Cannabidiol: Difference between revisions

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The exact mechanism of action of CBD and THC is not currently fully understood. However, it is known that CBD acts on cannabinoid (CB) receptors of the endocannabinoid system, which are found in numerous areas of the body, including the peripheral and central nervous systems (such as the brain)). The endocannabinoid system regulates many physiological responses of the body including pain, memory, appetite, and mood.

More specifically, CB1 receptors can be found within the pain pathways of the brain and spinal cord where they may affect CBD-induced analgesia and anxiolysis, and CB2 receptors have an effect on immune cells, where they may affect CBD-induced anti-inflammatory processes.<ref name="CBDDrugBank"/> CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body.<ref>{{cite journal | vauthors=((Laprairie, R. B.)), ((Bagher, A. M.)), ((Kelly, M. E. M.)), ((Denovan-Wright, E. M.)) | journal=British Journal of Pharmacology | title=Cannabidiol is a negative allosteric modulator of the cannabinoid CB 1 receptor: Negative allosteric modulation of CB 1 by cannabidiol | volume=172 | issue=20 | pages=4790–4805 | date= October 2015 | url=https://onlinelibrary.wiley.com/doi/10.1111/bph.13250 | issn=00071188 | doi=10.1111/bph.13250}}</ref> Allosteric modulators differ from receptor agonists in that they alter the activity of the receptor by binding to a functionally distinct binding site rather than directly to the receptor.

More specifically, CB1 receptors can be found within the pain pathways of the brain and spinal cord where they may affect CBD-induced analgesia and anxiolysis, and CB2 receptors have an effect on immune cells, where they may affect CBD-induced anti-inflammatory processes.<ref name="CBDDrugBank" /> CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body.<ref>{{cite journal | vauthors=((Laprairie, R. B.)), ((Bagher, A. M.)), ((Kelly, M. E. M.)), ((Denovan-Wright, E. M.)) | journal=British Journal of Pharmacology | title=Cannabidiol is a negative allosteric modulator of the cannabinoid CB 1 receptor: Negative allosteric modulation of CB 1 by cannabidiol | volume=172 | issue=20 | pages=4790–4805 | date= October 2015 | url=https://onlinelibrary.wiley.com/doi/10.1111/bph.13250 | issn=00071188 | doi=10.1111/bph.13250}}</ref> Allosteric modulators differ from receptor agonists in that they alter the activity of the receptor by binding to a functionally distinct binding site rather than directly to the receptor.

In addition to the well-known activity on CB1 and CB2 receptors, there is further evidence that CBD also activates 5-HT1A/2A/3A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gamma-aminobutyric acid (GABA), and cellular uptake of anandamide, acts on mitochondria Ca2+ stores, blocks low-voltage-activated (T-type) Ca2+ channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH).<ref>{{cite journal | vauthors=((Ibeas Bih, C.)), ((Chen, T.)), ((Nunn, A. V. W.)), ((Bazelot, M.)), ((Dallas, M.)), ((Whalley, B. J.)) | journal=Neurotherapeutics | title=Molecular Targets of Cannabidiol in Neurological Disorders | volume=12 | issue=4 | pages=699–730 | date= October 2015 | url=http://link.springer.com/10.1007/s13311-015-0377-3 | issn=1933-7213 | doi=10.1007/s13311-015-0377-3}}</ref><ref>{{cite journal | vauthors=((Zhornitsky, S.)), ((Potvin, S.)) | journal=Pharmaceuticals | title=Cannabidiol in Humans—The Quest for Therapeutic Targets | volume=5 | issue=5 | pages=529–552 | date=21 May 2012 | url=http://www.mdpi.com/1424-8247/5/5/529 | issn=1424-8247 | doi=10.3390/ph5050529}}</ref>

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==Subjective effects==

{{effects/base

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==Medical use==

Cannabidiol is currently approved in the United States under the name Epidiolex as a treatment for epilepsy disorders.<ref name="FDA2018"/>

Cannabidiol is currently approved in the United States under the name Epidiolex as a treatment for epilepsy disorders.<ref name="FDA2018" />

At lower doses, some studies have shown cannabidiol to have various antioxidative, anti-inflammatory, and neuroprotective properties. For instance, CBD is more effective than vitamin C and E as a neuroprotective antioxidant and can ameliorate skin conditions such as acne.<ref>{{cite journal | vauthors=((Hampson, A. J.)), ((Grimaldi, M.)), ((Axelrod, J.)), ((Wink, D.)) | journal=Proceedings of the National Academy of Sciences | title=Cannabidiol and (−)Δ 9 -tetrahydrocannabinol are neuroprotective antioxidants | volume=95 | issue=14 | pages=8268–8273 | date=7 July 1998 | url=https://pnas.org/doi/full/10.1073/pnas.95.14.8268 | issn=0027-8424 | doi=10.1073/pnas.95.14.8268}}</ref><ref>{{cite journal | vauthors=((Oláh, A.)), ((Tóth, B. I.)), ((Borbíró, I.)), ((Sugawara, K.)), ((Szöllõsi, A. G.)), ((Czifra, G.)), ((Pál, B.)), ((Ambrus, L.)), ((Kloepper, J.)), ((Camera, E.)), ((Ludovici, M.)), ((Picardo, M.)), ((Voets, T.)), ((Zouboulis, C. C.)), ((Paus, R.)), ((Bíró, T.)) | journal=Journal of Clinical Investigation | title=Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes | volume=124 | issue=9 | pages=3713–3724 | date=2 September 2014 | url=http://www.jci.org/articles/view/64628 | issn=0021-9738 | doi=10.1172/JCI64628}}</ref> It should be noted that cannabidiol has been the subject of sensational health claims in the popular media. A 2016 study found that there is only limited high-quality evidence for cannabidiol having any neurological effect in people.<ref name="pmid26056464">{{cite journal | vauthors = Prud'homme M, Cata R, Jutras-Aswad D | title = Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence | journal = Substance Abuse | volume = 9 | pages = 33–8 | year = 2015 | pmid = 26056464 | pmc = 4444130 | doi = 10.4137/SART.S25081}}</ref>

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===Research===

CBD is under preliminary research for its potential antipsychotic effect, possibly mitigating some of the negative, psychosis-like effects of THC.<ref name="pmid31570536">{{cite journal | vauthors = Hudson R, Renard J, Norris C, Rushlow WJ, Laviolette SR | title = Cannabidiol Counteracts the Psychotropic Side-Effects of Δ-9-Tetrahydrocannabinol in the Ventral Hippocampus through Bidirectional Control of ERK1-2 Phosphorylation | journal = The Journal of Neuroscience| volume = 39 | issue = 44 | pages = 8762–8777 | date = October 2019 | pmid = 31570536 | pmc = 6820200 | doi = 10.1523/JNEUROSCI.0708-19.2019}}

*{{cite press release |date=September 30, 2019 |title=Cannabis study reveals how CBD offsets the psychiatric side-effects of THC |website=ScienceDaily |url=https://www.sciencedaily.com/releases/2019/09/190930131115.htm}}</ref><ref>{{cite web |url=https://www.scielo.br/j/bjmbr/a/5sGSHxqFkYHxCYhRZh6fWKH/?format=pdf&lang=en}}</ref>

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*'''Australia:''' Cannabidiol (in preparations for therapeutic use containing 2 per cent or less of other cannabinoids found in cannabis) was placed in Schedule 4 as a "Prescription Only Medicine OR Prescription Animal Remedy" in 2015. It was previously listed in Schedule 9 as a prohibited substance.<ref>Australian Government Department of Health Therapeutic Goods Administration. (2017, August 1). Retrieved from https://www.tga.gov.au/book/part-final-decisions-matters-referred-expert-advisory-committee-2</ref>

*'''Canada:''' Cannabidiol is specifically listed in the Schedule II Controlled Drugs and Substances Act. However, in 2016 Canada’s "Access to Cannabis for Medical Purposes Regulations" came into effect. These regulations improve access to cannabis used for medicinal purposes, including CBD.<ref>{{Citation | title=Consolidated federal laws of Canada, Controlled Drugs and Substances Act | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html}}</ref>

*'''Hong Kong''': <span style="color:red">Illegal</span> in Hong Kong since 1st February 2023, punishable by 7 years imprisonment.<ref>https://hongkongfp.com/2023/02/01/cannabis-compound-cbd-now-banned-in-hong-kong-7-year-jail-term-for-possession-to-match-meth-cocaine/</ref>

*'''New Zealand:''' Cannabidiol is a controlled substance in New Zealand. However, by passing the Misuse of Drugs Amendment Regulations 2017 in September 2017, many of the restrictions currently imposed by the regulations are removed since then. The changes will mean that CBD products, where the level of other naturally occurring cannabinoids is less than 2% of the cannabinoid content, will be easier to access for medical use.<ref>{{Citation | title=Medicinal Cannabis Agency - Cannabidiol (CBD) products | url=https://www.health.govt.nz/our-work/regulation-health-and-disability-system/medicinal-cannabis-agency/medicinal-cannabis-agency-information-industry/medicinal-cannabis-agency-working-medicinal-cannabis/medicinal-cannabis-agency-cannabidiol-cbd-products}}</ref>

*'''Switzerland:''' Cannabidiol is not subject to the Narcotics Act in Switzerland because it does not produce a psychoactive effect. It is still subject to standard Swiss legislation.<ref>Swiss Agency for Therapeutic Products. (2017, August 1). Retrieved from https://www.swissmedic.ch/aktuell/00673/03778/index.html?lang=en</ref>

*'''United Kingdom:''' In 2016, the Medicines and Healthcare products Regulatory Agency (MHRA) issued a statement that products containing CBD used for medical purposes are considered as a medicine subject to standard licensing requirements.<ref>{{Citation | title=MHRA statement on products containing Cannabidiol (CBD) | url=https://www.gov.uk/government/news/mhra-statement-on-products-containing-cannabidiol-cbd}}</ref>

*'''United States:''' Cannabidiol is ~~one of many cannabinoids present in cannabis, and as such is in Schedule I of~~ the ~~Controlled Substances Act.{{citation needed}} FDA-approved drugs that contain CBD derived from cannabis and no more than 0.1% THC, such as Epidiolex, are Schedule V substances.~~<ref>https://www.~~deadiversion.usdoj~~.gov/~~fed_regs~~/~~rules~~/~~2018/fr0928.htm~~</ref>

*'''United States:''' Cannabidiol is legal under the 2018 Farm Bill<ref>https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd#farmbill</ref>. The rest of the [[cannabis]] plant (anything with more than 0.3% Delta-9-THC) is still under Schedule I of the Controlled Substances Act.{{citation needed}}

==External links==

@@ Line 29: / Line 29: @@
 The exact mechanism of action of CBD and THC is not currently fully understood. However, it is known that CBD acts on cannabinoid (CB) receptors of the endocannabinoid system, which are found in numerous areas of the body, including the peripheral and central nervous systems (such as the brain)). The endocannabinoid system regulates many physiological responses of the body including pain, memory, appetite, and mood.
-More specifically, CB1 receptors can be found within the pain pathways of the brain and spinal cord where they may affect CBD-induced analgesia and anxiolysis, and CB2 receptors have an effect on immune cells, where they may affect CBD-induced anti-inflammatory processes.<ref name="CBDDrugBank"/> CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body.<ref>{{cite journal | vauthors=((Laprairie, R. B.)), ((Bagher, A. M.)), ((Kelly, M. E. M.)), ((Denovan-Wright, E. M.)) | journal=British Journal of Pharmacology | title=Cannabidiol is a negative allosteric modulator of the cannabinoid CB 1 receptor: Negative allosteric modulation of CB 1 by cannabidiol | volume=172 | issue=20 | pages=4790–4805 | date= October 2015 | url=https://onlinelibrary.wiley.com/doi/10.1111/bph.13250 | issn=00071188 | doi=10.1111/bph.13250}}</ref> Allosteric modulators differ from receptor agonists in that they alter the activity of the receptor by binding to a functionally distinct binding site rather than directly to the receptor.
+More specifically, CB1 receptors can be found within the pain pathways of the brain and spinal cord where they may affect CBD-induced analgesia and anxiolysis, and CB2 receptors have an effect on immune cells, where they may affect CBD-induced anti-inflammatory processes.<ref name="CBDDrugBank" /> CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body.<ref>{{cite journal | vauthors=((Laprairie, R. B.)), ((Bagher, A. M.)), ((Kelly, M. E. M.)), ((Denovan-Wright, E. M.)) | journal=British Journal of Pharmacology | title=Cannabidiol is a negative allosteric modulator of the cannabinoid CB 1 receptor: Negative allosteric modulation of CB 1 by cannabidiol | volume=172 | issue=20 | pages=4790–4805 | date= October 2015 | url=https://onlinelibrary.wiley.com/doi/10.1111/bph.13250 | issn=00071188 | doi=10.1111/bph.13250}}</ref> Allosteric modulators differ from receptor agonists in that they alter the activity of the receptor by binding to a functionally distinct binding site rather than directly to the receptor.
 In addition to the well-known activity on CB1 and CB2 receptors, there is further evidence that CBD also activates 5-HT1A/2A/3A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gamma-aminobutyric acid (GABA), and cellular uptake of anandamide, acts on mitochondria Ca2+ stores, blocks low-voltage-activated (T-type) Ca2+ channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH).<ref>{{cite journal | vauthors=((Ibeas Bih, C.)), ((Chen, T.)), ((Nunn, A. V. W.)), ((Bazelot, M.)), ((Dallas, M.)), ((Whalley, B. J.)) | journal=Neurotherapeutics | title=Molecular Targets of Cannabidiol in Neurological Disorders | volume=12 | issue=4 | pages=699–730 | date= October 2015 | url=http://link.springer.com/10.1007/s13311-015-0377-3 | issn=1933-7213 | doi=10.1007/s13311-015-0377-3}}</ref><ref>{{cite journal | vauthors=((Zhornitsky, S.)), ((Potvin, S.)) | journal=Pharmaceuticals | title=Cannabidiol in Humans—The Quest for Therapeutic Targets | volume=5 | issue=5 | pages=529–552 | date=21 May 2012 | url=http://www.mdpi.com/1424-8247/5/5/529 | issn=1424-8247 | doi=10.3390/ph5050529}}</ref>
@@ Line 38: / Line 38: @@
 ==Subjective effects==
-{{EffectStub}}
+{{EffectStub|Cognitive Effects=|Depression Reduction=}}
 {{Preamble/SubjectiveEffects}}
 {{effects/base
@@ Line 62: / Line 62: @@
 ==Medical use==
-Cannabidiol is currently approved in the United States under the name Epidiolex as a treatment for epilepsy disorders.<ref name="FDA2018"/>
+Cannabidiol is currently approved in the United States under the name Epidiolex as a treatment for epilepsy disorders.<ref name="FDA2018" />
 At lower doses, some studies have shown cannabidiol to have various antioxidative, anti-inflammatory, and neuroprotective properties. For instance, CBD is more effective than vitamin C and E as a neuroprotective antioxidant and can ameliorate skin conditions such as acne.<ref>{{cite journal | vauthors=((Hampson, A. J.)), ((Grimaldi, M.)), ((Axelrod, J.)), ((Wink, D.)) | journal=Proceedings of the National Academy of Sciences | title=Cannabidiol and (−)Δ 9 -tetrahydrocannabinol are neuroprotective antioxidants | volume=95 | issue=14 | pages=8268–8273 | date=7 July 1998 | url=https://pnas.org/doi/full/10.1073/pnas.95.14.8268 | issn=0027-8424 | doi=10.1073/pnas.95.14.8268}}</ref><ref>{{cite journal | vauthors=((Oláh, A.)), ((Tóth, B. I.)), ((Borbíró, I.)), ((Sugawara, K.)), ((Szöllõsi, A. G.)), ((Czifra, G.)), ((Pál, B.)), ((Ambrus, L.)), ((Kloepper, J.)), ((Camera, E.)), ((Ludovici, M.)), ((Picardo, M.)), ((Voets, T.)), ((Zouboulis, C. C.)), ((Paus, R.)), ((Bíró, T.)) | journal=Journal of Clinical Investigation | title=Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes | volume=124 | issue=9 | pages=3713–3724 | date=2 September 2014 | url=http://www.jci.org/articles/view/64628 | issn=0021-9738 | doi=10.1172/JCI64628}}</ref> It should be noted that cannabidiol has been the subject of sensational health claims in the popular media. A 2016 study found that there is only limited high-quality evidence for cannabidiol having any neurological effect in people.<ref name="pmid26056464">{{cite journal | vauthors = Prud'homme M, Cata R, Jutras-Aswad D | title = Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence | journal = Substance Abuse | volume = 9 | pages = 33–8 | year = 2015 | pmid = 26056464 | pmc = 4444130 | doi = 10.4137/SART.S25081}}</ref>
@@ Line 68: / Line 68: @@
 ===Research===
 CBD is under preliminary research for its potential antipsychotic effect, possibly mitigating some of the negative, psychosis-like effects of THC.<ref name="pmid31570536">{{cite journal | vauthors = Hudson R, Renard J, Norris C, Rushlow WJ, Laviolette SR | title = Cannabidiol Counteracts the Psychotropic Side-Effects of Δ-9-Tetrahydrocannabinol in the Ventral Hippocampus through Bidirectional Control of ERK1-2 Phosphorylation | journal = The Journal of Neuroscience| volume = 39 | issue = 44 | pages = 8762–8777 | date = October 2019 | pmid = 31570536 | pmc = 6820200 | doi = 10.1523/JNEUROSCI.0708-19.2019}}
 *{{cite press release |date=September 30, 2019 |title=Cannabis study reveals how CBD offsets the psychiatric side-effects of THC |website=ScienceDaily |url=https://www.sciencedaily.com/releases/2019/09/190930131115.htm}}</ref><ref>{{cite web |url=https://www.scielo.br/j/bjmbr/a/5sGSHxqFkYHxCYhRZh6fWKH/?format=pdf&lang=en}}</ref>
@@ Line 92: / Line 93: @@
 *'''Australia:''' Cannabidiol (in preparations for therapeutic use containing 2 per cent or less of other cannabinoids found in cannabis) was placed in Schedule 4 as a "Prescription Only Medicine OR Prescription Animal Remedy" in 2015. It was previously listed in Schedule 9 as a prohibited substance.<ref>Australian Government Department of Health Therapeutic Goods Administration. (2017, August 1). Retrieved from https://www.tga.gov.au/book/part-final-decisions-matters-referred-expert-advisory-committee-2</ref>
 *'''Canada:''' Cannabidiol is specifically listed in the Schedule II Controlled Drugs and Substances Act. However, in 2016 Canada’s "Access to Cannabis for Medical Purposes Regulations" came into effect. These regulations improve access to cannabis used for medicinal purposes, including CBD.<ref>{{Citation | title=Consolidated federal laws of Canada, Controlled Drugs and Substances Act | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html}}</ref>
+*'''Hong Kong''': <span style="color:red">Illegal</span> in Hong Kong since 1st February 2023, punishable by 7 years imprisonment.<ref>https://hongkongfp.com/2023/02/01/cannabis-compound-cbd-now-banned-in-hong-kong-7-year-jail-term-for-possession-to-match-meth-cocaine/</ref>
 *'''New Zealand:''' Cannabidiol is a controlled substance in New Zealand. However, by passing the Misuse of Drugs Amendment Regulations 2017 in  September 2017, many of the restrictions currently imposed by the regulations are removed since then. The changes will mean that CBD products, where the level of other naturally occurring cannabinoids is less than 2% of the cannabinoid content, will be easier to access for medical use.<ref>{{Citation | title=Medicinal Cannabis Agency - Cannabidiol (CBD) products | url=https://www.health.govt.nz/our-work/regulation-health-and-disability-system/medicinal-cannabis-agency/medicinal-cannabis-agency-information-industry/medicinal-cannabis-agency-working-medicinal-cannabis/medicinal-cannabis-agency-cannabidiol-cbd-products}}</ref>
 *'''Switzerland:''' Cannabidiol is not subject to the Narcotics Act in Switzerland because it does not produce a psychoactive effect. It is still subject to standard Swiss legislation.<ref>Swiss Agency for Therapeutic Products. (2017, August 1). Retrieved from https://www.swissmedic.ch/aktuell/00673/03778/index.html?lang=en</ref>
 *'''United Kingdom:''' In 2016, the Medicines and Healthcare products Regulatory Agency (MHRA) issued a statement that products containing CBD used for medical purposes are considered as a medicine subject to standard licensing requirements.<ref>{{Citation | title=MHRA statement on products containing Cannabidiol (CBD) | url=https://www.gov.uk/government/news/mhra-statement-on-products-containing-cannabidiol-cbd}}</ref>
-*'''United States:''' Cannabidiol is one of many cannabinoids present in cannabis, and as such is in Schedule I of the Controlled Substances Act.{{citation needed}} FDA-approved drugs that contain CBD derived from cannabis and no more than 0.1% THC, such as Epidiolex, are Schedule V substances.<ref>https://www.deadiversion.usdoj.gov/fed_regs/rules/2018/fr0928.htm</ref>
+*'''United States:''' Cannabidiol is legal under the 2018 Farm Bill<ref>https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd#farmbill</ref>. The rest of the [[cannabis]] plant (anything with more than 0.3% Delta-9-THC) is still under Schedule I of the Controlled Substances Act.{{citation needed}}
 ==External links==