Y
ChemSpider	15266^Y
UNII	7J8897W37S
KEGG	D00306^Y
ChEBI	CHEBI:66964^N
ChEMBL	ChEMBL465^Y
CompTox Dashboard (EPA)	DTXSID6021327
ECHA InfoCard	100.153.676
Chemical and physical data
Formula	C₂₁H₃₀O₂
Molar mass	314.469 g·mol⁻¹
3D model (JSmol)	Interactive image
Specific rotation	−152° (ethanol)
Boiling point	155–157 °C (311–315 °F) 0.05mmHg,^[6] 157–160°C @ 0.05mmHg^[7]
Solubility in water	0.0028 mg/mL (23 °C)^[8]
SMILES CCCCCc1cc(c2c(c1)OC([C@H]3[C@H]2C=C(CC3)C)(C)C)O
InChI InChI=1S/C21H30O2/c1-5-6-7-8-15-12-18(22)20-16-11-14(2)9-10-17(16)21(3,4)23-19(20)13-15/h11-13,16-17,22H,5-10H2,1-4H3/t16-,17-/m1/s1^Y Key:CYQFCXCEBYINGO-IAGOWNOFSA-N^Y
^NY (what is this?) (verify)

Overview

Primary Cannabinoid

Tetrahydrocannabinol (THC) is a prominent cannabinoid naturally occurring within the Cannabis plant. It is recognized as the principal psychoactive constituent of cannabis, and among the more than 113 identified cannabinoids, THC is the most widely recognized for its psychoactive properties.

Chemical Identity

While the chemical formula C₂₁H₃₀O₂ applies to multiple isomers, the term "THC" most commonly refers to the specific isomer known as delta-9-THC, chemically designated as (−)-trans-Δ⁹-tetrahydrocannabinol. In its pure form, THC presents as a colorless oil.

Pharmaceutical Applications

Under the pharmaceutical name dronabinol, THC is utilized medically. Its approved applications include the management of chemotherapy-induced nausea, HIV/AIDS-related anorexia, and specific symptoms associated with multiple sclerosis, such as neuropathic pain and spasticity.

Medical Applications

Approved Pharmaceutical Uses

In the United States, THC, under its pharmaceutical designation dronabinol, is approved in capsule and solution forms. Its primary indications are to alleviate chemotherapy-induced nausea and vomiting and to manage anorexia associated with HIV/AIDS.

Botanical Drug Formulations

THC is also a key component in nabiximols, a specific extract of the cannabis plant. Approved in the UK in 2010 as an oromucosal spray, nabiximols is indicated for patients with multiple sclerosis to help manage symptoms including neuropathic pain, spasticity, and bladder dysfunction. It is available by prescription in Canada and was approved for medical use in Ukraine in 2021.

Adverse Effects

Common Side Effects

The administration of THC can elicit a range of side effects. These commonly include red eyes, dry mouth, drowsiness, and impairments in short-term memory and concentration. Other reported effects include ataxia, increased appetite, and psychological effects such as anxiety and paranoia. In some instances, particularly with chronic use, cannabinoid hyperemesis syndrome (CHS), characterized by cyclical nausea and vomiting, may develop.

Overdose Considerations

Understanding Lethal Dose

The precise median lethal dose (LD50) of THC in humans remains subject to conflicting evidence and is not definitively established. While some studies in animal models have indicated toxicity at specific doses, reports regarding fatal overdoses in humans are rare or absent. The U.S. Drug Enforcement Administration, for instance, has noted that no deaths from marijuana overdose have been reported. However, caution is advised regarding potential interactions with other substances.

Drug Interactions

Limited Formal Studies

Formal, comprehensive drug-drug interaction studies involving THC are notably limited. However, available data suggests potential interactions. For example, the elimination half-life of the barbiturate pentobarbital has been observed to increase when administered concurrently with oral THC, indicating a possible pharmacokinetic interaction.

Pharmacological Profile

Mechanism of Action

THC exerts its effects primarily through partial agonism at the cannabinoid receptors, specifically CB₁ and CB₂. CB₁ receptors are predominantly located within the central nervous system, mediating most of THC's psychoactive effects. CB₂ receptors are mainly found in the immune system. Activation of these receptors influences intracellular signaling pathways, including the modulation of cyclic adenosine monophosphate (cAMP) levels. The discovery of these receptors in the brain led to the identification of endogenous cannabinoids, such as anandamide and 2-arachidonoyl glycerol (2-AG).

Antioxidant and Autotaxin Inhibition

THC, along with other cannabinoids possessing a phenol group, exhibits mild antioxidant properties, potentially offering neuroprotection against oxidative stress. Furthermore, emerging research suggests THC acts as a partial inhibitor of autotaxin (ATX), an enzyme crucial for generating lysophosphatidic acid (LPA), a lipid mediator implicated in various physiological and pathological processes, including inflammation and neurological functions. The clinical significance of this ATX inhibition by THC warrants further investigation through clinical trials.

Chemical Composition

Molecular Structure and Properties

THC is a complex molecule synthesized from polyketides and terpenoids. Its hydrophobic nature results in very low solubility in water but good solubility in many organic solvents. This lipophilicity influences its distribution and accumulation within the body, particularly in adipose tissue. Its presence in the cannabis plant is hypothesized to play a role in the plant's defense mechanisms against insect predation, UV radiation, and environmental stressors.

Synthesis and Preparation

The chemical synthesis of THC was first reported in 1965, involving specific reactions to form its fused ring structure and ether linkage. While naturally occurring, THC can also be produced via chemical synthesis or through biotechnological methods, such as in genetically modified yeast strains.

Biosynthesis Pathway

From Precursor to THC

Within the cannabis plant, THC is primarily synthesized via its precursor, tetrahydrocannabinolic acid (THCA). The process begins with the reaction of geranyl pyrophosphate and olivetolic acid, catalyzed by an enzyme, to form cannabigerolic acid. This intermediate is then cyclized by THC acid synthase to yield THCA. Subsequent decarboxylation, either through aging or heating, converts THCA into the active THC molecule. This biosynthetic pathway shares similarities with the production of humulone in hops.

Biosynthesis Diagram

Diagram illustrating the biochemical pathway leading to THC synthesis.

Historical Context

Key Discoveries

The isolation and identification of cannabinoids, including THC, have a significant history. Cannabidiol (CBD) was first isolated in 1940 by Roger Adams, who also documented the synthesis of THC isomers from CBD in 1942. THC itself was first isolated in 1964 by Raphael Mechoulam and Yehiel Gaoni, marking a pivotal moment in understanding cannabis chemistry.

Societal Impact

Culture, Law, and Economics

THC and cannabis are deeply intertwined with culture, influencing art, music, and social practices globally. The legal status of cannabis and THC varies significantly across jurisdictions, ranging from prohibition to regulated medical and recreational use. Economically, the cannabis industry encompasses cultivation, processing, retail, and related services, creating complex regulatory and market dynamics.

Research Findings

Multiple Sclerosis Symptoms

Research, including reviews by the American Academy of Neurology, indicates that cannabis extracts containing THC are effective for improving patients' subjective experience of spasticity and are possibly effective for objective measures of spasticity in multiple sclerosis. Similarly, these formulations are rated as effective for central pain and painful spasms. However, evidence for efficacy in treating bladder complaints associated with MS is considered insufficient.

Neurodegenerative Disorders

For neurodegenerative conditions like Huntington's disease, the available trial data is insufficient to draw reliable conclusions regarding the effectiveness of THC or cannabis extracts. Similarly, for Parkinson's disease, studies on oral CBD extract for levodopa-induced dyskinesia have yielded limited positive results. Research into THC's efficacy for Alzheimer's disease has also found insufficient evidence to date.

Other Neurological Conditions

The effectiveness of THC and cannabis extracts in managing tics associated with Tourette syndrome remains inconclusive due to insufficient data. Likewise, the efficacy of these treatments for cervical dystonia has not been reliably assessed due to limited available studies.

Regulatory Landscape

International and National Controls

THC and its isomers are subject to international control under the UN Convention on Psychotropic Substances. While initially placed in Schedule I, it was reclassified to Schedule II, with recommendations for further down-scheduling to Schedule III based on its medical utility. In the United States, cannabis remains a Schedule I controlled substance federally, despite varying state laws permitting medical use. However, pharmaceutical forms of THC, like dronabinol (Marinol, Syndros), have received FDA approval for specific medical indications.

Canadian Regulations

Following the legalization of recreational cannabis in Canada in October 2018, numerous health products containing THC extracts were approved for general health claims related to minor conditions. This regulatory framework allows for the sale of certain products with low concentrations of THC, subject to specific guidelines.

References

Source Citations

The information presented on this page is derived from a comprehensive review of scientific literature and regulatory documents. Detailed citations are provided below for further academic exploration.

^ Anvisa (2023-07-24). "RDC N° 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control" (in Brazilian Portuguese). Diário Oficial da União (published 2023-07-25). Archived from the original on 2023-08-27. Retrieved 2023-08-27.
^ "Marinol" (PDF). Food and Drug Administration. Archived from the original (PDF) on 2014-05-13. Retrieved 2014-03-14.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o Grotenhermen F (2003). "Pharmacokinetics and pharmacodynamics of cannabinoids". Clinical Pharmacokinetics. 42 (4): 327–60. doi:10.2165/00003088-200342040-00003. PMID 12648025. S2CID 25623600.
^ The Royal Pharmaceutical Society of Great Britain (2006). "Cannabis". In Sweetman SC (ed.). Martindale: The Complete Drug Reference: Single User (35th ed.). Pharmaceutical Press. ISBN 978-0-85369-703-9.^{[page needed]}
^ Garrett ER, Hunt CA (July 1974). "Physiochemical properties, solubility, and protein binding of delta9-tetrahydrocannabinol". Journal of Pharmaceutical Sciences. 63 (7): 1056–64. Bibcode:1974JPhmS..63.1056G. doi:10.1002/jps.2600630705. PMID 4853640. Dronabinol has a large apparent volume of distribution, approximately 10 L/kg, because of its lipid solubility. The plasma protein binding of dronabinol and its metabolites is approximately 97%.
^ Gaoni Y, Mechoulam R (April 1964). "Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish". Journal of the American Chemical Society. 86 (8): 1646–47. Bibcode:1964JAChS..86.1646G. doi:10.1021/ja01062a046.
^ Adams R, Cain CK, McPhee WD, Wearn RB (August 1941). "Structure of Cannabidiol. XII. Isomerization to Tetrahydrocannabinols". Journal of the American Chemical Society. 63 (8): 2209–13. Bibcode:1941JAChS..63.2209A. doi:10.1021/ja01853a052.
^ ^a ^b Garrett ER, Hunt CA (July 1974). "Physiochemical properties, solubility, and protein binding of delta9-tetrahydrocannabinol". Journal of Pharmaceutical Sciences. 63 (7): 1056–64. Bibcode:1974JPhmS..63.1056G. doi:10.1002/jps.2600630705. PMID 4853640.
^ Pichersky E, Raguso RA (November 2018). "Why do plants produce so many terpenoid compounds?". The New Phytologist. 220 (3): 692–702. Bibcode:2018NewPh.220..692P. doi:10.1111/nph.14178. hdl:2027.42/146372. PMID 27604856.
^ Shulgin A (1995). "THC Chemistry". www.druglibrary.org. Archived from the original on 2020-11-12. Retrieved 2020-11-12.
^ "Marinol (Dronabinol)" (PDF). U.S. Food and Drug Administration. September 2004. Archived from the original (PDF) on February 10, 2017.
^ "Sativex Oromucosal Spray – Summary of Product Characteristics". UK Electronic Medicines Compendium. March 2015. Archived from the original on 2016-08-22. Retrieved 2017-06-01.
^ Multiple Sclerosis Trust. October 2014 Sativex (nabiximols) – factsheet Archived 2015-09-20 at the Wayback Machine
^ ^a ^b "Health products containing cannabis or for use with cannabis: Guidance for the Cannabis Act, the Food and Drugs Act, and related regulations". Government of Canada. 11 July 2018. Archived from the original on 19 October 2018. Retrieved 19 October 2018.
^ "В Україні легалізували використання медичного канабісу, але не всього" [In Ukraine, some medical cannabis has been legalized, but not all]. УП.Життя (UP.Life) (in Ukrainian). 9 April 2021. Archived from the original on 9 April 2021. Retrieved 10 April 2021.
^ ^a ^b Ng T, Keshock MC (2024). "Tetrahydrocannabinol (THC)". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 33085321. Retrieved 2024-08-20.
^ Lucas CJ, Galettis P, Schneider J (November 2018). "The pharmacokinetics and the pharmacodynamics of cannabinoids". Br J Clin Pharmacol. 84 (11): 2477–2482. doi:10.1111/bcp.13710. PMC 6177698. PMID 30001569.
^ Thompson GR, Rosenkrantz H, Schaeppi UH, Braude MC (July 1973). "Comparison of acute oral toxicity of cannabinoids in rats, dogs and monkeys". Toxicology and Applied Pharmacology. 25 (3): 363–72. Bibcode:1973ToxAP..25..363T. doi:10.1016/0041-008X(73)90310-4. PMID 4199474. In dogs and monkeys, single oral doses of Δ9-THC and Δ8-THC between 3000 and 9000/mg/kg were nonlethal.
^ Hartung B, Kauferstein S, Ritz-Timme S, Daldrup T (April 2014). "Sudden unexpected death under acute influence of cannabis". Forensic Science International. 237: e11 – e13. doi:10.1016/j.forsciint.2014.02.001. PMID 24598271.
^ Nahas GC (1 January 1972). "UNODC - Bulletin on Narcotics - 1972 Issue 2 - 002". United Nations: Office on Drugs and Crime: 11–27. Archived from the original on 2022-12-11. Retrieved 2022-12-11.
^ "Drug Fact Sheet: Marijuana/Cannabis" (PDF). Drug Enforcement Administration. United States Department of Justice. April 2020. Retrieved 9 February 2025.
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Overview 🔬

🌿 Primary Cannabinoid

🧪 Chemical Identity

⚕️ Pharmaceutical Applications

Medical Applications ⚕️

💊 Approved Pharmaceutical Uses

🌿 Botanical Drug Formulations

Adverse Effects ⚠️

😵 Common Side Effects

Overdose Considerations ⚖️

❓ Understanding Lethal Dose

Drug Interactions ↔️

⚠️ Limited Formal Studies

Pharmacological Profile 🧠

🎯 Mechanism of Action

🛡️ Antioxidant and Autotaxin Inhibition

Chemical Composition ⚗️

⚛️ Molecular Structure and Properties

💡 Synthesis and Preparation

Biosynthesis Pathway 🌱

➡️ From Precursor to THC

📊 Biosynthesis Diagram

Historical Context 🕰️

📜 Key Discoveries

Societal Impact 👥

🌐 Culture, Law, and Economics

Research Findings 📈

🔬 Multiple Sclerosis Symptoms

🧠 Neurodegenerative Disorders

❓ Other Neurological Conditions

Regulatory Landscape ⚖️

📜 International and National Controls

🇨🇦 Canadian Regulations

References 📚

🔗 Source Citations

Teacher's Corner 🧑‍🏫

Edit and Print this course in the Wiki2Web Teacher Studio

True or False? 🤔

❓ Test Your Knowledge! ❓

Gamer's Corner 🎮

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References

📜 References

Feedback & Support 👍

To report an issue with this page, or to find out ways to support the mission, please click here.

Disclaimer ⚠️

📜 Important Notice

Overview

Primary Cannabinoid

Chemical Identity

Pharmaceutical Applications

Medical Applications

Approved Pharmaceutical Uses

Botanical Drug Formulations

Adverse Effects

Common Side Effects

Overdose Considerations

Understanding Lethal Dose

Drug Interactions

Limited Formal Studies

Pharmacological Profile

Mechanism of Action

Antioxidant and Autotaxin Inhibition

Chemical Composition

Molecular Structure and Properties

Synthesis and Preparation

Biosynthesis Pathway

From Precursor to THC

Biosynthesis Diagram

Historical Context

Key Discoveries

Societal Impact

Culture, Law, and Economics

Research Findings

Multiple Sclerosis Symptoms

Neurodegenerative Disorders

Other Neurological Conditions

Regulatory Landscape

International and National Controls

Canadian Regulations

References

Source Citations

Teacher's Corner

True or False?

Test Your Knowledge!

Gamer's Corner

Discover other topics to study!

References

Feedback & Support

Disclaimer

Important Notice