Description
Tetrahydrocannabinol (THC) is the main active compound in marijuana. It comes from the
plant Cannabis sativa (cannabis), which is a dioecious (monoecious varieties do exist) annual
herb naturally found in many tropic and temperate regions of the world. Many varieties of
cannabis exist, and two related species (Cannabis indica and Cannabis ruderalia) are main
sources of THC. Cannabis sativa is also known as hemp, although this name is not unique to
the species; its stem is a source of fiber that has been used throughout history for hundreds
of applications including rope, twine, paper, and cloth. Hemp seeds are edible and high in
protein. The seeds are also a source of fatty oil that can be used for food, cosmetics, medicines,
and as a fuel source. Cannabis contains chemicals called cannabinoids; of the 60 cannabinoids
found in Cannabis, one is THC, , which is the psychoactive ingredient in marijuana.
Marijuana is produced from the leaves and fl owers of cannabis, and hashish is a resin collected
from the female fl owers. The THC content, which determines the effect of cannabis drugs,
varies with plant structure, variety, and preparation. Buds and fl owers specifically cultivated
for drug use have greater THC content than leaves. THC content may vary from a few tenths
of a percent to more than 10%, but good quality marijuana has a THC content of approximately
10%, and good hashish and hashish oils generally have THC contents between 30%
and 80%.
Chemical Properties
Thick Brown Oil
History
THC was first isolated from hashish in 1964 by Raphael Mechoulam (1930–) and Yehiel
Gaoni at the Weizmann Institute. In the
early 1990s, the specific brain receptors affected by THC were identified. These receptors
are activated by a cannabinoid neurotransmitter called arachidonylethanolamide, known as
anandamide. Anandamide was named by Mechoulam using ananda, which is the Sanskrit
word for ecstasy. Anandamide is thought to be associated with memory, pain, depression, and
appetite. THC is able to attach to and activate anandamide receptors. These receptors are actually
called THC receptors rather than anandamide receptors because researchers discovered
that THC attaches to these receptors before anandamide was discovered. The areas of the brain
with the most THC receptors are the cerebellum, the cerebral cortex, and the limbic system.
This is why marijuana affects thinking, memory, sensory perception, and coordination.
Uses
Medical marijuana remains a controversial topic, but synthetic THC, dronabinol, marketedunder the trade name Marinol, has been available by prescription since 1986. Th edronabinol analog nabilone is another THC prescription drug marketed under the nameCesamet. Marinol and Cesamet, taken as capsules, have Food Drug Administration approvalas an antinausea agent and appetite stimulant (for AIDS patients), but they are also prescribedfor depression and muscle spasms. In 2005, Canada was the first country to approve Sativex,a cannabis spray that relieves pain in people with multiple sclerosis.
Uses
Δ9-Tetrahydrocannabinol (Δ9-THC) is a natural psychoactive compound found in plants of the genus Cannabis. This cannabinoid (CB) binds with high affinity to both the central CB1 receptor (Ki = 41 nM) and the peripheral CB2 receptor (Ki = 36 nM). Δ9-THC, working primarily through these receptors, has diverse effects on perception, cognition, pain sensitivity, body temperature, the immune system, fetal development, and more. This product is intended for forensic and research purposes.[Cayman Chemical]
Uses
It is the principal active constituent of cannabis. Agonist at CB1 and CB2 cannabinoid receptors. Antiemetic; appetite stimulant. Controlled substance (hallucinogen).
Definition
ChEBI: A diterpenoid that is 6a,7,8,10a-tetrahydro-6H-benzo[c]chromene substituted at position 1 by a hydroxy group, positions 6, 6 and 9 by methyl groups and at position 3 by a pentyl group. The principal psychoactive constituent
f the cannabis plant, it is used for treatment of anorexia associated with AIDS as well as nausea and vomiting associated with cancer chemotherapy.
Manufacturing Process
δ-9-Tetrahydrocannabinol (THC, also known as dronabinol) is the main
biologically active component in the Cannabis plant extracted from the resin of
Cannabis sativa (marihuana, hashish).
One kg of the fine powdered marijuana plant material [average % of THC was
about 5.21%] was macerated with 6 L hexanes (Hexanes GR from EM
Sciences) in a percolator (9" in diameter from the top and 20" long, cone
shaped) for 24 hours at room temperature and filtered. The macerate was
reextracted with 5 L hexanes for another 24 hours. The hexane extracts were
combined and evaporated under reduced pressure at low temperature to give
110.7 g residue (11.07% extractives). The % of THC in the hexane extract
was 41.21%.
Column Chromatography.
The hexane extract (110.7 g) was mixed with 150 g silica gel (silica gel 60,
Art.# 9385-3) and 50 ml hexane. The air dried slurry was transferred to the
top of a silica gel column (800 g silica gel 60, particle size 0.04-0.063 mm,
from EM Science, Art.# 9385-3). The column was eluted with hexane:ether
mixtures in a manner of increasing polarities. Fractions were collected and TLC
screened (analytical silica gel plates, developing system: Hexane:Ether
(80:20), Visualizing agent: Fast blue). The fractions collected with hexane (3
L) and hexane-ether (95:5, 2 L) were discarded. The following fractions
collected with hexane-ether (95:5, 3 L) and hexane-ether (9:1, 5 L) were
combined and evaporated to yield 77.2 g of residue. GC analysis of the
residue showed THC concentration to be 54.74%.
Fractional Distillation
A portion (30.5 g) of the residue collected above was subjected to fractional
distillation under reduced pressure (0.1-0.15 mm/Hg). The temperature was
slowly raised to 125°C and the materials collected were kept separate. The
temperature was then raised between 140°-160°C where the major fraction
was collected (14 g). GC analysis showed >96% THC. Further purification on
a silica gel column gives THC with at least 98% purity. An improvement of this
process includes the use of high pressure liquid chromatography (HPLC). The
preparation of dronabinol and related compounds have employed acidcatalyzed electrophilic condensation of a 5-alkylresorcinol such as 5-npentylresorcinol (commonly known as olivetol) and a menthadienol, followed
by cyclization; yield of desired product is about 17-22% (Petrzilka et al., Helv.
Chim. Acta, 52, 1102 (1969)).
brand name
Marinol (Unimed).
Therapeutic Function
Appetite stimulant
General Description
Brown amorphous semi-solid, viscous oil or chunky golden yellow solid.
Air & Water Reactions
Slightly soluble in water.
Reactivity Profile
DELTA9-TETRAHYDROCANNABINOLis very unstable to light and high temperatures. DELTA9-TETRAHYDROCANNABINOL should be protected from air during all handling due to its extreme instability. . Flammable and/or toxic gases are generated by the combination of alcohols with alkali metals, nitrides, and strong reducing agents. They react with oxoacids and carboxylic acids to form esters plus water. Oxidizing agents convert them to aldehydes or ketones. Alcohols exhibit both weak acid and weak base behavior. They may initiate the polymerization of isocyanates and epoxides.
Fire Hazard
Flash point data for DELTA9-TETRAHYDROCANNABINOL are not available; however, DELTA9-TETRAHYDROCANNABINOL is probably combustible.
Biological Activity
Cannabinoid receptor agonist (K i values are 5.05 and 3.13 nM for CB 1 and CB 2 receptors respectively; EC 50 values are 6, 0.4 and 8 nM at CB 1 , CB 2 and GPR55 receptors respectively). Major psychoactive constituent of marijuana.
Clinical Use
Dronabinol (synthetic △9-THC) i s a n antinauseant approved for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetics. A related cannabinoid, nabilone, was introduced in Canada for his indication in 1982.
Safety Profile
Poison by intraperitoneal and intravenous routes. Moderately toxic by ingestion. Experimental reproductive effects. Questionable carcinogen with experimental tumorigenic and teratogenic data. Human mutation data reported. A hallucinatory drug. When heated to decomposition it emits acrid smoke and irritating fumes. See also CANNABIS.
References
[1] JOHN W. HUFFMAN . 1-Alkyl-2-aryl-4-(1-naphthoyl)pyrroles: New high affinity ligands for the cannabinoid CB1 and CB2 receptors[J]. Bioorganic & Medicinal Chemistry Letters, 2006, 16 20: Pages 5432-5435. DOI:
10.1016/j.bmcl.2006.07.051[2] PERTWEE R. Pharmacology of Cannabinoid Receptor Ligands[J]. Current medicinal chemistry, 1999, 1 1. DOI:
10.2174/0929867306666220401124036[3] GROTENHERMEN F. Pharmacokinetics and pharmacodynamics of cannabinoids.[J]. Clinical Pharmacokinetics, 2003, 42 4: 327-360. DOI:
10.2165/00003088-200342040-00003[4] LIESL K. JANSSENS. Investigation of the intrinsic cannabinoid activity of hemp-derived and semisynthetic cannabinoids with β-arrestin2 recruitment assays—and how this matters for the harm potential of seized drugs[J]. Archives of Toxicology, 2024, 98 8: 2619-2630. DOI:
10.1007/s00204-024-03769-4[5] HANNAH C. HUFF. Differential Interactions of Selected Phytocannabinoids with Human CYP2D6 Polymorphisms[J]. Biochemistry Biochemistry, 2021, 60 37: 2749-2760. DOI:
10.1021/acs.biochem.1c00158[6] ELIZABETH A CAIRNS. The In Vivo Effects of the CB1-Positive Allosteric Modulator GAT229 on Intraocular Pressure in Ocular Normotensive and Hypertensive Mice.[J]. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2017: 582-590. DOI:
10.1089/jop.2017.0037[7] JOHN MERRICK. Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid.[J]. Cannabis and Cannabinoid Research, 2016, 1 1: 102-112. DOI:
10.1089/can.2015.0004
