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→‎CBD-enhanced cannabis: Explained the differences in molecular target between THC and CBD, and rationale behind growing certain THC/CBD-rich strains. Added information about the two molecules working in combination.
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==CBD-enhanced cannabis==
==CBD-enhanced cannabis==
Selective breeding by growers in the USA dramatically lowered the CBD content of cannabis; their customers preferred varietals that were more mind-altering due to a higher THC, lower CBD content.<ref name=autogenerated1>{{cite news| url=http://articles.latimes.com/2012/sep/13/local/la-me-customized-marijuana-20120914 | work=Los Angeles Times | first=Lee | last=Romney | title=On the frontier of medical pot to treat boy's epilepsy | date=13 September 2012}}</ref> To meet the demands of medical cannabis patients, growers are currently developing more CBD-rich strains.<ref>{{cite news| url=http://www.telegraph.co.uk/health/8080247/The-rise-of-high-CBD-marijuana-Cannabis.html | location=London | work=The Daily Telegraph | first1=Alastair | last1=Good | title=Growing marijuana that won't get you high | date=26 October 2010}}</ref>
Selective breeding by growers in the USA dramatically lowered the CBD content of cannabis; their customers preferred varietals that were more mind-altering due to a higher THC, lower CBD content.<ref name="autogenerated12">{{cite news|url=http://articles.latimes.com/2012/sep/13/local/la-me-customized-marijuana-20120914|title=On the frontier of medical pot to treat boy's epilepsy|last=Romney|first=Lee|date=13 September 2012|work=Los Angeles Times}}</ref> This is because cannabidiol's relatively low affinity for the CB1 and CB2 receptors does not produce the effects of intoxication and memory loss commonly experienced by THC users.<ref>{{Cite web|url=http://www.hhs.gov/asl/testify/2015/06/20150624a.html|title=Cannabidiol: Barriers to Research and Potential Medical Benefits|last=Volkow|first=Nora D.|date=24 June 2015|website=U.S. Department of Health and Human Services|publisher=|access-date=16 March 2016}}</ref> These individuals are generally less interested in alleviating medical symptoms, and more interested in pursuing the euphoria-inducing effects of cannabis with a higher THC, lower CBD content. However, it is significant to consider the synergistic nature of the two cannabinoids and their ability to enhance one another's therapeutic effects.<ref name=":1">{{Cite web|url=https://www.projectcbd.org/article/cbd-misconceptions|title=CBD Misconceptions|last=Lee|first=Martin A.|date=18 February 2015|website=www.projectcbd.org|access-date=15 March 2016}}</ref> For example, research suggests CBD may augment the anti-inflammatory benefits of THC. The two molecules in combination have also been reported to more aptly reduce neuropathic pain in users.<ref name=":1" /> To meet the demands of medical cannabis patients, growers are currently developing more CBD-rich strains.<ref>{{cite news|url=http://www.telegraph.co.uk/health/8080247/The-rise-of-high-CBD-marijuana-Cannabis.html|title=Growing marijuana that won't get you high|date=26 October 2010|work=The Daily Telegraph|location=London|first1=Alastair|last1=Good}}</ref>


== Industrial hemp ==
== Industrial hemp ==

Revision as of 02:35, 18 April 2016

Not to be confused with cannabinol or cannabinodiol.
Cannabidiol
Clinical data
Trade namesEpidiolex
AHFS/Drugs.comInternational Drug Names
ATC code
  • None
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: Schedule II
  • UK: POM (Prescription only)
  • US: Unscheduled
Pharmacokinetic data
Bioavailability13-19% (oral),[1] 11-45% (mean 31%; inhaled)[2]
Elimination half-life9 h[1]
Identifiers
  • 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.215.986 Edit this at Wikidata
Chemical and physical data
FormulaC21H30O2
Molar mass314.4636 g·mol−1
3D model (JSmol)
Melting point66 °C (151 °F)
Boiling point180 °C (356 °F)
(range: 160–180 °C)[3]
  • Oc1c(c(O)cc(c1)CCCCC)[C@@H]2\C=C(/CC[C@H]2\C(=C)C)C
  • InChI=1S/C21H30O2/c1-5-6-7-8-16-12-19(22)21(20(23)13-16)18-11-15(4)9-10-17(18)14(2)3/h9,12-13,17-18,22-23H,2,5-8,10-11H2,1,3-4H3/t17-,18+/m0/s1 checkY
  • Key:ZTGXAWYVTLUPDT-ZWKOTPCHSA-N checkY
  (verify)
Part of a series on
Cannabis
Cannabis
Chemistry
  • Semi-synthetic cannabinoids
Pharmacology
Consumption
Economics
Effects
Forms
Law
Variants
  • Genus
  • Species
Related

Cannabidiol (CBD) is one of at least 113 active cannabinoids identified in cannabis.[4] [5] It is a major phytocannabinoid, accounting for up to 40% of the plant's extract.[6] CBD is considered to have a wide scope of potential medical applications despite its reputed lack of psychoactivity.

Research

The bud of a Cannabis sativa flower coated with trichomes bearing cannabidiol and other cannabinoids

Neurological effects

Cannabidiol has been seen to be an anticonvulsant in animals, but controlled studies in humans are lacking.[7]

Transdermal CBD is neuroprotective in animals.[8]

Dravet syndrome

Dravet syndrome is a rare form of epilepsy that is difficult to treat. It is a catastrophic form of intractable epilepsy that begins in infancy. Initial seizures are most often prolonged events and in the second year of life other seizure types begin to emerge.[9] A number of high profile and anecdotal reports have sparked interest in treatment of Dravet syndrome with CBD.[10] GW Pharmaceuticals is seeking FDA approval to market a formulation of CBD, under the tradename Epidiolex, as a treatment for Dravet syndrome. Epidiolex was granted fast-track status and is in late stage trials following positive early results from the drug.[10][11][12][13][14] Some cannabis extract preparations containing CBD are marketed as dietary supplements and claim efficacy against Dravet Syndrome. One such preparation is marketed under the tradename Charlotte's web.[15][16]

Psychotropic effect

A 2014 Cochrane Review concluded that the evidence is insufficient to conclude that CBD has anti-psychotic effects.[17] Others have concluded it may have antipsychotic effects and may counteract the potential psychotomimetic effects of THC on individuals with latent schizophrenia;[6] some reports show it to be an alternative treatment for schizophrenia that is safe and well-tolerated.[18] Studies have shown CBD may reduce schizophrenic symptoms due to its apparent ability to stabilize disrupted or disabled NMDA receptor pathways in the brain, which are shared and sometimes contested by norepinephrine and GABA.[18][19] Studies have shown cannabidiol decreases activity of the limbic system [20] and decreases social isolation induced by THC in rats.[21] Additionally, a study focusing on the inhibition of cocaine-induced seizures in rats displayed the potential anti-epileptic benefits of CBD.[22]

Chronic cannabidiol administration in rats was found to produce reactions suggesting anxiety, indicating that prolonged treatment with cannabidiol might lead to anxiety.[23] Those results have been contested by Gururajan,[24] and contradict Réus,[25] whose experimentation cover the same duration. The results of one study indicate that the administration of cannabidiol may reduce subjective anxiety in patients diagnosed with SAD.[26]

Research on cannabidiol has shown its efficacy in improving the psychotic symptoms of patients with Schizophrenia by elevating levels of anandamide, an antipsychotic endocannabinoid, in the body. These studies also showed that patients given CBD displayed less adverse side-effects than patients given other antipsychotic drugs.[27] Patients with Huntington's disease reported reduction in chorea severity after taking CBD.[28]

Other research indicates CBD as a possible form of therapy and intervention for those suffering from substance abuse, due to its association with the neural circuits involved in addictive behaviors. CBD has an effect on the 5-HT1A receptor which controls stress responses and compulsive behaviors.[29] Studies in rats show that CBD has in impact on opioid addiction and psychostimulant addiction. There have been studies showing cannabidiol as having a positive impact on cannabis and tobacco addictions in humans.[29]

CBD-enhanced cannabis

Selective breeding by growers in the USA dramatically lowered the CBD content of cannabis; their customers preferred varietals that were more mind-altering due to a higher THC, lower CBD content.[30] This is because cannabidiol's relatively low affinity for the CB1 and CB2 receptors does not produce the effects of intoxication and memory loss commonly experienced by THC users.[31] These individuals are generally less interested in alleviating medical symptoms, and more interested in pursuing the euphoria-inducing effects of cannabis with a higher THC, lower CBD content. However, it is significant to consider the synergistic nature of the two cannabinoids and their ability to enhance one another's therapeutic effects.[32] For example, research suggests CBD may augment the anti-inflammatory benefits of THC. The two molecules in combination have also been reported to more aptly reduce neuropathic pain in users.[32] To meet the demands of medical cannabis patients, growers are currently developing more CBD-rich strains.[33]

Industrial hemp

Several industrial hemp varieties can be legally cultivated in western Europe. A variety such as "Fedora 17" has a cannabinoid profile consistently around 1% cannabidiol (CBD) with THC less than 0.1%.[34]

Extraction can be done with olive oil, ethanol, or CO2, and other nonpolar to semipolar solvents.[citation needed]

Pharmacodynamics

Cannabidiol has a very low affinity for CB1 and CB2 receptors but acts as an indirect antagonist of their agonists.[35][36] While one would assume that this would cause cannabidiol to reduce the effects of THC, it may potentiate THC's effects by increasing CB1 receptor density or through another CB1-related mechanism.[37] It may also extend the duration of the effects of THC via inhibition of the cytochrome P-450-3A and 2C enzymes.[38]

Recently, it was found to be an antagonist at the putative new cannabinoid receptor, GPR55, a GPCR expressed in the caudate nucleus and putamen.[39] Cannabidiol has also been shown to act as a 5-HT1A receptor partial agonist,[40] an action which may be involved in its antidepressant,[41][42] anxiolytic,[42][43] and neuroprotective[44][45] effects. Cannabidiol is an allosteric modulator of μ and δ-opioid receptors.[46] Cannabidiol's pharmacological effects have also been attributed to PPAR-γ receptor agonism and intracellular calcium release.[6]

Research suggests that CBD may exert some of its pharmacological action through its inhibition of FAAH, which may in turn increase the levels of endocannabinoids, such as anandamide, produced by the body.[47]

Pharmacokinetic interactions

There is some preclinical evidence to suggest that cannabidiol may reduce THC clearance, modestly increasing THC's plasma concentrations resulting in a greater amount of THC available to receptors, increasing the effect of THC in a dose-dependent manner.[48][49] Despite this the available evidence in humans suggests no significant effect of CBD on THC plasma levels.[50]

Pharmaceutical preparations

Nabiximols (USAN, trade name Sativex) is an aerosolized mist for oral administration containing a near 1:1 ratio of CBD and THC. The drug was approved by Canadian authorities in 2005 to alleviate pain associated with multiple sclerosis.[51][52][53]

Epidiolex is an oil formulation of CBD extracted from the cannabis plant undergoing clinical trials for refractory epilepsy syndromes.[54]

Isomerism

Cannabidiol numbering
Cannabidiol numbering
7 double bond isomers and their 30 stereoisomers
Formal numbering Terpenoid numbering Number of stereoisomers Natural occurrence Convention on Psychotropic Substances Schedule Structure
Short name Chiral centers Full name Short name Chiral centers
Δ5-cannabidiol 1 and 3 2-(6-isopropenyl-3-methyl-5-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol Δ4-cannabidiol 1 and 3 4 No unscheduled
Δ4-cannabidiol 1, 3 and 6 2-(6-isopropenyl-3-methyl-4-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol Δ5-cannabidiol 1, 3 and 4 8 No unscheduled
Δ3-cannabidiol 1 and 6 2-(6-isopropenyl-3-methyl-3-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol Δ6-cannabidiol 3 and 4 4 ? unscheduled
Δ3,7-cannabidiol 1 and 6 2-(6-isopropenyl-3-methylenecyclohex-1-yl)-5-pentyl-1,3-benzenediol Δ1,7-cannabidiol 3 and 4 4 No unscheduled
Δ2-cannabidiol 1 and 6 2-(6-isopropenyl-3-methyl-2-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol Δ1-cannabidiol 3 and 4 4 Yes unscheduled
Δ1-cannabidiol 3 and 6 2-(6-isopropenyl-3-methyl-1-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol Δ2-cannabidiol 1 and 4 4 No unscheduled
Δ6-cannabidiol 3 2-(6-isopropenyl-3-methyl-6-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol Δ3-cannabidiol 1 2 No unscheduled

Based on: Nagaraja, Kodihalli Nanjappa, Synthesis of delta-3-cannabidiol and the derived rigid analogs, Arizona University 1987.

See also: Tetrahydrocannabinol#Isomerism, Abnormal cannabidiol.

Chemistry

Cannabidiol is insoluble in water but soluble in organic solvents such as pentane. At room temperature, it is a colorless crystalline solid.[55] In strongly basic media and the presence of air, it is oxidized to a quinone.[56] Under acidic conditions it cyclizes to THC.[57] The synthesis of cannabidiol has been accomplished by several research groups.[58][59][60]

Biosynthesis

Cannabis produces CBD-carboxylic acid through the same metabolic pathway as THC, until the last step, where CBDA synthase performs catalysis instead of THCA synthase.[61]

Cannabidiol is not scheduled by the Convention on Psychotropic Substances.

Australia

Prescription Medicine (Schedule 4).[62]

Canada

Cannabidiol is a Schedule II drug in Canada. Prescription medication.[63]

United States

Cannabidiol (CBD) has received orphan drug status in the United States, for treatment of Dravet syndrome which will allow it to be studied.[64]

UK

Cannabidiol, in an oral-mucosal spray formulation combined with delta-9-tetrahydrocannabinol, is a prescription product available for relief of severe spasticity due to multiple sclerosis (where other anti-spasmodics have not been effective).[65]

EU

Cannabidiol is listed in EU Cosmetics Ingredient Database.[66]

References

Template:Research help

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