Cannabidiol

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Cannabidiol
CBD.svg
Chemical Nomenclature
Common names Cannabidiol, CBD, Epidiolex
Substitutive name Cannabidiol
Systematic name (-)-trans-2-p-Mentha-1,8-dien-3-yl-5-pentylresorcinol
Class Membership
Psychoactive class Cannabinoid
Chemical class Cannabinoid
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold 2 mg
Light 5 - 15 mg
Common 15 - 30 mg
Strong 30 - 60 mg
Heavy 60 mg +
Duration
Total 1.5 - 4 hours
Come up 15 - 30 minutes
Offset 1 - 1.5 hours









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Cannabidiol (also known as CBD and Epidiolex®) is one of the naturally-occurring cannabinoids found in the cannabis plant. It is one of some 113 identified cannabinoids in cannabis plants, accounting for up to 40% of the plant's extract.[1]

Cannabidiol can be administered by multiple routes, including by inhalation of cannabis smoke or vapor, as an aerosol spray into the cheek, and by mouth. It may be supplied as CBD oil containing only CBD as the active ingredient (i.e. no added THC or terpenes), a full-plant CBD-dominant hemp extract oil, capsules, dried cannabis, or as a prescription liquid solution.[2]

Cannabidiol does not have the same psychoactivity as tetrahydrocannabinol (THC), the psychoactive ingredient in cannabis. It is commonly described as non-intoxicating. Reported effects include anxiety suppression, muscle relaxation, and pain relief.

In the United States, the cannabidiol drug Epidiolex has been approved by the Food and Drug Administration for treatment of two epilepsy disorders.[3] The U.S. Drug Enforcement Administration has assigned Epidiolex a Schedule V classification, while non-Epidiolex CBD remains a Schedule I drug prohibited for any use.[4] Cannabidiol is not scheduled under any United Nations drug control treaties.[5]

Cannabidiol is generally well-tolerated with a good safety profile. However, it may have the potential to cause adverse drug-drug interactions. As a result, it is advised to use harm reduction practices if using this substance.

History and culture

Cannibidiol was first isolated from Mexican marijuana by Roger Adams and from Indian charas by Alexander Todd, both in 1940. On the basis of chemical degradation and correlation with cannabinol, a general structure was proposed. In 1963, Raphael Mechoulam isolated CBD from Lebanese hashish and established its structure and relative stereochemistry.[6] Its absolute stereochemistry was determined in 1967.[6]

Chemistry

Cannabis contains more than 400 different chemical compounds, of which 61 are considered cannabinoids, a class of compounds that act upon endogenous cannabinoid receptors of the body.[7] CBD accounts for up to 41% of the plant's extract.

At room temperature, cannabidiol is a colorless crystalline solid.[8] It is insoluble in water.

Cannabis produces CBD-carboxylic acid through the same metabolic pathway as THC, until the next to last step, where CBDA synthase performs catalysis instead of THCA synthase.[9]

Pharmacology

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, including 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.[10] 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.[11] 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).[12][13]

The oral bioavailability of CBD is 13 to 19%, while its bioavailability via inhalation is 11 to 45% (mean 31%).[14][15] The elimination half-life of CBD is 18–32 hours.[16]

Cannabidiol is metabolized in the liver and intestines by enzymes CYP2C19 and CYP3A4, and UGT1A7, UGT1A9, and UGT2B7 isoforms.[17]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
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Cognitive effects
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Medical uses

At lower doses, cannabidiol has physiological effects that promote and maintain health, including antioxidative, anti-inflammatory, and neuroprotection effects. For instance, CBD is more effective than vitamin C and E as a neuroprotective antioxidant and can ameliorate skin conditions such as acne.[18][19]

Toxicity and harm potential

According to clinical studies, cannabidiol is well-tolerated and shows little to no toxicity.[20] According to a 2011 literature review, CBD does not alter physiological parameters such as heart rate, blood pressure, and body temperature. Moreover, psychological and psychomotor functions are not adversely affected. Chronic use and high doses of up to 1500 mg per day have been repeatedly shown to be well tolerated by humans. As a result, it is considered to have a good safety profile.[21]

However, this information should be interpreted cautiously as cannabidiol has been subject to relatively few human studies. Further research is needed to fully establish its safety profile.

Commonly reported side effects from prescribed cannabidiol use include tiredness, diarrhea, and changes of appetite/weight.[22]

Dependence and abuse potential

Cannabidiol is considered to have low abuse potential compared to THC and other recreational substances. Cannabidiol administration does not produce euphoria or other reinforcing effects and there is no evidence that it produces dependence.

Dangerous interactions

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This dangerous interactions section is a stub.

As such, it may contain incomplete or invalid information. You can help by expanding upon or correcting it.

Cannabidiol is an inhibitor of CYP enzymes (including CYP34A),[23] which are involved in the metabolism of many psychoactive substances. As a result, it has the potential to cause dangerous interactions. Caution is advised when combining cannabidiol with other substances, particularly with higher doses.

Legal status

Internationally, cannabidiol is not scheduled under the Convention on Psychotropic Substances or any other UN drug treaty.

  • Australia: In 2015, 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". Previous to this it was listed in Schedule 9 as a prohibited substance.[24]
  • 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.[25]
  • 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.[26]
  • 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.[27]
  • 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.[28]
  • 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]

Literature

  • Mechoulam, R., Peters, M., Murillo-Rodríguez, E., & Hanuš, L.O. (2007). Cannabidiol--recent advances. Chemistry & Biodiversity, 4 8, 1678-92.
  • Mechoulam, R., Parker, L. A., & Gallily, R. (2002). Cannabidiol: an overview of some pharmacological aspects. The Journal of Clinical Pharmacology, 42(S1).
  • Devinsky, O., Cilio, M. R., Cross, H., Fernandez‐Ruiz, J., French, J., Hill, C., ... & Martinez‐Orgado, J. (2014). Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 55(6), 791-802. https://doi.org/0.1111/epi.12631

References

  1. Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS (December 2012). "Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences (Review). 367 (1607): 3364–78. doi:10.1098/rstb.2011.0389. PMC 3481531. PMID 23108553.
  2. "Epidiolex (Cannabidiol) FDA Label" (PDF). fda.gov. Retrieved 28 June 2018. For label updates see FDA index page for NDA 210365
  3. "FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy". US Food and Drug Administration. 25 June 2018. Retrieved 25 June 2018.
  4. "DEA reschedules Epidiolex, marijuana-derived drug, paving the way for it to hit the market". CNBC. September 27, 2018.
  5. Angell T (13 August 2018). "UN Launches First-Ever Full Review Of Marijuana's Status Under International Law". Marijuana Moment. Retrieved 1 November 2018.
  6. 6.0 6.1 Mechoulam, R., & Hanuš, L. (2002). Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects. Chemistry and physics of lipids, 121(1-2), 35-43. https://pdfs.semanticscholar.org/04c5/048289fd0ed9fa28769ac1a729f4cfd92ccf.pdf
  7. Sharma P, Murthy P, Bharath MM: Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012 Fall;7(4):149-56. PMID:23408483
  8. Jones PG, Falvello L, Kennard O, Sheldrick GM, Mechoulam R (1977). "Cannabidiol". Acta Crystallogr. B. 33 (10): 3211–3214. https://doi.org/10.1107/S0567740877010577
  9. Marks MD, Tian L, Wenger JP, Omburo SN, Soto-Fuentes W, He J, Gang DR, Weiblen GD, Dixon RA (2009). "Identification of candidate genes affecting Delta9-tetrahydrocannabinol biosynthesis in Cannabis sativa". Journal of Experimental Botany. 60 (13): 3715–26. https://doi.org/10.1093/jxb/erp210. PMC 2736886. PMID 19581347.
  10. https://www.drugbank.ca/drugs/DB09061
  11. Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM: Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol. 2015 Oct;172(20):4790-805. https://doi.org/10.1111/bph.13250. Epub 2015 Oct 13. PMID:26218440
  12. Ibeas Bih C, Chen T, Nunn AV, Bazelot M, Dallas M, Whalley BJ: Molecular Targets of Cannabidiol in Neurological Disorders. Neurotherapeutics. 2015 Oct;12(4):699-730. https://doi.org/10.1007/s13311-015-0377-3. PMID:26264914
  13. Zhornitsky S, Potvin S: Cannabidiol in humans-the quest for therapeutic targets. Pharmaceuticals (Basel). 2012 May 21;5(5):529-52. https://doi.org/10.3390/ph5050529. PMID:24281562
  14. Scuderi C, Filippis DD, Iuvone T, Blasio A, Steardo A, Esposito G (May 2009). "Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders". Phytotherapy Research (Review). 23 (5): 597–602. https://doi.org/10.1002/ptr.2625. PMID 18844286.
  15. Mechoulam R, Parker LA, Gallily R (November 2002). "Cannabidiol: an overview of some pharmacological aspects". Journal of Clinical Pharmacology. 42 (11 Suppl): 11S–19S. https://doi.org/10.1002/j.1552-4604.2002.tb05998.x. PMID 12412831.
  16. Devinsky, Orrin; Cilio, Maria Roberta; Cross, Helen; Fernandez-Ruiz, Javier; French, Jacqueline; Hill, Charlotte; Katz, Russell; Di Marzo, Vincenzo; Jutras-Aswad, Didier; Notcutt, William George; Martinez-Orgado, Jose; Robson, Philip J.; Rohrback, Brian G.; Thiele, Elizabeth; Whalley, Benjamin; Friedman, Daniel (22 May 2014). "Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders". Epilepsia. 55 (6): 791–802. https://doi.org/10.1111/epi.12631. PMC 4707667. PMID 24854329.
  17. "Epidiolex (Cannabidiol) FDA Label" (PDF). fda.gov. Retrieved 28 June 2018. For label updates see FDA index page for NDA 210365
  18. Hampson AJ, Grimaldi M, Axelrod J, et al. Cannabidiol and Δ9-tetrahydrocannabinol are neuroprotective antioxidants. PNAS. 1998;95:8268–8273
  19. Oláh A, Tóth BI, Borbíró I, et al. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. J Clin Invest. 2014:124:3713.
  20. Cunha, J.E., Carlini, E.D., Pereira, A., Ramos, O.L., Pimentel, C., Gagliardi, R., Sanvito, W.L., Lander, N., & Mechoulam, R. (1980). Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology, 21 3, 175-85.
  21. Bergamaschi MM, Queiroz RH, Zuardi AW, et al. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011;6:237–249
  22. Iffland, K., & Grotenhermen, F. (2017). An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis and cannabinoid research, 2(1), 139-154. https://doi.org/10.1089/can.2016.0034
  23. Zendulka, O., Dovrtělová, G., Nosková, K., Turjap, M., Šulcová, A., Hanuš, L., & Juřica, J. (2016). Cannabinoids and Cytochrome P450 Interactions. Current Drug Metabolism, 17(3), 206–226. https://doi.org/10.2174/138920021766615121014205
  24. 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
  25. Government of Canada Justice Laws Website. (2017, August 1). Retrieved from http://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html.
  26. New Zealand Government Ministry of Health. (2017, September 6. Retrieved from http://www.health.govt.nz/our-work/regulation-health-and-disability-system/medicines-control/medicinal-cannabis/cbd-products.
  27. Swiss Agency for Therapeutic Products. (2017, August 1). Retrieved from https://www.swissmedic.ch/aktuell/00673/03778/index.html?lang=en
  28. Medicines and Healthcare products Regulatory Agency. (2017 August 1). Retrieved from https://www.gov.uk/government/news/mhra-statement-on-products-containing-cannabidiol-cbd