Tetrahydrocannabinol (THC) is a cannabinoid found in cannabis. It is the principal psychoactive constituent of '' Cannabis'' and one of at least 113 total cannabinoids identified on the plant. Although the

chemical formula A chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, such as pare ...

for THC (C₂₁H₃₀O₂) describes multiple

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

s, the term ''THC'' usually refers to the delta-9-THC isomer with chemical name (−)-''trans''-Δ⁹-tetrahydrocannabinol. It is a colorless oil.

Medical uses

THC, referred to as dronabinol in the pharmaceutical context, is approved in the United States as a capsule or solution to relieve chemotherapy-induced nausea and vomiting and

HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

-induced anorexia. THC is an active ingredient in nabiximols, a specific extract of '' Cannabis'' that was approved as a botanical drug in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

in 2010 as a mouth spray for people with

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

to alleviate neuropathic pain,

spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...

, overactive bladder, and other symptoms. Nabiximols (as Sativex) is available as a prescription drug in Canada. In 2021, nabiximols was approved for medical use in

Ukraine Ukraine is a country in Eastern Europe. It is the List of European countries by area, second-largest country in Europe after Russia, which Russia–Ukraine border, borders it to the east and northeast. Ukraine also borders Belarus to the nor ...

Side effects

Side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of THC include red eyes, dry mouth, drowsiness,

short-term memory Short-term memory (or "primary" or "active memory") is the capacity for holding a small amount of information in an active, readily available state for a short interval. For example, short-term memory holds a phone number that has just been recit ...

impairment, difficulty concentrating,

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

, increased appetite,

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

, paranoia,

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

(i.e., hallucinations,

delusions A delusion is a fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or some other m ...

), decreased motivation, and time dilation, among others. Chronic usage of THC may result in cannabinoid hyperemesis syndrome (CHS), a condition characterized by cyclic nausea, vomiting, and abdominal pain that may persist for months to years after discontinuation.

Overdose

The median lethal dose of THC in humans is not fully known as there is conflicting evidence. A 1972 study gave up to 90 mg/kg of THC to dogs and monkeys without any lethal effects. Some rats died within 72 hours after a dose of up to 36 mg/kg. A 2014 case study based on the toxicology reports and relative testimony in two separate cases gave the median lethal dose in humans at 30 mg/kg (2.1 grams THC for a person who weighs 70 kg; 154 lb; 11 stone), observing cardiovascular death in the one otherwise healthy subject of the two cases studied. A different 1972 study gave the median lethal dose for intravenous THC in mice and rats at 30–40 mg/kg. A 2020 fact sheet published by the U.S.

Drug Enforcement Administration The Drug Enforcement Administration (DEA) is a Federal law enforcement in the United States, United States federal law enforcement agency under the U.S. Department of Justice tasked with combating illicit Illegal drug trade, drug trafficking a ...

stated that " deaths from overdose of marijuana have been reported."

Interactions

Formal drug–drug interaction studies with THC have not been conducted and are limited. The elimination half-life of the barbiturate pentobarbital has been found to increase by 4hours when concomitantly administered with oral THC.

Pharmacology

Mechanism of action

The actions of Δ⁹-THC result from its

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

activity at the cannabinoid receptor CB₁ (K_i = 40.7 nM), located mainly in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

, and the CB₂ receptor (K_i = 36 nM), mainly expressed in cells of the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

. The psychoactive effects of THC are primarily mediated by the activation of (mostly G-coupled) cannabinoid receptors, which result in a decrease in the concentration of the second messenger molecule cAMP through inhibition of adenylate cyclase. The presence of these specialized cannabinoid receptors in the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

led researchers to the discovery of endocannabinoids, such as anandamide and 2-arachidonoyl glyceride ( 2-AG). THC is a lipophilic molecule and may bind non-specifically to a variety of entities in the brain and body, such as adipose tissue (fat). THC, as well as other cannabinoids that contain a phenol group, possess mild antioxidant activity sufficient to protect neurons against oxidative stress, such as that produced by

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

-induced excitotoxicity. THC targets receptors in a manner far less selective than endocannabinoid molecules released during retrograde signaling, as the drug has a relatively low cannabinoid receptor affinity. THC is also limited in its efficacy compared to other cannabinoids due to its partial agonistic activity, as THC appears to result in greater

downregulation In biochemistry, in the biology, biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell (biology), cell decreases the production and quantities of its cellular ...

of cannabinoid receptors than endocannabinoids. Furthermore, in populations of low cannabinoid receptor density, THC may even act to antagonize endogenous agonists that possess greater receptor efficacy. However while THC's pharmacodynamic tolerance may limit the maximal effects of certain drugs, evidence suggests that this tolerance mitigates undesirable effects, thus enhancing the drug's therapeutic window. Recently, it has been shown that THC is also a partial autotaxin inhibitor, with an apparent IC50 of 407 ± 67 nM for the ATX-gamma isoform. THC was also co-crystallized with autotaxin, deciphering the binding interface of the complex. These results might explain some of the effects of THC on inflammation and neurological diseases, since autotaxin is responsible of LPA generation, a key lipid mediator involved in numerous diseases and physiological processes. However, clinical trials need to be performed in order to assess the importance of ATX inhibition by THC during medicinal cannabis consumption.

Pharmacokinetics

Absorption

With oral administration of a single dose, THC is almost completely absorbed by the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

. However, due to first-pass metabolism in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

and the high lipid solubility of THC, only about 5 to 20% reaches circulation. Following oral administration, concentrations of THC and its major active metabolite 11-hydroxy-THC (11-OH-THC) peak after 0.5 to 4hours, with median time to peak of 1.0 to 2.5hours at different doses. In some cases, peak levels may not occur for as long as 6hours. Concentrations of THC and 11-hydroxy-THC in the circulation are approximately equal with oral administration. There is a slight increase in dose proportionality in terms of peak and area-under-the-curve levels of THC with increasing oral doses over a range of 2.5 to 10mg. A high-fat meal delays time to peak concentrations of oral THC by 4hours on average and increases area-under-the-curve exposure by 2.9-fold, but peak concentrations are not significantly altered. A high-fat meal additionally increases absorption of THC via the

lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...

and allows it to bypass first-pass metabolism. Consequently, a high-fat meal increases levels of 11-hydroxy-THC by only 25% and most of the increase in bioavailability is due to increased levels of THC. The bioavailability of THC when

smoking Smoking is a practice in which a substance is combusted, and the resulting smoke is typically inhaled to be tasted and absorbed into the bloodstream of a person. Most commonly, the substance used is the dried leaves of the tobacco plant, whi ...

or inhaling is approximately 25%, with a range of 2% to 56% (although most commonly between 10 and 35%). The large range and marked variability between individuals is due to variation in factors including product matrix, ignition temperature, and inhalational dynamics (e.g., number, duration, and intervals of inhalations, breath hold time, depth and volume of inhalations, size of inhaled particles, deposition site in the lungs). THC is detectable within seconds with inhalation and peak levels of THC occur after 3 to 10minutes. Smoking or inhaling THC results in greater blood levels of THC and its metabolites and a much faster onset of action than oral administration of THC. Inhalation of THC bypasses the first-pass metabolism that occurs with oral administration. The bioavailability of THC with inhalation is increased in heavy users. Transdermal administration of THC is limited by its extreme water insolubility. Efficient skin transport can only be obtained with permeation enhancement. Transdermal administration of THC, as with inhalation, avoids the first-pass metabolism that occurs with oral administration.

Distribution

The volume of distribution of THC is large and is approximately 10L/kg (range 4–14L/kg), which is due to its high lipid solubility. The plasma protein binding of THC and its metabolites is approximately 95 to 99%, with THC bound mainly to lipoproteins and to a lesser extent albumin. THC is rapidly distributed into well-vascularized organs such as

lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

, and

, and is subsequently equilibrated into less vascularized tissue. It is extensively distributed into and sequestered by fat tissue due to its high lipid solubility, from which it is slowly released. THC is able to cross the placenta and is excreted in human breast milk.

Metabolism

The

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

of THC occurs mainly in the

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s CYP2C9, CYP2C19, and

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

. CYP2C9 and CYP3A4 are the primary enzymes involving in metabolizing THC. Pharmacogenomic research has found that oral THC exposure is 2- to 3-fold greater in people with genetic variants associated with reduced CYP2C9 function. When taken orally, THC undergoes extensive first-pass metabolism in the liver, primarily via hydroxylation. The principal active metabolite of THC is 11-hydroxy-THC (11-OH-THC), which is formed by CYP2C9 and is psychoactive similarly to THC. This metabolite is further oxidized to 11-nor-9-carboxy-THC (THC-COOH). In animals, more than 100 metabolites of THC could be identified, but 11-OH-THC and THC-COOH are the predominant metabolites.

Elimination

More than 55% of THC is excreted in the

feces Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...

and approximately 20% in the

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

. The main metabolite in urine is the ester of glucuronic acid and 11-OH-THC and free THC-COOH. In the feces, mainly 11-OH-THC was detected. Estimates of the elimination half-life of THC are variable. THC was reported to have a fast initial half-life of 6minutes and a long terminal half-life of 22hours in a population pharmacokinetic study. Conversely, the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

label for dronabinol reports an initial half-life of 4hours and a terminal half-life of 25 to 36hours. Many studies report an elimination half-life of THC in the range of 20 to 30hours. 11-Hydroxy-THC appears to have a similar terminal half-life to that of THC, for instance 12 to 36hours relative to 25 to 36hours in one study. The elimination half-life of THC is longer in heavy users. This may be due to slow redistribution from deep compartments such as fatty tissues, where THC accumulates with regular use.

List of related compounds

Chemistry

THC is a molecule that combines polyketides (derived from acetyl CoA) and terpenoids (derived from isoprenylpyrophosphate). It is hydrophobic with very low

solubility In chemistry, solubility is the ability of a chemical substance, substance, the solute, to form a solution (chemistry), solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form su ...

in water, but good solubility in many organic solvents. As a phytochemical, THC is assumed to be involved in the plant's evolutionary

adaptation In biology, adaptation has three related meanings. Firstly, it is the dynamic evolutionary process of natural selection that fits organisms to their environment, enhancing their evolutionary fitness. Secondly, it is a state reached by the p ...

against insect predation, ultraviolet light, and environmental stress. The preparation of THC was reported in 1965. that procedure called for the intramolecular alkyl lithium attack on a starting carbonyl to form the fused rings, and a tosyl chloride mediated formation of the ether.

Biosynthesis

In the '' Cannabis'' plant, THC occurs mainly as tetrahydrocannabinolic acid (THCA, 2-COOH-THC). Geranyl pyrophosphate and olivetolic acid react, catalysed by an

to produce cannabigerolic acid, which is cyclized by the enzyme THC acid synthase to give THCA. Over time, or when heated, THCA is decarboxylated, producing THC. The pathway for THCA

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

is similar to that which produces the bitter acid humulone in

hops Hops are the flowers (also called seed cones or strobiles) of the hop plant ''Humulus lupulus'', a member of the Cannabaceae family of flowering plants. They are used primarily as a bittering, flavouring, and stability agent in beer, to whic ...

. It can also be produced in genetically modified yeast. : THC biosynthesis labeled

History

Cannabidiol Cannabidiol (CBD) is a phytocannabinoid, one of 113 identified cannabinoids in ''Cannabis'', along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. Medically, it is an anticonvulsant used to treat multiple f ...

was isolated and identified from ''Cannabis sativa'' in 1940 by Roger Adams who was also the first to document the synthesis of THC (both Delta-9-THC and Delta-8-THC) from the acid-based cyclization of CBD in 1942. THC was first isolated from Cannabis by Raphael Mechoulam and Yehiel Gaoni in 1964.

Society and culture

Comparisons with medical cannabis

Female cannabis plants contain at least 113 cannabinoids, including

cannabidiol Cannabidiol (CBD) is a phytocannabinoid, one of 113 identified cannabinoids in ''Cannabis'', along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. Medically, it is an anticonvulsant used to treat multiple f ...

(CBD), thought to be the major anticonvulsant that helps people with

, and cannabichromene (CBC), an anti-inflammatory which may contribute to the pain-killing effect of cannabis.

Drug testing

THC and its 11-OH-THC and THC-COOH metabolites can be detected and quantified in blood, urine, hair, oral fluid or sweat using a combination of immunoassay and chromatographic techniques as part of a drug use testing program or in a forensic investigation. There is ongoing research to create devices capable of detecting THC in breath.

Regulation

THC, along with its double bond isomers and their stereoisomers, is one of only three cannabinoids scheduled by the UN Convention on Psychotropic Substances (the other two are dimethylheptylpyran and parahexyl). It was listed under Schedule I in 1971, but reclassified to Schedule II in 1991 following a recommendation from the WHO. Based on subsequent studies, the WHO has recommended the reclassification to the less-stringent Schedule III. Cannabis as a plant is scheduled by the Single Convention on Narcotic Drugs (Schedule I and IV). It is specifically still listed under Schedule I by US federal law under the Controlled Substances Act for having "no accepted medical use" and "lack of accepted safety". However, dronabinol, a pharmaceutical form of THC, has been approved by the FDA as an appetite stimulant for people with AIDS and an antiemetic for people receiving

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

under the trade names Marinol and Syndros. In 2003, the

World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

Expert Committee on Drug Dependence recommended transferring THC to Schedule IV of the convention, citing its medical uses and low abuse and addiction potential. In 2019, the Committee recommended transferring Δ⁹-THC to Schedule I of the Single Convention on Narcotic Drugs of 1961, but its recommendations were rejected by the United Nations Commission on Narcotic Drugs.

In the United States

As of 2023, 38 states, four territories, and the

District of Columbia Washington, D.C., formally the District of Columbia and commonly known as Washington or D.C., is the capital city and Federal district of the United States, federal district of the United States. The city is on the Potomac River, across from ...

allow medical use of cannabis (in which THC is the primary psychoactive component), with the exception of Georgia, Idaho, Indiana, Iowa, Kansas, Nebraska, North Carolina, South Carolina, Tennessee, Texas, Wisconsin, and Wyoming. As of 2022, the federal government maintains cannabis as a schedule I controlled substance, while dronabinol is classified as Schedule III in capsule form (Marinol) and Schedule II in liquid oral form (Syndros).

In Canada

As of October 2018 when recreational use of cannabis was legalized in Canada, some 220

dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...

s and 19 veterinary health products containing not more than 10 parts per million of THC extract were approved with general health claims for treating minor conditions.

Research

The status of THC as an illegal drug in most countries imposes restrictions on research material supply and funding, such as in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

where the National Institute on Drug Abuse and

continue to control the sole federally-legal source of cannabis for researchers. Despite an August 2016 announcement that licenses would be provided to growers for supplies of medical marijuana, no such licenses were ever issued, despite dozens of applications. Although cannabis is legalized for medical uses in more than half of the states of the United States, no products have been approved for federal commerce by the Food and Drug Administration, a status that limits cultivation, manufacture, distribution, clinical research, and therapeutic applications. In April 2014, the American Academy of Neurology found evidence supporting the effectiveness of the cannabis extracts in treating certain symptoms of

and pain, but there was insufficient evidence to determine effectiveness for treating several other neurological diseases. A 2015 review confirmed that medical marijuana was effective for treating spasticity and chronic pain, but caused numerous short-lasting adverse events, such as dizziness.

Multiple sclerosis symptoms

* ''

Spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...

''. Based on the results of three high-quality trials and five of lower quality, oral cannabis extract was rated as effective, and THC as probably effective, for improving people's subjective experience of spasticity. Oral cannabis extract and THC both were rated as possibly effective for improving objective measures of spasticity. * ''Centrally mediated pain and painful spasms''. Based on the results of four high-quality trials and four low-quality trials, oral cannabis extract was rated as effective, and THC as probably effective in treating central pain and painful spasms. * ''Bladder dysfunction''. Based on a single high quality study, oral cannabis extract and THC were rated as probably ineffective for controlling bladder complaints in multiple sclerosis

Neurodegenerative disorders

* ''Huntington disease''. No reliable conclusion could be drawn regarding the effectiveness of THC or oral cannabis extract in treating the symptoms of Huntington disease as the available trials were too small to reliably detect any difference * ''Parkinson's disease''. Based on a single study, oral CBD extract was rated probably ineffective in treating levodopa-induced dyskinesia in Parkinson's disease. * ''Alzheimer's disease''. A 2009 Cochrane Review found insufficient evidence to conclude whether cannabis products have any utility in the treatment of Alzheimer's disease.

Other neurological disorders

* '' Tourette syndrome''. The available data was determined to be insufficient to allow reliable conclusions to be drawn regarding the effectiveness of oral cannabis extract or THC in controlling tics. * '' Cervical dystonia''. Insufficient data was available to assess the effectiveness of oral cannabis extract of THC in treating cervical dystonia.

Potential for toxicity

Preliminary research indicates that prolonged exposure to high doses of THC may interfere with chromosomal stability, which may be hereditary as a factor affecting cell instability and cancer risk. The carcinogenicity of THC in the studied populations of so-called "heavy users" remains dubious due to various confounding variables, most significantly concurrent tobacco use.

References

External links

U.S. National Library of Medicine: Drug Information Portal – Tetrahydrocannabinol
{{Navboxes , title = Pharmacodynamics , titlestyle = background:#ccccff , list1 = {{Acetylcholine metabolism and transport modulators {{Cannabinoid receptor modulators {{Glycine receptor modulators {{Opioid receptor modulators {{Transient receptor potential channel modulators {{Xenobiotic-sensing receptor modulators Acetylcholinesterase inhibitors Amorphous solids Antiemetics Appetite stimulants Aromatase inhibitors Benzochromenes CB1 receptor agonists CB2 receptor agonists Entheogens Euphoriants Glycine receptor agonists Natural phenols metabolism Cannabis Phytocannabinoids Terpeno-phenolic compounds Transient receptor potential channel modulators Opioid receptor negative allosteric modulators