Cannabinoids

Cannabinoids (pron-en|kəˈnæbɨˌnɔɪdz [cite book |title=The American Heritage Dictionary |year=2000 |publisher=Houghton Mifflin |edition=4th ed. |isbn=0395825172] ) are a group of terpenophenolic compounds present in Cannabis ("Cannabis sativa" L). The broader definition of cannabinoids refer to a group of substances that are structurally related to tetrahydrocannabinol (THC) or that bind to cannabinoid receptors. The chemical definition encompasses a variety of distinct chemical classes: the classical cannabinoids structurally related to THC, the nonclassical cannabinoids, the aminoalkylindoles, the eicosanoids related to the endocannabinoids, 1,5-diarylpyrazoles, quinolines and arylsulphonamides and additional compounds that do not fall into these standard classes but bind to cannabinoid receptors. [cite journal |author=Lambert DM, Fowler CJ |title=The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications |journal=J. Med. Chem. |volume=48 |issue=16 |pages=5059–87 |year=2005 |pmid=16078824 |doi=10.1021/jm058183t |url=http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/jm058183t] The term cannabinoids also refers to a unique group of secondary metabolites found in the cannabis plant, which are responsible for the plant's peculiar pharmacological effects. Currently, there are three general types of cannabinoids: "phytocannabinoids" occur uniquely in the cannabis plant; "endogenous cannabinoids" are produced in the bodies of humans and other animals; and "synthetic cannabinoids" are similar compounds produced in a laboratory.

Cannabinoid receptors

Before the 1980s, it was often speculated that cannabinoids produced their physiological and behavioral effects via nonspecific interaction with cell membranes, instead of interacting with specific membrane-bound receptors. The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common in animals, and have been found in mammals, birds, fish, and reptiles. There are currently two known types of cannabinoid receptors, termed CB1 and CB2.

* CB1 receptors are found primarily in the brain, specifically in the basal ganglia and in the limbic system, including the hippocampus. They are also found in the cerebellum and in both male and female reproductive systems. CB1 receptors are essentially absent in the medulla oblongata, the part of the brain stem that is responsible for respiratory and cardiovascular functions. Thus, there is not a risk of respiratory or cardiovascular failure as there is with many other drugs. CB1 receptors appear to be responsible for the euphoric and anticonvulsive effects of cannabis.

* CB2 receptors are almost exclusively found in the immune system, with the greatest density in the spleen. While generally found only in the peripheral nervous system, a report does indicate that CB2 is expressed by a subpopulation of microglia in the human cerebellum cite journal |author=Núñez E, Benito C, Pazos MR, "et al" |title=Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study |journal=Synapse |volume=53 |issue=4 |pages=208–13 |year=2004 |pmid=15266552 |doi=10.1002/syn.20050] . CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis.

Phytocannabinoids

Phytocannabinoids, also called "natural cannabinoids", "herbal cannabinoids", and "classical cannabinoids", are only known to occur naturally in significant quantity in the cannabis plant, and are concentrated in a viscous resin that is produced in glandular structures known as trichomes. In addition to cannabinoids, the resin is rich in terpenes, which are largely responsible for the odour of the cannabis plant.

Phytocannabinoids are nearly insoluble in water but are soluble in lipids, alcohols, and other non-polar organic solvents. However, as phenols they form more water-soluble phenolate salts under strongly alkaline conditions.

All natural cannabinoids are derived from their respective 2-carboxylic acids (2-COOH) by decarboxylation (catalyzed by heat, light, or alkaline conditions).

Types

At least 66 cannabinoids have been isolated from the cannabis plant [Burns TL, Ineck JR. "Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain." "The Annals of Pharmacotherapy". 2006 Feb;40(2):251-60. PMID 16449552] To the right the main classes of natural cannabinoids are shown. All classes derive from cannabigerol-type compounds and differ mainly in the way this precursor is cyclized.

Tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) are the most prevalent natural cannabinoids and have received the most study. Other common cannabinoids are listed below:

* CBG Cannabigerol
* CBC Cannabichromene
* CBL Cannabicyclol
* CBV Cannabivarin
* THCV Tetrahydrocannabivarin
* CBDV Cannabidivarin
* CBCV Cannabichromevarin
* CBGV Cannabigerovarin
* CBGM Cannabigerol Monoethyl Ether

Tetrahydrocannabinol

Tetrahydrocannabinol (THC) is the primary psychoactive component of the plant. Medically, it appears to ease moderate pain (analgetic) and to be neuroprotective. THC has approximately equal affinity for the CB1 and CB2 receptors. [cite journal |author=Huffman JW |title=The search for selective ligands for the CB2 receptor |journal=Curr. Pharm. Des. |volume=6 |issue=13 |pages=1323–37 |year=2000 |pmid=10903395|doi=10.2174/1381612003399347] Its effects are perceived to be more cerebral.Fact|date=October 2007

"delta"-9-Tetrahydrocannabinol (Δ⁹-THC, THC) and "delta"-8-tetrahydrocannabinol (Δ⁸-THC), mimic the action of anandamide, a neurotransmitter produced naturally in the body. The THCs produce the "high" associated with cannabis by binding to the CB₁ cannabinoid receptors in the brain.

Cannabidiol

Cannabidiol (CBD) is not psychoactive, and was thought to not affect the psychoactivity of THCcite web |url=http://www.behaviouralpharm.com/pt/re/bpharm/abstract.00008877-200509000-00023.htm |title=Behavioural Pharmacology - Abstract: Volume 16(5-6) September 2005 p 487-496 Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids. |accessdate=2007-06-24 |format= |work=] . However, recent evidence shows that smokers of cannabis with a high CBD/THC ratio were less likely to experience THC-induced psychosis. Fact|date=May 2008 This is supported by psychological tests, in which participants experience less intense psychotic effects when intravenous THC was coadministered with CBD (as measured with a PANSS test). cite web |url=http://www.bbc.co.uk/programmes/b009nyxf |title=Should I Smoke Dope? |accessdate=2008-05-24 |format= |work=] . It has been hypothesised that CBD acts as an allosteric antagonist at the CB1 receptor and thus alters the psychoactive effects of THC.Fact|date=May 2008

Medically, it appears to relieve convulsion, inflammation, anxiety, and nausea.Fact|date=October 2007 CBD has a greater affinity for the CB2 receptor than for the CB1 receptor. It is perceived to have more effect on the body.Fact|date=October 2007

CBD shares a with THC and is the main cannabinoid in low-THC "Cannabis" strains.

Cannabinol

Cannabinol (CBN) is the primary product of THC degradation, and there is usually little of it in a fresh plant. CBN content increases as THC degrades in storage, and with exposure to light and air. It is only mildly psychoactive.

Tetrahydrocannabivarin

Tetrahydrocannabivarin (THCV) is prevalent in certain South African and Southeast Asian strains of Cannabis. It is an antagonist of THC at CB₁ receptors and attenuates the psychoactive effects of THC. [cite web |url=http://www.nature.com/bjp/journal/v146/n7/abs/0706414a.html |title=British Journal of Pharmacology - Abstract of article: Evidence that the plant cannabinoid delta-9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist |accessdate=2007-06-24 |format= |work=]

Cannabichromene

Cannabichromene (CBC) is non-psychoactive and does not affect the psychoactivity of THC .

Double bond position

In addition, each of the compounds above may be in different forms depending on the position of the double bond in the alicyclic carbon ring. There is potential for confusion because there are different numbering systems used to describe the position of this double bond. Under the dibenzopyran numbering system widely used today, the major form of THC is called delta-9-THC, while the minor form is called delta-8-THC. Under the alternate terpene numbering system, these same compounds are called delta-1-THC and delta-6-THC, respectively.

Length

Most herbal cannabinoid compounds are 21 carbon compounds. However, some do not follow this rule, primarily because of variation in the length of the side chain attached to the aromatic ring. In THC, CBD, and CBN, this side chain is a pentyl (5 carbon) chain. In the most common homologue, the pentyl chain is replaced with a propyl (3 carbon) chain. Cannabinoids with the propyl side chain are named using the suffix "varin", and are designated, for example, THCV, CBDV, or CBNV. It appears that shorter chains increase the intensity and decrease the duration of the activity of the chemicals.

Plant profile

Cannabis plants can exhibit wide variation in the quantity and type of cannabinoids they produce. The mixture of cannabinoids produced by a plant is known as the plant's cannabinoid profile. Selective breeding has been used to control the genetics of plants and modify the cannabinoid profile. For example, strains which are used as fiber (commonly called hemp), are bred such that they are low in psychoactive chemicals like THC. Strains used in medicine are often bred for high CBD content, and strains used for recreational purposes are usually bred for high THC content, or for a specific chemical balance. Some strains of more than 20% THC in their flowering buds have been created. Fact|date=September 2007

Quantitative analysis of a plant's cannabinoid profile is usually determined by gas chromatography (GC), or more reliably by gas chromatography combined with mass spectrometry (GC/MS). Liquid chromatography (LC) techniques are also possible, although these are often only semi-quantitative or qualitative. There have been systematic attempts to monitor the cannabinoid profile of cannabis over time, but their accuracy is impeded by the illegal status of the plant in many countries.

Pharmacology

Cannabinoids can be administered by smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, sublingual absorption, or rectal suppository. Once in the body, most cannabinoids are metabolized in the liver, especially by cytochrome P450 mixed-function oxidases, mainly CYP 2C9. Thus supplementing with CYP 2C9 inhibitors leads to extended intoxication.

Some is also stored in fat in addition to being metabolized in liver. Delta-9-THC is metabolized to 11-hydroxy-delta-9-THC, which is then metabolized to 9-carboxy-THC. Some cannabis metabolites can be detected in the body after several weeks.

Production

Production of cannabinoids include both the synthesis in the plant, and separation of certain types from this material.

Plant synthesis

Cannabinoid production starts when an enzyme causes geranyl pyrophosphate and olivetolic acid to combine and form CBG. Next, CBG is independently converted to either CBD or CBC by two separate synthase enzymes. CBD is then enzymatically cyclized to THC. For the propyl homologues (THCV, CBDV and CBNV), there is a similar pathway that is based on CBGV.

eparation

Cannabinoids can be separated from the plant by extraction with organic solvents. Hydrocarbons and alcohols are often used as solvents. However, these solvents are flammable and many are toxic. Supercritical solvent extraction with carbon dioxide is an alternative technique. Although this process requires high pressures, there is minimal risk of fire or toxicity, solvent removal is simple and efficient, and extract quality can be well-controlled. Once extracted, cannabinoid blends can be separated into individual components using wiped film vacuum distillation or other distillation techniques. However, to produce high purity cannabinoids, chemical synthesis or semisynthesis is generally required.

History

Cannabinoids were first discovered in the 1940s, when CBD and CBN were identified. The structure of THC was first determined in 1964.

Due to molecular similarity and ease of synthetic conversion, it was originally believed that CBD was a natural precursor to THC. However, it is now known that CBD and THC are produced independently in the cannabis plant.

Endocannabinoids

Endocannabinoids are substances produced from within the body which activate cannabinoid receptors. After the discovery of the first cannabinoid receptor in 1988, scientists began searching for an endogenous ligand for the receptor.

Types of endocannabinoid ligands

*Arachidonoyl ethanolamide (Anandamide or AEA)In 1992, the first such compound was identified as arachidonoyl ethanolamide and named anandamide, a name derived from the Sanskrit word for bliss and -"amide". Anandamide is derived from the essential fatty acid arachidonic acid. It has a pharmacology similar to THC, although its chemical structure is different. Anandamide binds to the central (CB1) and, to a lesser extent, peripheral (CB2) cannabinoid receptors, where it acts as a partial agonist. Anandamide is about as potent as THC at the CB1 receptor.Grotenhermen F. "Cannabinoids." "Current Drug Targets - CNS & Neurological Disorders". 2005 Oct;4(5):507-30. PMID 16266285] It is found in nearly all tissues in a wide range of animals.Fact|date=October 2007

Two analogs of anandamide, 7,10,13,16-docosatetraenoylethanolamide and "homo"-γ-linolenoylethanolamide, have similar pharmacology. All of these are members of a family of signalling lipids called "N"-acylethanolamides, which also includes the noncannabimimetic palmitoylethanolamide and oleoylethanolamide which possess anti-inflammatory and orexigenic effects, respectively. Many "N"-acylethanolamides have also been identified in plant seeds [cite web |url=http://www.plantphysiol.org/cgi/content/abstract/120/4/1157 |title=N-Acylethanolamines in Seeds. Quantification of Molecular Species and Their Degradation upon Imbibition -- Chapman et al. 120 (4): 1157 -- PLANT PHYSIOLOGY |accessdate=2007-06-24 |format= |work=] and in molluscs. [cite web |url=http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1X-3SXDXJ8-C&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=2bb2860f5331075a2ed6b97b17cbdb47 |doi=10.1016/S0005-2760(97)00132-X |title=ScienceDirect - Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism : Bioactive long chain N-acylethanolamines in five species of edible bivalve molluscs: Possible implications for mollusc physiology and sea food industry |accessdate=2007-06-24 |format= |work=]

*2-arachidonoyl glycerol (2-AG)Another endocannabinoid, 2-arachidonoyl glycerol, binds to both the CB1 and CB2 receptors with similar affinity, acting as a full agonist at both. 2-AG is present at significantly higher concentrations in the brain than anandamideStella N, Schweitzer P, Piomelli D. "A second endogenous cannabinoid that modulates long-term potentiation." "Nature". 1997 Aug 21; 388(6644):773-8. PMID 9285589] , and there is some controversy over whether 2-AG rather than anandamide is chiefly responsible for endocannabinoid signalling "in vivo"reviewed in Pacher P, Batkai S, Kunos G. "The endocannabinoid system as an emerging target of pharmacotherapy." "Pharmacological Reviews". 2006 Sep;58(3):389-462. PMID 16968947] . In particular, one "in vitro" study suggests that 2-AG is capable of stimulating higher G-protein activation than anandamide, although the physiological implications of this finding are not yet known. [Savinainen JR, Jarvinen T, Laine K, Laitinen JT. "Despite substantial degradation, 2-arachidonoylglycerol is a potent full efficacy agonist mediating CB(1) receptor-dependent G-protein activation in rat cerebellar membranes." "British Journal of Pharmacology". 2001 Oct; 134(3):664-72. PMID 11588122]

*2-arachidonyl glyceryl ether (noladin ether)In 2001 a third, ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), was isolated from porcine brain. [cite journal |author=Hanus L, Abu-Lafi S, Fride E, "et al" |title=2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue=7 |pages=3662–5 |year=2001 |pmid=11259648 |doi=10.1073/pnas.061029898] Prior to this discovery, it had been synthesized as a stable analog of 2-AG; indeed, some controversy remains over its classification as an endocannabinoid, as another group failed to detect the substance at "any appreciable amount" in the brains of several different mammalian species.Oka S, Tsuchie A, Tokumura A, Muramatsu M, Suhara Y, Takayama H, Waku K, Sugiura T. "Ether-linked analogue of 2-arachidonoylglycerol (noladin ether) was not detected in the brains of various mammalian species." "Journal of Neurochemistry". 2003 Jun;85(6):1374-81. PMID 12787057] It binds to the CB1 cannabinoid receptor ("K"_i = 21.2 nmol/L) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It binds primarily to the CB1 receptor, and only weakly to the CB2 receptor.

*N-arachidonoyl-dopamine (NADA)Discovered in 2000, NADA preferentially binds to the CB1 receptor. [Bisogno, T., D. Melck, M. Bobrov, N. M. Gretskaya, V. V. Bezuglov, L. De Petrocellis, V. Di Marzo. "N-acyl-dopamines: novel synthetic CB1 cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo." "The Biochemical Journal". 2000 Nov 1;351 Pt 3:817-24. PMID 11042139] Like anandamide, NADA is also an agonist for the vanilloid receptor subtype 1 (TRPV1), a member of the vanilloid receptor family.Bisogno T, Ligresti A, Di Marzo V. "The endocannabinoid signalling system: biochemical aspects." "Pharmacology, Biochemistry, and Behavior". 2005 Jun;81(2):224-38. PMID 15935454] [cite journal
journal =European journal of pharmacology
year=2003
month=July
volume=472
issue=1-2
pages=1–21
title=Cannabinoid modulation of peripheral autonomic and sensory neurotransmission.
author=Ralevic V.
pmid=12860468
doi =10.1016/S0014-2999(03)01813-2]

*Virodhamine (OAE)A fifth endocannabinoid, virodhamine, or "O"-arachidonoyl-ethanolamine (OAE) was discovered in June 2002. Although it is a full agonist at CB2 and a partial agonist at CB1, it behaves as a CB1 antagonist "in vivo". In rats, virodhamine was found to be present at comparable or slightly lower concentrations than anandamide in the brain, but 2- to 9-fold higher concentrations peripherally. [cite journal
journal= The Journal of pharmacology and experimental therapeutics
author=Porter AC, Sauer JM, Knierman MD, Becker GW, Berna MJ, Bao J, Nomikos GG, Carter P, Bymaster FP, Leese AB, Felder CC.
title = Characterization of a Novel Endocannabinoid, Virodhamine, with Antagonist Activity at the CB1 Receptor
url = http://jpet.aspetjournals.org/cgi/reprint/301/3/1020.pdf
pmid=12023533
year=2002
pages=1020–1024
volume=301
month=June
issue=3
doi= 10.1124/jpet.301.3.1020]

Function

Endocannabinoids serve as intercellular 'lipid messengers', signaling molecules that are released from one cell and activate the cannabinoid receptors present on other nearby cells. Although in this intercellular signaling role they are similar to the well-known monoamine neurotransmitters, such as acetylcholine, GABA or dopamine, endocannabinoids differ in numerous ways from them. For instance, they use retrograde signaling. Furthermore, endocannabinoids are lipophilic molecules that are not very soluble in water. They are not stored in vesicles, and exist as integral constituents of the membrane bilayers that make up cells. They are believed to be synthesized 'on-demand' rather than made and stored for later use. The mechanisms and enzymes underlying the biosynthesis of endocannabinoids remain elusive and continue to be an area of active research.

The endocannabinoid 2-AG has been found in bovine and human maternal milk. [cite journal | author = Fride E, Bregman T, Kirkham TC.
year = 2005
month = April
title = Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood.
journal = Experimental Biology and Medicine
volume = 230
issue = 4
pages = 225–234
doi = 10.1371/journal.pbio.0020286
pmid = 15792943
url = http://www.ebmonline.org/cgi/reprint/230/4/225.pdf | format = | accessdate = ]

Retrograde signal

Conventional neurotransmitters are released from a ‘presynaptic’ cell and activate appropriate receptors on a ‘postsynaptic’ cell, where presynaptic and postsynaptic designate the sending and receiving sides of a synapse, respectively. Endocannabinoids, on the other hand, are described as retrograde transmitters because they most commonly travel ‘backwards’ against the usual synaptic transmitter flow. They are in effect released from the postsynaptic cell and act on the presynaptic cell, where the target receptors are densely concentrated on axonal terminals in the zones from which conventional neurotransmitters are released. Activation of cannabinoid receptors temporarily reduces the amount of conventional neurotransmitter released. This endocannabinoid mediated system permits the postsynaptic cell to control its own incoming synaptic traffic. The ultimate effect on the endocannabinoid releasing cell depends on the nature of the conventional transmitter that is being controlled. For instance, when the release of the inhibitory transmitter, GABA, is reduced, the net effect is an increase in the excitability of the endocannabinoid-releasing cell. Conversely, when release of the excitatory neurotransmitter, glutamate, is reduced, the net effect is a decrease in the excitability of the endocannabinoid-releasing cell.

Range

Endocannabinoids are hydrophobic molecules. They cannot travel unaided for long distances in the aqueous medium surrounding the cells from which they are released, and therefore act locally on nearby target cells. Hence, although emanating diffusely from their source cells, they have much more restricted spheres of influence than do hormones, which can affect cells throughout the body.

Other thoughts

Endocannabinoids constitute a versatile system for affecting neuronal network properties in the nervous system.

"Scientific American" published an article in December 2004, entitled "The Brain's Own Marijuana" discussing the endogenous cannabinoid system. [cite journal |author=Nicoll RA, Alger BE |title=The brain's own marijuana |journal=Sci. Am. |volume=291 |issue=6 |pages=68–75 |year=2004 |pmid=15597982 |doi=]

The current understanding recognizes the role that endocannabinoids play in almost every major life function in the human body.Fact|date=October 2007 Cannabinoids act as a bioregulatory mechanism for most life processes, which reveals why medical cannabis has been cited as treatments for many diseases and ailments in anecdotal reports and scientific literature. Some of these ailments include: pain, arthritic conditions, migraine headaches, anxiety, epileptic seizures, insomnia, loss of appetite, GERD (chronic heartburn), nausea, glaucoma, AIDS wasting syndrome, depression, bipolar disorder (particularly depression-manic-normal), multiple sclerosis, menstrual cramps, Parkinson's, trigeminal neuralgia (tic douloureux), high blood pressure, irritable bowel syndrome, and bladder incontinence.

U.S. Patent # 6630507

In 2003, the U.S. Government as represented by the Department of Health and Human Services filed for, and was awarded a patent on cannabinoids as antioxidants and neuroprotectants. [http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6630507.PN.&OS=PN/6630507&RS=PN/6630507 U.S. Patent 6630507.]

ynthetic and patented cannabinoids

Historically, laboratory synthesis of cannabinoids were often based on the structure of herbal cannabinoids and a large number of analogs have been produced and tested, especially in a group led by Roger Adams as early as 1941 and later in a group led by Raphael Mechoulam. Newer compounds are no longer related to natural cannabinoids or are based on the structure of the endogenous cannabinoids.

Synthetic cannabinoids are particularly useful in experiments to determine the relationship between the structure and activity of cannabinoid compounds, by making systematic, incremental modifications of cannabinoid molecules.

Medications containing natural or synthetic cannabinoids or cannabinoid analogs:

* Dronabinol (Marinol), is Δ9-tetrahydrocannabinol (THC), used as an appetite stimulant, anti-emetic and analgesic.
* Nabilone (Cesamet), a synthetic cannabinoid and an analog of Marinol. It is Schedule II unlike Marinol which is Schedule III.
* Sativex, a cannabinoid extract oral spray containing THC, CBD, and other cannabinoids used for neuropathic pain and spasticity in Canada and Spain. Sativex develops whole plant cannabinoid medicines.
* Rimonabant (SR141716), a selective cannabinoid (CB1) receptor antagonist used as an anti-obesity drug under the proprietary name, Acomplia. It is also used for smoking cessation.

Other notable synthetic cannabinoids include:

* CP-55940, produced in 1974, this synthetic cannabinoid receptor agonist is many times more potent than THC
* Dimethylheptylpyran
* HU-210, about 100 times as potent as THC [http://www.marijuana.org/mydna10-12-05.htm] .
* SR144528, a CB2 receptor antagonists
* WIN 55,212-2, a potent cannabinoid receptor agonist
* JWH-133, a potent selective CB2 receptor agonist.
* Levonantradol (Nantrodolum), an anti-emetic and analgesic but not currently in use in medicine.

Table of natural cannabinoids

References

Notes

*

*

*Hanuš L., Krejčí Z. Isolation of two new cannabinoid acids from Cannabis sativa L. of Czechoslovak origin. Acta Univ. Olomuc., Fac. Med. 74, 161-166 (1975)

*Hanuš L., Krejčí Z., Hruban L. Isolation of cannabidiolic acid from Turkish variety of cannabis cultivated for fibre. Acta Univ. Olomuc., Fac. Med. 74, 167-172 (1975)
* [http://pubs.acs.org/cgi-bin/archive.cgi/jnprdf/1981/44/i01/pdf/np50013a005.pdf Turner C. E., Mole M. L., Hanuš L., ElSohly H. N. Constituents of Cannabis sativa L. XIX. Isolation and structure elucidation of cannabiglendol. A novel cannabinoid from an Indian variant. J. Nat. Prod. - Lloydia 44 (1), 27-33 (1981)]

*

*

*

External links

* [http://www.biotrend.com/download/BT-Review_0208_Cannabinoids.pdf Bela Szabo: Pharmacology of Cannabinoid Receptors, BIOTREND Reviews No. 02, February 2008]
* [http://www.cannabinoidsociety.org The International Cannabinoid Research Society]
* [http://chemicalheritage.org/pubs/ch-v25n2-articles/feature_cannabinoids.html Cannabinoids: A Secret History] by Tom Geller, Chemical Heritage Newsmagazine, 25 (2), Summer 2007
* [http://www.hiwe.info/index.php?type=special&area=1&p=articles&id=12 Pharmacokinetics and Disposition of Cannabinoids]
* [http://www.hiwe.info/index.php?type=special&area=1&p=articles&id=3 Stereochemical Requirements for Cannabimimetic Activity]
* [http://www.endocannabinoid.net The Endocannabinoid System Network] (ECSN)
* [http://www.trimbos.nl/Downloads/English_General/Cannabis2002_Report.pdf Cannabis Report] 2002 Ministry of Public Health of Belgium
* [http://www.parl.gc.ca/common/Committee_SenRep.asp?Language=E&Parl=37&Ses=1&comm_id=85 Senate Report on Cannabis (Canada) - 2002] at the Parliament of Canada
* [http://www.health.gov.au/pubhlth/publicat/document/mono44.pdf The Health and Psychological Effects of Cannabis Use (Australia - Monograph 44) - 2001] at Department of Health and Ageing (Australia)
* [http://books.nap.edu/html/marimed/ Marijuana and Medicine - Assessing the Science Base (Institute of Medicine) - 1999] at National Academies Press
* [http://www.parliament.the-stationery-office.co.uk/pa/ld199798/ldselect/ldsctech/151/15101.htm House of Lords Report - Cannabis (United Kingdom) - 1998] at Parliament of the United Kingdom
* [http://whqlibdoc.who.int/hq/1997/WHO_MSA_PSA_97.4.pdf Cannabis: A Health Perspective and Research Agenda - 1997] at World Health Organization
* [http://www.endocannabinoid.net/ecsoverview/glance.aspx Overview of the Endocannabinoid Signalling System]
* [http://www.hempfood.com/IHA/iha01201.html Chemical Ecology of Cannabis (J. Intl. Hemp Assn. - 1994)]
* [http://www.ccrmg.org/journal/03sum/doctorshouldknow.html What Every Doctor Should Know About Cannabinoids] at California Cannabis Research Medical Group
* [http://www.ccrmg.org/journal/04spr/potential.html Therapeutic Potential in Spotlight at Cannabinoid Researchers' Meeting] at California Cannabis Research Medical Group
* [http://www.hempreport.com/issues/17/malbody17.html THC (tetrahydrocannabinol) accumulation in glands of Cannabis (Cannabaceae)]
* [http://www.genetics.org/cgi/reprint/163/1/335.pdf Inheritance of Chemical Phenotype in Cannabis Sativa (Genetics)] at Genetics Society of America
* [http://www.cannabishq.com/forum/index.php?www;board=8 Medicinal marijuana laws, policies and news]
* [http://www.erowid.org/plants/cannabis/cannabis_info2.shtml Compounds found in "Cannabis sativa"]
* [http://springerlink.com/content/978-0-387-74348-6 Cannabinoids and the Brain] - The most recent biomedical book on the endocannabinoid system